摘要:

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ISSN:0365-6217    

DOI:10.1039/AR94340FP001

出版商:RSC    

年代:1943

数据来源: RSC

摘要:

ANNUAL REPORTSON THEPROGRESS OF CHEMISTRY.RADIOACTIVITY AND SUB-ATOMIC PHENOMENA.THE study of subatomic phenomena has been made possible through thedevelopment of a number of special research tools. Some of them have beenknown for several years, but others have been invented quite recently. Onthe whole, the methods of nuclear physics have been fairly stationary forsome time, and it is felt that a survey might be welcome to chemists.Only few subatomic phenomena occur spontaneously in Nature, viz.,those connected with natural radioactivity and with cosmic radiation. Allothers have to be produced by artificial means, and because of the greatstability of all nuclear structures it is necessary to concentrate large energyon a single particle. The only known way of doing this is to place anelectrically charged particle in a strong electrical field in which it getsaccelerated.The ultimate kinetic energy achieved is equal to the potentialdifference through which the particle moved in the process of acceleration,multiplied by its charge. Since the charge is, in general, equal to the chargeof the electron (or a small multiple of it) it is usual to give its energy inelectron volts (eV. or e.v.). The energies concerned in nuclear reactions aremostly of the order of a million electron volts (MeV), i.e., the energy of anelectron which has fallen through a potential difference of lo6 volts. Hence,these energies are vastly greater than those involved in chemical reactions :1 e.v. corresponds to about 23,000 cals.per mole, and the mean kinetic energyof a molecule a t room temperature, Qlcl', is only about 0.04 ev.High-tension Apparatus.-Ions are produced in a special discharge tubeand are then accelerated in a high vacuum by the application of a highpotential. The acceleration tube generally consists of a number of shortglass (or porcelain) sections separated by metal plates. Each insulatingsection thus carries only a part of the total voltage, and the danger of electricalbreakdown is reduced. Each metal plate has a short length of metal tube inits centre, which nearly touches the metal tube belonging to the next plate.Thus the beam runs down the axis of one long metal tube with a number ofshort gaps in it, and deflection of the beam caused by fluctuating charges onthe insulators is minimised.The unevenness of the field (strong a t the gaps,weak in the tubes) has a desirable focusing action on the beam. The ionsource has to contain a certain pressure (of the order of 0.01 mm.) of thegas in question (hydrogen, deuterium, or helium) and powerful pumps(mostly oil diffusion pumps) are required to keep a sufficiently high vacuumin the accelerating tube.For the production of the necessary high potential there are mainly tw6 RADIOACTIVITY AND SUB- ATOMTC PHENOMENA.ways. The one consists in the use of a transformer, with subsequent recti-fication of the alternating potential (the use of “rt~w,” that is unrectified,A.C. has considerable drawbacks and has been abandoned). By using severalrectifier tubes in cascade arrangement, it is possible to get a D.C.potentialseveral times (say 10 times or more) the peak voltage of the transformer.The other system is essentially the same as in the old electrostaticmachines. Sometimes rotating discs are used, but in the most common form-developed by Van der Graaff-an endless insulating belt (of paper or rubber-ised silk) is stretched over two pulleys which are rotated as fast as possible.One.of the pulleys-say, the lower one-is at ground potential, while theother is inside the H.T. electrode, a large metal box, mostly spherical.Electric charge is “ sprayed ” on to that side of the belt which moves up-wctrds by means of a small rectifier and a number of sharp points whichalmost touch the belt.On arrival at the H.T. electrode the charge is takenoff the belt by means of a similar “ comb.” The H.T. electrode thus getsgradually charged up and its potential goes on increasing either until there isa breakdown (spark) to ground, or until the insulation losses just balance theflow of charge carried by the belt.Both systems have their advantages and drawbacks. The transformer-rectifier arrangement gives large currents (several millirtmps.) and is stableand easy to control. On the other hand it is expensive, and there is alwaysa “ ripple ” (a remnant of A.C.). A Van der Graaff generator can be built atfairly small cost and the potential is quite “ smooth ” ; but it gives no morethan a few tenths of a milliamp. at most, and as the potential depends on theinsulation losses, it takes some skill to get a constant potential.It seems, tobe the general tendency to prefer reotifiers for less than, say, 1 M Y andelectrostatic machines for higher potentials.The limiting potential for each machine depends on the amount of spark-ing from the H.T. electrode to ground. Sparking along the insulator can beinhibited by appropriate design, and the sparking potential may be raised byabout 50% by adding a small amount of dichlorodifluoromethane (“ Freon ”)to the air. For considerably higher potentials it is usual to place the wholesystem, generator and discharge tube, in a tank filled with compressed air.The largest plant of this kind has been built in Pittsburgh and consists of apear-shaped container 47 ft.long, placed with its thin end downwards. TheH.T. electrode i s at the centre of the thick portion of the pear, and the dis-charge tube, 6ome 30 ft. long, extends from there to the bottom end. Thisgenerator can produce up to about 4 Mv. In Wisconsin another high-pressure electrostatic generator has been in use for some years.2The Cyclotron.3LIh this apparatus (invented and developed by E. 0.Lawrence and originally called the magnetic resonance accelerator) the useof excessively high potentials is avoided by the ingenious expedient of1 W. H. Wells, R. 0. Hrtxby, W. E. Stephens, and W. E. Shoupp, Phyaicat Rev.,1940, 68, 162.R. G. Herb, D. B. Parkinson, and D. W. Kerst, cibid., 1937, 51, 75.See W. B. Mann, “ The Cyclotron,” Methuen & Co,, 1940; E.0. Lawrence andD. Coolssey, P h y k E Rev., 1836, 50, 1131FRISCH. 7aooelerating the ions many times by the 8ame potential. The accelerationtakes plaoe between two “ Dees,” hollow semicircular electrodes, like a pillbox cut in two along a diameter. The “ Dees ” are placed in a strongmagnetio field which benda the path of the ions and thus forces them to passrepeatedly from one electrode to the other. A high-frequency potential ieapplied to the ‘‘ Dees ” and synchronised with the motion of the ions so thatthey get aooelerated every time they pass from one “ Dee ” to the other. Asthe ion8 get faster the curvature of their path in the magnetio field decreases,an& they spiral outwards until they (or rather, some of them) esoape througha slit in one “ Dee ” and are directed on to the target by means of a defleotingelectrode.* All this happens inside an &-tight container (called the tank)which ia oontinudy exhausted by powerful pumps.The limiting speed of the ions is given by the strength and diameter ofthe magnetic field.In most cyclotrons the region over which the field issuffioiently homogeneous has a diameter of about 2-23 ft. ; with a fieldof 16000 gauss the limiting energy then becomes about 8 MeV for deuteronsand 16 MeV for doubly-charged helium ions (a-particles, sometimes calledhelions). It would appear that by increasing the size of the magnet onecould produce ions of any desired energy, but as the speed of the ions ceasesto be very small compared to the velocity of light their mws increasesaccording to relativity theory and it becomes inoreasingly difEcult to maintainthe necessary synchronism between their motion and the high-frequenoyvoltage which.accelerates them.The Berkeley 60” cyclotron (60” pole pieoediameter) produces deuterons of 16 MeV (and .a-partiolea of 32 MeV), andyet bigger cyclotrons are under construction. With protons the relativisticdifjiaulty is felt already in cyclotrons of the usual size, and proton energiesare on the whole limited to about 10 MeV or less.A recently developed instrument, called the induction accelerator orbetatron> produces electrons (“ artificial p-particles ”) of energies up to20 MeV. Electrons circulate inside a dough-nut shaped evacuated container,which encloses the iron core of a transformer. On each revolution theelectrons gain a few ev.energy, corresponding to the voltage which would begenerated in a secondary yinding of one turn; but during one half-cycle ofthe A.C. (about 1000 oyules per sec.) which is fed to the transformer, theelectrons make a large number of revolutions and thus accumulate very largeenergy. The instrument is still being improved and its future uae in nuclearphysics is diffioult to predict.N e e o n 8ources.-Radioactive bodies as sources of particles for nuclearexperiments have on the whole been superseded by artificial sources, becauseof the enormously greater intensity of the latter (an ion current of loop amp.,as is customary with artificial sources, means 6 x 1014 particles a, second,whereas 1 g.of radium emits only 2 x loll a-particles per second). TheD. W. Kerst, Rev. Sci. Instr., 1942, 13, 387.* Or else the substance to be bombarded may be placed at the end of a ‘‘ probe ”which is inserted between the “ Dees ’’ so as to intercept the ions before they reach theedge of the “ Dees,” This gives greater intensity but has certain drawbacks8 RADIOACTIVITY AND SUB-ATOMIC PHENOMENA.main use of radioactive sources nowadays is for the production of moderateneutron intensities, their smallness, constancy, and easy manipulation thenbeing of great advantage. The commonest type of neutron source is a tubepacked with beryllium powder and filled with some hundred millicuries ofradon. Such a source emits about 20,000 neutrons per sec.per millicurie,some of which have energies up to 10 MeV. The source decays, of course,with the half-life (5.82 days) of radon. A practically constant source(half-life 1700 years) with practically identical neutron spectrum is obtainedby mixing a radium salt with the beryllium, both finely powdered. Theneutron yield is in general about 12,000 neutrons per sec. per mg. of radium,depending on the thoroughness of mixing. In both cases the neutrons comemainly from the disintegration of beryllium by the a-particles of radium-C’.If a y-ray source (radium, radon, or radio-thorium) is placed inside a berylliumblock, so-called photo-neutrons are obtained, with a line spectrum extendingup to about 1 MeV. The intensity is somewhat smaller than from a “ mixed ”source.With a H.T.tube or a cyclotron one can get much stronger sources, and ELconsiderable selection of different neutron spectra. Bombardment of deuter-ium with deuterons of a few hundred KeV (1 KeV. = 1000 eV.) gives almosthomogeneous neutrons of about 2.5 MeV. Carbon gives slower neutrons,and lithium a very intense emission of fast ones (up to 14 MeV). If born-barded with energetic deuterons (8 MeV or more) from a cyclotron, lithiumemits neutrons of more than 20 MeV. Intense sources of slower neutronsare obtained by bombarding lithium or beryllium with protons from a cyclo-tron. The reactions Li(p,n) and Be(p,n) are endothermic by about 2 MeV;therefore protons of more than 2 MeV are necessary and the maximum energyof the neutrons is about 2 MeV lower than the proton energy. The systematicinvestigation of different neutron sources and of their relative merits is onlya t the beginning.Detection Methods.--For the detection of the particles emitted in nucleartransformations, the time-honoured electroscope has come into its own again,since the development of powerful cyclotrons and H.T.tubes made possiblethe production of artscial radioactive elements with a radiation equivalent tomany milligrams of radium. It is unsurpassed for simplicity and accuracy, inparticular in its more recent forms, among which the one due to C. C. Lauritsenand T. Lauritsen is particularly popular. Increased sensitivity is achieved-though with considerable complication-by the use of an electrometer valve.All these devices, where the bulk current in an ionisation chamber ismeasured, do not allow one to analyse the radiation producing the ionisationinto its different components, except by the slow and laborious process ofinserting absorbing screens between the source and the instrument.It istherefore very fortunate that the development of radio valves has made itcomparatively easy to study the ionisation pulses produced by individualdisintegration particles.65 Rev. Sci. Instr., 1937, 8, 438.6 See W. B. Lewis, “ Electrical Counting,” Cambridge Univ. Press, 1942FRISCH. 9A fast electron or positron (of 1 MeV or more) produces about 20 ionpairs per cm. of path in air at N.T.P. At lower energies this so-called specificionisation is greater, but not very much.On the other hand, a movinglight nucleus (proton, deuteron, a-particle) of a, few MeV energy producesseveral thousand ion pairs per cm., and the heavy, fast moving nuclear frag-ments resulting from nuclear fission make about a million ion pairs per cm.It is therefore possible to count light nuclei in the presence of large numbersof electrons, by counting only those ionisation pulses which are greater thanthe greatest pulses caused by an electron. Similarly? in counting fissionfragments, a-particles can be " out-biased."The amplifier used coiisists of several radio valves, usually with resistance-capacity coupling. At least one of the coupling links has to have a shorttime constant (a millisecond or less) so that the output potential of theamplifier recovers quickly after each pulse. This is particularly important ifthere are large numbers of electrons (or of a-particles in fission counting), inorder to prevent their individual pulses from piling up and thus being counted.The counting is mostly done by mechanical meters such as are madecommercially for use in telephone exchanges. The meter may be driven bya power valve or a thyratron, biased so that only pulses above a certain sizeare counted.By varying the bias, the size distribution of the pulses may beobtained. At high counting rates (above a few hundred pulses per minute)the meter begins to miss pulses because some of them follow too closely forthe meter to count them both.Meters with a resolving time as low as onemillisecond have been constructed, but the more usual procedure is to passthe pulses through a scaling circuit, a " scale of n," which lets only everynth pulse get through to the meter. Most frequently used are scales of2,4, 8, 16, 32 . . . (a scale of 8 being really a cascade of 3 scales of 2), butscales of 10 have also been made.An ionisation chamber may be constructed and used in such a way that'the primary ions produce additional ions by collisions with gas molecules.The pulse may thus be enhanced by a factor of 1000 or more. The mostcommon form is the tube counter, where a moderate potential (1000-2000 volts) between a tube and an axial wire produces a sufficiently intenseelectric field near the wire (which is positive).The amount of multiplicationobtained depends critically on the potential. Up to a certain potential thepulse is proportional to the number of primary ions, and the counter is saidto work as a proportional counter. At higher potential the size of the pulseis determined only by the operating conditions and a single primary ion issufficient to produce a pulse. The counter then operates as a Geiger-Mullercounter and records every particle which makes at least one pair of ionsinside it. The pulse produced by a Geiger-Muller counter is fairly large(one volt or more) so only little further amplification is required for theoperation of a mechanical recorder.The Geiger-Muller counter has perhaps done more than any other singleresearch tool towards the progress of nuclear physics.By increasing thesensitivity of the detection of p-particles it was largely responsible for theA 10 RADIOACTIVITY AND SUB - ATOMIC PHENOMENA.discovery of artificial radioactivity. Its comparative simplicity and cheap-ness made it possible for many laboratories to take up research based onradioactive elements, for instance on their use &s tracers in chemistry andbiology. Moreover, our present knowledge of the cosmic radiation is basedalmost entirely on results obtained with these counters. It is then sur-prising that there should be, to the best of the Reporter’s knowledge, nomonograph on this important instrument (see, however, ref. 6). Perhapsone reason is that there is as yet no agreement about the best way of makingand using Geiger-Muller counters, and each laboratory has its own devicesand methods. In some places, counters are made with considerable care andof an elaborate design and are expected to give years of reliable service,whereas others prefer to make counters by some simple method so that theycan be easily replaced (or refilled) when they fail after a few weeks or months.For the filling gas, a mixture of argon (say under 8-9 cm.of mercurypressure) and alcohol vapour (2-1 cm.) has become very popular in thiscountry and in Europe, because it gives constant counting rate over a con-siderable range of voltage (say 1400-1600 volts) and produces sharp pulsesof uniform size. If very large numbers are counted, the alcohol is eaduallydecomposed and the counter deteriorates. Greater constancy is achievedby filling the counter with hydrogen, possibly with the addition of a noblegas to lower the required voltage.Such counters are not “ self-quenching ”like the alcohol counters; the discharge, once started, would continue if itwere not quenched by the circuit attached to the counter. The simplest(and oldest) way of quenching a counter is to include a high resistance (lo9ohms or more) in the path of the discharge current ; this makes the voltageacross the counter drop, as soon as the discharge develops, and therebyextinguishes the discharge. After that it takes some time for the voltage torise again to its full value, and therefore this arrangement is unsuitable athigh counting rates.Methods have been developed * by which the voltageon the counter is lowered for a short time by an amplifier system, and a long“ plateau ” JT together with high counting rates can be obtained with almostany filling gas. These methods are being used mainly in America.The Coincidence Method.*-It is possible to make an arrangement wherebyonly those events are recorded when two counters are “ triggered ” simul-taneously, or, more correctly, within a time interval A t ; this is called theresolving time of the system and can be made as short as sec. Suchcoincidences occur if one particle goes through both counters, or if the twoparticles which trigger the two counters are emitted within the resolvingtime from the same nucleus.In addition there are always some chancecoincidences; their number is BN,N,At (where N , and N , are the numbers7 See, e.g., 0. S. Dfiendack, H. Lifschutz, and M. M. Slawsky, Physical Rev., 1937,6g, 1231.* See ref. (6).f The “plrtteftu” is the voltage range over which the counting rate is more or lessconstant, extending from the ‘‘ threshold ” up to the point where spurious dischargesbecome numerous. A long plateau (of 100 v. or moro) is desirable, since it means thatthe adjustment and constancy of the voltage supply are not criticalFRISCH. 12of pulses per unit time, in the two counters). This formula shows that it isimportant to make At small in order to minimise the chance coincidences.Applications of the coincidence method are too numerous for more thana small selection to be given.In the study of the cosmic radiation, two ormore counters in a row are used to select particles moving in some particulardirection ; this arrangement, called ‘‘ counter telescope,” is used for measur-ing the angular distribution of cosmic rays.under various conditions. If thecounters are spread out so that one particle cannot go through all of them,they permit the study of the so-called showers of cosmic ray particles. Instudying radiation from radioactive substances by interposing screensbetween two counters, the absorption of those particles which cause coinci-dences can be observed. For instance, if a source of y-rays is placed near thecounterg, electrons are knocked out of the counter walls; by observingtheir absorption in screens placed between the counters, one can determinetheir maximum energy and thereby the energy of the y-rays. If a radio-active substance emits both 8- and y-rays, it is possible to obtain coincidencesbetween two counters, one of which has a thin window (of mica or aluminiumfoil) to admit the p-particles.The usefulness of the coincidence method incombination with the p-ray spectrograph was pointed out in the Report for1940.Compared with the prodigious spread and development of electricalcounting methods, the cloud chamber, once the most powerful tool of nuclearphysicists, has been rather relegated to the background. Its most commonapplication now is the study of neutron-energy spectra, from observations ofthe lengths and directions of the tracks formed by protons or other nucleiin the chamber which have been set in motion on being hit by a neutron.However, the main importance of the cloud chamber lies in its power to givequalitative information on new processes rather than quantitative resultsconcerning known ones. For instance, the slowing down of fission fragmentswas shown, by a number of beautiful cloud-chamber photographs,8 to belargely due to collision with nuclei; these knock-on nuclei show up asnumerous branch tracks, making the track of the fission fragment lookalmost like a Christmas tree.For the study of the tracks of heavy particles such as protons, specialfine-grained photographic emulsions are being more and more widely used.”The particles penetrate only a fraction of a millimetre in the emulsion, butin doing so, each particle causes a chain of silver grains to be formed in thedeveloping process, and under a high-power microscope the length anddirection of these tracks can be determined with considerable accuracy.A photographic plate of this sort is therefore in some way equivalent to acloud chamber which is permanently sensitive and can be made to accumulatetracks for hours or days. This advantage is only partly offset by the con-siderable labour and eye strain involved in the microscopic survey of even afew square millimetres of emulsion. 0. R. FRISCH.’ J. K. Bsggild, Phyrrical Rev., 1941, 60, 627.See C. F. Powell, Endeavour, 1942,1, 151

ISSN:0365-6217    

DOI:10.1039/AR9434000005

出版商:RSC    

年代:1943

数据来源: RSC

摘要:

GENERAL AND PHYSICAL CHEMISTRY.1. THE ABSORPTION SPECTRA OF ORGANIC SUBSTANCES,MODERN physics deals with the problem of spectra somewhat as follows.The completeness of the information obtainable by measurement on smallobjects appears to be limited by the Uncertainty Principle.1 For instance,if a distance is measured with a high degree of accuracy the momentum of theobjects measured is correspondingly vague, being disturbed by the act ofmeasurement. A similar relationship exists between measurements of timeand energy. Time and length (period and wave-length) are the attributesof wave motion, whereas momentum and energy characterise a particle.When we make measurements on an electron forming part of an atom weare necessarily dealing with very small distances; the momentum of theelectron-cannot therefore be fixed with any precision, and it ceases to bepracticable to treat the electron within the atom as a particle.The electronis more appropriately regarded as a stationary wave, and as certain wavesonly are possible, just as a fundamental and its harmonics are the only modesof vibration of a string, we arrive at a kind of an explanation of the exist-ence of electrons in atoms only in quuntised states of certain fixed energyvalues. Transitions of an electron from one quantised state to others giverise to the limited number of monochromatic lines which characterise thespectra of atoms. The equations of wave motion which must be used toreproduce the behaviour of ail electron in an atom have been developed byde Broglie, Schrodinger, Dirac, and others ; they are differential equationsof wave motion in the three dimensions of space involving Planck’s constant,the charge and mass of the electron, and the potential-energy field in whichit moves.I n any example other than the simple case of the hydrogenatom, the equations are excessively difficult or impossible to solve rigorously.However, approximate solutions of varying accuracy can be obtained, andthe symmetry properties of the wave motion in space can be utilised withprofit in attempting t o understand the absorption of light.It is natural to try to form some physical concept of the “ wave ” whichexpresses the electron’s motion in an atom. An examination of this mattershows that the square of the amplitude of the hypothetical wave motion a tany region in the atom represents the probability of the electron occupyingthat region.The “ waves ” may be regarded as a “ probability calculus ”giving the most likely regions for the electron round the atomic nucleus,any closer specification of its position being unattainable by measurement.From this standpoint we can proceed to a qualitative geometrical con-sideration of the three-dimensional wave motion representing the electronin a hydrogen atom. The mathematical problem consists in specifying theN.Y., 1937, Chap. 8.AND WAVE-MECHANICS .See, e.g., Physics Staff, Pittsburg University, “ Atomic Physics,” Wley 8: SonsROWEN : ABSORPTION SPECTRA OF ORGANIC SUBSTANCES. 13positions of the nodes of stationary waves about a point in space.The" fundamental," or wave motion of lowest energy, has the highest ampli-tude at the centre of the atom, a spherical node at infinity, and the ampli-tude falling off rapidly almost to zero in all directions outwards from thecentre. This means that the most probable position of the electron is some-where within a small spherical region round the atomic nucleus. We cannever ascertain where it i s a t any instant within that region by any physicalmeasurement. The wave function representing this is called the electronorbital, since i t corresponds to the Bohr concept of electron orbits in theoriginal theory of atomic structure. Excited hydrogen atoms, having theirFIG. 1.Energy states and absorption spectrum of the hydrogen atom.electrons in higher energy states, are represented by harmonics of thefundamental.These harmonics have an increasing number of nodes thehigher their energy, and they fall geometrically into a number of types.Those of the first type have spherical nodes separating regions of oppositephase (" onion " type) and are called s orbitals. The fundamental is Is,the first harmonic 28, the next 38, etc. (Fig. 1). The second type, called porbitals, is characterised by a node at the centre of the atom, and assumesthree forms, (a) point node a t centre (" spherical shell " form), ( b ) linearnode through centre (" smoke-ring " form), and ( c ) planar node throughcentre (" hour-glass " form). The last form is of chief importance inmolecule formation, and in it the electron is " most probably " situated i14 GENERAL AND PHYSIOAL UHEMISTRY.two regions on the opposite sides of the nodal plane (ABCD, gig. 2 ; oppositephases indicated by shading).We cannot discover “ how ” the electronca,n be in two places at once, but a useful hypothesis is to regard an electronin such an orbital as rapidly oscillating from side to side across the nodalplane. We can then form a kind of picture of the absorption of light.When a light racy (electromagnetic radiation) interacts with a hydrogenatom (electron in 1s orbital) the electron is set into “ vibration.” I n Fig. 2such a light ray is shown, polarised with its electric vector in the plane ofthe paper. If its frequency is appropriate, and it is absorbed, its energybeing taken up by the atom, an excited atom with electron in a p orbitalresults, the nodal plane of the p orbital being a t right angles to the electricvector direction, Le., the electron may be regarded as set into vibrationalong the electric vector direction of the absorbed light.Fig. 1 shows partof the absorption spectrum of the hydrogen atom in the far ultra-violet, andthe transitions involved. The Is orbital can pass as described to p orbitalsFIG. 3.Light absorption by a hydrogen atoni.but not directly to higher s orbitals, for the symmetry of these is such tha,tthere is no “ dipole moment of transition,” and an ordinary light ray can-not stimulate the necessary (‘ electronic vibration; ” s+p transitions aretherefore described as “ permitted ” and s+s as “ forbidden.” If s orbitalshave their perfect spherical symmetry destroyed by the near presence ofother atoms, etc., s+s traiisitions become partially permitted, i.e., wouldcorrespond to a weak absorption of light.Electrons in atoms can occupy higher orbitals of more complex types,d, f, etc., distinguished by nodal surfaces of differing patterns, and thecomplexities of atomic spectra can be interpreted in terms of transitionsbetween such orbitals.For an understanding of simple molecular spectra,however, it is not necessary to pursue these complexities. Reference mustnevertheless be made to (‘ electron spin,” The wave-mechanical repre-sentation of spin is difficult to visualise; it can be shown’mathematically todepend on the theory of relativity.On the “ particle ” concept i t means.that the electron is a body extending in space and rotating on an axis whichcan assume one of two orientations in the atom. According to the Pauliprinciple, every electron in an atom containing several must be distinguishBOWEN : ABSORPTION SPEUTRA OF ORGANIC SUBSTANCES. 16able from the others; this means that they must occupy (Le., be repre-sented by) different orbitals. The orbitals described above take no accountof “ spin,” and each can take two forms with opposite “ spin.” Each ofthe orbitals above therefore can “ contain ” one electron, or can “ contain ”two if the “ spins ” are opposite. This limitation of numbers of electronsin orbitals interprets the arrangement of electrons in “ shells ” in the PeriodicTable of the elements.Every atom has one 1s orbital, one 2s orbital, three2p orbitals with nodal planes mutually a t right-angles, together with fixednumbers of higher orbitals 38, 3p, 3&, etc., determined by the geometry ofthree-dimensional wave motion. Along the first row of the Table, eachatom has two electrons paired in the 1s orbital; lithium has one in the 29FIG. 3.Orbitals of the hydrogen molecule.orbital, and hence is univalent, having one unpaired elc?ctron. Berylliummay be non-valent with two electrons paired in the 2s orbital, or bivalentwith one electron each in the 2s and one 2p orbital. Carbon may be non-valent with two electrons paired in the 2s orbital and two paired in a 2porbital, bivalent with the last two placed in two of the three available 2porbitals, and quadrivalent with one electron each in the 2s and the three2p orbitals.These different atomic states represent different energy levelsof the atom; the one of lowest energy being called the “ ground state.”The shapes of the orbitals of electrons in molecules differ from those ofatoms because of the presence of more than one atomic nucleus. Fig. 3shows some of the simpler types of orbital of the hydrogen molecule. Thefundamental, corresponding to unexcited H,, can be visualived aa formedby the coalescence of two Is hydrogen atom orbitals in phase, forming anellipsoidal orbital with an axis of rotational symmetry along the H-16 GENERAL AND PHYSICAL CHEMISTRY.direction.Because of its derivation from atomic s orbitals, this type isdesignated og, the subscript g standing for the fact that the wave hasthe same phase on both sides of its centre of symmetry. An orbital ofFIG.- I I I 287III II1I I264272264. J680Spins : €nergy /eve/sOPPOsite and permittedtransitions. orJ,4.Energy states artd absorption spectrum of the hydrogen molecule.higher energy with opposite phases across the centre of symmetry is desig-nated oU ; this type has a nodal plane a t right angles to the molecular axis.Two other orbitals are derived from atomic p orbitals by coalescence in anBOWEN : ABSORPTION SPECTRA OF ORGANIC SUBSTANCES. 17out of phase respectively on the two nuclei, called xu and xg.The formerhas a nodal plane containing the molecular axis, and the latter an additionalnodal plane a t right angles to the axis.Fig. 4 shows some states of the hydrogen molecule, with their transitionsand the absorption spectrum. The ground state of H, has the two elec-trons in C T ~ orbitals with opposite spins, a state whose total resultant s p -metry is designated lXg. By the absorption of light of about 1100 A., oneelectron passes to a cru orbital, giving a state represented in symmetrynotation by I&. Owing to the alteration of equilibrium inter-nucleardistance in the transition the higher state may have one or more vibrationalquanta excited simultaneously (Franck-Condon principle 2, ; hence theabsorption is not confined to one wave-length, but consists of a series ofpartial bands differing in frequency by that of a vibrational quantum ofthe higher state.The partial bands are themselves built up of a series oflines of still finer frequency differences owing to the simultaneous changesof rotational energy during the transition. As shown in Fig. 4, another bandsystem appears a t about 1000 A. due to the transition of the ground stateto one of symmetry Inu, where one electron passes to a xu orbital. Threeother excited H, states are also shown; an upper state lCg, to whichtransition from the ground state is “ forbidden ” because of the absence of“transition moment,” and two “ triplet ” states, 3Cg and 3Cu, to whichtransitions are forbidden from the ground state because they would involvereversal of an electron “ spin.’’ The existence of these states is thereforenot apparent in the absorption spectrum.To understand recent work on molecular polarisabilities and orient -ations, it is necessary to form a clear idea of the processes of absorption ofplane-polarised light.Let us imagine an oriented assembly of lCg hydrogenmolecules, with their molecular axes all along one direction. When plane-polarised light a t 1100 A. falls on the molecules it will be strongly absorbedif its electric vector lies along the molecular axis, and one electron will passto a 0, orbital. If the electric vector is at right angles to the molecularaxis the light is not absorbed (dichroism). Plane-polarised light at 1000 A.behaves in just the reverse way.Here the light is strongly absorbed onlywhen its electric vector is at right angles to the axis, since at this wave-length the excited electron passes to a xu orbital with a planar node con-taining the molecular axis (cf. remarks on atomic s - + ~ transitions above).The development of new nodal planes on excitation is always a t right anglesto the electric vector direction. If the wave-lengths of the light do notcoincide with positions of absorption bands, the occupied electronic orbitalsare merely set into forced vibrations by the light waves with a phase lagwhich gives rise to the refraction and dispersion of the transparent substance.We are now in a position to understand qualitatively the absorptionprocesses of organic compounds. The carbon atom in its quadrivalent statesee, e.g., E.J. Bowen, “ Chemical Aspects of Light,” Clarendon Press, Oxford.“ Molecular Spectre JDistomic Molecules),” Herzberg, Prentice-Hall, 1942, p. 75 ;1939, p. 41318 GENERAL AND PHYSICAL CHEMISTRY.has its four valency electrons arranged one in the 2s orbital and in each ofthe three 2p orbitals which the geometry of wave motion permits having ax88along three mutually perpendicular directions in space. When the atomcombines with other atoms of carbon or hydrogen, the shapes of the atomicorbitals are necessarily considerably altered in becoming molecular orbitals.In methane, for example, four identical molecular orbitals are formed atthe tetrahedral angle and of essentially as character, a trace of p characterremaining as an attenuated region of opposite phase on the other sides ofthe carbon atoms away from the C-H links.The ground state of all single-b o d e d organic compounds contains such os type orbitals; ie., ellipsoidal orplum-shaped orbitals having an axis of rotational symmetry along theSide viewOrbitals of the ethylene molecule.FIG. 5 .T Orbitals of the butudiene molecule.chemical link and containing two electrons of opposed spin. Their absorp-tion is like that of the hydrogen molecule; diamond, methane, and ethaneabsorb in the far ultra-violet region only, and in the excited state one electronin a GH or G-C Link passes to a a, or X, orbital without change of spin.The double bond of organic chemistry is supposedly modelled on thegraphite modification of ~ a r b o n .~ Fig. 5 shows the orbitals in ethylene.There is a single-bond skeleton of G H and C-C links a t 120” to each otherand in a plane, all of og type orbitals. The remaining pair of electrons maybe regarded as occupying hour-glase shaped p orbitals on the carbon atomsand having coplanar nodes, which coalesce t o give IL x,‘ orbital whose nodalplane is the plane of the single links. The binding of the electrons in thisE. Hiickel, 2. Elektrochem., 1037, 43, 752, 827; T . Forster, ibid., 1939, 45, 648.* J. E. Lennard-Jones and C. A. Coubon, [I’runs. P a r ~ d a y SOC., 1939, 36, 811BOWEN ABSORPTION SPECTRA OF ORUANJ[C SUBSTANCES. 19orbital is less than that of the og orbitals, and the two types do not overlapmuch. Ethylene absorbs at longer wave-lengths than ethane because oforbital changes of its more weakly bound x electrons.Its longest-waveabsorption corresponds to one electron passing from the xu to a xg orbital,i.e., developing a new nodal plane across the C-C link, the light absorbedbeing that polarised with electric vector along the link. By excitation, theenergy necessary to cause rotation about the link is reduced; hence thefacilitation of cis-trans-changes by ultra-violet light.* In the moleculebutadiene (Fig. 5 ) we have the simplest conjugated system of double bondswith four electrons to dispose in x orbitals. We may start by imaginingeach carbon atom in the chain to have one electron in an atomic p orbitalof hour-glass shape.By coalescence of these in phase all along the moleculea xu orbital as shown marked 1 is produced. This by the Pauli principlecan contain only two electrons. The second pair must be accommodatedin an orbital of partial xS character with one additional nodal plane acrossthe molecular axis, i.e., the left and the right half of the molecule are ofopposite phase. This approximately represents the structure of the normalmolecule. Absorption of ultra-violet light causes an electron from eitherof the orbitals 1 or 2 to pass to either of the orbitals 3 and 4 which havestill more nodal planes across the axis. Four band systems will result, ofwhich the longest wave (lowest energy) will correspond to an orbital change2+3.Electrons in orbitals with nodal planes of this kind are calledanti-bonding, since they weaken the strength of the link. This process ofregarding the structure of conjugated molecules as built up of non-localisedx orbitals superimposed on the G orbital skeleton is easily extended to thepolyenes. For example, p-carotene, with 22 carbon atoms alternatelysingly and doubly linked, has in its ground state 11 x orbitals, having 0-10nodal planes across the molecular axis ; and by absorbing light one electronpasses to a still higher x orbital. It is easy to see that with increasingdegree of conjugation the more bands will a molecule show and the longerwill be the wave-length of the transition of least energy change, since theenergy differences between higher orbitals grow less and less.Fig. 6 illus-trates the arrangement of nodes and approximate energy levels of orbitalsin conjugated polyenes. Fig. 7 shows how the longest wave-length ofabsorption varies with increasing conjugation. The reciprocal of thefrequency squared is nearly a linear function of the number of double bonds.Similar relationships are obtainable for dyes of cyanine type, e t ~ . ~The molecule of benzene is one of peculiar interest on these views.Fig. 8 shows six x orbitals of the “ aromatic sextet.” All these have a nodalplane in the plane of the ring. Orbitals 2 and 3 have in addition a nodalplane across the ring so that the two halves are out of phase; two orbitalsof equal energy but of opposite character are possible. The normal moleculehas a pair of electron8 in each of these three orbitals. On the absorptionSee, e.g., G.K. Rollefson and M. Burton, “ Photochemistry,” Prentice-Hall, N.Y ..1939, p. 248.Rev. Mod. Physics, 1942, 14, 29420 GENERAL AND PHYSICAL CHEMISTRY.Approx.Nodes o f T orbitals energy Wave- Orbita inumber - 7312 .e.----Molecular axis.--*- 71- 10-9- 8-7- 6-5- 4- 3- 2- IEthylene : CH ICH,.Butadiene : C&T=CH-CH=CH,.Octatetraene : CH2=CH.CH=CH.CH=CH.CH=CH2.fl-Carotene :CH,-C=C-(-CH=CH*CMe=CH-) 2-CH:CH-(-CH=CMe- CH=CH-) ,-C=C--C'HMe2 c/ \HZ\ /H 2 H2c-cFIG. 6.T Molecular orbitals of conjugated polyenes.Orbitals filled (i.e., containing two electrons) in ground state enclosed in rectangles.Passage of one electron from highest filled orbital to next higher orbital correspondsto longest-wave electronic absorption band of molecule (e.g., ethylene absorption =1750 A.; carotene absorption = 4600 A.).H2<P2 H, I-IBOWEN : ABSORPTION SPECTRA OF ORGANIC SUBSTANCES. 21of ultra-violet light, one electron passes to a higher orbital, 4, 5, or 6, whichhave extra nodal planes. It is clear that for light to be absorbed its planeCarotenePo/yene 20Polyene 5PoLyene 4Nap/ltha/ene Poi'yenes,B enz en c C, H 5 - (C H = C H),C gH 5.Each benzene ring i s countedas 2.5 doubfe bonds.Octate trazneButa dimeEthyleneI I I I I I I ' i 2 2 6 7 8 9 10 71 12Number of double bonds.FIG. 7.1 2 34 5 6FIG. 8.n Orbitals of benzene.of polarisation must lie in the plane of the ring, since the new nodal planesdeveloped on a,bsorption are at right angles to this plane (cf.above). Thi22 QENERAL AND PHYSICAL CHEMISTRY,effect is clearly shown in light-absorption (dichroism) and fluorescence-emis-aion phenomena in crystalline anthracene and its solid solutions withnaphthacene (tetracene), and in other aromatic crystals whose moleculesare orientated approximately in layers.6Orbitals 2-6 in benzene may be represented in a different but mathe-matically equivalent way; 2 and 3 may be regarded as formed by “ wrap-ping one wave-length round the ring,” clockwise or anti-clockwise, andsimilarly, orbitals 4 and 5 correspond to two waves wrapped round thering, and 6 to three waves. The nodal planes a t right angles to the ringrotate on this model.The discussion so far has been of a qualitative geometric character.If“ colour ” is to be put on a quantitative basis, it is important to attempt toapply the algebraic equations of wave-mechanics to organic molecules.This cannot be done directly because of the intractable nature of differentialequations of waves. The fundamental equation for a “ wave ” representingan electron in an atom is that due to Schrodinger : 7a2+ 8n2mwhere 4 is the amplitude of the wave a t any point whose co-ordinates arex, y, and x, m is the electron mass, and E and ‘v its total and potentialenergy respectively. For the hydrogen atom Y is of the form - e2/r, where eis the electroll charge and T its distance from the nucleus, and the differentialequation can be rigorously solved, giving the “ radius ” of the hydrogen atomand its energy levels which are in complete agreement with observation.Other atoms, and still more, molecules, have Y terms of more complicatedtype, so that the equation becomes insoluble.However, we may proceedroughly and tentatively along the following lines. Suppose we wish tocalculate the longest-wave absorption of ethylene. We disregard all thesingle bonds and imagine the two carbon atoms placed a t their knowndistance apart in the molecule. Each is assigned one electron in a 2~atomic orbital. Very roughly we may approximate to this orbital by usingthe Schrodinger equation as for the hydrogen atom, choosing a suitablevalue for the apparent nuclear charge of the carbon (since this is effectivelydiminished by the inner electrons of the atom).We thus have equationsfor #a and $8, A and B referring to the two atoms. The two atomic orbitalsare now imagined to coalesce to give a molecular orbital t,bH. Two differentmodes of approximating to tjJf have been developed. In the first (Heitler-London method) the electron configuration in the molecule is taken as thesum of the configurations of the separated atoms, and in the second (Hund-Lennard- Jones-Mulliken method) the molecular orbital is computed as alinear combination of the atomic orbitals. The chief difference in themethods is that the former neglects, and the latter over-emphasises, theMod. Physics, 1942,14, 336.- a2+ +$ + +,(E - V)4 = 0 ax2I<. S.Krishnen and P. K. Seshan, Proc. Indian Acad. Sci., 1938, 8, 487; Rev.See, s.g., H. S. Taylor, “ Physical Chemistry,” Vol. 11, Mecmillan, 1931BOWEN : ABSORPTION SPECTRA OF ORGANIC SWSTANCES. 23possibility of both electrons in a Link being simultaneously on one of thetwo atoms. Whichever method is adopted the calculation is then similarto that of the problem of finding the resultant frequencies of a vibratorcomposed of two coupled vibrators. A one-dimensional mechanical analogueis that of the frequencies of a system of two pendulums suspended from ahorizontal piece of elastic atretched between two points. In this wayapproximate energies of the molecular orbitals are calculable from theatomic orbitals, and hence the wave-hngths of absorption bands. Atpresent the approximate nature of such calculations does not recommendtheir direct use.8 The methods of approximate treatment have beenextended, however, to molecules with conjugated structures.The con-jugated polyenes may be treated by more than one method t o try to derivethe experimental relationship of the linearity of (absorption wave-length)2and number of double bonds (Pigs. 6 and 7).5 The orbitals resemble thevibrations (fundamental and harmonics) of a stretched string, or the o d -lations set up from side to side in a glass plate. The phenylpolyenes,C,H,*[CH:CH],*C,H,, or cyanine and related dyes containing the group>kCH-[CH=CH],--N<are somewhat more complicated because of the influence of the end groups,the orbitals resembling the oscillations in a plate sandwiched between twoother different plates. The mathematical problem is to combine a numberof vibrators (atomic orbitals) into one vibrating system to determine theresulting wave motion (molecular orbitals).Calculations along these linesare valuable for finding out how legitimate the approximations made arefor the estimation of molecular orbitals.The molecule of benzene has been very thoroughly treated by approx-imate methods, so its spectrum is now well understood.9 Two modes ofreaching solutions have been used. Attention is fixed only on the x orbitalsround the carbon ring skeleton. In the first (L.C.A.O. = linear combinationof atomic orbitals) method the lowest five or six molecular orbitals areconstructed by linear combinations of six equal atomic p orbitals withnodes co-planar with the ring, and their energies computed.The accuracyof this depends on the degree of approximation to which the lengthycalculations are taken. The energy of the x electrons in the ground stateof the molecule is then 2(0 + p + p), the energy of the lowest orbital being0 and that of the second and third p, each containing two electrons. Ahigher molecular level will have an energy 2(0 + p) + p + y, where y isthe energy of a higher orbital into which an electron from the second orthird orbital goes. These quantities are calculable (allowance being madefor the effects of electron spins). The second method (V.B. = valency bond)divides the problem of passing from atomic to molecular orbitals into two* R.S. MulIiken, J . Chem. Physics, 1939, 7, six papers; Rep. Progr. Phyeics, 1939,6, 212; Rev. Mod. Phyeics, 1942,14, 266. * A. L. Skler, J . Chem. Physics, 1937, 5, 669; 1938, 6, 645; 1939, 7, 374; Rev.Mod. Physics, 1942, 14, 23224 GENERAL AND PHYSICAL CHEMISTRY.artscial halves.1° Instead of attempting to evaluate the vibrations of ahexagonal assemblage of coupled p orbitals by direct combination, it pro-ceeds by first coupling the p orbitals in pairs to form ‘( valency ” structures,and then “ combines ” all conceivable valency forms. All modes of writingthe benzene molecule by “ valency ” symbols are set down, vix., two Kekuli:structures, three Dewar structures, and some “ ionic ” forms.The “ ener-gies ” of these hypothetical molecules are calculated by simple combinationof atomic p orbitals in pairs along the “ double bonds.” The energy levelsof the “ real ” molecule are then approximated to as linear combinationsof the valency structures, the coefficients of the linear combinations beingderived by the use of a determinant just as if the problem were one offinding the resultant vibrations of a complex vibrator having several differentfrequencies operating together, This method, of “ resonance betweenvalency structures,” enables the energy levels to be estimated if a parameteris known; and this can be derived by comparing the heats of hydrogenationof benzene and of cydohexadiene.Calculations along these lines show that the first three higher energylevels of benzene are 35-70 kg.-cals./mole above the ground state, andtherefore potentially capable of giving absorption bands in the visibleregion.Transitions to them, however, are “ forbidden ” because they are‘‘ triplet ” levels, involving change of electron spin on excitation. Thelowest “ permitted ” transition has a calculated energy change of 184 kg.-cals./mole, and is identified with the strong absorption band at 1800 A. inthe far ultra-violet (= 153 kg.-cals./mole). Benzene also shows a feeblerbut long-known absorption band at 2600 A . This is now identified withthe transition (expressed in symmetry notation) as lAlg (ground state)+lBZU (calc., 115 kg.-cals./mole). This transition is permitted only whensimultaneous changes in vibrations of the atomic nuclei of symmetry typeEg+ occur.The “ partial band ” structure of the 2600 A. benzene band dueto changes of nuclear vibrations shows a series of equally-spaced partialbands due to the accompaniment of the electronic activation by the excit-ation of nuclear vibrations of the upper state, one quantum of Es+ type(lengthening and contraction of hexagon) and 0, 1, . . . quanta of Algtype (symmetrical expansion and contraction ; “ breathing frequency ”).A fainter series arises from molecules of the ground level already with onequantum of Eg+ nuclear vibration passing to the upper state with 0, 1,quanta of Alg type; the intensity of this series increases with rising tem-perature owing to the increasing population of vibrationally excited groundstates.The frequency differences of the partial bands amount to 923 cm.-l,the value of the nuclear “ breathing frequency ” Alg of the upper state.The corresponding frequency of the ground state, obtained from the Ramanspectrum, is 992 cm.-l. No absorption occurs at the point correspondingto the electronic transition unaccompanied by the Eg+ nuclear vibrationalchange except in solid benzene a t low temperatures, where a feeble bandcan be recognised due to the partial removal of the quantum restrictionslo See L. Pauling, “ The Nature of the Chemical Bond,” Cornell Univ. Press, 1940BOWEN : ABSORPTION SPECTRA OF ORGANIC SUBSTANCES. 25owing to the distortion of the molecule from perfect hexagonal symmetryby crystal forces.The allied hydrocarbons naphthalene, anthracene,naphthacene, and pentacene show similar equally-spaced vibration bandstructure in their near ultra-violet absorption. These doubtless also corre-spond to symmetrical expansion and contraction frequencies, which increaseprogressively with the molecular weight in this series of molecules. Theelectronic excitation here is polarised in the plane of the ring and in thedirection of the greatest length of the molecule; other absorption bands a tshorter wave-lengths probably arise from excitation polarised in otherdirections in the molecular plane. Studies of dichroism and of the polaris-ation of fluorescence are needed to throw light on these matters.The replacement of carbon by oxygen or nitrogen in an organic com-pound does not greatly alter the energy values of orbitals of the typementioned ; hence little change occurs in the light absorption. Anthracene(I) and acridine (11), for example, have almost identical absorption bands,and only minor differences exist between those of such dyes as uranin,rhodamine, resorufin, (iso)quinoline red, safranine, and acriflavine, whichring the changes between C, 0, and N in the 9,lO positions of the anthracenestructure.Aldehydes and ketones have a strong absorption region a t1900 A., corresponding to the absorption of ethylene, and due to a xlL+xgorbital change in the CSO link. These substances also have a characteristicabsorption band in the longer ultra-violet, about 3000 A., of low extinctioncoefficients, but having no counterpart in ethylenic molecules.The originof this band must be sought in the oxygen atom. This has a shell of eightelectrons; one pair in a u9 orbital and one pair in a xu orbital are sharedwith the carbon in the C=O link. The other four must be in the tworemaining 2p orbitals of the oxygen, being in almost undisturbed atomicorbitals and taking little part in the chemical binding (two “ lone pairs ”).One of the orbitals of these “ non-bonding ” electrons will have its nodalplane normal to the link, and the other’s nodal plane will be along the linkand a t right angles to the nodal plane of the xl‘ bonding orbital. It hasrecently been shown l1 that the weak absorption characteristic of carbonylcompounds a t 3000 A.arises from an orbital change of one of these “ non-bonding’’ electrons, an electron passing from the p orbital whose nodalplane is a t right-angles to that of the xu orbital to the excited zg molecularor bit a1 .The absorption a t 3000 A. isaccompanied by the passage of one electron from the hour-glass shapedorbital d,d to the unoccupied anti-bonding molecular orbital b. The absorp-tion in the blue region by diazomethane and azomethane must be ascribedto similar orbital changes among the electrons in “ non-bonding ” atomic pl1 H. L. McMurry, J . Chem. Phy8iC8, 1 94 1, 9, 23 1.These orbitals are depicted in Fig. 926 GENERAL AND PHYSICJAL CHEMISTRY.orbitals of the nitrogen atom. The exact nature of the changes may beascertainable if precise determinations of the polarisation directions of theabsorbed light in oriented systems (crystals) prove possible.The lightabsorption of azobenzene in the blue appears to be of too long a wave-length to be analogous to the absorption of 1 : 2-diphenylethylene; hereagain, therefore, essentially non-binding p electrons on the nitrogen atomsprobably play the chief r61e.The organic dyes, by reaaon of their intense colour, variety of absorptionin the visible region, and commercial importance, have long been in the - - - - - - f l// h, , O H O - - -- --,/ \ 4’ \/ ’r ’ ’.FIG. 9.Orbitals of the carbonyl group S O .Thick lines = u, type orbitals (“ single links”),a = w,, orbital characterised by ti nodal lane in the H*CHO molecular plane.I tcontains two electrons in the ground state ofthe molecule.b = 7rg orbital characterised by one nodal plane in the molecular plane and anotherat right angles t o the C-0 link.c, c and d, d = non-bonding p-type orbitals of the oxygen atom, each containingtwo electroae in the ground state (“ lone pairs ”) ; c, c has a nodal plane at right anglesto the C-0 link and d, d one in the plane of the paper.Excitation of one electron from orbital a to b occurs on light absorption near 1900 A.,corresponding to the absorption of ethylene at 1750 A. The characteristic absorptionof carbonyl compounda near 3000 A. cauaes one electron to pass from orbital d to b.No electrons occupy this orbital in the ground state.forefront of older theories of colour and constitution.Before discussingthem here a few general remarks may be made. For a substance to benotable for its ‘‘ colour,” it must show two features, absorption in thevisible region of the spectrum, i.e., at long wave-lengths, and high values ofits extinction coefficients. In addition, the “ width ” of its absorption bandor bands determines the selectivity of its colour. Absorption a t longwave-lengths becomes possible when energy differences between molecularstates are small enough; high conjugation brings this about, as alreadydescribed for the polyenes, while changes in the orbitals of non-bonding ”electrons of nitrogen, oxygen, or sulphur may also be important (Figs. 6and 9). High intensity of tlbaorption, as measured by the integrated areBOWEN : ABSORPTION SPECTRA OF ORGANIC SUBSTANCES.27under the absorption curve (extinotion ooeffioientfrequency) is determinedby the “dipole transition moment,” which is roughly the charge shift onabsorption. Transitions are “forbidden ” if this is zero, as is sometimesthe case with molecules of high symmetry. Lowering of symmetry bymolecular vibrations, and still more by the introduction of substituents,then allows of absorption increasing in strength with the loss of the sym-metry. An example is found in the 2600 A. band of benzene, which is“ allowed ” by the co-operation of certain vibrations and is enhanced bythe presence of CH,, *OH, *NH,, or 421 in the molecule. Intensities ofabsorption in “ forbidden ” bands are also increased by the neighbourboodof a “ permitted ” transition.12 In dyes the extinction coefficients are verylarge, corresponding to molecular orbital changes almost equivalent to thetransfer of an electron acrow an interatomic distance, i.e., to the develop-ment of “ionic ” links in the molecule.Dyes also often have narrowabsorption bands. Band width is determined by the slopes of the upperpotential energy curve in the regions nearly vertically over the minimum ofthe lower curve (Franck-Condon principle). Owing to the flattening of theupper curve near its minimum a plot of extinotion coefficient againstfrequency is always steeper on the red than on the blue side of the band.Recent attempts to explain the “ colour ” of dyes have mostly been bythe use of the ‘‘ valency bond ” mode of approach, on lines such a8 thefoUowing.13 p-Nitrophenol itself is not “ highly coloured ” ; the intensecolour of its ion is attributed to the increased “ resonance ” between altern-ative electronic valency structures :Un-ionised.IonisedThe ions of phenolphthalein, (111) and (IV), of phenylene-blue, (V) and (VI),and of other xanthen, azine, cyanine, and triphenylmethane dyes may beb,H,*CO*O(111.)C6H,* CO 0(V.1 WI.)represented by approximate “ mirror-image ” valency structures whose“ resonance ” may be held to account for the colour. Perhaps this explan-ation by means of the artihial concepts of “ valency ” structures is a littletoo facile. Wedo not yet clearly understand the detail8 of the structure of the aboveL.Pauling, Proc. Nat. Acad. Sci.. 1939, 26, 677; L. C. 9. Brooker, Rev. Mod.The azo-dyes are not easily comprehended on this scheme.12 Rep. Progr. Physics, 1941, 8, 231.Phy8iC8, 1942, 14, 27525 GENERAL AND PHYSICAL CHEMTSTRY.dye ions in terms of the orbitals occupied by the electrons in both groundand excited states. Where ionisation leads to intense absorption, as withp-nitrophenol, we believe i t brings about a greater degree of “ non-local-isation ” of electrons in the molecule with new orbitals of small energydifferences. An important field awaits exploration by which semi-quantit-ative correlations may be established between such orbital changes anddye structure.Recent work has enabled interesting deductions to be made about thegeometrical nature of orbital changes when light is absorbed by dyes.14I n crystalline anthracene and naphthacene the long-wave absorption isfound to correspond to light polarised in the molecular plane and along theline of greatest width of the molecule, i.e., the accompanying orbital changeof the electrons involves the production of a new nodal plane normal to thisline.The visible absorption band of the fluorescein (uranin) ion a t 4950 A.also probably corresponds to light absorption polarised along the line ofgreatest width of the molecule. The emitted green fluorescence is alsopolarised along the same line. The same green fluorescence emitted whenlight is absorbed by an ultra-violet band of the uranin ion a t 3125 A.is“ negatively polarised,” i.e., its vibration direction is at right angles tothat of the light absorbed. It thus appears that the 3125 A. band corre-sponds to light absorption polarised along the short axis of the molecule,and that a rapid internal rearrangement occurs to the excited level reacheddirectly by absorption a t 4950 A., followed by fluorescence. At high con-centrations in water this dye (and many others) dimerises, and a new bandappears a t 4710 A. The polarisation direction of this band is unknown,but in the case of the dye $-isocyanine, measurements on molecules orientedon mica show clearly that the corresponding dimer band is polarised alongthe short axis, and the monomer band along the wider molecule axis.Atvery high concentrations, 4-isocyanine forms a peculiar fibrillar colloid witha new very narrow absorption band. The fibrils appear to be formed bythe stacking together of the flat molecules like piles of coins, and the newband is polarised along them and therefore normal to the molecular planes.We are thus enabled to identify three absorption regions with orbitalchanges in three mutually perpendicular directions in space in the molecule.In the fibrils the bonding forces must be of van der Waals type, possiblyinvolving intercalated water molecules ; yet the light absorption shows thatthe whole fibril behaves as a unit. This implies that there must be con-siderable overlap and intermolecular interaction between the ~i electronorbitals which bulge out from the molecular planes into the spaces betweenthe molecular pile.This interaction is optically sufficient to be called anelectronic linkage between the molecules, but it is certainly not strongenough to warrant representation by a “ chemical ” valency bond. Doubt-less the coloured compounds formed in the solid state between certain flatmolecules, as between 2 : 4-dinitrophenol and diphenylamine, also owe their14 G. N. Lewis and M. Calvin, Chem. Reviews, 1939, 25, 2 7 3 ; Ann. Reports, 1941,33, 23BANGHAM : PHYSICAL CHEMISTRY OF CARBONACEOUS MATERIALS. 29bands to the development of this somewhat elusive type of electronic inter-action of the x 0rbita1s.l~ The forces between the atomic planes of graphite,the peculiar behaviour of chlorophyll in plants where about 1000 moleculesappear to be energetically coupled as a “ photosynthetic unit,” l6 and thefluorescence of crystalline aromatic substances such as anthracene, chrysene,and diphenyl, which is so modified by minute traces of certain impuritiessuch as naphthacene as to require the assumption of the free movement ofelectronic energy (“ excitons ”) within the crystal, almost certainly owetheir features to a similar loose coupling of x electrons.E.J. B.(The 6 c pola.risation direction ” of light referred to above means diredtion ofelectric vector, not the conventional perpendicular direction used by earlyphysicists. )2. PHYSICAL CHEMISTRY OF COAL AND CARBONACEOUS RIATERIALS.The members of the coal series, together with their solid carbonisationproducts, appear to form a series of intermediate links between the ligninson the one hand and micro-crystalline graphite on the other.It is nowbecoming better understood that differences between the behaviour of onecoal and another, instead of indicating specific constitutional differences,may be more concerned with the aggregational states of the coal substance.Although F. Fischer,l W. A. Bone,2 R. V. Wheeler,3 and others assumedspecific constitutional differences between those portions of coal substancewhich could be extracted with the aid of solvents and those which resistextraction, yet the interpretation of their experimental results clearly requiresrevision in the light of new knowledge as to the solubility relations of highpolymer^.^ &.I.W. Kiebler has established a statistical correlation betweenthe internal pressures of a series of solvents at a given temperature and theirsolvent powers for coal a t that temperature.The behaviour of coal in technical use appears to depend upon allaggregational magnitudes from the molecular to the macroscopic lump,and i t will be clear from the foregoing that physical methods of examinationare often more advantageously applied than chemical in its study.Metamorphic Development of Coals.-Coals have been formed from decayedplant detrital matter which, becoming buried under other sedimentarydeposits, has become indurated and passed through various stages of meta-morphic development by the action of pressure and moderate heat.TheF. Fischer, H. Broche, and J. Strauch, Brennstoff-Chern., 1925, 6, 33.W. -4. Bone, A. R. Pearson, and R. Quarendon, Proc. Roy. SOC.. 1924,105, A , 608 ;C. Cockram and R. V. Wheeler, J., 1927, 700; 1931, 854; J. Ashmore and R. V.Compt. rend. Trav. Lab. Carlsbery, SBr. chim., 1938, 22, 99 ; J. N. Brensted andI n d . Eng. Chem., 1940, 32, 1389.l5 Cf. J . , 1943, 435. Ref. (4), p. 406.W. A. Bone, L. Horton, andL. J. Tei, ibid., 1928, 120, A, 523.Wheeler, J . , 1933, 1405.K . Volquartz, Trans. Paraday SOC., 1939, 35, 57630 GENERAL AND PHYSICAL CFIEMISTRY.metamorphic process whereby the carbon content of the deposit is increasedat the expense of the oxygen and hydrogen is usually described as increaseof rank, or, more briefly, as “ coalification.”Though the chemical changes which accompany (‘ coalification ” involvesplitting off part of the carbon (as carbon dioxide, methane, or both a), muchthe same topochemical factors are likely to be operative as in the later stagesof polymer-condensation reactions, and the prima facie resemblance of coalsto solid substances of the polymer-condensation type has been remarkedupon by several It has been shown inter alia by W.‘Francisand R.V. Wheeler that bright bituminous coals are readily converted bymild oxidation into alkali-soluble humic acids resembling those present inpeat. It appears, therefore, that during at least some of the evolutionarystages of coalification the inner structure of the molecules has remainedunaffected, the chemical change being confined to one or more of theperipheral groups.Although in a general way the continuity of the series peat-lignite-bituminous coal-anthracite is widely recognised,lO yet the first three membersdo not necessarily represent successive stages of development related to theage of the deposit; for instance, samples from the same seam in the SouthWales coalfield showed a consistent increase of rank on traversing the seamfrom east to west.11In the case just cited, the variation in rank appears directly related tothe degree of pressure metamorphism (A.Brammall and J. G. C . Leech 12have traced parallel metamorphic changes in the associated rocks), but othercases are known in which increase of rank has been brought about by quiteother agencies.For instance, fusain, a petrological constituent of highcarbon content, has been identified by E. McKenzie Taylor * in an Egyptianpeat of geologically recent origin, and by C . A. Seyler l4 in a Greek lignite.McKenzie Taylor l5 has pointed out that during the initial rapid decay of theplant material the permeability to air and water of the overlying deposit islikely to have a determining influence on the nature of the product. Heconsiders peat, lignite, and bituminous coals to be alternative end-products,formed, respectively, without a roof, under a roof which is freely permeabIe,and under a roof containing mainly sodium days which cause alkaline andanaerobic conditions to be closely approached.Coal Petrology.-It was pointed out by M.C. Stopes and by Stopes and6 G. Hickling, J . Inst. Fuel, 1932, 5, 326. ’ H. E. Armstrong, Chem. and Ind., 1929, 48, 760.M. J. L. Megson and K. W. Pepper, ibid., 1940, 59, 247.J., 1925, 127, 112; see also H. H. Lowry, J . Inst. Fuel, 1937, 10, 291.Seams,” London, 1939, p. 223.of the National Coal Resources, No. 55.lo A. Raistrick and C. E. Marshall, “The Nature and Origin of Coal and Coall1 Departmont of Scientific and Industrial Research, Physical and Chemical Surveyl2 Medical Res. Council Spec. Report Series, No. 244 (1943), 125.l3 Fuel, 1926, 5, 195.l4 J. Inst. Fuel, 1943, 16, 134.Fuel, 1928, 7, 230BANOHAM : PHYSICAL UHEMISTRY OF CJARBONACEOUS MATERIALS. 31Wheeler 16 that coal seams generally contain visibly distinct bands of organicmaterial conforming to types which they called respectively vitrain, clarain,durain, and fusain.Of these, the fist two are ‘I bright ” coals, the third isdull and usually hard, and the fourth dull and’friable (“ mineral charcoal ”).Although the refined methods of petrological analysis (referred to below)have thrown an entirely new light upon the inter-relation between these‘‘ banded ” constituents, yet the distinction between bright and dull coalsw i l l be repeatedly referred to in what follows, and it is convenient here toemphasise some points relating to their physical and chemical structure.Durain diEers somewhat in composition from the bright coal with which itit associated 17; it has a different pore structure (rendering it more per-meable to liquids, as Beeching18 has shown) and does not swell whencarbonised. According to R.Lessing,l9 its content of mineral matter isgenerally greater than that of bright coal. On the other hand, H. H.Lowry 20 emphasised that there was no evidence to show that the two classescontain distinct types of chemical compound, and their behaviour on the“ micellar ” scale of aggregational magnitudes appears not very different.21Fusain, which is much richer in carbon and poorer in hydrogen thanthe associated bright coal, is markedly more resistant to oxidation orhydrogenation.It is now recognised that the visibly-distinct “ banded ” constituents ofStopes and Wheeler l6 represent rock-types rather than homogeneous petro-logical components.The pioneering work of C. A. Seyler 2~ on the opticalproperties of coals appears to indicate the existence of physically homo-geneous components whose relation to the macroscopic lump can be com-pared with that of the constituent minerals in a piece of inorganic sedi-mentary rock. The main components derived from lignified plant tissueare limited in number (about ten), and each is characterised by its ownoptical reflectance coefficient. Since the reflectance coefficient is a functionof the refractive index and the absorption coefficient, and it appears unlikelythat a change in the one would just compensate for a change in the other, itmay be presumed that each of these constituents would represent a physico-chemical entity defined as t o composition and density of atomic packing,though minor variations in composition which leave the packing undis-turbed are not, perhaps, precluded.Values for the refractive indices of somecoals have been given by C. G. Cannon and W. H. George.22“ Bright ” coal (the vitrain and clarain of Stopes and Wheeler) is found bySeyler to be markedly less heterogeneous than “dull” coal (durain andfusain) , and generally contains one predominant c~nstituent.~~l6 PTOC. Roy. SOC., 1919, 90, B, 470; Fuel, 1923, 2, 5.I f F. V. Tideswell and R. V. Wheeler, J., 1919, 115, 619.l 8 R. Beeohing, J . Imt. Fuel, 1938, 12, 35; J. G. King and E. T. Wilkins, Con-19 Fuel, 1922, 1, 6.21 C. G. Cannon, M. Griffith, and W. Hirst, Conference, etc., London, 1943, p.131.21a C. A. Seyler, Proc. South Wale8 Inst. Eng., 1937,53,254; J . In&. Fuel, 1943,16,134.2 2 Conference, etc., London, 1943, p, 290.ference on the Ultra-fine Structure of Coals and Cokes, London, 1943, p. 46.J . Geology, 1942, 50, 357.23 C. A. Seyler, ibid., p. 27032 GENERAL AND PHYSICAL CHEMISTRY.Some Generalisations relating to Bright Coals.-Of the physical andchemical properties of coal substance, some (such as refractive index, opacitycoefficient, " volatile " content, and thermal stability) increase or decreasemonotonously with increase of rank, whilst others (notably calorific value," pore " volume, and extent of inner surface) pass through maximum orminimum values. The maximum (or minimum) generally occurs a t (ornear) the range of coking coals, characterised by their ability to form macro-scopic masses of maximum resistance to shattering impact when the crushedcoal is carbonised in ovens.The various empirical tests in use for the assessment of technical cokingqualities have been reviewed by R. A.Mott p4 and subjected to a searchingscrutiny by R. E. Brewer.25Evidence of X-Ray Crystallography.-Since the original discovery byP. Debye and P. Scherrer 26 of the pseudo-graphitic nature of the" amorphous " carbons, numerous workers 27 have attempted to trace thechanges in the aggregational state of carbonaceous materials by using X-raymethods. The basic assumption is made that the substances are essentiallymicrocrystalline and that the size of the " crystallites " can be found frommeasurements of the degree of line broadening on the X-ray photographs.The rigorousness of this procedure has been questioned28 on the groundsthat other factors such as disorder and strain can contribute to the breadthof the diffraction lines, and the absolute values of crystallite size so obtainedare therefore somewhat open to question.Moreover, as will appear later,in some cases, e.g., lignin, it is by no means certain that we are dealing with" aromatic " crystallites a t all.Provided, however, that the X-ray measurements are made strictlycomparative, the calculated " crystallite dimensions " can a t the very worstbe regarded as an index of the degree of order (in an otherwise disorderedstructure) and as such are of unquestionable value.There is remarkablygood agreement between different workers 29 as to the size of the " crystal-lites," and notwithstanding the doubts expressed as to the interpretation ofline-broadening data, it will be convenient to follow H. E. Blayden,J. Gibson, and H. L. Rile~,~O who have carried out the most extensive workon coals, cokes, and chars, in regarding the crystallites as structural entities.I n general, the model arrived a t by the X-ray workers is that coal andits carbonised products consist largely of platelets in considerable disorder.2* Fuel, 1942, 21, 51.2 8 PhysikaZ. Z., 1917, 18, 291.2 5 U.S. Bureau of Mines, Bulletin 445, 1942.U. Hofmann, Ber., 1928,61, 435 ; I. D. Sedletzky and B. Brunowsky, KoEloid-Z.,1935, 73, 90; R.Jodl, Bremnstoff-Chesn., 1941, 22, 78, 157, 217, 256; H. L. Riley,Trans. I n s t . Min. Eng., 1038, 95, 48.28 W. A. Wooster, Contribution to Discussion, Conference on Ultra-he Structiireof Coals and Cokes, London, 1943, p. 254.2* I. D. Sedletzky and B. Brunowsky, KoZEoid-Z., 1935,73,90 ; G. Agde, H. Schuren-berg, and R. Jodl, Braunkohle, Feb. 1942; H. E. Blayden, J. Gibson, and H. I,. Riley,Conference, etc., London, 1943, p. 176.so Ibid., p. 176BANGHAM : PHYSICAL CHEMISTRY OF CARBONACEOUS MATERIALS. 33Each platelet consists of a small number of layer-planes, the carbon atoms ineach layer-plane being arranged hexagonally (as in graphite) but the edgeatoms being linked to peripheral groups containing the non-carbon atomspresent, which limit the growth of the platelet.Of the numerous diffractionlines which characterise the prototype graphite structure, however, onlytwo generally appear in the case of coals and their carbonisation products(carbonised below lOOO"), these being related respectively to the interlayerspacing and the C-C bond distance. One reason for this (pointed out byB. E. Warren 31 for the carbon blacks) may be that the layer planes, althoughparallel, are arranged a t random so that the carbon atoms do not satisfy theconditions either for a true hexagonal lattice, as in gra~hite,~2 or for a truerhombohedra1 lattice, as in the form of graphite described by H. Lipson andA. R. Stokes.33 This type of " shuffle " disorder is called by Warren a" turbostratic " system.The crystallographic changes accompanying coalification and carbonis-ation have been followed by Blayden, Gibson, and Riley; 30 using the line-broadening method, they find strong evidence of growth factors common toboth processes. Two crystallite dimensions are quoted, the a (parallel tothe layer planes) and the c (normal to the layer planes), and, in accordancewith Warren's theory for turbostratic systems, a modified expression is usedin the former case. The c / 2 (interlayer) spacings found for coals, cokes, andchars by Blayden, Gibson, and Riley are all slightly greater than the value3.35 A.for graphite. According to A. the a spacings derived fromtheir data are normal (ca. 2.46 A.) when correction is made for the " cross-grating " effect by the method devised by B.E. Warren.35 Both with thecokes and the coals the a dimension (platelet breadth) increases slowly withcarbon content until ca. 90% of carbon is reached, whereupon it increasesrapidly. The c dimension (platelet thickness) also increases with the carboncontent up to ca. 92% of carbon, slowly at first and then more rapidly, butthereafter it decreases quite rapidly, indicating a more disordered stackingof the platelets as lOOy& of carbon is approached. Viewed in greater detail,the processes of coalification and carbonisation show less similarity, and it isclear that the nature of the starting material exercises an important influencewhich persists to very high temperatures. Thus they find that the charsprepared from pure cellulose, lignin, and glycine, whilst showing withincreasing temperature of carbonisation (and therefore increasing carboncontent) a growth in the a dimension similar to that with the carbonisedproducts from bituminous coals, give constant values for the c dimensionuntil 1400" is reached.At still higher temperatures, and consequentlygreater carbon content, growth in this direction occurs, slowly for celluloseand lignin and rapidly for glycine. Pusain, a friable charcoal-like constituentof coal seams, behaved similarly. Samples of peat and brown coal, on thes1 J . Chem. Physics, 1934, 2, 551 ; J. Biscoe and B. E. Warren, J . Appl. Physics,s2 J. D. Bemal, Proc. Roy. SOC., 1924,106, A , 749.s4 Nature, 1942, 150, 462.1943, 13, 364.3s Nature, 1942, 149, 328.9 5 Physical Rev., 1942, 49, 693.REP.-VOL.XL. 34 GENERAL AND PHYSICAL CHEMISTRY.other hand, showed marked growth in the c dimension a t temperatures belowlOOO", as well as pronounced increases in the a dimension.Blayden, Gibson, and Riley 30 indicate other peculiarities in the powderphotographs of bituminous coals and their carbonised products. The bandindexed as 002 was found by them to be asymmetric and was thereforeresolved into two symmetrical constituents, The additional band, pre-viously reported by C. Mahadevan,36 has been called by these workers they-band, and is attributed by them to large lamellar molecules held togetherby relatively weak intermolecular forces, the interlayer spacing being greaterthan 4 A.The y-band is especially conspicuous with those constituents ofbituminous coal which are soluble (or can be dispersed in) pyridine, i.e., they-compounds of Wheeler.3 It tends to disappear in the course of coalifi-cation or carbonisation and is absent in the high-rank anthracite.The lamellae responsible for the y-band are considered to be only partlyaromatic, and are therefore somewhat buckled, and the various groupsattached to the periphery lead t o less close packing. Carbonisation andcoalification are both accompanied by aromatisation-the buckled lamellaetend to flatten out and pack together more closely, and the y-band to dis-appear. Blayden, Gibson, and Riley suggest that it is this process whichcauses a decided increase in the c dimension a t temperatures up to 500".These workers also distinguish between two types of turbostratic system,mobile and rigid, rigidity being a function of the amount of oxygen attachedto the lamellze.In a general way these findings of the X-ray school of workers are inharmony with W.A. Bone's view37 that coal substance is essentially aromatic,and that the degree of aromatisation increases as coalification or carbonis-ation proceeds. Not wholly satisfying in this connection, however, are thefindings of I. D. Sedletzky and B. Brunowsky38 and of R. Jodl 39 that thetwo characteristic X-ray diffraction lines (to which nearly all the aboveevidence refers) are also given by Zignin, to which a cross-linked polymeric,and not a polynuclear aromatic structure is now assigned.40 D.P. Riley 41and also W. A. Wooster 28 have critically reviewed the crystallographicevidence which can unequivocally be derived from such diffuse X-ray photo-graphs as are given by members of the coal series.A principal characteristic of X-ray diffraction photographs of carbonaceousmaterials is the large amount of scattering a t low angles, even when a well-collimated beam of monochromatic (crystal reflected) radiation is used. Theeffect, first observed by P. Krishnamurbi42 for carbon blacks, has beenshown by A. Guinier 43 to be related to the scattering produced by gases, andoriginates in a random arrangement and loose packing of constituent particles.The method, which can be applied to give measurements of true particle36 Fuel, 1930, 9, 574.3Q Brennstoff-Chem., 1941, 22, 78, 157, 217, 256.41 Contribution t o Discussion, Conference, etc., London, 1943, p.256.4 2 Indian J . Physics, 1930, 5, 473.37 J . SOC. Chem. Ind., 1935, 54, 1048. '' Kolloid-Z., 1935, 73, 90.4O Ann. Reports, 1942.43 Thesis, Univ. of Paris, 1939BANGHAM : PHYSICAL CHEMISTBY OF CARBONACEOUS MATERIALS. 35size; has been used for the study of colloids of the dried-gel type. J. Biscoeand B. E. Warren44 have used the technique to study carbon blacks, andshow that the true particle or aggregate size is often many times greaterthan that of the crystallite itself as deduced from the usual line-broadeningmethods. Using a somewhat similar technique, D. P. Riley45 has shownthat, although the " gas " type scattering, indicative of large lacune in thepacking of structural units, is present both with anthracite and with coth oflow carbon content, yet the Welsh coals examined gave a diffuse rhg'indi-cative of the close-packing characteristic of liquids.From the mean diameterof the ring it is possible to calculate the mean particle size, and Riley thusfinds evidence for the existence of structural units of 30-35 A. diameter inthe coals in question. He also infers from the relative absence of diffusescattering from Welsh coal samples known to contain minerals of the mica orkaolinite types (but in which the coal substance was nevertheless present inpreponderant amount) that the degree of disorder of the organic matter isliable to become greatly reduced by intimate contact with inorganic layerstructures. The identification by X-ray methods of the minerals 60 associatedwith Welsh coals has been carried out by G .Nagelschmidt and D." Fibre " type X-ray photographs, indicative of preferred orientation ofstructural units persisting throughout the specimen, have also been reported 47in coals in which macrocrystalline inorganic matter was probably absent.These were in all cases anthracites, and it is perhaps significant that W. A.and N. Wooster 48, in the course of a survey of the diamagnetic properties ofBritish coals, found unequivocal evidence on anisotropy only in anthracite.Seyler 23 has shown that the anthracites, unlike the bituminous coals of lowerrank, generally show considerable optical anistropy.Adsorption Studies.-Some of the earlier studies of coal properties areopen to the objection that chemical " reactivity " was frequently confhsedwith the accessibility of the surface to the attacking molecules.Coals amstrong adsorbents, and J. I. Graham,49 H. Briggs and R. P. Sinha,60 ahdL. Coppens 51 have pointed out that the methane they contain is present(at least in greater part) in the form of adsorbed films. A systematic studyof the adsorptive capacities of British coals has recently been made byM. Griffith and W. Hirst 52 with the object of correlating their behaviour oncarbonisation and combustion with the extent of the inner surface. Itappears that up to a point the process of " coalification " is associated witha loss of inner surface and is therefore analogous to the syneresis or ageingof a gel.In the range of coking coals, however, the inner surface passesthrough a minimum, and increases again as the coals become more anthracitic.These results are in harmony with the earlier findings of King and Wilkins l8that the porosities of coals are minimal in the intermediate range, and increaseu J . Appl. Physics, 1942,13, 364.4 6 Ibid., p. 240.Conference, etc., London, 1943, p. 322.bo Proc.Roy. SOC. Edinburgh, 1936,53,48.5 2 Conference, etc., London, 1943, p. 80.45 Conference, etc., London, 1943, p. 232. '' H. G. Turner and H. V. Anderson, Fuel, 1932, 11, 262.4s Trans. Imt. Min. Eng., 1937, 04,122.61 Bull. SOC. chim. Be&., 1935, 44, 21536 GENERAL AND PHYRTCAL CHEMISTRY.both with lower and with higher rank ; also with D.P. Riley’s 45 resultsfor the low-angle scattering of X-rays which indicate that these coals ofintermediate rank show the nearest approach to a close-packed liquid-typestructure. I n view of the “plastic ” nature of coal substance (even a tordinary temperatures) it is reasonable to associate the large inner surfaceof the coals of high oxygen content with some form of oxygen cross-linking,and that of the anthracites with carbon-carbon cross links.The chief interest of these adsorption studies lies in the attempts to devisetechniques for the absolute evaluation of the surface area per unit weight ofmaterial, and to correlate with other methods of measurement the “ micellar ”sizes calculated therefrom.The term “ micelle ” is here used to denoteregions impenetrable to the films of the adsorbed substances and withoutimplications as to their degree of mutual detachment.Evidence of a micellar structure for charcoal is to be found in the experi-ments of Bangham and his co-worker~,~~ who measured the linear swellingof blocks of charcoal when exposed to gases and vapours, an effect originallydiscovered by F. T. Meehan.54 It was found that the swelling is proportional,not to the quantity of gas or vapour adsorbed, but to the free energy decre-ment of the charcoal as calculated from Gibbs’s equation :m,dG, + m2dG, = 0where m, is the weight of vapour adsorbed per g. of charcoal and GI and G,are the partial free energies per g.of adsorbate and adsorbent respectively.*This equation applies to any two-component system in equilibrium. Bang-ham, Fakhoury, and Mohamed 53 found justification, however, for identifyingthe free energy decrement (-AG2) of the adsorbent with the decrease ofsurface energy due to the formation of a film, for, in so doing, they obtainedtwo-dimensional equations of state similar in all respects to those character-istic of adsorbed films on liquids. This point was tested further by measure-ments carried out with the series of lower alcohols as adsorbates. It wasfound that the films reproduced in detail the equations of state derived fromthe data of H. Cassel and F. Salditt 55 for the adsorption of the same vapourson mercury.Before discussing the bearing of these results on the evaluationof the surface ateas of porous carbons, it will be convenient to mention theirimplications regarding the “ micellar ’’ structure of such carbons.The direct proportionality between the swelling and the surface-energylowering becomes intelligible if we regard the block of solid adsorbent as con-sisting of micelles adhering to each other by the action of surface forcestending to deform them by increasing the areas of contact between them.The micelles being supposed to behave elastically, it then becomes under-standable that a, mechanical force such. as would arise from the film “ pres-53 D. H. Bangham and N. Fskhoury, Proc. Roy. SOC., 1930, 130, A , 81 ; J . , 1931,1324; D. H.Bangham, N. Fakhoury, and A. F. Mohamed, Proc. Roy. SOC., 1932,138, A,162; 1934,147, A , 152; D. H. Bangham and R. I. Razouk. ibid., 1938,166, A , 572.Proc. Roy. SOC., 1927, 115, A , 199.* It will be clear that with such material as charcoal the more usual equation in5 5 2. physikal. Chem., 1931, 155, 321.terms of partial molar free energies cannot be usedBANQHAM : PHYSTCAL CHEMISTRY OF CARBONACEOUS MATERIALS. 37sure” should cause a proportionate movement. Of interest in this con-nection are some measurements by J. Sandor 56 of the electrical resistivitiesat different temperatures of carbonised artefacts of compressed coal in avacuum and in the presence of vapours. Sandor found that, whilst thepresence of the vapour markedly increased the resistance a t a given temper-ature, the energy barrier to the passage of electrons (shown by a linear plotof log resistance against 1/T) remained ~naffected.~’ Though capable ofother interpretations, these results appear most readily explicable if wesuppose that the resistance is determined by the areas of contact betweenthe micelles, which are reduced by the presence of films.On the basis of a model which makes no assumptions of critical importanceas to the shape of the micelles (or their degree of detachment from theirneighbours), but assuming that the swelling is resisted by elastic forces,D.H. Bangham and F. A. P. Maggs 5* have calculated from adsorption andswelling data values for elastic constants of coals for comparison with directlymeasured values of Young’s modulus.I n view of the fact that these lastwere measured in compression, and that the elastic forces called into playare by no means identical in the two cases, the order of agreement foundbetween the two sets of results must be considered satisfactory. Betteragreement was found with monolith samples of coals than with compressedartefacts, prepared from powdered coal.Absolute Ewalmtion of Surface.-The calculation of elastic constants fromadsorption and swelling data involves only the free-energy changes relatingto unit weight of adsorbent, so a comparison with the directly determinedYoung’s modulus affords no independent evidence as to the adsorbing area.’For the latter purpose, however, we have the comparison of the two-dimen-sional equations of state of the alcohol films on charcoal and on mercury.Directly comparable with the usual diagrams in which the product PA isplotted against F ( F = surface-tension lowering; A = area per molecule)we have the “molecular expansion” graphs in which the expansion perg.-mol. is plotted against the expansion.By so adjusting the scale of thelatter graphs as to obtain the best coincidence with Cassel and Salditt’s datafor the series of alcohols, Bangham s9 was able to assign values both to thearea of the charcoal and to the constant A of the equation x = 13, where xis the percentage linear expansion of the charcoal. This method makes noassumption as to the films being unimolecular, and, in point of fact, Casseland Salditt’s data show clearly that on mercury they were not so.Both onmercury and on charcoal the orientation appears to have been of an unusualkind, and, in the case of each of the alcohols, two distinct types of film wererecognisable. The graphs are reproduced in the figure. No evidence wasfound of thicker films being formed (for a given surface pressure) with thelengthening of the carbon chains.Having thus established the adsorbing area of this charcoal, Banghamand his co-worker6 measured its heat of wetting in methyl alcohol, thus5E Conference, etc., London, 1943, p. 342.Conference, etc., London, 1943, p. 118.5 7 J. Sandor, private communication.59 Proc. Roy. SOC., 1934,147, A , 17538 GENERAL AND PHYSICAL CHEMISTRY.enabling the heat of wetting per unit area of carbon to be calculated.Thisdatum enables the surface area of an unknown carbon to be evaluated fromits heat of wetting in this liquid. Further reference to heat of wettingmethods for the evaluation of surface areae is made later.The general similarity of behaviour as regards phase changes and equationsof state of physically adsorbed films on s6lids and films on liquids has beenemphasised by S. J. Gregg,so who points out that in favourable cases themonolayer capacities per g. of adsorbent can be calculated from the form ofthe FA curves even though the isotherm may not be of the Langinuir type.d/ cd'r 0.0 0.20 0 20/'TXP- ,ACx x0 0/0/ O - 1000..xftx x- 5 0 0I I4 0o n-Bufy/ a/coho/. Benzene.A n-Propg/ a/cohol:x Ethyl alcohoL u Methyl a/coho/A,-Molecular expansion curves for films adsorbed on charcoal (reduced to 0").Time-dependent observations relating to unstable films thus --.Time-independent observations relating to stable films thus - - - - - -.for films on mercury at 50" (Cassel and Salditt).B.-Abscissa, values of P ; ordinates, values of FA (P in dynes, A in Angstroms)The further calculation of adsorbent areas, however, involves assumptionsas to the molecular orientations and cross-sectional areas.Method of Brunauer and Emmett.-A method now widely used in Americafor determining surface areas has been developed by S. Brunauer and P. H.Emmett.61 In their attempts to estimate the surface area of an ironcatalyst, these authors found that the adsorption of carbon monoxide a t-183" was in part irreversible, and that although the reversibly adsorbedportion obeyed an isotherm very similar to that of nitrogen at this temper-ature, yet the total adsorption was nearly double this.They concluded thatthe innermost layer of carbon monoxide was irreversibly chemisorbed.J., 1942, 697.J . Arne?. Chem. SOC., 1937, 59, 1553; S . Brunauer, P. H. Emmett, and E. Teller,ibid., 1938, 60, 309BANGHAM : PHYSICAL CHEMISTRY OF CARBONACEOUS MATERIALS. 39Uaing this clue as to the monolayer capacity, they examined the isotherms ofa number of other gases in order to decide how best to calculate themonolayer capacity in cases of physical adsorption where the isotherm issigmoid, i.e., concave to the pressure axis at low pressure and becomingconvex aa saturation is approached, The best agreement was obtained byconsidering the monolayer complete (and layer thickening to begin) a t thepoint where the curve ceases to be concave to the pressure axis and thecentral linear portion begins.In a later paper these authors attempted a theoretical justification of theprocedure adopted, based upon the detailed balancing of the rates of con-densation and evaporation in the different layers.If so, s*, <q, . . . si arethe areaa of adsorbent covered by 0 , 1 , 2 . . . i layers, and E l , E,, E, . . . Eithe corresponding adsorption energies in these layers, then according toBrunauer and Emmett we should havea l p o = b,sle-EIIRTa2ps1 = b2s2e-EJRT..aipsi, = bisie-h’@Twhere a,, a2, etc., are constants relating the pressure p to the number ofmoleodes arriving in a given area in a given time, and b,, b,, etc., are similarconstants relating to their departure. The total area A is then given by ofand the (averaged) number of layers n present a t equilibrium byn = xi i.-0 = iSi /$=om 8,The simplifying assumption is now made that with the exception of E ,all the adsorption energies E,, E,, etc., are equal to the normal energy ofliquefaction of the vapour E s ; and that the terms a2, b,, a3, b,, etc., are suchthat their ratios a,&, a,/b, . . ., etc., can be equated. The relations givencan then be used to derive the equationwhere c approximates to e(E1-Ez)IRT and p , is the saturation pressure.Mono-layer capacities are computed by plotting p / y ( p - p,,) against p3/po,where y is the adsorption value at p .The above equation reproduces fairly accurately the sigmoid isothermalsup to pressures of ca.0.35 of saturation, and the monolayer capacities calcu-lated are in general agreement with those given by Brunauer and Emmett’searlier graphical method. The theory has been extended to cases where thewidth of the pores is ao small as to set a limit t o the layer thickening. Wherethere is space for only a single layer of molecules the isotherm reduces to anequation of the Langmuir form in which, however, the saturation pressureatill appears40 GENERAL AND PHYSICAL CHEMISTRY.The assumptions made by Brunauer and Emmett are clearly too crudefor the equations to be of wide validity, or even of great theoretical signifi-cance.As S. J. Gregg 62 has pointed out, the appearance of the term poin the case of gases above their critical temperature is wholly anomalous.No account is taken of orientational effects which give rise to phase changesin the innermost layer, or of the fact that, where supersaturated vapour canpersist in contact with the solid, the adsorbed film must necessarily be offinite thickness and, as a phase, thermodynamically distinct from the bulkMoreover, the assumption is made throughout that the whole ofthe exposed surface of an incomplete layer is available for condensation,without allowance being made for the disorder arising from the lateralmobility of the molecules.D. H. Bangham and N. Fakhoury 6* have givenevidence that in a mobile monolayer the space available for the condensationof further molecules ofjnite size involves an exponential term which becomesimportant when the surface is only half covered. I. Langmuir, it may berecalled, derived his simple isotherm by assuming that adsorption occurredonly a t lattice points, these being sufficiently widely spaced for each toaccommodate one adsorbed molecule.Notwithstanding these drawbacks, Brunauer and Emmett’s methodundoubtedly gives consistent results which agree fairly well with independentestimates of the adsorbing surface in cases where these can be made. Theassumption that the difference between the adsorption energy and the heatof liquefaction becomes small once the first monolayer is (more or less)complete appears well supported by independent 66 thoughexceptions are Outside the innermost layer, the difference betweena thick adsorbed film (in equilibrium with vapour at a fraction of saturation)and the bulk liquid must relate to differences of entropy rather than ofenergy in the two states and requires a model capable of refined statisticaltreatment for its elucidation.The fact that the typical sigmoid isotherms indicative of layer thickeningare so much more commonly encountered with finely particulate than withporous solids has given rise to the suspicion that with the latter there is noroom for their development.Although prima facie there is much evidencefor this suggestion, yet the swelling of the solid must not be overlooked inthis connection.Coal and cellulose appear to be examples of porous solidst o which the generalisation does not apply. Sigmoid water isotherms forwater adsorbed on charcoal are also of frequent occurrence.Methods based on Heat-of-wetting Determinution.-F. E. Bartell and Y. Fu68pointed out that, given the value of the wetting energy per unit surface,D. H. Bangham and R. I. Razouk, Trans. Faraday SOC., 1937, 33, 1459; D. H.J . , 1931, 1324.82 Conference, etc., London, 1943, p. 110.Bangham and Z. Saweris, ibid., 1938, 34, 554.6 5 D. H. Bangham and S. Mosallam, Proc. Roy. SOC., 1938, 166, A , 558.66 S. J. Gregg, J . , 1943, 351.6 7 D. H. Bangham and R. I. Razouk, Proc.Roy. SOC., 1938,166, A , 572.g 8 Coll. Symp. Ann., 1930, 7, 138BANGHAM : PHYSICAL CHEMISTRY OF CARBONACEOUS MATERLALS. 41a simple measurement of the heat of wetting of a porous solid would sufficeto assess its surface. These authors failed to take into account the contribu-tion of the adsorption energy to the wetting energy.63 More recently, R. I.R a ~ o u k , ~ ~ and M. Griffith and W. Hirst 52 have described routine techniquesfor the measurement of heats of wetting based on the method first used byH. C. Porter and 0. C. Ralston.'O Methyl alcohol was used by Banghamand his co-workers, since the energy changes per unit surface were believedto be known from the swelling experiments with charcoal, and an independentcheck on the adsorption data was available in A.S. Coolidge's 71 results.There was also reason to believe that on account of its polar-non-polarcharacter the wetting energy would be less susceptible to the presence orabsence of polar oxygen-containing groups such as coals are liable to contain.F, A, P. M a g g ~ , ~ ~ who studied the adsorption of methyl alcohol and n-hexaneby coal, was able to obtain values for the specific surface, both by Gregg'sand by Emmett's method of calculation, in fair agreement with thosecalculated from the heats of wetting (in methyl alcohol) and the wettingenergy per unit surface derived from Bangham's data for charcoal.The choice of wetting liquid is, however, most important from the stand-point of the rapidity of heat liberation.With liquids of more complexmolecular structure the heat liberation-even with a well-evacuated carbon-may continue for hours, and a fictitiously small value necessarily results in acalorimeter subject to heat losses. Methyl alcohol liberates the heat rapidly,and with this liquid good agreement was found by Griffith and Hirst 52 onchecking their results with the aid of an ice calorimeter.A method for measuring the areas of non-porous, finely particulate solids,which appears wholly unassailable from the theoretical standpoint, has beensuggested by W. D. Harkins and G . J ~ r a . ~ ~ These authors first saturate thepowder with the vapour of the wetting liquid, allow the heat of adsorptionto become dissipated, and then measure the heat of immersional wetting.The choice of liquid is limited to those known to wet the solid completely(zero contact angle) in the presence of its saturated vapour, and the energychange per unit surface is equal to the total surface energy of the liquid.Unfortunately, the limitation is serious, for liquids of high surface tension(such as would give large energy release per unit interface) do not as a rulegive complete wetting; moreover, the obligation to prove that the contactangle is really zero under these conditions may not easily be met.Structural Changes in Coals and Carbons on Heating.--It is well knownthat chars heated above 800" (the actual temperature depends markedlyon the starting material) lose much of their adsorptive capacity unless theheating is carried out in an atmosphere that promotes activation.Withcompressed artefacts the deactivation is often accompanied by pronouncedshrinkage and increase of mechanical strength (elasticity) 5* and is probablyJ . Physical Chem., 1941, 45, 179.' 0 U.S. Bureau of Mines, Tech. Paper, No. 113.J . Amer. Chetn. SOC., 1924, 46, 596.7 z Conference, etc., London, 1943, p. 95. J . Chenz. Physics, 1943.B 42 GENERAL AND PHYSICAL CBXMISTRY.due to some form of sintering. F. A. P. Maggs 74 has shown that the innersurface becomes progressively inaccessible to sma,ller and smaller moleculesas the temperature is raised, and very long times are required for the estab-lishment of equilibria.G. Wlner, E. Spivey, and J. W. Cobb 75 have traced the changes ofdensity, adsorptive capacity, and reactivity (towards carbon dioxide at 900')of a series of chars prepared from cellulose, sugar, bituminous cod, andanthracite on heating to different temperatures.These authors attributeadsorptive capacities of the products to the gasification of nuclear carbon byoxygen surviving in the char at temperatures above 500".Extensive studies of the structural changes accompanying the carbonis-ation of coals (in inert gas) have been made by C. G. Cannon, M. GrifEth,and W. H i r ~ t , ~ ~ who used the heat of wetting in methyl alcohol as a measureof inner surface. Though some variation of the wetting energy per unitsurface is not perhaps precluded, there are strong indications that suchvariations are not responsible for the highly characteristic curves obtainedby these authors by plotting the heats of wetting against carbonisationtemperature.The curves for coals of low and intermediate rank pass through at lea&two maxima, high-rank coals through only one.A remarkable feature ofthe results is the evidence for the persistence of some of the inner surfaceeven in coals cooled from temperatures a t which they have " softened " andbecome nearly fluid. Moreover, the microcapillary structure characteristicof each kind of coal reappears in products heated beyond this softening stage.When the carbonisation is carried out in a pressure bomb the general featuresof the curves remain unchanged, though the maxima are displaced somewhat.These results have this much in common with the X-ray line-broadeningdata of Blayden, Gibson, and Riley,30 that in both cases there is evidenceof the development, with rise of temperature, of a less open (or more ordered)structure, the process being interrupted at intermediate temperatures in thecase of medium and lower-rank coals.Elastic and Rheological Properties of Coals.-Studies of the elastic andrhedogical properties of coals are rendered difficult by the fact that naturalmonolith samples invariably contain internal cracks which greatly influencetheir behaviour.Exhaustive studies 77 of the size-distribution laws ofbroken coal (valid from the lump-sized material right down to sub-sievesizes) have led to the conclusion that cod lumps are traversed by a randomsystem of pre-existing cracks.These flaws are probably of a grosser orderof magnitude than the micellar or micropore structure, though they may wellowe their existence to unequal shrinkage consequent upon the desorptionof volatile constituent^.^^74 Conference, etc., London, 1943, p. 147.7 6 Conference, etc., London, 1943, p. 131.i7 J. G. Bennett, J. Inst. Fuel, 1936-1937, 10, 22, 105, 210; J. G. Bennett, R. L.Brown, andH. G. Crone, ibid., 1940-1941, 14, 111, 129, 135.' 8 D. H. Banghsm, Conference, etc., London, 1943, p. 18.7 5 J., 1943, 578BRlTTON : APPUCATION OF ELECTROMETRIC METHODS. 43In spite of these difficulties C. A. Seyler 79 was able to measure theviscosity coeffioients of coals in the “ softening ” range of temperatures, andto show that their temperature dependence is of the usual Arrhenius-equationtype. Apart from Seyler’a results, there is a distinct paucity of data relatingto the rheological properties of coals.In other fields, notably those relatingto glasses 80 and polflerised resins,*l such studies have yielded valuableinformation as to structure.It has been demonstrated by R. G. H. B. Boddy B2 that coal substancecan be made Co flow at ordinary temperatures provided the deforming forcebe great enough. The response to small forces is almost entirely elastic.Boddy’e method is to apply prewure to a field of coal particles enclosedbetween a microscope slide and the cover glass. The particles spread to formcoherent films which can be made to flow into one another and are thinenough to be transparent.Even anthracites and fusains (with carboncontents ranging as high as 95%) can be made t o show this effect. Dis-cussing measurements (by Berkowitz) of the variation with temperature ofthe critical force which must be applied, Bangham 78 has pointed out thatprim facie the deformation-force-temperature characteristics of coals aresimilar to those found by G. Tammann for the typical thermoplastic resincolophonium. It is inferred that very small stmctural units (perhapsidentifiable with the “ micelles ”) are held together by secondary forces ofthe van der Waals type. D. H. B.3. THE APPLICATION OF ELECTROMETRIC METHODS TO THE STUDY OFSOME IONIC REACTIONS.Electrometric methods afford a means by which chemical reactions canbe fouowed as they actually take place in solution, and it is the purpose of theReporter to give a r6sum6 of the work which has been carried out along theselines.Certain branches, however, of electrometric investigations, such asthose on heteropoly-acids and complex formation between metallic oxidesand hydroxy-acids, are as yet incomplete, and have therefore been omitted.Precipitation of Hydrozides.-Although metallic hydroxides are rarelyprecipitated in states which correspond with the formulae usually ascribedto them, e.g., Al(OH),, Cu(OH), (the amounts of water always being higherthan those indicated by the simple hydroxide formuls), the conditions underwhich precipitation occurs are largely governed by the solubility productsof the hydroxides.when considered in terms of the ordinary hydroxideformulae. This is all the more surprising when it is remembered that thebase undergoing precipitation through the addition of alkali is generallyassociated with some unattacked metallic salt, in an amount which is too‘Is D.S.I.R. Fuel Research Board, Annual Report, 1938, p. 65.*O E. Preston and E. Seddon, J . SOC. Glass Tech., 1937, 21, 123.R. F. Tuckett, Trans. Paraday go,., 1943, 39, 158; R. N. Haward, ibid., 1943,39, 267; L. R. G. Treloar, ibid., 1943, 39, 241 ; R. M. Bamer, ibid., pp. 48, 59.8a Nature, Jan. 9, 1943 ; Fuel, 1913,23, 56; Conference, etc., London, 1943, p. 33644 GENERAL AND PHYSICAL CHEMISTRY.great to be attributed to entrainment. Very often the proportion of un-attacked salt associated with the base depends on the manner in whichthe alkali is added, and whether the mother-liquor is being agitated during theaddition of the alkali.Thus, if alkali is slowly added to a copper sulphatesolution with thorough stirring, a pale blue, heavy, finely divided precipitateis obtained and precipitation is complete immediately 1-5 equivs. of alkalihave been added per mol. of copper su1phate.l This is also true of copperchloride and bromide solutions, and phase-rule work has proved that definitebasic salts are produced, viz., 3Cu0,CuS0,,4H20 ; ~CUO,CUC~,,~H,O.~If care is not taken to ensure thorough mixing and the precipitant is addedrapidly, a green gelatinous precipitate is formed which is more basic than theforegoing salts, as may be seen from the fact that precipitation does notbecome complete until about 1.8 equivs.of alkali have been added. Pro-vided the amount of alkali added is not more than 1.5 equivs., the gelatinousprecipitate on agitation with the mother-liquor gradually becomes convertedinto the pale blue, less basic salt. Copper hydroxide, Cu(OH),, as such,is only precipitated under special conditions .3Hence, the conditions which must be established before the precipitationof a hydroxide or basic salt can ensue are to be found in the solubility productof the hydroxide, L, and the ionic product of water, K,; e.g., for the pre-cipitation of a basic salt containing hydrated alumina, as L = [A1"'][OH']3and K , = [H'][OH'], the hydrogen-ion concentration a t which precipitationoccurs will be given by [H'] = K , .V[Al"']/L; or generally, for thehydroxide of a metal of valency, x ,~-[He] F K,([M""J/L)"'For ordinary analytical procedures, the concentrations of salts employeddo not vary over a wide range, Le., [M""] is confined to a narrow range ofconcentration, usually between 10-1 and M. Hence, the hydrogen-ionconcentration set up during precipitation will be constant within a narrowpH range, and this will be particularly the case with salts of ter- and quadri-valent metals. With bi- and uni-valent metal salts the hydroxide pre-cipitation pH range is somewhat wider. For instance, the precipitationrange of silver oxide from 0. lM-silver nitrate with 0.2N-sodium hydroxideis from pH 7.48 (at 10% precipitation) to pH 8.56 (at go%), whereas from0.025~~silver nitrate the corresponding range is pH 7.97 to 9 ~ 0 4 .~ Incident-ally, silver oxide is exceptional in that it is not precipitated as a basic salt.The progressive addition of alkali to solutions of zinc sulphate causesprecipitation to be complete with 1.53 equivs. of sodium hydroxide, thebasic sulphate thus being approximately ZnSO,,SZn(OH),. When 0.1-1 H. T. S. Britton,,J., 19-35, 127, 2152; H. T. S. Britton and F. H. Meek, J.,2 H. T. S. Britton, J., 1925, 127, 2796; 1926, 2868.1932, 184.H. M. Dawson, J., 1909, 95, 370.H. T. S. Britton and R. A. Robinson, Trans. ParucEay SOC., 1932, 28, 531; seealso I. M. Kolthoff and T. Kameda, J . Amer. Chem. SOC., 1931, 53, 832; M.Prytz, 2.anorg. Chern., 1931, 200, 133; W. Feitknecht, HeEu. c;him. Acta, 1933, 16, 1302BRITTON : APPLICATION 0.F ELECTROMETRIC METHODS. 451.4 equivs. of sodium hydroxide are added to 0-025~1-zinc sulphate the pHvaries from 6.77 to 7.71, whereas from 0.0025~-sulphate the pH range issomewhat higher, uix., 7.36-4.11. From zinc chloride solutions the pre-cipitate is only slightly basic, but the pH ranges for 0.1-1.8 equivs. ofsodium hydroxide from 0.025~- and 0.0025~-zinc chloride are respectivelypH 7.13--8.15 and 7-43-8-42. Here again, the effect of the smaller zincsalt concentration is to raise the pH at which precipitation occurs.In the case of precipitations from zinc salt solutions the anion is thusseen to have an appreciable effect on the pH range, and this is also true ofcadmium and mercuric salt solutions; with other metal salts the anion haslittle effect on the pH range of precipitation, although anions have often adefinite influence on the type of precipitate obtained, bhloride in particulartending to produce colloidal solutions which coagulate when the greater partof the necessary alkali has been added.With solutions of tervalent (e.g., aluminium) and quadrivalent (e.g.,thorium) metal salt solutions, concentration of the salt has very little effecton the pH range in which precipitation ensues.gives the pH values, determined electrometrically,at which hydroxides begin to precipitate from solutions of concentrationsabout 0 .0 2 ~ .The following tableKation, etc.Mg"Mn'La"'&I,Ce"'Pr"'Nd"'Zn"Srt"HgCLPH-10.58.5-8.88.47.5-8.07.67-47.37.17.06.86.8-7.1Kation, etc.CO"CdSO,Ni"'Yb"'Pb"Be"Fe"CU"Cr"'VO"VO,"PH.6.86.76.76.26.05.75.55.35.34.34.2Kation, etc.Al"Th""In"'Zr""Fe"'Ti""PH.4.13-53-43.02.7222222Soluble. Basic Salts and Basic Ions.-When alkali is progressively addedto solutions of most metallic salts, the first few drops cause a rapid rise inpH to the appropriate, hydroxide precipitation pH, whereat the precipitateimmediately begins to separate.With salts of very weak bases, however,precipitation does not usually begin until an appreciable amount of alkalihas been added; for instance, ca.1.5 equivs. of sodium hydroxide have tobe added to a zirconium chloride solution before opalescence begins to appear,which subsequently increases in intensity until 3.8 equivs. are added,coagulation then suddenly o~curring.~ Incidentally, the change in pH isvery gradual and there is no evidence of the existence of either ZrOC1, orzirconyl ions, ZrO", in solution, such as E. Chauvenet states he obtainedby a parallel conductometric titration.H. T. S. Britton, J., 1925, 127, 2110, 2120, 2142, 2148; H. T. S. Britton andA. E. Young, J., 1932, 2467; H. T. S. Britton and R. A. Robinson, ZOC. c i t . ; J. A. C.Bowles and H. M. Partridge, Id. Eng. Chem., Anal., 1937, 9, 124; T. Moeller, J . AnLer.Chem. SOC., 1941, 83, 2625.Ann. CAim. Phys., 1920, 18, 8246 GlNEBAL AND PHYSICAL CHEMISTRY.Towards several reagents, zirconium sulphate solutions react quitedifferently from either the chloride or nitrate, so much so that R.Ruer 7postulated the existence of a complex zirconium sulphuric acid. Whensodium hydroxide i8 added to zirconium sulphate solution, the precipitationof a basic salt, Zr02,0.5S0,,xH20 begins immediately and the change inpH thereafter, measured with the hydrogen electrode, reveals that t h i abasic salt must have existed in the original sulphate solution in equilibriumwith 1.5 equivs. of sulphuric acid which had been set free by hydrolysis.Presumably, some kind of equilibrium must exist between the basic salt andthe acid.5Quinhydrone and conductometric alkali titration curves of solutions ofuranyl chloride in hydrochloric acid show that very little combination ofmanic hydroxide with hydrochloric acid occurs beyond the stage indicatedby the salt, UO,Cl,, and the curves provide good reason to believe that a basicion approximating closely to the so-called uranyl ion UO," does exist insolution.Vanadium pentoxide dissolves in solutions of acids to differentextents which are determined by the strengths of the acids, and glass-electrode pW measurements have shown that the salts formed are bestrepresented by VO,Cl, thus giving VO,' ions in strong acid solutions.8Hydrogen-electrode and conductometric titration curves of vanadiumtetroxide in sulphuric and hydrochloric acid solutions show that neitherof these acids combines beyond the stage VOSO, and VOCI,, and the inflexions(and breaks) then produced point to the individuality of these vanadyl saltsand therefore to the vanadyl ion, VO".sThe violet chromium sulphate and chloride and chrome alum give solu-tions which are appreciably acidic, pH ca.3; on treatment with alkali,they change from violet to green and undergo a linear increase in pH untilthe hydroxide precipitation pH (5.3) is reached. This occiirs when exactly1 equiv. of alkali has reacted. Chromium hydroxide being regarded as atriacidic base, it follows that the first hydroxyl group behaves, thoughanomalously, as a distinctly weaker base than the remaining two hydroxylgroups, and this disparity leads to the formation of soluble basic salts,Cr(OH)S04 and Cr(OH)C12.5 It should be stated that boiling of solutionsof the normal violet salts produces enhanced hydrolysis and a change incolour from violet to green, and on treatment with alkali precipitation doesnot beginuntil 1.2-1.4 equivs.have been added. The pH curve corre-sponding to this stage suggests that the act of boiling must cause much of thefirst equivalent of loosely combined acid to be liberated and the soluble basicsalts, Cr(OH)SO, and Cr(OH)C12, to decompose still further.loBeryllium hydroxide as a base is somewhat similar to chromium hydroxidein that one hydroxide group is much weaker than the other, and that theneutralisation of the weaker hydroxide by strong acids yields soluble basicsalts of the type BeOH(SO,),, and Be(0H)R (R = C1, Br, I).This is7 2. anorg. Chem., 1904, 42, 85. a H. T. S. Britton and G. Welford, J . , 1940, 875.9 H. T. S . Britton, J., 1934, 1842; H. T. S. Britton and G. Welford, J . , 1940, 768.10 H. T. S. Britton, " Hydrogen Ions," 3rd Edn., 1042, Vol. 2, p. 229BRITTON : APPLICAmON OF ELECTROMETRIO METHODS. 47reflected in the hydrogen-electrode alkali titration curves of berylliumsulphate,6 and ohloride, bromide, and iodide. During the addition ofthe first equivalent of sodium hydroxide the solutions remain perfectly clear,and the hydroxide does not begin to separate until just after the equivalenthas been added. Moreover, the change in pH is similar to that normallygiven when a strong base hydrolyses the salt of a weak organic acid.Fromthe pH values set up when 0.5 equiv. of sodium hydroxide reacts withsolutions of beryllium sulphate, chloride, bromide, and iodide over anextensive range of concentrations, (Miss) M. Prytz l1 has calculated theequilibrium constants referring to the following syefema :and(a) Be** + H,O(b) either 2Be" + 2H20 =+ Be,(OH)2** $-' 2H'BeOH' + H'or 2Be" + H,O =Be,O" + 2H'The calculations based on (b) led to exceptional constancy of the equilibriumconstant: for solutions of the four beryllium salts in the order named,K = 1-4, 1.7, 6.9, and 4.4 xThesolubility data of C. L. Parsons l2 show that, in solutions of berylliumsulphate ranging from 0.15 to 1 . 1 4 ~ ~ the amounts of beryllia which dissolvecorrespond with the formation of soluble basic salts, which, probably throughthe non-attainment of true equilibria, vary irregularly from Be(OH)09,(S04)o.51to Be(OH),.,6(S0,), 62, with an average composition corresponding toBe(OH),.,o(S04)0.56.N. V. Sidgwick and N. B. Lewis l3 found thatsolutions already saturated with respect to beryllium sulphate were able todissolve beryllium hydroxide, and as a' result the solubility of berylliumsulphate itself was also increased. This is also true of beryllium selenatesolutions. The solid phases in equilibrium with these basic salt solutions,however, were respectively BeS0,,4H20 and BeSe0,,4H20. Calculationof these workers' data reveals that their most concentrated liquid phasescontained beryllium sulphate and beryllia in the proportion required byBe(OH),.,,(SO,),.,, and Be(OH),.7,(Se0,)o.GS, but they attributed the increasedsolubility of beryllium sulphate (and selenate) to the amounts of berylliawhich made these increases possible and found that there were roughly4 mols.of beryllia per mol. of sulphate (or selenate) increase in solubility.They therefore postulated that the excess of sulphate (or selenate) over thatdemanded by the normal solubility must have been in the form of salts :~ e o + ~ ~ o ~ e ] ~ + so," (or + SeO,")Beryllium hydroxide is soluble in beryllium sulphate solutions.l1 2. anorg. Chm., 1929,180,366; 1931,197,103.la J . Anur. Chem. Soc., 1904, 96, 1433. la J., 1926, 128748 GENERAL AND PHYSICAL CHEMISTRY.In other words, the liquid phases must have contained two solutes, thenormal salt being in the greater quantity and the 4 co-ordinated '' beryl-lated" beryllium salt in the smaller.Seeing that normal beryllium saltspresent in solutions which are far from saturated will cause approximatelyan equimolecular amount of beryllium hydroxide to dissolve, this argumentis obviously untenable. C. L. Parsons, W. 0. Robinson, and C. T. Fuller l 4observed that when beryllium hydroxide dissolves in a solution of berylliumsulphate the equivalent conductivity is slightly decreased and the freezingpoint is slightly raised. According to Sidgwick and Lewis the dissolutionof beryllium hydroxide in beryllium chloride solutions has a similar effecton the conductivity. This reduced conductivity might possibly be ascribedto the lower ionic mobility of the heavier kation, BeiO", and the smallerionisation of the soluble basic salt, Be,(OH),SO, or Be,O,SO,.Arnphoteric Hydroxides.-Of the metallic hydroxides which dissolve inalkali solutions only three, viz., Al(OH),, Au,O,, and V,O,, of the many sofar investigated function as acids which are sufficiently strong for theirneutralisation with sodium hydroxide, and their consequent dissolution inalkaline solution, to be reflected in pH and conductometric titration curves.If solutions of either aluminium sulphate or chloride are titrated with thehydroxide of sodium, calcium, strontium or barium,l maximum precipitationis obtained when 3 equivs.(per 1 Al) of base are added, whereas during theaddition of the fourth equiv.the aluminium gradually dissolves, the pHincreasing from 8 to 10.5. Conductometric titration also shows that saltformation occurs with the fourth equiv. of alkali.16 The soluble aluminatesthereby formed are NaA10, and M(A102),, M being Ca, Sr, Ba..If sodium hydroxide is added to a dilute solution of gold chloride, noprecipitation of auric oxide may occur, but pH measurements, .made with theglass electrode,17 show that the auric chloride is being decomposed to forman apparently soluble basic chloride, probably existing in the form of acomplex basic anion. When about two-thirds of the auric chloride have beendecomposed the solution immediately becomes alkaline. After additionof more alkali the basic complex decomposes completely on standing, asshown by the fall in pH (8 to 5 ) and the solution does not again begin tocontain free alkali until after 4 equivs.of alkali (per mol. of AuCl,) have beenadded which is indicated by a well-defined inflexion in the pH curve, therebyshowing that NaAuO, is then formed in the solution.On adding sodium hydroxide to the blue solution of vanadyl chloride,VOCl,, or sulphate, VOSO,, a greyish-white precipitate is formed a t pH4.3, which turns dark brown. If the alkali is added rapidly the precipitatewill dissolve readily in excess of alkali to give a clear red solution of sodiumvanadite, Na20,2V,0,, but if it is added slowly, the combination with theexcess of alkali is comparatively slow, as may be seen from the hydrogen-electrode curves.Back-titration of the alkaline vanadite solution with1 4 J . Physical Chem., 1907, 11, 651.16 R. A. Robinson and H. T. S. Britton, J,, 1931,2817.1 7 H. T. S. Britton and E. N. Dodd, J., 1832, 2464.l6 H. T. S. Britton, J., 1927, 422BRITTON : APPLICATION OF ELECTROMETRIC METHODS. 49hydrochloric acid, the hydrogen electrode being used, showed that the vanaditehas the composition, Na2V,0,, and that it is decomposed within the pHrange 9-6.The Action of Alkali on Xolutions of Mercuric and Cadmium Salts in theAbsence and Presence of Alhli 8aEts.-Solutions of .mercuric nitrate, sulphate,and perchlorate have low pH values and high conductivities, and E.M.F.data show that the concentrations of mercuric ions are of the same order asthe respective salt concentrations, These salts are thus typical of salts formedfrom a weak base and strong acids.Glass-electrode titrations l8 with alkalishow that mercuric oxide begins to precipitate a t very low pH values, ca.pH 2. This is in accord with the small solubility product of mercurichydroxide, viz., [Hg"][OH'I2 = 10-z6.Mercuric chloride, bromide, cyanide, nitrite, and acetate in solutionnot only give rise to exceedingly small concentrations of mercuric ions andelectrical conductivities but undergo very little hydrolysis ; in fact, thesmall concentrations of hydrolysed hydrochloric acid account almostcompletely for the electrical conductivities of solutions of mercuric chloride.l8In consequence, as their mercuric-ion concentrations are extremely low,much greater hydroxyl-ion concentrations have to be established beforeprecipitation on adding sodium hydroxide begins.For instance, fromapproximately 0.01x-solutions of mercuric acetate, nitrite, chloride, andbromide, the respective precipitation pH ranges are 4.2-6.6, 4.0-7.2,701-9.0, and 7.5-104. In the case of mercuric cyanide no precipitateis formed with 0-h-sodium hydroxide even though a pH of above 12 isestablished.If alkali salts of the respective acid be included in the solution of themercuric salt, e.g., potassium chloride with mercuric chloride, precipitationdoes not take place until considerably higher pH values are reachedonadding alkali. The precise pH value is determined by (i) the equilibriumHgC1," =+ Hg" + 4C1' and (ii) the solubility product, [Hg"][OH']2.The mercuric-ion concentration is controlled by the mass-law constant of(i), viz., 10-16'8, and the concentration of free alkali chloride.If the latter isrelatively very large, alkali may fail to precipitate mercuric oxide a t all;e.g., 250 mols. of potassium chloride per mol. of mercuric chloride give asolution which is not precipitated with 0.1N-sodium hydroxide. Complexanions of the type HgR," are also formed with the bromide, nitrite, andacetate, which are rendered increasingly stable by the presence of increasingproportions of the appropriate alkali salt, with the result that the pH ofprecipitation with alkali is correspondingly raised. (The comparablecomplex anion, HgI,", in Nessler's reagent is so very stable that alkali causesno precipitation even though the excess of potassium iodide is not great-in fact, too great an excess increases the stability of the complex anion somuch that the reagent loses sensitivity.)Two points of analytical importance follow from these investigations :(i) the amount of free acid present in a solution of mercuric nitrate, sulphate,la H.T. 5. Britton and (Mias) B. M. Wilson, J . , 1932, 266060 GENERAL AND PHYSICAL CHBMIB!l!RY.or perchlorate may, after an excess of alkali iodide, bromide, or chloridehas been added to convert the mercuric salt into a complex salt, be titratedwith alkali and methyl-orange as indicator; (ii) pure mercuric oxide maybe used to standardise solutions of acid by dissolving a weighed quantity ofmercuric oxide in a concentrated solution of potassium iodide, bromide,or chloride and titrating by means of an acid and methyl-orange the alkaliset free by the reaction HgO + 4K.I + H,O + K,HgI, + 2KOH.Thishas been confirmed by glass-electrode titrations.lQThough to a lesser extent, cadmium salts exhibit characteristics similarto the foregoing, and the effect of alkali salts in raising the pH a t whichcadmium hydroxide precipitates on treatment with’ alkali has recently beendemonstrated.20The Reaction between lMetullic Hydroxides and Weak Acids.-The problemof assessing the basic strengths of sparingly soluble metallic hydroxides isof some difficulty. Basic dissociation constants cannot be computed, as isthe case with the soluble organic bases, from hydrolysis data, for the systemsthen involved are nearly always heterogeneous, the base (or basic salt)often being colloidally dispersed.It happens, however, that the order,in terms of pH values, in which the bases separate fiom solutions of theirsalts with strong acids, excepting certain mercuric and cadmium salts, bearsa direct relationship to the extent to which their salts are hydrolysed insolution. If this pH arrangement represents the relative sequence of basicstrengths, then those bases which precipitate a t low pH values, e.g., zir.conium hydroxide, are the weakest, and those which separate from solutionsat high pH values, e.g., magnesium hydroxide, are the strongest.In any case, the hydroxide precipitation pH imposes on acids withwhich these bases can combine in the wml way the necessity of beingneutralised at pH values which are lower than the precipitation pH.ThuB,if acetic acid be considered as a typical weak acid, K , = 1.8 x 10-5, it canbe shown that for the acid to combine with a strong base, e.g., sodiumhydroxide, to the extent of 50%, a pH of 4-74 must be set up, for 90% apH of 5-69, and for 90% the pH to be reached is 4.74 + 2 = 6 ~ 7 4 . ~ ~ Withweak bases, such as the hydroxides of thorium, aluminium, copper, andberyllium, which begin to precipitate at pH 3.5,4.1,5.3, and 5-7 respectively,it will be seen that the incidence of precipitation of the base before pH 6.74is reached makes it impossible for these bases to form acetates completelyin solution in the same way as sodium acetate, for example, can be formed.Yet copper acetate can be prepared in the crystalline form and dissolvedin water without the separation of copper hydroxide.The pH of 0 . 0 1 ~ -copper acetate is 5434,22 which, although higher than the hydroxide precipit-ation pH, 5.3, is much below pH 6.74, required by a strong base for 99%neutralisation. The pH of comparable solutions of acetates of thorium,1* Idem, J . , 1933, 9.ao T. Moeller and P. W. Rhymer, J . Physical Chem., 1942,40,477.H. T. S. Britton, op. cit., Vol. I, p. 179.H. T. S. Britton and F. H. Meek, J . , 1931, 2831BRITTON : APPLIOATION OF ELEUTROMETRIC METHODS. 51aluminium, and beryllium are 4.31, 4-64, and 4.85 respectively. In no camtherefore can the combination of acetic acid with the different weak brtseabe comidered as normal.Because the hydroxide pH is often exceeded, itfollows that the concentrations of metal ions in the acetate solutions must bemuch lower than in solutions of corresponding salts of strong acids. Froma, study of pH and conductivity data, Britton and Meek found that in solu-tion these metal acetates undergo considerable hydrolysis , with the resultthat some of the metallic base exists in solution either in the uncombinedstate or, much more probably, as a soluble (or perhaps a very highly dis-persed) basic acetate. Basic lead acetates are known which are soluble inwater giving clear solutions, and conversely, solutions of lead acetate (pHof 0-01M-salt = 5-89) can dissolve appreciable amounts of lead oxide. Lead-electrode measurements of solutions of basic lead acetate, Pb( OAo),,,and Pb( OH)o.96( OAc),.,, indicated lead-ion concentrations which repre-sented 0.07 and 0.12% of the total lead in the solutes.It is significantthat the pH of 0.01M-beryllium acetate should be 4-85, for such a pH valueis caused by the ratio [OAc']/[HOAc] being 1.32/1, ahd, by assuming that theacetate in the basic beryllium acetate ionises, it follows that the solutioncontained Be(0H),.,,(0Ac),.,, and 0.89 mol. of free acetic acid, which showsthat a little more acetic acid had reacted than that required to formBe(OH)(OAc) or Be,O(OAc), (see above).In a subsequent paper,a3 Britton and Meek show that the diminishedmetal-ion concentration of solutions of the acetates of lead, copper, beryllium,aluminium, and thorium results in the delay of precipitation of the respectivehydroxide with alkali until much higher pH values are attained than is thecase from the corresponding salts of strong acids.Purther physicochemicalevidence is advanced for the view that acetic acid is too weak to neutralise theweaker hydroxyl group of beryllium hydroxide.Linked up with this weakness of acetic acid and its reaction, or failure toreact, with weak metallic bases are the facts that (i) sodium acetate may beadded to solutions of the chlorides of zirconium, thorium, aluminium, andcopper without the appearance of a precipitate even though the ordinary" hydroxide pH " may be well exceeded,24 (ii) lead sulphate dissolves insolutions of sodium acetate and ammonium acetate.The pH values corre-sponding to the progressive addition of sodium acetate to solutions of theacetates of thorium, aluminium, beryllium, copper, and lead show that thebasic acetates existing in the original metal acetate solutions persist and,in fact, become increasingly basic as the proportion of sodium acetate isincreased. Potential measurements with the lead solutions reveal thatthere is a parallel diminution in the concentration of lead ions.23 Theexistence of soluble basic lead acetate in the presence of sodium and arn-monium acetate in solution and the low lead-ion concentrations supply anexplanation of the solubility of lead sulphate in solutions of alkali andammonium acetates, the limit of the solubility being imposed by the solubilityproduct of lead sulphate.There are no grounds for the view that complexJ., 1932, 183. 2o H. T. S. Britton, J . , 1926, 26952 GENERAL AND PHYSICAL CHEMISTRY.anions, e.g., Pb(OAc)’,, are formed, though it is not a t present certain pre-cisely how the basic lead acetate is stabilised in solutions of sodium acetate.To test the foregoing observations still further,25 the reaction of malonicacid with typical metallic bases was investigated.. Malonic acid is a par-ticularly suitable dibasic acid for this purpose, as its two stages are fairlydistinct from one another, the first stage being that of moderately strongacid, viz., H2M =$= H’ + HM’, K , = 2 x lo-,, and the second stage,HM‘ =+= H’ + M’, K , = 4.4 x that of an acid weaker than acetic.26Hence the neutralisation of the first stage by a base should be complete(99%) at pH 4.7, whereas the second stage is neutralisable between pH3.36 (1%) and pH 7.36 (99%).In other words, in order for a metallicbase to form the hydrogen malonate, e.g., Cu(OH), +- 2H,M -+ Cu(HM), +H,O, it must be able to set up a pH slightly higher than 4.7, and in order toreact with the hydrogen ion originating from the second stage of ionisation,e.g., Cu(OH), + Cu(HM), ---+ CUM + H20, it must do so between pH3.36 and 7.36 and set up a pH slightly higher than 7-36. H. T. S. Brittonand M. E. D. Jarrett 25 selected as typical bases the hydroxides of magnesium,zinc, chromium, beryllium, copper, and aluminium and measured the specificconductivities and pH values corresponding to successive stages of theneutralisation of malonic acid.Compared with the conductivity curvecome sponding to the neutralisation with sodium hydroxide, the curvesfor the metallic bases make it apparent that only the stronger bases, vix.magnesium and zinc hydroxides, react completely with the first stage, butthey fail to combine completely with the second stage. Both pH andconductivity measurements show that the weaker bases, ‘uix., the other four,react partly with the first stage of ionisation of malonic acid in somethingakin to the normal manner, but evidently, through the pH for 99% neutralis-ation of the second stage-pH 7.36-being well above the respectivehydroxide pH values, any reaction which occurs between the bases and thesecond stage is abnormal and, in any case, it is extremely small, as exemplifiedby the remarkable fall in conductivity as the proportion of the bases (tomalonic acid) was increased and the pH values of the solutions when the amountof bases were those required to form what appeared to be the normal malon-ates, zliz., Mg, pH 5.85; Zn, pH 6.27; Cr, pH 2.68; Be, pH 3.57; Cu, pH5-31. The pH value of the O.O4~-magnesiurn malonate shows that the solu-tion must have contained hydromalonate and malonate ions in the ratioof about 1 : 3. The lower pH value of copper malonate solution indicatesan even greater ratio of HM’ to M”, whereas the very low pH values of thechromium and beryllium malonate solutions show that the malonate-ionconcentrations were negligibly small as the neutralisation had not proceededbeyond the first stage.D.J. G. Ives and H. L. Riley 27 observed that the conductance ratios ofthe malonates and several alkylmalonates become smaller in passing through25 J . , 1935, 168, 1728. 26 H. T. S. Britton, J., 1925, 1906.27 J., 1931, 1998, K. L. Riley and (Miss) N. I. Fisher, J., 1929,2006BRITTON : APPLICATION OF ELECTROMETRlC METHODS. 53the series : Mg, Zn, Ni, Cu, which incidentally is the sequence of the respective“ hydroxide pH ” values. They also observed that the smaller secondarydissociation constants of diethylmalonic (5.9 x and dipropylmalonicacids (3.42 x had no effect on the electrolytic dissociation of copperdialkylmalonates formed therefrom, and attempted to account for thison the basis of a complete electron grouping around the central copperatom.If copper hydroxide is unable to neutralise the second stage ofmalonic acid, it certainly cannot react with weaker acid stages, requiringthe attainment of pH 9.23 and 9-47 respectively for 99% neutralisation,and consequently no difference could be expected on this basis.N. V. Sidgwiclr and N. B. Lewis 28 state that “ no doubt ” the lowconductivity of beryllium malonate solutions is due to the presence of anon-polar cyclic form Be<o-CO>CH2. A view more in accord with thecombining character of beryllium hydroxide and malonic acid is that thestronger hydroxyl group of the base must have reacted with the “ stronger ”hydrogen ion of the malonic wid, thus Be(OH), + H,M+ BeOH,HM +H,O, so that instead of beryllium malonate being present, basic berylliumhydrogen malonate was the principal salt formed (see above).This view issupported by the fact that the pH of a O.O2~-beryllium malonate solutionis approximately equal to that of a O.02w-sodium hydrogen malonatesolution. Britton and Jarrett 25 also found that such a solution can be madeeven more basic by saturating it with beryllium hydroxide, whereupon thepH rises to 5.59, this being very nearly the hydroxide precipitationpH, viz., 5.7. The basic solute then corresponds with the formulaBe(OH),.,,(HM),.,,. The relatively high pH value, 5.59, shows that thereaction had proceeded to the second stage to a small extent so as to set up anequilibrium between HM’ and M” ions.It seems certain, therefore, that insolution, malonates of weak bases exist largely as soluble or very highlydispersed basic malonates in equilibrium with a little hydrolysed acid. Thiswould account for their exceptionally low conductivity, which, as Sidgwickand Lewis 28 have shown, does not change much with dilution.Although the normal malonates of the weaker metallic bases, e.g., thehydroxides of iron, aluminium, and chromium, have not been isolated in goodcrystalline form, yet well-defined complex malonates with the alkali metalsare known; those formed from tervalent metals, R, may be representedby Na3RM3. H. L. Riley 29 prepared the sodium cuprimalonate,Na2CuM2,2H,0.The constitution of the complex malonates, Na,RM3, isgenerally expressed on the basis of Werner’s theory of stereoisomerism, but itis highly probable that their mode of formation is to be attributed to the abilityof these weak metallic bases to react only with the first, and stronger, stage ofionisation of malonic acid, thus : Cr(OH), + 3H2M --+ Cr(HM), + 3H20,leaving the second, and much weaker, stage of ionisation to be reacted uponby the strong base or alkali : 3NaOH + Cr(HM), + Cr(NaM),, * i.e.,0-coaa J., 1926, 2538. 2m J., 1930, 164254 GENHIRAL AND PEYSICAL CHEMISTRY.Na,CrM,.30 This does not explain the entrance of the heavy metal into thecomplex anion, which may be due to some inhibiting effect imposed on thecomplex salt by the separation of the baser sodium ions, in the same wayt b t the ionisation of the fist stage of a dicarboxylic acid may depress theionisation of the second stage.The foregoing conditions refer to the formation of soluble salts as theresult of the combination of weak metallic bases with weak acids.Whenthe salt happens to be sparingly soluble in water, then the solubility productof that salt becomes a determining factor in the formation of that salt.As an example, the chromate, oxalate, and phosphate of thorium are allwell-defined sparingly soluble salts, vix., Th(Cr0,),,3H,0,31 Th(C204)2,6H20,32Th3(P04)4,33 yet they are formed from an exceedingly weak base; theprecipitation pH of thorium hydroxide is 3.5 and chromic and oxalic acidsare both weak acids in their second stages of ionisation, whilst phosphoricacid is weak in its second stage and extremely weak in its third stage ofionimtion.To form a eoluble thorium chromate, thorium hydroxidewould have to react with the hydrogen chromate ion, K, = 4.4 x 10-7,HC.h-0,' + H' $- Cr04", i.e., within the pH range between pK - 2 =6.4 - 2 = 4.4 and pK + 2 = 6.4 + 2 = 8.4. As thorium hydroxide ispreeipitated at pH 3.5, reaction with the second stage in such a way is clearlyimpossible; in fact, reaction with even the first stage would be far fromcomplete. Similar conditions apply to thorium oxalate, whereas the extremesmallness of K , of phosphoric acid, 2.7 x requires a pH range of 9-6-13.6, the last pH only being reached in very alkaline solutions.Thoriumoxalate is precipitated from fairly acid solutions, whereas the addition oftrisodium phosphate to 0-Oh-thorium chloride causes thorium phosphateto precipitate a t pH 2.7.s3 Potassium dichromate, added to a thoriumsalt solution, precipitates the normal thorium chromate, whereas potassiurnchromate precipitates basic thorium chromate at pH 3.45,34 this being verynearly the hydroxide precipitation pH. As will be seen from the hydrogen-electrode curve of chromic acid,35 the pH of potassium dichromate is about4, whereas that of potassium chromate is about 9. The pH of thoriumchloride solutions is about 2.5 (pH of O-OlM-ThCl, = 2.02). Hence, whenpotassium dichrornate is added to a thorium chloride solution the pH willrise but slightly above that of the salt solution, and if [Th""] and [CrO,"]are large enough to exceed L = [Th"" ][Cr0,ll2, a sparingly soluble crystallinethorium chromate separates, whereas the normal potassium chromate gooncauses the hydroxide pH to be rertched and an indehite thorium basicchromate separates.To prepare sparingly soluble normal salts, the con-ditions for their precipitation must be set up in the rnother-liquor at a pHbelow the hydroxide pH.3O H. T. S. Britton and M. E. D. Jsrrett, J., 1935, 1728; cf. H. T. S. Britton J.,31 H. T. S. Britton, J . , 1923, 123, 1429.1926, 280.H. T. S. Britton and M. E. D. Jmett, J., 1936, 1404.H.T. S.Britton, J . , 1927,614. 3 p Idem, J., 1926,126. * 6 Idem, J., 1924,126,1672BRITTON : APPLIOATION OF ELECTR0YE:TB;IC METHODS.56This applies particularly to the precipitation of carbonates and explhslwhy the few carbonates which are preoipitated &g B U C ~ , e.g., MgC0,,3H20,ZnCO,, Ag,CO,, are precipitated by means of sodium bicarbonate and notby the alkaline sodium oarbonate. In the caae of carbonates of the weakerbases the reaction mixture must be saturated with carbon dioxide 80 as tokeep the pH as low as possible below the hydroxide pH.Basic chromates, carbonates, and borates are precipitated at the respectivemetal hydroxide pH values.34 This is also true of silicates precipitatedby means of an alkali silicate, e.g., water glass, except of silicates of thealkali earths, which are usually precipitated between pH 10 and pH 11.36It is extremely doubtful, therefore, whether these heavy metal silicates areanything more than mixtures of the hydrated metallic hydroxide and silica.Thus for the precipitation of indefinite aluminium silicates the hydroxideprecipitation pH, 4.1, has first to be reaohed, whereas if aluminium silicatewere a definite salt in the true sense one would have expected it to have beenprecipitated at a lower pH.As H. T. S. Britton3' has shown, silicio acidhas defmite acid properties between pH 7 and 12, corresponding to theformation of alkali metasilicate, Na,SiO,. Aluminium hydroxide obviouslycould not combine with silicic acid under these conditions, but it is possiblethat some union might take place if the resulting salt were exceedinglyinsoluble, and this possibly would be made manifest by precipitation at apH below 4.1.In addition to the formation of insoluble salts, there is the possibilitythat the resulting salt might be soluble but.un-ionised, which makes posaiblethe combination of a weak base with a weak acid.Por instance, KEOH =4.5 x 1 W 0 , which indicates for hydrocyanic acid a reaction range of pH 7.35-11.35, and mercurio oxide is an exceedingly weak base, hydroxide pH 2,and yet hydrocyanic acid and mercuric oxide react together to form soZubEemercuric cyanide. The explanation is that mercuric cyanide is un-ionisedin solution so that mercuric and cyanide ions are removed from the reactionsystem.Complex Cyanides.-On the basis of the foregoing considerations, it is noteasy to understand why weak bases can react with hydrocyanic acid a t all;yet, in conjunction with alkali cyanides, ferric hydroxide is able to combineto form well-defined and readily soluble salts.There is no doubt that incomplex compound formation, involving hydrocyanic acid, co-ordinatelinkages come into play so much so that in the complex acids and saltshydrocyanic acid entirely loses its individuality.In general, the complex acids from which the complex cyanides arederived have not been prepared, and must be regarded as hypothetical.This, however, is not the case with hydro-ferrocyanic and -ferricyanic acids.A solution of H,Fe(CN), has been titrated by use of the glass electrode byH. T. S . Britton and E. N. Dodd,38 who find it to be a relatively strong acidThis instance is exceptional, however.3 6 J ., 1927, 425; see also G. Hagg, 2. anorg. Chem., 1926, 165, 20.37 H. T. S. Britton and R. A. Robinson, J . , 1931,469.3a J . , 1933, 164356 GENERAL AND PHYSICAL CHEMISTRY.in all its four stages, and 0. E. Lanford and S. J. Kiehl 39 extrapolate a valueof 6.8 x as being its fourth, and therefore, smallest constant.To ascertain how many molecules of potassium cyanide react with thevarious metallic salts in solution to form complex cyanides, three methodshave been employed: (i) a method depending on the vapour pressure ofhydrogen cyanide of solutions containing free potassium cyanide, (ii) themeasurement of pH as potassium cyanide is progressively added, (iii)wherever possible, the measurement of the metal-ion concentrations duringand after the formation of the complex cyanide.The technique of the first method was based on that devised by F.P.Worley and (Miss) V. R. Browne 4O and later used to measure the hydrolysisof potassium cyanide in solution.41 It consists in bubbling pure air veryslowly through the cyanide solution and thence through 10 C.C. of 0.2%picric acid in 2% sodium carbonate for a suitable time. The hydrocyanicacid causes the picric acid solution to develop a brown colour after immersionin boiling water for 2 - 3 minutes, the intensity of which is directly propor-tional to the amount of hydrogen cyanide absorbed, which thus makes itpossible, after standardisation with solutions of known hydrogen cyanideconcentration, to estimate the degree of hydrolysis of potassium cyanidesolutions.Solutions of the complex metal cyanides containing varyingexcess amounts of potassium cyanide were investigated, and the total amountsof free hydrogen cyanide determined.,, It was found that when the solutionscontained an excess of about 6 mols. of potassium cyanide to 1 mol. of thecomplex cyanides, viz., KAg(CN),, K,Zn(CN),, K,Cd(CN),, K,Ni(CN),,K,Fe(CN),, the hydrolysis of the complex anions was completely repressed.This amount of potassium cyanide was not sufficient to repress the hydrolysisof potassium cuprocyanide, K,Cu(CN),, or of KAu(CN),.,~ On the otherhand, the hydrolysis of K,Hg(CN), increased as the excess of potassiumcyanide was increased.,,The second method depends on the difference in the degrees of hydrolysisof the complex cyanides and potassium cyanide. It consists of measuringthe pH as the latter salt is progressively added to solutions of metal salts.Idexions in the curves, indicating the pH against the amount of cyanideadded, appeared when this was exactly that required to form KAg(CN),,K,Ni(CN),, K,Zn(CN)4,44 K,CU(CN)~, and KAu(CN):3.The inflexionscorresponding to K,Cd(CN), and K,Hg(CN), were indefinite.The third method consisted of measuring the metal-ion concentrationspotentiometrically. Inflexions in the E.M.F.-potassium cyanide curvesshow that KAg(CN),, K,Zn(CN),, and K,Cd(CN), are formed. By re-J . Physical Chem., 1941, 45, 300; see also I. M. Kolthoff and 0.Tomsicek, ibid.,1935, 39, 955.40 J., 1917, 111, 1057.42 H. T. S. Britton and E. N. Dodd, J . , 1931, 2332.4 3 Idem, J., 1935, 100.44 Idem, J., 1932, 1940.R. W. Harman and F. P. Worley, Trans. Faraday SOC., 1924,20,502BRITTON : APPLICATION OF ELXCTROMETRIC METHODS. 57versing the titration, mercuric chloride being added t o potassium cyanidesolution, an inflexion was obtained proving the existence of K,Hg(CN),.Complex Katiom of Silver and Ammonia and Substituted Ammonias.-Potentiometric titrations with the glass and the silver electrode 45 havebeen performed to study the formation of complex silver kations in solution.When a solution of ammonia, or of an alkyl-substituted ammonia, is added toone of silver nitrate, silver oxide is partly precipitated if (i) the reactant is asufficiently strong base t o set up the hydroxide precipitation pH and (ii)the stability of the complex kation simultaneously being formed is not toogreat to prevent [Ag'] from reaching the requirements demanded by thesolubility product of silver hydroxide. Generally, precipitation reaches amaximum when 1 equiv.of base is added, but more base causes the silveroxide to dissolve; with ammonia, dissolution is complete with 2 mols.,but greater amounts of the organic bases are required, the precise amountsdepending on the stability of the complex kation being formed. Inflexionsappear in both the pH and the silver-electrode potential curve. Withammonia and free bases (e.g., methyl- or ethyl-amine) these inflexions extendfrom the addition of the first to the second equivalent, but if sufficientnitrate of the respective base is, inserted in the silver nitrate solution beforethe addition of the base, the inflexions occur sharply when exactly 2 equivs.of base have been added (i.e., 1 mol.of ethylenediamine). The pH valuesthereafter set up correspond to the buffer systems established by the addedbase and its salt already in the solution. Complex salts are therefore formedhaving the general formula AgR2N0, (R = I equiv. of base).These complex nitrates were shown to be the salts of strong bases of theformula, AgR,OH, and it was found that the solubility of silver oxide inaqueous solutions of ammonia and the substituted ammonias could besatisfactorily calculated from the " instability constants " of the complexkations, vix., K = [Ag'][R]2/[AgR2'], and the solubility product of silverhydroxide.Glass-electrode titrations of these solutions with nitric acidrevealed that such complex bases existed therein, and the pH values corre-sponding to their neutralisation, together with parallel conductometrictitration curves, showed that these complex bases were as strong as sodiumhydroxide.45* 46 Complex silver kations are also formed with secondaryand tertiary bases, including pyridine, bat the stability rapidly diminishesin the order primary > secondary > tertiary. Curiously enough, however,the stability of the aniline kation is less than that of the pyridine kation.The Action of Ammonia on Certain Mercuric Salts and on PotassiumMercuri-iodide Solutions.-The pH;(glass electrode) and electrical conductivityof solutions of mercuric salts were measured during the addition of ammonia,47and from the data it was found that the composition of the resulting whiteprecipitates depended on the concentrations of the reactants and on whether45 H.T. S. Britton, J., 1925, 127, 2956; H. T. S. Britton and (Miss) B. M. Wilson,46 Idem, J., 1935, 796.4 7 H. T. S. Britton and (Miss) B. M. Wilson, J . , 1933, 601, 1046.J., 1933, 105; H. T. S. Britton and G. W. Williams, J . , 1936, 9658 GENERAL AND PHYSICAL CHEMISTRY.the ammonia is added to the salt solution or vice versa. If sufficient am-monium salt is included in the mercuric salt solution to repress the ionisationof the added ammonia, then the 2-co-ordinated mercuric salt is precipitated,e.g., Hg(NH,),CI, or fusible white precipitate.On adding 0-1N-sodiumhydroxide to 0.025M-merCuriC chloride, the precipitate is 3HgO,HgCl,,but when 0-1N-ammonia is used the precipitate is 3Hg0,Hg(NH3),C1,.From more concentrated solutions, the precipitate approximates closely tothat of " infusible " white precipitate, Hg0,Hg(NH,),C12, although generallyit is indefinite and may be represented as HgO,xHg(NH,),Cl,, in whichx depends on the extent to which the ionisation of the ammonium hydroxidehas been repressed and therefore on the concentration of ammonia in thesolution. . This also is true of the precipitates produced by adding ammoniato solutions of mercuric sulphate, nitrate, bromide, and perchlorate.These basic ammoniated salts are precipitated a t lower pH values thanare the ordinary basic mercuric salts on addition of alkali. During theprecipitation of mercuric oxide (and basic salts) the solubility product,[Hg"][OH'I2 = is of course obeyed, but during precipitations withammonia the value of this ionic product is about This explains Nessler'stest for ammonia. Nessler's solution is approximately O.09MM-pOtaSSiumrnercuri-iodide and 24~-potaasium hydroxide. Its concentration of mercuricions is 10-26.7 and [OH'] = 100, and therefore [Hg"][OH'Ia i= which,being but slightly smaller than the value of the solubility product,shows that the solution is just on the verge of precipitating merctiric oxide.As a smaller *value, is necessary for the separation of the oxide in t h eform of a basic ammoniated mercuric salt, e.g., 3Hg0,Hg(NH3)&,, i t followsthat precipitation must ensue as soon as ammonia is allowed to react withthe solution.Ionisation of Acids.-W. Pugh 4* has followed the back-titration of sodiumgermanate with hydrochloric acid, using the hydrogen electrode, and findsgerrnanic acid t o dissociate as an ordinary dibasic acid, H,GeO,, of whichK,, = 2.6 xChromic acid in solution dissociates as a normal dibasic acid, H2Cr04,the first stage of ionisation, H,CrO, H' + HCrO,' being that of astrong acid, whereas K,, (for the second stage) = 4.4 x O9 The exist-ence of di- and poly-chromic acids in solution is extremely doubtful.Telluric acid, according t o A. Rosenheim and M. Weinheber,m is hexa-basic, i.e., H,TeO,. In solution it behaves as a norm1 dibasic acid, H,TeO,,being weak in its first stage of ionisation, K,, = ca. and very weakin its second, K,, = ca. 10-12*5 5lAs far as can be ascertained from pH measurements with the glasselectrode, arsenious acid is monobasic, presumably HAsO,, having a dis-sociation constant of 104.07.52and K,, = 1-9 x 10-13 a t 20".4 8 J . , 1929, 1537, 1994.61 H. T. S. Britton and R. A. Robinson, J., 1931, 458.sa a. T. S. Britton and (Miss) P. Jackson, J . , 1834, 1048.49 H. T. S. Britton, J . , 1925, 125, 1672.2. nnorg. Chem., 1911, 69, 201BRITTON : APPLICATION OF ELECTROMETRTC METHODS. 59AbnormaZ Acids.-Conductometric and quinhydrone electrode titrationswith hydrochloric acid of solutions of sodium molybdate 53 and sodiumtungstate have shown that both molybdic and tungstic acids function asnormal dibasic acids, HJMoO, and H2W04, in one respect only, i.e., in regardto their maximum neutralisation with alkali. Instead of breaks (andinflexions) occurring when 1 equiv. of hydrochloric acid had reacted, thesewere delayed until 1.5 equivs. had been added and, thereafter, both theconductivity and the pH curve indicated that the hydrochloric acid wasnot reacting further. Similar conductometric titrations performed byG. Jander, K. F. Jahr, .and W. Heukeshoven 55 and G. Jander and W.Heukeshoven 56 on solutions of sodium molybdate and sodium tungstateyielded data which gave continuous curves similar to those obtained by theprevious authors. To interpret the curves, however, Jander et al. drewtangents to them in the vicinity of continuous bends and, from the points ofintersection of successive tangents, arrived a t invalid conclusions regardingthe composition of polymolybdate and polytungstate anions. The factthat inflexions (and breaks) occur with 1.5 equivs. of hydrochloric acid ledH. T. S. Britton and W. L. German to conclude that sodium poly-salts corre-sponding to the formula Na,[O(WO,),] and Na,[O(MoO,),] were then formedwhich were not decomposed readily on adding further amounts of the acid.S. C. B e ~ a n , ~ ~ from the respective hydrated oxides, has prepared solutionsof molybdic and tungstic acids, which on direct titration with alkali showthat in aqueous solution these acids exist and are neutralised as H,[O(MoO,),]and H,{ 0 (WO,),]. Glass-electrode pH and conductivity measurementsreveal that they are very strong poly-acids, which fact explains why anexcess of hydrochloric acid neither precipitates tungstic oxide nor completelydecomposes the poly-salts, Na,2[O(W03)p], in dilute solutions. The poly-tungstate anion, O( W03)i’, unlike O(MoO,),”, does not react readily withalkali except on boiling or long standing. Bevan’s observations on theacid nature of phosphotungstic and phosphomolybdic acids as they behavein solution are not in accord either with L. Pauling’s theoryS8 or withJ. F. Keggin’s X-ray crystallographio observation^.^^ The following ab-normal acids have been studied potentiometrically and conductometrically :van ad i c , 6O n i o bi c , tan t ali c .62 11. r r . s. B.sg H. T. k. Britton and W. L. German, J., 1930, 2154.54 Idem, J . , 1930, 1249. 6 6 2. anorg. Chem., 1930, 194, 383.5 6 Ibid., 1930, 187, 60. 6 7 Ph.D. Thesis, Londofi, 1940.68 J . Amer. Chem. SOC., 1929, 51, 2868.Proc. Roy. Soc., 1934, A , 144, 75; J. W. Illingworth and J. F. Keggin, J., 1936,6o H. T. S. Britton and R. A. Robinson, J., 1930, 1261 ; 1932, 1955; H. T. S. Britton576.and G. Welford, J., 1940, 764.62 Idem, J . , 1933, 419.H. T. S. Britton and R. A. Robinson, J., 1932, 2266

ISSN:0365-6217    

DOI:10.1039/AR9434000012

出版商:RSC    

年代:1943

数据来源: RSC

摘要:

INORGANIC CHEMISTRY.THIS Report is divided into two sections, the first of which is a review ofrecent publications of general interest. I n the second section an account isgiven of experimental work on the preparation of pure solid elements, basedon a survey af the literature of the last 15 years or so. Some overlap withearlier AnnuaE Reports has inevitably occurred, but this is not serious.The subject has not hitherto been reviewed systematically, and the classi-fication of the various experimental methods, together with illustrativematter drawn from recent literature, will, it is hoped, be of particular valueto the non-specialist.1. GENERAL.During the past year there has again been great interest in the applicationsof isotopes as indicators of reaction mechanism.Methods of preparation ofthe enriched non-radioactive isotope or of the radioactive isotope whichserves as the indicator are now well established, but only for deuterium andits compounds are the necessary materials widely available, In this case acomprehensive series of experiments has been described on the exchange ofdeuterium in deuterated water with ammonia in the complex ammines ofcobalt,l platinum, and palladium., I n the cobalt complexes it was shownthat the hydrogen of the salts [Co(NH,),]C13 and [Co(en),]Cl, undergoesexchange with deuterium when dissolved in water enriched in deuteriumoxide, This fact had been established by earlier observations on complexcompounds of this class,3 but in the present work kinetic measurementshave been made.I n buffered solutions the interchange reaction proceedsaccording to a pseudo-unimolecular rate law, the rate being also inverselyproportional to the hydrogen-ion concentration. The stability of the com-plex is such that the exchange of deuterium and hydrogen cannot occurby an initial dissociation of ammonia molecules, followed by exchange ofammonia in solution. The observations are readily interpreted, however,by assuming that the metal-ammine group, M-NH,, ionises as an acid,forming a metal amide group, M-NH,, and a hydrogen ion. This behaviourparallels that of aquo-ammines, which form hydroxo-ammines by dis-sociation. There is some evidence from these experiments that the easeof acid dissociation runs parallel to the stability of the ammines.The experiments made with the two salts [Pt(NH3),]C1,,2H20 and[Pd(NH3),]C1,,H20 accord in general with the results obtained with thecobalt complexes.Tetramminopalladous chloride was found to undergointerchange by the acid dissociation mechanism referred to above, and also,in acid solution, by reversible dissociation of ammonia from the complex.J. S. Anderson, H. V. A. Briscoe, and N. L. Spoor, J., 1943, 361.J. S. Anderson, H. V. A. Briscoe, L. H. Cobb, and N. L. Spoor, ibid., p. 367.See, e.g., J. Horiuti and G. Okamoto, Sci. Papers Inst. Phys. Chem. Res. Tokyo,1937, 31, 205EMELBUS : QIWERAT,. 61A study of the homogeneous gas exchange with various halides of thechlorine of HW1 in a product containing 3% of H3'Cl and 9776 of H35Clhas also been r e p ~ r t e d .~ Reaction was found to be rapid with phosphorusand arsenic trichlorides, slower for phosphoryl chloride, very slow for silicontetrachloride and sulphur monochloride, and negligible for carbon tetra-chloride. A mechanism involving additive compounds such as HPCl, andH2SiC16 was postulated to account for the occurrence of the exchange.Exchange between the chlorine of hydrogen chloride and solid potassiumchloride was shown to be limited to the surface layers of the solid.Comparative data on the physical properties of deuterium and hydrogencompounds have been published by A. B. Hart and J. R. Partingt~n,~ whohave measured the dissociation pressures of the ammonia and trideutero-ammonia addition complexes of a variety of metallic halides and of coppersulphate.Similar comparative data on the association of hydrogen anddeuterium fluorides have also been obtained.6 The experiments entailedthe isolation of a quantity of HF or DF in a constant-volume container,and simultaneous measurements of pressure and temperature over a consider-able range. The deviations from perfect-gas behaviour were then used tocalculate the association factor of the gas. Degrees of association of thevapour ranging from 1.2 to 4.5 were observed, and the data as a wholeconformed with a single equilibrium 6HF + (HF),, though the existenceof other polymers is not excluded. The heats of polymerisation were- 40,800 and - 41,100 g.-cals. for (HI?), and (DF),, respectively; further,the polymer in each case being assumed to be a single ring, the correspond-ing strengths of the hydrogen and deuterium bonds between fluorine atomswere 6800 and 6850 g.-cals.The use of a radioactive bromine isotope in studying the exchangebetween methyl bromide and certain inorganic bromides has been describedby G.B. Kistiakowsky and J. R. van Wazer.' Radioactive 80Br with a34-hr. half-life was prepared by irradiating bromoform containing a traceof bromine with slow neutrons. The free bromine, which contained a largepart of the bromine radioactivity, was extracted with cold ammoniumhydroxide solution, time being allowed for the decay of short-lived productspresent. Solid ammonium bromide was then isolated and converted intomethyl bromide by heating with sulphuric acid and methyl alcohol.Theexchwge of bromine between the resulting radioactive alkyl bromide andthe bromides of aluminium, barium, and potassium was followed by measur-ing the loss of radioactivity by the gaseous phase. The experiments, whichwere made in the temperature range 22--227", showed that with aluminiumbromide, which is a good catalyst for the reactions of methyl bromide,exchange of bromine between the solid bromide and the vapour occurred4 K. Clusius and H. Haimerl, 2. physikal. Chem., 1942, B, 51, 347; A , 1943, I, 63.6 R. W. Long, J. H. Hildebrand, and W. E. Morrell, J . Amer. Chem. SOC., 1943,J., 1943, 104.66, 182.Ibid., p. 182962 INORGANIC CHEMISTRY.readily, the activation energy of the reaction being only 4.6 kg.-cals.Forbarium bromide, which is a poor catalyst, the activation energy was 12 kg.-cals., whilst for potassium bromide, which is devoid of catalytic activity,there was no measurable exchange. The use of the radioactive indicatorhas thus served t o indicate a relationship between exchange and catalyticactivity. A somewhat similar use of the radioactive iodine isotope 1281of 25 mins. half-life is described by H. A. C. McKayY8 who has studied theexchange of iodine and alkyl iodides in alcoholic solutions.The structure of diborane, which for many years has been a controversialsubject,g has been re-examined by H. 0. Longuet-Higgins and R. P. Bellylowho have revived a formula (I) in which two hydrogen atoms form a bridgebetween the boron atoms.This formula, which is analogous to that of thedimeric aluminium halides (11), has much chemical and physical evidencein its favour. In particular it accounts for the ease of interconversion of(1.1 (11.) (111.)the boron hydrides, in all of which similar bridges are thought to exist.The existence of products derived from the borine radical, such as BH,,COand BH3,NMe3, is also readily explained, as is the non-existence of methyl-substituted diboranes containing less than two hydrogen atoms. Trimethyl-boron itself is monomeric and pentamethyldiborane is unknown. The boro-hydrides n are formulated similarly, beryllium borohydride, for example,being assigned the formula (111). Physical evidence for these structuresand for the nature of the bonds is fully discussed by the authors in termsof the theory of resonance.There is uncertainty in the interpretation ofelectron-diffraction measurements of bond length, but the vibrational andinfra-red spectra of diborane are more consistent with a hydrogen-bridgestructure than with one resembling ethane.The relative strengths of the N+B bonds in the additive compoundsof trimethylamine with boron fluoride and its methyl derivatives have beenstudied by A. B. Burg and (Miss) A. A. Green.12 This work, in the courseof which the new compounds Me,NBF,Me and Me,NBFMe, were prepared,has shown that the substitution of one methyl group for fluorine in Me,NBF,leads to a large decrease in the N+B bond strength, whereas furthersubstitution causes only a small further decrease.Evidence that gallium forms an unstable borohydride under conditionssimilar to those yielding borohydrides of aluminium, beryllium, and lithiumhas now been obtained.13 Trimethylgalliuni, the improved preparation of* J .Amer. Chem. SOC., 1943, 65, 702.9 For recent reviews, see A. B. Burg, Chem. Reviewe, 1942, 31, I; S. H. Bauer,10 J . , 1943, 250.12 J . Amer. Chem. SOC., 1943, 65, 1838.l3 H. I. Schlesinger, H. C. Brown, and G. W. Schaeffer, ibid., p. 1786.ibid., p. 43.11 Cf. Ann. Reports, 1941, 38, 65EMEL$US : GENERAL. 63which by the action of dimethylmercury on gallium has recently beendescribed,l* was treated with an excess of diborane at room temperature.After an induction period a rapid reaction occurred with deposition of afilm of gallium ;.the reaction was represented by the eqllationIt was considered probable from these preliminary experiments that aborohydride of gallium was the first reaction product and that it underwenta rapid autocatalytic decomposition. When the reaction was carried outa t -45" a new compound, dimethylgallium borohydride, (CH,),GaBH4, wasobtained. This substance, which had an extrapolated boiling point of 92",underwent slow decomposition at room temperature. Its reactions arebeing further studied.A non-volatile aluminium hydride, (AlH& has been prepared by0. Stecher and E. Wiberg l5 by passing trimethylaluminium with a largeexcess of hydrogen through a glow discharge. The volatile products werecomplex, but the authors succeeded in isolating and characterising twocompounds, AI,H, (CH,), and Al,H,(CH,)3.Unlike the corresponding galliumderivative, Al,H,(CH,), did not disproportionate to aluminium hydride andtrimethylaluminium.From the non-volatile reaction products a compound having the formulaAIH,,N(CH,), was isolated by treatment with trimethylamine. This losttrimethylamine as it was heated, giving a series of intermediates of the type(AlH,),,N(CH,), and (AlH3)5,N(CH3)3. At 100-135" a product was leftwhich had the empirical formula, AlH,. This was a white, non-volatilesolid, the chemistry of which has not yet been studied.Evidence for the existence of an unstable volatile lower fluoride ofaluminium, (AlF),, has been obtained by W.Klemm and E. Voss.l6 Thiswork arose from the observation 17 that aluminium volatilises at a lowertemperature than usual in the presence of a metallic fluoride. Klemm andVoss showed that when aluminium was heated with aluminium fluoride a ttemperatures between 600" and 1000" and a t pressures of a few mm. asublimate of aluminium and aluminium fluoride was formed. In this tem-perature range the metal is not appreciably volatile, though its fluoridevolatilises to a small extent. Repeated revolatilisation of the sublimatewith excess of aluminium finaily gave a product in which the ratio A1 : Fwas 1 : 1. This result was interpreted by supposing that a volatile fluoride(AlF),, which disproportionates into metal and the trifluoride on condens-ation, is responsible for the transport of metal through the gas phase.The preparation of fluoro-derivatives of non-metallic elements by theSwarts reaction has been further studied by H.S. Booth and his co-workers.l*Fluorination of thiophosphoryl tribromide by antimony trifluoride at 60-70"without a catalyst has yielded the bromofluorides PSF,Br (b. p. 35.6") andl4 E. Wiberg, T. Johannsen, and 0. Stecher, 2. anorg. Chem., 1943, %l, 114.l5 Ber., 1942, 75, 2003.17 C. B. Willmore, U.S. Patent 2,184,706, 1939.16 2. anorg. Chem., 1943, 251, 233.18 Cf. Ann. Reports, 1941,38,16064 INORGANIC CHEMISTRY.PSFBr, (b. p. 125.3").19 These two compounds are noteworthy because oftheir high resistance to hydrolysis : PSF,Br, which was the more resistant,was almost unattacked in 24 hours by aqueous potassium hydroxide a t roomtemperature, though reaction was rapid a t 100".It is of interest that thepartly fluorinated derivatives of phosphorus tribromide are very much lessstable.Attempts to fluorinate sulphur monochloride by the above methodresulted only in decomposition. Boron trichloride has also been examined,and although reaction was carried out at reduced pressure so as to facilitatethe escape from the reaction mixture of partly fluorinated products, onlyboron trifluoride was obtained.20 Reaction temperatures down to - 78"were employed. In addition, the interaction of boron trifluoride and borontrichloride a t 500", fluorination of boron trichloride with calcium fluoride a t160", and the use of the less reactive SbC1,F in place of SbF, were examined,but in each case the result was the same.The preparation of germanium isocyanate has been reported by A.W.Laubengayer and L. ReggeL21 The method of preparation was similar tothat used in preparing isocyanates of silicon, boron, and phosphorus.22Germanium tetrachloride was dissolved in benzene, silver isocyanate added,and the mixture refluxed. The formula of the compound, which had anextrapolated boiling point of 196", was established by analysis, and it wasfound to be rapidly hydrolysed by water and to undergo thermal decom-position a t temperatures above 140".Chlorine azide, which ranks among the most unstable compounds known,has recently been reinvestigated and more fully characterised.,, The pre-ferred method of preparation was by the gradual addition of acetic acid toequimolecular amounts of sodium azide and sodium hypochlorite, followedby distillation in a stream of air or nitrogen a t atmospheric pressure.Thoughthere were many detonations in the course of this work, the compound wasisolated and analysed, and a number of its properties were studied. Liquidchlorine azide did not conduct electricity appreciably, nor did it conductin contact with sodium azide. (Sodium azide dissolved in liquid hydrogenazide conducts readily.24) The compound was soluble in ten organic solventsexamined and thus behaved neither as an ionising solvent nor as a polarcompound. When carried by a stream of Fitrogen into an excess of liquidammonia it reacted quantitatively according to the equation3NR,ClChlorine azide reacted with pentane, forming hydrogen azide and mono-chloropentane, and with metals both a chloride and an azide were produced.I* H.S. Booth and C. A. Seabright, J. Amer. Chem. SOC., 1943, 65, 1834.20 H. S. Booth and C. G. Frary, ibid., p. 1836.21 Ibid., p. 1783.22 G. S. Forbes and H. H. Anderson, ibid., 1940, 62, 761.2s W. J. Frierson, J. Kronrad, and A. W. Browne, ibid., 1943, 66, 1696.24 A. W. Browne and G. E. F. Lundell, ibid., 1909, 31, 435.The term isocyanate is used here for a product which may be acyanate, an isocyanate, or a mixtureEMEL~~US : GENERAL. 65A further series of experimentsZ5 on the interaction of silver azide andchlorine azide in ethyl ether gave a deep blue solid compound of the formulaN,AgCl, which was stable below - 30" but decomposed at higher temper-atures into silver chloride and nitrogen.Cupric azide, which hitherto was believed to be a particularly unstablesubstance, has been re-examined in the course of the past year.2s Thesubstance previously described under this name was found to bk a basicazide, two definite compounds of this class of the formulae Cu(OH)N, andCu(N,),,Cu(OH), being prepared.The pure azide was obtained by theinteraction of cupric nitrate and sodium azide in aqueous solution. Theflocculent precipitate was freed from basic salts by treatment with dilutehydrazoic acid. The pure salt, which when dry was only moderatelysensitive to shock, was also prepared by heating the ammoniate describedby L.M. Dennis.27 Various 4-co-ordinated complex derivatives were alsoprepared, including the tetrammino- complex [ Cu ( NH3)4] (N,) ,, analogousderivatives containing amines and diamines, and also complexes of thetype [Cuxx(NH,),(N,),] which were shown to be, non-electrolytes. Thecomplexes containing ammonia were considerably less sensitive to deton-ation by shock than was the parent azide, whereas the amine complexescould not be detonated, though they burned readily when heated.The study of metallic carbonyls by W. Hieber and his co-workers hasbeen extended to include carbonyls of rhodium and osmium.28 A series ofrhodium carbonyl halides of the type Rh(CO),X, where X = C1, Br, or I,has been prepared by the action of carbon monoxide on the trihalide a tordinary or elevated temperatures, according to the halide ~ s e d .~ g Thesecompounds were volatile and crystalline, and the molecular weight of thechloride corresponded to a dimeric formula, represented in all probabilityby the structure (OC),Rh<Cl>Rh(CO),. c1Rhodium metal, when heated in carbon monoxide at 200"/280 atm.,gave a carbonyl of the formula [Rh(CO),],, which formed orange-yellowcrystals, m. p. 76". This compound resembles cobalt tetracarbonyl, andalso illustrates a point of difference between rhodium and iridium, foriridium carbonyls are not formed directly from the metal.Rhodium halides, when heated in carbon monoxide at 50--80"/200 atm.in the presence of cadmium, zinc, or silver to act as a haIogen acceptor,gave a carbonyl of the formula [Rh(CO),],.If the preparation was carriedout similarly but a t temperatures between 80" and 230°, the product was anew carbonyl of the formula Rh,(CO),,, which was characterised by com-paratively high stability. It was not, for example, attacked by dilute acidsor alkalis, and its solubility in organic solvents was low.25 W. J. Frierson and A. W. Browne, J . Amer. Chem. Soc., 1943, 65, 1698.26 A. Cirulis and M. Straumanis, 2. anorg. Chem., 1943, 251, 332, 335, 341.27 J . Arner. Chem. SOC., 1907, 29, 18.28 Cf. Ann. Reports, 1941, 38, 71 ; 1942, 39, 72.29 W. Hieber and H. Lagally, 2. anorg. Chem., 1943, 251, 96.REP.-VOL. XL. 66 INORGANIC CHEMISTRY.Rhodium carbonyl hydride, Rh( CO),H, was prepared by heating rhodiumin a mixture of hydrogen and carbon monoxide, the former being a t 50 andthe latter at 200 atm.This preparation is analogous to that of cobaltcarbonyl h~dride.~O The best method of preparation was by tho autoclavereaction of hydrated rhodium trichloride and carbon monoxide at 2OO0/2OOatm. The compound had a melting point of - 10" to - 12", and aboveits melting point lost hydrogen readily, forming the tetracarbonyl.Osmium carbonyl halides and carbonyls have now been fully described.31The former have been obtained from osmium halides by the usual high.pressure reaction with carbon monoxide, and are of several types. Inaddition to the characteristic tetracarbonyl halides, Os(CO),X2, corre-sponding with the iron compounds, compounds of the type OS(CO)~X, andOs(CO),X,, where X = C1, Br, or I , were prepared.In addition, iodidesand bromides of the type Os(CO),X were obtained, the molecular weight ofthe latter corresponding with the double formula (OC),Os<x>Os(CO),. XFor the preparation of pure osmium carbonyls two methods were avail-able. The first, which gave carbonyl halides as well as carbonyls, was bythe action of carbon monoxide on osmium halides in presence of a secondmetal to act as halogen acceptor. The second was by the action of carbonmonoxide on osmium tetroxide, and was similar to the preparation ofrhenium carbonyl from its hept~xide.~, The pentacarbonyl Os(CO), wasisolated from the mixture of products formed in the reaction betweenosmium halides and high-pressure carbon monoxide in presence of a metallicpowder. The oxyiodide, formed from the tetroxide and hydriodic acid,gave the best results.This carbonyl was remarkable for the readiness withwhich it lost carbon monoxide to form OS,(CO)~; indeed, the latter com-pound was the main product of the reaction, and was also formed in quan-tity by the interaction of osmium tetroxide and carbon monoxide a t150°/200 atm. Strong evidence for the existence of osmium carbonylhydride, Os(CO),H,, was also obtained, though this substance has not yetbeen fully characterised.Copper carbonyl, the existence of which has for some time been suspected,has now been prepared by the action of carbon monoxide on heated cuprousoxide.33 It is described as a white, readily sublimable solid, the vapour ofwhich is dissociated at a higher temperature with deposition of copper.The empirical formula Cu(CO), is assigned from preliminary analyses.Inthe same communication the formation of small yields of tellurium oarbonylby the action of carbon monoxide on tellurium is reported, though noneof the properties of this substance has so far been described.Reactions in liquid sulphur dioxide have already been described inthese Reports.34 Further work on the amphoteric behaviour of sulphites80 Cf. W. Hieber et al., 2. anorg. Chem., 1939, 240, 261 ; 243, 145, 156.31 W. Hieber and H. Stahan, Ber., 1942,75, 1472 ; 2. Elektrochem., 1943,49,288.s2 W. Hieber and H. Fuchs, 2. anorg.Chem., 1941, $248, 266.94 Ann. Reports, 1939, 36, 136.P. L. Robinson and K. R. Stainthorpe, Nature, 1944,158, 24EMELLUS : QENERAL. 67in this solvent has now been reported.35 Aluminium chloride has beenfound to react in liquid sulphur dioxide solution with tetramethylammoniumsulphite according to the equations :The second equation represents the redissolution of the sulphite, which isf i s t precipitated, by an excess of the soluble tetramethylammonium sulphite,the latter behaving as a base and being analogous to hydroxides in aqueoussystems or to amides in liquid ammonia. The course of the reaction inliquid sulphur dioxide is readily followed by a conductimetric titration.The extension of this observation on amphoteric behaviour is made moredifficult by the low solubility of many halides in sulphur dioxide.Conducti-metric titration of stannic chloride with tetramethylammonium sulphiteshows, however, that it behaves like aluminium chloride : a sulphite, orwhat is more probably a compound of the type Sn0,,sS02 analogous to anoxyhydrate in aqueous systems, is first precipitated and then redissolves inexcess of the precipitant, forming [ (CH,),N],(Sn( SO,),) (tetramethyl-ammonium orthosulphitostannate), or the corresponding meta-compound[ (CH,)4N],{Sn(S0,),}. Ageing of the precipitated sulphite occurs rapidlyand renders it incompletely soluble. Normally, therefore, in studying thesereactions excess of the aulphite is added and the excess is determined byback titration with thionyl chloride, which behaves as an acid in sulphurdioxide.Silicon tetrachloride and boron trichloride behaved similarly, thoughthere is some doubt as to the composition of the precipitate.With theformer, for example, formation of a true sulphite is very doubtful, and thecomposition is best represented as Si02,xS02. With antimony trichlorideand pentachloride the reaction was again similar. It was found that, whenthe solid precipitated from antimony pentachloride was redissolved in excessof tetramethylammonium sulphite and was treated with excess of thionylchloride, the compound [(CH,),N]SbCI, was formed and could be isolated.The reaction between a solution of tetramethylammonium sulphite andtin illustrates further the analogy between reactions in water, ammonia,and sulphur dioxide.I n the case of the first two solvents the action of an'' alkali " on zinc is represented by the equation :The titrations are made at - 30".Zn + 2KOH + 2H,O = K,[Zn(OH),] + H,Zn + BKNH, + 2NH, = K,[Zn(NH,),] + H,With a solution of sulphite in sulphur dioxide evolution of hydrogen can-not occur, but in its place one would expect sulphur monoxide, since thethionyl radical is the counterpart of the hydrogen ion in water or ammonia.Actually tin was found to dissolve in a solution of tetramethylammonium36 G. Jander and H. Hecht, 2. a w g . Chcm., 1943, ab0, 287, 30468 INORGANIC CHEMISTRY.sulphite in sulphur dioxide, the reactions being represented by theequationsSn -k [(CH,)gN12SO3 + 4so2 = [(CH3).&]2(Sn(SO&) + 2so2so = so2 + sII(CH3)gNI,SO, + s = [(CH,),N12S20,.Analysis of the reaction products showed a ratio of tin dissolved to thio-sulphate formed of 1 : 0.7-0.8, proving that this reaction scheme is sub-stantially correct.H. J. E.2. THE PREPARATION OF THE SOLID ELEMENTS IN A STATE OF PURITY.The preparation of the elements in a state of high purity has engagedconsiderable attention during the past fifteen years, and the Reportersconsider that the subject merits review a t the present stage of its develop-ment. Recent advances have been concerned chiefly with the metals andwith non-metallic elements which are solid under ordinary temperatureand pressure conditions, and it is to these solid elements that discussionis confined in this Report.The subject has been approached from theviewpoint of experimental methods, this approach leading to a better apprecia-tion of modern developments than a discussion of individual elements.The methods treated are designed for use on the laboratory scale, whereeconomic considerations are not paramount, rather than for applicationin industrial practice.An excellent monograph on pure metals,l in which their preparationand properties are authoritatively discussed, has appeared recently, and thisshould be consulted for details and bibliographies relating to earlier methodsof preparing the metallic elements. Two reviews on the availability and useof high-purity metals 2a may also be cited. In one of these an accountis given of efforts by the American Society for Testing Materials to obtainmetal samples of consistently high and accurately known purity; thefollowing percentage purity values for samples obtained or promised illustratethe high purity standards attained in individual cases by the use of specialmethods of preparation or purification : lead, zinc, and platinum, 99.9999 ;bismuth, 99.9984 or better ; cadmium, 99.999 ; gold, 99.998 ; aluminium,99.997-99-991 ; tin, about 99.995 ; copper, 99.994 or better ; silver, 99.983or better ; nickel, 99.97 or better ; magnesium, 99.97.Further improvement8have no doubt been effected since these values were published.The purity values given above and elsewhere in this Report, and in theliterature generally, are in most cases based on determinations (usually byspectrographic methods) of the various impurities present in the samples,since chemical methods for determination of the element concerned ark rarelycapable of establishing its content with the necessary accuracy in an almost1 A.E. van Arkal, " Reine Metalle," Berlin, 1939.T . A. Wright et al., Proc. Amer. SOC. Test. Mat., 1937, 37, I, 531, 538.C. H. Desch, Vortrage Hauptversammlung, 1938, Deut. ffes. Metallk., 1938, 1 ;Met. and Alloys, 1939, 10, No. 4, 204WELCH : PREPARATION OF SOLID ELEMENTS IN A STATE OF PURITY. 69pure sample. This " difference " method of assessing purity must clearlybe used with extreme care, since it presupposes that every impurity has beendetected and determined ; a number of purity estimates made in the literatureare suspect because the absence of conceivable contaminants has not beenfully established, and a need for caution in this respect is evident.The preparation of pure compounds by conventional methods of fractionalcrystallisation, distillation, etc., is outside the scope of this Report, althoughattention may be directed to a recently described technique for manipulatingreadily oxidisable solutions and precipitate^.^ Special methods of separ-ation applied to groups of closely similar elements are of special importance,however, in the preparation of the pure elements themselves, and the mostrecent work in this field is briefly discussed below.Methods of isolating orpurifying the elements are then considered under appropriate sub- headings.Separation of Closely Similar Elements by Chemical Means.-The difficultyof separating scandium from rare earths, thorium, etc., is well known, andan exhaustive experimental study and comparison of the available methodsis of considerable interest.Almost all the previously known methods areconsidered to be unsatisfactory, except fractional condensation of thechloride or sublimation of the acetylacetone complex ; the former givessatisfactory separation from all the common impurities except thorium,and possibly manganese, and the latter permits sharp separation from thorium,zirconium, hafnium, and rare earths, although iron, aluminium, and probablyberyllium, accompany the scandium. Both methods suffer from the dis-advantage that moderate or large quantities of material cannot be ex-peditiously handled, and the yields of purified material are poor.A newand useful method investigated in some detail consists in extracting withether an acid solution of the scandium preparation containing ammoniumthiocyanate ; the scandium is strongly concentrated in the ether phase.A single extraction permits recovery of 94% of the scandium present,separation from magnesium, calcium, rare earths, thorium, and manganesebeing almost complete ; ferrous iron, titanium, zirconium, hafnium, anduranium are largely removed, but beryllium , aluminium, indium, molyb-denum, rhenium, ferric iron, and cobalt may accompany the extractedscandium. Application of the method to a large quantity of 75--80~0pure scandium oxide resulted in extraction of 90% of the contained scandiumin a spectroscopically pure form.A recent method for separation of the rare-earth elements, depending ondifferences in the stability of their amalgams, shows considerable promise.When rare-earth acetate solutions are shaken with sodium amalgam,europium, samarium, and ytterbium are rapidly transferred to the amalgamphase ; the other rare-earth metals give amalgams much less readily underthe conditions proposed, their amalgam-forming power diminishing withincreasing atomic number.The method has been successfully applied t oseparation of neodymium-samarium and samarium-gadolinium mixtures,S. Rihl and R. Fricke, 2. anorg. Chem., 1943, 251, 405.W. Fischer and R.Bock, ibid., 1942, 249, 116. J. K. Marsh, J . , 1942, 39870 INORGANIC CHEMISTRY.from which samarium amalgam is rapidly obtained with little contaminationby neodymium or gadolinium.' Further purification is carried out byfractional decomposition of the amalgam with water or dilute acid, thesamarium dissolving preferentially and leaving the other rare-earth metalsin the amalgam. By one application of this two-fold reaction the neodymiumcontent of a mixture with samarium is reduced from 70 to O.O1~o-a separ-ation which is remarkable in comparison with those achieved by the classicalfractionation methods. Separation from gadolinium is considered to beequally rapid. By a very similar process, ytterbium may be isolated frommixtures with lutecium and thulium,* ytterbium preparations containingless than O .O l ~ o of the accompanying rare-earth metals being readilyobtained. By addition of samarium and its subsequent removal as amalgam,small quantities of ytterbium remaining iu lutecium preparations may beremoved, the ytterbium being co-extracted with the samarium; by thismeans lutecium salts containing only 0.001 % of ytterbium are obtainable.Application of the same amalgam procedure to a mixture of gadolinium,samarium, and europium acetates affords a pure gadolinium acetate solutionand an amalgam containing the europium and samarium; these two metalscan be separated subsequently .Q An electrolytic method of amalgam form-ation gives results similar to those just described in that europium, ytterbium,and samarium are concentrated in the mercury phase.lo These new methods,judiciously combined with the older processes of fractionation, have greatlyfacilitated the separation of some of the individual rare-earth metals.Incertain caaes, however, the exclusive use of the fractionation methodsappears essential, and such methods have recently been used to isolateabout 12 g. of holmium oxide containing not more than O.l')'o of erbiumand less than 0.08% of dysprosium and yttrium.llA preliminary investigation of the possibility of separating the rareearths by fractional base-exchange with zeolites has recently been de-scribed.12 Fractionation is obtained if a concentrated solution of rare-earth salts is treated with a quantity of zeolite insufficient to exchangewith all the earths; the metals most strongly held by the zeolite are thosewhioh show the smallest ionic radii in their crystalline compounds.Fractional removal from the zeolite is also possible, the ions of larger radiusbeing removed preferentially. A chromatographic separation prooess hasalso been applied to the rare-earth elements.13The separation of zirconium and hafnium still remains a process in whichmethods of fiactionation are indispensable.A careful study has now beenmade of the optimum conditions for effective separation of these two metalsby fractional precipitation of their ferrocyanides.14 Four successive7 J. I(. Marsh, J., 1942, 523.10 H. N. McCoy and R. P. Hammond, J . Amer. Chem. Soc., 1942,64,1009.11 W.Feit, 2. anorg. Chm., 1940, 243, 276.1) R. G. Ruseell and D. W. Pearce, J . Amer. Chem. SOC., 1943, 65, 1924.13 0. Eriimetrii, T. G. Sahama, and V. Ksnula, Ann. Acad. Sci. Fennicoe, Ser. A,16 W. C. Schumb and F. K. Pittman, Ind. Eng. Chem. (Anal.), 1942,14,512.Idem, ibid., 1943, 8 . 9 Idem, ibid., p. 531.1943, 67, No. 3, 6 WELCH: PREPARATION OF SOLID ELEMENTS IN A STATE OF PURITY. 71fraotionations by the procedure recommended have increased the hafniumoxide content of a mixture of the two oxides from 12 to 20,36, 62, and SO%,respectively. The precipitation of zirconium and hafnium phosphates hasalso been investigated in a similar manner ; 15 phosphate fractionationshave hitherto been rendered difficult in this case by the gelatinous natureof the precipitates, but in the new procedure precipitation of the zirconium-hafnium phosphate in a granular form which is easily filtered off is securedby spraying the sulphate solution [Z-5 yo of (Zr,Hf)OSO,] and phosphoricricid (245%) (both in 10% sulphuric acid) at equivalent rates into a largevolume of lo?; sulphuric acid held at 75".This technique, combined with anew method of reconverting the phosphates into the soluble sulphates for thenext fractionation, has given new scope to a classical separation process.In a typical series of seven precipitations, in each of which about 56% of thedissolved material was converted into phosphate, hafnium oxide was en-riched from 13% in the original oxide mixture to 93%, the hafnium in theconcentrates representing 10% of the total quantity of hafnium in thestarting material.Two successive treatments of material low in hafnium,followed by recrystallisation of the oxychloride, have yielded zirconiumsalts in which hafnium could not be detected by spectrographic examination.Preparation of Elements by Thermal Decomposition of their Compounds.-Thermal decomposition of 'a suitable compound appears t o be the simplestconceivable method of isolating &n element, and although this method hasrelatively few applications to solid elements it has certain interestingpossibilities and deserves brief mention. Pure metals of the platinum groupare customarily prepared by ignition of the purified salts obtained in thecourse of their separation.ls Sodium, potassium, rubidium, and cesiumhave been prepared by pyrolysis of their azides in a high vacuum; 1' thereactions occur at moderate temperatures (275-395"), and after distillation(in the same apparatus) the metals are spectroscopically pure and gas-free.Decomposition methods are particularly applicable to the less volatileelements, which cannot distil out of the heated zone and recombine withother decomposition products.This is well illustrated by C. W. von Bolton'soriginal method of preparing tantalum,l8 in which rods of tantalum dioxidewere heated to a high temperature in a vacuum by passage of an electriocurrent. An interesting recent example of a reaction of the same generaltype occurs in the preparation of pure germanium by decomposition of itsnitride ; l9 treatment of germanium tetrachloride with ammonia affords theimide, Ge(NH),, together with ammonium chloride ; the latter is washedout of the product with liquid ammonia, and the imide heated in nitrogen.A t about 150" germanam, Ge,N3H, is formed, and at 350" this is convertedl6 E.M. Larsen, W. C. Fernelius, and L. L. Quill, Id. Enp. Chem. (Awl.), 1943,15,l6 E. Wichers, R. Gilchriat, and W. H. Swanger, Trans. Amer. Inst. Min. Met. Eng.,512.1928,76, 602; E. Wichere, J. Res. Nat. Bur. Stand., 1933,10, 819.R. Suhrmann and K. Clusius, 2. anorg. Chem., 1926, 152, 52.l 8 2. Elektrochem., 1906,11, 45.le R. Schwarz, Die Chemie, 1042, 66, 4672 INORGANIC CHEMISTRY.into the nitride, Ge,N,; dissociation of the nitride into germanium andnitrogen takes place at 1000".Interesting information on the properties of carbonaceous materialobtained by heating sucrose a t temperatures between 300" and 1100" isgiven in a recent paper.20 Material prepared by heating sucrose in hydrogenat 1000-1100" for 10 hours consists of substantially pure carbon in the formof graphite crystallites about 10 x 30 x 30 A.; specimens prepared at lowertemperatures contain several yo of hydrogen and oxygen." Hot-wire " Metha&.-In " hot-wire " methods the vapour of a volatilecompound of the desired element is thermally decomposed or reduced a t thesurface of a wire heated to a suitable high temperature by passage of anelectric current, the element being deposited on the wire as a more or lesscoherent coating.In the preparation of a metal by this means a thin" starting wire " may be drawn from a previously prepared specimen of themetal itself, the thermal reaction then being employed to build up a homo-geneous rod which may reach a diameter of several millimetres; since thedeposited metal does not come into contact with any extraneous material,contamination is minimised.The apparatus generally used in the hot-wire technique consists of asuitably designed glass or quartz bulb with heavy sealed-in leads whichconduct the heating current for the wire, the latter being supported by theleads in the centre of the bulb. Suitable provision is made for introdu9ingthe reactants into the bulb, and for pumping off any volatile decompositionproducts.The principal experimental difficulty is the maintenance of thewire at a constant temperature; if, as in most cases, the material depositedconducts electricity, the current passing must be continuously increasedas deposition proceeds, sometimes from a fraction of an ampere at thebeginning of the experiment to several hundred amperes at the end.A review of applications of the hot-wire technique, by one of its principalexponents,21 illustfates its versatility. In the majority of the applicationsthe reaction taking place a t the wire is thermal decomposition of a halide ofthe element (frequently the iodide); if a supply of the element in a finely-divided form, prepared by some other method, is placed in the bulb andheated to a suitable temperature, the liberated halogen may react con-tinuously with it, and thus replenish the halide required for decompositiona t the wire.Copper, titanium, zirconium, hafnium, thorium, vanadium,chromium, molybdenum, tungsten, rhenium, iron, and nickel have allbeen prepared by this form of the hot-wire technique, the deposition temper-atures for these elements varying from 600" t o 2000°, and the temperatureof the "reserve" of crude metal ranging from 20" to 800". In otherapplications a mixture of hydrogen with the vapour of a halide is passedover the heated wire, and the halogen hydride liberated in the consequentreduction is pumped off; beryllium, silicon, and vanadium have beenprepared by this method. Niobium, tantalum, and platinum are best20 U.Hofmann and F. Sinkel, 2. anorg. Chern., 1940, 245, 85.21 A. E. van Arkel, Metallw., 1934,13,405,511WELCH: PREPARATION OF SOLID ELEMENTS IN A STATE OF PURITY. 73obtained by decomposing a halide (or carbonyl halide in the case of platinum)at the hot wire, and removing the gaseous products by direct pumping. Inall these methods, essential conditions for deposition of the element are thatthe compound employed should be appreciably dissociated at temperaturesbelow the melting point of the element, and that the vapour pressure of theelement should be considerably less than that of the compound at thetemperature chosen for the heated wire.The most fruitful applications of hot-wire methods have been to elementsof high melting point which are not readily obtained in massive form byfusion, notably to titanium, zirconium,22 hafnium,23 thorium,24 niobiumand tantalum,Z5 rhenium,26 and boron.In several of these examples hot-wire methods afford the only means of preparing the element in a highlyductile form, other methods giving products which are rendered brittle bytraces of oxygen, nitrogen, or other impurities. I n one of the more recentaccounts of hot-wire methods 27 the preparation of ductile titanium isdescribed ; crude titanium, prepared by reduction of the tetrachloride (or,less satisfactorily, potassium or sodium titanifluoride) with metallic sodium,is confined with a little iodine in a bulb heated to 500" or more, the titaniumbeing deposited on a wire heated to 1300".As indicated above, the halogenis continuously re-used to form titanium tetraiodide, in which form the metalis conveyed from the supply of crude material and deposited by decom-position on the wire. The titanium is o.btained in rods up to 7 mm. indiameter, which contain about 0.14% of iron (introduced from the vesselused in preparing the crude metal) and a little silicon, but are otherwise pure.In the original paper the effects of wire temperature and other conditionson the reaction and its products are discussed in some detail.Commercial " pure " boron from various sources has recently been shownto contain less than 80% of the element ; the balance consists of oxygen andaluminium or magnesium, the latter evidently being introduced during thereduction process.28 Special intere.st therefore attaches to a new preparationof genuinely pure boron by the hot-wire method.29 The reaction employedwas the reduction of boron tribromide by hydrogen, rendered particularlysuitable by the ease with which the tribromide can be purified by con-ventional vacuum fractionation methods in all-glass apparatus.Since boroncould not be used in the " starting wire," deposition was carried out onLz A. E. van Arkel and J. H. de Boer, 2. anorg. Chern., 1925, 148, 345; J. H. deBoer and J. D. Fast, ibid., 1926, 153, 1 ; 1930, 187, 177; C. J. Smithells, Metal Ind.(Lond.), 1931, 38, 336.aa J. H. de Boer and J. D. Fast, 2. ar2.org. Chern., 1930,187, 193.24 Ref. (I), p. 215.25 W. G. Burgers and J. C. M.Basart, 2. anorg. Chern., 1934, 216, 223; K. Moers,a6 C. Agte, H. Alterthum, K. Becker, G. Heyne, and K. Moers, 2. anorg. Chem.,Metallw., 1934,13, 640.1931,196, 129.J. D. Fast, ibid., 1939, 241, 42.A. W. Laubengeyer, D. T. Hurd, A. E. Newkirk, and J. L. Hoard, ibicE., 1943,a6 E. H. WhslowandH. A. Liebhafsky, J. Amer. Chem. SOC., 1942,84, 2725.66, 1924.0 74 INORGANIC CHEMISTRY.0.01-in. tungsten or (preferably) " hydrided " tantalum wires, the latterconsisting merely of tantalum filaments pre-treated with hydrogen at a hightemperature before use. With the wire a t about 1300" and a partial pressureof 18 mm. of boron tribromide in the reacting mixture (total pressureatmospheric), the boron was produced as crystals up to 1 mm. in lengthwhich were readily detachable from the wire ; as much as 0.5 g.of crystallineproduct could be obtairled in a single run. The boron wm shown by spectro-graphic examination to be free from non-volatile impurities such as silicon,carbon, or tantalum from the wire. In this case an application of the hot-wire method has permitted a complete re-examination of the properties ofboron, carried out on material of proved purity. It is noteworthy that thecrystalline boron had a hardness of 9.3 on the modified Moh scale, approach-ing that of boron carbide. An amorphous form of boron could be pre-pctred by using a lower wire temperature, or increasing the boron tribromidepressure in the reaction zone.Reduction Metho&s.-Conventional methods of reducing oxides, halides,and other compounds by purely chemical means have in recent years beenrefined by the introduction of new reducing agents and a variety of newtechniques. The classical method of reducing a metallic oxide with hydrogenis still applicable, however, in some cases ; it is stated, for example, that purecobalt and nickel are obtained by this simple method: and the percentagepurity of cobalt prepared from cobaltous oxide and hydrogen at 550-1200"has been given as 99.81-99*89~&~ Iron of purity superior to that of elec-trolytic iron has recently been produced on a fairly large scale (about 500 g.of product per day) by a process involving hydrogen reduction of ferricoxide.31 The starting material for this process was commercial electrolyticsheet iron containing O - O l l % of copper and 0.018% of phosphorus.Theseimpurities were largely removed by dissolving the metal in high-purityhydrochloric acid and allowing the solution to stand in contact with excessof the iron. The ferrous chloride was crystallised, dried, and convertedinto ferric oxide by treatment with steam and air at 250" ; after being washedwith dilute hydrochloric acid and water, the oxide contained only one-quarter to one-third of the nickel (04014%) present as impurity in the originaliron. The ferric oxide, contained in alumina boats, was reduced by hydrogena t 760", electrically heated tube furnaces being employed for this operation ;in order to minimise spontaneous oxidation of the metal powder on removalfrom the furnace, the reduced material was sintered in nitrogen at 900"before the furnace tubes were opened.A preliminary melting of the ironpowder was carried out in a nitrogen atmosphere; slight oxidation duringthis process was unavoidable, but it served to remove some of the morereadily oxidisable impurities from the metal. Finally, the oxygen wasremoved from the main bulk of material by a process of melting in anatmosphere of hydrogen at successively reduced pressures (15,6, and 3 cm.).The product from the last melting operation was estimated to contain atG. F. Huttig and R. Kassler, 2. anorg. Chem., 1930, 187,25.mal F. Adcock, J . SOC. Chem. Ind., 1940,69,28WELCH : PREPARATION OF SOLID ELEMENTS IN A STATE OF PURITY. 75most 0-006~0 of total impurities.Melting of the iron was in each case carriedout in a high-frequency induction furnace; heating in such furnaces isproduced within the mass of metal itself by alternating currents of largemagnitude, induced in the metal by a suitably placed primary coil suppliedfrom a high-frequency oscillator. The simplicity, flexibility, and all-roundefficiency of induction furnaces renders them eminently suitable for meltingor heat-treatment of moderate masses of metal; high temperatures arereadily attained, and the complete absence of fuel combustion productsand of external heating devices simplifies the problem of preserving the moltenmetal from contamination. The choice of a suitable inert refractory materialstill remains, and is a source of difficulty in many studies on pure metals;in the work on iron just described, impervious sintered alumina crucibleswere selected for the melting operations.Brief reference may be made to several other elements which are preparedin the pure state by hydrogen reduction processes.Molybdenum is obtainedby reducing the dioxide in hydrogen at 900-1200"; the resulting powderis pressed into bars, which are heated electrically to just below the meltingpoint in an atmosphere of hydrogen. This sintering process expels volatileimpurities, and completes the reduction of any residual oxide. The ingotsof metal can afterwards be '' swaged " and drawn into wire, or rolled intosheet.32 Pure rhenium metal is prepared by hydrogen reduction of am-monium per-rhenate, the reaction being completed a t 1000°?3 Metallicvanadium, stated to be 99435% pure, is obtainable by reduction of speciallyprepared vanadium trichloride with hydrogen, but the reaction is slow.3aElemental arsenic containing less than 0.002 yo of antimony, 0.0002~0of iron, 0.005% of sulphur, and 0.01% of phosphorus is stated to be obtainedby reducing recrystallised ammonium dihydrogen arsenate with ammoniaa t 1000°.35The use of novel methods of reduction is well illustrated by two processesfor the preparation of pure metallic chromium.36 An essential conditionfor effective reduction of chromic oxide by hydrogen is the maintenance ofthe pressure of water vapour produced in the reaction a t a low value.37In the first method this condition is secured by placing thin layers of chromicoxide (prepared by heating redistilled chromium trioxide) between platesof metallic tantalum, and " hydriding " the tantalum by heating in com-mercial hydrogen, from which the impurities are not absorbed; when thetantalum ia saturated with hydrogen the pressure in the reaction chamber,heated at lOOO", is reduced, and the chromic oxide then undergoes reductionby the pure hydrogen evolved by dissociation of the tantalum hydride;the low pressure prevailing ensures rapid removal of water vapour fromthe reaction zone.In the second method calcium hydride, CaH',, is em-31 C . J. Smithells, Metal. Ind. (Lond.), 1931, 38, 336.33 L. C . Hurd and E. Brimm, Inorganic Syntheses, 1939, 1, 175.34 T. Doring and J.Geiler, 2. anory. Chem., 1934,221, 56.35 -4. dePassill6, Compt. rend., 1934, 198, 1781.3' P. P. Alexander, Met. and Alloys, 1934, 6, 37.37 H. von Wartenberg and S. Aoyama, 2. Elektrochem., 1927,33, 14476 INORGANIC CHEMISTRY.ployed as the reducing agent; this liberates hydrogen on heating, and themetallic calcium set free is available to react with water vapour formedwhen the chromic oxide is reduced. The water is thus removed rapidlyby chemical means, and the reaction responsible for its removal yields a freshquantity of hydrogen gas for reduction purposes. The effectiveness of thisingenious process may be judged from the claim that chromic oxide can bereduced completely by calcium hydride in 30 minutes at a temperature aslow as 470".The chromium produced is 99.95% pure, the chief impuritybeing calcium. It is stated that a similar method of reduction has beensuccessfully used with oxides of thorium, beryllium, vanadium, and boron.Metallic calcium proves to be a valuable reducing agent for the preparationof certain pure metals. Granules of metallic chromium which are moderatelyductile can be obtained by reducing chromic chloride or chromic oxide withcalcium in a steel bomb heated (by induction) in an atmosphere of argon.38The successful preparation of even moderately pure chromium from theoxide and calcium is remarkable, for under low pressures calcium oxide isitself reduced by chromium; evidently the equilibrium is to a large extentdependent on pressure, the high pressure developed in a bomb favouring theformation of metallic chromium. This pressure effect may well repay furtherstudy in other similar cases.In its simple form the reduction of chromicoxide by calcium is of little practical value, for chromium is not readilymelted and cast, and the granular product cannot be pressed or sintered to acoherent mass of metal. A chromium powder that can be sintered is pre-pared by carrying out the reduction at 1000" in a flux of molten calciumand barium chlorides, in an argon atmosphere; the use of a bomb is un-necessary in this case. The initial product, obtained by extracting solublematerial from the cooled melt with water and dilute nitric acid, is given asecond similar treatment with a small quantity of calcium to ensure reductionof small inclusions of oxide.Sintering of pressed bars of the pure chromiumis carried out first at 1300" in a vacuum, and then at 1600-1700" in argon,the bars being placed on beryllium oxide refractory supports; the sinteredmetal is brittle at room temperature, but can be rolled under barium chlorideat about 1250". It is stated that thorium, uranium, and vanadium can beprepared by methods similar to that just described.The preparation of pure titanium and zirconium by reduction of theiroxides and halides has been discussed in some and particulars havebeen given of the reduction of the dioxides with calcium in a calcium chlorideand barium chloride flux. Although they are ductile at moderate temper-atures, the metals obtained still contain a little oxygen, the presence of whichis admittedly due to the equilibria referred to above.This oxygen cannotbe removed by any known deoxidiser.A simple and elegant method for preparation of pure rubidium or casiumfrom a halide by reduction with calcium has been described.*O The halide-t 8 W. Kroll, 2. anorg. Chem., 1936, 226, 23.40 F. C. Schmidt, F. J. Studor, and J,. Sottysiak, J . Amer. Chem. SOC., 1938, 60,as Idem, ibid., 1937, 234, 42.2780WELCH: PREPARATION OF SOLID ELEMENTS IN A STATE OF PURITY. 77calcium mixture is placed in a nickel tube, which is practically sealed by bend-ing over the ends and suspended in an evacuated glass enclosure. Thenickel tube is heated by induction; the alkali metal then distils through theseams, and is collected in a suitably placed bulb.The very strong affinity of elemental zirconium for oxygen, combinedwith the refractory nature of the oxide, renders the metal a particularlyuseful, if expensive, reducing agent.The alkali metals have been obtainedin a very pure state by reduction of their sulphates, chromates, dichromates,molybdates, and tungstates with zirconium.41 Excess of zirconium must beused, otherwise the reactions are explosive. For the preparation ofpotassium, rubidium, and czsium, heating of mixtures of the chromates withzirconium powder (1 part to 4 parts, by weight) at 700-800" is recom-mended; a similar mixture with the molybdate, heated at 550", is preferredfor sodium. Lithium is obtained from the chromate (1 part to 8 of zirconium,at 450-600"), but the yield is small.These reactions are useful because themixed starting materials are stable for indefinite periods in air, the reactiontemperatures are moderate, no readily volatile products other than thealkali metals are obtained, and under optimum conditions the yields aregood.Preparation of Metals by Electrolytic Methods.-A number of metals areprepared in the pure state by electrolysis of solutions or fused salt meltscontaining their compounds ; methods of electrolytic refining in which ananode of previously prepared crude metal is employed are discussed separatelybelow.Metallic gallium is successfully prepared by electrolysis of a solutionof gallium hydroxide in sodium hydroxide solution, platinum electrodesbeing used.42 The temperature of the solution is kept above'30°, the meltingpoint of the metal, and the liquid gallium is collected in a shallow glass cupbelow the cathode, with which it remains in electrical connection.Theinitial product is freed from traces of lead, tin, and platinum by washingsuccessively with hydrochloric acid (1 : l), concentrated nitric acid, and dilutehydrochloric acid ; the purified gallium is spectroscopically pure exceptfor a faint trace of iron. Direct electrolysis of an alkaline extract of germaniteore has recently been employed to give a deposit of gallium and ger-manium; 43 the latter is removed b'y treating the deposit with chlorine anddistilling off the resulting germanium tetrachloride, and the residual galliumtrichloride, after removal of lead, antimony, and molybdenum by precipit-ation with hydrogen sulphide, is used for the electrolytic preparationof galliummetal. This new method affords a simple and rapid means of obtainingpure gallium from its principal natural source.Tin is an interesting example of a metal the properties of which areconsiderably affected by traces of impurity; it has been shown that as littleas 0.0035% of bismuth imparts an unusual " cored " structure to the cast41 J.H. de Boer, J. Broos, and H. Emmens, 2. anorg. Chem., 1930,191, 113.4a F. Sebba and W. Pugh, J., 1937, 1371.D. J. Lloyd and W. Pugh, ibid., 1943, 878 TNORQANfC CHEMISTRY.metal, and inhibits the transition to grey tin a t low temperatures.44 Com-mercial samples of supposedly “ pure ” tin all showed the cored structureafter casting, and a “ structurally pure ” product, shown to be free frombismuth, was obtained only by electrolysis of a solution of stannous chloridecontaining some suspended metastannic acid to adsorb impurities.Needle-like crystals of pure thorium are stated to be obtained by electro-lysis of an aqueous solution of thorium sulphamate.*5The technique of preparing metals by electrolysis of salt melts is illustratedby the production of pure tantalum,4* and niobium 40from melts containing complex fluorides of the metals.In the case of uraniumthe electrolyte consists of equal parts by weight of calcium and potassiumchlorides containing the green complex fluoride KUF,; this is fused at775” in an electrically heated graphite crucible, which serves as the anode.The cathode is a molybdenum strip suspended in the centre of the crucible.As electrolysis (requiring 30 amp.at about 5 volts) proceeds, uraniumseparates as a tree-like deposit on the cathode, which is removed and re-placed by a new molybdenum strip a t intervals; additions of the electrolyteconstituents are made when necessary. The cooled cathode material,containing solidified salts from the bath, is washed with water, dilute aceticacid, alcohol, and ether, and dried ; insoluble calcium fIuoride in the productis readily washed away from the very much denser uranium metal. Theuranium is obtained as a coarse, grey powder, which is pressed into pelletsand fused in a vacuum in an induction furnace. The metal then contains0.06% of carbon, 0.05% of iron, and 0.01 yo of silicon. I n this process thecomplex fluoride was adopted as electrolyte after tests had shown theunsuitability of a uranyl salt or uranium trioxide; these gave a deposit ofuranium dioxide at the cathode during electrolysis.A closely similar technique is used in the case of the thorium,47 exceptthat potassium and sodium chlorides, with KThF,, are employed in themelt to obviate difficulties due to formation of calcium fluoride, which inthis case is not easily washed out of the product.The pressed, sintered,and degassed metal is stated to be very soft, and to contain only 0.02%of carbon, 0.05% of silicon, and 0.005% of iron.Tantalum and niobiumproduced by electrolysis, under similar conditions, of the complex fluoridesK,TaF, 48 and K,NbF, 49 are of comparable purity; in these instances,however, the “ anode effect,” well known in the electrolysis of melts of thistype, is troublesome unless tantalum or niobium pentoxide is also added tothe molten electrolyte.Further useful details of the technique of electrolysis of fused salts areprovided by a long paper on the isolation of pure rare-earth metals,50 and afull description of the preparation of pure metallic scandium.51 Pure4 4 C. W. Mason and W. D. Forgeng, Met. and Alloys, 1935, 6, 87.15 R. Piontelli and A. Giulotti, Chim. e Z’InCE., 1939,21,478.46 F. H. Driggs and W. C . Lillienduhl, I d . ErLg. Chem., 1930, 22, 518.4 7 Idem, ibid., p.1302. 4 8 Idem, &id., 1931,23, 634.49 C. W. Bake, ibid., 1935, 27, 1166.O1 W. Fischer, K. Briinger, and H. Grieneisen, 2. a w g . Chcm., 1937, 231, 54.F. Trombe, Ann. Chim., 1936,6,349WELCH : PREPARATION OF SOLID ELEMENTS IN A STATE OF PURITY. 79cerium, for example, is prepared by electrolysis, a t 800-850", of a fusedmixture of anhydrous cerous chloride (60%) and potassium chloride (40%),with an addition of about 5% of calcium fluoride. The apparatus foundmost suitable is a graphite crucible (anode), with a central rotating cathodeof molybdenum or tungsten, shielded along most of its length by a concentricquartz tube ; the metal collects in a, sintered fluorite or quartz crucible fittedinto the bottom of the graphite container, into which the lower end of thecathode projects.The cerium obtained contains potassium, which is re-moved by fusion in a vacuum in a tube furnace, or in a cathode-ray furnaceof interesting design which permits efficient attainment of very hightemperatures. Lanthanum, neodymium, and praseodymium are obtainedby very similar methods, but in the preparation of samarium and gadoliniumthe method is modified by the u8e of a pool of molten cadmium as the cathode ;the cadmium is afterwards distilled from the resulting alloy by heatingin a vacuum a t 1300". An analogous method is applied in the preparationof s~andium,~l the cathode consisting of molten zinc of high purity; evenwith special precautions during electrolysis, some oxidation of the scandium-zinc alloy is difficult to prevent, and the oxide is subsequently " filtered off ''from the molten metal, with inevitable loss of scandium, by passing it througha tungsten crucible with a perforation in the bottom. The zinc is finallydistilled off by slow heating to 1250" in a vacuum ; the scandium then remainsin a highly sintered condition.Although the percentage purity of themetal obtained is given as only 94-98%, this figure must be consideredin relation to the high reactivity and affinity for oxygen associated withscandium metal.Puri$cation of Solid Elements by Distillation.-A number of solid elementsare prepared in the pure state by applying some method of purification to acrude material, rather than by direct production from a purified compound.I n a number of cases, distillation at high temperatures has been investigatedas a means of effecting the necessary purification. A review is available 52covering the technique and experimental difficulties involved in some detail,and describing experiments (on the laboratory scale) on the distillationof chromium, aluminium, silicon, beryllium, iron, copper, nickel, tin, andlead.The purification of magnesium by distillation methods has also beendiscussed. 53A particularly difficult case of purification of a metal by distillationarose in work carried out at the National Physical Laboratory on the pro-duction of pure beryllium,54 and this merits brief description. Berylliumprepared by electrolysis of fluoride melts, although 99.6-99.7 yo pure,obstinately retains a little oxygen, which cannot be excluded by any simplemodification of the electrolysis technique ; the oxygen present causes51 W.Kroll, iWetaZZw., 1934, 13, 726, 789; Metal Ind. (Lond.), 1935, 47, 3, 39, 103,53 W. Kaufmann and P. Siedler, Z. Eleklrochem., 1931, 37, 402; J. HQenguel and54 H. A. Sloman, J . Inst. Metals, 1938, 49, 366.155.G. Chaudron, Cornpt. rend., 1931,193, 77180 INORGANIC CHEMISTRY.deposition of a beryllium-beryllium oxide eutectic in the solidified metal,and this is said to be responsible for the brittleness previously associatedwith metallic beryllium. A distillation apparatus was eventually constructedin which the beryllium, contained in a crucible of sintered beryllium oxide,was heated to about 1900" by induction; the vapour issued through a" baffle," designed to prevent collection of splashes of the molten metal,and was condensed on a water-cooled silica surface.The whole apparatuswas kept under high vacuum. Although distillation was slow and thequantity of product small, beryllium of purity estimated a t 99.95-99-97was obtained; this met'al was ductile, and contained none of the eutecticpreviously mentioned. Attempts to deoxidise beryllium by chemicalmeans-including fusion in the flame of an atomic hydrogen blowpipe-were unsuccessful, and apparently distillation is the only known means ofpreparing an oxygen-free metal.A simple and ingenious apparatus designed for the distillation of zincon the laboratory scale 55 is noteworthy as a prototype ; the zinc is condensedon a graphite sleeve so designed that the crystals grow downwards awayfrom the surface, and are readily removed without metal which has beenin contact with graphite.I n the commercial distillation of zinc a productof 99.994% purity is stated to be obtainable; 56 the use of carborundumas a refractory material in the apparatus may be noted.Tellurium is obtained in the pure state by vacuum distillation of a com-mercial electrolytic product containing selenium, copper, iron, and someoxide. 57Puri$cation of Metals by Xintering or Fusion in a Vacuum.-Passingreference has already been made to sintering and vacuum fusion processes,which are of special value in dealing with metals of high melting point andhigh oxygen affinity, respectively.Both methods are used in the preparationof pure, ductile tantalum and A crude tantalum powder isobtained by reduction of the double potassium fluoride, K,TaF,, withsodium ; this is pressed into bars and sintered in a vacuum a t a temperaturejust below the melting point to remove volatile impurities. Alternatively,the crude metal is converted into tantalum hydride by heating in hydrogenat IOOO", and the hydride is decomposed by sintering at 1500" or above.The sintered bars of tantalum produced,in either process are brittle, andvacuum fusion is necessary to render the metal ductile; since the meltingpoint is very high (2800-2850"), the fusion process is carried out by strikingan electric arc between a block of the sintered material and an electrode oftantalum or tungsten.The final product is sufficiently ductile to be rolledwithout difficulty into sheets 0.1 mm. thick. Ductile niobium is producedby an exactly similar method.5 5 E. C. Truesdale and G. Edmunds, h e r . Inst. Min. Met. Eng., Inst. Metalss6 H. Matthies, Metall u. Erz, 1936, 33, 280.5 7 F. C. Kracek, J. Amr. Chem. SOC., 1941, 63, 1989.5 a C. J. Smithells, Metal I d . (Lond.), 1931, 38, 336.Divn., Tech. Publ. 1033 (1939)WELCH : PREPARATION OF SOLID ELEMENTS IN A STATE OF PURITY. 81Final purification of cathodic nickel has been effected by annealingthe metal in hydrogen a t 1050" to remove carbon and sulphur, and thenfusing in a vacuum in specially bonded magnesia crucibles.59 The productis 99.94% pure, the chief impurities being iron (0.03%) and cobalt (0.016%).Attention may be directed to two papers dealing with the theoreticalaspects of degassing of metals,m in which it is shown that maximum ratesof degassing are reached over certain temperature ranges, which are simplyrelated to the melting points of the metals.The results clearly have apractical bearing on the purification of metals by sintering in a vacuum.Electrolytic Puri$cation of &etch.-This method of refining, so wellknown in industrial practice, finds useful applications in the preparationof high-purity metals on the laboratory scale. Recent work in this directionis well exemplified by a method for producing 99.999% pure copper.61The first stage in the refining of commercial electrolytic copper to this purityis an electrolysis at low current density through a bath of sulphuric acidand copper sulphate, anodes of the crude metal and cathodes of pure coppersheet being employed in the usual manner.This electrolysis is stated tofree the copper from all the important impurities except sulphur ; the latteris removed by air-blowing the surface of the molten metal, a process whichnecessarily introduces oxygen, with clay, iron, and graphite from the meltingcrucible. Final purification is effected by a second electrolysis through acopper nitrate electrolyte. In each of the electrolyses " starting sheets ')are first obtained by deposition on stainless steel plates, from which they canafterwards be stripped.The purified metal is cast into oxygen-free rods bymelting in hydrogen in a specially designed casting apparatus.Metallic indium estimated to contain not more than O - O O l ~ o of totalimpurities has been prepared by electrolytic refining of a, " pure )' com-mercial product through an indium chloride solution, two successive electro-lyses being required.62 Other metals to which electrolytic refining is par-ticularly applicable include zinc,63 lead,64 mangane~e,~5 and silver.66A particularly novel method of electrolytic purification of aluminium,in which both electrodes are composed of molten metal, has been de~cribed.~'The lowest and densest layer in the cell is an aluminium-copper alloy con-taining 33% of copper ; above this is the electrolyte, consisting of moltenalkali-metal and aluminium fluorides and barium chloride ; the upper layeris the cathode of pure, molten aluminium, which is less dense than the fused6' L.Jordan, W. H. Swanger, et al., J. Reg. Nut. Bur. Stand., 1930, 5, 1291.60 G. F. Huttig, H. Thiemer, and W. Breuer, 2. anorg. Chem., 1942, 249, 134; G. F.61 J. S. Smart, jun., A. A. Smith, jun., and A. J. Phillips, Amer. Inst. Min. Met.Huttig and H. H. BIudau, ibid., 1942, 250,36.Eng., Inst. Metals Divn., Tech. Publ. 1289 (1941).G. P. Baxter and C. M. Alter, J. Amer. Chem. SOC., 1933, 55, 1943.R. S. Russell, Proc. Awl. Inst. Min. Met., 1932, 87, 145.63 W. Hiinig, Metallu. Erz, 1936, 33, 274.6 5 H. H. Oaks and W. E. Bradt, Trans. Amer. Electrochem.SOC., 1936,69,567.66 G. P. Baxter and 0. W. Lundstedt, J. Amer. Chem. Soc., 1940, 62, 1829.H. Diirr, Gieeeereipraxb, 1938, 69, 11482 INOROBNIC CHEMISTRY.salt bath. During electrolysis the less electropositive impurities (iron,silicon, etc.) remain in the anode layer, and the more electropositive ones(magnesium and lithium) dissolve in the electrolyte 86 their chlorides.Special Purification Methods applicable to Individual Elements,-Inaddition to the more or less general methods of preparation and purificationdescribed above, there are numerous special methods designed to removespecific impurities from particular elements. These cannot be enumeratedhere, but brief reference may be made to the purification of iodine by re-moval of other halogens and organic matter,66 and the extraction of iron,silica, and other impurities from commercial silicon by means of acids.68It has recently been pointed out 69 that the most troublesome impurityin commercial sulphur is organic material originating from the hydro-carbons always associated with non-volcanic sulphur deposits.Decom-position of organic material leads also to the presence of hydrogen per-sulphides. Four successive distillations of commercial sulphur do notsuffice to remove the impurities, the presence of which is indicated by thedevelopment of black specks when the sulphur is boiled in a clean glass tube.The method of purification recommended i s as follows : the sulphur (1 kg.)is raised slowly to the boiling point in a Pyrex flask, and boiling continuedfor 3 4 hours after addition of 6 g. of magnesium oxide; this aerves toremove acid impurities and decompose hydrogen persulphides. Thesulphur is allowed to stand for some hours a t 125", and the clear moltenmaterial is decanted from a black sludge of impurities, through a Pyrexwool filter. The sulphur is then heated a t the boiling point for four suc-cessive periods of about 30 hours with 10-g. portions of magnesium oxide,the liquid being filtered after each period of boiling. The purified sulphurcontains no detectable impurity. The method described is intended foruse with Amerioan sulphur, in which there is no arsenic, selenium, ortellurium.Preparation of Elements in Special Allobropic -Forms.-Attention may bedirected here to recent work on the synthesis of diarn~nd,~o in which Moissan'sexperiments were repeated under a variety of conditions with moderntechnique ; molten iron containing carbon was quenched in water- or liquid-air-cooled vessels after heating a t temperatures as high as 3000". Graphitewaa also subjected to a momentary pressure of about 120,000 kg. per sq. cm.at 3000-3200". Although a few very small fragments with the propertiesof diamond were produced in some experiments, consistent yields of diamondswere never obtained. ' These experiments lend added interest tothe discovery,made by X-ray analysis, that eleven out of twelve (' artificial diamonds "allegedly prepared by J. B. Hannay in 1879-1880 are indeed diamonds, a tleast one of them having the rare " type I1 " structure.'l Hannay's attempts6 a N. P. Tucker, J. Iron Steel Inst., 1927,115,412 ; -4. B. Kinzel and T. R. Cunning-ham, Amer. Inst. Min. Met. Eng., Inst. Metals Divn., Tech. Publ. 1138 (1939).6D R. F. Bacon and R. Fanelli, lnd. Eny. C'hem., 1912, 34, 10.13.'13 P. L. Giinther, P. Geselle, and W. Rebentisoh, 2. anorg. C'hem., 1943, 250,357.71 F. A. Bannister and (Mrs.) K. Lonsdale, Nature, 1943,151, 334; (Lord) Rayleigli,ibid., p. 394; F. A. Bannister and K. Lonsdale, Min. Mag., 1943, 26, 315WELCH : PREPARATION OF SOLID ELEMENTS IN A STATE OF P ~ I T Y . 83a t diamond synthesis were carried out by heating paraffin, bone oil, andmetallic lithium to a red heat in a very strong iron tube.72Black phosphorus has recently been prepared from the white form bymomentary application of a pressure of about 100,000 kg. per sq. cm., a troom temperaf~re.~~ The black form is stated to be unstable under ordinarytemperature and pressure conditions, and to revert to white phosphoruson keeping; the red form is the most stable allotrope. A. J. E. W.H. J. EMEL~US.A. J. E. WELCH.7 2 Nature, 1880, 22, 355; Proc. Roy. SOC., 1880, A , 30, 188, 450; 1882, A , 32,407.P. L. Giinther, P. Geselle, and W. Rebentisch, 2. anorg. Chem., 1943, 250, 373

ISSN:0365-6217    

DOI:10.1039/AR9434000060

出版商:RSC    

年代:1943

数据来源: RSC

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CRYSTALLOGRAPHY.1. INTRODUCTION AND GENERAL.THE inorganic and the organic section in this Report review most of the newstructure determinations made by X-ray and electron-diffraction methodsduring the year. A considerable volume of work is still being carried out incertain quarters, but restrictions on space and inaccessibility of many of thejournals combine to make the present Report rather incomplete. It ishoped, however, that the more important structural work has been covered.The structures of nitrous oxide, hydrogen azide, hydrazine, and ozonehave now been accurately determined, and the inorganic field includes someinteresting work on the structure and polymorphism of the oxides Pb30,,Bi203, As406, and P401,. The crystal structure of boron carbide B,C is aninteresting one, and electron-diffraction studies have been made on a numberof boron fluoride compounds.(The boron hydrides are dealt with in anotherpart of this volume.1) Finally, there is an interesting structure determin-ation on the trimer of phosphonitrile chloride.A fairly wide variety of organic structures have received attention, andthe constitutions of pirylene (C,H6) and of diphenylene have been established.The first reasonably quantitative studies of aromatic molecular compoundshave been published and these reveal the rather surprising absence of anykind of intimate contact between the component molecules. Distortionsare reported in the dinitrodiphenyl molecule, but it is difficult to estimate theaccuracy of this work.Both structural and physical investigations havebeen made on a number of porphin and phthalocyanine compounds. Amino-acids and peptides have received some attention, and amongst more complexsubstances there has been some promising work on starch derivatives. Veryfull analyses are reported for the rubber hydrochloride polymer, and for thesimple di-isoprene derivative geranylamine hydrochloride, for which someinteresting and unusual bond distances are found.There is also an increasing volume of work on natural and synthetic fibrestructures which it is not possible to cover in this Report, but mention maybe made of a special article by I. MacArthur on the structure of a-keratin.This is the first detailed account of the very complete fibre pattern obtainedfrom the cortex of African porcupine quill tip.More than 100 reflectionshave been obtained in the range 1-150 A. The repeat unit along the fibreaxis may be 198 or 658 A. It is to be expected that the detailed analysis ofthis pattern will ultimately add greatly to our knowledge of protein structure.I n the meantime, the results obtained appear to substantiate and check insome detail the new model for a-keratin recently advanced by W. T.Astbury.3X-Ray diffraction methods are being applied in LL number of other direc-tions which are beyond the scope of the present Report. These include work1 P. 62. a Nature, 1943, 152, 38. Ann. Reports, 1941, 38, 109ROBERTSON : INTRODUCTION AND GENERAL. 85on metal structures and transformations,* and on coal and carbonisationprocesses, some of the latter being discussed elsewhere in these Reports.6Another new development of interest is that of divergent-beam X-ray photo-graphy; 6 here, the crystal is placed in direct contact with the point sourceon the anticathode and a pattern of deficiency lines is obtained, marking theplaces where the primary intensity has been reduced by reflection.Themethod enables lattice constants to be determined easily and with greataccuracy, and it has been found, for example, that individual diamonds havelattice constants varying over a range of about 3.55970&0-00020 kX (1 kX =A number of general works which themselves constitute useful reviewsmay be briefly mentioned. Sir Lawrence Bragg has provided a fascinatingand most readable account of the history of X-ray analysis from the firstexperiments up to the present time.M. J. Buerger 8 has given a compre-hensive account of X-ray crystallography, limiting that title to mean onlythe investigation of the space pattern of the crystal, and excluding theinterpretation of data relating to the chemical constitution or nature of thecrystal itself (a much wider subject covered by the title “ X-ray analysis ”).Within this limited field a very full and useful account is given, particularlyof the interpretation of rotating crystal, oscillation, and moving-filmphotographs.Amongst papers of a review nature, reference may be made to an X-raystudy of crystal dynamics by (Mrs.) K. Lonsdale 9 in which the whole subjectof diffuse, anomalous, temperature, or non-Laue reflections is very fullydiscussed, together with their theoretical interpretation.The Faxkn-Waller theory, which explains the spread of reflecting power as due chieflyto the thermal (elastic) vibration of atoms and molecules, is found to give thebest account of the results obtained from all kinds of crystals.An early paper by A. Charlesby, G. I. Finch, and H. Wilman 10 concernedwith certain new diffuse features in the electron-diffraction patterns obtainedfrom single crystals of anthracene is of considerable interest in this con-nection. These authors reached the conclusion at that time that the effectswere due to thermal vibrations of the molecules as complete units.Intensity measurement presents one of the outstanding practical problemein X-ray crystal analysis.A summarising article dealing with the techniqueof intensity measurement by photographic methods l1 may therefore be1000 X.U.).A. J. C. Wilson, Proc. Roy. Soc., 1943, A , 181, 360; (Miss) V. Daniel and H.Lipson, ibid., p. 368; (Miss) 0. S. Edwards and H. Lipson, J . Inst. Metals, 1943,69, 177.P. 32.(Mrs.) K. Lonsdale, Nutwe, 1943,151, 52; 1944,163, 22.’I “ The History of X-Ray Analysis.” Science in Britain series, Longmans, Green A* “ X-Ray Crystallography,” John Wiley & Sons, Inc., and Chapman BE Hall, Ltd.,Co., 1943.1942.Proc. Physhxal Xoc., 1942, 54, 314.lo Ibid., 1939, 51, 479; see also Ann. Reports, 1939, 36,179.l1 J. M. Robertson, J . Sci. Instr., 1943, 20, 17686 CRYSTULOURAI'HY.useful. This article does not describe photometers, but rather the variousconditions and precautions necessary for the production of accurate records,and means whereby intensities of widely differing range may be correlated.Visual estimates of intensities from reliable records may be better than themost elaborate measurements made on films where some of these precautions(shape and size of specimen, development conditions, etc.) have beenneglected.2.INORQANIU STRUUTUEES.A number of elements and simple compounds have been examined in theliquid form by scattering experiments with monochromatic X-radiation, withresults that give information about the structure of the liquid, and inter-atomic distances in general.Work carried out over a range of temperatureson liquid mercury, xenon,l nitrogen, nitrous oxide, nitric oxideY2 and carbontetrachloride may be mentioned. The radial distribution curve for mercurygives a h t peak a t 3.00 A., but the number of atoms in the fist co-ordinationlayer is only about 6, this being the lowest number yet found for a monatomicelement. In xenon the number of nearest neighbours is 9-10 at 4.43-4 . 5 0 ~ . Diatomic aggregates are shown by the distribution curves fornitrogen and nitric oxide, and for nitrous oxide the data are consistent witha linear molecule. In carbon tetrachloride the peaks at 1.74 and 2.92 A.(25") correspond very closely to L. 0. Brockway's determination4 of theinteratomic distances by electron diffraction (Gm = 1-75 A.; m-C1 =2.87 A.). These results indicate that the technique of X-ray diffraction asapplied to liquids is becoming more perfect, and we may expect applicationsto more complicated systems in the future.An electron-diffraction study of hydrogen peroxide and hydrazine hasnow been reported 5 which was made with a view to determine the length ofthe 0-0 and the N-N covalent single bond. The values found, both1*47-J=0.02 A., are considerably greater than those indicated by the Pauling-Huggins radii for those atoms 6 which were 1-32 and 1.40 A., respectively.This upwards revision of the covalent single bond radii has already been dis-cussed in these Reports.' The sequence of values now reported for the com-pounds ethane, hydrazine, hydrogen peroxide, and fluorine is 1*54,1*47,1*47,and 1-43 A.It is a little surprising that the same values should be obtainedfor nitrogen and oxygen, but the distance in hydrogen peroxide may actuallyJ. A. Cempbell and J. H. lilildebrand, J. Chm. Physics, 1943, 11, 330, 334.P. c. Sharreh, ibid., p. 436.E. E. Bray and N. S. Gingrich, ibid., p. 351; A. Eisenstein, Physical Rev., 1943,Rev. Mod. Physics, 1936, 8, 231.P. A. Gigudre and V. Schomaker, J . Amer. Chem. SOC., 1943, 65, 2025.L. Peuling and M. L. Huggins, 2. Krbt., 1934, 87,205.Ann. Reports, 1941,38, 100; V. Schomaker and D. P. Stevenson, J . .Amer. Chem.* L. 0. Brockway, ibid., 1938, 60, 1348; M. T. Rogers, V. Schomaker, and D. P.63, 304.SOC., 1941, 63, 37.Stevenson, W., 1941, 63,2610ROBERTSON : INORUANIC STRUCTURES.87be a little less, as indeed is indicated by the very careful crystal-structluredetermination of hyper019 which gives 0-0 = 1.46 A.The structures of nitrous oxide and hydrogen azide have also beenexamined by elecfron-diffraction methods.10 These two essentiaUy linearmolecules present very much the same problem, the expected resonatingstructures being (1)-(111) and (1V)-(VI), respectively. The diffractionresults give N-N = 1.14&0.01 A. and N-NH = 1-25&0.01 A. for the azide.For nitrous oxide the central atom cannot be precisely fixed, but the resultsconfirm Pauling's prediction l1 of N-N = 1-12 A. and N-0 = 1-19 A.Pauling's adjacent charge rule is thus confirmed, in that structures (111) and(VI) can make but little contribution to the normal state of these molecules.Any considerable contribution from these structures would drastically alterthe above distances.These results are also in agreement with the resultsof earlier spectroscopic investigations.12313Ozone.-The first complete structural investigation of ozone has now beenmade by W. Shand and R. A. Spurr,l* using the method of electron diffrac-tion. Precautions were taken to ensure that the ozone had a purity of 95%or better, but the calculations show that even a much larger oxygen impuritywould have little effect on the results. Both radial distribution and thecorrelation methods were used in interpreting the results, which show thatthe molecule has a symmetrical angular form with the 0-0 bond distance1.26&0.02 A., and the 0-0-0 angle 127'53".The non-bonded oxygendistance is only 2.24 A., which must involve considerable repulsion betweenthe terminal oxygens. The results are in reasonable agreement with thespectroscopic work of W. G. Penney and G. B. B. M. Sutherland; l5 theycorrespond to a double-bond character of about 30%, and the most importantresonating structures are probably (VI1)-(X), ..0..0(VII.) (VIII.) (IX.) (X-)See Ann. Reports, 1942, 39, 103; C. S. Lu, E. W. Hughes, and P. A. Giguere,J. Amer. Chem. SOC., 1941, 63, 1507.l o V. Schomaker and R. Spurr, ibid., 1942, 64, 1184.l1 " The Nature of the Covdent Bond," Cornell Univ. Press, 2nd edtn., p. 200, 1940.Ls E. H. Eyster, J. Cbm. Physics, 1940, 8, 141.I' J.AWT. Ohem. Xoc., 1943, 65, 179.E. Plyler and E. F. Barker, Phybical Rev., 1931, 38, 1827.16 Proc. Roy. SOC., 1936, A , 166,578, 65488 CRYSTALLOGRAPHY.Oxides.-Single crystals of minium, Pb304, have now been obtained inthe form of transparent red needles,16 and a fairly complete analysis of thestructure has been made by S. T. Gr0ss.l' The crystals are tetragonal, andapproximate closely to the space-group P4/mbc. The relatively smallscattering power of the oxygen atoms makes it impossible to determine theirpositions directly from the X-ray data, but these positions can be inferredfrom the cell dimensions and co-ordination rules. The structure can beconsidered roughly as compounded from PbO (red) and PbO, units. As inPb02,18 the plumbic ions are associated with chains of oxygen octahedrawith opposite edges shared.Adjacent chains approach in such a mannerthat three oxygen ions are further co-ordinated with each plumbous ion,giving an arrangement similar to that found in red Pb0.u It is to be hopedthat further work will reveal the structure of Pb,O,, of which single crystalsare also available,16 and ultimately show how the transition from one formto the other is effected.The polymorphism of Bi,O,, about which some conflicting data exist, hasnow been re-examined by W. C . Schumb and E. S. Rittner.20 Pure Bi203 isfound to crystallise in a t least 3 distinct forms : the low-temperature a-formis monoclinic with a transition point a t 710" to the high-temperature p-modi-fication, which is tetragonal. The third, or y-form, is body-centred cubic,but is without any stable region between 25" and the melting point, and so isprobably monotropic.The polymorphism of arsenious oxide, As406, has also been re-examinedby J. H.Schulman and W. C . Schumb,21 and they find no definite evidencefor the existence of any forms other than the well-known cubic and mono-clinic varieties. The structure of the latter is known to be of a moleculartype containing clusters of discrete As,O, units,,, but that of the monoclinicvariety has not yet been fully determined. An enantiotropic relationshipis now shown to exist between these two forms, the transition temperaturebeing in the neighbourhood of -13". Although above this temperature thecubic form is thermodynamically unstable with respect to the monoclinicform, nevertheless the cubic form may remain untransformed indefinitely inthe natural state.A very interesting but more complex problem is presented by the poly-morphism of phosphoric oxide.23 In this case there are three distinctcrystalline modifications, exhibiting monotropic relationships, a t least twodistinct liquids, and some interesting glasses.The crystalline form familiaras a laboratory reagent is the low-temperature or volatile form. Thisbelongs to the rhombohedra1 division of the hexagonal system, and the unitof structure has now been shown24 to contain two P4OlO molecules of theG. L. Clark, N. C. Schieltz, andT. T. Quirke, J . Amer. Chem. SOC., 1937, 59, 2305.W.L. Bragg, " Atomic Structure of Minerals," Cornell Univ. Press, 1937, p. 103.pa R. M. Bozorth, ibid., 1923, 45, 1621.l7 I b d . , 1943, 65, 1107.'9 R. G. Dickinson 8nd J. B. Friauf, J . Amer. Chern. SOC., 1924, 46, 2457.20 Ibid., 1943, 65, 1056. a1 Ibid., p. 878.23 W. L. Hill, G. T. Faust, and S. B. Hendricke, ibid., 1943, 65, 794.H. C. J. de Decker and C. H. MacGillavry, Rec. Trav: chirn., 1941, 60, 153ROBERTSON : RVORQANIC STRUCTURES. 89same configuration as exists in the vapour phase25 (phosphorus atoms a tthe corners of a regular tetrahedron, and surrounded, again tetrahedrally,by oxygen atoms).By heating in a sealed tube, high-temperature crystalline modificationscan be obtained, which have low vapour pressures and fundamentallydifferent structures.First, there is the orthorhombic modification whosestructure has now been determined26 and shown to consist of an infinitesheet polymer containing interlocking rings, the phosphorus atoms beingsurrounded by shared tetrahedra of oxygen atoms. The second high-temperature form has not so far been analysed by X-ray methods, but it isprobably tetragonal z3 and very likely again consists of an infinite polymer,but this time of a three-dimensional type.The different crystalline modifications of phosphoric oxide thus corre-spond to different states of polymerisation, and a knowledge of their structureexplains their strikingly different behaviour in reactions, for example, withwater. The violent reaction of the ordinary hexagonal form is replaced by acomparatively slow reaction in the case of the orthorhombic form, thisprobably taking place first of all along the cleavage cracks of the sheets,with slow degradation into small crystals.The three-dimensional tetragonalform also reacts slowly compared with the ordinary form, but more rapidlythan the orthorhombic (sheet) form.These structure determinations also serve to explain the phenomena ofdifferent phosphoric oxide liquid types, because, according to moderntheories,27 the liquid will inherit some of the structural features of the solidfrom which it is derived. On rapid heating the low-temperature hexagonalform melts to a liquid consisting mainly of P40,, molecules, but these poly-merise rapidly with decrease in the vapour pressure.Transformation ofthe different liquid types is seen to correspond essentially to chemicalreactions.Boron Carbide.-The interesting structure of crystalline B4C has nowbeen determined with considerable accuracy.28, 29 The rhombohedra1 unitcell (space group D;d-Rjm) with a = 5.19 A., a = 66" 18', contains 3stoicheiometric B4C molecules. The structural units, however, consist ofcompact groups of 12 boron atoms and linear chains of 3 carbon atoms,these groups alternating approximately as in the NaCl type of structure.The 12 boron atoms are arranged a t the vertices of a nearly regular icosahe-dron, each boron atom having &fold co-ordination, being bonded to fiveothers in the same group and to either a carbon or a boron in an adjoininggroup.The appreciable electrical conductivity of the crystals points to ahigh degree of resonance and a binding with some metallic characteristics.2 5 G. C. Hampson and A. J. Stosick, J. Amer. Chern. SOC., 1938, 60, 1814.2( H. C. J. de Decker, Rec Truv. chim., 1941, 60,413.4 7 J. G. Kirkwood and E. Monroe, J . Chem. Physics, 1941, 9, 514.28 G. S. Zhdanov and N. G. Sevast'yanov, Compt. rend. Acad. Sci. U.R.S.S., 1941,2e H. K. Clark and J. L. Hoard, J . Amer. Chem. SOC., 1943,06, 2115.32, 43290 CRYSTALTAOQRAPHY.There appears also to be room in the structure for additional atoms, whichaccounts for the existence of material with a variable boron-carbon ratio.Boron Fluorides.-An electron-diffraction investigation by S. H. Bauerand J.M. Hastings on dimethylboron fluoride and methylboron difluoridehas now completed the observed interatomic distance data for the series ofoompounds B(CH,),, B(CH,),F, B(CH,)F,, and BF,. Roughly, it is foundthat all these compounds have the same configuration and essentially thesame interatomic distances, 'uix., planar molecules with B-C = 1-55-1.60 A.,B-F = 1*29-1*30 A., and valency angles of about 120". There are certaindifficulties in interpreting these results in terms of the dependence of bonddistance on bond type, and especially in comparison with the corresponding'sgries of fluorine-substituted methanes.,l Thus, the contribution of excitedstructures of the type X2B-::E'+:: and of the normal structure X,B:F::: mustvary in these different compounds, but a t present it is difficult to explainthis in terms of the observed results.I n the molecular compoiind, dimethyl ether-bofon trifluoride,(CH,),O:BF,, the boron trifluoride unit necessarily undergoes a ratherdrastic structural change.32, 33 The boron valency angles become tetrahedral,with B-I? = 1-41&0.02 A.This is substantially the normal B-F separationfor tetrahedral bonding, as in the alkali fluob0rates.H The dimethyl etherpart of the molecule remains practically unaffected, and the co-ordinate linkO+B has a length of 1*52&0.06 A.Phosphonitrile ChZorides .-A1 t hough the p hosp honitrile chloride seriesof compounds have been known for many years,S5 the structures of even thesimple members have been in doubt until quite recently.An advance wasmade in 1939 by the full X-ray crystallographic determination of the struc-ture of the tet~arner,,~ which was shown t o consist of a puckered 8-memberedring of alternate nitrogen and phosphorus atoms, each of the latter carryingtwo chlorine atoms. L. 0. Brockway and W. M. Bright 37 have now made afull determination of the structure of the trimer, P,N,Cl,, by the method ofelectron diffraction in the vapour. A number of earlierproposed structures involving chlorine attached tonitrogen, a three-membered nitrogen ring, open chain,etc., have been tested and eliminated, and the modelwhich finally gives best agreement with the diffractioncl-p p-cl data is found to be (XI). The ring appears t o beplanar (although models with staggered rings have notbeen direotly tested) and the P-N bond distance of1 .6 5 ~ . indicates a Kekul6 type of resonance (P-NThe P-C1 distanceCl\,ClP.( >*.C l / \ N & 3 1I..(XI.)single bond = 1-80 A., and P-N double bond = 1.61 A.).30 J . Arner. Chern. SOC., 1942, 64, 2686.31 L. 0. Brockway, J. Physical Chem., 1937, 41, 747.02 A. W. Laubengayer and G. R. Finlay, J . Arner. Chem. SOC., 1943, 65, 884.8s S. H. Bauer, G. R. Finlay, and A. W. Laubengayer, ibid., p. 889.34 J. L. Hoard and V. Blair, ibid., 1935, 67, 1986.t 6 H. Rose, Annulen, 1834, 11, 129; J. Liebig and F. WClhler, ibicl., p. 139.36 See Ann. Reportu, 1940,37, 186. s7 J . Amer. Chern. Soc., 1943, 65, 1661ROBERTSON : ORGANIU STRUCTURES.91of 1.97 A. is in fair agreement with that reported in other compounds, e.g.,phosphorus trichloride, fluorodichloride, and phosphoryl chloride, etc.Miscellaneous Structures.-A series of gallium alums have been measuredby H. P. Klug and G. L. Kieffer,38 and the structure types determined.Both the potassium-aluminium or a- and the cssium-aluminium or p -alumtype are found t o occur.. A number of gallium and indium trihalide bonddistances obtained by W. R. Brode 39 by electron-diffraction methods havenow been corrected by D. P. Stevenson and V. S~homaker.~O The structureof silver chlorate, with atomic parameters, has been reported,4l but detailsare not available. Silver bromide crystals are isomorphous.3. ORGANIC STRUCTURES.The very complete analysis of the infra-red spectra of ethylene andtetradeuteroethylene reported by W.S. Gallaway and E. F. Barker 1 yieldsnew data for all the dimensions of the ethylene molecule which may haveimportant consequences in organic structural work. They find in particularthat the G C double bond distance is 1.353&-0.01 A . , a value somewhat higherthan has previously been accepted. I n most X-ray work it is difficult tomeasure this bond length accurately; e.g., in stilbene the resolution of thedoubly linked carbon atoms is poor. I n such cases it has usually been thepractice to assume the spectroscopic value for this linkage in order to fixthe position of such atoms definitely. Although the difference between theold value (1.33 A.) and the new one (1.35 A.) is not large, this bond length israther fundamental and is used, for example, in the bond order-distancecurves for estimating the contribution of possible resonance structures tothe normal state in the case of various molecules.Direct precision X-raymeasurements of this bond length in more complex molecules would now beextremely interesting.Amongst simple structures that of gadolinium formate has been deter-mined by A. P a b ~ t . ~ The dimensions of the formate group obtained by X-rayanalysis are in good agreement with previous determinations, G O distancesof 1.27 A. and 1.33 A. with a bond angle of 121" being reported. The radiusof the gadolinium ion is estimated to be 0.98 A., and it shows a nine-foldco-ordination with the surrounding oxygen ions.An electron-diffraction study of methyl isocyanide has now been carriedout with the latest improved te~hnique,~ and the results verify that themolecule is linear, a t least to within about 20".This is in agreement with38 J . Amer. Chem. SOC., 1943, 65, 2071.4O J . Amer. Chem. SOC., 1942, 64, 2514.41 S. von NAray43zcLbb and J. Pbcza, 2. K ~ i s t . , 1942, 104, 28.* J. M. Robertson end (Miss) I. Woodward, Proc. Roy. SOC., 1937, A , 162, 568.39 Ann. Physik, 1940, 37, 344,J . Chem. Phyeics, 1942, 10, 88.L. Pauling, L. 0. Brockway, and J. Y. Beach, J . Amer. Chem. SOC., 1935,57, 2706;J . Chem. Phyclics, 1943, 11, 145.W. Gordy and L. Pauling, J . Amer. Chem SOC., 1942, 64, 2962.W. G. Penney, Proc. Roy. SOC., 1937, A , 158, 30692 CRYSTALLOGRAPHY.earlier work(I) and (11) the contribution of (11) must be small.are H,C-N = 1-44&0.02 A , , and N-C = 1.18ri_T0.02 A.and with spectroscopic data,' and shows that of the structuresThe interatomic distances..(1.) CH, - b C : CH,-N=C: (11.1Constitution of PiryEene.--The hydrocarbon C,H,, named pirylene, wasfirst obtained by A.Ladenburg from piperidine. The structure remainedobscure, although later investigators favoured a doubly-unsaturated ring,possibly methylenecyclobuteiie. The subject has now been re-examined,both chemically l o and by electron diffraction.ll The latter work is of ratherspecial interest, being a structure determination by vapour electron-diffrac-tion methods in a case where only the molecular formula was known.Although this formula is comparatively simple, C&,, there are actuallyabout 30 possibilities, and the correct solution proves to be quite differentfrom that indicated by the later chemical eviden~e.~ The method employedconsisted of a rather accurate radial distribution summation, followed by astudy of the intensity curves for the most probable models, based on knownbond distances and angles.The final result eliminates all ring structures andshows quite clearly that pirylene is actually a-methyl- p-vinylacetylene.The molecular dimensions which give the best agreement with the observ-ations are shown in (111), in A.CH,125O//1*35 (111.)CH,---C~C--CH1.47 1.20 1.42Structure of DiphenyZene.-W. C . Lothrop l2 recently synthesised thearomatic hydrocarbon CI2H, and assigned to it the structure (IV), which hassince been the subject of some discussion.It represents the first definitearomatic four-membered ring, and a8 such the structure must be under con-siderable strain. cycZoButadiene has never been prepared, although cyclo-butane and other four-membered rings are well known.13 In view of thesefacts, and as a result of certain catalytic reduction experiments, W . Baker 14concluded that Lothrop's compound should be represented by (V), an arrange-ment where the bonds are under considerably less strain. This conclusionwas supported by C. A. Coulson l5 by calculations of the striin and resonanceL. 0. Brockway, J . Amer. Chem. SOC., 1936, 58, 3516.K. M.Badger and S. H. Bauer, ibid., 1937, 59, 303.Ber., 1882, 15, 1024; Annalen, 1888, 247, 56.J. von Braun and W. Teuffert, Ber., 1928, 61, 1092.10 H. Sargent, E. R. Buchman, and J. P. Farquhar, J . Asner. Chem. SOC., 1942, 64,l1 R. Spurr and V. Schomaker, ibid., p. 2693.l2 Ibid., 1941, 63, 1187; 1942, 64, 1689.l P Nature, 1942, 150, 211.2692.See Ann. Reports, 1942, 39, 104.Ibid., p. 577ROBERTSON : ORGANIC STRUCTURES. 93The problem obviously demands investigation by modern physicalmethods, and this has now been carried out by J. Waser and V. Schomaker.16Their very detailed electron-diffraction investigation was made on the vapourof diphenylene, and the results are reported to confirm structure (IV) anddefinitely eliminate structure (V).The radial distribution curve obtainedshows peaks corresponding to interatomic distances at 1.42 A. (averageC-C), at 2.1 A. (diagonals of the four-ring) and a t 2.44 A. and 2-78 A. (m- andp-distances in the six-ring). The curve also continues to be in satisfactoryagreement with the structure (IV) out to quite large distances. Any reasonablemodel of structure (V) appears to be ruled out, particularly because of theabsence of any distances which would correspond to the 10 diagonals of thepentagons, i.e., distances of the order of 2.30 A. The higher reaches of thecurve are also quite unsatisfactory for structure (V). The model whichfinally gives the best agreement with the experimental results is the diphenylenestructure with the sides of the hexagons equal to 1.41&-0.02 A., the lateralconnecting links of the four-ring equal to 1*46&0-05 A., and the hexagonangle a equal to 121"*3".Only preliminary results of the crystal-structure investigation of di-phenylene are available,16 and these are peculiar in so far as they indicate6 molecules of C1,H, per unit cell for space gtoup P2Ja.This would indicatethat a t least two of the molecules must exhibit a centre of symmetry, inconformity with structure (IV). Final judgment should perhaps be reserveduntil the crystal has been fully investigated, especially as with a moleculeof this complexity the electron-diffraction method can a t best only giveaverage values for many of the structural parameters.Aromatic Molecular Compounds.-The structures of these molecularcompounds are of great interest, but necessarily complex from an X-raypoint of view as they all involve rather large numbers of atoms.However,a quantitative X-ray determination of the structure of p-iodoaniline-s-trinitrobenzene has now been made.1' The monoclinic unit cell (spacegroup P2,/c) contains four molecules of each of the components, and theanalysis proceeds from a preliminary determination of the iodine positionsby Patterson-Fourier methods to a final location of all the atoms by two-and three-dimensional Fourier synthesis. The accuracy of the determinationis difficult to estimate in such a complex structure, but it is unlikely thatthere are any large errors, and the main features are quite clear. The mostnotable and rather unexpected result is that there are no short interatomicdistances between the component molecules.These are arranged in such away that the C------ C distances between neighbouring benzene rings arenever less than 3.5 A. The shortest intermolecular distance occurs betweenthe nitrogen of the amino-group and a neighbouring oxygen, where theseparation is 3.1 A. This may correspond to a very weak type of hydrogenbond, but such a bond cannot, of course, play any essential part in thegeneral problem of the aromatic molecular compounds. One nitrogen-l6 J . Amer. Chem. SOC., 1943, 06, 1451.l7 H. M. Powell, G. Hum, and P. W. Cooke, J . , 1943, 15394 CRYSTALLOGRAPHY.carbon separation of 3.25 A. is mentioned, which seems rather less than usual,and may be of some significance.Molecular compounds formed between the picryl halides and hexamethyl-benzene have also been studied.18 These structures are still more complexand appear to be disordered to some extent, but the significant features areagain fairly clear.The structures consist essentially of alternate layers ofthe two components with a separation of about 3.5 A,, indicating relativelyweak binding. This is confirmed by a Patterson-Fourier projection, andindependently by a study of certain diffuse reflections which are formed.In particular it is shown that the evidence is against the existence of ionsin the structure.Miscellaneous Complex Crystab.-An investigation of the many crystallinemodifications of sodium stearate has been made,lg9 2O from room temperatureto the melting point.The subject is one of extreme complexity, and nofewer than seven different phases of the y-modification, which is dealt within these papers, are recognised in this region. Numerous data are provided,but the subject is hardly yet suitable for a detailed report. Very finelyoriented fibre photographs of sodium laurate, sodium palmitate, and sodiumstearate have also been studied.20A full account of the crystal-structure of 4 : 4’-dinitrodiphenyl has beengiven by J. N. van Niekerk.21 This crystal can be referred to orthogonalaxes, but structurally it appears to belong to a monoclinic space group (Pc)which does not impose any molecular symmetry. The results of the analysislead to molecular dimensions which are rather difficult to reconcile withknown data for the types of bond involved.For instance, the C-C distancebetween the rings is given as 1.42 A., and the C-N distance as 1.56 A. Thereis also considerable distortion in the disposition of the nitro-groups withrespect to the benzene rings. In such a complex structure it is d s c u l t toestimate the accuracy of these figures, but they are probably subject to con-siderable errors. It seems possible that the initial assumption (made inorder to simplify the analytical treatment) of a symmetry centre in thedouble ring system, which is not demanded crystallographically, may haveintroduced certain distortions. The structure is, however, a very interestingone and it should receive further attention.The constitution of calycanine22 has been further examined by X-raymethods, and the results appear to exclude the formula CzIHl5N3 proposedby R.H. F. Manske and L. Marion23 and support the simpler formulaA planar porphin ring is reported for tetramethylh~matoporphyrin ’* byC 16HldNZ -1* H. M. Powell and G. Huse, J., 1943, 435.2o A. de Bretteville and W. McBain, ibid., p. 426; J. W. McBain, 0. E. A. Bolduan,and S. Ross, J . Amer. Chem. SQC., 1943, 65, 1873.21 Proc. Roy. SOC., 1943, A , 181, 314.2s See Ann. Rev. Biochem., 1942, 11, 572.24 H. O’Dsniel and A. Damsschke, 2. Krist., 1942, 104, 114.J. W. McBain, A. de Bretteville, and S . ROSS, J. Chem. Physics, 1943, 11, 179.22 A. Hargreaves, Nature, 1943, 153, 600ROBERTSON : ORGANIC STRUCTURES.95X-ray analysis, but further details are not available. Aetioporphyrin-1 25has also been examined and a brief report made. In these studies compari-sons are made with the ring form of phthalocyanine,Z6 a closely relatedstructure which has been fully determined.Some very interesting measurements on the thermal expansion of certainporphin and phthalocyanine compounds have been made by A. R. Ubbelohdeand (Miss) I. Wood~ard.~' The work involves a, new technique in dealingwith single crystals over a alarge range of temperature which should begenerally useful. Attention is particularly directed to the different behavioursof hydrogen and platinum phthalocyanine. The amplitude of the atomicvibrations (average) is calculated from the fading of the intensities, and themolecular movements in different directions -are deduced from the observedexpansions. The increased space requirement imposed by the platinumatom as the temperature rises, as compared with the central atoms of theother molecules, appears to be capable of explaining the observed results.Amino-acids and Peptide$.-The first quantitative X-ray study of a linearpeptide has now been briefly reported.28 Glycylglycine exists in at least 3different crystalline modifications,29 and the needle-like (3-form, with a veryshort b axis (4.62 A.), has been selected for detailed study.The parametersare not yet sufficiently refined for a discussion of interatomic distances, butit is clear that the crystal is built from essentially planar moleoules of theC NH CH, 5)configuration (VI).The molecules are linked by hydrogen bonds of theusual type, these being disposed tetrahedrally about the terminal nitrogenatom and connecting it to one carbonyl and two carboxyl oxygen atoms ofsurrounding molecules. The imino-nitrogen also forms a hydrogen bond toa neighbouring carboxyl oxygen.Complete structural determinations of compounds of this type aredifficult owing t o the many degrees of freedom, but a useful preliminarydetermination of unit-cell and space-group data has now been made for thefollowing higher amino-acids 30 : dl-valine, dl-threonine, dl-serine, dl-norleu-cine, and dl-methionine.A large air-dried crystal of p-lactoglobulin has been measured by I.Fankuchen,31 and his results confirm the earlier measurements reported by25 C.L. Christ and D. Harker, Anzer. Min., 1942, 27, 219.4 6 J. M. Robertson, J . , 1936, 1195.2 7 Proc. Roy. SOC., 1943, A , 181, 415.2 8 E. W. Hughes and W. J. Moore, J . Amer. Chem. SOC., 1942, 84, 2236.2Q J. D. Bernal, 2. Krist., 1931. 78, 363.so G. Albrecht, C. W. Sohnakenberg, M. S. Dunn, and J. D. McCullough, J . P h y s h ls1 J . Amer. Chem. SOC., 1942, 64, 2504.Chem., 1943, 4?,2496 CRY STALLOORAPHY.(Miss) D. The cell shrinkage in different crystal directionswhich occurs on drying can now be estimated from the figures 111 x 60 x6 2 ~ . (dry) and 154 x 67.5 x 6 7 . 5 ~ . (wet). The importance of suchobservations in connection with the determination of protein structures isdiscussed in last year’s Repat.33Starch.-The first fibre diagram reported from a starch derivative isdescribed briefly by R.L. Whistler and N. C. S ~ h i e l t z . ~ ~ Amylose, thecomponent which can be extracted by water from swollen starch granules,yields strong, pliable acetate films, and these when elongated some 400-600% produce a well-defined fibre pattern with X-rays, indicating linearmolecules with a high degree of orientation. The periodicity is 18.3 A.along the fibre axis, and the sharpness of the picture would seem to indicateconsiderable possibilities in the direction of detailed structure analysis.A powder diagram showing over 20 reflections has also been obtainedfrom the amylose-iodine complex by R. E.Rundle and D. French.35 Thedata conform to a hexagonal (or pseudo-hexagonal) cell with a = 12.97 A., andc = 7-91 A. These figures appear to confirm a proposed helical structurefor the starch-iodine complex, a representing the diameter of the helix andc the length of a turn, dimensions which are in agreement with a space-filling model of a helix with six glucose residues per turn.Further diffraction diagrams from butanol-precipitated amylose 36indicate a larger orthorhombic unit cell, but confirm the helical chain struc-ture for starch.Rubber and Isoprene Derivatives.-The long-chain polymer rubber hydro-chloride [-CH*CH,*CH,*C(CH,)Cl-], has been investigated in detail by C. W.Bunn and (Mrs.) E. V. Garner.37 The fibre diagrams show that two long-chain molecules pass through the monoclinic (pseudo-orthorhombic) cell, andthe positions of the atoms have been determined in conformity with theobserved intensities. The chain form already predicted by Bunn 38 has beenconfirmed, the plane zigzag (of the paraffin-hydrocarbon type) being con-siderably shortened by partial folding about the >CMeCl units. The bonddistances and angles appear to be approximately normal except for a dis-tortion of the methyl group from the ideal position, similar to that found inrubber.39In last year’s Report 39 a paper by C. J. B. Clews dealing with poly-chloroprene was mentioned. It now seems likely that the unit cell dimen-sions recorded in that paper are erroneous, as the data given appear to beinconsistent with these dimen~ions.~OA brief report has appeared41 of a very comprehensive investigationof an interesting di-isoprene derivative, geranylamine hydrochloride,s2 Chern. Reviews, 1941, 28, 215.34 J . Amer. Chem. SOC., 1943, 85, 1436.36 R. E. Rundle and F. C. Edwards, ibid., p. 2200.37 J . , 1942, 654.ss See Ann. Reports, 1942, 39, 108.33 Ann. Reports, 1942, 39, 11 1.35 Ibid., p, 1707.38 Proc. Roy. SOC., 1942, A , 180, 67.*O C. W. Bunn, private communication.L. Bateman and G. A. Jeffrey, Nbture, 1943, 152, 446ROBERTSON : ORUANIC STRUCTURES. 97CH,*C(CHJCH*CH,*CH,*C( CH3) :%H*CH,*NH,,HCl. From an extensivesurvey of the intensities a complete structural determination is reportedwhich places all the atoms to within about &0.03 A. The value given for theC-C double bond distances seems rather low at 1-31 A., especially in view ofthe latest spectroscopic resu1ts.l The most interesting feature of thestructure, however, lies in a contraction reported for the middle C-C bond in-c=c---C-c---~C- (m.)a bthe system (VII). The bond length ab is given as 1-43 A., indicating a con-jugation effect comparable in magnitude with that observed in butadieneand similar systems.42 This is a surprising result and further details of theanalysis will be awaited with interest.J. M. ROBERTSON.4* See Ann. Reports, 1939, 36, 175; J. M. Robertson, J., 1938, 131.REP.-VOL. XL.

ISSN:0365-6217    

DOI:10.1039/AR9434000084

出版商:RSC    

年代:1943

数据来源: RSC

摘要:

ORGANIC CHEMISTRY.1. hTRODUCTION.A NEW general reaction has been described by K. Ziegler and his collabor-ators, who show that N-bromosuccinimide will effect direct brominationat the allyl position. Another interesting reaction involving the allylposition has been examined by K. Alder, who finds that monoethylenichydrocarbons will react with philodienes such as maleic anhydride to givesubstituted succinic anhydrides. The use of hydrogen fluoride as a con-densing agent has received considerable attention; apart from the fact thatits use requires special apparatus, it has many attractive features andappears particularly useful in the cyclisation of y-arylbutyric acids andsimilar acids, and also in the alkylation of aromatic hydrocarbons.In view of the many investigations which have been made in recent yearson the chemistry of acyclic sugars and related compounds, the Report onCarbohydrates is mainly concerned with a review of the more importantdevelopments in this field.Many new al&eh$do-derivatives of the acetaltype R*CHXY have been prepared, and it has been possible to isolate someof them in the two forms necessitated by the asymmetry of the aldehyde-carbon atom. The Amdt-Eistert synthesis has been successfully appliedto the conversion of penta-acetyl gluconyl chloride into the correspondingheptonic acid ; the intermediate diazo-deoxy sugar, which can be isolatedas the primary product of the action of diazomethane on the acid chloride,is readily transformed into glucoheptulose, a reaction which is of considerablevalue for the synthesis of ketoses.The importance of periodic acid as a reagent for the investigation of ringstructures is now fully realised, and it has been used in the study of hexosans,substances which appear to be of great promise for synthetic purposes, asexemplified by the recent syntheses of cellobiose and lactose.The use of thisreagent has been largely responsible for the rapid progress made in theexamination of partly substituted pentitols and hexitols, though in caseswhere more than one chelate group is involved an outstanding problem isoften the determination of the fine structure. Previous assumptions thatmethylene derivatives contain either five- or six-membered rings are vitiatedby the isolation of 2 : 5-dimethylene mannitol; possible formulae are there-fore more numerous than were originally supposed.The partial scission of amethylene residue has been reported, in which the linkage to a primaryhydroxyl is broken whilst that to a secondary is unaffected. The longcontroversy concerning the configurations of styracitol and polygalitol hasbeen resolved by a synthesis of the latter substance which leaves no doubtthat it is 1 : 5-anhydrosorbitol, from which it follows that styracitol is1 : 5-anhydromannitol.Research directed towards the synthesis of the natural secondary seINTRODUUTION. 99hormones and related steroids, although inevitably reduced in volume inpresent circumstances, has tended in the period under review towards theexploitation of the more promising of the many and varied methods pre-viously examined.In particular, applications of the Bachmann synthesisof the oestrogenic hormone d-equilenin (I) have added to our knowledge ofMe Methe structural and stereochemical features essential for maximal biologicalactivity in this series, and have also resulted in the synthesis of an oestronestereoisomer. It would seem that further development of the latter applica-tion will inevitably lead to the synthesis of the natural hormone.The Robinson Mannich base method, so obviously suited to the pro-duction of the male hormones of the androstane series, has been employedin a synthesis which has yielded a product containing a maximum of eightof the sixteen possible &I-stereoisomerides of androstenedione (11).Notableprogress can be reported in the development of methods for the introductionof the angular methyl group into preformed tetracylic systems, and applica-tions of the Diels-Alder addition reaction and the Robinson diketone synthesishave received further attention. It has now been proved that cyclisationof dicyclohexenylacetylenes, originally believed to yieId perhydrophenanthreneketones, gives compounds containing spiran systems.There is little doubt that one of the most far-reaching developments inthe sex hormone field in recent times is the discovery of highly activesynthetic oestrus-producing substances such as stilboestrol, the trans-isomerideof structure (111). The interesting physiological properties of these hormonesand their successful clinical application have provided a powerful stimulusto further research and numerous studies of the methods of preparationand of the steric configurations of the more active substances have been made,Much interest centres around investigations of the effect, known to be quiteprofound, of structural and spatial configuration on biological activity,since it is thought that the results of such studies may in due course helpto shed light on the mode.of action of these hormones. Recently it hasbeen reported that one of the stereoisomers of (IT) is only three or fourtimes less active than dihydrostilboestrol (hexoestrol), which suggests thatconfigurational resemblance between synthetic and natural oestrogens ma100 ORGANIC CHEMISTRY.be of less importance than has hitherto been supposed, a suggestion whichreceives some support from recent work on the triphenylethylene oestrogens.The systematic examination of extracts from the adrenal cortex hasresulted in the identification of nearly thirt'y steroid constituents.Pa,rtialsyntheses of several adrenal steroids which are not oxygenated in ring Chave previously been reported. T. Reichstein and his collaborators have nowcompleted a partial synthesis of dehydrocorticosterone, which is a ring4oxygenated cortical hormone. This partial sjmthesis affords an unequivocalproof of the position of the ring-C oxygen atom in the adrenal steroids;the methods developed for the synthesis of dehydrocorticosterone areof a general nature and will no doubt be applicable to the partial synthesisof the other ring C-oxygenated adrenal hormones. Furthermore the successfulpart-synthesis of ring C-oxygenated adrenal hormones means that they cannow be obtained from a bile acid, whereas hitherto they could only be obtainedin very small yield by a tedious extraction process from adrenal cortex.The isolation of 17- P-hydroxyprogesterone from adrenal cortex has beenconfirmed and a partial synthesis establishes its structure; the ease ofisomerisation of this adrenal steroid to a perhydrochrysene derivative hasbeen demonstrated.A new adrenal steroid-substance U has been isolated,and its structure established by conversion into an adrenal steroid of knownconstitution.I n the section of the Report devoted to heterocyclic compounds, anumber of new or improved methods are described for the preparation ofderivatives of indole, pyridine, quinoline, pyrimidine and purine. Themechanisms involved in the synthesis of indoles by two well-known methodshave been studied, and the properties of the monoaminoacridines have beenexplained in terms of their electronic structures.A further study of thesynthesis of isoquinolines under biologically possible conditions has beenmade, and the applicability of the Mannich reaction to the production ofheterocyclic compounds has been considerably broadened. An investig-ation of the behaviour on dehydrogenation of tetrahydropyridine derivativesand of bicyclic compounds having a nitrogen atom a t the bridge head is ofimportance owing to the use of this method for structural determinationin the alkaloid field, The biological importance of the nucleotides is beingincreasingly realised, and has stimulated fresh attacks on the problem ofsynthesising such compounds. Derivatives of a new tricyclic system,flavazole, have been obtained from sugars, and their structures have beenconfirmed by degradative and synthetic experiments.I n the field of naturalproducts, the elucidation of the structure of biotin is the outstanding feature,and the investigations by which this result has been achieved are reviewed.E. R. H. JONES.H. T. OPENSHAW.L. N. OWEN.F. S. SPRINGSPRING : GENERAL METHODS. 1012. GENERAL METHODS.Reactions of Ethyleyze Derivatives involving the A11g1 Position.1.Various reactions of ethylenic derivatives involving the allyl positionhave been cited in these Reports. Of these may be mentioned the directintroduction of oxygen at this centre (a), oxidation at the allyl position bymeans of selenium dioxide, and the reaction of certain quinones with ethylenichydr0carbons.l To these should be added the well-known direct oxidationa t the allyl position by means of oxidising agents such as chromic acid leadingto a reaction of the type2>C:&CH,-- -+- >C:&CO-(a)Another reaction involving the allyl position has been described byK. Alder, F. Pascher, and A. Schmitz,h who show that propylene andmaleic anhydride react at 220-230"/110 atm. to yield allylsuccinic anhydride :>o CH,:CH*CH,*$lH-COCH2*C0 >o - CH3*CH:CH, + GHCOCH*COSimilar substituted succinic anhydrides were obtained from maleic anhydrideand A2-butene, isobutene, cycbpentene and cyclohexene.2. Halogenation in the Ally1 Position.-Many cases of direct halogenationin the allyl position have been described in the literature, but an analysis ofthese cases shows that at normal temperatures, direct halogenation of thet m e--6:(!',-CH< % -d:&-h-- + HHalis limited to hydrocarbons in which one of the unsaturated carbon atoms isfully substituted.In 1884, Sheshukov 3 demonstrated that treatment ofisobutene with chlorine under normal conditions of temperature and pressuregives largely P-methylallyl chloride (methallyl chloride).This reaction is usedfor the manufacture of this allyl halide, which can be obtained in approxi-mately 90% yield.4 A similar substitution in the allyl position occurs when2-methyl-A2-butene 5v is treated with chlorine.J. Meisenheimer 7 studied the case of triphenylmethylethylene (I) andshowed that on treatment with bromine this hydrocarbon does not give adibromo-addition product as claimed by J. Levy,8 but a monobromo-sub-IHalAnn. Reports, 1937, 34, 230.F. W. Semmler and W. Jakubowicz, Ber., 1914, 47, 1141; A. Windaus, Ber.,1920, 53, 491 ; F. S. Spring and T. Vickerstaff, J., 1937, 249.ao Ber., 1943, 76, 27.* J. Burgin, W. Engs, H. P. A. Groll, and G. Hearne, Ind. Eng. Chem., 1939, 31,ti N. Kondakov, J. Russ. Phys. Chem.SOC., 1885,17,290. ' D. V. Tischenko, J . Ben. Chem. U.S.S.R., 1936,6, 116, 1549.J . Russ. Phys. Chem. SOC., 1884, 16, 478.1413; Ann. Reports, 1940, 37, 205.Annalen, 1927, 458, 126. 8 Bull. SOC. c h h . , 1921, 29, 895102 ORQANIC CHEMISTRY.stituted derivative (11). The structure of (11) was established by oxidation,which gives a mixture of benzophenone and phenacyl bromide :(11.)CH,Br CH3(I.) Ph2C:C/ Bra Ph,C:C/\Ph --+ \PhMeisenheimer concluded that the reaction proceeds by direct substitution.Although W. Schlenk and E. Bergmann9 have used the observation ofMeisenheimer as a proof that the original hydrocarbon has structure (111),addition of bromine, followed by loss of hydrogen bromide, giving (11), theCHPh,fPh + Br, --+ CHPh,*yBrPh ---+ (IT.) - HBrCH2 CH,Br(111.)true mechanism of the reaction was established by K.Ziegler and K. Bahr.loZiegler and Bahr showed that treatment of I : l-diphenyl-2 : 2-dimethyl-ethylene (IV) with bromine gives a dibromide (V) which readily loses hydrogenbromide, yielding the bromo-substituted unsaturated hydrocarbon (VT),the reaction involving an allylic rearrangement :Although in the case of triphenylmethylethylene the intermediate dibromo-adduct is less stable and cannot be isolated, a similar mechanism operates,a remark which also applies to the direct halogenation of p-cyclogeranic acidto give the allyl halide (VII).llMe, Me,Early attempts to apply this direct substitution reaction to a straight-chain unsaturated hydrocarbon were not successful.In 1936, however,T. D. Stewart and B. Weindenbaum 12 succeeded in preparing pentenylchlorides by the direct chlorination of 2-pentene, but only in very smallyield :CH,*CH:CH*CH,*CH, + CH,Cl*CH:CH*CH,*CH,and possibly CH3*CH:CH*CHCl*CH3Various attempts to increase the extent of allyl substitution by the useof catalysts and by irradiation of the reaction mixtures were unsuccessful,Annalen, 1928, 468, 1. Ber., 1929, 62, 1695.l1 (3. Wendt, Ber., 1941, 74, 1242. I t J . Anrst. C h n . Soc., 1936, 6$,98SPRING : GENERAL METXIODS. 103but the desired effect was obtained by usiug relatively high t e r n p e r a t u r ~ . ~ ~The reaction haa been studied most in the cage of propylene. At temper-ature between 300" and 600°, chlorine and propylene react t o give mainlyally1 chloride.Although the commercial value of this reaction is great, as ageneral method the reaction is limited, since i t can clearly only be applied t oethylenic derivatives which are stable at the high temperature employed.A general approach t o the problem of devising a method for directhalogenation in the ally1 position under reaction conditions which are capableof general application has been made with conspicuous success by K. Ziegler,A. Spath, E. Schaaf, W. Schumann, and E. Winkelmann.14 A limitedsucceas had been realised previously by A. W0hl,15 who found that N-bromo-aoetamide reacts with tetramethylethylene in ethereal solution to give a16% yield of CMe,:CMe-CH,Br. Later A. Wohl and K. Jaschinowdri l6showed that the same reagent reacts with crotonic acid t o give, in very smallyield, a bromocrotonic aoid, the constitution of which was not established,and that propylene on treatment with N-bromoacetamide gives a dibromide,probably CH,Br*CBr:CH,.Ziegler and his co-workers have examined a large number of N-halogen compounds and a summary of the results obtained is instruc-tive.N-Halogenated sulphonamides such as N-dichlorotoluene-p-sul-phonamide (dichloramine-T) and N-halogenated sulphonimides such a8p - C,H,Me*SO,*NCl*COPh, (p-C,H,Me*SO,) ,NCI, and N - o hloro- and N -bromo-saccharin were not satisfactory. On the other hand, N-bromo-phthalimide was found to react readily with cycbhexene, giving 3-bromo-A'-cyclohexene (50%), but a considerable quantity (21%) of a stablea, X, = X, = C1, R = Me6 , XI = X, = C1, R = Phc, X, = C1, X, = Br, R = Med, X, = C1, X, = Br, R = Ph0I0 NCI*COR(VIII.) (IX.)addition product (VIII) was .produced.N-Chlorophthalimide is much lessreactive than the corresponding bromo-derivative.The members ofthis group, such as N-chloroacetsnilide, which readily rearrange t o nuclearsubstituted isomers, are obviously unsuited. A number of triply substitutedmembers of the group (IX, a&) were found to react with cyclohexene togive 3-chloro-A1-cycZ~hexene in yields of the order 70-90y0, carbon tetra-chloride being used as solvept. Although this result at first sight seems veryattractive, this group of oompounds has the great disadvantage that theproportion of active halogen in the molecule is extremely small and thisrequires the use of relatively large volumes of diluent.This disadvantagewas slightly mitigated by the observation that Np-dichloro-, N-chloro-Attention was next directed to N-chloroacylanilides.H. P. A. Groll and G. Heerne, Ind. Eng. Chem., 1938, 81,1630.Anntrlen, 1942, 551, 80. 16 Ber., 1919, 62, 61. 1' Ber., 1921, 54, 476104 ORGANIC CHEMISTRY.p-nitro-, and Nop-trichloro-acetanilides are sufficiently stable (i.e., do notisomerise) under the conditions employed, and react more quickly withcyclohexene than the compounds (IX, a 4 ) . The use of this group ofcompounds is the most efficient general method available for chlorinationin the allyl position.Bromination.Ziegler and his co-workers have shown that N-bromo-phthalimide is an ideal reagent for bromination in the allyl position. Incontrast to N-bromoacetanilides it is easily prepared. It contains 45% ofactive halogen and the succinimide which is produced after reaction of thebromo-imide with an unsaturated compound is very sparingly soluble incarbon tetrachloride. After reaction is complete it is recovered and readilyreconverted into the bromo-imide-pccinimide acts as a bromine carrier.I n the considerable number of reactions between unsaturated compoundsand bromosuccinimide that have so far been examined, no case of additionhas been observed and monosubstitution as distinct from disubstitution is thegeneral rule.The reactivity of N-bromosuccinimide is highly specific ; N-chlorosuc-cinimide does not chlorinate in the allyl position, and attempts to obtain acorresponding chlorinating agent were unsuccessful.Furthermore, otherN-bromodiacylimides, such as N-bromoglutarimide, N-bromohexahydro-phthalimide and N-bromodibenzamide, do not resemble N-bromosuccinimidein this reactivity.In view of its wide applicability several examples of the use of N-bromo-succinimide may be given. The reactions are usually carried out in boilingcarbon tetrachloride solution.I n the case of simple olefins containing a t least onemethylene group in the allyl position, yields of monosubstituted derivativesof the order of 80% are obtained, the time taken for the reaction to proceedto completion being illustrated by the following examples : l-methyl-A1-cyclohexene (5 mins.), Af-dodecylene (25 mins.), pinene (25 mins.),cyclohexene (30 mins.), A4-nonene (40 mins.).I n suitable cases, e.g., cycZo-hexene, the product is homogeneous, whereas in others mixtures of isomersare formed and complications arise due t o the intervention of allylicrearrangements.Concerning the orientation of the allyl halide formed, it was observed thata methylene group is much more easily substituted than a methyl group;thus a hydrocarbon R*CH,*CH:CHMe gives mainly R*CHBr*CH:CHMe ;it is noteworthy that N-bromosuccinimide fails to convert propylene intoallyl bromide. The exceptional slownese of the reaction between thebromo-imide and diisobutylene (5 hours for completion), the product ofwhich, according to F.C. Whitmore and J. M. Church,17 is mainlyCH,:CMe*CH,*CMe, (X), is probably to be attributed to the heavily sub-stituted carbon atom immediately attached to the a-methylene group.A useful test for an allyl bromide was discovered by Ziegler and co-workers, who found that, when mixed with cyclohexylamine, these bromides17 J . Arner. Chern. SOC., 1932, 54, 3710.Mono-olejinsSPRING : GENERAL METHODS. 105undergo a strongly exothermic reaction, the reaction temperature increasingspontaneously to approximately 160' ; this reaction is not shown by eitheralkyl bromides or vinyl bromides.Mono-olefins can be dibrominated in certain cases, but the interestingobservation was made in the case of cyclohexene that, when treated with twomoles of the bromo-imide, the monobromide 3-bromo- A1-cyclohexene is themajor product.If, however, 3-bromo-A1-cyclohexene is treated with onemole of bromo-imide, the dibromide 3 : 6-dibromo-A1-cyclohexene is obtainedin good yield.Dienes. Non-conjugated dienes react normally with two moles ofN-bromosuccinimide, but conjugated dienes cannot be successfully halogenatedby this reagent.In a preliminary study of various classesof unsaturated compounds it has been shown that the presence of freehydroxyl and carboxyl groups is contra-indicated, since they lead to de-composition of the reagent with formation of hypobromous acid, which addsto the ethylene linkage. Unsaturated esters, on the other hand, are readilybrominated in the ally1 position. cycloHexeny1 acetate gives the bromo-ester (XI) and cholesteryl esters are brominated in a few minutes withquantitative formation of succinimide. Of considerable interest is the con-version of methyl crotonate and methyl P-methylcrotonate into the corre-Other unsaturated compounds.OAc/\(/' BrCH,Br*CH:CH*CO,Me WI.)CH,Br*CMe:CH-C0,Me (XIII.)sponding y-bromo-esters, (XII) and (XIII) respectively, in high yield.Themethod has also been applied to P-amyrin acetate, a-amyrin acetate andmethyl acetylursolate ; l 8 here the intermediate bromo-substitution productsare not isolated, the reaction leading to the introduction of two ethyleniclinkages (with formation of a conjugated triene-ester) in the case of p-amyrinacetate, and the introduction of one ethylenic linkage in the cases of a-amyrinacetate and methyl acetylursolate to give conjugated diene-esters.Reactions catalysed by Hydrogen Fluoride.Hydrogen fluoride is a useful catalyst for the alkylation of aromatichydrocarbons by means of 0lefi1y.l~ The olefin does not polymerise, the onlyobserved reaction being alkylation.I n general, hydrogen fluoride is itcatalyst of fairly wide applicability and it will effect reactions which proceedin the presence of sulphuric acid, aluminium chloride or boron fluoride.20I n the presence of hydrogen fluoride, propylene and benzene give iso-propylbenzene (84%), isobutene and benzene give tert.-butylbenzene (40%)L. Ruzicka, 0. Jeger, and J. Redel, Helv. Chim. Acta, 1943, 26, 1235.1) J.H. Simons and S . Archer, J . Amer. Chem. Xoc., 1938,60, 986, 2953.30 J. H. Simons, S . Archer, and H. J. Pessino, ibid., p. 2956; J. H. Simons andS. Archer, ibid., 1040, 63, 461.D 106 ORGANIC CHEMISTRY,and di-tert.-butylbenzenes (40 %), and cyclohexene and benzene give cycb-hexylbenzene (60%). Benzene and cyclopropane react in the presence ofhydrogen fluoride to give n-propylbenzenes only.W. S. Calcott, J. M. Tinker, and V. Weinmayr 21 find that at the ordinarytemperature benzene is alkylated by propylene in the presence of hydrogenfluoride to give either a mixture of isopropylbenzene (74.7y0) and diiso-propylbenzene (17%) or 1 : 2 : 4 : 5-tetraisopropylbenzene (77%) accordingto the molecular proportions employed. Other alkylations which have beenrealised by means of hydrogen fluoride are : naphthalene and propylene yieldtetraisopropylnaphthalene, phenol and propylene give 2 : 4 : 6-triisopropyl-phenol (94~5%)~ benzene and ally1 alcohol give ap-diphenylpropane (62%),toluene and diisobutylene give p-tert.-butyltoluene (77 %), m-xylene andtert.-butyl alcohol give tert.-butyl-m-xylene (97 yo).Similarly, in the presenceof hydrogen fluoride, both naphthalene and phenanthrene are tert.-butylatedin excellent yields when treated with tert.-butyl alcohol. isoPropy1 ether,tert.-butyl alcohol, isopropyl alcohol, ethylene oxide, and dibenzyl ethercan also be used as alkylating agents for aromatic hydrocarbons in thepresence of hydrogen fluoride.Hydrogen fluoride catalyses the alkylation of aromatic hydrocarbonsby means of alkyl halides ; 22 in this reaction it is superior to metallic halides.in that self-oondensation of the aromatic hydrocarbon does not occur.Direct alkylations of phenol and ethyl furoate (with tert.-butyl alcohol),20and of a-nitronaphthalene, benzoic acid, p-aminophenol, pdimethylamino-phenol, and p-anisidine (with isopropyl ether) 21 have also been reported.Although acylations of aromatic hydrocarbons by means of acid chlorides,acid anhydrides, and carboxylic acids do not proceed in high yieldY23 hydrogenfluoride is an excellent reagent for the cyclisation of a number of y-aryl-butyric acids and @-arylpropionic acids.24Hydrogen fluoride can effect a number of molecular rearrangements;e.g., in the presence of hydrogen fluoride, tert.-butylbenzene and phenolgive benzene and tert.-butylphenol; again, in the presence of hydrogenfluoride, benzophenoneoxime undergoes a Beckmann rearrangement toyield benzanilide.Although at room temperature, hydrogen fluoride willnot effect a Fries rearrangement,24 at 100" phenyl acetate is converted insmall yield into p-hydroxyacetophenone, and p-tolyl benzenesulphonate (I)gives 2-hydroxy-5-methyldiphenylsulphone (11).21 J . Amer. Chem. SOC., 1939,61,949,1010;~ J. H. Simons and S. Archer, i6id., 194029 J. H. Simons and S. Archer, ibid., 1938,60,2953,2955; 1930,61, 1521.23 J. H. Simons, D. I. Randall, and S. Archer, &id., p. 1796.24 L.'F. Fieser and E. B. Hershberg, ;bid., p. 1272.62, 1623SPRING : GENERAL METHODS.107Oxidations with Hydrogen Peroxide.E. Weitz and A. Scheffer 25 have shown that ap-unsaturated ketones areoxidised to the corresponding oxides when treated with alkaline hydrogenperoxide, whereas under the same conditions saturated ketones such asacetone and acetophenone, unsaturated hydrocarbons such as stilbeneand 2 : 3-dimethylbutadiene, and ap-unsaturated acids such as cinnamic,fumaric and maleic acids are not attacked by the reagent. a-Diketones,on the other hand, suffer fission when treated with alkaline hydrogen peroxide,diacetyl and benzil giving acetic and benzoic acids respectively.N. A. Milas and S. Sussman26 have developed a particularly usefulhydroxylating agent consisting of an anhydrous solution of hydrogenperoxide in tert.-butyl alcohol.The reagent is stable over long periodsof time and is inert towards olefins; in the presence of a small amount ofosmium tetroxide, likewise dissolved in tert. -butyl alcohol, olefins are quicklyoxidised to give the corresponding glycol. Oxidation of ethylenic compoundsis effected by the reagent with vanadium pentoxide 27 as catalyst, trimethyl-ethylene and ethyl fumarate thereby giving trimethylethylene glycol andethyl racemate respectively. On the other hand, ethylenic compounds inwhich the double bond is conjugated with an aromatic ring, such as anethole,isoeugenol, and isosafiole, suffer fission with formation of anisaldehyde,vanillin, and piperonal respectively. By the same reagent and vanadiumpentoxide, benzene is oxidised to phenol.The oxidation of ethylenic com-pounds by means of hydrogen peroxide in tert.-butyl alcohol is also catalysedby means of chromic anhydride, but the reaction is less effective.R. Criegee 28 has employed hydrogen peroxide in ether catalysed byosmium tetroxide for the oxidation of ethylenic compounds, and therebyobtained carbonyl compounds. This ether reagent has been used in thesterol and triterpene group. One cam may be singled out for special com-ment; A. Butenandt and H. Wolz 29 find that ap-unsaturated ketones areoxidised to the corresponding keto-glycols thus :>c&-c- + >$-)-----b. OHOH 0a, reaction of especial interest in view of inert nature of @-unsaturatedketones to perbenzoic acidAnother interesting oxidation by means of hydrogen peroxide is describedby N. A.Milas, P. F. Kurz, and W. P. A n ~ l o w . ~ ~ There is considerableand to osmium tetroxide in ether.2825 Ber., 1921, 54, 2327; E. Weitz, Annalen, 1919, 418, 4.26 J . Amer. Chem. Soc., 1936, 58, 1302 ; 1937,59,2345.27 Ibid., 1937, 59, 2342; 1927, 49, 2005.28 Annalen, 1936, 522,75 ; Ann. Reports, 1937,34,233.20 Ber., 1938, 71, 1483.8o J. Baeseken, Rec. Trav. chim., 1926, 45, 838; K. Bodendorf, Arch. Pharm., 1930,268, 491.J . Amer. Ohem. SOC., 1937, 59, 543108 ORGANIC CHEMISTRY.spectroscopic evidence 32 that, when exposed to light of wave-length approxi-mating to 3000 A., hydrogen peroxide dissociates into two hydroxyl radicals.Milas and his associates exposed mixtures of hydrogen peroxide with ally1alcohol, crotonic acid, and maleic acid to the light from an ultra-violetlamp and thereby obtained glycerol (43'73, dihydroxybutyric acid (30%),and mesotartaric acid (12-22%) respectively.W.Treibs33 has described the oxidation of olefins, using hydrogenperoxide with pervanadic acid [VO,(OH), or HVO,] as catalyst, and acetoneas solvent, the products being either glycols or oxides. Using the sameoxidising agent and water and methanol as solvents, Treibs34 found thatcycbhexanone is oxidised to the half aldehyde of adipic acid and cyclo-pentanone gives the half aldehyde of glutaric acid as major products. Inthe case of cycbhexanone this catalysed hydrogen peroxide oxidation alsoyields cyclohexane-1 : 4-&one, a reaction which bears a resemblance to thebiological oxidation of camphor 35 and of fen~hone.~~ Under similar con-ditions aldehydes are not attacked.Reactions of A crylonitrile.Cyanoethylation.-Acrylonitrile reacts with liquid ammonia to give amixture of NH,-CH,*CH,*CN and NH(CH,*CH,*CN),.Similar cyano-ethylations of aliphatic primary and secondary amines, hydrazines, hetero-cyclic bases, and amino-acids have been reported.37 Acrylonitrile also reactswith hydrogen sulphide 38 and with water to give (I) and (11) respectivelyand cyanoethylations of alcohols and glycols 40 proceed in the same manner.CH,*CH,.CN(I.) '<CH,*CH,*CNPhenols are readily cyanoethylated to yield p-aryloxypr~pionitriles,~~ andoximes react with acrylonitrile thus : 42CMe,:NOH --+ CMe,:N*O*CH,*CH,*CNThe cyanoethylation of compounds containing active methylene groups,such as fluorene and cycbpentadiene, was mentioned in a previous Report.43Further examples of the addition of active methylene compounds to acrylo-31 H.C; Urey, L. H. Dawsey, and F. 0. Rice, J . Amer. Chem. SOC., 1929, 51, 1371 ;G. von Elbo, ibid., 1933, 55, 62; W. H. Rodebush and M. H. Wahl, J. C h m . Physics,1933,1,696; 0. Oldenberg, ibid., 1935,3,266; A. A. Frost and 0. Oldenberg, ibid., 1936,4, 642, 781 ; V. Kondrat'ev and XI. Ziskin, Acta physicochim., U.S.S.R., 1936, 5, 301.38 Ber., 1939, 72, 7.35 Y . Asahina, Bey., 1928, 61, 533; 1931, 64, 1931; 1933, 66, 1673.3a E. Rimini, Gazzetta, 1909, 39, 186; F. Reinartz and W. Janke, Bey., 1936, 69,3 7 E.P. 404,744; 457,621; 466,316; U.S.P.1,992,615; 2,017,637.99 H. A. Bruson and T. W. Riener, J . Amer. Chem. SOC., 1943,65,23.' 0 U.S.P. 9,280,790; 2,280,791 ; 2,280,792.4 1 D.R.-P., 670,357; F.P. 833,734.43 F. S. Spring, Ann. Reports, 1942, 39, 140.34 Ibid., p. 1194.2269.' 0 D.R.-P. 669,961; U.S.P. 2,163,176.42 J . Amer. Chem. Soc., 1943, 05, 23OWEN : CARBOHYDRATES. 109nitrile have since been reported.42 Phenylacetonitrile is converted into amono- 4p and a di-p-cyanoethyl derivative, and ethyl cyanoacetate andethyl malonate are both converted into the corresponding di- P-cyano-ethyl derivative. According to C. F. K0elsch,4~ acrylonitrile reactswith aryldiazonium chlorides to give unstable compounds of the typeAr*CH,*CHCl*CN, which are readily converted into the correspondingcinnamonitriles.H. A. Bruson and T. W. Riener 46 have studied the reactionbetween acrylonitrile and ketones. They show that in the presence ofbenzyltrimethylammoniium hydroxide, aromatic methyl ketones are convertedinto tri- @ - cyanoet h yl derivatives ArG0.C (CH,*CH,*CN), . Propiop henone,a-tetralone and deoxybenzoin give the corresponding di- p-cyanoethylderivatives. cycbHexanone and cyclopentanone yield tetra- p-cyanoethylderivatives, and corresponding cyanoethylations of aliphatic ketones arereported. Ethyl acetoacetate likewise reacts with acrylonitrile to give theester CH,*CO~C(CH2*CH,*CN),*C0,Et. Camphor, isophorone and diisobutylketone could not be cyanoethylated.H. A.Bruson and T. W. Riener*’ have studied the reaction betweenap-unsaturated ketones and acrylonitrile. Benzyltrimethylammoniumhydroxide or potassium hydroxide being used as catalyst, mesityl oxidereacts with acrylonitrile to give a mixture of (111) and (IV). Furthercyanoethylation of (111) converts it into (IV). Acrylonitrile reacts withH,*CH,.CN yH,*CH,*CN0 0 CH,*CH,*CNCMe,:CH*CMe --+ CMe,:C*CMe --+ CH,:CMe*y*COMe(111.) (IV.)crotononitrile in a similarof which yields (VI).CHMe:CH.CN -way, the reaction giving (V), further cyanoethylationTH,*CH,*CN y H,.CH,.CN(V.) CH,*CH,*CN-+ CHMe:C.CN --+ CH,:CH.y.CN(VI.1P. 8. s.3. CARBOHYDRATES.Acyclic Derivatives.It has long been realised that an aqueous solution of a reducing sugarmay contain a trace of the open-chain form, but apart from a few specialinstances, some of which are mentioned below, the proportion’is so smallthat detection is difficult.The absorption spectra of fructose and sorbosein aqueous solution give faint indications of the acyclic forms, but withaldoses the results are negative.l It has been shown, however, thataldoses, contrary t o previous reports, are reducible at the dropping mercury44 C. F. Koelsch, J . Anter. Chern. SOC., 1943, 85, 437.46 Ibid., p. 57. 46 Ibid., 1942, 64, 2850. ‘7 Ibid., 1943, 65, 18.1 W. Bednarczyk and L. Marchlemski, Biochem. Z., 1938, 300,42110 ORGAN10 CHEMISTRY.cathode, and that the amount of aldehyde-sugar present in a solution canthereby be determined.2 The reactions of fructose l-phosphate and, evenmore readily, of fructose 1 : 6-diphosphate with hydrogen cyanide, underconditions ineffective with fructose itself, indicate a tendency to react inthe keto-form which increases as phosphate groups are introduced.3 3'.Hartley and W.H. Linnel14 have stated that in view of the absence ofmutarotation in solutions of 6-methyl fructose, 3 : 4 : 6-trimethyl fructose,1 : 3 : 4 : 6-tetramethyl fructose, and 5-methyl glucose, the commonlyaccepted furanose forms should be replaced by open-chain structures, but,since these substances have not yet been obtained in crystalline condition,the absence of mutarotation is inconclusive; indeed it is evident from theconsiderable variations in reported specific rotations that some preparationshave been of doubtful purity.The positive SchS tests given by 5-methylglucose and 5 : 6-dimethyl glucose do suggest, however, that the proportionof aldehyde-form in solutions of these derivatives is not inconsiderable, and itwould be of interest to examine. their light-absorbing properties and theirbehaviour under polarographic analysis.It has been established that 3 : 6-anhydro-sugars can readily be trans-formed into aZdehydo-derivatives in which the anhydro-ring is still present.T. L. Cottrell and E. G. V. Perciva18 have now found that treatment of3 : 6-anhydro- p-methyl-d-galactopyanoside with acetic anhydride andsulphuric acid results in scission of both rings and the production of penta-acetyl aldehyde-dl-galactose, a transformation reminiscent of the formationof the same product from 6-iodo- and 6-tosyl-2 : 3 : 4 : 5-tetra-acetyld-galactose.lO Racemisation in the ordinary sense is of course impossible,and there is as yet no direct evidence to show how the dl-product is formed.The action of lead tetra-acetate on 1 : 2-monoacetone-&-glucofuranoseand on 2 : 3-monoacetone-d-mannofuranose, followed by removal of theacetone residues, has given d-xylo- and d-lyxo-trihydroxyglutardialdehydes,llthe first members of the dialdose class to be prepared.Octa-acetyl aldehydo-maltose, the fist crystalline uldehydodsaccharide derivative, has beenobtained by M. L. Wolfrom and M. Konigsberg l2 from the correspondingdiethylmercaptal .A large number of acyclic derivatives of 'the general formula R*CHXYare now available, where the substituents X and Y, attached to C,, .areS.M. Cantor and Q. P. Peniston, J . Amer. Chm. Soc., 1940, 62,2113.* A. V. Stepanov and B. N. Stepanenko, Biokhimiya, 1940,5,198, 567.Quart. J. Phurm., 1940,13, 332.L. von Varghe, Ber., 1936, 69,2098.6 M. R. Salmon and G. Powell, J . Amer. Chem. SOC., 1939, 61, 3507; K. Freuden-7 W. N. Haworth, J. Jackson, and F. Smith, J., 1940, 620; W. N. Haworth, L. N.8 J., 1942, 749. ' F. Micheel, H. Rlihkopf, and F. Suckfiill, Ber., 1936, 68, 1523.lo F. Micheel and H. Ruhkopf, Ber., 1937, 70, 860.l1 K. Iwadare, Bull. Chem. SOC. Japan, 1941, 16, 40, 144.l2 J . A m r . Chem. Soc., 1940, 62, 1163.berg and E. Plankenhorn, Ber., 1940, 73, 621.Owen, and F. Smith, J ., 1941, 88OWEN : UARBOHYDRATES. 111selected from the five groups SEt, OH, OAc, OM0 (or OEt), Cl (Br or I).Of the pos8ible types i-xv (see Table), thirteen have been prepared, andeight of these show asymmetry on C,; it is therefore of great interest thattypes iii, viii, xi, xii, and xiv have been isolated in the two modificationsdemanded on stereochemical grounds.Tspe i 11 111 iv V vi vii * viiiX = SEt SEt SEt SEt SEt OH OH OHY = SEt OH OAc OMe C1 OH OAo OMe...XV... Type ix * x xi xii Xlll XiVX = OH OAc OAc OAc OMe OMe C1Y = c1 OAc OMe C1 OMe C1 c1* Not known.Although the dimethyl acetals of glycollaldehyde, glyceraldehyde,and some partly substituted sugars have been known for many yews,it is only recently that the acetals of unsubstituted pentoses and hexoseshave been obtained.E. M. Montgomery, R. M. Ham, and C. S. Hudson,l3by the use of 4% of sulphurio acid in acetic acid-acetic anhydride, found thattriacetyl p-methyl-d-arabinoside (I) was converted into hexa-acetyl aldehyde-d-arsbinose (11). When the sulphuric acid was replaced by 8% of zincchloride, the methyl group was not removed and the product consisted laxgelyof the penta-acetyl methylhemiacetd, which was isolated in the two stereo-isomeric forms (111) and (IV). Each of these, with aluminium chloride orhydrogen chloride in ether, gave the corresponding tetra-acetyl d-arabinose1-chloro-1-methylacetals (V) and (VI), from which w&s obtained tetra-AH*((3OAc 0 (111.) (."<"\ (V.1 OM0/ IH<OMe (VII.)CHJ \CH<E +(iH<:k -> vH<g&eMe0 $Z€-AcO*V*H 1 / AH*V*OAcA A .1 (I.)CH<% (IV.) WI.)* A (11.)acetyl d-arabinose dimethylacetal (VII) by treatment with ailver oxide andmethanol.The crystalline d-arabinose dimethylacetal, obtained by deacetyl-Is J . Amr. Chem. Soc., 1937,59, 1124. * The following abbreviations are used in this Report :-IAcO*C*HH* *OAcH. *OAcA = 1CH,*OAO CH,-OA112 ORGANIC CHEMISTRY.ation, is readily hydrolysed to d-arabinose by aqueous acid, and in acidmethanol it gives the usual equilibrium mixture of methylarabinosides.M. L. Wolfrom, L. J. Tanghe, R. W. George, and S. W. Waisbrot,l* andH. A. Campbell and K. P. Link15 have shown that in methanol, in thepresence of mercuric chloride and cadmium carbonate or mercuric oxide,penta-acetyl galactose diethylmercaptal (VIII) is converted into the penta-acetyl dimethylacetal (IX).Similarly, the corresponding glucose l6 andmannose l7 compounds have been prepared. In each instance the crystallinehexose dimethylacetal is obtained on deacetylation. The direct formationof d-fructose dimethylacetal 18+ and Z-rhamnose dimethylaceta120 fromthe corresponding unsubstituted diethylmercaptal has also been achieved.The first member of the hemiacetal series (type viii) to be isolated in twoforms is methyl tetra-acetyl d-galacturonate ethylhemiacetal (X), preparedfrom methyl tetra-acetyl aldehydo-d-galacturonate.21 Fractional crystal-lisation gave both an a- and a p-form. The absolute condipation on C,has not been determined, and the prefix o! is assigned to the isomer with thehigher positive rotation in the d-series, a convention which has also beenadopted by M.L. Wolfrom.Acetylation under mild conditions of penta-acetyl d-galactose methyl-hemiacetal (XI) yields the u- and the p-form of hexa-acetyl l-methoxy-aldehydo-&galactose,* (XII) which with hydrogen chloride in ether areconverted into the same penta-acetyl 1 -chloro-1 -methoxy-aldehy&o-d-galac-tose (XIII),22 a result which differs from that observed l3 with the correspond-ing arabinose compounds (111) and (IV). (XIII) has also been obtained 23by the action of acetyl chloride on penta-acetyl galactose dimethylacetal(IX). The halogen in these substances is highly reactive; the ethoxy-analogue of (XIII), for example, with silver carbonate in dry benzene givespenta-acetyl aIdehydo-d-galactose (XIV) .22The acyclic analogues of the aceto-halogen sugars were originally obtainedin only one form,24 but by the application of the zinc chloride reagent l3 ithas been possible to prepare from (XIV) the two stereoisomers of hexa-acetyll-chloro-aldehydo-d-galactose (XV) .25 Treatment of (XIV) in dry benzenewith phosphorus pentachloride yields penta-acetyl 1 : 1 -dichloro-aldehyde-&-galactose (XVI), the first substance of this type to be obtained in the sugarl4 J .Amer. Chem. SOC., 1938, 60, 132. l6 J . Bwl. Chem., 1938, 122, 635.1’ M. L. Wolfrom and S . W . Waisbrot, J . Amer. Chem. Soc., 1938, 60, 864; 1939,1 7 A.Scattergood and E. Pacsu, ibid., 1920, 62, 903.18 E. Pacsu, ibid., 1938, 60, 2277.20 J. W . Green and E . Pacsu, ibid., 1938, 60,2288.21 R. J. Dimler and K. P. Link, ibid., 1940, 62,1216.22 M. L. Wolfrom, M. Konigsberg, and F. B. Moody, ibid., p. 2343.z3 Rl. L. Wolfrom and D. I. Weisblat,ibid., p. 878.24 M. L. Wolfrom, ibid., 1935, 57, 2498.25 M. L. Wolfrom and R. L. Brown, ibid., 1941, 63, 1246.* The nomenclature at present in use for open-chain derivatives is not altogethersatisfactory ; b b hexa-acetyl d-galactose methylhemiacetal ” would be preferable, and inconformity with the names adopted for (111) and (IV).61, 1408.lo Idem, ibid., 1939, 61, 1671OWEN : CARBOHYDRATES. 113series.26 Hexa-acetyl l-bromo-aklehydo-d-galactose with ethanol and silvercarbonate gives penta-acetyl d-galactose ethylhemiacetal ; 22 this curiouscH<:Ei + CH<oMe OMe CH<gE(VIII.) (IX.1 \ YHGF H*b*OAcAcO.7-HAc0.y.H (X.)OMe OMe/ (XIII.)TH<OH --+ YH<OAc(XI.) (XU.) 1 ! H*V*OAc + C0,Me SEt SEtCH<CI --+ VH<OR CHOG (XVII.) (XVIII.) G -> yH<gAc(XV.)G (XVI.)SEt tcH<Eyc f- YH<oHG (XX.) G (XIX.)change is of interest inasmuch as hexa-acetyl 1 -halogeno-hexoses maythemselves be prepared from penta-acetyl hemia~etals.~~By treatment with acetyl chloride and phosphorus oxychloride, one of thethioethoxy-groups in penta-acetyl d-galactose diethylmercaptal (VIII) isreplaced by chlorine, and the product, penta-acetyl 1 -chloro-1 -thioethoxy-aEdehydo-d-galactose (XVII), reacts readily with ethanol in the presence ofsilver carbonate to give penta-acetyl d-galactose diethylmonothioacetal(XVIII, R = Et), from which d-galactose diethylmonothioacetal is obtainedon dea~etylation.~~ The use of methanol in place of ethanol results in theformation of the mixed acetal (XVIII, R = Me).Dialkyl monothioacetalshave been postulated by E. Pacsu l9 as intermediates in the conversion ofdialkylmercaptals into thioglycosides, alkylglycosides, and dialkylacetals,and it should now be possible to test the validity of this theory.The thiohemiacetal (XIX) has been obtained by M. L. Wolfrom, D. I.Weisblat, and A. R. Hanze 27 by the addition of ethylthiol to penta-acetylaldehydo-d-galactose (XIV) . Acetylation to (XX), followed by replacementof the l-acetyl group by chlorine, yields (XVII).Galactose is the only sugar which has given derivatives of all the thirteenknown types, but considerable progress has been made in the glucose,l6# 21e 24p 27mannose,17.21p 28 and arabinose 2l*29030 series, in each of which stereo-isomerism of type xi has been demonstrated.l3. 21 The glucose series affordsthe only example of the isolation of stereoisomers of type iii, this having beenaccomplished 27 by preparing the glucose analogues of (XIX) and (XX).The hexa-acetyl 1 -thioethoxy-aldehyde-d-glucose [analogue of (XX)] was2G M. L. Wolfrom and D. I. Weisblat, J . Amer. Chew. SOC., 1940, 62, 1149.2 7 Ibid,, p. 3246.2 * M. L. Wolfrom, M. Konigsberg, and D. I. Weisblat, ibid., 1939, 61,574.29 M.L. Wolfrom and M. Konigsberg, ibid., 1938,80,288.a. M. L. Wolfrom and R. L. Brown, ibid., 1943,66, 961114 ORGANIC CHEMISTRY.separated into two different crystalline products, but unfortunately only thea-isomer was obtained in sufficient quantity to be carried through to d-glucoseO-methyl-S-ethylmonothioacetal [deacetylated analogue of (XVIII)]. Itis possible that the p-form, similarly treated, would give the hithertounrecorded stereoisomers of types iv and v.The reaction of diazomethane with the aldehyde group was shown to beapplicable to aldehydo-sugars by P. Brigl, H. Miihlschlegel, and R. S ~ h i n l e , ~ ~and this reaction has now been applied 32 to the d- (XXI) and the Z-form oftetra-acetyl aEdehydo-arabinose for the preparation of d- (XXII) and Z-tetra-acetyl 1 -deoxy-Eeto-fructose.Under similar conditions, penta-acetyl keto-d-fructose (XXIII) gives (XXlV) .33FH3 YH,*OAc YH,*OAcCHO --+ 00A A I(XXI.) (XXII.) (XXIII.). (XXIV.)An acid chloride reacts with diazomethane to give, as primary produbt,a diazomethyl ketone which can often be isolated in good yield.34 I n thesugar field, non-crystalline products were obtained from diethylideneZ-xylonyl chloride 35 and from acetone d-glyceryl chloride,36 but it has nowbeen shown that penta-acetyl d-gluconyl chloride (XXV) gives crystalline v1 qHN2 yo-7 ?H2*OAc?*A A A~O.V*H j A ~ O ~ ~ XCH,*OAc 70H*V*OAovo --j co -> i H*F*OAc H*?*OAc H*V*OAc 0(XXV.) H.?--] AcO *V *HH*C/*OAc H*F*OAc(XXVII.) CH,*OAc/ (xTI-) rcp w r vH,*OAc(XXX.) P + V0 H*C/*OAc H*Y*OAcA A(XXVIII.) (XXIX.)penta-acetyl l-diazo-l-deoxy-keto-d-glucoheptulose (XXVI), whioh undergoesthe Amdt-Eistert rearrangement 37 to give tetra-acetyl 2-deoxy-8-d-gluco-81 Bey., 1931, 64,2921.32 M.L. Wolfrom, D'. I. Weisblat, W. H. Zophy, and S. W. Waisbrot, J . Amer.33 M. L. Wolfrom, D. I. Weisblat, and S. W. Waisbrot, aid., p. 632.34 F. Amdt, B. Eistert, and W. Partale, Ber., 1927, 60, 1364; F. Arndt and J.35 K. Giitzi and T. Reichstein, Helv. Chim. Acta, 1938, 21, 186.3t3 K. Iwadare, Bull. Chern, SOC. Japan, 1939, 14, 131.ST F. Amdt and B. Eistert, Bey., 1936,68,200; W. E. Bachmann and W. S. Struve,Chem. Soc., 1941, 83, 201.Amende, Ber., 1928,61,1122; W. Bradley and R. Robinson, J ., 1928, 1310.Organic Reactions, 1, 38OWEN : UARBOHYDRATES. 115heptonolaotone (XXVII).33n 38 This substance, in common with the deacetyl-ated &lactone, is remarkable in that it shows no mutarotation. (XXVI)with hydrogen bromide in ether yields the l-bromo-compound (XXVIII),33v38and with acetio acid it gives hexa-acetyl keto-d-glucoheptulose (XXIX),which is also obtained from (XXVIII) with acetic anhydride and potassiuma~etat0.3~ Deacetylation yields crystalline d-glucoheptulo~e.~* This seriesof reactions provides a new synthetic route for the preparation of ketosesand has been used for the conversion of penta-acetyl d-galactonyl chlorideinto d-galaheptulose,40 of tetra-acetyl d-arabonyl chloride into penta-acetylketo-d-fructose (XXIII),3*.39 and of tetra-acetyl mucyl dichloride into theinteresting diketose acetate (XXX).39 In the galactose series, the inter-mediate (XXXI) undergoes the Curtius reaction41 with iodine to give the1 : l-di-iodo-compound (XXXII), reduced by hydriodic acid to penta-acetyl 1 -deoxy-keto-d-galaheptulose (XXXIII), also obtained from (XXXI)by direct reduction.42YHN2 YHI, VH3TO + yo _3 yoG G G(XXXI.) (XXXII.) (XXXIII.)IOxidation of a-Glycol Qroups.Maidy as a, result of the work of C. S. Hudson and his school, periodicacid hasbecome a reagent of great importance for structural work in thecarbohydrate field. The oxidation is stoicheiometric, and considerablediagnostic value may therefore be attached to the quantitative estimationof the products and of the oxidant required.a-Methyl-d-hexopyranosidestake two moles of periodic acid and yield one mole of formic acid md onemole of d'-methoxy-d- hydroxymethyl diglycollaldehyde * (XXXIV) .438 44The same product (XXXIV), but no formic acid, is given by a-methyl-d-arabofuranoside, only one mole of oxidant being required,43 whereasa-methyl-d-pentopyranosides yield formic acid and d'-methoxy diglycoll-aldehyde (XXXV) .43 I 45 Experiments with p -methyl-& hexopyranosides 43v46and p-methyl-d-pentopyranosides 4 3 a 4 7 e 48 have given results similar to thoseM. L. Wolfrom, S. W. Waisbrot, and R. L. Brown, J . Amer. Chem. Soc., 1942,04,1701.Idem, ibicE., p. 2329.40 M. L. Wolfrom, R. L. Brown, and E. F. Evans, &id., 1943,65,1021.41 T.Curtius, Ber., 1885, IS, 1283.42 M. L. Wolfrom.andR. L. Brown, J. Amer. Chem. SOC., 1943,66,1616.4s E. L. Jackson and C. S. Hudson, aid., 1937, 69,994.u I&m, &id., 1939,61,1530.46 W. D. Maclay and C. S. Hudson, ibid., 1938, 60,2059.46 E. L. Jackson and C. S. Hudson, ibid., 1939, 61, 959.47 Idem, ibid., 1941, 63, 1229.48 H. S. Iabell and H. L. Fwh, J . Res. Nat. Bur. Stand., 1940, 24, 126.* d' and I' distinguish the configuration of C,, corresponding to a- and fi-formsrespectively of the original glycoside in the d-series. In the Z-series the reverse holds ;thus a-meth yl- Z - glucop yrmoeide would give I '-methox y - Z- hydroxymeth y 1 dig1 ycoll-aldehyde, the enantiomorph of (XXXIV)116 ORQANIC CHEMISTRY.obtained with the a-glycosides, except of course that the correspondingZ’-aldehydes are produced.Characterisation is effected by oxidation of thealdehydes with bromine water in the presence of an alkaline-earth carbonate,leading to the isolation of crystalline salts (usually of strontium) which nowserve as reference compounds. For example, in the d-series all a-methyl-hexopyranosides and a-methylpentofuranosides give strontium d‘-methoxy-d-hydroxymethyl diglycollate (XXXVI).H OMe Y 72HI0, $X*OH IVH-OH Q ---+~ H ~ O H IH.(-i--’6 7CH,*OHa -Me th ylhexopyranosi de.H\ OMeCHO I 0-co 1Q -Sr/ 0 \H*CO,H +\O-FO iH.7-JYH0 ] I€*?--CH,*OH CH,-OH(XXXIV.) (XXXVI.)YH*OH 1CH2u-Methylpentopyranoside.CH2*OHP O 1 CH,--(XXXV.) a-Methylpentofuranoside.The methylpyranosides of the methylpentoses have also been subjectedto oxidation with periodic acid, and each of the four reference compoundsd’ (and I’)-methoxy-d (and I)-methyl diglycollaldehydes (XXXVII) havebeen obtained in crystalline form ; 43e 49 hydrolysis of the correspondingdibasic acids gives either d- or Z-lactic acid and thus provides a direct correl-ation between the latter and the sugar configurations. The dialdehydesreadily undergo an intramolecular Cannizzaro reaction to give the hydroxy-acids (XXXVIII) and (XXXIX) of corresponding configuration. 50r---O-----lMeO*CH*CHO CHO-CHMe (XXXVII.)I-- 0- .1 7 - 0 - 1MeO*CH*CH,*OH CO,H*CHMe MeO*CH*CO,H CH,( OH) GHMe(XXXVIII.) (XXXIX.)Applications of the reagent to a#-trehalose and sucrose 5l have con-firmed the structures previously assigned to these disaccharides.A veryinteresting development is reported by V. C. Barry,52 who points out that4Q W. D. Maclay, R. M. Ham, and C. S . Hudson, J . Amer. CILem. Soc., 1939, 61,6o E. M. Fry, E. J. Wilson, and C. S. Hudson, ibid., 1942, 64, 872.51 P. Fleury and 5. Courtois, Compt. rend., 1942, 214, 366.63 J., 1942, 678; Nature, 1943, 152, 537.1660OWEN : CARBOHYDRATES. 117a non-reducing polysaccharide of the laminarin type, in which consecutivepyranose units are linked through C, and C,, contains an a-glycol grouponly on the terminal residue. This unit is therefore the only part of the chainto be attacked by periodic acid, and subsequent treatment of the oxidisedpolysaccharide with phenylhydrazine results in complete removal of the end-group fragments, with the result that the recovered material has a chainlength one unit less than the original.A step-wise degradation is achievedby alternate treatments with periodic acid and with phenylhydrazine, aprocess which is obviously of great importance, since it may well provideinformation on the presence of cross-linkages in the macro-molecule.Lead tetra-acetate in certain instances behaves in the same way as periodicacid, and it will for example oxidise a-methylmannopyranoside (XL) to(XXXIV).53 It has been suggested 54 that the usual attack on the cis-glycol group to yield (XLI) is followed by formation of the cyclic acetal(XLII), the glycol group of which is then attacked by the second mole oftetra-acetate.I n support of this mechanism is the observation 54 thatglycosides with no hydroxyl on C,, such as 6-trityl a-methylmannoside anda-methylrhamnoside, which cannot form cyclic acetals analogous to (XLII),react with a second mole of reagent only with difficulty.*HVOMe 7-1CHO ICHO 0 -H*C*OH ICH,*OH(XLI.)H.7- _I-CH,(XLII.)H\/OMeZ&l? -+?KO ICH,*OH(XXXIV.)He?--’Glycosans.Periodic acid has been used with striking success in the elucidation ofstructures of the laevoglucosan type (XLIII), in which the anhydro-ring--(XLIII.) (XLIV.) (XLV.)63 W. S. McCIenahan with R. C. Hockett, J. Amer. Chem., SOC., 1938, 60,2061.64 R. C. Hockett and W. S. McClenahan, ibi&., 1939, 61,1667.* A related mechanism, involving the intermediate formation of a $-glycol, has beenadvanced by E.Baer ( J . Amer. Chem. SOC., 1940, 62, 1597) to explain the oxidation bylead tetra-acetate of simple a-keto-alcohols, which occurs in the presence of water,ethanoI, etc. An aqueous or alcoholic solution of a-methylrhamnoside or 6-trityl a-methylmannoside would probably react readily with 2 mols of the reagent (compare E.Baer, J. M. Grosheintz, and H. 0. L. Fischer, ibid., 1939, 61, 2607)118 ORGANIC CHEMISTRY.engages Cl. Laevoglucosan itself, 1 : 6-anhydro- p-d-glucopyranose (ord-glucosan (1, 5 ) (1, 6)), reacts with two moles of the oxidant and yieldsone mole of formic acid and one mole of 7,‘-oxy-d-methylene diglycollaldehyde(XLIV), characterised as the strontium salt of the corresponding dibasicacid.55 Identical results have been obtained with d-altrosan,66 d-mannosan,57and d-galacto~an.~~Hexosans are conveniently prepared by pyrolysis, and under such con-ditions lactose gives lmoglucosan and d-galactosan ; 58 only the latter ,has aconfiguration amenable to the formation of an acetone compound, andseparation is thereby readily accomplished.The structure of the 3 : 4-monoacetone- 1 : 6-anhydro- p-d-galactopyranose has been established byD. McCreath and F. Smith,59 who isolated it as a by-product in the preparationof diacetone galactose. The d-galactosan, obtained on mild hydrolysis,can also be prepared by pyrolysis of galactose, but it is then accompaniedby. small proportion of 1 : 3-anhydro-P-d-galactopyranose (d-galactosan<1, 5 ) p <1,3)), the structure of which is indicated by itsresistance to periodicacid and consequent absence of an a-glycol group in the molecule.60Pyrolysis of ivory nut (PhyteEepas macrocurpu) yields a crude d-mannosanwhich may be purified through the triacetate 61 or the 2 : 3-monoacetonecompound (XLV).57 The latter has been of considerable value in thes3;nthesis of new C4 derivatives of mannose. Methylation and hydrolysisgives crystalline 4-methyl mannose,* 57e 62 and the 4-tosyl mannosan withaqueousanhydroalkali gives a tricyclic- p-d-talopyranose (XLVI)(XLVI.)an63.hydrohexosan, probably 1The 1 : 6- and 3 : 4-ringsHOH O€€: 6-3 : 4-di-are opened(XLVII.)by acetolysis, and the resulting penta-acetyl hexoses on deacetylation andsubsequent hydrogenation yield d-mannitol and d-iditol.The formation66 E. I,. Jackson and C. S. Hudson, J . Amcr. Chem. SOC., 1940,62,958.66 N. K. Richtmyer and C. S . Hudson, ibid., p. 961.6 7 A. E. Iinauf, R. M. Hann, and C. 8. Hudson, ibid., 1941,63,1447.56 R. M. Hann and C. S. Hudson, ibid., p. 1484; 1942,64,2435.69 J . , 1939, 387.80 R. M. Hann and C. S . Hudson, J . Amer. Chem. SOC., 1941, 63,2241.6; G. Zemplh, A. Gerecs, and T. Valatin, Ber., 1940, 73, 675.62 W. T. Haskins, R. M. Hann, and C. S . Hudson, J . Amer. Chem. SOC., 1943,845.70.63 R. M. Eann and C. S. Hudson, ibicl., 1942,64,925.* E. Pacsu and S. M. Trister ( J . Amer. Chem. SOC., 1941,63,925), by the preparationof crystalline 2-methyl mannose, have finally confirmed that the supposed 4-methylmannose of E.Pacsu and C. von Kary (Ber., 1929,62,2811) is the 2-methyl compound.4-Methyl mannose has also been eynthesised by hydrogenation of 4-methyl6-msnnonolectone (0. T. Schmidt end H. Mtiller, ibid., 1943, 76, 344)OWEN : CARBOHYDRATES. 119of (XLVI) and its behaviour on hydrolysis are thus in conformity with theviews now held concerning Walden inversion in such reaction^.^^ Condens-ation of the acetone mannosan (XLV) with acetobromoglucose, followed byremoval of the acetone residue and subsequent acetolysis, results in theformation of octa-acetyl 4- p-d-glucopyranosido-d-mannose, which on de-acetylation gives crystalline epicellobiose.66 The conversion of octa-acetylepicellobiose, via hexa-acetyl cellobial, into cellobiose 66 provides a newand structurally definitive synthesis of this disaccharide.Similarly,67 bythe use of acetobromogalactose, it has been possible to synthesise epilactoseand lactose.The formation of glycosans by alkaline treatment of p-phenylglycosidm 68is likely to be of use in configurational studies, since the reaction is not givenby any of the a-phenylglycosides so far investigated.All attempts to prepare 1 : 2 : 3-triacetyl ribofuranose by detritylationof 1 : 2 : 3-triacetyl-5-trityl ribose have given 2 : 3-diacetyl 1 : 4-anhydro-a-d-ribopyranose (2 : 3-diacetyl 1 : 5-anhydro-p-d-ribofuranose), from whichribosan (XLVII) is obtained on deacetylation ; 69 the simultaneous posseasionof a pyranose and a furanose structure makes this a substance of peouliarinterest.Polyhydric Alcohols.Considerable attention has for a long time been directed towards theproduction of these substances by catalytic hydrogenation, and manyrecent studies have been concerned with the introduction of more efficientcatalysts and with the determination of optimum conditions.The use ofRaney nickel has resulted in the preparation in crystalline form of xylitol,70cellobiot01,~l rnelibiot01,~~ and 6-~-d-glucosidodulcit01.~3 Z-Gulomethylitoland d-rhamnitol are obtained by the condensation of diacetone-aldehyde-d-arabinose with methylmagnesium iodide, followed by removal of the acetoneresidues.74 Direct condensation of glucose and phenol is claimed to yieldp-hydroxyphenyl d-~orbitol.~~Much progress has been made in the determination of the structures ofpartly substituted derivatives.The dibenzylidene dulcitol prepared fiftyyears ago by Emil Fischer 76 gives a dibenzyl derivative, hydrolysed t o adibenzyl dulcitol which takes only one mole of periodic acid and gives no66 W. T. Haskins, R. M. Hann, and C. S. Hudson, J . Amr. Chem. Soc., 1941, 63,66 Idem, ibid., 1942, 64, 1289.6 * E. M. Montgomery, N. K. Richtmyer, and C. S. Hudson, ibid., 1942, 64, 1483;60 H. Bredereck, M. Ktbthnig, and E. Berger, Ber., 1940, 73, 956.70 M. L. Wolfrom and E. J. Kohn, J . Amer. Chem. SOC., 1942,64,1739; J. F. Carson,71 P. A. Levene and M. Kuna, J . Bid. Chem., 1939,137,49.72 M.L. Wolfrom and T. S. Gardner, J . Amer. Chem. Soc., 1940, 62, 2553.73 P. A. Levene and R. S. Tipson, J . Bwt. Chm., 1938,125,365.i4 K. Gatzi and T. Reichstein, Helu. C&m. Acta, 1938, 21, 914.S. Peat, Ann. Reports, 1939, 36, 258.1724.6 7 Idem, ibid., pp. 1490, 1852.1943, 65, 3, 1848.S. W. Waisbrot, andF. T. Jones, ibid., 1943,65, 1777.B.P. 518,586.. '* Ber., 1894, a7, 1524120 ORUANIC CHEMISTRY.formaldehyde. The dibenzyl dulcitol therefore contains one cc-glycolgroup, which cannot be of the CH,(OH)*CH(OH)- type ; hence the benzylresidues must be on Cz and C,, a conclusion which is confirmed by oxidationwith lead tetra-acetate to benzyl-dl-glyceraldehyde. The original compoundis therefore 1 : 3-4 : 6-dibenzylidene dulcitol, and this formulation is supportedby its resistance to lead tetra-acetate and the non-reactivity of the ditosylderivative towards sodium iodide.?' The di-o-nitrobenzylidene dulcitolof I.Tanasescu and E. M a c ~ v s k i , ~ ~ formerly thought to be 1 : 2-5 : 6-,and the dimethylene dulcitol of K. Weber and B. Tollens 79 are also said to be1 : 3-4 : 6-derivative~,~~ but the fine structures are based on the supposedpreference for six-membered rings (see p. 121). From 1 : 6-dibenzoyldulcitol, the structure of which follows from its reaction with three moles oflead tetra-acetate to yield two moles each of formic acid and benzoyl-glycollaldehyde,81 two new 2 : 3 : 4 : 5-dibenzylidene dulcitols have beenprepared, which presumably represent a pair of the possible fine structures2 : 3-4 : 5, 2 : 4-3 : 5, and 2 : 5-3 : 4, though it is conceivable that theisomerism is concerned with the presence of the asymmetric carbon atom inthe benzylidene residue.82 I n this connection, it is of interest that isomerismof this type has recently been demonstrated 83 in the ortho-ester form(XLVIII) of the octa-acetyl disaccharide prepared by the condensation of1 : 2 : 3 : 4-tetra-acetyl p-d-glucose with acetobromomannose; in additionto the normal biose, two distinct modifications of (XLVIII) were isolated,It has been emphasised 81 that care must be exercised in the applicationof oxidative methods to acetone derivatives, owing to their sensitivitytowards acids.I n place of periodic acid, sodium periodate or lead tetra-acetate in acetic acid may be used, and under such conditions it has beenshown that the diacetone dulcitols formerly thought 84 to be 1 : 2-3 : 4- and3 : 4-5 : 6-compounds are in fact the 2 : 3-5 : 6- and 2 : 3-4 : 5-derivati~es.~~Furthermore, from the anomalous behaviour of tetratosyl erythritol (inwhich all the tosyl groups react with sodium iodide) 85 i t is evident thatthe Oldham-Rutherford rule can no longer be extended with safety toindicate the number of free primary alcoholic groups in a polyhydricalcohol.R. M. Hann, A. T. Ness, and C. S. Hudson 86 conclude that atosyl group in a secondary position is reactive if it is contiguous to one ina primary position.Derivatives of other sugar alcohols for which structures have now been7 7 W. T.Haskins, R. M. Hann, and C. S. Hudson, J . Amer. Chcm. SOC., 1942, 64,78 Bull. SOC. chim., 1933, 53, 1097.132.79 Annalen, 1898, 299,316.R. M. Henn, W. T. Haskins, and C. S. Hudson, J . Amer. Chem. SOC., 1942, 64,R. M. Hann, W. D. Maclay, and C. S. Hudson, ibid., 1939, 61, 2432.W. T. Haskins, R. M. Hann, and C. S. Hudson, ibid., 1942,64,136, 137.83 E. A. Talley, D. D. Reynolds, and W. L. Evans, ibid., 1943, 65,575.R. A. Pizzarello and W. Freudenberg, ibid., 1939, 61, 611.R. S. Tipson and L. H. Cretcher, J. Org. Chm., 1943, 8, 95.J . Amer. Ohm. SOC., 1044.66, 73.986, 1614OWEN : CARBOHYDRATES. 121proposed include 1 : 2 : 3 : 4-dibenzylidene d-~orbitol,~' 2 : 3 : 4 : 5-dimethyl-ene 88 and 2 : 3 : 4 : 5-dibenzylidene 89 d-mannitol, 1 : 3- and 2 : 3-benzylideneCH,*OAcCH, O-T*H 0C.HAcO*CH,*O*$l*H P"' '-IH-Q O*CH,*OAcC,*H,9O,O>~O--C, 7 HA c : : r q Hey- H.Y-0 _ICH,*OAc CH,*OAc(XLVIII.) (XLIX.)d-arabit01,~O and 2 : 3 : 4 : 5-&acetone Z-fu~itol.~~ A partial rupture ofmethylene-acetal residues is reported by A.T. Ness, R. M. Hann, and C. S.HudsonYg2 who have found that acetolysis of trimethylene-d-mannitol givesa product which is probably 1 : 6-diacetyl-3 : 4-di(acetoxymethyl)-2 : 5-methylene d-mannitol (XLIX), from which 2 : 5-methylene d-mannitolis formed on saponification. It is suggested 92 that trimethylene d-mannitolhas a 1 : 3-2 : 5-4 : 6 structure, on the grounds that (a) it must contain a2 : 5-methylene group, and (b) a precursor is a dimethylene d-mannitol whichmust be 2 : 3-4 : 6 or 1 : 3-5 : 6.It would appear, however, that the isolationof a methylene compound with a seven-membered ring throws doubt on allfine structures which have been based on the alleged preference for five- orsix-membered rings, and the dimethylene mannitol may well be 1 : 4-3 : 6,and'the trimethylene mannitol 1 : 4-2 : 5-3 : 6 (a model shows clearly thatthe latter structure is almost strainless). It is necessary, therefore, to providerigid proof of fine structures by other methods, and this has been achievedby W. N. Haworth and L. F. Wiggins, 93 who have shown that in the dimethyl-ene-1 : 6-dibenzoyl derivatives of mannitol and sorbitol the methyleneresidues are in the 2 : 4- and 3 : 5-positions, and that trimethylene sorbitolis the 1 : 3-2 : 4-5 : 6 compound.The answer has now been given to the controversial problem of thestructures of the naturally occurring anhydrohexitols, styracitol and poly-galitol.Early observations on the epimeric character of these substanceshad shown that they were 1 : 5-anhydro-derivatives of rnannitol and sorbitol ;this ring structure has recently been confirmed by periodic acid oxidation.94L. Zervas 95 prepared styracitol from triacetyl hydroxyglucal and assumedit to have the sorbitol configuration (LI), but W. Freudenberg and E. F.Rogers 96 pointed out that the mannitol structure (L) was also compatible*' J. K. Wolfe, R. M. Hann, and C. S. Hudson, J. AmeT. Chem. Soc., 1942, 64, 1493.In W. T. Haskins, R. M. Hann, and C.S. Hudson, ibid., 1943, 65, 67.@O Idem, ibid., p. 1663.@l A. T. Ness, R. M. Hann, and C. S. Hudson, ibid., 1942, 64, 982.st Ibid., 1943, 65, 2215.@3 J., 1944, 58; and private communication from Professor W. N. Haworth.94 N. I<. Richtmyer and C. S. Hudson, J . Amer. Chem. SOC., 1943, 65, 64.9 5 Ber., 1930, 63, 1689.O 6 J . Amer. Chem. Soc., 1937, 59, 1602.Idem, ibid., p. 1419122 ORGAN10 CHEMISTRY.with the method of synthesis, a view which was upheld by the observationthat styraoitol was oxidised more readily than polygalitol with lead tetra-Hs*q*H H-Y-OAo IH0.Y.H 0 AcO.7.H IH O q % THO*$!*H 0H*Y*oAc i H.?----' H*?-- He?--H*V*OH 1 H*Y*OH JCH,*OH CH,*OH CH,*OAc(L.1 GI.) (LII.)acetate and should therefore contain a cis-glycol group.This conclusion,which was supported by L. Zervas and I. Papadimitri~u,~' was reversedin a later paper 98 on the grounds that tetramethyl styracitol (a liquid) wasalmost identical in physical properties with the product formed by hydro-genation and dehydration of 2 : 3 : 4 : G-tetramethyl glucose. The oxidationexperiments, however, have been confirmed by R. C. Hockett, M. T. Dienes,and H. E. R a m ~ d e n , ~ ~ who compared the reaction rates with those obtainedwith substances of known configuration, and the synthesis of tetra-acetylpolygalitol by treatment of tetra-acetyl P-d-glucothiose (LII) with Raneynickel proves that polygalitol is 1 : 5-anhydrosorbitol (LI). The isolationof this substance as a by-product from the Zervas synthesis provides afinal proof of the epimeric relationship and shows conclusively that styracitolis 1 : 5-anhydromannitol (L).lO0 L.N. 0.4. STEROID SYNTHESES.Since the last review in the Annual Reports for 1939 interest in the syn-thesis of steroids has been maintained and significant progress may be saidto have been made, although naturally the output of published researchhas diminished appreciably. No strikingly original routes have beendevised and progress has been largely confined to the exploitation of methodsdeveloped earlier. Consequently in the first section of this Report the variousinvestigations have been reviewed, as far as possible, according to the mainplan of the general synthetic scheme employed. These comprise (a) ex-tensions of the Bachmann equilenin synthesis, (b) developments of theRobinson diketone method, ( c ) syntheses based on the Robinson-Mannichbase method, (d) applications of the Diels-Alder reaction, ( e ) introductionof angular methyl groups into preformed cyclic systems, and (f) studies on thecyclisation of dienynes.It may be noted here that the discovery within the laat few years ofmethods of converting members of the steroid sex hormone series intoD-homo-derivatives (such as 11) containing the perhydrochrysene skeleton8 ' Ber., 1940, 73, 174.98 W.Freudenberg m d J. T. Sheehan, J. Amer. Chem. Soc., 1940, 62, 558.99 Ibid., 1943, 65, 1474.100 N. K. Richtmyer, C. J. Cam. and C. S . Mudaon, ibid., p. 1477JONES : STEROID SYNTHESES. 123may possibly simplify the task of synthesis, in that it introduces an elementof symmetry and at the same time provides a considerably inareased numberof objectives.Such syntheses would be of added interest in view of the highlypotent hormone activity of the D-homoandrostane derivatives.The second section contains a comprehensive survey of the literature onthe chemistry of the purely synthetic estrogens, a subject mentioned brieflyin the last Report. It has been found convenient t o discuss the moreimportant of these substances in separate sections.(a) Following on the notable achievement of the synthesis of d-equilenin[ I ; R = OH), detailed in the last Report on this topic,l Bachmann and hiscollaborators have synthesised a variety of related compounds, including astereoisomer of oestrone, by employing the same basic procedure.Thiswas evolved initially with such scrupulous attention to detail that 90%yields were attained a t almost every stage, and it is worthy of mention thatfrom 10 g. of l-keto-7-methoxytetrahydrophenanthrene, 2.5 g. of dl-equileninand an equal amount of its stereoisomeride * were obtained in spite of the factthat some twelve distinct operations were involved .2The lack of biological activity (in 50O-y doses) of the dl-forms of thestereoisomeric deoxyequilenin and deoxyisoequilenin (I ; R = H) (termedcis- and trans-equilenones) emphasises the importance of the C,-hydroxylgroup in addition to the known stereochemical effect (Z-equilenin and thediastereoisomeride dZ-isoequilenin are relatively inactive), in relation tocestrus-producing pr~perties.~ The racemic forms of 6-hydroxyequilenoneand its stereoisomer have been synthesised4 but this transference of the3-hydroxyl group t o Cs results in complete loss of activity.of the synthesis have rendered possible variations inthe mture of the angular group of dl-equilenin, and it appears that cestro-genic potency is largely preserved in the homologues up to n-propyl, but then-butyl compound and a 16-methyl-dl-equilenin are inactive, as also are allthe dl-isoequilenin homologues.The effect of the absence of the angular1 H. D. Springall, Ann. Repork, 1939, 36, 307.2 W. E. Bachmann, W. Cole, and A. L. Wilds, J . Amer. Chem. SOC., 1940, 62, 824:3 W. E. Baehmann and A. L.Wilds, ibid., p. 2084.4 W. E. Bachmann and D. W. Hslmes, ibid., p. 2750.5 Idem, ibid., 1941, 63, 595, 2692.Other extensions* Bachmann employs the prefix iSo- in the equilenin series to denote the atericconfiguration arising from the alternative mode of linking of the two hydroaromaticrings. This is believed to be a trans-fusion in the naturally occurring steroids (c.g.,equilenin) and convincing evidence in support of this contention has been obtained byK. Dimroth and H. Jonsson (Ber., 1941, 74,620)124 ORQANIC (JHEMISTRY.methyl group on biological activity has yet to be established and a synthesisof norequilenin by some variant of this method would be of considerableinterest, especially for comparison with the x-norequilenin prepared earlierby a different route.6 *to be estrogenic only in 10 mg.doses. z-Norequilenin might belong to theiso-series, but H. A. Weidlich and M. Meyer-Delius,g on the basis of com-parative hydrogenation experiments in acid and alkaline solutions, concludethat the terminal rings in the x-norequilenin of Koebner and Robinsonare trawlinked (see p. 126). A racemate which may belong to thenorcestrone series has been found to be appreciably estrogenic (see p. 132).Syntheses of dl-D-homoequilenin (11) (see also p. 126) and its stereoisomerwere achieved by repetition of the Amdt-Eistert homologation process, theformer compound proving as potent as dl-equilenin. This is surprising,since D-homo-astrone has been reported to be thirty times less active thanThe acetate of the latter has now been reportedthe natural h~rmone,~ but on the contrary derivatives of the D-homo-androstane series have been found to be as potent as their natural steroidanalogues ; l o for example, ( I I a ) is indistinguishable from androsterone inbiological activity.' A.Koebner and (Sir) R. Robinson, J., 1938, 1994.Idem, J., 1941, 666.* M. W. Goldborg and S. Studer, Helv. Chim. Acta, 1941, 24, 478.lo M. W. Goldberg and R. Monnier, ibid., 1940, 23, 840; M. W. Goldberg andE. Wydler, ibid., 1943, 26, 1142.* Since this Report was written W. E. Bachmann, R. A. Gregg, and E. F. Pratt(J. Amer. Chem. SOC., 1943, 65, 2314) have described a new synthesis of a norequilenin.The lreto-triester (A), prepared by condensation of the appropriate naphthylethyl-malonic ester with the acid chloride of ethyl hydrogen succinate, was smoothly cyclisedwith phosphoric acid to (B) and the corresponding crystalline trimethyl ester washydrogenated by means of a palladium-charcoal catalyst. Unfortunately only one form* Ber., 1941, '74, 1195, 1213.of the acid (C) was produced on decarboxylation of the dihydro-acid, and cyclisation(Dieckmann) and simultaneous demethylation gave the s-norequilenin of A.Koebnerand (Sir) R. Robinson.6 Hydrogenation of the ethenoid linkage after decarboxylationwould appear t o offer a better opportunity of obtaining the diastereoisomeric form of (C).An extension of the method yielded a D-homonorequilenin (11, without the angular MegrOUP)JONES : STEROID SYNTHESES.125W. E. Bachmann, S. Kushner, and A. C. Stevensonll studied theapplication of the equilenin method to the synthesis of aestrorie (V), wheremore complicated stereochemical problems are involved. The structureof the unsaturated keto-ester (111), synthesised by standard methods, wasreadily established by hydrogenation to the already known dihydro-com-pound.12 Dehydration of the hydroxy-ester obtained by the Reformatskyreaction, with dry hydrogen chloride in benzene or with formic acid, gave thecrystalline unsaturated ester (IV), and hydrogenation of the two ethenoidlinkages was effected with a palladium-charcoal catalyst. The resultantmixture of stereoisomers was converted by the Arndt-Eistert chain-lengthen-ing process into the propionic acid derivative and after Dieckmann ringclosure, hydrolysis and demethylation the ultimate product [containing a tmost 8 dl-forms and obtained in 75% overall yield from (IV)] readily yieldedMe Mea crystalline substance (dl-oestrone-a) which is undoubtedly an cestrone (V)stereoisomer.dl-CEstrone-a, however, is only fully active in doses of 2507(cf. l y for d-cestrone), but the resinous mixture of the remaining stereo-isomers is considerably more active and may contain dl-oestrone itself.Since the stereochemical configurations a t the four asymmetric centres ofthe final product are determined during the saturation of the two ethyleniclinkages of (IV) it seems safe to predict that a detailed study of this vita.1stage will lead to the ultimate synthesis of the racemic form of the naturalhormone.A structural isomer of (V), containing an aromatic B ring and a 6-hydroxylgroup is devoid of activity (at 1000y).13 A simplified oestrone model (VI)aynthesised l4 by the standard route from 6-methoxy-a-tetralone exhibitedMe Me Me(VII.) (VIIU.)negligible estrogenic properties.route l5 to cis-%methyl- l-hydrindanoneThe Bachmann synthesis affords a new(VII) and the previously unknownJ.Amer. Chem. SOC., 1942, 84, 974.** (Sir) R. Robinson and J. Walker, J., 1936, 747; 1937, 60; 1938, 183.I t W. E. Bachmannand A. B. Ness, J. Amer. Chem. Soc., 1942,64,536.I4 W. E. Bachmann and D. G. Thomas, ibid., p. 94; tho corresponding deoxy-l6 W. E. Bachmann and S. Kushner, ibid., 1943, 65, 1963.l G See also V.C. E. Burnop and R. P. Linstead, J., 1940, 720.compound was synthesised earlier, ibid., 1941, 63, 598126 ORGANIC CHEMISTRY.trans-form. The former ketone has been synthesised by C. D. Nenitzescuand V. Przemetzky l7 by simultaneous ring closure and reduction when theacid chloride (VIIa) was treated with aluminium chloride in cyclohexanesolution.The “ pentenyl ” method of G. H. Elliott and R. P. Linstead l8 has beenapplied l9 to l-keto-7-methoxy-2-methyl-1 : 2 : 3 : 4-tetrahydrophenanthrene.Condensation with A*-n-pentenylmagnesium bromide gave a carbinol, whichwas oxidised with permanganate to the acid (VIII) and after cyclisation(VIII.) (VIIIa.) VX.)with phoephoric oxide, partial hydrogenation of (VIIIa) with a platinumcatalyst gave a saturated methoxy-ketone.This was formulated as (IX),although the authors expressed uncertainty as to the direction of the finalcyclisation. to be identical withthe methyl ether of dl-D-homoequilenin (11) and it is to be noted that hydro-genation of the C,,,, ethenoid linkage leads to a stereochemical configurationa t C14 identical with that in equilenin itself, it being assumed that the morecestrogenic isomers of each pair have the same C,, configuration.(b) One of the most elegant routes to the steroid ring system is by (Sir) R.Robinson’s diketone method involving the condensation of an acetyl-naphthalene with furfural, fission of the furan ring with acids t o a diketone(X), which is then cyclised to a naphthylcyclopentenoneacetic acid (XI)with dilute alkali.The final cyclisation to (XII) can be effected with eithersulphuric acid or acetic anhydride. Cyclisation after hydrogenation of theethenoid linkage leads t o diketones such as (XIIa). Application of thismethod has already resulted in the synthesis of an x-norequilenin and anx-norms trone .zlH. A. Weidlich and M. Meyer-Delius8 have considered in detail thecatalytic hydrogenation of ap-unsaturated ketones, especially in relationto steroid synthesis. For those compounds which can give rise to geo-metrically isomeric dihydro-ketones, they conclude that hydrogenation inalkaline media proceeds by means of 1 : 4-addition, followed by tautomeris-ation to the stable trans-form, and that in acid solutions direct cis-additionof hydrogen occurs to either the carbon-carbon or the carbon-oxygendouble linkage, leading to cis-ketones, alcohols or hydrocarbons. A.Koebnerand (Sir) R. Robinson obtained dihydro-keto-acids by hydrogenation of1 7 Ber., 1941,74,676. See also C. D. Nenitzescu, E. Cloranescu, and V. Przemetzky,Ber., 1940, 73, 313.Is J., 1938, 660.19 V. C. E. Burnop, G. H. Elliott, and R. P. Linstead, J., 1940, 727.20 J., 1938, 1390; Ann. Reports, 1939, 36, 297.21 (Sir) R. Robinson and H. N. Rydon, J., 1939, 1395.The compound (IX) has now been founJONES : STEROID SYNTHESES. 127(XI; R = H and OMe), using palladium-strontium carbonate catslysts,but in an acidic medium (XI; R = H) was found to yield a new kefo-wid,o:fji-:o W\/d (XIIa.) Ralubelieved to be the cis-form.8 Since (XI; R = OMe) was an intermediatein the synthesis * of 2-norequilenin, Weidlich and Meyer-Delius conclude thatthe C and D rings in the latter are trans-fused.A variation of the diketone synthesis 22 starting with 6-chloro-6-methoxy-2-acetonaphthone gave a final product (XII; R = OMe, R‘ = Ac, Cl aaindicated), from which the chlorine atom was unexpectedly difficult to remove.H.A. Weidlich and M. Meyer-Delius 23 were successful in removing a bromineatom fiom a similar compound (XIu) by partial hydrogenation (Pd-CaCO,in KOH-EtOH) without reducing the ethylenic linkage. Subsequenthydrogenation in alkaline solution gave the trans-dihydro-compound. Theintroduction of either angular methyl or acetio acid groups into dihydro-compounds corresponding to (XI) and (XIa) has been attempted.’The carbonyl group is usually reduced when the phenanthrene nucleusin ketones of type (XII) is hydrogenated and it is clearly desirable to have areactive yet non-reducible group suitably sited in the five-membered ring.The method already employed 21 of opening the ring prior to hydrogenationis rather tedious and attempts have been made to protect the carbonylgroup in various ways.7 For example, a Reformatsky reaction on (XII;R = OMe, R’ = Me), followed by dehydration and hydrogenation with aRaney nickel catalyst, gave a product believed to be (XIII).a In somerelated model experiment^,^^ however, hydrogenation (Raney nickel) ofboth the ketone (XIV) and the acid (XV) resulted in reduction of the terminalbenzene ring, and from the latter two crystalline acids, probably stereo-isomers of atructure (XVI), were isolated.Hydrogenation of chloro-22 (Sir) R. Robinson and J. Willenz, J., 1941, 393.1a Ber., 1939, 72, 1941.er ( S i r ) R. Robinson and S. N. Slater, J., 1941, 376.*s L. C. Bateman and ( S i r ) R. Robinson, J . , 1941, 398; R. H. Martin and ( S i r ) R.Robinson, J . , 1943, 497128 ORGANIC CHEMISTRY.(XII; R = OMe, R‘ = Ac) 22 gave complex mixtures, the only recognisableconstituent being it deacetylated 9 : 10-dihydro-compound corresponding to/\--CH,*CO,Et(XIII.) A/\ ‘ A ‘ /Me01 ,! \/\(XIV.) WV.) (XVI .)chloro-(XII; R = OMe, R’ = H). J. W. Cornforth and (Sir) R. Robinsonz6devised a very satisfactory method of preparing 2 : 7-dihydroxyphenanthrene,involving cyclisation of 6 : 6’-di-iodo-3 : 3’-dimethoxydibenzyl by theUllmann reaction, and studied the hydrogenation of its monomethyl ether.With a “ copper chromite ” catalyst, reduction proceeds most readily in thephenolic ring, giving (XVIa) as main product, probably accompanied by someoctahydrophenanthrene derivative.( c ) There is little doubt that application of the Robinson-Mannich basemethod 27 offers the most promise of success for the synthesis of non-benzenoidsteroids of the testosterone (XVIII) type.Thus, application of this methodto a ketone such as (XVII), assuming that it could be procured in the requisitestereochemical form, would give testosterone itself, and there are analogiesindicating that this final stage would proceed in the manner indicatedMe Me-TOH Methiodide of Mf? PI--above.A. L. Wilds and C. H, ShunB28 have made a detailed study of theapplication of the method to the synthesis of the hydrochrysene derivative(XIX), isolating intermediate keto-esters and obtaining an overall yieldof 83 yo from Z-carbomethoxy- 1 -ketotetrahydrophenanthrene. The purityof the dialkylaminoethyl ketone seems to be an important factor.No conclusive evidence is as yet available to determine the orientationof the new six-membered ring in condensations of Mannich base methiodideswith either 5 - keto- 8-methylhydrindane or cis-5- ket~hydrindane.~~ However,although the decalone (XX) gives a hydroanthracene derivative on condens-*’ E.C. du Feu, F. J. McQuillin, and (Sir) R. Robinson, J . , 1937, 53; Ann. Reports,z8 J. Arner. Chem. SOC., 1943, 65, 469.zB F. J. McQuillin and (Sir) R. Robinson, J., 1911, 586; 1938, 1097.20 J . , 1942, 684.1939, 38, 295JONES : STEROID SYNTHESES. 128ation with 4-diethylaminobutan-2-one methiodide,2' 1 -methyl-cis-2-decaloneyields the unsaturated ketone (XXI), the structure of which was proved byAMn I I '\/) I e nthe isolation of phenanthrene and 2-phenanthrol after selenium dehydrogen-ation.30 It seems clear from the examples so far available that the Robinson-Mannich base reaction invariably involves a keto-methin (-CO-CHMe-) inpreference to a keto-methylene (-CO-CH2-) system.R. H. Martin and (Sir) R. Robinson31 have prepared the importantdiketone (XXV) as a mixture of stereoisomers in the following manner.Starting from 6-methoxy-5-methyl- 1 -tetralone, the keto-ester (XXII) was(XXII.) (XXIII.)Me(XXIV.)Mesynthesised by well-known methods and converted by a Reformatskyreaction, dehydration and subsequent reduction, into the two stereoisomericforms of the di-ester (XXIII).These were transformed separately into the01- and p-tricyclic phenolic ketones (XXIV) by the procedure (Amdt-Eistertchain lengthening and Dieckmann cyclisation) developed in the Robinsonand Bachmann schools. Advantage being taken of the valuable observationthat hydrogenation with supported palladium catalysts at high temperaturesand pressures effectively reduces substituted benzenoid systems, one of thetwo stereoisomers (a) of the phenolic ketone (XXIV) was reduced to thesaturated diol, which was in turn oxidised to the saturated diketone-a (XXV).A compound of this structure can exist theoretically in sixteendl-forms, eight derived from the a-series of (XXIV) and an equal number fromthe p-series, but, since (XXV) contains a keto-methin system, it appearslikely that only eight stable racemic forms of the diketone would exist.The diketone-a, which is considered therefore to comprise a t most fourdl-forms (it actually appears to consist largely of a single stereoisomer),was condensed with the methiodide of 4-diethylaminobutan-2-one, yielding30 (Sir) R. Robinson and F. Weygand, J., 1941, 386. 91 J., 1943, 491.REP.-VOL. XL. 130 ORGANIC CHEMISTRY.a product (XXVI) which, on the reasonable assumption that the keto-methin rather than the two keto-methylene systems are involved in thiscondensation, could contain half of the sixteen possible dl-forms of andro-stenedione.Biological results on this material will be of interest, althoughthe authors consider it more likely that dl-androstenedione itself will be foundin the second group of stereoisomerides which will result from the continuationof the synthesis with the p-isomer of the phenolic ketone (XXIV), in whichthe trans-configuration a t the linkage of rings C and D is thought to be moreprobable.Investigating a related route, J. G . Cook and (Sir) R. Robinson32 con-verted 4-methoxycyclohexanone into the Mannich base (XXVII), which withethyl p-ketovalerate yielded the unsaturated ketone (XXVIII).Hydro-genation, followed by a second Mannich base condensation, gave (XXIX;R = OMe) and, with ethyl cycEohexanone-4-carboxylate as starting materialin an analogous process, (XXIX; R = C0,Et) was obtained. Another(=x.)variant33 involves inclusion of the cyclopentanone ring in the form of theappropriate adipic acid. The keto-diester (XXX) has been prepared, sofar in only 8% yield, and the complete scheme envisages reduction of theethylenic linkage and the building up of a further six-membered ring by aMannich base condensation, followed by Dieckmann cyclisation to a com-pound similar to (XXV).Following up earlier researches 34 in which sodio-cyclohexanone wascondensed with styryl methyl ketone to give an octalone, the employmentof furfurylideneacetone (XXXI) in such condensations has been exploredby L.E. E n g and (Sir) R. Robinson.35 2-Methylcycbhexanone and (XXXI)gave an unsaturated ketone (XXXII), reduced in two stages (catalytic and(J?J@ :o -(XXXII.) (XXXIII.) (XXXIV.)Kishner-Wow) to a furylmethyldecalin (XXXIII), which after hydrolyticfission of the furan ring, followed by permanganate oxidation, yielded theacid (XXXIV), the configuration of which has yet to be determined. Themethod has been utilised to synthesise (XXXV) from the known octahydro.32 J., 1941, 391.83 ( S i r ) R. Robinson and E. Seijo, J., 1941, 582.34 W. 8. Rapson and (Sir) R. Robinson, J., 1936, 1285. 36 J., 1941, 465JONES : STEROID SYNTHESES.131phenanthrene ketone, and its degradation to an 2-cestrone methyl ether isbeing attempted. A. L. Wilds36 has described the pqeparation of thediketone (XXXVI ; R = H) from 2-bromo-1 -ketotetrahydrophenanthreneby condensation with the sodio-derivative of acetoacetic ester. Both theCHRdiketone and the diketo-ester (XXXVI ; R = C0,Et) are converted in 86-90% yields into the cyclic ketone (XXXVII) with aqueous alkali. Hydro-genation of (XXXVII) with a palladium-charcoal catalyst (in neutralsolution 8 ) gave the expected mixture of diastereoisomers. The difficultiesinvolved in modifying this method so as to introduce an angular methylgroup and a suitable substituent in the 17-position seem formidable.(d) The most successful attempt t o utilise the Diels-Alder reactionin steroid synthesis has been that of E.Dane and her collaborators37 inwhich a stereoisomer, or possibly an isomer, of oestrone was synthe-dependent upon the orientation of the addition reaction, a point whioh stillremains unclarified. The convenience of the diene synthesis has much tocommend it and several applications have recently been made, mainly,however, in the form of model experiments. E. Dane and 0. Ho~s,3*extending their earlier work, have employed the substituted vinylacetylene(XXXVIII) as a " diene" component in condensations with both acrylicand propiolic esters. The product (XXXIX) from the former was tetra-/\COMe(XXXVIII.) . (XL.)hydrogenated and converted via the acid chloride and diazo-ketone into thephenolic ketone (XL).Both this and the corresponding 9 : 10-dihydro-phenanthrene analogue derived from propiolic ester (the hydrogenationstage was omitted in this case) proved to be physiologically inactive. Itwas intended to continue the synthesis via the hydroxy-methylene derivativeFollowing model experiments which demonstrated that trans-1 : 2-di-acetylethylene functioned as a philodiene and that the resultant y-diketonescyclised normally, M. W. Goldberg and P. Mullera9 condensed the dienecorresponding to (XXXVIII) with the diacetylethylene and obtained twoof (XL).36 J.'Amer. Chem. SOC., 1942, 64, 1421.3* Annalen, 1942, 652, 113.39 HeZv. Chirn. Acta, 1940, 23, 831 ; B.P. 636,769.37 Ann. Rep&, 1939, 30, 291132 ORGANTC CHEMISTRY.isomeric adducts (XLI), which differed only in the location of the ethenoidlinkage, since they both gave the same dihydro-compound on hydrogenation.,'\-LO /\--Me I I I ' I I II//\/\/\/ //\/\/\/\/\//\COMeICOMe //\/\/\/\ Hot 11 1 Me Hob,,,,,!() 0(XLIII.)MeO' )(XLI.) (XLII.)Cyclisation of dihydro-(XLI) with sodium methoxide, followed bydemethylation with hydrobromic acid in acetic acid, gave a product [either(XLII) or (XLIII)] which was fully estrogenic in lOOy doses (d-aestroneis active a t about 0.77). This fact, the probable trans-nature of the philo-diene and the known relative inactivity of the isoequilenins, combine to suggestthat structure (XLII), including trans-fusion of the terminal rings, is highlyprobable.Further development of this synthesis would appear to be ofinterest.The successful addition of but adiene to 2 -met h y lcycb hexen- 3 - one,*Ogiving a product formulated as (XLIV), is surprising in view of earlierfailures with similar. philodiene~.~~ The ketone has been converted intothe ethynylcarbinol, and the latter partially hydrogenated and then de-hydrated to a diene with which further addition reactions are contemplated.L. W. Butz and, his collaborators 42 have developed p divinylacetyleneaddition reaction which from dicyclohexenylacetylene and maleic anhydrideleads to (XLV ; R = H). Dehydrogenation provides evidence for the?--co ?-cooc I R oc \Ap-:o \/\/\I I/\/\/\/I I '/\/\/\)(XLIV.) co-0(XLV.)(XLVI.)carbon skeleton of the dianhydride and the location of the ethenoid linkagesis based partly on analogy and partly on light absorption evidence.Thesteroid analogue of (XLV ; R = H) containing one cycbpentane ring has alsobeen synthesised, but introduction of a' methyl group into the dienynesystem gives (XLV; R = Me) in only 2% yield, the angular location of the' 0 W. Nudenberg and L. W. Butz, J . Amer. Chenz. SOC., 1943, 65, 1436.41 (Sir) R. Robinson and A. R. Todd, J . , 1935, 1530; E. Dane, J. Schmidt, andC. Rsutenstrauch, Annulen, 1937, 532, 29.4% L. W. Butz, A. M. Gaddis, E. W. J. Butz, and R. E. Davis, J . Org. Chem., 1940,5,379; L. W. Butz and L. M. Joshel, J . Amer. Chem. SOC., 1941, 63, 3344; L. 'M. Joshel,L. W. Butz, and J. Feldman, ibid., p., 3348; L.W. Butz and J. M. Joshel, ibid., 1942,64, 1311 ; W. Nudenberg and L. W. Butz, ibid., 1943, 65,2059JONES : STEROID SYNTHESES. 133methyl group being adduced from the isolation of chrysene on dehydrogen-ation. Dimethyl fumarate has also been employed as the philodiene com-ponent. Extending an earlier observation,43 A. Koebner and (Sir) R.Robinson have employed a diene synthesis to prepare a ketone to whichthe structure (XLVI) has been provisionally assigned.(e) The presence of angular methyl groups in the steroid hormonesconstitutes a stern challenge to the ingenuity of the synthetic organicchemist. The majority of the synthetic methods so far developed involvesintroduction of the requisite methyl groups prior to final cyclisation to thetetracyclic system, but undoubted advantages would accrue if methodswere available for C-methylation of preformed tetracyclic ketones such as(XLVII) in the 13-position.Direct substitution would appear to be ruledout in view of the methylation of trans-a-decalone essentially in theD. A. Peak and (Sir) R. Robinson45 methylated a 12-keto-compound in the hydrochrysene series with methyl iodide in the presence ofpotassium tert.-butoxide, and although dehydrogenation gave chrysene, suchobservations do not furnish complete proof of the angular location of themethyl group, since G . R. Ramage and W. E. Jones 46 have reported methylgroup elimination from methylhydrochrysenes on dehydrogenation, I n anycase the Robinson-Peak process eventually requires a suitable substituentor point of attack in ring D and (Miss) N.A. McGinnis and (Sir) R. Robinson 47sought t o furnish this by employing 3-acetyl- A3-dihydrothiopyran in theRapson-Robinson synthesis.48 The unsaturated ketone so obtained wasreduced and C-methylated to give a product believed to be (XLVIII).The 16-piperonylidene derivative of 2-norequilenin methyl ether onC-methylation (methyl iodide and potassium tert.-butoxide) furnished acompound (XLIX) which is apparently not identical with the correspondingderivative of dl-equilenin methyl ether. Since the validity of this method hasbeen established by experiments with the piperonylidene compound of 2-rnethylcycZ~hexanone,~~ it would appear that (XLIX) must belong to the iso-equilenin series.W. S. Johnson 50 has contributed to the generality of theabove methylation procedure by devising means for the subsequent removal ofthe arylidene group. The benzylidene derivative of a-decalone on C-methyl-43 W. E. Bachman and M. C. Kloetzel, J . Amer. Chem. SOC., 1938, 00, 3204.*4 J. W. Cook and C. A. Lawrence, J., 1937, 817.4~ J . , 1937, 1581.4 8 J., 1935, 1285; Ann. Reports, 1939, 36, 295.I9 A. J. Birch, J., 1943, 661.J . , 1038, 1853. 47 J., 1941, 404.J. Amer. Chem. SOC., 1943, 65, 1317134 ORQANIC CHXMISTRY.ation gave two crystalline isomers (L), which were separately converted bythe procedure indicated into cis- and trans-9-methyl-1 -decalones.\ NaOEt \ acid c6'cHph -%+ CCl*CHClPh __3 Ico Me 0CH*COPh/ \IBy taking advantage of an abnormal Reimer-Tiemann synthesis firstobserved by von Auwers, R.B. Woodward 61 has devised a method whichsuggests the possibility of converting compounds of the cestrane intothe androstane series. In addition to the normal aldehyde, the tetra101(LI) gives a product which must be (LII), since (inter alia) on catalytichydrogenation the methyldecalol (LIII) was obtained, which was oxidised toCHCl, fn CHCh- //\/A ___, Ha-Pdin-EZ+ O$\/,,J alc.KOH(LII.) (LIII.)Ho\(LI.1the known cis-10-methyl-2-decalone. Another observation of considerablesignificance is that 2-keto-A1:9-octalin (LIV) can be converted in 60% yieldinto cis-9-methyl-Z-decalone (LV) by 1 : 4-addition of methylmagnesiurniodide in the presence of cuprous bromide.52J.English and G. Cavaglieri 53 carried out some model experimentsin the decalin series in attempts to introduce an angular methyl group bypinacolic dehydration of a glycol such as (LVI) to the methyldecalone(LVII). The mixture of methyloctalins obtained by elimination of waterfrom l-methyl- 1 -decal01 was converted into the oxides with perbenzoicacid, which were hydrolysed to the glycols with mineral acid. One of the5 1 J . Amer. Chem. SOC., 19.10, 62, 1208.62 A. J. Birch and (Sir) R. Robinson, J . , 1943, 501.63 J . Amer. Chem. SOC., 1943, 65, 1085; see also ( S i r ) R. Robinson and S. N. Slater,J., 1941, 376JONES : STEROID SYNTRESTS. 136crystalline glycols so produced was assigned the structure (LVI), butdehydration of this ensued predominantly without rearrangement.J.W. Cornforth, (Mrs.) R. H. Cornforth, and (Sir) R. Robinson 64 foundthat reduction of 2-methoxynaphthalene with sodium and alcohol, followedby acid hydrolysis, produced (3-tetralone in 56% yield. The process wouldappear to be applicable to all 2-methoxynaphthalenes, and should provevaluable for obtaining some hitherto difficultly accessible (3-tetralones such asthe 6-methoxy-compou~nd,~5 Equilenin methyl ether, treated in this way,yields the interesting keto-alcohol (LVIII).(f) C. S. Marvel and his collaborators 56 have made it study of thecyclisation of various dienynes with sulphuric and formic acids, exemplifiedin the simplest case by the conversion of the 8.-divinylacetylene (LIX),prepared by dehydration of the acetylene glycol from methyl ethyl ketone,into the tetramethylcycbhexenone (LX).There has been much discussionas to the structures to be assigned to the cyclisation products from morecomplex dienynes such as (LXI), and although Marvel has carried out aconsiderable number of such cyclisations, and has . examined thoroughlythe structural features essential for this reaction to occur, it is only in thecase of (LXI) that the products have been subjected to detailed investigation.Dicycbhexenylacetylene (LXI), derived from cycbhexanone acetyleneglycol, gave a product which was originally formulated as the @unsaturated(LXI.)f \I ;o0 v,(LXII.)n \/\/\1 II\/I ):o(LXIII.)Q(LXIV.) 8 : Operhydrophenanthrene ketone (LXII), since a substance thought to beas.-octahydrophenanthrene was obtained after Clemmensen reduction64 J., 1942, 689.56 A.T. Blomquist and C. S. Marvel, J. Amer. Chem. SOC., 1933, 55, 1656; D. T.Mitchell and C. S. Marvel, ibid., p. 4276 ; P. S. Phkney, G. A. Nesty, R. H. Wiley, and C. S.Marvel, ibid., 1936, 58, 972; G. A. Nesty and C. S. Marvel, ibid., 1937, 59,2662; P. S.Pinkney, G. A. Nesty, D. E. Pearson, and C. S. Marvel, ibid., p. 2666; P. S. Pinkneyand C. S. Marvel, ibid., p. 2669; C. S. Marvel, R. Mozingo, and E. C. Kirkpatrick,ibid., 1930, 01, 2003; C. S. Marvel, D. E. Pearson and L. A. Patterson, ibid., 1940,63,2659; C. S. Marvel and R. V. White, ibid., p. 2739; C. S. Marvel, D. E. Pearson, andR. V. White, ibid., p. 2741; C. S. Marvel and L.A. Patterson, ibid., 1941, 63, 2218;C. S. Marvel and L. A. Brooks, aid., p. 2630; C. S. Marvel and W. L. Walton, J . Org.Chern., 1942, 7, 88.55 G. P. Crowley and (Sir) R. Robinson, J., 1938,2001136 ORGANIC CHEMISTRY.and selenium dehydrogenation. It seemed that the method might usefullybe developed for steroid syntheses. R. P. Linstead and A. L. Walpole 57investigated the cyclisation of (LXI) in greater detail and isolated two crystal-line ketones (m. p. 39" and 94"), the latter proving to be identical with asubstance separated in small yield by the previous workers from the mainliquid product. Clemmensen reduction of each ketone, followed by vapour-phase dehydrogenation over palladised charcoal, gave phenanthrene (laterconfirmed by Marvel), and the dihydro-ketones, obtained by catalytichydrogenation, after reaction with methylmagnesium iodide gave 9-methyl-phenanthrene on dehydrogenation.It merely remained to determine thepositions of the ethenoid linkages and ultra-violet absorption spectra de-terminations readily revealed that both ketones were aP-unsaturated. Finally,the fact that a mixture of two saturated ketones [m. p. 51" (main product)and a liquid isomer] was obtained on hydrogenation of each isomer, andthat the liquid ketone was converted into the solid isomer a t elevatedtemperatures, appeared to establish the structures as (LXIII) and (LXIV).However, having shown that a substance believed to be an octahydro-phenanthrene was actually a spiran type, M. Levitz, D.Perlman, and M. T.Bogert 5* suggested that the Marvel cyclisation products might be similarlyconstituted and they cited several cases where spirans undergo rearrangementand give benzenoid hydrocarbons on dehydrogenation. While examiningthis suggestion, C. S. Marvel and W. L. Walton 56 observed that spiro-decane and methylspi'rodecane gave naphthalene and methylnaphthalenerespectively in about 30 yo yields on dehydrogenation over platinised charcoalat 325". Subsequently R. P. Linstead and his associates 59 prepared andinter-related all six of the perhydro-2 : 2'-diphenic acids (LXV) demandedby classical stereochemical theory. None of these compounds, however,proved to be identical with the supposed perhydro-2 : 2'-diphenic a c d whichhad been obtained by nitric acid oxidation of the alcohol derived from thesaturated ketone (m.p. 51') mentioned above. Further, unlike all theauthentic acids (LXV) which yielded ketones on pyrolysis, this acid gaveonly an anhydride. The formulation of the acid having thus proved incorrect,(LXV.) (LXVI.) (LXVII.) (LXVIII.)i t followed that the ketone (m. p. 51") and its precursors could not belong tothe perhydrophenanthrene series at all and that phenanthrene and its67 J . , 1939, 842.69 R. P. Linstead, W. E. Doering, S. B. Davis, P. Levine, and R. R. Whetstone,60 R. P. Linstead and A. L. Walpole, J., 1939, 843.(m. p. 39".) (m. p. 94".)6 8 J . Org. Chem., 1941, 8, 105.J . Amer. Chem. SOC., 1942,84,1985, 1991,2003,2006,2009,2014,2023JONES : STEROID SYNTHESES.137homologues had originated by means of rearrangements during dehydrogen-ation. then formulated the originalcyclisation products (formerly LXIII and LXIV) as spirans with structuresrepresented by (LXVI) and (LXVII) and the acid degradation product as(LXVIII), which according to the Blanc rule would be expected to give ananhydride rather than a ketone on pyrolysis. The individual structures(LXVI) and (LXVII) of the isomers were readily assigned on the basis ofR. B. Woodward’s 62 generalisations concerning the influence of substituentsand other environmental features on the ultra-violet absorption propertiesof @-unsaturated ketones. Their application in this particular case hadalready been noted by L. K. Evans and A. E. Gillam.63R.P. Linstead and W. E. DoeringSynthetic QCstrogens of the Stilbmtrol Type.This topic received only brief mention in the Report for 1939, but inthe intervening years much attention has been paid to the development ofthe chemical as well as the physiological aspects of this field. It may berecalled that E. C. Dodds and his collaborators, working originally withsubstances containing the phenanthrene nucleus, later demonstrated the wideincidence of low potency oestrus-producing properties among organic com-pounds of many types,64 studies which led to the isolation of a highly potentestrogen from the product obtained on demethylating a n e t h ~ l e . ~ ~At the same time speculation as to possible spatial relationships betweennatural and synthetic estrogens resulted in the notable discovery of highlyactive stilbene and diphenylethane 66a particularly stilboestrol */CH3HO*C,H4*CHEt*CHEtoC,H,oOH HO*C,H,*C( :CHMe)C( :CHMe)*C,H4*OH(4 : 4’-dihydroxy-cccc’-diethylstilbene) (I), hexestrol (3 : 4-bis-p-hydroxy-phenylhexane) (11), and dienoestrol (3 : 4- bis-p-hydroxyphenylhexa-2 : 4-(11.) (111.)61 J .Amer. Chenz. SOC., 1942, 64, 1996.62 Ibid., 1941, 63, 1123; 1942, 64, 76.64 For Bummary, see E. C. Dodds and W. Lawson, Proc. Roy. SOC., 1938, B, 125,222.‘5 E. C. Dodds and W. Lawson, Nature, 1937,139,1068 ; N. R. Campbell, E. C. Dodds,and W. Lawson, Proc. Roy. SOC., 1940, B, 128,253.E. C. Dodds, L. Golberg, W. Lawson, and (Sir) R. Robinson, Nature, 1938, 141,247; Proc. Roy. SOC., 1939, By 127, 140.66a E.C. Dodds, L. Golberg, E. I. Griinfeld, W. Lawson, C. M. Saffer, and (Sir) R.Robinson, Proc. Roy. SOC., 1944, B, 132, 83 (added in proof). * The name stilbaestrol, which now seems to be widely employed, is used in thisreport in preference to diethylstilbcestrol.63 J . , 1941, 818.E138 ORGANIC CHEMISTRY.diene) (111), which are practically as potent as, and considerably moreacoesaible than, the natural female aex hormones. They have the additiunaladvantage of being effective when administered orally.8tilb&roZ (I).-The designation of this substance on general groundsas the trans-isomer, which form ia more clearly related sterically to oesfradiol(IV), has been oonfirmed by crystallographic measurements 67 and also byhydrogenation experiments in whioh its behaviour was compared withthat of cis- and tra~-aa'-dimethylst~benea.Bs The latter gave practicallyquantitative yields of meso- and racemic 2 : 3-diphenylbutanes respectivelyand hydrogenation of stilbceatrol with pallsdium-black in acetic acid gavean 88% yield of the racemic dihydro-compound, The latter result disagreeswith an earlier report,66 but it has been confirmed independently.69In the original synthesis B6 the carbinol (V), when treated with phosphorustfibroinide, gave stilboestrol dimethyl ether and an oil, the latter yieldingon demethylation a +-stilboestrol, whioh it was suggested might be thecis-burner, especially since its ether was converted ihto the normal stilbcestrolether in sunlight. It has been shawn, however, that the non-arystallinematerial formed on dehydration of (V) with potassium pyrosulphate consistseesentially of the two geometrical isomers of (VI), their structures beingproved by the isolation of acetaldehyde and a-ethyldeoxyanisoin onozonolysis.They are both readily converted in the presence of iodine into(v.) MeO*C,H,*CHEt*C( OH)Et*C,H,*OMe( VI . ) Me O*C,H,*C ( : cme) *CH Et*C,H,*OMethe dimethyl ether of trans-stilboestrol (I). Alcoholic potash at temperaturesabove 200" and palladium in ethereal solution are also effective in isomerising+~tilboestrol.~l F. von Wessely and A. Kleedorfer 72 indicate that oneof the diols (m. p. 153" and 143.5") corresponding to (VI) is fully cestrogenic(rats) in doses of 24y, whereas the isomer is inactive at 1OOy.This &dingdoes not appear to be confirmed, however, in the later paper.'') E. Waltonand G. Brownlee 73 have also examined the +-stilboestrol mentioned above,isolating a substance with m. p. 151", one fourteenth as active as stilbcestrolitself, which is presumably identioal with von Wessely 's higher-melting diol.These authors also describe a new stilboestrol dipropionate, obtained in theusual manner and giving stilbcestrol on alkaline hydrolysis, yet possessingonly 11600th of the activity of the normal dipropionate. This may be aderivative of the unknown cis-isomer of (I).Many attempts have been made to imprave upon the original synthesis 6667 a. Qiacomello and E. Bianchi, Qazkettu, 1941,71, 667 ; see dso C. H.Carlisle and6* F. von Wessely and H. Wellebe, Ber., 1941, 74, 777:'s A. M. Docken and M. A. Spielman, J. Amer. Chm. SOC., 1Q40,63, 2163.70 F. von Wessely, E. Kerschbaum, A. Kleedorfer, F. Prillinger, and E. Zajio,D. Crowfoot, J., 1941, 6.Monatsh., 1940, 73, 127.A. Serini and K. Steinruck, U.S.P. 2,311,093.Naturwiss., 1939, 27, 667, 664.v3 Nature, 1943, 151, 305.JONES : STEROID SYNTHESES. 139of stilbosstrol (I) from deoxyanisoin (VII). One modification 74 involvesthe preparation of ethyldeoxyanisoin (IX) from the glycol (VIII), the latterbeing prepared by a Grignard reaction on anisoin. Another variation 76comprises the reaction of the ketol (XI) with anisylmagnesium bromide,followed by dehydration of the carbinol to the ketone (XII), which, &erR*CO*CH& R-CH(OH)*C(OH)EtR 3 R=CO*CHEtR + EtMgBrVI.) (VIII.) (IX.1R*C(OH)Et*CHEtR a Dimethyl ether of (I)(X.)RMgBr RMgBr Et*CO*CH(OH)Et + R*CHEt*COEt -+ (X) -Ha0(XI.) (XII.)(R = p-MeO*C,H,)another treatment with the Grignard reagent gives the carbinol precursor(X) of stilboestrol dimethyl ether. The ketone (XII) has also been madeby a devious route from p-methoxyphenylacetonitrile. ‘0E. P6teri 76 attempted to effect a rearrangement-dehydration of thecarbinol (XIII), prepared from the corresponding aldehyde with ethyl-magnesium bromide, by treatment with acids, a method originally employedfor the synthesis of ad-dialkylstilbenes. The yield of stilbtxstrol dimethylether (XIV) was negligible and the parent aldehyde proved rather in-accessible.It was found, however, that (XIV) could be obtained in moderateyield by rearrangement of the carbinol (XV) on dehydration with phosphorusoxychloride in toluene, (XV) being prepared in several stages from anisalde-hyde cyanohydrin. Closely related is an attempt by Z. Foldi and I. Demjdn 77CEtR,*CH(OH)Et --+ R*CEt:CEtR +- CHR,*CH(OH)Et, 7’’ EtMgBr(XIII.) (XIV.)R*CHCI*COR (XVI.) t (xvrr.) CEtR,-COEt(R = (p-MeO*C,H,)to prepare the carbinol (X) by treating a-chlorodeoxyanisoin (XVI) withethylmagnesium bromide, which resulted somewhat unexpectedly in theisolation of the carbinol (XV) obtained by PBteri. An analogous rearrange-ment is that of the oxide of stilboestrol, which on distillation or merely ondrying is converted into a ketone, the dimethyl ether (XVII) of which isreconverted into stilboestrol dimethyl ether (XIV) by a retropinscolinicchange on reduction with sodium and amyl alcohol.7*The method used by H.Staudinger and F. Pfenninger 78 for converting7 p S. Kuwada and Y. Sasagawa, J. Phurm. SOC. Japan, 1940, 60, 93.76 S. Kuwada, Y. Sasagawa, and M. Nisikawa, ibid., p. 224 ; see also L. F. Fieser73 J., 1940, 833.78 B ~ T . ~ 1916, 49, 1946.and W. G. Christiansen, U.S.P. 2,248,019.7 7 Ber., 1941, 74,930; see also B.P. 537,976; 637,993140 ORUANIC CHEMISTRY.benzophenone into tetrapheiiylethylene has been successfully employed 79to prepare stilbmtrol dimethyl ether (XIV) in an overall yield of 25% fromp-methoxypropiophenone. The hydrazone (XVIII) of the ketone is oxidisedto the substituted diazomethane, which is converted by treatment withsulphur dioxide into the sulphone, the latter yielding (XIV) on pyrolysis.CEtR:N*NH, --+ CEtRN, -I-+ CEtR-CEtR % (XIV) H60 so(XVIII.) \ /so2Possibly the most direct approach to the synthesis of stilbmstrol is thatof M.S. Kharasch and M. Kleiman,m who, following up their earlier discoverythat ally1 chloride gives hexatriene on treatment with sodamide in liquidammonia, treated anethole hydrobromide (XIX) likewise and obtained a40% yield of a substance believed to be (XX), or the isomeric cyslopropaneEaNH,11q. hH,(XIX.) R*CHBr*CH,*CH, + R*CH(CH:CH,)*CHEtR (xx.)derivative, which isomerised on demethylation (alkali and glycol) and gavea 55% yield of stilbcestrol (I).Nexmtrol (II).-During an investigation of the oestrogenic propertiesof a wide variety of organic compounds, E.C. Dodds and W. Lawsonalreported that anol (p-HO*C6H4*CH:CH*CH,) (XXI) was as active as cestrone.It was subsequently realised 82 that this activity was due to the presenceof a persistent impurity produced during the preparation of anol by demethyl-ation of anethole with alcoholic potassium*hydroxide at 200°, and eventuallythe potent by-product was isolated as a crystalline solid, m. p. 184--185°.83It proved to be identical with a dihydrostilbcestrol (11) which had alreadybeen obtained by hydrogenation of diencestrol (111) 84 and was evidentlyderived from an anol (XXI) dimeride which had undergone reduction.A detailed investigation 85 of the complex mixture obtained on demethyl-ating anethole has revealed the presence, in addition to anol (XXI) and theCHEt/\/ \\/\ /( p ) MeO*CBH4*CH:CMe*CHEt*C6H4*OMe ( p ) C1*CHMe MeOl I(XXII.) A (XXIII.)I Idihydrostilbestrol (11), of the phenol corresponding to “ isoanethole ”(XXII), the structure of which had already been proved by G.D. Goodall’* L. von Vargha snd E. Kovacs, Ber., 1942,75,794; B.P. 526,927.*O .T. Amer. Chem. Soc., 1043, 65, 11.8 1 Nature, 1937, 139, 627.83 N. R. Campbell, E. C. Dodds, and I+’. Lawson, ibid., 1938,142, 1121.aP Idem, ibid., p. 1068.E. C. Dodds, L. Golberg, W. Lawson, and (Sir) R. Robinson, ibid., p. 34.N. R. Campbell, E. C. Dodds, and W. Lawson, Proc.Roy. Soc., 1940, B, 128, 253JONES : STEROID SYNTHESES. 141and R. D. Haworth.86 In this connexion it may also be noted that W. Bakerand J. Enderby87 have shown that the crystalline anethole dimeride," metanethole," has the structure (XXIII), and that N. R. Campbell 88isolated 1 : 3-di-p-methoxyphenyl-2-methylpropane from the productobtained after prolonged heating of anethole.Hydrogenationof stilboestrol itself with palladised charcoal as catalyst gave a,form, m. p.128", whereas hydrogenation of either +stilboestrol, dienaestrol (111) or of thedimethyl ether of #-stilboestrol, followed by demethylation, yielded a form,m. p. 185°.6s1 68* 69 The latter substance, now known as hexoestrol, is probablythe most potent of the known estrogens, whereas its stereoisomer (iso-hexoestrol, m.p. 128") is only about 1/100th as active. C. H. Carlisle andD. Crowfoot 67 have demonstrated by X-ray crystallography that thehigher-melting isomer is the meso-compound, and the racemic nature of thesecond form has been established by its resolution,68 the d-form (active onlyin lOOy doses) proving to be about ten times as powerful an estrogen as itsenantiomorph. F. von Wessely and H. Welleba68 have made a detailedstudy of the hydrogenation of stilboestrol and related compounds 89 and itseems that a convenient route to hexoestrol is by hydrogenation of the residues(mainly VI) obtained after removal of stilboestrol dimethyl ether from thedehydration product of (V), followed by demethylation by heating withethylmagnesium iodide.The interconversion of the dl- and meso-formscan be effected by heating with either palladised charcoalg0 or hydrogensulp hide .glAn alternative route to compounds of the hexoestrol type, modelledon the thermal decomposition of 8.-diphenylazomethane into diphenyl-ethane,92 has been developed 909 93 and applied 94 to the synthesis of thedimethyl ethers of hexoestrol, its stereoisomer and other related compounds.Hydrogenation of the ketazine (XXIV) from p-methoxypropiophenone witha palladium-charcoal catalyst gave an unstable hydrazine, which was readilyoxidised in air to a mixture of two compounds. These have been shownspectrographically 95 to be either cis-truns- or meso-dl-isomers of the azo-compound (XXV) and on heating they gave a 60% yield of a mixture ofDihydrostilboestrol (11) can exist in meso- and dE-forms.7 20-30° R*CEt:N*N:CEtR R*CHEt*N:N*CHEtR R*CHEt*CHEtR(XXIV.) (XXV.) (XVI.)(R = p-MeO*C6H4)equal amounts of stereoisomers of (XXVI). It is interesting to note thatby simultaneous decomposition of a mixture of the dihydroketazines from86 J., 1930, 2482.See also references 66 and 69.90 H.Bretschneider, A. de Jonge-Bretschneider, and N. Ajtai, Ber., 1941, 74, 671.D. A. Peak and W. F. Short, J . , 1943, 232.92 J. Thiele, Animlen, 1910, 376, 244.~34 Z. F6ldi and G. von Fodor, Ber., 1941, 74, 589.95 G. von Fodor and P. Szeruas, Ber., 1943, 76, 334.J., 1940, 1094. 8 8 J., 1941, 672.93 B.P. 640,966142 ORGANIC CHEMISTRY.p-hydroxy- and p-methoxy-propiophenones the monomethyl ether ofhexmtrol was obtained, also that O h 0 of the forms of (XXV) is formed by theaddition of two moles of ethylmagnesium bromide to anisaldazine.06Wurtz-type reactions on anethole hydrobromide or hydrochlorideemploying magnesium 97 or sodium 98 gave hexoestrol dimethyl ether inyields up to 20%.Recently M. 5. Kharasch and M. Kleiman Qg increasedthis to 40% by treating the hydrobromide with a Qrignard reagent in thepresenoe af cobaltous ohloride.Dienwtroll (XXVIII) .-This other highly active estrogen was preparedoriginally 66 from the pinacol (XXVII) by dehydration with acetic anhydrideand acetyl chloride, followed by hydrolysis. The pinacol is obtained by(XXVII. ) HO*C,H,*C( OH) Et*C( OH) Et*C,H,*OH .1 (XxV111.) HO*C&,-C ( :CHMe)*C ( :CHMe)*C6H4* OH(XXIX .) ( HO*C6H4) ,CE t *COE treduction of p-hydroxypropiophenone with aluminium amalgam in moistether,66 or electrolytically,l and its dimethyl ether is formed by reaction ofanisylmagnesium bromide with dipropionyl.2 An isopinacol, probablythe dl-form of (XXVII), obtained by modification of the electrolytic method,is characterised by the ease with which it rearranges in the presence of acidsto the ketone (XXIX), a behaviour analogous to that already noted withstilbaestrol oxide (p. 139).The dimethyl ether synthesised 3 from (XXX), then believed to be theMeO*C6H4*CH:cMeBr 4 MeO*C6H4*CH:CMe*CMe:CH*CBH,*OMel-bromo-isomer, by treatment with magnesium has been shown2 to be(XXXI) by isolation of anisaldehyde and diacetyl on ozonolysis.Theauthentic l-bromo-isomer of (XXX), obtained by addition of hydrogenbromide to 1 -p-anisylprop-1 -yne (MeO*C,H,*CiCMe), can be converted withmagnesium and cnpric chloride into the dimethyl ether of dienoestrol(XXVIII). This ether undergoes normal demethylation on heating withmethylmagnesium iodide, but with alcoholic potash it gives a substance(isodiencestrol) believed t o be a stereoisomer of (XXVIII).Miscellaneous Studies.-The search for new purely synthetic cestrogensand studies of the relationship between structure and physiological activitycontinue. Various stilbcestrol isomers and analogues containing m- insteadof p-hydroxyl groups, prepared by the original method,66 are much less128, 253.(=.) (XXXI.)See also N.R. Campbell, E. C. Dodds, and W. Lawson, Proc. Roy. SOC., 1940, B,9 7 W. F. Short, Chem. and Ind., 1940, 703; B.P. 523,320.9 8 S. Bernstein and 33. S. Wallis, *J. Amcr. Chem. Soc., 1940, 62, 2871.B9 Ibid., 1943, 65, 491.1 Glaxo Laboratories Ltd., F. A. Robinson, and J. C. L. Resuggan, B.P. 523,515.3 British Colloids Ltd., I. E. Balaban, and J. I. M. Jones, B.P. 647,027.G. I. Hobday aid W. F. Short, J . , 1943, 609JONES : STEROXD SYNTJSESES. 143active than stilboestr01.~~ 660 4 : 4'-Dihydroxy-2 : 2'-diethylstilbene, madefrom o - et h ylanisalde h y de through the thio - aldehyde, followed by treat men twith copper powder and finally demethylation, possesses only 1 /lOOOth ofthe activity of the isomeric stilboestrol.6 On the other hand, the hexestrolisomer (XXXII) is practically as potent as hexoestrol it~elf.~O J.B. NiederlMe MeHO</-CHMe*CHMe-(>OH (XXXII.)and A. Ziering 6 have made a number of a-cyano- and ap-dicyano-stilbehes[e.g., R*C(CN):CHR] which show but feeble oestrogenic activities. L. vonVargha and E. Kovacs 79 report that the pp'-diamino-analogue of stilboestroland various related compounds are relatively biologically inert, as a180 iEi thecorresponding hexoestrol analogue in both its meso- and its dl-form.' Inthe latter case replacement of the p-hydroxyphenyl groups by either 3 : 4-di-hydroxyphenyl or p-hydroxybenzyl groups has been found largely to destroythe activity. The examination of many variants of the stilboestrol andhexmtrol types has recently been reported,6" but dono is as potent as theparent compounds.The trans-hexahydrochrysene diol (XXXIII) has been found to beweakly oestrogenic.66 A.A. Plentl and M. T. Bogert 8 suggested that partiallycyclised stilboestrol and hexmstrol types such as (XXXIV; R = Et)and the related indene derivative might be of interest, in view of their clomsteric similarity to cestradiol (IV). The corresponding hydrocarbons weresynthesised as a preliminary. The dimethyl ether of (XXXIV; R = Et)had already been synthesised, but on demethylation, disproportionationoccurred and the dihydro-compound which was isolated was found to becomparatively inactive.66 Undeterred by this failure, W. Salzer effecteda comparatively simple synthesis of the methyl analogue of (XxxIV),the ether (XXXV) being smoothly demethylated to (XXXIV; R = Me)by heating with methylmagnesium iodide, whereas disproportionationoccurred with hot alcoholic alkali.Both (XXXIV; R = Me) and theCorresponding indene derivative (XXXVI), the latter being synthesisedfrom m-methoxybenzyl chloride, proved to be highly oestrogenic (in 0.3 and0 . 5 ~ doses), thus providing further striking evidence of the profound influenceof molecular architecture on - physiological behaviour. HydrogenationW. H. Linnell ancl V. R. Sharma, Quart. J. Pharrn., 1941,14, 259.W. H. Linnell and H. S. Shaikmahamud, ibid., 1942, 16, 384.J . Amdr. Chem. SOC., 1942, 64, 885, 2486.R. R. Baker, ibid., 1943, 65, 1572. * Ib.W., 1041, 63, 989.Z . physiol.Ciiem., 1042, 374, 89144 ORGANIC CHEMISTRY.of (XXXVI) to the dihydro-compound largely destroyed the activity,*but the symmetrical tetrahydrochrysene diol (dehydro-XXXIII), closelyA\/\ /CH2Me01 CH,BrOHMe /\\OH I II I\/ (XXXVII.) HOk,(XXXVI.) (XXXV.) OHrelated to dienoestrol and synthesised by Salzer from the methoxy- p-tetralone,was moderately (1%) active.In a series of homologous bis-p-hydroxyphenylmethane derivatives(XXXVII), prepared by condensing phenol with various aldehydes andketones, the highest activities were observed with the hexoestrol isomers(XXXVII; R, = H, R, = CHEt, and R, = Et, R, = n-Pr), but eventhese compounds were only 1 /50,000th and 1 /5000th as potent respectivelyas hexoestrol itself.lO A large number of polynuclear analogues of hexoestrolhave been synthesised by the Wurtz method and it is abundantly clear thatin this series the presence of the p-hydroxyphenyl groups is essential ifactivity of a high order is to be attained.ll Hydroxy-derivatives of fluorenehave been found to possess only weak estrogenic activity.12 B.R. Baker 7synthesised hexoestrol isomers such as 1 : 3- and 1 : 6-bis-p-hydroxyphenyl-hexane by the dihy&o-azine method?* but they proved to be relativelyinactive.The first of a series of papers on alkylated bis-p-hydroxyphenylpropanes(XXXVIII) describes the preparation of the monoalkyl compounds(XXXVIII ; R, = R, = H or R, = R, = H) from the correspondingchalkones by 1 : 4-Grignard addition, or by condensation of anisaldehydewith p-acylanisoles, followed in both cases by either Clemmensen reductionor hydrogenation with " copper chromite " catalysts and dernethy1ati0n.l~These phenols show only low-order wstrogenic potency.However, E. W.lo N. R. Campbell, Proc. Roy. SOC., 1940, B, 129, 528.l1 N. R. Campbell and F. W. Chattaway, ibid., 1942, B, 130,436.12 A. Novelli and M. H. Giunti, Ciencia, 1940, I, 19; Chem. Abstracts, 1940, 34,l3 A. H. Stuart and R. C. Tallman, J . Amer. Chem. SOC., 1943,65,1579. * U. V. Solmssen ( J . Asner. Chem. SOC., 1943,& 2370) reports that the ethyl analogueof a dihydro-(XXXVI), prepared by a method different from those of Salzer and ofPlentl and Bogert, is about 1 /20th as active as etilboestrol.3330JONES : STEROID SYNTHESES. 145Blanchard, A.H. Stuart, and R. C. Tallman14 have made a preliminaryreport on the testing of some 134 synthetic compounds of type (XXXVIII).The trialkyl derivatives are the most potent and one of the stereoisomera of(XXXVIII; R, = Me, R, = R, = Et) is apparently only three or fourtimes less active than hexoestrol. This rather surprising finding seems tocast some doubt on the validity of the fairly well-established stereo-relation-ship between the natural and the synthetic Estrogens, although it is stillpossible to write the formula of the compound in a manner (XXXIX) which(XXXIX.)\ I .C'HMepreserves a superficial resemblance. Further information about the activitiesof the many stereoisomers in this series will be awaited with interest.It has long been considered desirable to synthesise and examine partiallyor fully hydrogenated compounds of the stilbcestrol type, and those deriv-atives resembling other sex hormones such as progesterone (XL ; R = H),testosterone and corticosterone in the constitution of their terminal functionalgroups. (Mrs.) R.Jaeger and (Sir) R. Robinson15 have prepared twoketones of structure (XLI; R, = R, = Me and R, = Et, R, = Me) byGrignard reactions on the corresponding nitriles, the latter being synthesisedby the general method devised earlier.66 Unfortunately the estrogenic/ \ p VO:' \/\ ) (XL.)( p ) MeO*C6H4*CHEt*CHEf*C,H4.C0.CH,R ( p )(XLII.)properties of these substances are sufficiently powerful effectively to inhibitany progesterone-like activity they might possess.The preparation ofvarious ketones of the stilboestrol and hexoestrol series by means of Friesand Friedel-Crafts reactions has been claimed l6 and these substances aresaid to be active hormones. For example, (XLII; R = H) and (XLII;R = OH) are mentioned as possessing progestational and corticosterone-likeactivity respectively.The restricted availability of the steroid hormones of the adrenal cortexencourages particularly the search for purely synthetic materials possessingthis type of activity. Some preliminary experiments along these lines arel4 Endocrinology, 1943, 32, 307.le Wellcome Foundation Ltd., G. Brownlee, and W. M. Duffin, B.P. 650,262.1 6 J., 1941, 744146 ORGANIC CHEIIIISTRY.reported l7 and it has been found l 8 that both benzoylcarbinol and the stil-bastrol-like a-ketol (XLIII) (containing one meta-substituent however)are qualitatively similar to deoxycorticosterone (XL; R = OH) in their( p ) HO*C,H,CEt:CEt*C,H,*CO*CH2*OH (m) (XLIII.)physiological action.A number of derivatives of hydroxydiphenyl etheroontaining the wketol side chain have also been synthesised.19In a preliminary note J. F. Lane and E. 8. Wallism describe experimentswith one of the isomeric perhydrohexczstrols (XLIV) obtained by completehydrogenation of hexczstrol. This has been converted into the diketone,and the keto-ol has been prepared by partial acetylation of (XLIV), followedby oxidation and hydrolysis. No information concerning biological testsis as yet available.A number of unsuccessful attempts to prepare a hexa-hydrostilboestrol have been reported.21Many of the synthetic oestrogens have been shown to possess growth-inhibitory properties, and G. M. Badger 22 has synthesised a number ofhydrocarbons of the stilhoestrol type, by the original method,66 for testingits tumour inhibitors.2TriphenyZethyZene QZstrogens.-E. C. Dodds and W. Layson 28 investigatedthe estrus-producing properties of a number of substituted ethylenes andfound that stilbene, as-diphenylbutadiene and triphenylethylene were fullyactive in rats in doses of 10-25 mg. J. M. Robson and A. Schonberg e4independently reported the activity of triphenylethglene. Triphenyl-chloroethylene (CPh,:CClPh) is more potent 25 and further investigationswith more highly substituted derivatives have revealed substances [e.g.,(p-EtO*C,H,),C:CBrPh] of greater activity which, aIthough requiringconsiderably greater threshold doses than stilboestrol, produce muchmore prolonged effects.Tri-p-anisylbromoethylene (Ar2C:CBrAr ; Ar =p-MeO*C,H,), which also possesses the latter property and appears to beapproximately one-twentieth as active as stilboestrol, has been prepared 27from deoxyanisoin by yeaction with anisylmagnesium bromide, followed bydehydration of the resulting carbinol and treatment of the trianisylethylenewith bromine, hydrogen bromide being readily eliminated. The trianisyl-17 L. Long and A. Burger, J. Org. Chem., 1941,8,882.l* J. Walker, J., 1942, 347.21 P. Ruggli and A.Businger, Helv. Chim. Acta, 1941, 24,112.22 J., 1941, 635.23 Nature, 1937, 139, 627 ; Proc, Roy. SOC., 1938, B, 125, 222.Nature, 1937, 140, 197.26 J. M. Robson, A. Schljnberg, and H. A. Fahim, Nature, 1938,142,292.2a A. SohBnberg, J. M. Robson, W. Tadros, and H. A. Fahim, J., 1940, 1327; J. M.Robson and A. Schanberg, Nature, 1942, 150, 22; W. Tadros and A. Schiinherg. J .1943, 394.W. H. Linnell and I. M. Roushdi, Quart. J. P h m , , 1041, 14, 270.20 J . Amer. Chem. Soc., 1943, 65,994.27 J. S. H. Davies and Imperial Chemical Industriea Ltd., B.P. 649,200SPRl3G : HORMONES OF ADRENAL CORTEX. 147propenes and -butenes (Ar,C:CRAr; R = Me and Et) have also been pre-pared by Qrignttrd reactions and are equally active.28Vitamin D Synthesirr.The section of the Report written on this topic has been deleted in viewof the announcement 29 that six published papers,30 in which considerableprogress in this field was described, must be disregarded. E.R. H. J.5. HORMONES OF ADRENAL CORTEX.Since the last Report dealing with the steroids isolated from the adrenalcortex, many outstanding advances have been made mainly as a result of theresearches of T. Reichstein and his collaborators. The most spectacularaccomplishment is the elaboration of a general method for the introductionof a carbonyl (or hydroxyl) group at C,, in the cholane nucleus and the applic-ation of this method to effect a partial synthesis of 1 l-dehydrocorticosterone.To assess the value of this achievement in proper perspective it may berecalled that, of the large number of steroids isolated from the adrenalcortex, six [(I)-(VI)] are “ cortical hormones.’’ That is, when a solutionof any one of the six compounds is injected daily into young adrenalectomisedrats, the animals continue to live.The six hormones comprise those whichare oxygenated in ring C [(I), (11), (111) and (IV)] and those which are not[(V) and (VI)]. The complete structures of the simpler group [(V) and (VI)]have been verified by partial synthesis; the partial synthesis of deoxycorti-costerone (V) from cholesterol has been described in a previous report and apartial synthesis of substance S (VI) from cholesterol is described below.In the earlier stages of this work the fact that the hormone most readilyavailable by partial synthesis from cholesterol [deoxycorticosterone (V)]was the most physiologically potent member of the group appeared as afortunate circumstance.Subsequently,2 however, it became clear that, incontrast to (V), the ring C-oxygenated hormones [(I)-(IV)] exhibit a re-markable effect on carbohydrate metabolism; in the anti-insulin testand the Ingle test4 the compounds (1)-(IV) show a strong diabetogenicaction, whereas deoxycorticosterone (V) and substance S (VI) (in so far as thishas been available for test) show little if any activity. Consequently theavailability of compounds (I)-( IV) became a matter of some importancefor the clinical treatment of such conditions as Addison’s disease and surgical2 * J. S. H.Davies, L. A. Elson, and Imperial Chemical Industries Ltd., B.P. 549,353.29 K. Dimroth, Ber., 1943, 76, 634.30 K. Ilimroth and E. Stockstrom, Ber., 1942, 75,180, 326,510,582, 1263; Annulen,1941, 549, 256..1 F. 8. Spring, Ann. Reports, 1940, 37, 332.a C. N. H. Long, B. Kstzin, and E. G. Fry, Endocrinology, 1940, 26, 309; B. B.3 J. F. Gratton and H. Jensen, J. BioE. Chenb., 1940, 135, 511.4 D. J. Ingle, Endocrinology, 1940, 20, 472; 27, 297; E. C. Kendall, Proc. StaffWells and E. C. Kendall, Proc. Stuff Meetings, Mayo Clinic, 1940, 15, 297.Meetings, Mayo clinic, 19@,16, 297148 ORGANIC CHEMISTRY.shock. Hitherto the sole method for obtaining compounds (1)-(IV)was by a laborious isolation process from adrenal cortex ; the part-synkhesis(I.) Corticosterone *(111.)- 17~~HydroxycorticosteroneCO*CH,*OH PI4(V.) DeoxycorticosteroiieCO*CH,*OH0:pl-l /\I\/\/'\/\/0:1 I I(11.) Dehydrocorticosterone(IV.) 17S-HydroxydehydrocorticosteroneCO*CH,*OH1 /y/\/'\/' I03 \/\/(VI.) 17/?-Hydroxydeoxycorticosterone(Substance S)H/\I--/--COeCH,~OAc * In the steroid formulae used through-out this Report, the angular methyl groupsattached to C,, and C,, will be representedI 1 (\I/\/\/' I by strokes.O:\/\/ (IX.)of dehydrocorticosterone (11) from a bile acid derivative constitutes a veryvaluable achievement and will no doubt be followed by the synthesis of(I), (111) and (IV) by suitable variation of the methods now developed.The partial synthesis of (11) also provides complete confirmation of thelocation of the ring C-oxygen atom in the adrenal steroids.More information is available concerning the specificity of physiologicalaction of members of the group.haveprepared the compounds (VII) and (VIII) from 3a : 12~-diacetoxyiitiocholanicacid.6 These compounds differ from dehydrocorticosterone (11) and corti-H. G . Fuchs and T. ReichsteinHelv. C l ~ i m . Acta, 1943, 26, 51 1.13 T. Reichstein and 33. von Arx, ibid., 1940, 23, 747SPRING : HORMONES OF ADRENAL CORTEX. 149costerone (I) solely in the location of the ring O-oxygen atom. A preliminarybiological test shows that the acetates of (VIT) and (VIII) are at least con-CO*CH( OMe), , (jZ€(OH)*CH(OMe),\-\A/, (XI.)HOCH(OH)*CHO CH( OH)*CH( OMe),c- /\/\/\/ I ! /\/\/ 611.)0: \/ \/ (XIII.)0:Isiderably less active than either corticosterone or deoxycorticosteroneacetate in the Everse-de Fremery test ; anti-insulin tests have not yet beenreported.17-isoDeoxycorticosterone acetate 7 (IX), which differs fromdeoxycorticosterone acetate solely in the orientation around CI7, is inactivein the Everse-de Fremery test, in doses of 1 mg. per day.Deoxycorticosterone.-A new partial synthesis of deoxycorticosterone(V) has been described by W. Schindler, H. Prey, and T. Reichsteh8starting from the unsaturated hydroxy-keto-acetal (X), the preparationof which was described in the last rep0rt.l Reduction of (X) by the Meerwein-Ponndorf method gave {XI), only one of the two theoretically possibleisomers being isolated.Partial oxidation of this diol-acetal by the Oppenauermethod gave (XII), hydrolysis yielding the hydroxy-aldehyde (XIII),which when treated with pyridine gave deoxycorticosterone.Partial Synthesis of Substance #.-Treatment of dehydroandrosterone(XIV) (obtained from cholesterol) with ally1 bromide in the presence ofmagnesium gave 17-allylandrostendiol (XV), which on oxidation withaluminium tert .- butoxide and acetone yielded the corresponding ap-un-saturated ketone (XVI), dehydration of which gave the trienone (XVII).Oxidation of (XVII) with osmium tetroxide gave a tetrahydroxy-ketone(XVIII), which formed a monoacetone derivative (XIX). The acetateof the last compound (XX) was treated with aqueous acetic acid, whichhydrolysed the acetone group to give the tetrol mono-acetate (XXI),oxidation of which with periodic acid gave the aldehyde (XXII).g TheIbid., 1940,23, 1114.Helv. Chirn. Acta, 1940, 23, 925. 8 Ibid., 1941,24,360160 ORGANIC CHEMISTRY.partial synthesis of substance S wag completed by J. v. Euw and T. Reich-stein,lO who showed that hydrolysis of (XXII) with potassium bicarbonate?H2*o>CMe2 qH-0/$I+ t- /\/ I I (\'-'-OH /\/ .:Pl\;v \/ WI.) Oj\/\/ (XXIII.)gave (XXIII), which when treated with pyridine isomerised t o a productwhich proved to be identical with the natural cortical hormone substance S(VI). This part-synthesis is partioularly important, since the amount ofsubstance S which has been available from adrenal cortex has hitherto beentoo emall to allow of a full biological examination.The method described has been very considerably simplified by the sameauthors l1 in a later paper.They show that oontrolled oxidation of thetetrol (XVIII) with periodic acid gives a mixture which must contain thealdehyde (XXIII), since treatment of this mixture with pyridine, followedby acetylation, gives an overall yield of 30% of substance S acetate.11 Ibid., 1941, 24, 1140. lo Helv. Chim. Actu, 1940, 23, 1268SPRING: HORMONES OF ADRENfi CORTEX. 151Partial Synthesis of Dehydrocortiwsterone.-The most readily availablestarting material for the synthesis of an ll-oxygenated steroid is clearly a12-oxygenated bile acid or a degradation product thereof. Reichstein andhis tonaborators, after many unsuccetmful attempts to prepare 11 -oxygenatedcholane derivatives from bile acids, developed a method for the conversionof a, 12-hydroxycholane derivative into a, All-cholene derivative.Thenext stage oonsisted in the elaboration of a method for the conversion of theAll-cholene derivative into an 11-ketocholane derivative and finally the twomethods were combined with an established method for the attachmentof the requisite side ohain.H. B. Alther and T. Reich-stein,la applying a method used by H. Wieland,l3 showed that 12p-hydroxy-(i) Preparation of A1l-chdene derivatiues.(=.) (=w ( m u . )cholanic acid1* (XXIV), on being heated in a vacuum, gave A%holenicacid (XXV), the constitution of which was established by its conversion intol2 Helv. Chim. Ada., 1941, 24, 1268.l4 J.Barnett and T. Reichatein, Helv. Chirn. A&, 1938,81,926.2. physiol. Chem., 1912, 80,287 ; 1916,98, 62 ; 1980,110, 143; 1920, 111, 123152 ORGANIC CHEMISTRY.the tricarboxylic acid (XXVI) previously obtained by H. Wieland and P.Weygand l5 by oxidation of 12-ketocholanic acid. In a similar manner V.Burchhardt and T. Reichstein l6 showed that thermal degradation of3-keto-12p-hydroxycholanic acid l7 gives 3-ket0-A~~-cholenic acid (XXVII),and that 3-keto-12~-hydroxy-A4-cholenic acid gives 3-keto-A* : ll-choladienicacid (XXVIII). J. Press and T. Reichstein l8 showed that (XXVII)can be partially reduced to give a mixture of 30(- (XXIX) and 3p-(XXX)hydroxy- All-cholenic acids, which are separable by means of digitonin.The method was improved by subjecting the 12p-benzoyloxycholanic esters(instead of the 12-hydroxy-acids) to thermal de~adati0n.l~ A.Lardonand T. Reichstein20 applied the method to the preparation of methyl3-ket0-A~~-atiocholenate (XXXIII). Methyl 3a : 12p-dihydroxyatiocho1-anate (XXXI) 21 was converted into its diacetate, partial hydrolysis of whichyielded the methyl ester of 3a-hydroxy- 12p-acetoxyatiocholanic acid.Oxidation gave the corresponding 3-keto-derivative, which was hydrolysedand converted into methyl 3-keto-12-hydroxyatiocholanate (XXXII),the benzoate of which, on pyrolysis, gave the required methyl S-keto-A%itiocholenate (XXXIII) .Many attempts to introduce an oxygenat C,, in the cholane nucleus have hitherto only led to substances whichcarry a second oxygen a t C12.22 A method for the introduction of oxygenat C,, only, in ring C, has now been developed by T.Reichstein and H.Rei~h.~3 Treatment of methyl All-cholenate (XXXIV) with hypobromousacid gave a mixture of products in which the presence of the bromohydrin(XXXV) was established by subsequent reactions. The mixture wasoxidised with chromic acid [thereby giving (XXXVI)] and debrominatedwith zinc to give a mixture from which methyl ll-ketocholanate (XXXVII)was isolated as major component. The constitution of (XXXVII) is estab-lished, since (a) it differs from methyl 12-ketocholanate, and (b) the positionof the ethylenic linkage in methyl All-cholenate has been unambiguouslyestablished.Using the same method, A. Lardon and T.Reichstein 24 have convertedmethyl 3-keto-All-cholenate (XXXVIII) into methyl 3 : 1 l-diketocholanate(XXXIX). A further development of the method is described by J . Press,(ii) Cl,-Ketocholane derivatives.lC 2. physiol. Chem., 1920, 110, 141.l7 K. Yamasski and K. Kyogukcs, 2. physiol. Chern., 1935,233,29.Helv. Chim. Acta, 1942, 25, 878.A. Lardon, P. Grcsndjean, J. Press, H. Reioh, and T. lteichstein, ibid., p. 1144.16 Helv. Chim. Acta, 1942, 25, 821.2o Ibid., 1943, 26, 607.a1 w . M. Hoehn and H. L. Mason, J. Amer. Chem. SOC., 1938, 60, 1493; H. L.Mason and W. M. Hoehn, ibid., p. 2824; 1939, 61, 1614.'* H. Wieland and T. Postern&, 2. physiol. Chem., 1931, 197, 17; H. Wieland andE. Dane, ibid., 1933, 216, 99; J. Barnett and T. Reichstein, Helv.Chim. Acta, 1938,21, 926; 1939, 22, 75; R. E, Marker and E. J. Lawson, J. Amer. Chem. SOC., 1938, 60,1334; B. B. Longwell and 0. Wintersteiner, ibid., 1940, 62,200; P. N. Chakravortyand E. S. Wallis, ibid., p. 318; H. €3. Alther and T. Reichstein, Helv. Chim. Acta,1942,25,805; S. Bergstrem and G. A. D. Haslewood, J . , 1939, 540-23 Helv. Chim. Acta, 1943, 26, 562. 2' Ibid., 1943, 26, 586SPRING : HORMONES O F ADRENAL CORTEX. 153P. Grandjean, and T. Reichstein,25 who also show that on partial catalytichydrogenation, the diketone (XXXIX) gives mainly methyl 38-hydroxy-ll-ketocholanate (XL), characterised by the fact that it gives an insolubledigitonide and is reconverted into (XXXIX) on mild oxidation with chromicacid.Finally, A. Lardon and T.Reichstein26 have applied the method tomethyl All-atiocholenate (XLI) and thereby obtained methyl 3 : 1 l-diketo-iitiocholanate (XLIV). In this case, the pure bromohydrin (XLII) wasisolated (it seems that only one of the four theoretically possible isomers isformed), oxidation of which gave the pure bromo-ketone (XLIII). Partialcatalytic reduction of (XLIV) yields as major product methyl ll-keto-3p-hydroxyatiocholanate (XLV), the structure of which follows from itsBrre-oxidation to (XLIV), from the fact that it gives an insoluble digitonide(in contrast to the 3a-isomer), and from its facile conversion into a mono-acetate, a behaviour not shown by ll-hydroxysteroids. Of great interestis the conversion of the diketone (XLIV) into a .Q-bromo-derivatire, treatmentof which with pyridine yields methyl 3 : 1 l-diketo-A4-atiocholenate (XLVI)identical with the characteristic degradation product previously obtained26 Helv.Chim. Actu, 1943, 26, 698. *a Ibid., p. 705154 ORGANIC CHEMISTRY.from cortioosterone and dehydrocorticosterone ; 27 this result constitutesthe first confirmation by synthesis of the structures of these hormones.28BrC0,Meo:f\j-lC0,Me(XLI.)Bro:/.l-rz o:<\l--; 3+"I(y" T Y " HO/\/H .:cry Oj",H(XLV.)The starting point for thefinal stages in the synthesis of dehydrocorticosterone is methyl ll-keto-3p-hydroxyatiocholanate (XLV), which after hydrolysis and acetylationgave the 1 l-keto-3p-acetoxy-acid (XLVII). This was converted into thecorresponding acid chloride and thence into ;the diazo-ketone (XLVIII),hydrolysis of which (note the stability of the diazo-ketone) gave the corre-sponding alcohol (XLIX), which on decomposition with acetic acid yieldedthe 21-monoacetate of pregnane-3p : 21-diol-11 : 20-dione (L).This mono-acetate was oxidised to the acetate of pregnan-21-01-3 : 11 : 20-trione (LI),which gave a 4-bromo-derivative (LII), treatment of which with pyridinegave (LIII), which proved to be identical with the acetate of dehydro-corticosterone (11) obtained from adrenal cortex.2917 p-Hydroxyprogesterone .-This compound (LIV) was first isolatedfrom adrenal cortex by J. J. Pfiffner and H. B. N0rth.~0 It has now beenisolated from the same source by J. v. Euw and T. Reichstein3l by twomethods. In one of these the " hydroxy-free ketone " fraction 32 wasacetylated and separated by chromatographic methods into (1) allo-pregnanolone acetate, (2) progesterone, (3) androstenedione, (4) %mono-acetate ofallopregnane-3 : ll-dio1-17-one, ( 5 ) adrenosterone, (6) 17p-hydroxy-T.Reichstein, Helv. China. Acta, 1937, 20, 953; H. L. Mason, W. M. Hoehn,B. F. McKenzie, and E. C. Kendall, J. BioZ. Chem., 1937,120, 719.28 M. Steiger and T. Reichstein, Helv. Chim. Acta, 1938, 21, 161 ; T. Reichstein andK. G. Fuchs, ibid., 1940, 23, 676; C. W. Shoppee, ibid., p. 740.80 A. Lardon and T. Reichstein, ibid., 1943, 26, 747.SO J . Bwl. C h . , 1940, 1$2,469.91 Helv. Chirn. Adu, 1941, 84, 880.vH(XLIII.) (XLIV.)(iii) Completion of the partial synthesis.** Ibid., 1938,21, 1197, 1201SPRING : HORMONES OF ADRENAL CORTEX.155progesterone (LIV) (50 mg. from 500 kg. of adrenal cortex), (7) 17a-methyl-D-homo-A4-androsten-17cz-ol-3 : 17-&one (LV), together with several otherunidentified products. Of these, (l)F3 (2),33 (4) 34 and (5) 35 have previouslybeen isolated from adrenal cortex, but this is the first time that the presencetherein of androstenedione has been reported. The amount isolated is small,and it is probably an artefact produced by aerial oxidation of substance-S(or of a similmly constituted compound).17p-Hydroxyprogesterone shows an anomalous melting point whichis due to its rearrangement to a mixture of (LV)S6 and an isomer, m. p.p%C0,H co(XLV.) (XLVII.) (XLVIII.)vH2*OAc yH2*OAc THN2co co co(XLIX.)IQH2*OAc co .1 vH2*OAccdo:f\l--lo:(&)/\/ o:(Y-l - o:(:!/y..(L1ll-)Br (LII.)162-164'. On prolonged heating with alkali, 17 P-hydroxyprogesteroneis isomerised to a mixture of (LV) and an isomer, m. p. 182". It is veryprobable that (LV) and the compounds, m. p. 162-164" and m. p. 182",are three of the four theoretically possible isomers of structure (LVu and b)and (LVIa and b).37 The isolation of (LV) from adrenal cortex has probably88 D. Beall and T. Reichstein, Nature, 1938, 142, 479; D. Beall, Biochem. J . , 1938,33, 1957.34 T. Reichstem and J. v. Euw, Helv. Chim. Acta, 1938, 21, 1197.56 T. Reichstein, ibid., 1936, 19, 29, 223.86 Ibid., 1939,23,626; L. Ruzicka and H. F. Meldahl, {bid., 1940,87 C.W. Shoppee and D. A. Prim, ibid., 1943, a, 185.364156 ORGANIC CHEMISTRY.t o be attributed to a rearrangement of 17P-hydroxyprogesterone during oneor more of the processes employed in its isolation.YH,-OHCOMe(LIV.) (LVIII.) (LVII.)The structure of 17P-hydroxyprogesterone 3O has been confirmed by apartial synthesis 38 based upon a method developed by D. A. Prins and T.Reich~tein.~~ Controlled oxidation of A4-pregnene-17P : 20p : 21-triol-3-one 40(LVII) with periodic acid gives the hydroxy-aldehyde (LVIII), treatmentof which with diazomethane yields 17p-hydroxyprogesterone (LIV). Thispartial synthesis establishes the configuration at C1,, since that in (LVII)is established and the changes do not involve rearrangement at this centre.An alternative partial synthesis has been de~cribed.~~9- and 11 -Dehydroprogesterones.-Corticosterone (I) has been convertedinto ll-hydroxyprogesterone (LIX) 42 and this, by treatment with hydro-chloric acid, into 9-dehydroprogesterone (LX).43 The isomeric 1 l-dehydro-HO(\, y0*cH2*0H COMeH*/\I-j -&z /\/\/\/ (LIX.)\/\/I0:I I tCOMe PI-I(LXI.) (\I/)/\/*:\/\/+ COMe38 Helv.Chim. Acta, 1941, 24, 945.40 W. Logemann, Naturwiss., 1939, 27, 196; L. Ruzicka and P. Muller, Helv. Chim.4 1 P. Hegner and T. Reichstein, Helv. Chim. Acta, 1941, 24, 828.42 T. Reichstein and H. G. Fuchs, ibid., 1940, 23, 684.49 C. W. Shoppee and T. Reichstein, ibid., 1941, 24, 351 ; P. Hegner and T. Reich-Ibid., p. 396.Ada, 1939, 22, 755.atein, ibid., 1943, 20, 715SPRING : HORMONES OF ADRENAL CORTEX.157progesterone (LXI) has been obtained by P. Hegner and T. Reichstein43by thermal degradation of the benzoate of 1Z-hydroxyproge~terone.~~9- and 11 -Dehydroprogesterone, like 6-dehydroproge~terone,~~ show strongprogesterone-activity, whereas the isomeric 16-dehydroprogesterone 46is inactive in this respect.Other Steroids from Adrenal Cortex.-A new member of the C210,-groupof adrenal steroids has been isolated and ~haracterised.~, It is substanceU, C,,H3,05; it is an @-unsaturated ketone. Its structure (LXIII, R = H)has been established by a partial synthesis from substance E,48 the diacetateof which (LXII) is converted into the diacetate of substance U (LXIII,HO_3 --+/\I/\/#\/ /\I/\/ \/I l lAcOl ' 1 AcO\/i\/ (LXV.1H \ / a \ /OAc OAcco HOYH2 co YH2IJ HSubstance-A triacetate( L x IV . )Ho:~\~-~-co~cH,~oA~ 0:/\1---1-~ /\I/\/\/ - \/\/ AcOl t AcOH H\/\/HSubstance-N diacetate Substance-R diacetate(LXVI.) (LXVII.) (LXVIII.)HO , H-!:tc\/\---OHISubstance U (R = H)0:I ' \/\/Substance-E diacetate(LXII.) (LXIII.)R = COMe) by oxidation with chromic acid.Furthermore, substances A,E and U have the same configuration at C,, and C,, (and substances Aand E have the same configuration a t C,,!, since hydrogenation of E-di-acetate, followed by acetylation, gives the triacetate of substance A (LXIV).44 M. Bockmiihl, G. Ehrhart, W. Ruschig, and W. Aumuller, A.P. 2,142,170.45 A. Wettstein, Helv.Chirn. Acta, 1940,23,388.48 A. Butenandt and J. Schmidt-Thome, Ber., 1939, 72, 182.4 7 Helv. Chim. Acta, 1941, 24, 2473.T. Reichstein, ibid., 1937, 20, 953158 ORGANIC CHEMISTRY.Using a method developed by K. H. Slotta and K. Nei~ser,~~ C. W.have converted the triacetate of substance A Shoppee and T. ReichsteinCH,*OHH- -OH CHOHO H HSubstance K (LXIX.)Substance L(LXXIII.)Substance 0(LXXII.)Substance J(LXXI.)Substance-P diacetate (LXXIV.)into substance-N diacetate. Distillation of A-triacetate with zinc dustgives iso-R diacetate (LXV), which differs from substance-R diacetate in49 Ber., 1938,71,2342 ; A. Serini, W. Logemann, and W. Hildebrand,Ber., 1939,72,391.Helv. Chim. Acta, 1940, 23, 729SPRING : HORMONES OF ADRENAL CORTEX.169the orientation around C17. Although in the case of the similarly consti-tuted 17-isopregnenolone acetate,S1 isomerisation to the normal pregnenoloneacetate is caused by either acid or alka,li, iso-R diacetate (LXV) cannot beisomerised to substance-R diacetate (LXVIII), since alkali attacks the ketolgroup and the C,,-hydroxyl group is unstable in the presence of mineralacid, which effects dehydration. However, oxidation of iso-R diacetategives iso-N diacetate (LXVI), which is readily isomerised by mineral acid togive (LXVII), identical with the diacetate of substance N isolated fromadrenal cortex. (Substance-N diacetate has previously been obtained byoxidation of R dia~etate.5~)Substances J (LXXI) and 0 (LXXII) [and consequently substance L(LXXIII), which gives a mixture of substances J and 0 on hydrogenationhave been shown to possess a 17p-hydroxy-configuration by an indirectmethod.u (The C2,,-configurations assigned to substances J and 0 are onlycomparative and not absolute.) This has been confimed by a direct con-version of substance K (LXIX) into a mixture of substances J and 0.Oxidation of substance K (LXIX) with one equivalent of periodic acidgives the hydroxy-aldehyde (LXX), treatment of which with methyl-magnesium bromide yields a mixture of substances J (LXXI) and 0The hydroxy-aldehyde (LXX) has also served for a partial synthesis ofsubstance L (LXXIII), which is obtained by treatment of (LXX) withdia~omethane.~~A partial synthesis of substance K (LXIX) (as its triacetate) has beenaccomplished 58 starting from dehydroandrosterone (LXXVII) (i.e., fromcholesterol) and a similar method starting from t-androsterone acetate(LXXIV) has led to the partial synthesis of the diacetate of substanceP 57 (LXXV).In its turn, P-diacetate (LXXV) has been converted intosubstance L (LXXIII) ; treatment of the former with methylmagnesiumbromide gives a tetrol (LXXVI), which on controlled oxidation with periodicacid gives substance L (LXXIII).59 The methods mentioned above for thepart-syntheses of substances P and K are extremely laborious, but theyhave the advantage that they lead to established configurations at C17;they are, of course, the " master " syntheses in the series of inter-relationshipsdepicted.F. S. S.(LXXII) .5 5A. Butenandt, J. Schmidt-Thom6, and H. Paul, Ber., 1939, 72, 1112.5g T. Reichstein, HeEv. Chim. Acta, 1938, 21, 1490.53 T. Reichstein, C. Meystre, and J. v. Euw, ibid., 1939, 22, 1107.54 D. A. Prins and T. Reichstein, ibid., 1940, 23, 1490.5 6 Idem, ibid., 1941, 24, 396.5 7 J. v. Euw and T. Reichstein, ibid., p. 401.68 H. G. Fuchs and T. Reichstein, ibid., p. 804.69 J. Y. Euw and T. Reichstein, ibicE., p. 418.Idein, ibid., p. 945160 ORGANIC CHEMISTRY.6. HETEROCYCLIC COMPOUNDS.Nitrogen Ring Compounds.Indole Derivatives.-By the use of 15N as a tracer element, C. F. H. Allenand C. V. Wilson have shown that the nitrogen atom which is eliminatedas ammonia in Fischer’s synthesis is not that originally attached to thearomatic ring: :--+ ( \ m , p h $- NH3- /\I t\A vv 5NHCH35NH-N:CPhThey modify the mechanism of (Mrs.) G.M. and R. Robinson2 by assumingthat the tautomeric imine form (I) of the intermediately formed diamineundergoes an addition-elimination process :alternatively, the imine may first suffer hydrolysis to the ketone, whichthen undergoes a similar addition, followed by elimination of water. Themechanism of this synthesis has been reviewed by R. B. van Order and H. G.Lindwall.3 The conversion of phenacylarylamines (11) into 2-arylindoles(IV) 4 has been critically studied.5 The two reaction mechanisms previouslyproposed have been shown to be incorrect, and the reaction, which requiresthe presence of catalytic impurities such as amine hydrobromides, probablyproceeds by a Hofmann-Martius rearrangement.Migration of the phenacyl/\-v\/ 1 I IIPh _3/\/CH2\Coph\/\ NH*CH,-COPh ‘ d \ N H 2 NH(IV.)f\i(11.) (111.)group into the o-position is followed by the known cyclisation of the resultingphenyl o-aminobenzyl ketone (111).Ph*CO*CO*NRPh ___ + Ph2C( OH)*CO*NRPh PhMgBrFI.1 \+ f)-p2/* \ / \ P OPh2C( OAc)*COCl + PhNHR NR(VII.) (V.)3 : 3-Diphenyloxindoles (V, It = H or alkyl) have been prepared bythe action of phenylmagnesium bromide on phenylglyoxylic anilides (VI,J . Amer. Chem. SOC., 1943, 65, 611.J., 1918, 113,639; 1924,1!%, 827. Chem. Reviews, 1942, 30, 80.R. MGhlau, Ber., 1881, 14, 173; 1882,15,2480; 1885,18, 165.A. F. Crowther, F. G. Mann and D. Purdie, J., 1943,58.‘ E. Fischer and T. Schmitt, Ber., 1888, 21, 1071, 1811 ; A. Bischler, ibid., 1892,25, 2860.E. B. Womsck, N. Campbell, and G. B. Dodds, J., 1938, 1402OPENSHAW : HETEROCYCLIC COMPOUNDS. 161R = H or alkyl), and by the interaction of acetylbenzilyl chloride (VII)with alkylanilines.sThe synthetic reactions of oxindole, important for its relationship tohydroxytryptophan and indole alkdoids, have been studied by L. Horner.9Condensation with esters by Claisen's method affords 3-acyloxindoles(VIII) ; except in the case of ethyl oxindole-3-glyoxylate (VIII, R = CO,Et),the ketonic carbonyl of these products. cannot be reduced. 3- Alkyloxindolescan be obtained by the condensation of aldehydes with oxindole in thepresence of trimethylamine, followed by hydrogenation of the resultingalkylideneoxindoles. The abnormal, red condensation product of oxindole-3-aldehyde with hippuric acid l1 is probably the isatin derivative (IX) ;in contrast, (VIII, R = C0,Et) condenses normally in the Erlenmeyersynthesis, but reduction and hydrolysis of the resulting azlactone lead tothe dilactam (X) and not to the expected carboxy-derivative of Z-hydroxy-tryptophan.A similar rearrangement to a quinoline derivative (XI)(VIII.) ~ ) - - ~ H ~ C O Rvvco NHCO-NH, CO,HNH " B(X.) (XI.)occurs when the condensation product of ethyl oxindole-3-acetate and ethyloxalate is hydrolysed, and these reactions show a marked analogy to thetransformation of tryptophan, through kynurenine, into kynurenic acid.125-Hydroxyindole, also important for its relationship to physiologicallyactive substances, has been synthesised.13Indolyl and pyrryl bromomethyl ketones form quaternary salts withpyridine, which yield indole- and pyrrole-carboxylic acids quantitativelyon treatment with alkali, and which react with p-nitrosodimethylaniline toform nitrones (XII), hydrolysed by acid to indolylglyoxal hydrates (XIII) .I4(XIII.) (C8H,N)*CO*CH(OH)2* R.F. Reeves and H. G. Lindwall, J . Amer. Chem. SOC., 1942, 84, 1086.Annalen, 1941, 548, 117.H. Fischer and K. Smeykal, Ber., 1923, 56, 2370.lo cf. P. L. Julian, J. Pikl, and F. E. Wantz, J , Amer. Chem. SOC., 1935, 57,2026.l2 Ann. Reports, 1942, 39, 198.l3 F. Bergel and A. L. Morrison, J., 1913, 40.l4 G. Sanna, Gazzetta, 1942, 72, 367.REP.-VOL.XL. 1.62 OBQANIC CHEMISTRY.Pyridine Group.-W. W. Crouch and H. L. Lochte l5 h u e described anew synthesis of p-vridine ; treatment of glutarimide with phospbomspentachloride l6 affords 2 : 3 : 6-trichloropyridine, which can be reducedCataIytically to pyridino. Chloropicolines are similarly obtained froma- and p-methylglutarimides. A. Dornow and P. Karlson l7 have extendedtheir pyridihe synthesis fo include 2-aminopyridines (XIV) ; carbethoxy-acetiminoether (XV) condenses with 1 : 3-dicarbonyl compounds (or theirenol ether scetds) to yield the intermediate (XVI), which cyches, by fissionof ethyl rnalmate, to the 2-aminonicotinic ester (XIV, R” = CO,Et),convertible into (XIV, R” = M) by hydrolysis and decarboxylation.R’ R‘(XV.1 E t O*d*CH,*CO,Et (XIV.)(XVI.)As a model for the synthesis of quinine types, 4-methyl-3-vinylpyridine(XVII) has been synthesised by an adaptation of Guareschi’s method.lga-Acetobutyrolactone condensed with cyanoacetamide to the imide (XVIII),covverted into (XVII) by the route shown. Although pyridine-4-P-pro-Me Me Me(XVIII.)CH,*CH,*CO,H/\(XIX.) II I \<pionic acid (XIX) was obtained from ethyl p-ketoadipate by a similar seriesof reactions, the method could not be extended to the preparation of the3-vinyl derivative of (XIX), owing to the failure of ethyl p-keto-or-(2-ethoxy-ethy1)adipate to condense with cyan0acetarnide.m 2 : 5-Dialkylpyridinesare prepared by the condensation of ethyl alkylmalanrttes with ethyl p-alkyl-J.Amer. Chern. Soc., 1943, 65, 270.l6 Cf. 0. Bernheimer, Gaszetta, 1882, 12, 283.lT Ber., 1940, 75, 542; cf. Ann. Repoxts, 1941, 38, 224.J. R. Stevens, R. H. Beutel, and B. Chamberlin, J . Amer. Uhm. Soc., 1942,J. C. Bardhan, J., 1929, 2223.64, 1093.*O J. R. Stevens and R. H. Beutel, J . Amer. Ckem. ~ o c . , 1943,05,449OPENSHAW : HETEROCYCLIC COMTOUNDS. 163p-am.inoacrylates.al A new route to vitamin B, involves the conversionof 4-carbethoxy-5-cyano-2-methyl-6-pgTidone (XX, R = C0,Et) l9 throughthe amide into the dinitrile (XX, R = CN). Nitration, followed by theaction of phosphorus pentachloride, yielded (XXI) , two-stage catalytichydrogenation of which gave the triamine (XXII, R = NH,), convertedinfo the vitamin (XXII, R = OH) by the aotion of nitrous acid : 2aR CN CH2RRf\\CH,BMe1 1/\\m NO,/\\CNMe(,bO NH Me(& N \.((XX.1 (XXI.) (XXII.)3-Phenylpiperidine (XXIII, R = R' = H) and some of its 4-substitutedderivatives have been prepared by the following series of reactions : ~3CH,Ph.CN + CRR':CH*CO,Et --+ CHPh( CN)*CRR'*CH,*CO,Et a H,-NiCRR' CRR'/ \ / \PhvH FH2 N n + PhqH VHzCH, CO BuOB CH, CH, (XXTII-) 'AG.H. Coleman and J. J. Carnes24 have synthesised tropane by heatingN-chloro-N-methylcycloheptylamine with sulphuric acid.3-Bromopyridine is readily prepared by heating pyridine hydrochlorideperbromide at 160-170"; eome 3 : 5-dibromopyridine is a180 formed.Optimum conditions for the sulphonation of pyridine and the picolinea havebeen described.26 Pyridine can be mercurated in the 3-po~ition.~~ J.F.hens and J. P. Wibaut 27 have shown that the reaction between pyridine,aliphatic anhydrides and zinc dust 28 is general, and have prepared several4-alkylpyridines by this means. P ~ i d i n e - 2 - ~ ~ and -3-aldehyde~,~- 3O but notthe 4-is0rner,,~ can be prepared by alkaline fission of the benzenesulphon-hydrazides 31 of the corresponding carboxylic acids ; this method i s alsouseful in the thiazole,32 pyrimidine 33 and glyoxltline 34 series. Pyridine-21 V. Prelog, S. Szpilfogel, and E. Stahlberger, HeZv. Chim. Acta;, 1942, $36, 1306.22 J. H. Mowat, F. J. Pilgrim, and G. H. Carlson, J . Amer. Chem. SOC., 1943,65, 954.23 C. F. Koelsch, &id., pp. 438, 2093.24 Proc. Iowa Acad. Sci., 1942,49,288; of.Ann. Rep&, 1942,59, 195.26 S . M. McElvain and M. A. Goese, J . Amer. Chem. Soc., 1913, 65,2227, 2233.lo C. K. Kanvinde, R. S. Borkar, A. N. Kothare, and V. V. Nadkarny, J. Univ.28 Ibid., 1941, 60, 119; Ann. Reports, 1941, 38, 223.Bombay, 1942,ll A, Pt. 3, 101. 27 Rec. SPTav. c h h , 1942, 61, 59.c. Niemann, R. N. Lewis, and J. T. Hays, J . Arner. Chem. SOC., 1942, 84, 1678;1943, 66, 482.30 L. Panizzon, Helv. Chim. Acta, 1941, 24,24E.*I J. S. McFadyen and T. S. Stevens, J . , 1936, 684.sa E. R. Buchman and E. M. Richardson, J . Amr. C h . SOC., 1939,61, 891." D. Prim, (Miss) E. L. May, and F. D. Piokel, ibid., 1940,62,2818.J4 Y. Tamamushi, J . Pharm. SOC. Japan, 1940, 80, 184164 ORGANIC CHEMTSTRT.3-aldehyde can be converted into the -3-carbinol and -3-p-acrylic acid; 30pyridine-3-acetic acid has been prepared 35 from 3-acetylpyridine by theWillgerodt 36 method.The amination of heterocyclic bases by alkali amideshas been reviewed by M. T. Leffler.3’V. Prelog and co-workers38 have shown that the dehydrogenation ofhydropyridyl ketones is accompanied by rearrangement ; the compound(XXIV, R = CO-CH,) is converted into 2 : 3 : 4-trimethylpyridine bypalladised charcoal or by selenium at 300°, whereas the related substances[XXIV, R = CH(OH)*CH3 or R = Et] yield the expected p-collidine.The piperidyl ketone (XXV) similarly suffers rearrangement to 2 : 3-di-methylpyridine. The dehydrogenation of bicycloaza-alkanes has also beenstudied; 39 quinuclidine (XXVI, n = 2) was smoothly converted into(XXIV.) (XXV.) (XXVI.)(XXVII.) (CH,),/$\(CH,),\N/4-ethylpyridine, and (XXVI, n = 1) less readily afforded y-picoline, ontreatment with palladised charcoal or selenium a t 300”. Octahydro-pyridocoline (XXVII, x = y = 4) gave a trace of quinoline, but the bases(XXVII, z = 3 or 4, y = 3) and (XXVIII, x = 2 or 3, y = 3) gave nodefinite products.Quinolines and isoQuino1ines.-The Friedlgnder synthesis is often im-proved 40 by using o-aminobenzylidene arylamines 41 in place of the sensitiveo-aminobenzaldehydes. 3-Nitrocinchoninic acid is obtained by the alkalinecondensation of isatin with nitromethane; it can be reduced to the amino-acid or decarboxylated to 3-nitroq~iinoline.~2 Quinoline-2- and -4-aldehydesare best obtained by oxidation of the corresponding methylquinolines withfreshly prepared selenium dioxide,43 and the 3-, 5-, 6- and 8-isomeridesU35 M.Hartmann and W. Bosshard, Helv. Chirn. Acta, 1941, 24, 28E.36 Ber., 1887, 20, 2467.37 “ Organic Reactions,” Vol. 1, p. 91. Wiley and Sons, New York, 1942.3E V. Prelog and A. Komzak, Ber., 1941, 74, 1705; V. Prelog, A. Komzak, and E.Moor, Helv. Chim. Acta, 1942, 25, 1654; V. Prelog, E. Moor, and J. Fuhrer, ibid.,1943, 28, 846.SD V. Prelog and K. Balenovi6, Ber., 1941, 74, 1508.40 W. Borsche et al., Annalen, 1941,548,50; 1942,550, 160; 1943,554,269.41 A. Rilliet and L. Kreitmann, Helv. Chirn. Acta, 1921, 4, 596; 1922, 5, 547.4a M. Colonna, Boll. sci. facoltci cliirn. ind. Bologna, 1941, 89; Amer.Chem Abstr.,43 H. Kaplan, J . Anzer. Chem. Soc., 1941, 83, 2654.44 A. H. Cook, I. M. Heilbron, and L. Steger, J . , 1943,413.1923, 37, 3096OPENSHAW : HETEROCYCLIC COIMPOUNDS. 165from the appropriate carboxylic acids by the method of McPadyen andStevens.31 isoQuinoline-1 -aldehyde is prepared by the former method,and undergoes the normal condensation reactions.45 Reduction of theanilides of cinchoninic acids by the method of A. Sonn and E. Muller 46affords phenyl-lepidylamines (XXIX, R = Ph) and not the expected cin-choninaldehydes ; cinchoninic alkylamides similarly give rise to alkyl-lepidylamines (XXIX, R = Me or CHMefCH2],-NEt2).47 The conversionof 2-phenylcinchoninamide into 4-amino-2-phenylquinoline by the actionof potassamide in liquid ammonia, under the catalytic influence of potassiumnitrate or mercury, is considered to involve a Hofmann-type rearrangement .48/\VH,*NHR(XXIX.)C0,HR’l 1 )R/\/\Ph\/\N(XXX.) (XXXI.) (XXXII.)Many phenylquinolinecarboxylic acids in which the phenyl and thecarboxyl group occupy adjacent positions on the nitrogenous ring canbe cyclised to benzazafluorenones by sulphuric acid or by the Friedel-Craftsmethod; for example, (XXX, R = H, alkyl or Ph; R’ = H or OMe) affordthe corresponding derivatives of (XXXf), but in certain cases ring closurecannot be achieved. Cyclisation of the corresponding benzyl compounds(XXX, CH,Ph for Ph) to benzaza-anthrones (XXXII) is a less generalreaction.49 Naphthyridine derivatives could not be obtained by thecyclisation of 2-anilinonicotinic acid, N-( 3‘- or 4’-pyriclyl)anthranilic acids 5Oor o-benzamidophenyl-pyridines or -quinolines,5l but cyclo-dehydration of3-benzamido-2-phenylquinoline (XXXIII) gave the dibenz- 1 : 5-naphthyri-dine derivative (XXXIV).51NThe synthesis of 1- benzyltetrahydroisoquinolines from arylacetaldehydesand p-arylethylamines occurs under “ physiological conditions,” providedthat the aryl group in the latter carries a substituent, such as hydroxyl,which activates the position ortho to the basic side-chain. The rate of re-q5 R. S. Barrows and H. G. Lindwall, J . Amer. Chem. Xoc., 1942, 64, 2430.4 G Ber., 1919, 52, 1927. 4 7 T. S. Work, J., 1942,426,430.4 8 H. C. White and F. W. Bergstrom, J . Ory. Chem., 1942, 7 , 497.40 W.Borsche et al., Annalen, 1937, 532, 127, 146; 1938, 537, 22; 1939, 638, 283,292; 1910, 544, 272, 280, 287; 1941, 548, 64, 74; 1943, 554, 269.5O W. 0. Kerrnack and (Miss) A. P. Wostherhead, J., 1942, 726.61 V. A. Petrow, M. V. Stack, and W. R. Wragg, J., 1943, 316aotion between p-( 3 : 4-dihydroxypheny1)ethylamine and homopiperonalat 25" and over the pH range 3-7 has been studied; the tetrahydrobo-quinoline (XXXV) was produced in 77-85 yo yield. Piperonylglyoxylicacid reacts more slowly than homopiperonal, suggesting that the biologicalsynthesis proceeds by way of the aldehydes rather than the pyruvic acids.52Ho//\/CH2\vH2 HoH\/CH2bH2KOl\/l NH2 H0!\XCH,NHCH2-/--\ VHO /O\CH,-> o/ CH2-H-N I /%H, O /\=/- \-/- (XXXV.) -Munnich Reaction.~3--Isol~ted examples of the formation of heterocycliccompounds from the products of interaction of simple ketones with form-aldehyde and methylamine have been known for some time; acetoneaffords the piperidine (XXXVI),U and p-methylaminopropiophenone canbe converted into the tetrahydropyrimidine (XXXVII) or the pyrazoline(XYXVIII) by means of the appropriate reagents.55 The applicationof such methods was strictly limited, since with most ketones the initialMe, ,OHBCH,*CO*CH, + 2CH,O -t NR2Me + CH,*CO*QH 7H2 (XXXV~:)CH, CH,\ /' m eNMe/ \ Ph$--QH2 (1) HNO, KCYO 70 YH,cH2 j- Ph*CO*CH,CR2*NHMe,HCl -'-+ N(R*CO*CH,*C'H,),NMe(XXXVIII.) (XXXIX.) (XXXVII.)condensation either produced a complex mixture of products,56 or affordedo d y tertiary amines of the type (XXXIX), frequently in poor yield.C. Mannich and 0.Hieronimus 57 have recently shown that the useof benzylamine (or piperonylamine) in place of methylamine gives a muchsmoother reaction, and moderate yields of p- benzylaminoketones areobtainable ; under these conditions, cyclohexanone gives mainly (XL),with a smaller amount of the spiran (XLI). Condensation of (XL) withformaldehyde and a ketone (R-COCH,) affords the decahydroisoquinoline(XLII ; R - Me or Ph, R' = OH) converted by dehydration and subsequentWiley and Sons,N n 7 C h \/NMe62 C. Sch6pf and W. Solzer, Annalen, 1940, 544, 1.53 Review : 3'. 3'. Blicke, " Organio Reactions," Vol. 1, p. 303.New Pork, 1942.s4 C. Mannich and G. Ball, Arch.Pham., 1926,264,66.b6 C. Mannich and G. Heilner, Ber., 1922,65, 366.G 6 C. Mannich, Arch. Pharm., 1917, $266,261. Ber., 1942, 76, 49OPENSRAW : HETEROCYCLIC COMPOUNDS. 167hydrogenation into (XLII, E' == H). Wit4 potassium cyanate, tlee hydro-bromide of (XE) yields the 2-keto-ootahydroquinazoh~e (XLIII), dis-CH, CH, C*, CH,\ / \CH r-CH2Ph \ / \/ '\ /(XL.) / \VH v*CH2Ph/ \ / \\ /cJ32CH2 VH NH*CH,PhCH, CO C(0H) CH2 CR' CH,/ 'cdLORc (XLI.)CH, co\ / (XLII.)W,),proportionated by hot acid to the deca;bydro- and Ohe hexahydro-compowd.The condensation product obtained from a-tetralone (analogaus to XL)rmots similady with pobsium oywate, and reduction of its N-nitroso-derivative yields the benzindazole (XLIV), but the keto-&mines derivedfrom acetone, aoetophenone and cyclopentanone give only uregs withpotassium cyanztte.As a, model for the synthesis af alkaloidal types, c y c bhexanana was condensed with phenylacetaldehyde and benzylamine, thesubstance (XLV) being obtained in very small yield.CH, CH-CB2PhACH, CH, I I/ \ / \ \/\ / \ / \NH*CH,Ph CH2 (P iyCH2Ph v=-">N.CH,ph p 2 , p\ /y \ / \ /CH, C CO H2 CH-CH, CHa CO(XLV .)cfl,(XLTV , )CH,(XLIII.)( 3 3 2Acridines.-A. Albert and R. Goldacrc 58 have measured the basicdissociation constadts of the frvc rnonoaminoacridines. Only the 2- and the5-isomer have appreciably stronger basicity than acridine, and their higberdegree of ionislttion parallels their high antiseptic activity.59 The ringnitrogen is the proton-binding centre in each case, and the enhanced basicityof the 2- and the 5-amino-compound is attributed to the heightened resonanceeffect in the ion (XLVI or XLVIT) as compared with the free base.?Ha AH2A/c\/\ /\/?\AI It I I -++ I II II I (XtYI.) \/\ /\/NH+J., 1943, 454.6v S.D. Rubbo, A. Albert, and M. Maxwell, Brit. J . E q . Path., 1942,88,6Q168 OROANTC CHEMISTRY.The low basicity of 4-aminoacridine indicates that there is no increase inresonance energy in passing from the base to an ion of which the o-quinonoidstructure (XLVIII) is a component. l-Aminoacridine is more weaklybasic than acridine, and this is ascribed to an " ortho-effect "; possiblythe nitrogen atoms are linked by a hydrogen bond (XLIX). The varyingchemical reactivity of the aminoacridines is in accord with the aboveconsiderations.60Pyrimidines and Purines.-In recent years much fresh stimulus has beengiven to the study of the pyrimidine group by the demonstration of thepresence of this ring system in riboflavin and aneurin,61 by the discoveryof the co-enzyme functions of the dinucleotides derived from adenine andnicotinamide or riboflavin,g2 and by the investigation of the therapeuticproperties of sulphanilamidopyrimidines. Numerous new synthetic methodshave been developed in studies related to these topics, and further insight hasbeen gained into the chemistry of pyrimidines.The most widely applicable method for the synthesis of pyrimidinesis represented by scheme ( A ) ; the group R may be alkyl,aryl, hydroxyl, alkoxyl, thiol, alkylthio, or amino, and thegroups CX and CY in the second reactant may be carboxylicester, cyano or carbonyl groups, or various derivatives of(As) cy these.Traube's synthesis of 4-amino-6-hydroxypyrimidinesby the condensation of amidines with a-cyano-esters i s often improved 63by the replacement of the latter reactant by its imino-ether [ A , R = alkyl ;CX = C0,Et ; CY = C(:NH)*OEt] ; the condensation of acetamidine withthe imino-ether (L) derived from ethyl a-cyanosuccinate results in a doublecyclisation, however, the pyrimazole (LI) being obtained, whereas the cyano-ester affords the expected pyrimidine. Although the formyl (hydroxy-methylene) derivative of methyl ethyl ketone affords the pyrimidine (LII,NR,-</ FX/' NEtO*$XNHHNH + ,CH*CH2*C02EtMeV&Hz Et0,C(L.1N NH.I (LI.) (LII.)R = R' = Me) on condensation with guanidine, the formyl derivatives ofthe higher alkyl methyl ketones (RGOMe) give rise to (LII, R = n-C3H,,6o A. Albert and B. Ritchie, J., 1943, 458.61 Ann. Reports, 1935, 32, 354 ; 1937, 34, 352.82 Ibid., 1939, 36, 343, 353; F. Lipmann, Ann. Rev. Biochern., 1937, 6, 19.63 2. Faldi, G. von Fodor, I. Demjh, H. Szekeres, and I. Halmoe, Ber., 1942,75, 755OPENSHAW : HETEROCYCLIC COMPOUNDS. 169iso-C,H,, n-C5H11, or n-C,H,,; R' = H), showing that in these cases theformyl ketone is R*CO*CH:CH*OH.64The majority of combinations of reactants represented in scheme ( A )yield pyrimidines when brought together in the presence of basic, or lesscommonly acidic, catalysts, but a number of failures have been reported.Neither urea nor thiourea affords pyrimidines when treated with act-dialkyl-acetoacetic esters 65 or ethyl dicyanoacetste,66 and urea also fails to condensewith ethyl propionylacetate 67 or ethyl cyanomalonate.66 Condensationof urea with ethyl ethoxymethyleneacetoacetate and of acetamidine withethyl ethoxymethylenecyanoacetate (LIII) 69 proceeds in two stages,and the cyclisation of the intermediate (e.g., LIV) may proceed in differentdirections according to the conditions employed.NMe(/\,/ r H EtO*sH M e v p \ C H-k y*Co2Et --+ NH, &C02Et*CN / N NH,(LIII.) CN Me//\(LIV.) N\~/CNOHPyrimidines having a free 2-position have previously been prepared onlyby indirect methods involving the removal of a 2-substituent; the possibleuse of formamidine for the synthesis of such compounds has now beenstudied.'O* 71 With ethyl malonate 71 or with benzeneazomalononitrile,70condensation proceeds normally to yield the expected pyrimidines, butnitromalondialdehyde 72 does not yield 5-nitropyrimidine.With substancescontaining a more reactive methylene group, such as ethyl cyanoacetate oracetoacetate, the methylene group is attacked and the products are notpyrimidines ; in the former case ethyl aminomethylenecyanoacetate (LV ;R = H, R' = C0,Et) is obtained, and analogous products (LV; R = Meor Ph, R' = C02Et) are produced with acetamidine or benzamidine in theabsence of alkali.Malononitrile reacts with formamidine, acetamidine orbenzamidine to give the pyrimidines (LVI, R = H, Me or Ph); that this134 J. M. Sprague, L. W. Kissinger, and R. M. Lincoln, J . Amer. Chem. Soc., 1941,63, 3028; G. W. Raiziss and M. Freifelder, ibid., 1942, 64, 2340; cf. W. T. Cddwell,E. C. Kornfeld, and C. K. Donnell, ibid., 1941, 68, 2188.66 T. S. Ma, Dissertation, Chicago University, 1940.o6 J. C. Ambelang and T. B. Johnson, J. Amer. Chem. SOC., 1941, 63, 1289.6 7 A. R. Todd, F. Bergel, and Karimullah, J., 1936, 1557.13* W. Bergmann and T. B. Johnson, Ber., 1933, 66,1494.6g F. Bergel and A. R. Todd, J., 1937, 364; Z. Foldi and A. Saloman, Ber., 1941,70 J. Baddiley, B. Lythgoe, and A. R. Todd, J., 1943, 386.71 G. W. Kenner, B.Lythgoe, A. R. Todd, and A. Tophem, ibid., p. 388.72 R. 0. Roblin, P. S. Winnek, and J. P. English, J . Amer. Chem. SOC., 1942, 64,74, 1126.S67.F 170 ORGANIC UH.EMISTRY.reaction proceeds by the intermediate formation af compounds (LV, R = H,Me or Ph; R‘ = CN), followed by condensation with it second molecule ofNRthe amidine, is shown by the behaviour of a-furylamidine, which withmalononitrile affords (LV; R = C,H,O, R‘ = CN) in the absence, and(LVI, R = C4H30) in the presence of sodium ethoxide, and also by thesuccessful preparation of (LVI, R = H) by the reaction of aminomethylene-malononitrile (LV; R = H, R’ = CN) with formamidine. Thus the success-ful use of formamidine, and, to a lesser extent, of other amidines in synthesesof the type (A) is dependent on the absence of a highly reactive methylenegroup in the second reactant.71Other types of synthesis of pyrimidine derivatives which have recentlybeen described include the reaction of thioacetamide 719 73 (LVII, R = SH)or of-acetiminoether 74 (LVII, R = OEt) with aminomethylenemalononitrile(LVIII, R’ = CN) or ethyl aminomethylenecyanoacetate (LVIII, R’ =C02Et) and of iminoethers with a-carbethoxyamidines 75 (LIX, It’ = Hor alkyl) .NH VNMef +RR’-R Hp-CH(LVII.) (LVIII.)NMe/\NH,3 N!,)R~NHRSf +OEtNH,The hitherto 76 difficultly accessible 4 : 6-diaminopyrimidine (=I,R = H) is readily obtained by the condensation of ethyl formate withmalondiamidine (LX), and ethyl acetate gives the corresponding 2-methylderivative (LXI, R = Me).77Xanthine (LXII) has been synthesised from methyl 5-aminoglyoxaline-4-carboxylate by treatment with potassium cyanate, followed by hydrolysisand cyclisation of the resulting ureido-ester.An attempt to extend thismethod to the synthesis of xanthine-9-glucoside failed owing to the inaccessi-bility of the required gluco~idoglyoxaline,~~ A new synthesis of adenine(LXIII, R = R‘ = H) has been achieved; 7* 5-benzeneazo-4 : 6-diamino-pyrimidine (from formamidiiie and benzeneazomalonitrile) is reduced to7 3 B.P. 546,624.7 5 Hung. Patent 126,792.7 7 G. W. Kenner, B. Lythgoe, A. R. Todd, and A. Topham, J., 1943,574.7 ) W. E. AUsebrook, J. M. Gullsnd, andL. F. Story, J., 1943, 232.74 0. Hromatka, D.R.-P. 667,990.7 6 E.Biittaer, Ber., 1903, 36,2227OPENSHAW : HETEROCYCLIC COMPOUNDS. 1714 : 6 : 6-triaminopyrimidine, which is cmvertsd by sodium dithioformate 67into the 5-thioformamido-compound (LXIV, R = R’ =r H), and this readilyoyclises on heating in water, pyridine or quinoline. This method of purinesynthesis, which appears to be general, involves the use of mild conditionsN N(LXII.)NA &\NHR’ $nIE& + 3 lIT$CH J4JNH2(LXV.)\/ x2 (LXIII.)NH2(LXIV.)only, and should be suitable for the synthesis of nucleosides, since a modelexperiment with the pyrimidine (LXIV; R = SMe, R’ = Me) showed thatcyclist-i,tion proceeds in the desired direction, producing a 9-alkylpurine(LXIII; R = SMe, R‘ = Me).79 Attention has therefore been turned 8Oto the preparation of suitable 4-glycosidaminopyrimidines, and the 4 : &didamino-compounds (LXV; R = Me or SMe, R’ = H) have been convertedinto the 4-d-xylosidamino-derivatives (LXV, R‘ = C6H90q) by applyingthe method developed by R.Kuhn and R. Strobele for the preparation ofN-glycosides in the benzene series.PZavaxok.-H. Ohle and G. A. Melkonian 8a have described a number ofderivatives of a new ring system derived from sugars, which they call Aavazole(LXVI). The tetrahydroxybutylquinoxaline (LXVII) obtained by inter-action of glucose and o-phenylenediamine 83 reacts with phenylhydrazine(LXVII.)acetate to yield 1 -phenyl-3- (d-erythro-trihydroxypropy1)flavazole (LXVIII,R = [CH*OHj’,*CH,*OH). The nature of the side chain w&s confirmed bythe usual reactionsf and on treatment with lead tetra-acetate the aldehyde(LXVIII, R = CHO) was obtained.Oxidation with chromic acid affordedthe 3-carboxylic acid, which could be decarboxylated to 1 -phenyMavazole7D J. BaddiIey, B. Lythgoe, D. McNeil, and A. R, Todd, J., 1943,383.80 J. Baddiley, B. Lythgoe, and A. R. Todd, ibid., p. 571.33 K. Maurer and B. Schiedt, Ber., 1934, 87, 1980; Ann. Reporta, 1938, 36, 318.Ber., 1937, 70, 773. aa Bar., 1941, 74, 279172 ORGANIC CHEMISTRY.(LXVIII, R = H), the structure of which was confirmed by its synthesisfrom 4 : 5-diketo- 1 -phenylpyrazoline (LXIX) and o-phenylenediamine.Flavazole itself (LXVI) has been prepared from (LXVII) and hydrazine by asimilar series of reacti0ns.~4hot dil. NsOFIr (LXVIII, R = H)The Chemistry of Biotin.The constitution of biotin (bios I1 B) (I) has now been completelyelucidated by V.du Vigneaud and his collaborators in the Cornell laboratories.The results of the earlier parts of this investigationhave already been reported,l but will be summarisedhere in order to present a complete survey.F. Kogl and B. Tonnis first isolated crystallinebiotin methyl ester in relatively pure conditionCH*[CHz14*C0~ from egg yolk. The yield was extremely small,and the high cost of the raw material and thelong and tedious nature of the concentration (1.1processes rendered the accumulation of sufficient material for structuraldetermination very difficult. The molecular formula of the methyl esterwas found to be C,,H,,03r(T~S; it had only very weakly basic properties,was dextrorotatory and showed no specific ultra-violet absorption ; thefree acid titrated as a monocarboxylic acid.3* Having proved the identityof biotin with vitamin H (the factor preventing " egg-white injury '' in rats),V.du Vigneaud, K. Hofmann, D. B. Melville, and P. Gyorgy succeeded inisolating pure biotin methyl ester from a vitamin H concentrate preparedfrom liver.s The molecular formula agreed with that of Kogl, and onhydrolysis free biotin, Cl,H1,0,N2S, was obtained in crystalline condition.'The discovery that pure biotin could be obtained relatively easily from milkconcentrates,s and the supply of considerable quantities of such concentratesco/ \ TH T HP-VH'HZS\ /84 H. Ohle and A.Iltgen, Ber., 1943, 76, 1.1 Ann. Reports, 1941, 38, 235, 249; 1942, 39, 230.2 2. physiol. Chem., 1936, 242, 43.a F. Kogl, Naturwiss., 1937, 2!5,465; Chem. and Ind., 1938,67, 49.4 F. Kogl and L. Pons, 2. physiol. Chem., 1941, 269,61.6 J . Bid. Ghem., 1911, 140,643; (with C. S. Rose), Science, 1940, 92, 62, 609.6 P. Gyorgy, R. Kuhn, and E. Lederer, J. Biol. Chein., 1939, 131, 745.7 V. du Vigneaud, K. Hofmann, D. B. Melville, and J. R. Rachele, ibid., 1941,140,8 D. B. Melville, K. Hofmann, E. Hague, and V. du Vignesud, ibict., 1942, 142,763.616OPENSHAW : HETEROCYCLIC COMPOUNDS. 173by the S. M. A. Corporation, rendered available much larger amounts ofbiotin for degradative studies, although it was still necessary to work on thesemi-micro scale.Biotin is not inactivated by ninhydrin, and is therefore not an oc-amino-acid; it contains no primary amino-group, yields no methyl iodide on treat-ment with hydriodic acid, and is unaffected by hydr~genation.~ Vigoroushydrolysis with bary% 4* l o or concentrated hydrochloric acid l1 yielded adiamino-acid (11) , C,H,,O,N,S, containing two primary amino-groups andforming an alkali-soluble dibenzoyl derivative. The presence of a cyclicurea grouping, suggested by this degradation, was confirmed by the re-synthesis of biotin by the interaction of the diamino-acid with carbonylchloride.lO The sulphur atom could not be eliminated from the moleculeby the action of alkali, hydriodic acid, zinc and hydrochloric acid, or brominewater.The suspected presence of a thio-ether linkage was confirmed by thesmooth oxidation of biotin to a sulphone,lop l1 and by the interaction of biotinmethyl ester and methyl iodide to yield a sulphonium salt ; l1 its resistanceto complete fission suggested that the sulphur atom forms part of a ring.F. Kogl and T. J. de Man,ll seeking to prove the cyclic nature of thethio-ether linkage, obtained by oxidation of biotin methyl ester and subse-quent vigorous hydrolysis a product which they described as a C,-diamino-sulphocarboxylic acid, the sulphonic acid group of which must have arisenby the hydrolysis of a cyclic sulphone; the Cornell group, however, showedthat this substance was not a sulphonic acid, but was identical with thesulphone of the diamino-acid (11), which they also prepared by an independentmethod, and which was converted by carbonyl chloride into biotin sulphone.l2Oxidation of the diamino-carboxylic acid (11) with permanganate ornitric acid afforded adipic acid.13 Biotin methyl ester was converted by theCu'rtius method into a urethane, alkaline hydrolysis of which afforded atriamine, C8H1,N,S, in which the carboxyl group of (11) is replaced by anamino-group. Oxidation of the triamine yielded no adipic acid, indicatingthat this oxidation product was derived from a side chain terminated by acarboxyl group.l* From the foregoing evidence the partial structures (111)and (IV) may be formulated. In the case of (IV), the adipic acid wouldcoC'}C3H,{ >C-[CH, I J3--C0,H(IV.)arise from the decomposition of an intermediately-formed malonic or P-keto-acid.'O<NH- C3H5 >C-[CH,I,-CO,H?c NH-} s< (111.) i s<G. B. Brown and V. du Vigneaud, J . Biol. Chem., 1941,141,85.l o K. Hofmann, D. B. Melville, and V. du Vigneaud, ibid., p. 207; Science, 1941,11 F. Kogl and T. J. de Man, 2. physiol. Chem., 1941, 269,82.l2 J . Biol. Chem., 1942, 145, 101.l3 K. Hofmann, D. B. Melville, and V. du Vigneaud, J . Amer. Chem. SOC., 1941,14 Idem, ibid., 1942,64,188; J . Biot. Chem., 1942,144,613.94, 308.63, 3237174 ORGANIC CHEMISTRY.The diamino-acid (U) reacts with phenanthraquinone to form a quinoxalinederivative (V), showing that the amino-groups are attached to adjacenbcarbon atoms. Synthetic 3 : 4-diaminotetrahydrothiophen formed withphenanthraquinone the dihydroquinoxaline (VI), converted by heat into thequinoxaline (VII).15 The absorption spectra of (V) and (VII) were almostidentical, whereas that of (VI) was different; thus (V) is a true quinoxaline,and both the carbQn atoms carrying the amino-groupsin (11) must also bearhydrogen atoms.ls The possible structures for biotin are thus limited to(VIII) and (IX), derived from (111) and (IV) respectively, since structuresin which a sulphur and a nitrogen atom are attached t o the same carbonatom are excluded by the stability of the diamino-acid (11) to hydrolytioreagents. 3 : 4-Diaminotetrahy&othiophen, like (11), was extremely re-sistant t o hydrolytic fission; l5 in contrast, the 2 : 5-diamino-compoundcould not be obtained by hydrolysis of the urethane (X), decompositionoccurring with the formation of hydrogen sulphide, ammonia and succindi-a1dehyde.l'\ / \ / / c-v YH-TH\/ \/CH, CH, CH, CH,S S(VII.)>CH*[CH,],*CO,H &H--~Hc%<i3-CHaBiotin was finally shown to possessco/ \TH THCH-CHGH, CH-[CH,kCO,H\ /S(VIII. )(X-)the structure (VIII) by two in-dependent rnethods.lG* l9 The application of a modified Hofmann exhaustivemethylation procedure to the diamino-acid (11) afforded a small yield of16 G. W. Kilmer, M. D. armstrong, G. B. Brown, and V. du Vigneaud, ibicE., 1942,16 I(. Hofmann, G. W. Kilmer, D. B. Melville, V. du Vigneaud, and H. EL. Darby,l7 G. B. Brown and G. W. Kilmer, J . Amer. Chem. Soc., 1043, 85, 1674.145, 495.ibid., p. 503.D. B. Melville, A. W. Moyer, K. Hofmann, and V. du Vigneaud, J . Bid. Chm.,V. du Vigneaud, D. B. Melville, K. Folkers, D. E. Wolf, R. Mozingo, J. C.1942,146,487.Keresztesy, and S. A. Harris, i b i d , p. 476OPENSHAW : HETEROCYCLIC COMPOUNDS. 175a crystalline nitrogen-free aoid, which was shown to be identical with6-(2-thienyl)vaJeric aoid (XI), synthesised by the route shown.l*(1) Me,SO,,NeOH aq. -- p f z y H Z(W p-iH --+ 11 ~~*[CH,I,*CO,H (XI.) CH, CH*[CH,]4*C0,W (8) CO~C- HC* \/S \ /SThe removal of sulphur from organic sulphides by means of Itaneynickel was studied,lg* 20 and thc method, having been found satisfactoryin model experiments on the semi-micro scale, was applied to biotin methylester. The sulphur atom was replaced by two hydrogenbatoms, dethiobiotinmethyl ester (XI1 or XIII) being obtained in good yield; on hydrolysis, adiamino-carboxylic acid (XIV or XV) was produced, which contained oneC-methyl group (Kuhn-Roth), and which on oxidation with periodic acidafforded pimelic acid ; both these facts support the structure (XIV). Withphenanthraquinone it yielded a quinoxaline (XVI) which was opticallyinactive [the corresponding derivative from (XV) should be optically active],and which was identical with the quinoxaline derived from <q-diaminopel-argonic acid (XIV) synthesised by the route shown. The use of the quinox-alines facilitated comparison between the degradative and synthetic products,owing to the destruction of the molecular asymmetry.co CO/ \NH / \ TH NHCH, CH,*[CH2]4*C0,Me(XII).),cH--~H (XI11 )\CH*[CH2]3*C0zMeQH-CHCH3 /CH3CH3*CH(NHz)*CH(NH,)*[CH,],*C0,H /=\/=\(XIV.) \-/ \\ //\-/-/-\ (xvr.)N NCH3*CH(NH,)*CH(NH,)*CHMe*[CH,],*C0,H(XV.)3 stages Br*[CH,],*CO,Et + CH,*CO*CH,*CO,Et -+ CH,*CO*[CH,],*CO,Et(1) EtON0,HCl H,, Ni, liq. CH,*C( :NOH)*C( :NOH)*[CH,]5*CO,Et (XIV) (2)NH,OH ’20 R. Mozingo, D. E. Wolf, S. A. Harris, and K. Folkers, J. Arner. Chem. SOC., 1943,65, 1013176 ORGANIC CHEMISTRY.Note added in prooi.-On the basis of a stepwise degradation to p-carboxy-y-methylbutanesulphonic acid (XVII), F. Kogl and his collaborators 21 haveproposed the structure (XVIII) for biotin isolated from egg-yolk. Since thedegradation of liver biotin to adipic acid is inconsistent with this formula-tion, and since there is not complete agreement between the physical pro-perties of the biotins and biotin methyl esters isolated by the Utrecht andthe Cornell group respectively, F. Kogl and E. J. ten Ham2, undertookthe isolation of biotin from a liver concentrate. The material obtainedagreed closely in its physical constants and its physiological activity withthat isolated by the American workers, but it was not identical with theisomeric biotin of egg-yolk, and its activity in the yeast growth test wasapproximately twice as great. The structural differences between the twobiotins are remarkable in view of their similar biological properties.NH/ \CHMe,*CH( CO,H)*CH,*SO,H VO flH--VH*CHMe,(XVII. ) NH CH CH,\ / \ / (XVIII.)CO,H*CH SH. T. 0.21 F. Kogl, J. H. Verbwk, H. Erxleben, and W. A. J. Borg, 2. physiol. Chern., 1943,22 Ibid., p. 140.279, 121

ISSN:0365-6217    

DOI:10.1039/AR9434000098

出版商:RSC    

年代:1943

数据来源: RSC

摘要:

BIOCHEMISTRY.1. NUTRITION.Vitamin C and the Healing of Wounds.SOME interesting observations have accumulated during the past few yearson the influence of ascorbic acid on the repair of wounds. The implicationsare of both theoretical and practical importance, and a brief review of themore significant findings seems to be due.Experimental Studies on Guinea Pigs.-One of the first to record thefact that a deficiency of vitamin C in guinea pigs causes delay in the healingof experimentally induced wounds was B. Ishido.1 Observations of thiskind began oq this purely descriptive or qualitative plane; but later experi-mentation has introduced the quantitative element by measuring thetensile strength of the healing wound under varying conditions. Thisdevelopment has not only greatly increased the scientific value of thefindings but has also shown that the implications are more immediatelyapplicable to medical and surgical science than was at first realised.Per-haps the simplest way of summing up the results, in a single sentence,would be to say that it has been clearly demonstrated that the tensilestrength of the healing wound diminishes in proportion with the extent ofthe deficiency of the vitamin. From this point of view, varying degreesof “ partial deficiencies ” of vitamin C are seen to be of consequence, theeffect on the tensile strength not being limited to the last stages of scurvyor indeed to animals suffering from a complete lack of vitamin C. Valuablestudies of this kind have been carried out by T.H. Lanman and T. H.Ingalls,2 by M. K. Bartlett, C. M. Jones, and A. E. Ryan and by G. B ~ u r n e . ~Vitamin C, Gastric Disease, and Wound Healing in Man.-L. J. Harris,M. A. Abbasy, J. Yudkin, and S. Kelly observed that low reserves ofvitamin C were commonly found in patients suffering from gastric or duodenalulceration and similar ailments. The explanation was that the diets whichwere prescribed by medical advice in such cases, while they were designedto be low in any irritating residue or roughage, happened also to be frequentlydeficient in vitamin C as well. In consequence cases of scurvy have notbeen unknown in patients kept on such special diets. But, moreover, asH. E. Archer and G. Graham observed, these patients often exhibited anunsatisfactory healing of surgical wounds, as after an operation for duodenalor gastric ulcer.It has since become customary to add synthetic ascorbicacid (or alternatively strained citrus fruit juice) to “ gastric diets,” withVirch.ow’e Arch., 1923, 240, 241.Ann. Surq., 1940, 111, 1 ; New England J. Med., 1942, 226, 469, 474.Lancet, 1942, ii, 661 and literature there cited; also Proc. SOC. Esp. Biol., Cam-bridge, September 1943. The first-mentioned reference gives a very full review of thewhole question of vitamin C and wound heeling, which may be consulted for furtherdetails.Amer. J . Surg., 1937, 105, 616.Lancet, 1936, i, 1488. * Ibid., 1936, ii, 364178 BIOCHEMISTRY.the results not only that any danger of scurvy is obviated, but also thatwhen surgical treatment is necessitated the danger of unsatisfactory post -operative healing of the wound is said to be mmimised.Vitamin C Requirements and the Tensile Xtrength of Wounds in Man.-We have a fairly accurate knowledge of the relative requirements of guineapigs and man for vitamin C.The minimum dose needed to protect eachspecies from scurvy can therefore be defined reasonably closely. Now, it isfound bhart for optimal healing and tensile strength of wounds in g u h apigs mveral times more vitamin C are needed than the minimum dmerequired for mere protection against the gross symptoms of scurvy. It isthus possible to ames~ by calculation the amount of vitamin C which ahouldbe needed by a man for adequate repair of wounds.On this basis G. Bourne 7calculates that 40 mg. of the vitamin may be required each day to secureadequate healing of wounds and that less than 20 rng. may produee a scapof low tensile strength. These conclusions seem in keepirrg with theobservations of M. K. Bartlett, C. M. Jones, and A. E. Ryano,s who havegiven evidence that when the plasma, vitamin-C level in man fa& below0-2 mg. per 100 ml. there is likely to be a reduced tensile strength in healingwounds.Wound Healing in Experimental LScurvy in iWan.4. H. Crandon, C. C.Lund, and D. S. Dill described an experiment in which a human volunteerwas kept for many weeks on a diet deficient in vitamin C. A wound madeafter tihree months appeared to heal well, but one made after six monthscompletely failed to heal.It has been argued by some writers that, sincethere was apparently good healing after three months without any vitamin C,a shortage of this factor in the diet can have but little practical significance,a t any rate until an advanced stage of depletion is reached. Aa againstthis, however, the evidence cited in the previous paragraph, and furtherfacts to be mentioned later, musf be considered. The conclusion seems tofollow that even with apparently sakisfactory superficial healing (as afterthe three months in Crandon’s experiments; and also in some similarobservations by F. W. Fox lo) the tensile strength of wounds would pm-sumably be impaired in such ciroumstances 8s these, when the intake of thevitamin is low. As Bourne has remarked, it is the holding power which isthe really relevant point as fax as normal surgery is concerned. We mayadd also that, apart fiom the special considerations of surgery, the stateof normal healthy nutrition to aim at, for the population as a whole-andmom particularly for the fighting services-should surely be that in which,if an injury should be sustained, there ie no danger of its inadequate repairbecause of the past intake of vitamin C having been low.The desirableintake for this purpose, according to the conclusions already given, comesout a t about the same as the “ requirement ” propwed some years ago bythe League of Nations Commission, vix., 30 mg. per day; and ia therefore7 J. Physiol., 1943, quoted by Lancet, 1942, ii, 661.8 New England J.Med., 1942, 226,474.9 Ibid., 1940, 223, 363. 10 Brit. me&. J., 1941, i, 311HAR,RIS : NUTRITION. 179definitely higher than the minimum dose of about 7-10 mg. whkh sdiiceato protect from scurvy, and which some biochemists have h e n inclined toconsider a safe and adequate allowance for the average adult.S u ~ e ' d AppZications.-We know that many individuals habitually takeless than the 30 mg. of ascorbic acid daily, recommended as the standardrequirement by the League of Nations Commission, or than the 2 0 4 0 mg.cdoulated by Bourne to be needed to secure optimal tensile strength ofwounds. Correspondingly, the amount of ascorbic acid in the blood plasma,is often below the value of 0.2 mg.% found by Bartlett to be desirable ifrisk of a diminished tensile strength is to be precluded.What evidence isthere, then, that vitamin C has the fairly obvious use in surgery that thecleconsiderations would seem to imply? Various papers published of latemaintain that vitamin C has indeed an important practical application ofthis kind. For hstance, C. C. Lund and J. H. Crandon l1 found that post-operative re-opening of wounds occurred most commonly in subjects havinga, low level of vitamin C in the plasma. In explanation of such a finding,A. H. Hunt l2 records that an examination of surgical wounds post mwkmbrought to light the fact that there had been a poor formation of mhgenin those patienfs whose vitamin-C intake was known to have been low.This picture, an unsatisfactory laying-down of collagen fibres, is the samethat seen in guinea pigs suffering from sub-scurvy and helps us to under-stand the underlying nature of the mechanical defect in question.Variousclinical trials have been undertaken to test the effect of pre-medication withvitamin C before surgical operation, and some encouraging results amclaimed. A. H. Hunt l2 states that the administration of vitamin C broughfabout tb reduotion by 76% in the incidence of eventration and disruption ofsurgicaJ mounds. Among others, Bartlett and his colleagues3 also speakof the good results of premedication as a routine measure for preventingpost-operative herniae. A professor of surgery in the University of Londonrecords that early in the war, unexpected trouble was experienced withwounds failing to heal.It was not realised at Gsst that a drop in intake ofvibamin C had occurred as a result of war-time conditions. When vitamin Cwas administered as a routine, however, the position was restored.13Vitamin C and Bone Injuries.-Since it is recogniaed that vitamin C ieneeded for normal osteogenesis, it is not surprising that an animal sufferingfrom a deficiency of the vitamin experiences difficulty in effecting adequaterepair of a fracture or other bony injury. J. Hertz l4 and Bourne 4 andothers have described the delayed healing of fractures observed when guineapigs are kept on diets low in vitamin C. The underlying abnormalities area scarcity of collagen and an impaired function of fibroblasts and osteoblasts.In parallel with his work on the heallng of wounds in the soft $issues, Bournehas shown that the degree of healing in an injured bone is proportional tol1 An,.Burg., 1941, 114, 776.l3 J. Paterson Ross, Proc. Xoc. Exp. Biol., Cambridge, September, 1943.l4 " Studies on fhe Heeling of Fractures, with Special Refwrence to the Significancel2 Brit. J. Surg., 1941, 28, 436.of the Vitamin Content of the Diet," Copenhagen, 1936180 BIOCHEMISTRY.the adequrtcy of the vitamin supply, " partial deficiencies " being again ofconsequence and not only deficiencies so severe as to produce scurvy. Bycomparing the requirements of humans and guinea pigs (cf. supra) hecalculates that 40 mg. per day are needed by an adult man for the optimuniformation of bony trabeculae, and that an intake of less than 20 mg.mayseriously retard their formation.A remarkable condition of the bones in guinea pigs, kept for long periodson diets partially deficient in vitamin C, and characterised by hyperostosis,ankylosis, and arthrosis, has been described by E. Kodicek and P. D. F.Murray.15 The possible analogy with similar conditions seen in man shouldbe worth exploring.Theoretical Explanation.-The observed influence of vitamin C in pro-moting the healing of wounds and fractures can probably be explained onthe basis of the currently accepted theories of vitamin43 action, namely,(a) that the vitamin is needed for maintaining the functional activity andintegrity of formative cells,16 1' and (b) that in its absence there is a faultyformation of intercellular jellying substance.18 These two theories can beregarded as complementary and are not contradictory.It may be remem-bered that from their study of the effects of deficiency on dental and perio-dontal structure, E. W. Fish and L. J. Harris l7 concluded that with increas-ing degrees of deficiency there was increasing failure in the functionalactivities of the odontoblasts, ameloblasts, osteoblasts (cells laying downdentine, enamel, bone), and other similar formative cells. With a partialchronic deficiency of vitamin C there occurred a remarkable, irregular over-growth of amorphously formed dentine, whereas in acute total deficiency nonew tissue was laid down. Probably the irregular hyperostosis now describedby Kodicek and Murray15 may be given the same explanation as thatoffered by Fish and Harris l7 for the rather analogous overgrowth of irregulardentine in hypovitaminosis.Whereas in avitaminosis there is a completeloss of the specialised cell activity and hence failure to lay down the newtissues, in hypovitaminosis there is only partial loss of formative functionand the new tissues laid down are irregularly organised. It seems probablethat the influence of vitamin C in osteogenesis and in the repair of woundscan be explained along the same lines.L. J. H.2. ANTIBACTERIAL SUBSTANCES PRODUCED BY BACTERIA AND FUNGI.Introduction.The present considerable interest in the chemotherapeutic possibilities ofantibacterial substances produced by bacteria and fungi is of recent origin,but the idea of using such substances for the treatment of bacteria1 infectionslC, Nature, 1943, 151, 395.l6 L.J. Harris, Brit. med. *7., 1933, 2, 367.l7 E. W. Fi4h and L. J. Harris, Phil. Trans., 1934, B, 233,489.18 S. B. Wolbach and P, R. Howe, Arch. Puth., 1926,1, 1CHAIN AND FLOREY : ANTIBACTERIAL SUBSTANCES. 181is quite old. S. A. Waksman 1 and R. J . Dubos and R. D. Hotchkiss havepointed out that bacterial antagonism was noticed by Pasteur, who thoughtof the possibilities of using this phenomenon for curative purposes. Referenceshould be made to Waksman’s article for the numerous attempts dating from1885 to employ bacterial products for therapeutic purposes. Of theseattempts, that of R.Emmerich and 0. Low- has attracted the most notice.They tried to use the antibacterial substances produced by Ps. ~ ~ O G ~ Z T W Zagainst, in particular, B. anthrucis infections. Their preparation was knownas “ pyocyanase ” and appears to have been sold in Germany till a t least aslate as 1936.4 Its efficacy is, however, very doubtful. A. Gratia, and S.Dath noticed that culture filtrates of certain actinomycetes had the powerof dissolving some pathogenic organisms. Though they did not use theirpreparation directly for the treatment of infections, Gratia prepared“ mycolysates ” of organisms such as staphylococci and maintained thatvaccination with these solutions was beneficial in human diseases. A.Fleming noted the existence of a bacterial inhibitor produced by the mouldPeniciZZium notaturn, which he termed “ penicillin.” He investigated theantibacterial properties of his penicillin-containing broth medium in somedetail and suggested that it might form a useful “ antiseptic’’ dressingfor wounds,8 but this was not followed up. Weiland* suggested that theantibacterial substance produced by certain types of B. mesentericus shouldbe as effective as “ pyocyanase,” though he does not appear to have at-tempted to isolate or use it. R. J. Dubos isolated from €3. brevis an anti-bacterial material which was found later to contain two antibacterial sub-stances, gramicidin and tyrocidine. The crude mixture of gramicidin andtyrocidine, called tyrothricin, has been tried fairly extensively as an applicationto superficial wounds infected with susceptible organisms, but its toxicityprecludes its use parenterally.l0 Some success attended its use, but diffticul-ties were encountered owing to its insoluble nature.Chain et ~2.11 reportedthe results of a fresh investigation into the possibilities of the isolation ofpenicillin and the study of its properties. They obtained from culturefiltrates of PeniciZZium notatum a preparation containing penicillin in a stableform and showed that it not only possessed a high antibacterial activity andinhibited the growth of many pathogenic bacteria but was remarkably non-1 Baed. Rev., 1941, 5, 231.a Tram. Coll. Phys. Philadelphia, 1942, 10, 11.2. Hyg., 1899, 31, 1; R. Emmerich, 0. Low, and A. Korschun, Zentr.Bakt. Par.,1902, 1 Abt. Orig., 31, 1.4 P. Weiland, Zentr. Bakt. Par., 1936, 1 Abt. Orig., 136, 451.6 Compt. rend. SOC. Biol., 1924,91,1442; 1926,92,461, 1125; 93,451 ; 1926,94,1267.6 Ibid., 1930, 104, 1058; Bull. Acad. roy. Mkd. Belg., 1934, 14, 285.7 Brit. J . Exp. Path., 1929, 10, 226.9 J . Exp. Med., 1939, 70, 1, 11.lo C. H. Rammelksmp, War Medicine, 1942, 2, 830; J . Clin. Invest., 1941,20,433;W. E. Herrell and D. Heilman, ibid., p. 583; E. B. Schoenbach, J. F. Enders, cmdJ. H. Mueller, Science, 1941, 94, 217.11 E. Chain, H. W. Florey, A. D. Gardner, N. G . Heathy, M. A. Jennings, J. Om.Ewing, and A. G. Senders, Lancet, 1940, ii, 226.J . Path. Bact., 1932, 35, 831182 BIOUHEMISTRY.toxic. They demonstrated on mice the potentialities of penicillin as achemotherapeutic agent againet systemic bacterial infections, Later,12penioillin was employed successfully on man.Following these investigations it is fair to say that chemical interest inthese substances is now largely conditioned by the thought that they maybe of importance in medicine.It is certain that many organisms, bothbacterial and fungal, produce substances active against pathogenicbac3teria.l~~~ Waksman has suggested that the antibacterial substancesproduced by moulds and bacteria should be called antibiotics.l‘, footnob*p.The term has been used in this sense in the present review.The natural antibiotics can be divided into two classes : (1) Antibiotimwhich react with protoplasmic constituents and kill both bacterial andanimal cells.It would be convenient to restrict the term “antiseptic”to this type of substance. The antibiotics of the ‘‘ antiseptic ” type can besubdivided into those which are active against all types of pathogenicorganisms, both gram-positive and gram-negative, and those which exert aselective action, usually against gram-positive organisms (e.g., gramicidin,acfinomycin A, citrinin). The cause of this selectivity is not yet fullyunderstood. The selectivity may not be absolute; it has been shown thatgramicidin acquires strong bactericidal activity against gram-negativebacteria in the presence of protamines.15 The explanation offered for thissensitisation ” of gram-negative bacteria is .that protarnines removephospholipids, which are known t o inhibit the antibacterial action ofgramicidin. This class of ‘‘ antiseptic ” antibiotics is useless as a source ofnew chemotherapeutic substances for general adminiatration.It may,however, provide substances of use in local application, though even for thispurpose antibiotics belonging to the following class are clearly preferable.(2) Antibiotics which react with substances having a speci$c signijicancein the bacterial cell only. Some of these substances do not kill bacteria evenin very considerable concentrations, merely arresting their division. Theterm “ bacteriostatic ” has been suggested for this class of antibiotic.16 Forthe distinction between “ antiseptics ” and ‘‘ bacteriostatics ” the con-centra&ion at which only the bacteriostatic effect is observed is of primaryimporhum, shae many antiseptics have a merely bacteriostatic and not akilling action, when used in low concentrations.The bacteriostatics so far found are predominantly active against gram-positive bacteria.They may be expected to be relatively non-toxic to animalcells. It is in this class of antibiotics that one can hope to find newchemotherapeutic agents €or general administration and therefore of value12 E. P. Abrahrun, E. Chain, C. M. FIeteher, H. W. Florey, A. D. Gardner, N. G.Eeatley, and M. A. Jenningq Lancet, 1941, ii, 177.la W. H. Wilkins and G. C. M. Harris, Brit. J . Exp. Path., 1942, 23, 166 ; 1943, 24,141.14 S. A. Waksmrtn, E. S. Homing, M. Welsch, and H. B. Woodruff, Soil Science, 1942,54,281.16 B.F. W e r , R. Abrams, A. Dorfman, and M. Klein, Science, 1942, 96,428.16 A. D. Gardner and E. Chain, Brit. J . Ezp. Path.. 1942, 23. 123.(CHAIN AND FLOREY : ANTIBACTERIAL SUBSTANCES. 183in the treatmenk of systemic infections. It should be clearly undertatadthat any substance to be umd chemothmpeutkally must be so little tQxiothbbt a concentration sufficient to inhibit the gMswfh of; susceptible organismscan be maintained without hamn in the blood and tissue fluids for days andeven weeks. The fact that an antibacterial subatance can be used locallydoes not furnish evidence that i% can be used for general administration.R,ela,tively early in. an investigation it is possible to know whether anantibacterial substance has any chemotherapeutic prospects.The simpIestteat so far devised depends on the observation of bacterial respiration (ofstaphylococci or B. coli) in the Barcroft-Warburg apparatus in the presenceof the antibiotic. If respiration is rapidly abolished by the addition of theantibiotic to a final concentration of about 1 : 1000, one em say withcertainty that, since the organisms have been killed at this concentration, thesubstance is an antiseptic which will be toxic to animal tissues. If, however,a, preparation known to be strongly antibacterial produces little or no effecton the respiration, there is a good chance of the substance being importantfrom a chemotherapeutic point of view.(1) The toxiciby of theantibacterial substance t o leucocybes.12 When there is a wide gap bebweenthe concentration toxic to leucocytes and the dilution a t which the substr~a3wis completely bacteriostatic, there is a good chance of the substance beinguseful, a t least for local application.(2) The effect of blood, pus and tissue extracts on the bacteriostaticactivity. It is a serious disadvantage if these fluids depress the activity.The inhibition of antibacterial activity may be due to the chemical combinration of the active subsfance with a tissue constituent or to an inhibitorymeohanism simhr to that of p-aminobenzoic acid for the sulphonrtmides.The mice shouldtolerate the injection of a t least several milligrams of the mtibacteridsubstance.It is likely that any therapeutioally active substance will be t o a l a wextent excreted unchanged or little changed in the urine, since it may beexpected not to combine with the tissue cells.Oiily antibiotics which pass these biological teshs can be expected to beeffective as general chemotherapeutic agents and to be worth further investi-gation with mouse protection tests.Clearly i t is impossible to forecast thovalue of any antibiotic for chemotherapeufic purposes until it has beenpurified a t least sufficiently for the above-mentioned biological tests to becarried out.In addition to the chemical investigation of the antibiotics themselves, abiochemical problem is involved in the elaboration of media for the growth ofthe responsible bacteria or fungi. It is known thak the medium plays anessential part, for on some media good growth of a fungus oan be obtainedbut no antibiotic, while on other8 there is a poor growth but active substancesare produced.In addition, chaages in the composition of the medium mayinduce a fungus t o produce a different antibacterial substance. TheFurther observations should be made on :(3) The toxicity to mice when injected intravenously184 BIOCHEMISTRY.elaboration of these media has a t present much in common with cookery,and there is a wide field here for biochemical enquiry.Another field of biochemical enquiry which has as yet received littleattention is the study of the mode of action of the bacteriostatics, includingthe interesting phenomenon of the ability of susceptible bacteria to acquireresistance to increasing concentrations of many of these substances.Attention a t the present time is being directed almost exclusively to theantibacterial effects of antibiotics. Several antibiotics are fungicides 1 andmay be of use in the treatment of plant diseases.It is possible that theunusual biochemical mechanisms of the moulds and bacteria mayproduce substances active against protozoal and other infections of man.Only a negative result has so far been reported.16aAntibiotics produced by Bacteria." Pyocyanase."-Among the first antibacterial substances produced bybacteria to be studied chemically were those produced by Pa. pyocyunea.Concentrates of old culture-filtrates were found to contain substancesbactericidal to a number of gram-positive and gram-negative bacteria andcapable of lysing thick suspensions of V .cholerct! and B. anthracis; theseproperties were attributed to the action of a bacteriolytic enzyme termed~yocyanase.~ Recent investigations into the nature of pyocyanase havemade i t clear that the antibacterial activity of old culture-filtrates of Ps.pyocyuneu is due to the presence of several substances, none of which is ofenzymatic nature.17 The blue dye pyocyanine and a yellow degradationproduct of this substance, a-hydroxyphenazine, are bactericidal and an as yetchemically undefined oil of acidic nature, soluble in chloroform and alcohol,is bacteriolytic. It brings about lysis, accompanied by gel formation,of thick suspensions of V . cholerae in dilutions as high as 1 : 10,000.Pyocyanine, like many basic dyes, is strongly bactericidal and also verytoxic.17P18 The a-hydroxyphenazine, though less toxic, has a much lowerantibacterial activity; it is chemically unstable and of low solubility.Toolittle is as yet known about the physiological, biological and chemicalproperties of the lytic substance to assess its value as a disinfectant; it iscertainly too toxic for the treatment of systemic infections.Gramicidin and Tyrocidine.-Dubos 91 l9, 20# 21 and his collaborators haveshown that filtrates of a peptone culture of B. brevis, an aerobic spore-bearingorganism originally isolated from the soil, contain antibacterial substances.The antibacterial material can be obtained either in a protein fraction, inwhich it is non-dialysable, soluble in water but insoluble in organic so1vents,21 9166 H.J. Robinson, J . Pharm. Exp. TheTap., 1943, 77, 70.1 7 (a) H. 0. Hettche, KEin. Woch., 1933, 12, 1804; ( b ) idem, 2. Immun., 1934, 83,499; (c) R. Schoental, Brit. J . Exp. Path., 1941, 22, 137.10 J. F. Fazekas, H. Colyer, S . Nesin, and H. E. Himwich, Proc. SOC. Exp. Biol. Med.,1939, 42, 446.19 R. J. Dubos and C. Cattaneo, J . Exp. Med., 1939, 70,249.90 R. J. Dubos and R. D. Hotchkiss, ibid., 1941, 73, 629.21 R. D. Hotchkiss and R. J. Dubos, J . Bhl. Chm., 1941, 141, 156CHAIN ANT) FLOREY : ANTIBACTERIAL SUBSTANCES. 185or in a protein-free form in which i t is dialysable, insoluble in water butsoluble in organic solvents.~g~ 20 The water-soluble form is obtained byacidification of the culture medium and extraction of the precipitate withneutral buffer.The form soluble in organic solvents but insoluble in water isobtained by extraction of the acid precipitate with alcohol. The alcohol-soluble fraction has been termed tyrothricin;23 apparently it is present inthe original culture filtrates in some combination with proteins, from whichi t can be liberated by means of proteolytic en~ymes.1~1~ Tyrothricincontains two antibacterial substances, gramicidin and tyrocidine, both ofwhich have been obtained in the crystalline state.22 Both substances arepolypeptides resistant to the action of the ordinary proteolytic enzymes.Though of similar chemical constitution, gramicidin and tyrocidine havedifferent chemical and biological properties.Gramicidin,21 recrystallisedfrom acetone, melts sharply a t 230°, has a low [E]Y of + 5' in 95%alcohol, is soluble in the lower alcohols, acetic acid and pyridine, moderatelysoluble in dry acetone and dioxan, almost insoluble in water, ether andhydrocarbons. It contains no free amino- or carboxylic groups but gives acrystalline flavianate and r~fianate.2~. 25,26 On acid hydrolysis, 2-tryptophan,d-leucine, alanine and a 1 : 2-hydroxyamino-compound which is not ana-amino-acid have been 0btained.~~.2~ Quantitative chromatographicanalysis on silica gel columns of the acetyl derivatives of the amino-acidmixture obtained after acid hydrolysis of gramicidin 28 (partition chromato-graphy technique of A.J. P. Martin and R. L. M. Synge 2') shows that thegramicidin molecule contains 6 residues of leucine (mainly the d-isomer)and E-tryptophan, 5 of valine (optical configuration uncertain), 3 ofZ-alanine, 2 of glycine and 2 of the hydroxyamino-compound (isoserine 1 ) .The minimum molecular weight calculated from the analytical data is 2790,i.e., gramicidine is considered to be a cyclo-peptide with 24 amino-acidresidues.28 Molecular weight estimations by various methods givefigures from 600-3000.24~ 25,2G The presence of amino-acids of thed-configuration in hydrolysates both of gramicidin and of tyrocidine wasdemonstrated by the fact that oxygen uptake and ammonia liberation tookplace in the presence of the kidney enzyme d-amino-oxidase, which oxidisesspecifically amino-acids of the d-config~ration.~~ Tyrocidine is a basicpolypeptide which was crystallised as the hydrochloride.It melts unaharplya t 240' (decomp.), has [a]r - 101' in 95% alcohol, is moderately solublein methyl and ethyl alcohols, acetic acid and pyridine, sparingly soluble inwater and acetone and insoluble in ether and hydrocarbons. On acidhydrolysis, Z-tryptophan, tyrosine, phenylalanine, alanine, a dicarboxylic22 R. D. Hotchkiss and R. J. Dubos, J . Biol. Chem., 1940, 133, 791, 793.23 Idem, ibid., 1940, 138, 803.2 5 H. N. Christensen, R. R. Edwards, and H. D. Piersms, ibid., p. 187.28 M. Tishler, J. L. Stokes, N. R. Trenner, and J. B. Conn, ibid., p. 197.2 7 (a) A. J. P. Martin and R. L. M. Synge, Biochem.J., 1941, 35, 1358.28 A. H. Gordon, A. J. P. Martin, and R. L. M. Synge, Biochern. J . , 1943,37,86.2Q F. Lipmann, R. D. Hotchkiss, and R. J . Dubos, J . B i d . Chem., 1941, 141, 163.24 R. D. Rotchkiss, ibid., 1941, 141, 171.( b ) A. H.Gordon, A. J. P. Martin, and R. L. M. Synge, ibid., 1943, 37, 79186 BIOCHEMISTRY.amino-acid, ammonia, and nitrogenous substances of undefined natureprecipitable by phosphotungskic acid were 0btained.8~- 25 Gordon, Martin,and Synge, using their partition chromatography technique, have isolatedand identiffed (in the form of their acetyl derivatives) the following amino-acids from acid hydrolysis of tyrocidine : phenylalanine (predominantlythe &-isomer), I-leuoine, E-valine, I-proline, E-tyrosine, Z-glutamic acid,Z-ornithine, I-aspartio acid, tryptophan (optical configuration not deter-rnined).ab No alanine was found.Qramioidin is very aotive againstpractically all gram-positive bacteria with the exception of the aoid-fastorganisms, inhibiting their growth in concentrations of fractions of perC.C. It has no effect on most gram-negative bacteria, with the exceptionof gonocooci and meningoc~cci.~s~ 30 Tyrocidine possesses &th-&th of theactivity of gramicidin but inhibits both gram-positive and gram-negativebacteria. Gramicidin is stated to have a predominantly bacteriostaticaction, tyrocidine a, bactericidal aotion. Tyrooidine inhibits immediately,completely and irreversibly the respiration of streptococcal and shphy-lococoal suspensions.The effeot of gramicidin on the respiration of staphy-loeoaoal suspensions is more complex.30a In the presence of ammonium ions,it depresses the respiration of staphylocooei; in tho presence of phosphateions, it oauses an inorease of their oxygen uptake which may last for morethan 2 hours; this stimulation is then followed by a considerable inhibitionof the respiration. Almost complete inhibition of Eerobic glyoolysis ofsuspensions of lactobaoillus by gramicidin has been reported.81 Bothgramioidin and tyrocidine are hzmolytic ; hBmolysis by gramicidin is slowand does not oocur in the presence of 1 yo glucose solution ; that of tyrocidineis immediate and is not affected by glucoae.e0n3ae33 Serum inhibits theh~molysis.~3a Tyrocidine has a lytic effect on many baoteria ; gramicidincauses no bacteriolysis.2.20 Gramioidin has little effect on the respirationof white blood cells,2 whereas tyrocidine causes complete inhibition ofrespiration and disintegration of the cells.Gramicidin is toxio to sperma-tozoa, whose motility is destroyed in a dilution of 1 : 1O,OOO,OOO34 and tocells in tissue 0ulture.~4~ Both gramicidin and tyrocidine are surface-active substances, their biological activity probably being at least to ~omeextent due to this property. Tyrocidine precipitates proteins and itsantibacterial activity is therefore greatly diminished in the presence of tissuefluids. Gramicidin has no marked effect on proteins, but its antibacterialactivity is neutralised by phospholipids of the eephalin type,2D ws31 BO that ittoo suffers some reduction of activity in the presenue of tissue fluids.Both290 A. H. Gordon, A. J. P. Martin, and R. L. M. Synge, Biochern. J., 1943, 57, 313.30 E. B. Schoenbaoh and L. R. Seidman, Proo. Sw. Exp. Biol. Med., 1842, 89, 108.30a R. J, Dubos. R. D. Hotchkiss, and A. F. Coburn, J . Biol. Chem., 1943, 146, 421.B 1 Z. Baker, R. W. Harrison, and B. F. Miller, J. Exp. Med., 1941, 74, 621.32 D. Heilman and W. E. Herrell, Proo. Xoc. Exp. Biot. Msd., 1941, 46, 182.33 C. H. Rammelkamp and L. Weinstein, ibid., 1941, 48, 211.33a F. C. Mann, D. H. Heilman, and W. E. Herrell, dbid., 1943, 68, 31.d4 G. Henle and C. A. Zittle, ibid., 1941, 47, 193.346 W. E. Herrell and D. Heilman, Anzer. J . Med. Sci., 1943, 206, 167CHAIN AND F'LOREY ! ANTIBACTERIAL SUBSTANOES. 187gramicidin and tyrocidine are very toxic when injected intravenously intomice and dogs,*#35P35a which is not surprising in view of the fact that theyboth combine with vital cell constituents.Neither gramic'ldin nor tyrocidineprotects mice against systemic infeotions with even the most sensitivebacteria.mD3h9 S6 Injected a t the site of the infection, gramicidin protectsmice against pneumococci ;mI 35a these are, however, essentially in &tro oondi-tions. Successful results are reported from the application of tyrothricinsolutions to infected surfaoes or cavities in man 10 and in the treatment ofbovine maatitis.37 In many of their physicochemical and biological propertiesgramicidin and tyrocidine resemble closely the anionic and cationic deter-gents.e~*1~38n38cr The basic tyrocidhe has the properties of a cationic deter-gent, being active against both gram-positive and gram-negative bacteria ;gramicidin resembles the anionic type which acts predominantly againstgram-positive bacteria.The mode of action of the detergents on bacteriai s not fully understood,15* 31p38B 39 but there seems little doubt that the anti-bacterial activity of gramicidin and tyrocidine has its cause in similar factors,probably acting in combination, among which may be denaturation ofproteins 39 and lipoproteins and reactions with phospholipids. The viewhas been stated that tyrocidine is it general protoplasmic poison, whereasgrmnicidin has a more specific effect on certain reactions in the bacterial cellmetabolism.2sm It seems to the reviewers, however, that both gramicidinand tyrocidine fall into the class of antiseptics and should be regarded asgeneral protoplasmic poisons, since both substances have been shown tocombine with vital cell constituents occurring in all types of cells.H 1 .-An antibacterial substance active against gram-positive bacteriahas been isolated by Hoogerheide from an aerobic spore-forming organismand has been termed H 1.40ae*B Its chemical and biological properties leavelittle doubt that i t is identical with or very closely related to gramicidin.21Other Antibacterial Substances p o d w a by Spore- beuriny AerobicOrgunisms.-Many strains of the common spore-forming bacteria produoesubstances active against C.diphtherice, staphylococci and, in some cases,against gram-negative bacteria such as B. coZi.4B41- 43v43n4* Relatively littlew C. M. MacLeod, G. S. Mirick, and E. C. Curnen, Proc. SOC. Exp. Riol. Med., 1940,43,461.3b H. J. Robinson and 0. E. Graessle, J . Pharm. Exp. Therap., 1942, 76, 316.s6 R. J. Dubos, Ann. intern. Med., 1940, 13, 2025,s7 R. B. Little, R. J. Dubos, and R. D. Hotchkiss, J . Amer. Vet. Med. Assoc., 1941,38 2. Baker, R. W. Harrison, and B. F. Miller, J . Exp. Med., 1941, 73, 249; 1941,3*a D. Heilman and W. E. Herrell, Proc. SOC. Exp. Biol. Med., 1941, 47, 480.39 R. Kuhn and H. J. Bielig, Ber., 1940, 73, 1080.4O (a) 5. C. Hoogerheide, J . Fmnklin Inst., 1940, 2a9, 677; ( b ) idem, J .Bact., 1940,40, 325; ( c ) E. McDonald, J . Franklin Inat., 1940, 229, 805.'1 E. G. Pringsheim, Zentr. Bakt. Par., 1920, 2. Abt. Orig., 51, 72.4a H. Much, Med. REinik, 1924, So, 347.44 H. Auerawald, ibicE., 1938, 142, 32.98, 180.74, 611, 621.H. Franke and A. Ismet, Zentr. Bokt. Par., 1. Abt. Orig., 1926, 99, 570188 BTOCHEMISTRY.chemical work has as yet been done on .their isolation. H. 0. Hettche andB. Weber 45 claim that one species produces isovaleric and oleic acids, towhich they attribute the antibacterial effect.Dubos and Hotchkiss20 have studied a number of organisms of thistype and have isolated substances which appear to be identical withgramicidin and tyrocidine.Antibiotics produced by Fungi.1. Antibiotics produced by Penicillia.-Penicillin.noticed the presence of a substance with a powerful antibacterial action,particularly against gram-positive cocci, in culture filtrates of Penicilliumnotaturn and termed it penicillin.He did not isolate the substance butemployed culture filtrates containing penicillin for the preparation ofselective He suggested that the crude penicillin-containing brothmight be used for the local treatment of indolent septic wounds.8 P. W.Clutterbuck, R. Lovell, and H. Raistrick 46 showed that penicillin could beobtained on a synthetic medium and that it was a labile substance whichmuld be removed from the acidified culture medium by ether. Apartfrom a paper by R. D. Reid47 in which the instability of penicillin wasemphasised, little further interest seems to have been taken in penicillinuntil, in 1940, Chain et al.11 obtained from the culture medium of PeniciEZiumnotatum a preparation which contained penicillin in a stable form suitablefor study of its pharmacological, antibacterial and chemical properties, andultimately for chemotherapeutic experiments. The antibacterial activityof penicillin-like that of other physiologically very active substances-ismeasured biologically and is expressed in " Oxford units." 12p48 The" ring " method 12 (see 484 for a more detailed description) or the serialdilution technique 48b is used.Penicillin with an activity of 450-500 unitsper mg. was found to inhibit the growth of staphylococcus aureus in adilution of 1 : 25,000,000.48 The sensitivity of a number of differentbacterial species to a penicillin preparation with an activity of 250 units permg.has been investigated.48. 49 The antibacterial activity of penicillin isindependent of the number of bacteria within wide limits.12 Penicillinis a nitrogenous acid; considerable progress has been made in theelucidation of its structure, but for security reasons the results cannotbe published a t present. Previously suggested molecular formulae forIn 1929 Fleming4 5 Arch. Hyg., 1939, 123, 69.'O Biochem. J., 1932, 26, 1907.4 7 J . Bact., 1935, 29, 215. '' H. W. Florey and M. A. Jennings, Brit. J . Exp. Path., 1942, 23, 120."* J. W. Foster and H. B. Woodruff, J. Bact., 1943,46,187 ; N. G. Heatley, .B~~chem.J . , 1944, 38, 61.' 6 b J.W. Foster, J . Biol. Chem., 1042, 144, 285; J. W. Foster and B. L. Wilker, J .Bact., 1943, 46, 377; U. Wilson, Nature, 1943, 152, 475; C. H. Rammelkamp, proc.Sot. Exp. Biol. Med,, 1912, 51, 95. '' G . L. Hobby, K. Meyer, and E. Chaffee, Proc. S'oc. Exp. Biol. Med., 1942,50, 277CHATN AND FLOREY : ANTIBACTERIAL SUBSTANCES. 1 89penicillin 50,511 52 are incorrect. Penicillin is a strong acid which is easilysoluble in ether, chloroform, esters, alcohols and ketones, sparingly soluble inwater, benzene and halogenated paraffins, and insoluble in petrol. Its alkaliand alkaline earth salts are extremely soluble in water ; the barium salt is alsoeasily soluble in methyl alcohol, dioxan and pyridine, but insoluble in ether,esters, e t ~ . ~ O The barium salt in water is dextr~rotatory.~~ Penicillin isstable in water only in the form of its salts between pH 5 and 7 ; it is quicklyinactivated by H+ ions and OH- ions with the formation of new titratablegroups." Both free acid and salts are inactivated by primary alcohols, inparticular methyl alcohol.Penicillin is inactivated by various metal ions,in.particular copper, zinc, cadmium, and lead. It is also inactivated byoxidising agents but is fairly stable towards reducing agents. Ketonicreagents also cause inactivation. 5O The great sensitivity of penicillin to mostchemical reagents has limited considerably the choice of purification methods.Distribution between solvents, treatment with aluminium and chromato-graphy on Brockmann alumina have led to preparations of 1000 units permg.53 Partition chromatography on silica gel containing an inorganic basesuch as barium carbonate has also led to far-reaching p~rification.~~ Apotency of 250 units per mg.has been obtained by distribution between waterand solvents alone.54 The preparations of Abraham and Chain have nocharacteristic absorption,55 either in the visible or in the ultra-violet region ;the preparations of Catch et aL51 show an absorption band at 2650 A. (E ::m.ca. 390) which is unaffected by aluminium-amalgam treatment. Oninactivation of penicillin with dilute acid at room temperature and sub-sequent extraction with butyl alcohol a crystalline dextrorotatory derivative,termed penillic acid, has been 0btained.5~~ On hydrolysis a t 100" in acidsolution penicillin quickly loses 2 mola.of carbon dioxide per barium atom ; 5Oin alkaline solution carbon dioxide is also liberated. The acid hydrolysate ofpenicillin gives a blue coloration with the ninhydrin reagent,51 53 andamino-nitrogen is liberated under the conditions of the van Slyke method.With mercuric chloride a characteristic amino-acid, termed penicillamine, isprecipitated from acid hydrolysates of penicillin. 53 It has strong reducingpower, reducing iodine reversibly in acid solution, gives a transient bluecoloration with ferric chloride, a blue-violet coloration with the ninhydrinreagent, and contains all its nitrogen in the form of amino-nitrogen. Theformula suggested for penicillamine 53 is incorrect.Penicillin is predominantly a bacteriostatic agent, for even in highconcentrations it has no inhibiting effect on the respiration of staphylococcal50 E.P. Abraham and E. Chain, Brit. J . Exp. Path., 1942, 23, 103.61 J. R. Catch, A. H. Cook, and I. M. Heilbron, Nature, 1942, 1!50,633.L2 E. P. Abraham, W. Baker, E. Chain, H. W. Florey, E. R. Holiday, and (Sir) R.63 E. P. Abraham, W. Baker, E. Chain, and R. Robinson, ibid., 1943, 151, 107.64 K: Meyer, E. Chaffee, G. L. Hobby, M. H. Dawson. E. Schwenk, and G. Fleischer,s6 E. R. Holiday, Brit. J . Bxp. Path., 1942, 23, 115.550 W. M. DufYin and S. Smith, Nature, 1943, 151, 251.Robinson, ibid., 1942, 149, 356.Science, 1942, 96, 20190 BIOCHEMISTRY.suspensions.u Hobby et ~ 1 . 5 ~ maintain that, under certain conditions, itmay exert a slow bactericidal action on streptococcus hmolyiicw.It appearsto have the specific effect of arresting the division of bacteria; certainorganisms such as S. typhi produce elongated forms when grown in itsThough penicillin is chemically a highly reaotive substanoe,it does nof react with tissue constituents ; organ-extracts and autolysates,protein hydrolysatm, blood and pus do not significantly reduce its anti-baoterial mtivity.12.49 The antibacterial activity oan, however, be destroyedby enzymes present in certain bacteria,, both penicillin-sensitive and non-sensitive.5* As it does not react with tiasue constituents, its toxicity islow. The intravenous injection of doses as large as 20 mg. of sodiumpenicillin containing 325 units per mg.is tolerated without symptoms bymice.48 Hobby et aLS9 found that the dose lethal to an 18 g. mouse,injected intravenously, was 30 mg. of sodium penicillin or 18 mg. of am-monium penicillin, of 250 units per mg. Leucocytes are not killed quicklyby 8 dilution of even 1 : 100 of material containing 250 units per mg.48It has been a fortunate circumstance that even crude penicillin prepar-ations containing not more than 10% of penicillin can be safely usedon man in large doaes.12,aaeb The chemotherapeutic propertiea of peni-cillin were first demonstrated on mice infected with Staph. aurew,Stye@. hmolyticw and CZ. septicurn. Almost complete protection wasafforded to these animals when infected intraperitoneally or intramuscularlyby subcutaneous injections of penicillin a t frequent intervals.12 This waslater confirmed by Hobby et aZ.59 The observations on mice were followed bythe investigation of its action on natural infections in man.The first clinicalresults reported 12 have been amply substantiated 804, cs e and littledoubt can now remain that penicillin is both the moat effective and theleast toxic chemotherapeutic agent against bacteria at present known.Perhaps in the future chemical modification of the penicillin molecule maybe able to overcome its undesirable property of rapid excretion by thekidneys, and means may be found of making it more stable towards agentswhich a t present destroy its activity. Chemical modifications may also beactive against a greater range of bacteria.An antibacterial substance with the possible compositionC1,H,,O,N&3, was isolated from culture filtrates of P.(QZioctadium) Jimbriatumby R. Weindling and 0. H. Emerson.61 It has a decomposition point of219-222" and [a]r -239' in chloroform; is moderately soluble in acetoneQZiotoxin.66 G. L. Hobby, K. Meyer, E. Chaffee, Proc. SOC. Exp. Biol. Med., 1942, 50, 281.A. D. Gardner, Nature, 1940, 146, 837.E. P. Abraham and E. Chain, aid., p. 837.6s G. L. Hobby, K. Meyer, and E. Chaffee, Proo. SOC. Exp. Biol. Med., 1942, 50, 285.6o (a) M. E. Florey and H. W. Florey, Luncet, 1943, i, 387; (b) C. S. Keefer, F. G.Blake, E. K. Marshall, J. S. Lockwood, and W. B. Wood, J . Amer. Med. ASSOC., 1943,122, 1217; (c) A. M.Clark, L. Colebrook, T. Gibson, M. L. Thomson, and A.*Foster,Lancet, 1943, i, 606; ( d ) D. C . Bodenham, ibid., 1943, ii, 7 2 6 ; (e) M. E. Florey and R.Williams, ibid., 1944, i, 73.Phytqdh., 1936. 28, 1068; 27, 1176CHAIN AND FTJOREY : ANTIBACTERIAL SUBSTANCES. 1911and chloroform, less soluble in hot benzene and hot alcohol, sparingly in coldalcohol and ether, and very sparingly in water. The chemical nature of theactive substance has not yet been elucidated. It is active against gram-positive and gram-negative bacteria, in concentrations of 1 : 1,000,000 to1 : 100,000, but is toxic to animals in doses of 50-75 mg. per kg. body weighLs2Penicillic acid. This substance was first isolated by C. L. &berg and0. F. Black from culture filtrates of Penicillium puberzll~m.~~ Oxford andRaistrick found later that it was produced in considerable amounts byPenicillium cyclopium.J . H . Birkinshaw, A. E. Oxford, and H. Raistrickestablished its constitution as y-keto- p - me thoxy-6-methylene- ha-hexenoicacid.s4 Its inhibitory effect on the growth of yeast and B. coli was noticedby Alsberg and Black, who appear to be the first investigators to have isolatedfrom fungi an antibiotic active against a pathogenic bacterium ; they alsomade some pharmacological observations. A. E. Oxford, H. Raistrick, andG. Smith 65 and Oxford 66 showed that penicillic acid possessed qntibacterialaction against both gram-negative and gram-positive bacteria, inhibitingtheir growth in concentrations of 1 : 100,000 to 1 : 50,000.It reacts withammonia and substances containing amino-groups such as amino-acids,peptone, p-aminobenzoic acid, with a considerable diminution of its anti-bacterial Subcutaneous injection of 7 mg. kills mice, and 5 me.causes toxic symptoms.@ The substance appears to be a protoplasmicpoison, its reactivity with amino-groups probably being the cause of itsantibacterial and toxic action.Ckviformi?a (see also patulin and clavacin ; below). The antibacterialproperties of culture filtrates of PeniciEZiurn chviforrne were established byWilkins and Harri~c.1~ A substance with antibacterial properties againstboth gram-negative and gram-positive bacteria, acting in dilutions of1 : 160,000 to 1 : 40,000, wits obtained from these filtrates in the crystallinestate by E.Chain, H. W. morey, and M. A. Jennings and was termedclaviformin.68 The formula for this substance calculated from its elemenfarycomposition was given as CoHa05, but molecular weight determinationsbased on crystallographic X-ray data (D. Crowfoot and B. Low) G9 haveshown that the formula C,H,O, is more probable. It has a melting pointof 110", is fairly soluble in water, very soluble in alcohol and acetone,moderately soluble in ether and chloroform and insoluble in petrol.Though its chemical constitution was not investigated, it was shown t obe a neutral substance with strongly reducing properties. Its antibacterialactivity is quickly destroyed a t pH 10 at 37", but a t pH 2 i t withstandsboiling for 30 minutes.With ammonia and substances containing amino-groups, such as amino-acids and peptone, it reacts with the formation ofyellow solutions. Serum inactivates it. It is bactericidal, causing complete6 2 J. D. Dutcher, J . Bact., 1941, 42, 816.83 U.S. Dep. Agric. Bur. Plant Ind. Bull., 1913, No. 230.e4 Biochem. J., 1936, 80, 394.e6 Ibid., p. 48.** Brit. J . Exp. Path., 1942, 23, 203.a, Chem. and Ind., 1942,61,22.A. E. Oxford, BiocAern. J., 1942, 38,438.Lancet, 1944, i, 113192 BIOCHEMISTRY.inhibition of the respiration of B. coli suspensions. Toxicity to leucocytesis shown by the fact that it kills them in a dilution of 1 : 800,000, and it is alsovery toxic to mice, doses of 0.2 mg. being lethal. It is obviously a generalprotoplasmic poison, reactivity with amino-groups being a possible cause ofits antibacterial and toxic action.Recently Raistrick et aL70 have isolated an antibiotic fromculture filtrates of PeniciElium patulum which they name patulin.Thissubstance was subsequently shown to be identicalco with claviformin. 71 The constitution of clavi-H 2C<\ C==:CH formin (patulin) was established by RaistrickH2CJCH---CO>o et al. through degradation. It was shown to be apyrone derivative to which the annexed formulaor a tautomeric structure was assigned. Raistricket a,!. state that the antibiotic has a beneficial effect in the treatment of thecommon cold, but another group of workers 72 has failed to obtain favourableresults.The antibacterial effect of quinones is a well-established fact.73~.be ca & Raistrick and his colleagues have shown thatthe lower fungi produce several quinones and quinonoid substances. Twoof these, citrinin and spinulosin, are produced by penicillia, Penicilliumcitrinum and Penicillium spinulosum respectively, and were shown to exertantibacterial activity predominantly against gram-positive 75 The annexed formula is given o\ \\OH for ~ i t r i n i n , ~ ~ ~ whilst spinulosin has been shown to be3 : 6-dihydroxy-4-methoxy-2 : 5 - t o l ~ q u i n o n e . ~ ~ ~ ~ Onesting a number of derivatives of benzoquinone andCH,-CH-0 toluquinone with hydroxy-, methoxy- and hydroxy-methoxy-substituents, A. E. Oxford 77 found that the introduction of ahydroxy-group into the quinoqe nucleus often decreases, and that of amethoxy-group often considerably increases, its antibacterial activity.Quinones which react with proteins and amino-acids 6 7 1 73c are powerfulprotoplasmic poisons, and their practical value in medicine is thereforenecessarily limited.A glucose dehydrogenase, which converts glucose into gluconicacid with the formation of hydrogen peroxide, has been found in cultureMichael, and H.Raistrick, ibid., 1943, ii, 625.Patulin.CH2Citrinin and spinu2osin.\:&02H :"'"" ;Notatin.70 J. H. Birkinshaw, A. Bracken, M. Greenwood, W. E. Gye, W. A. Hopkins, S. E.E. Chain, H. W. Florey, and M. A. Jennings, ibid., 1944, i, 112.7 2 C. H. Stuart-Harris, A. E. Francis, and J. M. Stansfield, ibid., 1943, ii, 684.73 (a) G.T. Morgan and E. A. Cooper, Biochenz. J., 1921, 15, 587; ( b ) E. A. Cooperand G. E. Forstner, ibid., 1924, 18, 941 ; (c) E. A. Cooper and R. B. Haines, ibid., 1928,22, 317; ( d ) G. T. Morgan and E. A. Cooper, J . SOC. Chem. Ind., 1924, 43, 3 6 2 ~ ; ( e )E. A. Cooper and S. D. Nicholas, ibid., 1927, 46, 591..H. Raistrick and G. Smith, Chein. and Ind., 1941, 60, 828.76 A. E. Oxford, ibid., 1942, 61, 128.76 (a) W. K. Anslow and H. Raistrick, Biochem. J . , 1938,32,687 ; ( b ) idem, ibid., p. 803 ;v 7 Chenz. and Ind., 1942, 61, 189.(c) F. P. Coyne, H. Reistrick, and R. Robinson, PhiZ. Trans., 1931, B, 297CHAIN AND FLOREY : ANTIBACTERIAL SUBSTANCES. 193filtrates of a strain of Penicilliuin notatum and has been termed n ~ t a t i n . ' ~This enzyme inhibits the growth of many bacteria through hydrogenperoxide formation. Since it is inactive in the presence of catalase, i t isunlikely to have therapeutic uses.Substances very similar to and probablyidentical with notatin have been described under the names of penatin79and penicillin B.801 81Anti-biotics closely resembling penicillin in their chemical and biological propertieshave been isolated from culture filtrates of two aspergilli, Aspergillus Jlavus 82and Aspergillus gigante~s.8~ It is of interest to note that the production ofpenicillin is not limited to the species Penicillium notatum or even to thegenus Penicillium.Aspergillic acid. Culture filtrates of a strain of Aspergillus jlavus havebeen shown to exhibit antibacterial a c t i ~ i t y .~ ~ a ? b, cB 85 A crystalline anti-biotic, termed aspergillic acid, has been isolated from themma4a It has amelting p6int of 93", is optically active ([.ID = + 14"), and analysis andmolecular weight determination agree with the formula C,,H,OO~,. Itpossesses one hydroxy-group, and its absorption spectrum shows a charac-teristic band at 3250 A. It can be distilled with steam or in a vacuumwithout loss of biological acjivity and is stable towards acid and alkali.a6It shows antibacterial activity against both gram-positive and gram-negativeorganism^,^^^^^^ but appears to be too toxic to be of use in systemic bacterialinfections.The isolation of two new antibacterial sub-stances from Aspergil1u.s fuinigatw and Aspergillus clavatus, designatedfumigacin and clavacin, has been reported by Waksman et a1.88a* b Fumigacinhas been obtained crystalline, melts at 185-187", and is sparingly soluble inwater but soluble in ether and chloroform; it is recrystallised from alcohol.It contains 62-7 yo of C and 3.7 % of N ; no further details about its chemicalproperties are as yet available.88b It is toxic to mice, 1 mg. killing a 20 g.mouse when injected intraperitoneally.Clavacin isidentical with an antibiotic previously extracted by B. P, Wiesner from2. Antibiotics produced by Aspergil1i.-Penicillin-like antibiotics.Fumigacin and clavacin.(See note on p. 203.)7 8 C. E. Coulthard, R. Michaelis, W. F. Short, G. Sykes, G. E. H. Skrimshire, A. F. B.79 W. Kocholaty, J . Bact., 1942, 44, 143; 1943, 46, 313; Science, 1943, 97, 186.8o E.C. Roberts, C. K. Cain, R. D. Muir, F. J. Reithel, W. L. Gaby, J. T. vanBruggen,D. M. Homan, P. A. Katzman, L. R. Jones, and E. A. Doisy, J. Biol. Chem., 1943,147,47.Standfast, J. H. Birkinshaw, and H. Raistrick, Nature, 1942, 150, 634.Idem, ibid., 1943, 148,.365.82 M. T. Bush and A. Goth, J . Pharm. Exp. Therap., 1943, 78, 164.83 F. J. Philpot, Nature, 1943, 152, 725.( a ) E. C . White, Science, 1940, 92, 127; ( 6 ) E. C. White and J. H. Hill, J. Buct.,G . A. Glister, Nature, 1941, 148, 470.H. Jones, G. Rake, and D. M. Hamre, ibid., 1943, 45, 461.1942, 43, 12; ( c ) idem, ibid., 1943, 45, 433.86 A. E. 0. Menzel, 0. Wintersteiner, and G. Rake, J. Bact., 1943, 48, 109.8 8 (a) S. A.Wa.ksman, E. S. Homing, and E. L. Spencer, Science, 1942, 96,202; ( b )idem, J . Bact., 1943, 45, 233.REP.-VOL. XL. 194 BIOCHEMISTRY.A . clavutus e9 and has recently been shown to be identical with claviformin(pat~lin).~~an b Claviformin is also produced by A. g i g a n t e ~ s . ~ ~ ~Fumigutin. This substance is a quinorle produced by Aspergillus fumi-gutus. It is 3-hydroxy-4-methoxy-2 : 5-t0luquinone.~~at b Its antibacterialactivity has been investigated by A. E. Oxf0rd.~5Helvolic acid. Wilkins and Harris l3 found that culture filtrates ofAs~ergillusfumigatus, mut. helvoh, possessed antibacterial activity. Followingup this observation, E. Chain, H. W. Florey, M. A. Jennings, and T. I.Williams QO isolated in the crystalline state an antibiotic which they termedhelvolic acid.Elementary analysis shows that this substance contains C,H and 0 only. Crystallographic X-ray data (Crowfoot and Low, unpublishedresults) and molecular weight determinations in camphor give molecularweight values from 510 to 560. From these figures and those of the elementaryanalysis the most probable empirical formula for helvolic acid is C3,H,0,.Helvolic acid is a colourless monobasic acid, m. p. about 212' after crystallis-ation from glacial acetic acid. It is laevorotatory. The free acid is solublein ether, chloroform, esters, glacial acetic acid, pyridine, slightly soluble inbemne, very sparingly soluble in water. With diazomethane, helvolicauid gives a crystalline methyl ester, m. p. about 261'. Helvolic acid can beheated a t 100' for 10 minutes a t pH 2, 7 or 10 without diminution of itsantibacterial activity. N-Alkali causes slow inactivation.Helvolic acidacts mainly against gram-positive bacteria, but its action is affected by thesize of the inoculum, being less in the presence of a large number of bacteria,Thus the titre for complete inhibition of Stuph. uureus may be changed from1 : 80,000 to 1 : 1,280,000 by a thousandfold dilution of the culture. Itsaction is not diminished by blood, serum, peptone or p-aminobenzoic acid,but yeast extracts and to a lesser degree pus contain substances which reduceits activity. Helvolic acid does not affect the oxygen uptake of staphy-lococcal suspensions a t a dilution of 1 : 1000; its antibacterial action istherefore predominantly bacteriostatic. Intravenous injection of 10 mg.into a 20 g.mouse is lethal, but 4 mg. are tolerated without any apparenteffect. Doses as large as 20 mg. administered by mouth produce no symptoms,though it is absorbed from the alimentary tract. However, repeated injec-tions into mice during several days produce severe liver damage. It isexcreted in the urine and bile, Leucocytes are not affected by helvolic acidin a concentration of 1 : 1600.I n spite of its low toxicity to leucocytes and its high bacteriostatic powerhelvolic acid does not give complete protection to mice against infectionswith staphylocoaci and streptococci, though it causes a considerable pro-longation of life. Possibly the specific toxic effect of helvolic acid on theliver is one of the fautors responsible for its failure to act as an effectiveNature, 1942, 149, 356.a8 (a) F.Bergel, A. L. Morrison, A. R. Mqss, R. Klein, H. Rinderknecht, and J. I,.Ward, Nature, 1943, 153, 750; ( b ) I. R. Hooper, H. W. Anderson, P. Skell, and H. E.Carter, Soience, 1944, 89, 16; (c) H. W. Florey, M. A. Jennings, and I?. J. Philpot,Nature, 1944, 153, 139. Brit. J . Exp. Path., 1943, 24, 108CHAIN AND FLOREY : ANTIBACTERIAL SUBSTANCES. 195chemotherapeutic agent. Unless the molecule of helvolic acid can bemodified chemically in such a manner that it becomes less toxic to livertissue, it will have no significance as a general chemotherapeutic agent,though it may be useful for local application in wounds.3.Antibiotics produced by Actimycetes.-Actinumycetin. Many acti-nomycetes are known to produce antibacterial substances.l* l4, 926 I nculture filtrates of various actinomycetes bacteriolytic substances, termedactinomycetin, have been the subject of numerous studies by Gratia andW e l ~ c h . ~ l ~ g2a. Welsch 9% i, has shown that culture filtrates of an un-specified strain of actinomyces contain a protein with enzymatic propertiescapable of lysing suspensions of dead (but not living) pneiimococci andstreptococci. In addition ether-extractable bactericidal dubstances havebeen found. The bacteriolytic effect of actinomycetes on gram-positivebacteria appears to be due to the combined action of both types ofsubstances.Actinomycin .A and B.S . A. Waksman and H. B. Woodruff isolatedtwo antibacterial factors from Actinomyces antibioticus. These are termedactinomycin A and B.93a.b9c Actinomycin A, which has been obtainedcrystalline, is a red pigment, m. p. 250°, soluble in chloroform, benzene andalcohol, and slightly soluble in water and ether.94 It is stated to be apolycyclic nitrogenous compound with a molecular weight of 768-1000.It exhibits a characteristic absorption spectrum in visible and ultra-violetlight, and a quinonoid group which is reduced by hydrosulphite and re-oxidised by air forms part of its structure. This quinonoid group may beresponsible for its antibacterial action (see above, antibacterial action ofquinones). In alcohol-water solution it is stable to boiling for 30 mins.but isdestroyed by alkali in the cold and by acid on boiling. It has a high anti-bacterial power, particularly against gram-positive organisms, inhibiting thegrowth of S . Zutea and B. subtilis in dilutions of 1 : 100,000,000 and1 : 10,000,000 respectively. Its action is stated to be predominantlybacteriostatic, but this may only hold for low concentrations, for in higherconcentrations i t has been shown to have a pronounced bactericidal e f f e ~ t . ~ ~It has the properties of a general protoplasmic poison and is lethal to mice in adose of 1Oy when injected intra~eritoneally.9~ The properties of actinomycinBy which is a colourless bactericidal substance active against both gram-positive and gram-negative organisms, have not yet been studied in detail.From culture filtrates of an organism closely related to91 Compt.rend. SOC. Biol., 1936, 123, 1013; 1937, 124, 573, 1240; 125, 1053; 126,244, 247, 1254; 1938, 127, 347; 128, 795, 1172, 1175; 1939,130,104, 797, 800; 131,1296.Proactinomycin.92 (a) M. Welsch, J . Bact., 1941, 42, 801; ( b ) idem, ibid., 1942, 44, 571.93 (a) J. Bact., 1940, 40, 581; ( b ) ibid., 1941, 42, 231; (c) Proc. SOC. Exp. Bid. Med.,94 S. A. Waksman and M. Tishler, J . Biol. Chem., 1942, 142, 519.95 S. A. Waksman and H. B. Woodruff, J. Bact., 1942, 44,373.w S. A. Waksman, H. Robinson, H. J. Metzger, and H. B. Woodruff, Proc. Boc. Exp.1940, 45,609.Biol. Med., 1941, 47, 261196 BIOCHEMISTRY.the actinomycetes and designated as proactinomycin, Gardner and Chain l6have isolated an organic base with a powerful antibacterial effect, pre-dominantly against gram-positive bacteria and the Neisseriz.The sub-stance, proactinomycin, which is stable in acid and alkali a t room tem-perature, loses a small part of its antibacterial activity a t pH 2 and 7 whenkept at 100" for 10 minutes and the greater part of its activity at pH 10. Ithas not yet been obtained pure and its chemical properties have not beenstudied in detail. The substance is fairly toxic to mice, which is not sur-prising in view of its basic nature. The intravenous injection of 5 mg. wasimmediately fatal; 2 mg. caused toxic symptoms and, in a minority, death ;1 mg. had no effect.Streptothricin. An antibacterial substance termed streptothricin, activein a concentration of 1 : 100,000 against both gram-positive and gram-negative bacteria, has been obtained by s.A. Waksman and H. B. Woodruff sfrom a soil actinomyces closely resembling Actinornyces lavendulce. Waks-man g8 has studied the conditions of its biological production; it is formedon protein digest media and good aeration is essential for its production.Streptothricin is a N-containing base, soluble in water and alcohol butinsoluble in ether, chloroform and light petroleum. It is precipitated byprotein precipitants, but protein-free preparations with a nitrogen contentof 2-3% have been obtained. It has not yet been obtained in the crystal-line state and few data are given on its chemical and biological properties.It is stated 98 to possess a low toxicity to animals (no figures are given) andto prevent the growth of Brucella abortus in V ~ V O .~ ~The systematic study of antibiotics produced by bacteria and fungi,though still in its early stages, has already led to the discovery of a number ofnew types of antibacterial substances which have. considerable chemical,biochemical and medical interest. Apart from their significance as localantiseptics, the crystalline polypeptides gramicidin and tyrocidine may beuseful tools in the study of protein structure. The studies on penicillin haveshown that it has great antibacterial power combined with low toxicity toanimals and so is of considerable interest to medicine. Many of the otherantibiotics so far isolated have interesting chemical features.For instance,proactinomycin is an antibiotic with alkaloid-like properties, gliotoxin is asulphur-containing substance, actinomycin A is a quinone with much morepowerful antibacterial activity than the normal quinones, helvolic acid is arelatively non-toxic bacteriostatic containing only C, H and 0, but of complexnature. Obviously it will be of immediate importance to elucidate thechemical constitution of these antibiotics, In view of the result,s achievedso far the hope seems justified that further studies of antibiotics producedfrom bacteria, fungi and other natural sources will reveal the existence ofs7 Proc. SOC. Exp. Biol. Med., 1942, 49, 207.BE J. Bact., 1943, 40, 299.er H. J. Metzger, S.A. Waksman, and L. H. Pugh, Proc. SOC. Exp. Biol. Med., 1942,61, 261MARKHAM : VIRUSES. 197more new types of antibacterial substances with interesting chemical andbiological properties.E. C.H. W. F.3. VIRUSES.Viruses have not been reviewed in this Report in any detail since 1937.At that time the subject was beginning to attract much attention, and a tthe moment the publications cover many fields of research. In consequenceit is only possible to indicate the scope of the subject. A selection of thereviews on the various aspects of virus research is listed below.l* 2e 3v *The Isolation of Viruses.Properly speaking, the virus of vaccinia was the first virus to be isolatedin a form approximating to p ~ r i t y , ~ but, as it is a very large particle andeasily visible under ordinary microscopes, this feat did not attract suchattention as did the isolation of the tobacco mosaic virus by W.M. Stanleyin 1935.6 Stanley's success followed a detailed investigation of the propertiesof the infectious agent and would probably have proved impossible had itnot been for the discovery of the local lesion technique for the estimationof virus activity by F. 0. Holmes and improvements by G. Samuel andJ. G. Bald.E Prior to Stanley many attempts had been made to isolate thisvirus, but the various claims to have isolated the greater part of the virusfrom infectious sap were refuted by the discovery that the latter containedthe altogether unexpected quantity of 0.1-0-2~0 by weight of virus pro-tein.Stanley's isolation of a protein possessing the properties of thetobacco mosaic virus was soon c~nfirrned,~ and, in fact, was nearly antici-pated by R. J. Best,lo and F. C. Bawden and N. W. Pirie showed that thevirus was in fact a nucleoprotein.11 Subsequently several plant viruseswere isolated by similar methods involving precipitations with ammoniumsulphate and treatment with acid, alcohol, etc.l2* 1 3 0 l4* l5 Two of these,namely, the viruses of tomato bushy stunt 1* and tobacco necrosis,15 provedto be crystallisable.C. L. Hoagland, Ann. Rev. Biochem., 1943, 12, 615; W. M. Stanley and H. S.Loring, Symposia Quant. Biol., 1938, 6, 341 ; W. M. Stanley, Physiol. Rev., 1939, 19,524; Ann. Rev. Biochem., 1940, 9,545.Idem, J . Physical Chem., 1938, 42,55.A.S. McFarlane, Biol. Rev., 1939, 14, 223; R. W. G. Wyckoff, Ergeb. Enzym.J. E. Smadel and C. L. Hoagland, Bact. Rev., 1942, 6, 79.W. G. MacCallum and E. H. Oppenheimer, J . Amer. Med. ASSOC., 1922, 78, 410;J. C. G. Ledingham, Lancet, 1931, ii, 525; J. Craigie, Brit. J . Exp. Path., 1932, 13, 259.Science, 1935, 81, 644; Phytopath., 1936, 26, 305.Bot. Gaz., 1929, 87, 39.F. C. Bawden, N. W. Pirie, J. D. Bernal, and I. Fankuchen, Nature, 1936,138,1051.lo Australian J . Exp. Biol. Med. Sci., 1936, 14, 1 .l1 Proc. Roy. Soc., 1937, B , 123, 274. l2 Idem, Brit. J . Exp. Path., 1937, 18, 275.lS Idem, ibid., 1938, 19, 66. 14 Idem, ibid., p. 251.15 N. W. Pirie, K. M. Smith, E. T. C. Spoont , and W. D. MacClement, Parasitology,forsch., 1939, 8, 1 ; E.H. Lenette, Science, 1943, 98, 415.Ann. Appl. Biol., 1933, 20, 70.1938, 30,543198 BIOCRETvlISTRY.About the same time high-speed air-turbine-driven centrifuges weredeveloped in America for the study of viruses,16 and it was soon realisedthat the activity of preparations isolated by centrifugation was greaterthan that of those obtained by salt precipitation, the latter procedure beingshown to produce irreversible changes in the case of several viruses,l'* 18tobacco ringspot virus being almost completely inaotivated by precipitationwith ammonium sulphate. In consequence centrifugation ia now employedas a general routine method of isolation.The Isobtion of Viruses by " Differential " Centrifugation.-Normallyviruses are isolated from tissues which contain much protein and otherlarge molecules, such as glycogen, many of which have sedimentation ratescomparable with those of viruses.19 Consequently an attempt is usuallymade to obtain a starting material as free from extraneous contaminantsas possible.In the case of plant viruses young plants are generally used,as they contain appreciably less dark pigment, etc. Special techniques aresometimes used for individual animal viruses ; influenza A virus,20 forinstance, may be isolated from chick extra-embryonic fluid, and vacciniavirus is collected from the skin of inoculated rabbits in such a way as todamage the tissues as little as possible.21 The solution may then be .sub-jected to a preliminary treatment with a view to removing non-virusmaterial.Thus plant sap is often frozen or treated with phosphate oralcohol, and animal viruses may be adsorbed specifically,a2 but in manycases the infective juices are centrifuged alternately a t high and low speedswithout preliminary treatment. The final product generally consists of asubstance which, when examined on the ultracentrifuge or electrophoretic-ally, is apparently reasonably homogeneous. It is relatively simple to showqualitatively that by this method a complete separation of particles havingsimilar sedimentation constants is impossible, and, in fact, only a minormodification of the relative proportions of substance differing twofold insedimentation constant may be achieved. It is therefore evident that, inspite of the criticisms generally levelled against this method of isolation,*, 23a sharp sedimentation boundary may be taken to indicate that the sub-J. H.Bauer and E. G. Pickels, J . Exp. Med., 1936, 64, 603; R. W. G. Wyckoffl7 H. S. Loring, J . Biol. Chem., 1938,126,455; W. M. Stanley, ibid., 1939,129,405;and J. B. Langsdin, Rev. Sci. Instr., 1937, 8, 427.H. S. Loring, M. A, Lauffer, and W. M. Stanley, Nature, 1938, 142, 841.F. C. Bawden and N. W. Pirie, Brit. J . Exp. Path., 1942,23,314.l* A. R. Taylor, D. G. Sharp, D. Beard, and J. W. Beard, Science, 1941, 94, 615;W. C. Price and R. W. G. Wyckoff, Phyhpath., 1939,29,83 ; H. S. Loring, H. T. Osborn,and R. W. G. Wyckoff, Proc. Soc. Exp. Biol. Med., 1938, 38, 239; E. Chsrgaff, D. H.Moore, and A.Bendich, J . Biol. Chem., 1942, 14S, 593; H. S . Loring and J. G. Pierce,ibid., 1943, 148, 36.2o L. A. Chambers and W. Henle, J . Exp. Med., 1943, 77,261.21 R. F. Parker and T. M. Rivers, ibid., 1935, 62, 65.22 D. (3. Sharp, A. R. Taylor, I. W. McLean, D. Beard, J. W. Beard, A. E. Feller,J. E. Smadel, E. G. Pickels, T. Shedlovsky, and T. M. Rivers, J . Exp. Med.,and J. H. Dingle, Science, 1943, 98, 307.1940, 72, 623MARKHAM VIRUSES. 199stance isolated is fairly homogeneous. Whether this substance is the virusis quite another matter, and is largely dependent upon the concentration ofvirus in the original fluid, and on the fact that many contaminants seem tobe leus resistant to repeated sedimentation than are viruses.The Identity of the Isolated Substance with the Injective Agent.-In viewof the preoeding i t is evident that claims to have isolated pure viruses mustbe accepted with some reserve and it may be noted that several authorshave claimed only t o have isolated large molecules apparently having theproperties of the virus under l1 In an ideal case it mightbe expected that single virus particle would be able to cause an infeotion,but few purified virus preparations fulfil this requirement.In the oase ofthe plant viruses many particles are required for one infection, as themethod of inoculation used does not give an individual particle an appreciablechance of entering a viable cell. The conditions necessary for establishingan infection are, in addition, subject to complications other than thosearising fiom chance.F. C. Bawden and N. W. Pirie24 have drawn atten-tion to the well-known fact that, though the sensitivity of Nicotianaglutinosa to tobacco mosaic is less on the top leaves than on the lower leaves,the latter are less sensitive to bushy stunt than the former. It is not sur-prising that plant viruses rarely infect in quantities less than 10-7 or 10-8 g.,although this corresponds to some 108 particles. There is, however, noevidence that all the particles in the purified preparations are infective.Bawden and Pirie think it not unlikely that the greater part of their purifiedbushy stunt virus is inactive.24 In spite of the fact that the activity of avirus may be reduced by the isolstion procedure employed, and that anisolated virus may by appropriate treatments be wholly or completelyinactivated, there is in many cases good reason to identify the isolatedprotein with the virus. Tobacco mosaic virus, for instance, has beenisolated from such widely diverse plants as spinach, tobacco and PhZox,2and in no instance has activity been demonstrated in the absence of thecharacteristic protein.In the case of the vaccinia virus25 and some bacteriophage prepar-ations 26 it is possible to show that' one or a small number of particles issufficient to cause infection, while in the case of the Shope papilloma virus 27it is neoessary to use as many as 57 million particles of the molecular weightof the characteristic substance associated with this disease in the cottontailrabbit (no virus can be isolated from the papillomata produced artificially ondomestic rabbits).28 While there would seem to be no reason to doubtthe homogeneity of preparations of this virus, there appears to be insufficientevidence for the certain identification of the large particles with the virus.2p Biochem.J., 1943, 37, 70.25 J. E. Smadel, T. M. Rivers, and E. G. Pickela, J . Eq. Med., 1939,70,379.a6 G. Kalmanson and I. J. Bronfenbrenner, J. Ben. Physiol., 1939, 23,203.27 H. Neurath, G. R. Copper, D. G. Sharp, A. R. Taylor, D. Beard, and J. W. Beard,48 J. W. Beard, W. R. Bryan, and R. W. G. Wyckoff, J. Infect. Dis., 1930,65,43.J . Biol. Chem., 1941,140,293200 BIOCHEMISTRY.In view of the availability of methods, such as that of A.Tiselius, K. 0.Pedersen, and T. S ~ e d b e r g , ~ ~ which are capable of demonstrating identityof physical properties of the infective agent and the substance isolated, i tis surprising that so little evidence of this type is available. While centri-fugation is the obvious method and has been used with success by S. Gardand K. 0. Pedersen30 in their work on mouse encephalomyelitis, it isequally easy to use a Tiselius apparatus in a similar way. If such methodswere used more frequently, it would be a simple matter to avoid the con-fusion caused by the reports of various authors to have isolated " pure "viruses having entirely different physical properties, as in the case of theinfluenza A vir~s.~lP 32General Properties of Viruses.As a group viruses are extremely diverse in properties.Sedimentationconstants vary from 50 S.33 or less to owr 5000 S.34 Some viruses arespherical or nearly so, such as the bushy stunt, tobacco Shopepapilloma,36 and equine encephalomyelitis viruses,37 others, such as tobaccomo~aic,~ potato X,12 and the cucumber viruses 3 and 4, are long rods,l3and several bacteriophages are tadp~le-shaped.~~ Although there is littledoubt that several plant viruses are only of molecular complexity, this isby no means the rule and vaccinia virus, for instance, has a well-definedinternal structure 39 and besides containing co~per,~O fatsY4l and severalwhich are probably merely adsorbed by the particles, has acomplex antigenic structure.Of all the viruses, that of tobacco mosaic has been studied most inten-sively by physical methods.Sedimentation,43 diffusion,44 v i s ~ o s i t y , ~ ~ flow2* Nature, 1937, 140, 848.30 Science, 1941, 94, 493.31 L. A. Chambers, W. Henle, M. A. Lauffer, and T. F. Anderson, J. Exp. Med.,32 A. R. Taylor, D. G. Sharp, D. Beard, J. W. Beard, J. H. Dingle, and A. E. Feller,33 A. 0. Ogston, Brit. J. Exp. Path,., 1942, 23, 328.J. W. Beard, H. Finkelstein, and R. W. G. Wyckoff, J. Immunol., 1938, 35, 415.ss W. M. Stanley and T. F. Anderson, J . Biol. Chem., 1941,139,325.36 D. G. Sharp, A. R. Taylor, D. Beard, and J. W. Beard, Proc. SOC. Exp. Biol.37 Idem, ibid., 1942, 51, 206, 332.3s S. E. Luria and T. F. Anderson, Proc. Nat. Acad. Sci., 1942, 28, 127.39 R. H. Green, T.F. Anderson, and J. E. Smadel, J. Exp. Med., 1942, 75, 651.4o C. L. Hoagland, S. M. Ward, J. E. Smadel, and T. M. Rivers, J. Ezp. Med., 1941,41 C. L. Hoagland, J. E. Smadel, and T. M. Rivers, J . ESP. Med., 1940, 71, 737.l2 C. L. Hoagland, S. M. Ward, J. E. Smadel, and T. M. Rivers, ibid., 1942, 76, 163.43 M. A, Lauffer, J. Physical Chem., 1940, 44, 1137.44 H. Neurath and A. M. Saum, J. Biol. Chem., 1938, 126, 435; V. L. Frampton45 M. A. Lauffer, J . Biol. Chem., 1938, 126, 443; J. R. Robinson, Proc. Roy. SOC.,1943, 77, 265.J . Immunol., 1943, 47, 261.Med., 1942, 50, 205.74, 69.and A. M. Saum, Science, 1939, 89, 84.1939, A , 170, 519MARKHAM : VIRUSES. 201birefringen~e,~G X-ray cry~tallography,~~ and the electron microscope 48 allconfirm the elongated shape of the particles.Nevertheless the data arenot mutually consistent, probably because of the polydispersity of thepreparations investigated, and of the difficulty of applying theory to thecase of such asymmetrical particles.Very complete data are available on the bushy stunt virus 430 49 and itwould appear to have as much claim to homogeneity as any other protein.50It has a molecular weight of 10.6 million and is of interest as the first proteinin which all reliable data point to the conclusion that it is considerablysolvated, the amount of water bound being about 0.7 g./g.51Another spherical virus which is solvated is the Shope papilloma virus,which was deduced by Neurath et to be a rod with an axial ratio ofsome 9 : 1 from their measurements.Sedimentation, diffusion and viscositymeasurements can be shown to give a very poor estimate of the shape of aparticle, but, if combined with an estimate of the shape, may be used todeduce reliable values of wet and especially dry molecular weights. Thusthe data on the Shope papilloma are consistent with a molecular weightof 48 million, which is increased by solvation to 135 million.It is now generally accepted that all the plant viruses isolated so farare nucleoproteins, and almost without exception viruses are reported tocontain nucleic acid. Vaccinia and the rabbit papilloma virus containribodesose nucleic acid,52 and other viruses appear to have a pentose nucleicacid.9* 11, l 2 P 139 1* H. S. Loring 53 has studied the hydrolysis products oftobacco mosaic nucleic acid, and S.S. Cohen and W. M. Stanley 54 haveinvestigated the physical properties of this substance, confirming the observ-ation of Bawden and Piriel1 that it is larger than yeast nucleic acid asusually prepared. The size of the nucleic acid particles depends to a greatextent upon the treatment to which the acid is subjected, the size beinggreater when mild methods of isolation are used. This is similar to theobservations of G. Schmidt, E. G . Pickels, and P. A. Levene 55 on thymusnucleic acid. When isolated in a mild way, the virus nucleic acid forms abirefringent gel and has a molecular weight of about 3 x lo5. It depoly-merises spontaneously and is apparently very asymmetrical, the axial ratiobeing assessed a t about 30 : 1.The amino-acids of the tobacco mosaic virus and the related rib-grass(Plantago) virus and cucumber viruses 3 and 4 have been examined and4 6 J.W. Mehl, Symposia Quant. BioE., 1938, 6, 218.4' J. D. Bernal and I. Fankuchen, J.'Gen. Physiol., 1941, 25, 111, 147.48 G. A. Kausche, E. Pfankuch, and H. Ruska, Nuturwiss., 1930, 27, 202.48 H. Neurath and G. R. Cooper, J . Biol. Chem., 1940,135, 455.50 M. A. Lauffer, ibid., 1942, 143, 99.51 R. Markham, K. M. Smith, and D. Lea, Parasitology, 1942, 34, 315.52 C. L. Hoagland, G. I. Lavin, J. E. Smadel, and T. M. Rivers, J. Ezp. Med., 1940,72, 139; A. R. Taylor, D. Beard, D. G. Sharp, and J. W. Beard, J . Infect. Dis., 1942,71, 110.63 J . Biol. Chem., 1939, 130, 251.64 Ibid., 1942, 142, 863.55 Ibid., 1939, 127, 251.G 202 BIOCHEMISTRY .aome 68% of the weight of the virus has been accounted for in hydxolyeisproducts.56 This group of viruses is of interest in that, although themembers are morphologically similar and have a similar elementary com-position, their amino-acid compositions differ. All four me to Borne extantantigenically related, and the host range of the four is Merent, the cucumberviruses being confined to the Cucurbitacece, whereas the wide host rangesof the others do not include this plant family. The serological differencesobserved are paralleled by marked differences in the proportions of thevarious aromatic amino-acids present.67The Inactivation of Viruses.Just as they Wer in other properties, viruses react very differently tovmious treatments.As would be expected, elevated temperatures destroyall viruses, but some are surprisingly resistant. Purified tobacco mosaicvirus will readily withstand temperatures up t o 70°.11 On the other hand,bushy stunt virus is rapidly inactivated at temperatures of 60" or l ~ s , ~ *but apparently without clppreciable change in physical or chemical properties,and many viruses are inactivated at room temperature in a few hours.The phenomenon of loss of activity without gross physical change is observedin many viruses, and means presumably that the major part of the structureof the particle must be intact for it to be infectious. Treatments destroy-ing infectivity without causing gross change and loss of serological speci-ficity include the effect of various rahtions,ll hydrogen peroxide,6e form-nitrous ttcid,xl keten,gf and similar reagents. Up to 70% ofthe free amino-groups and a, smaller percentage of the phenolic hydroxylgroups may be substituted without loss of virus activity. An importantobservation is recorded by Miller and Stanley,62 who find that carbobernzyl-oxy-, benzenesdphonyl- , and p-chlorobemoyl-tobacco mosaic virus are &Bmuch as seven times as active when tested on Nbtianu glutinosa 8s onP h l w vulgaria. This may prove to be due to a toxic effect on theP. vutguris plants, but if this possibility is excluded and the observationsconfirmed, some revision of our views on virus activity will be necessitated.In general, enzymes have little effect on viruses and trypsin is oftenused in the purification procedures,ll* 12* l3. 63 although it is known to digestat least two viruses, potato virus X l3 and a&lfa mosaic virus.64 Pepsinalso is known to digest 8ome virusw, but as they are usually inactivatedby pH values at which pepsin is active, this is not unexpected. Reportedeffects of enzymes on plant viruses are usually found to be due to a non-specific inhibition of the plant, and some of the effects of crude trypsin6 6 A. F. R090, J . Biol. Chenz., 1942,143,686.57 C. A. Knight and W. M. Stanley, ibid., 1941, 141, 39.68 W. M. Stanley, ibid., 1940, 185,437.6o A. F. Ross and W. M. Stanley, J . Gen. fhysiol., 1938-9, 29, 166,6 1 G. L. Miller and W. M. Sb8&y, J . BWl. Chem., 1941, 141, 906.62 Ibid., 1942, 140, 331.63 J. E. Smadel and M. J. Wall, J . Ezp. Med., 1937, 66, 326.64 A. F. ROSS, Phgtqath., 1941, 81, 394.5* Idem, Science, 1936, 83, 626MARKHAM : VIRUSES. 203on other viruses have been shown to be due to lipoidal contaminants in theenzyme.65 Some enzymes and other large molecules form reversible com-plexes with viruses11.66s67 and their use for purification has beensuggested.The inactivation of viruses with simultaneous loss of characteristicphysical properties is caused by many treatments, including heat, highpressures,6* exposure to extremes of acidity and alkalinity, and the effectof artificial detergents,GQ urea and allied s~bstances,~O and various proteindenaturants.R. M.E. C?EAIN.H. W. FLOREY.L. J. HARRIS,R. MARKHAM.Note added in poof.-In -a recent paper by A. E. D. Menzel, 0.Wintersteiner, and 5. C. Hoogerheide ( J . Biol. Chem., 1944, 152, 419),which has just come to the notice of the authors, i t has been shown thatfumigacin, as described by Waksman et al., is not a chemical entity but amixture of helvolic acid (see p. 194) and gliotoxin (see p. p. 190).-E. C.,H. W. F’.6 5 A. Pirie, Brit. J . Exp. Path., 1935, 16, 497.66 H. S . Loring, J . Qen. Physiol., 1942, 25, 497.6 7 S. S. Cohen, J . Biol. Chem., 1942, 144, 353.6 8 31. A. Lauffer and R. B. DOW, ibid., 1941,140,609.69 M. SreenivaSays and N. W. Pirie, Biochern. J., 1938, 32, 1707.70 F. C. Bawden and N. W. Pirie,.ibid., 1940, 34, 1268

ISSN:0365-6217    

DOI:10.1039/AR9434000177

出版商:RSC    

年代:1943

数据来源: RSC

摘要:

ANALYTICAL CHEMISTRY.1. ANALYSIS OF STEELS.IN recent years the steel analyst has had to devise methods for the deter-mination of the elements found in steel which are not only quick and accuratebut can be easily adapted to the routine examination of a large number ofsamples. When it is remembered that nearly one third of all the elementsare to be found in steels, many of them in a single sample, details of themethods used in steel analysis will be of value to many besides the steelchemist. To a large extent the necessary speed and accuracy have beenachieved by the employment of physicochemical methods, either as individualmethods or in combination with chemical separations.In the following review the basis of accepted knowledge is the methodswhich are to be found in text books such as “ Chemical Analysis of Iron andSteel,” by Lundell, Hoffman, and Bright, and “ Sampling and Analysis ofCarbon and Alloy Steels,” being the methods of the United States SteelCorporation.Reports on the determination of each element are precededby three headings dealing with the general application of the spectrographto steel analysis, the use of the photoelectric absorptiometer, and polaro-graphic and potentiometric methods. To avoid repetition of matter dealtwith under these and other headings appropriate reference numbers arerepeated a t the head of the report on each element.Application of the Spectrograph.-It has been found possible to determinewith fair accuracy elements present in steel in small amount by using anarc and an hternal-standard method.Greater reliability, however, isobtained by the use of a spark,l particularly where the upper electrode ismade of graphite-a method which, when standardised, is applicable tohigher percentages of the alloying elements giving results varying only byO ~ O Z - O - l ~ o from the chemical figures. The graphite electrode may bereplaced by silver, and a counter electrode made of high-purity aluminiumhas given good results.2 Disturbance of the lines of one element due to thepresence of other elements may be a source of error. Such disturbanceshave been recorded by W. Holzmiiller,3 who gives a list of suitable lines foraome twenty elements present in steel. Characteristic lines in the ultra-violet have also been measured.4 The grating spectrograph, using a spark gapirradiated with ultra-violet light, has been adapted to routine use withsome success in the U.S.A.5 Modifications of the old spectroscope (“ steelo-scope ”) and of the modern spectrograph for use in the visible part of the1 F.G . Barker, Iron and Steel Inst., May 1939, No. 1.2 T. Torok, Spectrochim. Acta, 1941, 2, 26.4 L. A. Ignatieva, and N. N. Sobolev, Zavod. Lab., 1938, 7, 949.5 S. Vigo, A.S.T.M. Bull., 1940, No. 107, 7.Z . anal. Chem., 1938, 115, 81.V. K. Prokofiev, Zavod Lab., 1940, 9, 1267GIASKIN : ANALYSIS OF STEELS. 205spectrum (“ steelometer ”) 7 are in everyday use, Results obtained withthe latter instrument have an average deviation from the chemical figuresvarying from 0.03 to O.OS~O.Use of the Photoelectric Absorptiometer.-It has been remarked that thelaboratory is regarded as the bottle neck of production in metallurgicalwork.8 The removal of this bottle neck has been achieved by the applica-tion of the spectrograph and the photoelectric absorptiometer, and the authorquoted above has shown how satisfactorily this has been achieved by usingthe absorptiometer.8* Experienced users are able to obtain accuracy inthe determination of steel constituents as high as that obtainable with chemi-cal methods in only a fraction of the time required by the latter methods.Moreover, with only a slight loss of accuracy the absorptiometer can beeasily used for routine work by relatively inexperienced assistants with properdirection.Polarographic and Potentiometric Methods.-Although some success hasheen achieved with the polarograph the method cannot be said to be suitablefor routine testing,lO and clearly it is more likely to be of use in the deter-mination of micro-additions of alloying elements.The removal of all theiron is difficult, and traces left in solution adversely affect subsequentpolarograms.11 Greater success is possible when elements are determinedby amperometric titration.Potentiometric methods are not uncommon and they will be foundunder later headings. A. M. Zanko l2 has described suitable procedures forsome eight alloying elements.AZurninium.3~ 5-The separation of small quantities of aluminium fromlarge amounts of iron is the chief problem of this determination.P. Klingerl3has compared four methods, vix., ether extraction, electrolysis, oxidationwith sodium peroxide, and precipitation with cupferron. Of these, the firstgives the best results, the electrolysis giving low figures in the presence ofcopper and erratic results in that of titanium and vanadium. Cupferron isunsatisfactory. Sodium hydroxide precipitation of the iron gives a suitablefiltrate for precipitation of the aluminium with ammonia 14 or for its detectionby a colorimetric method using ammonium aurintricarboxylate,15 which willS. S. Rimlyand, Bull. Acad. Sci. U.R.S.S., 1040, 4, 225.E. J. Vaughan, “ The Use of the Spekker Photo-electric Absorptiometer in Metal-* Idem, “ Further Advances in the Use of the Spekker Photo-electric AbsorptiometerMonograph published by the Institute of Chemistry, 1942.lo M.Von Stackelburg, P. Klinger, W. Koch, and E. Krath, I’ech. Mitt. Krupp:l 1 G. Thanheiser and J. Willems, Mitt. Kaiser- Wilhelrn Inst. Eisenj’orsch., 1939, 21,l2 Trudy Vsesoyuz Konferentsii Anal. Khim. Akad. Nauk S.S.S.R., 1939, 1, 303;l3 Arch. Eisenhlittenw., 1939-40, 13, 21.1 4 S. Shinkai and T. Nagata, J . SOC. Chern. Ind., Japan, 1939, 42, 3970.16 L. P. Adamovich and A. J. Zagorulko, Zavod. Lab., 1939, 8, 1318; Khkm. Referat.lurgical Analysis.”in Metallurgical Analysis.”E’orschungsber., 1939, 2, 59.65 ; Arch. Eisenhattenw., 1939-40, 13, 73.Khisn. Referat. Zhur., 1940, No. 2, 64.Monograph pubiished by the Institute of Chemistry, 1941.Zhur., 1940, 6, 70206 ANALYTICAL cHIcMIeTBp.detect 0.01 "/o of aluminium.Determination of aluminium photometricallyis possible by using eriochrome-cyanine.16 Percentages of aluminium from0.1 to 0.001 present in the hydrochloric acid-soluble part of a steel can bedetermined spectrographically by using a strong spark and a long pre-sparking peri0d.l' The aluminium line 396143 is compared with iron linesat 3973066 and 3951.16. G. Hartlief,l* using Al 3961-5 and Fe 3963,describes a method employing the Feusner spark.Antimony3 and A~senic.~-No new methods other than those indicatedhave recently been described.Beryllium.-Percentages of this element between 0.1 and 1.0 have beendetermined without serious interference from nickel and chromium by aspectrographic method.19 Beryllium lines 2494.6, 3321.1, and 2650.6 werecompared with iron lines 2622.9, 3440.6 and 3286.8, and 2644.7 and it waslater found possible to extend the range of beryllium percentages to0 0 1 -2 * 0.Bor~n.~--hTo satisfactory chemical methods for boron present to theextent of 0.003% have been described, but a spectrographic method20using graphite electrodes impregnated with hydrochloric acid has given resulhfor boron percentages between 0-03 and 2.01.Unequal volatility of thesteel components cauaes changes in the intensities of the lines measured,the best pair being B 2497.72, Fe 2533.8.CuZcium.3-Determination of this element in cast iron as oxalate after aniron separation has been described.21Curbon.3-Chemical methods for the determination of carbon dependalmost exclusively upon combustion in oxygen, and variations in methodare mainly concerned with the treatment of the carbon dioxide and improve-ments in the apparatus. In both macro- and micro-chemical methods thegaa is absorbed in baryta.In the former case the carbonate formed isconverted into barium sulphate,22 contamination by atmospheric carbondioxide being avoided; in the latter case the excess baryta is titrated.23For this purpose A. Lassieur z4 recommends potassium hydrogen phthalate.G. Zaffuto25 has described a rapid method in which oxides of sulphur areabsorbed in aqueous sodium chloride and the carbon dioxide in standardsodium hydroxide, followed by titration with oxalic wid. Factors affectingthe accuracy of the combustion method have been discussed,26 and for rapidwork drying of the oxygen with magnesium perchlorate is re~ommended.~7l6 W.Koch, Arch. EisenhWtenw., 1939, 12, 69.1' 0. Schliesamann, &id., 1940, 14, 211., I e 0. Masi, Spectrochim. Acta, 1941, 1, 501.21 A. T. Sveshnikov and T. V. Boretskaya, Zauod. Lab., 1938, 7 , 1428.22 H. Kempf and K. Abresch, Arch. Eisenhtittenw., 1939-40, 13, 136.23 M. H. Kalina and T. L. Joseph, Heat Treat. Porg., 1939,%, 169.21 Compt. rend., 1938, 20'9, 731.25 Atti X Cong. intern. Chim., 1938, 111, 487.26 E. T. Saxer, R. E. Minto, and R. A. Clark, Blast Furnace Steel Plant, 1941, 29,27 Idem, &bid., p. 619.1* Ibid., 1939-40,13,295.2o Idem, ibi&., p. 462,718In the physical field, carbon contents of 06--1*1% have been correlatedwith magnetic saturation,28 and a similar rapid method compases themagnetic permeability of a sample with a known steel.29Chromium.1~ 3* 4, 5s 7, 8 0 9,119 120 16-Little change is to be noted in thechemical method for the determination of chromium. The steel is &a-solved in aulphuric and phosphoric 80 or perchloric acid,31 followed bypersulphate oxidation in the presence of silver nitrate and subsequenttitration of the dichromate with ferrous sulphrtte and permanganate. Vola-tilisation of the chromium as chromyl chloride enabled W.Dietz 32 to deter-mine this metal iodometrically in the condensate. Methods dependentupon the absorptiometer have shown great increases in speed combinedwith accuracy.Originally the coloured compound used was the dichromate.*Thk requires control of the acid ooncentration and the addition of urea toreduce silver complexes to colourless compounds and perchromate acid todichromate. For small amounts of chromium the violet-red compoundformed when diphenylcarbazide is oxidised by chromate in acid solutiongives a greater photo-cell response.9 For this method the chromate solutionis obtained after precipitation of the iron, etc., by sodium hydroxide andperoxide, with subsequent addition of sulphuric acid to the alkaline chromateaolution. Interference from 2 yo of vanadium was sucoessfully eliminatedby the use of spectrum-green filters. Both W. Koch and B. Bagshawe 33have used the diphenylcarbazide colour, the latter employing the Lovibondtintometer for comparison of his colours.V. F. Maltrtev and T. P. Temi-renko 34 used this same colour in the presence of the iron, comparing it withstandard steel solutions to which chromium had been added.Potentiometric methods allow of the determination in one solution ofchromium, manganese, and vanadium. In one of these35 three titrationswith ferrous sulphate with appropriate treatment of the solution in betweengives figures for all three elements. In another,36 the permanganate istitrated with sodium arsenite, the chromium and vanadium with ferroussulphate, and the quadrivalent vanadium with potassium permanganate.Some of the spectrographic methods have already been mentioned.Recently, P. Habitz 37 has discussed the choice of homologous pairs of linesand selects Ck 3128, Fe 3167, and Cr 3147, Fe 3167.In the visible spectrum,steeloscope methods38 for 0.02-@13:6 of chromium me Cr 6208, Fe 522728 B. A. Rogers, K. Wentzel, and J. P. Riott, Trans. Amer. SOC. Netals, 1941, 29,969.H. H. Blosjo, Trans. Amer. Found. ASSOC., 1939, 47, 469.30 E. C. Pigott, I d Chern., 1940, 18, 283.31 L. Silverman and 0. Gates, Ind. Eng. Chem. (Anal.), 1940, 12, 618.32 Angew. Chern., 1940, 53, 409.Zavod. Lab., 1941, 10, 357.36 J. Mummedal, Arch. Math. Naticrvidenskab, 1941, 44, 1 ; C'hem. Zentr., 1941, IT,8 0 A. S. Goralnik, Zauod. Lab., 1941, 10, 267.37 Spectrochim. Acta, 1941, 2, 158.33 J . SOC. Chem. Ind., 1938, 57, 260.641.L. V. VoIkova, Bull. Acad.Sci. U.R.S.S., 1940, 4, 216208 ANALYTICAL CHEMISTRY.for 0.1% or more and Cr 4254, 4274, 4289 respectively with Fe 4247, 4282,4271 for 0.1% or less.CobaZt.31 12-Although a-nitroso- p-naphthol remains a satisfactoryreagent for the determination of cobalt, greater speed with similar accuracyis claimed for an electrometric method 39 in which the cobalt and any man-ganese are titrated with potassium ferricyanide in the presence of ammoniumcitrate. Photometric methods depend upon the cobalt colour in hydro-chloric acid solution. K. Dietrich40 describes a variation of H. Pinsl's41method using a Leifo polarisation photometer with an incandescent lamp anda 668 filter. Pins1 treated the filtrate from a zinc oxide precipitation withstannous chloride and used a Nitra lamp with an S 66 filter.E. Bischof andG. G e ~ e r , ~ ~ using a Pulfrich photometer, measure the absorption due to acobalt ammino-complex. Interference due to manganese can be avoidedby the addition of ammonium chloride, and nickel in excess of 1% requiresthe preparation of an extinction calibration curve.Copper.3~ 5.12, 754opper can be determined electrolytically in thepresence of the iron by a number of methods. Working with a cell designedfor low temperatures, H. A. Frediani and C . H. Hale 43 obtained satisfactoryfigures over a range of copper content of 0.03-6.44y0. Alternatively, theelectrolysis may be carried out at 60-70" from a sulphate solution withthe addition of hydrazine, a pure aluminium rod being used as anode,u orfrom a sulphuric-phosphoric acid solution a t 0-6 amp.without stirring.45A colorimetric method 46 depending upon the photometric evaluation ofcolloidal copper sulphide is satisfactory in the presence of 20% of tungsten,2% of aluminium, 6% of molybdenum and20% of chromium. I n this methodand in another due to K. Quande14' vanadium interferes. Quandel,using a Zeiss Pulfrich photometer with an HG 578 filter, measures the coppercolour with rubeanic acid. After removal of the iron with ammonia, thisauthor also measures the copper colour with thiocyanate, using an HG 436filter with a mercury vapour lamp and correcting for the copper retained bythe iron precipitate. Two organic reagents are recommended, uix., salicyl-aldoxime 48 and dibromohydroxyquinoline 0xalate.4~ I n the latter casecopper is completely precipitated as a complex, the iron remaining in theacid solution.Titration of copper with potassium cyanide, solution of theiron being avoided, is proposed.5030 G. J. Steele and J. J. Phelan, Gen. Elect. Rev., 1939, 42, 218.40 Metallwirts., 1941, 20, 600.In&. Eng. Chem. (Anal.), 1940, 12, 736.I4 E. V. Smekh and A. M. Naigovzen, Zavod. Lab., 1940, 9, 1218. *46 L. Silverman, W. Goodman, rand D. Walter, Ind. Eng. Chem. (Anal.), 1942, 14,I6 G. Bogatzki, Arch. Eisenhuttenw., 1941,14,661.47 Ibid., p. 601.I8 E. Stengel, Tech. Mitt. Krupp: Porschungsber., 1939, 2, 87.'@ A. M. Zanko and A. J. Bursuk, Ber. Inst. physikal. Chem. Akad. Wiss. Ukr., 1938,I1 Arch. Eisefihuttenw., 1940, 13, 333.Angew.Chem., 1941, 54, 238.236.89; Khim. Referat. Zhur., No. 10, 92.P. I. Schportenko and V. F. Gtbren, Zavod. Lab., 1938, 7 , 1199UASKIN : ANALYSIS OF STEELS. 209Lead.4eparation of the lead as sulphide and subsequent determinationas sulphate 51 or electrolytically as dioxide 52 are suitable procedures.Reviewing available methods, E. Gregory and others 53 note that leadsegregates in steel and recommend its separation as sulphate.ikfanganese.l* 31 41 5. 7, 8 . 9 , 10- 12*35*36--Both volumetric and colorimetricmethods depend upon the formation of permanganate. Persulphateoxidation in the presence of silver nitrate as catalyst, followed by reductionwith atandard arsenite solution, appears to have superseded the bismuthatemethod.Osmic acid is also suitable as a catalyst.54 G. I. Rodin 55 suggeststhe use of thiosulphate for the final titration. Corrosion and heat-resistingsteels and carbide-bearing steels are best examined for manganese by per-sulphate oxidation after a zinc oxide separation of the iron and aluminiumfrom perchloric acid solution^.^^ C. M. Johnson 57 has reviewed the use ofperchloric acid in the manganese determination and has discussed the effectof molybdenum, vanadium and cobalt. uses the per-manganate colour for the absorptiometer, eliminating interference due tonickel and chromium by a difference method. A potentiometric titrationwith potassium permanganate 58 can give accuracy equivalent to the volu-metric bismuthate method. In addition to the spectrographic methodsalready noted, 0.MasiS9 suggests adapting for steel a method due toA. Rivas 60 used for determining manganese in pure salts.12* 37-Despite the considerable simpli-fication of the molybdenum method obtained by the use of the a-benzoin-oxime precipitation,61 considerable attention is still devoted to the deter-mination of this element. To avoid the ignition of the a-benzoinoximeprecipitate, W. W. Clarke G2 and C. Sterling and W. P. Spuhr 63 convert thisinto lead molybdate. Pure precipitates of lead molybdate can be obtained bytreating the neutral filtrate from a sodium hydroxide precipitation of theiron with formic acid, ammonium chloride and paper pulp and then precip-itating with lead acetate.64 W. W. Clarke 65 dissolves ignited molybdenumtrisulphide in sodium hydroxide, removes sodium tungstate, and thenprecipitates the lead molybdate.Butyl acetate can be used to extract thecoloured compound formed by the action of stannous chloride and potassiumE. J. VaughanMoZybdenum.l* 39 41 5* 7 p 8* 9 9 lo,6 1 A. E. Pavlish, J. D. Sullivan, and J. Shea, Met. and Alloys, 1939, 10, 150.52 G. E. F. Lundell, Met. Progr., 1939, a, 383.b3 E. Gregory et al., J. Iron Steel Inst., Advance Copy, Mid-April 1942.54 R. P. Forsyth and W. F. Berfoot, Ind. Cibem. Eng. (Anal.), 1939, 11, 626.5 5 Zavod. Lab., 1904, 9, 111.6 6 B. Bagshewe, J. SOC. Chem. Ind., 1939, 58, 106.s8 M. J. Eenis, E. I. Grenberg, A. M. Zanko, and L. N. Novikovca, Zavod. Lab., 1940,6s Met. ItaZ., 1938, 30, 111; Chim.et I d . , 40, 681.6o Berheft : Z . Ver. deut. Chem., No. 29; Angew. Chem., 1937, fio, 903.61 H. E. Knowles, J . Re8. Nut. Bur. Stand., 1932, 9, Paper No. 453.62 Chemist-Analyst, 1940, 29, 83.6s Chemist-Analyst, 1941, 80, 81.Iron Age, 1938, No. 26, 142, 16.9, 1082.In&. Eng. Chem. (Anal.), 1940, 12, 33E. Gregory, R. B. Foulston, and F. W. Gray, Analyst, 1941, 88,444thiooyanate on molybdenum solutions, and this ooloured extract can bewed for the colorimetric determination of the element.66 G. M. Poole 67has adapted this method for as muoh as 6% of molybdenum, and D. H.Heppell finds it satisfactory for rapid work. R. Sped 6v has used anether extracti~n,~O but E. J, Vaughan,& using controlled conditions, mewuresthe fhiocyanate colour in the presence of the iron.9.Klinger 71 has reviewed all the methods available for molybdenumother than the benzoinoxime separation as follows. Greater reliability isobtained by hydrogen sulphide separation under pressure, but this is notabsolutely necessary. Molybdenum may be weighed as trioxide or as leadmolybdate after separation as trisulphide, and the latter method is unaffectedby the presence of copper. Of colorimetric methods, those using thio-cyanate and stannous chloride, and phenylhydrazine are satisfaotory, butthe xmthate colour is not reliable. Photometric methods are useful forrapid work. Potentiometric methods give good agreement with the gravi-metric figures, but the stannous chloride titration requires great care.Spectrographic methods have been mentioned.The steeloscope can beused for rapid determinations of 0*05-0*3% of m0lybdenum.7~ P. Habitz 37selects as suitable homologous pairs Mo 2807, Fe 2783 apd Mo 2775, Fe 2779.NickeZ.1- 8 0 4 * 9 * 1 0 * 12~31, *5-Recent work haa dealt almost exclusivelywith the titration of nickel with cyanide either chemically 311 45 or potentio-metrically,73* 74 the latter method being preferred for rapid work. Separ-ation of the nickel is not necessary provided that all the iron be oxidised.A modification of an earlier method for copper 75 makes it possible to deter-mine nickel polarogrephicdy 76 in the presence of excess ammonia andprecipitated ferric hydroxide. The polarogram is started at -0.76 v., whichia beyond the copper steps at -0.09 v.and -0.34 v. Satisfactory resultshave been obtained in the presence of chromium, tungsten, titanium, andvanadium.Niobizam.4ee Tantalum.Phosphorw.8* 99 16- 53- @-Few gravimetric methods have been studiedreoently, but a satisfactory referee method eliminates arsenic with hydro-bromic acid and converts the precipitate of phosphomolybdate into leadmolybdate. The modern tendency has been to adopt a colorimetric methodin which the ammonium phosphomolybdctte is reduced to molybdenum-blueby stannous chloride.8 This method requires that interference from arsenic,silicon, and vanadium should be eliminated, and that allowance should bemade for the reduction of excess ammonium molybdate, a reaction which isL. H. James, Ind.Eng. Chem. (Anal.), 1932, 4, 89.6 7 Iron Age, 1941, 148, No. 15, 62, 145.69 Chem.-Ztg., 1940, 64, 363.7 1 Arch. EisenhUttenw., 1040, 14, 667.72 J. P. Belkevitch, L. E. Bruk, and N. S. Sventitskii, Zuvod. Lab., 1940, 9, 1279.73 R. Weihrich, Arch. Etkeoa?&Wew., 1940, 14, 55.74 0. Niezoldi, Chem. App., 1938, 26, 389.7 5 G. Thanheism and G. Msassen, Naturcoiss., 1937, 25, 426.76 J. S. Lialikov and J. I. Usatenko, Zavod. Lab., 1938, 7, 1100.6 8 Id. Chem., 1940, 16, 173.70 C. D. Braun, Z. anal. Chem., 1863,2, 36GASKIN: ANALYSIS OF STJEELS. 21 1largely inhibited by the presence of iron. Interference from silicon can beavoided by fuming, complex vanadium molybdates do not reduce to molybedenum-blue, and arsenic can be removed by boiling with hydrobromic mid.J.L. Hague and H. A. Bright 77 remove arsenic in this manner in a methodbased on measuring the trammittanoe of a phosphate solution to whichammonium rnolybdate and hydrazine sulphate have been added. A. J.Burmk,'8 measuring the molybdenum-blue colour, states that 0.03% ofmsenic causes no interference. T. P. Hoar,79 who uses an aliquot part of Bsodium hydroxide solution of a phosphomolybdate precipitate for treatmentwith ammonium molybdate and stannous chloride, fin& that as much 880.1 yo of arsenic does not affect the results.The yellow colour due to phoapho-vanrtdo-molybda;te is used by GIBogatzki 80 in a method where the iron colour is masked with sodium fluoride.H. H. Willard and 33. J. Center 81 use a Coleman spectrophotometer formeasurements with the same coloured compound.Diluted nitric acidsolution containing small amounts of phosphoric acid gives a delioate tur-bidity with strychnine molybdate, it reaction which can be used for a rapiddetermination of phosphorus.fsSiZicOlz.l* 3* 49 5# 7, 9-Separation of silioa from a hydrochloric aoidsolution is the basis of the chemical method, and to increaee the speed of theseparation S. N. Shkotova 82 adds a 0.1% solution of gelatin. This addition.does not affect a subsequent determination of phosphorus in the atrate.If this method is used in the presence of phosphoric acid, zirconium tmdtitanium are co-precipitated.& The volume of silicic acid which separateswhen a hydrochloric acid solution of steel is centrifuged is propurtional tothe amount of silica present.a This method is satisfactory down to a lowerlimit of 0.10/, of silicon, but tungsten interferes.A modified procedure canbe used for silica as low as 0°04y0.85 An unusual method for the separationof the silica depends upon an electrolysis with the sample as the anodein a bath oontaining sodium chloride, potassium bromide, and sodiumcitrate.g6 A high current is used and the silica remains in the insolubleresidue. A photometric method which can be used in the presence of tung-sten depends on the formation of soluble yellow sficomolybdatea in weaklyacid Spectrographically, some difficulties arise with siliconowing to a variation in intensity of the silicon line for the same concentrationof silicon in different alloys.88 In using the steeloscope and the line 3905,7 7 J .Res. Nut. Bur. Stand., 1941, 26, 405; Research paper 1386.78 Zavod. Lab., 1939, 8, 12. 7D Analyst, 1938, 6% 112.8o Arch. Ekenhfittenw., 1938-39, 12, 195.8 1 Ind. Eng. Chem. (AnaZ.), 1941, 13, 81. Zavod. Lab., 1939, 8, 213.K. L. Weiss, Arch. Eisenhuttenw., 1941, 15, 13.R. Ishii, Sci. Papers Inst. Phys. Chem. Res. Tokyo, 1930, 36, 491.Idem, ibid., 1940, 37, 143.A. Skrspski, A. Bielanski, and M. Sobieuki, Hutnuik, 1938, 10, 460; Met. Abetr.,1939, 10, No. 4, 226.87 R. Weihrich and W. Schwartz, Arch. EhnM$tenw., 1941, 14, 601.V. I(. Prokofiev, Compt. rand. A d . 8ci. U.B.B.S., 1941,239,449212 ANALYTICAL CHENZISTRY.and with a carbon steel as a standard electrode, a decrease of current pro-duces a greater decrease of intensity of the silicon line than of the iron wherethe proportion of silicon exceeds 1 yo .89SzcZph~r.~~--Sulphur is still determined by one of the three methods,combustion of the steel in oxygen and absorbing the sulphur gases produced,absorbing the hydrogen sulphide resulting from a hydrochloric acid attack onthe steel, or by dissolving the steel in an oxidising acid liquor with subsequentweighing of barium sulphate.The last method is the basis of a modernreferee meth0d,~3 which gives an accuracy within 0.0015% of the weight ofthe sample. Earlier, P. SchonggO had claimed high accuracy with thismethod in which analytical procedure is specified. By using the evolutionmethod and absorbing the gases in ammoniacal zinc sulphate it is possible totitrate this mixture directly with iodine after acidiiication.91 T.P. Hoarand G. E. S. Eyles 92 treat the steel with hydrochloric acid in an atmosphereof carbon dioxide, and after absorption of the hydrogen sulphide in am-moniacal cadmium chloride add an ice-cold mixture of sulphuric acid andpotassium iodate and iodide and titrate with thiosulphate. An accuracy of0.00270 is claimed. The nature of the absorbent of the sulphur trioxide inthe combustion method is not critical, hydrogen peroxide, iodine, andsilver nitrate being equally satisfactory.93 A combustion method D4 whichinvolved trapping the gases in potassium iodide and iodate has been criticisedby G. I ~ i m a r u , ~ ~ who states that carbon dioxide affects the result.A variantof this 96 is to absorb the oxides of sulphur in a little water to which a littleiodine and starch have been added, further additions of iodine being made asdecolorisation occurs, a method which has recently been recommended byS. M. Gutman and R. V. G~chfeld.~' Y. Kanamorigs obtains an accuracyof &O.OOl% by absorbing the gas in hydrogen peroxide and expellingcarbon dioxide from the absorbent with chlorine-free air. The use of tinas a catalyst during the combustion has been suggested.99Tantalum and Nwbium.3-T'he problem of the separation of these twoelements owing to the absence of selective reagents has not yet been entirelysolved. Spectrographically, 0. Schliessmann 100 has described a proceduresuitable for niobium contents greater than 0.1% and for tantalum greaterthan l.Oyo.The steeloscope has been used for niobium in the presence oftitanium and zirconium.101 Separation even of the mixed oxides is not anI. S. Kirin and N. S. Sventitskii, Zavod. Lab., 1940, 9, 1270.Ghem.-Ztg., 1930, 03, 364.91 J. Zeutzb, Z. anal. Chem., 1939, 116, 102.93 M. K. Chukavin rand M. N. Markelova, Zavod. Lab., 1938, 7, 1455.94 A. Vita, Stuhl und Eisen, 1920, 40, 033.Q6 Nippon Kinzonkii Sakkai-Si, 1939, 3, 60.O 6 I. Kassler, Chern.-Ztg., 1933, 57, 573.9 7 Zavod. Lab., 1938, 7, 399.sQ G . I. Stukanovskaja, Zavod. Lab., 1938, 7, 1455.loo Tech. Mitt. Kmpp : hrSChUngSbeT., 1939, 2, 186.Iol A. Fedorov, Bull. A d . Sci. U.R.S.S., 1940, 4, 212.02 Analyst, 1939, 64, 666.Tetsu-to-Hagane, 1940, 20, 630GASKIN: ANALYSIS OF STEE5S.213easy matter, and T. R. Cunningham lo2 has given details of the use of cup-ferron for this purpose. Photometric methods based on hydrogen peroxidecolours in specified conditions of acidity appear the most hopeful methodsfor individual determinations of these elements, care being taken to allowfor interference due to titanium. I n lOOyo sulphuric acid niobium gives acolour with hydrogen peroxide, titanium gives a colour which is only 30%of its colour in 20% sulphuric acid and tantalum shows no colour. Con-sequently photometric measurements in 20y0 and 100 yo sulphuric acidallow of a determination of niobium and titanium, tantalum being deter-mined by difference from the original weight of the mixed oxides.lo3 G.Thanheiser 104 determines niobium by its colour with hydrogen peroxide insulphuric acid and 40% phosphoric acid (a strength which eliminates thetitanium colour when the titanium is less than 1%) and tantalum by theyellow colour formed with pyrogallol in 3% ammonium oxalate.A correc-tion has to be made for titanium, determined with chromotropic acid in thesame solution.TeZZuriurn.3-Te 2385.76 is compared with Fe 2378.98, an A.C. arc beingused and log ratios of intensities being plotted.105Tin.3-Existing methods have been re-examined,loB and E. T. Saxerand R. E. Minto lo7 propose titration of the reduced tin with potassiumiodate after separation of the iron with ammonia from a hydrochloric acidsolution.Titanium.3* 5* 339 37* lol* 1°3-As has been indicated under tantalum, theperoxide colour is suitable for determinations of titanium in steel.Separ-ation of the titanium is not essential, although cupferron has been used forthis purpose.33 The Zavodskaya laboratory 108 has developed a rapidmethod by adding phosphoric acid and hydrogen peroxide to a perchloratesolution, a method which is unaffected by 1% of chromium. In addition tothe steeloscope method,lo1 L. E. Bruk and N. N. Sorokina lO9 use the linesTi 3088.032 and Fe 3083.747 for quick results with a 5% accuracy. Otherhomologous pairs of lines suitahle for titanium determinations are Ti 3078,Fe 3097 and Ti 3168, Fe 3167.37T~ngsten.~. 4 9 lo* 12* 68-Tungstic oxide can be separated from a varietyof solutions.This oxide and silica are precipitated quantitatively from aperchloric acid solution, and this precipitate can be ignited and weighed,the silica being removed with hydrogen fluoride.110 This method has recentlylo3 Ind. Eng. Chem. (Anal.), 1938, 10, 233.lo3 P. Klinger and W. Koch, Arch. Ebenhuttenw., 1939-40, 13, 127.lo* Mitt. Kaiser- Wilhelrn Inst. Ekenforsch., 1940, 22, 255.lo5 R. E. Nusbaum and J. W. Hackett, J . Opt. SOC. Amer., 1941, 81, 620.lo6 S. Mischonsniky, Congr. Chim. Ind. Compt. rend. 18drne Congr., Nancy, Sept.-lo’ Steel, 109, No. 3, 1941, 66, 91.lo* S. Ri. Gutman, $1. N. Zarogatskaya, apd Z. A. Vyvapaova, Zavod. Lab., 1940, 9,loo Bull. Acad. Sci. U.R.S.S., 1940, 4, 23.110 A.Clauberg and P. Behmenberg, 2. anal. Chem., 1936, 104, 245.Oct. 1938, 438.1012l4 ANALYTICAL CHEMISTRY.been advooated by S. M. Gutman and R. V, Gochfeld.ll1 8-Hydroxy-quinoline can be used to separate tungsten in an acetic acid solution, andthis precipitate can be ignited to tungstic oxide after treatment with oxdicaoid.l12 Vandiurn and molybdenum interfere in this method. BothD. )I. Heppell 68 and D. P. Chatterjee u3 reoommend dissolving precipitatedtungstic oxide in standard sodium hydroxide, the latter mixing the preoip-itate with warm water and neutral glycerol or mannitol to avoid hydrolysis.The time taken in using the hydrochloric acid solution method and subse-quent oxidation with nitric acid can be reduced if the steel is &st heated to1150-1200" for 15 minutes and quenched in water.l14 A photometricmethod, which requires some correction for chromium, depends upon thered colour formed by tungsten with quinol in a solution containing sulphuricand phosphoric a0idS.1~~ It is necessary to reduce both iron and molyb-denum with sfannous chloride.Urccniz~.~.-8-Eydroxyquinoline is B suitable reagent for separatinguranium after removal of the iron by electrolysis and manganese withsodium carbonate.116 Any aluminium in the uranium can be determinedby fusion and precipitation of the hydroxide.pmsibly the most difficult having regard to the amount of manipulationrequired by the ordinary chemical method.Much work has been done todevelop colorimetric methods. Of the colours available, that with hydrogenperoxide is suitable.68 H.Pins1 114 makes the determination in the presenceof the iron, and adds sodium fluoride to eliminate the colour due to titanium--&method which is satisfactory for 0-%23% of vanadium.finds it necessary for titanium-free steels to apply a correction for thecoloured complex due to molybdenum. The orange colour of the phospho-vanado-molybdate complex can be measured accurately for a percentagerange of vanadium 0.01-5~0,118 as much as 10% of molybdenum, titanium,and cobalt and 20% of tungsten causing no interference. A. L. Davydovand Z. M. Vaisberg119 have studied the formation of molybdenum-blueduring the reduction of the phospho-vanado-molybdate complex. Thisreduction can be used to give an aocuracy of 4% for 0*1-2'3/, of vanadium.E.J. Vaughang uses the same complex to separate small amounts of vana-dium, and after treatment with sulphuric acid and oxidation, memums thevanadium colour with stryohnine. A potentiometric titration of vanadiumwith ferrous sulphate, similar to that already has been madeby F. Eisermann.120Although some latitude can be dowed in the conditions for the spectro-?,7ana&um.l* 3 9 49 5, 8 9 9. 10. 111 12. 35, 369 68-The vanadium determination isE. J. Vaughan111 Zavod. Lab., 1938, 7, 698.114 A. A. Fedorov, Zavod. Lab., 1940, 9, 1319.116 G. Bogatzki, 2. awl. Chem., 1938, 114, 170.11* A. M. Dimov and R. 8. Moltschanova, Zavod. Id., 1938, 7, 663.11' Gksserei, 1940, 27, 441.ll0 Zavod. Lab., 1940, 9, 716.112 Z.S. Muchina, ibi&., p. 407.J. Indian Chern. Xoc., 1940, 17, 369.G. Bogatzki, Arch. EiaenhSttenw., 1938-9, 12, 639.180 Arch. Z&enh2tttenw., 193G-9, 12, 245GASKIN: ANALYSIS OF STEPJLS. 215graphic determination of vanadium, high resolution is necessary, and withthis an accuracy of &5% can be obtained by using V 3271.3, Fe 3212.1a1Por similar work, K. A. Suchenko 1% uses V 4379.24 and E'e 4376.0.Zirconium.-The use of propylaraonic acid as a specsc reagent forzirconium, by which means O*lyo of this metal can be determined in thepresence of many other elements, has been proposed.123Oxygen, Nitrogen, and Hydrogen.-The discussion of the methods for thedetermination of these elements given in " Sampling and Analysis of Carbonand Alloy Steel " is pertinent.Work has been done on the vacuum fusionmethod, tin being used as a flux for all three elements.lM1 lz6# lz6 All thehydrogen can be obtained by heating to 600" in a high vacuum, highertemperatures producing more nitrogen and carbon monoxide.lZ7 Thismethod of vacuum heating rather than vacuum fusion is preferred byK. TawctraThe residue from a hydrochloric acid solution of a steel contains some ofthe nitrogen, particularly in titanium steels, and treatment of this residuewith sulphuric acid and potassium and copper sulphates is necessary.129In this method the ammonia is distilled into standard hydrochloric acid,the excess of which is titrated with sodium hydroxide, sodium alizarin-sulphonate being the indicator. Errors may arise in the titration of excesesulphuric acid when this is used to absorb the ammonia, owing to thepresence of carbonate in the alkali and the indicator used.Bromocresol-blueis rec0rnmended.13~ Increased speed in the riitrogen determination may beobtained by dissolution in sulphuric acid, addition of tartaric acid andsodium hydroxide, and distillation of the ammonia.131 Colorimetric deter-mination of the nitrogen can be made by using the colour with Neasler'sreagent and measuring it photoelectrically.132 Alternatively, G. J. Vein-berg adds a 25% solution of thymol in alcohol to a hydrochloric acidsolution of the steel, followed by sodium hypobromite. The colouredcompound is extracted with ether, and the colour matched against standardammonium chloride.Substitution of isopropyl for ethyl ether producescolours which are intense and unchanging.134Reduction of oxides in nitrogen a t 1260", with tin as a flux, followed byconversion of the resulting carbon monoxide into dioxide by passage overlZ1 J. Wilken, Arch. Eisenhilttenw., 193l3-9, 12, 133.laa Zavod. Lab., 1938, 7 , 693.l Z 3 H. H. Geist and G. C. Chandlee, Ind. Eng. Chem. (Anal.), 193i, 9, 169.lZ4 P. S. Lebedev, Zavod. Lab., 1938, 7 , 1378.125 Eight Report, Heterogeneity of Steel Ingots, J . Iron Steel Inst., May 1939;la6 T . Yazima, IPetszc-to-Hagane, 1938, 24, 947.l Z 7 W. C. Newell, J . Iron Steel Inst., 1940, Advance Copy.lZ8 l'etsu-to-Hagane, 1939, 26;, 413.12' T. R. Cunningham and H. L. Hamner, In&.Eng. Chem. (And.), 1939, ll, 303.lS0 I. Wada and R. Ishii, Sci. Papers Inst. Phy8. Chem. Res. Tokyo, 1940, 3'7, 66.lS1 H. Kempf tmd I(. Abresch, Arch. Eisenrnttenw., 1940, 14, 250.132 H. F. Beeghly, I n d . Xng. Chem. (Anal.), 1942, 14, 137.133 Zavod. Lab., 1938, 7 , 1251.who heats 50-100 g. of steel at 800" for 1-2 hours.Third Report of the Oxygen Sub-committee, ibid., Advance Copy, May 1941.lS4 U. J. Veinberg, &id., 1940, 9, 1073216 ANALYTICAL CHEMISTRY.heated copper oxide affords a rapid method for the determination of oxygen. 135Results obtained by this method compare favourably with those obtainedby vacuum fusion methods and, apart from aluminium-killed steels, can beobtained in less than 20 minutes. Solid absorbents are satisfactory for thegases produced by reduction in hydrogen at 1250°.136J.G. N. G.2. FRACTIONAL DISTILLATION.The subject of fractional distillation has of recent years developed greatlyand become of such wide and rapidly increasing application and importancein Analytical Chemistry that no excuse is offered for considering it again sosoon after the Annual Reports of 1940.It is obviously impossible, in the space available, to deal with everyaspect of the subject, and for that reason careful selection has been madeof the Sections which appear in this Report. Hence, no mention is made ofsuch matters as the practical design, lay-out, and operation of columns, thetheoretical design of columns and the calculations involved, the solutionof problems in binary and multicomponent rectification, discussions of batchand continuous distillation, and the importance of reflux ratio.Instead,it was felt that, following the 1940 review, a rather wider consideration ofcertain branches of the subject might now be of use to indicate the manytypes of problem in which it is employed and to give some idea of the efficientapparatus which has recently become available. To that end, a fairlycomprehensive bibliography is provided.The sections on the determination of the number of theoretical platesin a column and on the choice of a column are included because such a mass ofunco-ordinated and apparently contradictory data has been published onthese matters that some confusion is likely to arise in the mind of the non-specialist.It is therefore hoped that these notes may assist in clarifyingthe position.(i) Normal Distillation.Laboratory Colunms and Accessories.-A review, containing manyreferences up to that date, of the literature on the construction, testing, andoperation of laboratory fractionating columns is given by C. C. Wad1He elaborates six essentials for consideration in the design of fractionatingequipment : (i) the still-pot should be of adequate size and of shape suitablefor maintaining a satisfactory evaporating area throughout the distillationand should be efficiently insulated; (ii) the column should have a height atleast 15 times the internal diameter, should be well insulated and providedwith a closely controllable heater jacket to compensate for heat losses;(iii) an effective packing or other means of bringing vapour and liquid intoclose contact is essential; (iv) the packing should have a large surface area,a small hold-up and pressure-drop and be capable of handling a large through-135 L. Singer, Id.Eng. Chem. (Anal.), 1940, 12, 127.lS6 G. J. Veinberg, Zavod. Lab., 1940, 9, No. 1, 23.l U.S. Bur. Mines, 1939, Tech. Paper 600FAY : FRACTIONAL DISTILLATION. 217put ; (v) bubble-plates should have similar properties to packings ; and (vi)the still-head should be capable of close regulation.Efficient laboratory columns, then, may be divided into two broadclasses, ( a ) those employing plates, which may be perforated or of thebubble-cap type, or a combination of both, and ( b ) those containing packings,which may consist of " dumped " or of uniformly arranged material.Ex-amples of the various types were given in 1940, but mention may be madehere of some which have been described recently.A perforated plate column for analytical batch distillations has beendeveloped by C. F. Oldershaw.2 The plates are of 25 mrn. diameter and have42, 44, or 81 perforations. Variation of the diameter of the holes showedthat with a reflux rate of 2.4 1. per hour the plate efficiency varied from68% with diameter 1.35 mm. up to 90% with diameter 0.65 mm. Forvarious reasons the author favours the use of 0.85 mm. perforations and aplate spacing of 26-30 mm. The paper includes the results of efficiencytests and comparisons with other columns, including the Stedman and thehelix-packed type." Dumped " glass helices are the packing material used in an efficientcolumn, designed by A.J. Bailey,3 with a hold-up of less than 0.1 ml. perplate and H.E.T.P. of 5 cm. A still-head suitable for use at reduced pressuresis also described. The same packing is used in an all-glass unit for thedistillation of corrosive liquids, such as chlorosulphonic acid, in the absenceof air and grease.* A continuous apparatus described by R. W. Hufferdand H. A. Krantz 5 employs nickel helices as packing material and has over50 theoretical plates and a throughput of 3 quarts per hour. Data ondistillation of toluene-methycycluhexane mixtures are given. An expandedshale aggregate packing has been investigated by H.G. Thode and F. 0.Walkling,6 who find that with hydrocarbons the efficiency and throughputcompare favourably with those of other packings, whereas with aqueoussystems it is even more effective. The authors suggest that this materialshould not only be applicable industrially but should also be of use in theseparation of isotopes. H. R. Snyder and R. L. Shriner 7 have designed acolumn, intended in particular for the use of students, packed with crystallinecarborundum, and other simple columns suitable for routine analysis havebeen described by L. SmithAn extremely efficient, uniformly packed column has been designed byH. S. Lecky and R. H. Ewel1.l0 A cupped, stainless-steel gauze spiral isfabricated around a central, grooved metal rod, the whole being fittedclosely into a glass tube.The efficiency is as high as 18 plates per foot withand by R. W. Harkness and R. E. Bland.9Ind. Eng. Chem. (Anal.), 1941, 13, 265.A. W. Hixson and A. H. Tenney, ibid., 1942, 14,345.Ind. Eng. Chem., 1941, 33, 1455.Canadian J . Res., 1942, 20, B, 61.Kgl. Pysdograf. Sallskap. Lund, Handl., 47, No. 5, 1.Oil @as J . , 1941, 39, No. 46, 149.a Ibid., p. 487.J . Chem. Educ., 1940, 17, 588.lo Ind. Eng. Chem. (Anal.), 1940, 12, 64421 8 ANALYTICAL CHEMISTRY.hold-up and pressure-drop only 0.4 ml. per plate and 0.1 rnm. of mercury perfoot respectively.R. H. Baker, C. Barkenbus, and C. A. Roswellll have developed thespinning-band type of column, which has a low hold-up : their design,546 om.high, showed 70 theoretical plates, when tested with the heptane-methylcyclohexane mixture, with a throughput of 2.7 ml. per minute andhold-up 0.1 ml. per plate. A description of a new fractionating column forthe temperature range -190" to 300" has been published by W, J. Podbiel-niak.12 The packing may be of two designs, both of the precision-wound,fine-wire type, so arranged that capillary films between the closely spacedturns provide a large liquid surface. Extreme care is taken to ensureadiabatic conditions of operation, for, in addition to highly efficient vacuumjacketing around the flask, column, head, and all connections, a method ofcompensating for residual leakage of heat is provided. The special vacuum-jacketed ground glass joints may be used for temperature ranges from - 190"to 300" while still remaining vacuum-tight.Complete interchangeabilityof columns and flasks allows the use of the apparatus for a wide variety ofpurposes. A low hold-up and good throughput are claimed, and testsshowed 75 plates in 14 in. length, the performance being maintained when thediameter was increased to 1 inch. Details of efficienoy data for varioussizes are given. Two arrangements of apparatus, one for preparative workand the other for analytical use, suitable for fractional distillation at lowtemperatures are also described by H. Koch and F, Hilberath,l3 and theSimons column has been modified for liquids of b. p. -30" to -5" by E. 0.Ramler and J. H. S i m ~ n s . ~ ~Several types of laboratory column for the separation of close-boilinghydrocarbons have been compared by G.R. Schultze and H. Stage,15 andthe same authors, with K. Klein,l6 discuss recent types and give details of aglass column, employing 4-chamber tubes, which contains 10 theoretioalplates in 62 cm. length. Fractional distillation in spirals with an oscillatingand eccentric movement has been accomplished by J, Piazza:' and F. Rosen-dahl l8 has described a column consisting of chambers through which thevapours pass and into which the reflux liquid is sprayed.and by A. R.Richards,ao who emphasise the advantage of vapour take-off systems, inwhich no liquid hold-up is involved. The latter gives constructional detailsof a head of this type and discusses a modification in which an automaticdevice is incorporated for increasing the reflux ratio as the cut-point isThe design of still-heads is reviewed by R.E. Gurovich11 Ind. Eng. Chem. (Anal.), 1940, 12, 468.lS Brennstoff-Chem., 1940, 21, 197.l4 Id. Eng. Chem. (Awl,.), 1942, 14, 430.2. physikal. Chem., 1941, A , 188, 163.1 7 Ind. y Quim., 1940, 3, 22; Anal. Inst. Invest. cient. tecn., 1938-9, 8-9. 56, 78;l2 Ibid., 1941, 13, 639.l5 2. Elektrochem., 1941, 47, 848.Anal, Soe. cient. Argentinu, 1941, 131, 239.Chem. App., 1941, 28, 70.ID Khim. Maahinostroenie, 1940, 9, No. 2, 17.2o I d . Eng. Chem. (Anal.), 1942, 14, 649FAY ; FRACTIONAL DISTILLATION. 21 9approached. A reflux regulator and head for laboratory columns, designedby F. D. Rossini,21 employs a non-lubricated glass valve and provides ameam of measuring throughput and of controlling and estimating the rateof take-off.A magnetically operated valve, which permits take-off of adefinite amount of distillate at regular time intervals, is incorporated in adesign by B. Ferguson, junr.,22 and with the addition of a timing devioe anda recording thermometer a distillation curve oan be automatically obtained.A vapour partition head, described by P. Arthur and C. L. Nickolls,a isclaimed fo remove impurities more efficiently than the normal type. Aneasily cleaned head is described by A. Turk and A. Matuszak 2p and a newtype of dephlegmator by A. A. G a u ~ h i n . ~ ~Among other subjects of interest to constructors of laboratory columns,mention may be made of an automatic device, employing it photoelectriorelay system, to control the heat input to a sti11,26 a glass needle valve, withgrooved stems, suitable for controlling vapour or liquid flow in distillationheads,27 a double spiral condenser for use in downward distillation or reflux-ing,z8 a device for overcoming frothing by superimposing a tube containingglass beads,29 and details of the construction of glass bellows for vacuumja~keta,~O and of glass helices for column packings.31The Determination of the Number of Theoretical Plates in a Column.-The number of theoretical plates oontained in a fraotionating column iscommonly determined by an application of M.R. Fenske's equation 32 €or abinary mixture under total reflux.If n = the number of theoretical plates in the column, xt = the mol.concentration of the more volatile component, x" = that of the leas volatilecomponent, and ct = the relative volatility of the two components, thenwhere the subscripts T and B refer,to the top and the bottom of the packingrespectively.The procedure is to charge the still with a suitable binary mixture,distil under total reflux until the column is in equilibrium, and then takesimultaneous samples of reflux from above and below the packing for analysis.In practice, the samples are usually withdrawn from the condenser and thestill-pot, allowance being made for the fractionation taking place in these zones.The first, a practical point, is that for Two considerations emerge.a1 J .Res. Nat. Bur. Stand., 1939, 23, 509.22 Ind. Eng. Chem. (Anal.), 1942, 14, 493.23 Ibid., 1941, 13, 356.O 6 Khim. Mashinostroenie, 1939, 8, No. 8, 9.26 S. A. Hall and S . Pdkin, Ind. Eng. Chem. (Anal.), 1942, 14, 652.2 7 G. P. Gibson, J . SOC. Chem. Ind., 1939, 58,317.p8 M. T. Bush, lnd. Eng. Chern. (And.), 1941, 13, 592.29 G. W. Harmsen, Chem. Weekblud, 1941, 38, 330.*" D. J. Pompeo and E. Meyer, Rev. Sci. Instr., 1941, 12, 368.81 E.g., R. W. Priae and W. C . McDermott, Ind. Eng. Chena. (And.)., 1938, 11, 289.32 I d . Eng. Chem., 1932, 24,482.aQ Ibid., 1942, 14, 72220 ANALYTICAL CHEMISTRY.accurate determinations of n, care should be taken so to choose the mixturethat very small concentrations of one component do not occur a t either endof the column.The second is that the value chosen for a will affect thedetermined number of plates. In many cases the arithmetic or geometricmean value of a proves satisfactory over a reasonably wide concentrationrange, but a common method of overcoming possible inaccuracies is illus-trated by L. B. Bragg.33 The concentrations of the components in thebenzene-ethylene dichloride system are measured by the refractive index,and a graph is constructed of this property against the number of theoreticalplates, use being made, not of an average value of a, but of the value corres-ponding to the particular conditions under consideration. Such a plothas, of course, no particular zero point, the theoretical plate scale merelyrepresenting differences, but by its use the number of plates in the columncan be obtained immediately from the difference between the values corres-ponding to the samples from the top of the column and from the still.Bragghas used " ideal " values, calculated from the vapour-pressure data of thepure components.Lecky and Ewell lo have concluded that the systemis not an ideal one, and use " apparent " volatility ratios. They show thatthe values obtained are in fair agreement with those obtained by Bragg'smethod, but for the purpose of determining the plates in a column they haveconstructed the corresponding plot for the " ideal '' n-heptane-methylcycl-hexane system.In short, it may be concluded that it is essential to compare columnsunder absolutely identical conditions.This is very strongly emphasisedby a recent publication of Bragg and A. R. Richards.= They have studiedbinary mixtures for the purpose of testing Stedman columns at reducedpressures, and have determined values of a for benzene-ethylene dichlorideand o-dichlorobenzene-diethylbenzene mixtures a t various subatmosphericpressures. Included in the data, however, is a plot for the former system atatmospheric pressure, and the values of n, for a 20-30 plate column, obtainedfrom the middle portion of this new graph are of the order of 50:/, higherthan those obtained from the previous plot.A recent summary by J. GriswoldN" provides a correlation betweenrelative volatility data for the benzene-ethylene dichloride and heptane-methylcycZohexane test mixtures.It follows that by using the datafavoured by this author for the latter system the agreement between testsmade with the two mixtures is good, and the differences found by Leckyand Ewell (see above) are explained.The Choice of a CoEumn.-Although great importance has been attachedin the literature to the H.E.T.P. of laboratory columns, it is not the only, orindeed the most important, factor to be considered in the selection of a suitablepacking for a particular purpose. The larger the H.E.T.P. value, of course,the greater will be the length of column to contain a given number of plates,Even so, the appropriate values of a are not absolutely fixed.Yo I n d . Eng. Chem. (Anal.), 1939, 11, 283. 34 I n d . Eng. Chem., 1942, 34, 1088.s40 Ibid., 1943, 35, 247FAT : FRACTIONAL DISTILLATION.22 1but this factor will normally enter only in the limiting case where there is in-sufficient height available to accommodate the required column. The shortlength of column obtained by using a packing with a low H.E.T.P. gives theadvantages of ease of manipulation and ease of obtaining adiabatic operatingconditions, but these facilities should not be allowed to over-rule the questionof the time taken to carry out the distillation. In many cases it is fairlysimple to overcome the difficulties associated with the H.E.T.P. a t someinitial expense and trouble, but if the apparatus selected is such as to requirea long time in order to carry out a satisfactory separation, the user willalways be faced with a considerable operating expense or loss of time.This question of the time required to carry out a given distillation isbound up with that of the hold-up of liquid in the column while it is operating.The factors which affect the efficiency of the separation obtained from thefractionating column are : the number of theoretical plates, the reflux ratio,the total hold-up in the packing under operating conditions, and the ratioof charge to the hold-up.The effect of the first two of these factors has beenmuch studied, but considerably less attention has been paid to the remainingtwo. The loss of fractionating efficiency due to increase in hold-up has beeninvestigated theoretically by A. Rose, L. M. Welshans, and H. H. L0ng.3~The point may be brought out by the following simple consideration.Suppose we have a column with a large number of theoretical plates andrunning a t a high reflux ratio, separating a mixture of two components,A and B, and the efficiency of the column is such that substantially pure Awill be taken overhead when the concentration of A in the still is 1%.Wewill suppose that the column hold-up is 50 ml. and that the mixture chargedto the still contains 100 ml. of component A and 900 ml. of component B.By the time distillation has proceeded to the point a t which there is 1% of Aremaining in the still, the contents of the latter will be approximately875 ml. of B, and 9 ml. of A. Inside the column itself the average composi-tion of the hold-up will be 50% of each component; and there will be, there-fore, 25 ml.of A held up. The result is that, up to this point, 66 ml. of Awill have been produced as distillate in a pure condition, and from now onthe degree of purity will gradually fall. Now consider a similar case inwhich the same column and mixture are used but the volume of materialcharged is increased ten times. At the critical point the still will containapproximately 9,000 ml. of B and 90 ml. of A, and the hold-up in the columnwill contain 25 ml. of A as before. Consequently, 885 ml. out of the initial1,000 ml. of A will have been produced in a pure state. The result of increas-ing the ratio of charge to hold-up has thus been to increase the recovery ofpure A from 66 to 88-5%, and furthermore the rate a t which the purity willfall off will be lower in the second case.From these considerations it will be seen that two columns containingthe same number of theoretical plates, operated a t the same reflux ratioand with the same ratio of charge to hold-up, will give comparable fraction-ating efficiencies.Thus, the construction of a still and column can be so96 Ind. Eng. Chem., 1940, 32, 668, 673, 675222 ANALYTICAL CHEMISTRY.arranged that any type of packing will give an identical degree of separationwith that of any other column, since the plates and ratio of charge to hold-upmay both be varied independently and therefore appropriate values may beselected; but once these values have been fixed, the time taken to carry outa distillation has also been automatically fixed.The question of the satisfactory ratio of charge to hold-up is one to whichit is difficult to give a specific amwer, but experience has shown that forefficient fractionation, particularly of complex mixtures, the still chargeshould be at least 20 times the hold-up.Having by these considerations chosen a column, a certain size of charge,and a reflux ratio, the time taken to carry out the distillation will have beenfixed, and it is desirable therefore, when considering column packings, tohave some factor which will allow one to see whether this time is going to belong or short.The factor chosen, called the “ hold-up factor,” is convenientlyexpressed as ml. of hold-up per theoretical plate divided by the operatingboil-up rate in ml. per second.s6 The value of this factor is a direct measureof the time taken to carry out any given distillation.In other words, if twocolumns are arranged with identical numbers of plates, charge, etc., one ofthem being packed with material having a hold-up factor of 4 and the otherwith material having a hold-up factor 8, any given distillation will taketwice as long in the second column as it will in the former. Factors of similarform have also been introduced by L. B. Bragg 37 and W. J. Podbielniak.12The determination of hold-up, particularly under actual operation con-ditions, is not easy, and only a few values are available in the literature.Moreover, their usefulness is somewhat impaired by the fact that whenmaking comparisons between columns it is advisable to ensure that the testahave been carried out by exactly the same methods.In Tables I and I1results of tests on a wide variety of column packings are given. In thefirst table the tests have all been made in exactly the same way under con-ditions similar to those which will occur in practice. In the second tablesome further results are given for the sake of interest, although the test datahave not been determined under strict operating conditions, but in separateexperiments in which cold light petroleum has been run down the columncounterourrent to a stream of air (presaturated with petroleum vapour).It is known that this method of determining hold-up gives high values, andtherefore it should be realised that the hold-up factors given in Table I1 &reprobably on the high side.Theefficiency of a packing is often greatly increased by flooding the columnbefore starting distillation. Several of the packings in Table I have beentested with and without this initial flooding, and the effect on the numberof theoretical plates and the hold-up factor will be apparent.There is one further point to be noted when considering the data.-3* Research Department, Anglo-Iranian Oil Co., Ltd.The author is indebted tothis Company for permission to use data included in this Section and would particularlylike to express his appreciation t o Messrs. P. Docksey and J. W. Hyde for so kindlyplacing their experience and advice at his disposal.37 Trans.A w r . Inst. Chem. Eng., 1941, 37, 19Z'mt Data on Column Packings.Data obtained under operating conditions.TABLE I.NO.12345678910Type of packing.Glass helices, 4 in.Steel ,, 5/32in.Stedman, type 114Spiral screen (cuppedPodbielnlkk (wirl spiral)Empty tubeEyelets (No. 2) **Glasskbe, I.D.6mm.,O.D.I , Y ? f in.spiral 4 mm core)7.5 mm., length 8 mm.Dimensions ofcolumn.mm. cm.20 15720 15735 20586.52o 20 86.525.4 6125.4 6146l7 17 46.Diam.,,-.3.7 1284.15 12836 13736 13749 51737.5 11937.5 119Boil-up rate,* ml./hr.Theoreti-At normal cal platesAt flood operating (C,Hs-point. rate. CsH,ClS).2,000 1,800 41-52,000 1,800 3210.00 8.500 22 ~~ 2;700 $200 13.52,700 2,200 131.800 1.400 231;SOO 1;400 1925 66066U 400 - 150 7 - 250 a7,000 6,000 13.57.000 m o o 13.5400 11.,__- ~- -13,500 lZ,k% 427,000 6,000 7.07.000 6.000 7-0H.E.T.P.,em.3.84.91.0.56.46.62.653.21.834.218.31610.112-3171710.1Light petroleum @.p . SO'). ** Tinned brass hohw cylinders, I.D. 4.14 mm.,TABLE 11.Data obtained by countercurrent method with cold lightEfficiencyDimensions ofcolumn.Diam., Length,mm. em.15714 2o 10014 10036 29102 945214415885 102204 24449 8730{ 1:;cBoil-up rate, ml./hr.-7 A t normalA t flood operating Thcoreti- H.E.T.P.,point. rate. cal plates. cm.2,000 1,800 32 4.9 - 960 4.5 22 - 960 3.5 2810000 8,000 1 43 18.113,000 11,OOO 12.9 16.533,000 25 16.821.63347,700 %E 4111,000 70,000 85 10.380:OOO 50,000 42 22.97.4 L 224 ANALYTICAL CHEMISTRY.Applications.-The requirements for columns for the separation ofhydrocarbon mixtures are enumerated by C.K ~ e p p e l , ~ ~ who describessuitable apparatus, expressing a preference for the long-vapour-path typeof column. Various applications are discussed. A comparison of Podbiel-niak and other type columns for this purpose is made by J. J. Savelli,W. D. Seyfried, and B. M. Filbert,39 and H. Macura and H. Grosse-Oetring-haus 4o have made experiments on the fractionation of aromatic and paraffinmixtures in columns containing various types of packings. A column isdescribed, packed with metal spirals, by means of which as little as 1% oftoluene can be detected, in mixtures with benzene and xylene, a t distillationrates of the order of 30 ml.per hour. Hexane can similarly be determinedin mixtures with pentane and heptane, and a modification of the columnincreases the sensitivity of the aromatic analysis to the extent of detecting0.5% of toluene a t a slightly higher distillation rate.This problem of the routine analysis of coal-tar spirits has assumedconsiderable importance during recent years. The matter is complicatedby the fact that the increasing popularity of the vertical retort has resultedin the production of what is known as “ low gravity ” benzole, i.e., materialin which the aromatic constitutents are associated with considerable quan-tities of other hydrocarbons. The use of empirical methods, such as theclassical Colman-Yeoman procedure, is not applicable with accuracy in suchcases, and a distillation test has been developed a t the Government Labora-tory.41 A small, metal-spiral packed column, known as G.L.1 design,containing 7 theoretical plates, with a low hold-up and a fixed reflux head tosimplify routine operation, is used. A charge of 25 ml. is adequate and adistillation rate of 10-20 ml. per hour may be employed. The accuracyis such that under these conditions small quantities of toluene may beestimated within 0.4% or less. By increasing the charge to 100 ml. theaccuracy is increased to O.lyo. To allow for associated non-aromatichydrocarbons, the percentage of toluene present in the toluene fraction isestimated by refractive index, specific gravity, or critical solution tempera-ture with acetic acid, and graphs have been constructed for this purpose.Applications of the G.L.1 column have also been extended to include theestimation of benzole in wash oil. In this test a “ bridge ” of cycbhexanolis added to prevent the column from flooding owing to distillation of washoil after the benzole has distilled over. The ordinary fractionation methodof determining the benzene content of wash oils has been criticised by W.BrOs~e,*~ who describes a new method involving the use of fine fractionatingcolumns. Several times as much benzene is claimed to be recovered withan error normally within 2%. The same system has also been studied byL.K ~ e p p e l . ~ ~ He concludes that phenol is an undesirable constituent of washOel u. Kohle ver. Petroleum, 1940, 36, 194.39 Ind. Eng. Chem. (Anal.), 1941, 13, 868.40 OeZ Kohle Erdoel Teer, 1939, 15, 591.42 Tech. Mitt. Krupp: Forschungsber., 1940, 3, 2.‘s Gas- u. Wasserfach, 1940,03,73 ; Gl.iickauf, 1939,75,465; Chem. Zentr., 1940, I, 487.41 J. W. J. Fay, unpublishedFAY : FRACTTOXAL DISTILLATION. 225oil for gas stripping, and that cracking of wash oil samples occurred duringlaboratory experiments in which they were heated above 190'. A develop-ment of the G.L. 1 column, known as the G.L. 2 design, is now being usedfor the estimation of phenols and other tar acids in mixtures which couldnot previously be analysed accurately and conveniently.The reported separation and identification, by Goldwasser and Taylor,of six isomeric hexenes with an overall b.p. spread of 2.5' has been criticisedby F. C, Whitmore and others4* and by A. Rose.45 The former, using aPodbielniak-Simons-Taylor column containing approximately 15 theoreticalplates, failed to effect separation of similar mixtures having up to 2.7'spread. Rose calculates that more than 400 theoretical plates would berequired for such sharp batch fractiona.tions and that a column with onlya few plates, even with a very small hold-up and with the use of a very highrefiux ratio, can give no appreciable separation.Stedman columns, the advantages of which have been reviewed by Bragg,37have been used for the fractionation of Turner Valley (Canada) crude oilsby R.M. Donald 46 and by L. M. Watson and J. W. T.. Spinks,4' and thephysical constants of many aliphatic hydrocarbons have been determined,after purification by fractionation, by D. B. Brooks, F. L. Howard, and H. C.Crafton, j ~ n r . ~ ~ F. C. Whitmore, L. H. Sutherland, and J. N. Cosby49have used 20-25 plate columns to prepare pure intermediates for thesynthesis and study of substituted docosanes. Among other applica-tions, mention may be made of the use of the Piazza column for the deter-mination of alcohol in foaming liquors 50 and wines; 51 a discussion of thegeneral laboratory applications of this still by R. Rouzaut ;52 studies of theremoval of entrained impurities from distilled water by a glass ring-packedcolumn 53 and of the packed tower collection of phosphoric acid; 54 thedehydration of methyl benzenesulphonate ; 55 and a description of a simyl-taneous chemical reaction and fractional distillation apparatus, applicableto any isomerisation process, in which the reaction vessel is used as thes till-pot of a continuous fractionating column.56A full account, with photographs, of the apparatus and methods used atthe National Bureau of Standards for the analytical separation and purifica-tion of gases by fractional distillation and rectification a t low temperatureis given by M.Shepherd.57 R. L. Geddes 58 has published an interesting4 4 J . Amer. Chem. SOC., 1940, 62, 795.4 6 Canadian J . Res., 1940, 18, B, 12.4 8 J . Res.Nat. Bur. Stand., 1940, 24, 33.49 J . Amer. Chem. SOC., 1942, 64, 1360.51 J. Piazza and R. Rouzaut, Anal. Inst. Invest. cient. tecn., 1938-9, 8-9, 82.62 Anal. SOC. cient. Argentina, 1941, 131, 251.63 Chi-Chuan Shen, J . Chinese Phurm. ASSOC., 1940, 2, 293.54 W. H. Baskervil, Trans. Amer. Inst. Chem. Eng., 1941, 37, 79.6 s A. M. Shuer, Khim. Mashinostroenie, 1939, 8, No. 8, 19.B. Longtin and M. Randall, Ind. Eng. Chem., 1942, 34,292.5 7 J . Res. Nut. BUT. Stand., 1941, 26, 227.5 8 Ind. Eng. Chem., 1941, 33, 795.REP.-VOL. XL. H4 5 Ibid., p. 793.4 7 Ibid., p. 388.Ind. y Quim., 1940, 3, 29226 ANALYTICAL CHEMISTRY.correlation between true b. p. and the standard A.S.T.M. distillation curvesof petrdeum fractions : on the baais of a large number af collected routineresults it is possible to estimate either of these curves if the other has beendetermined.The microfractionation of a single drop of liquid into 30-70 fractions isdescribed by A.A. Morton and J. F. Mah0ney.5~ A vertical tubular capil-lary, packed with glass wool and jacketed to prevent heat loss, is employed.A graph of the b. p. of each fraction shows the existence of one or more com-pounds and the percentage composition can be estimated from it. Detailsme given of the apparatus and procedure, together with results obtained withbenzene-toluene, benzene-xylene, ethyl alcohol-butyl alcohol, ethyl alcohol-methyl ether, and ethyl acetate-butyl acetate mixtures.A small selection of patents whidh have been taken out provides interest-ing evidence of the application of fractionation processes in this sphere.J.R. Bailey facilitates the separation of such materials as n- and iso-pentane by adding to the complex narrow boiling-range paraffin mixture achemically dissimilar and easily separable carrier having a wider boilingrange than the original mixture. By cutting into fractions and separatingoff the carrier, a series of sharply defined cuts of theinitialmixture is obtained.R. R. Dreisbach and J. E. Pierce retard the polymerisation of vinylaromatic compounds during distillation by packing the column with asubstantially insoluble agent effective in inhibiting polymerisation, and tbesame principle is applied by C. E. Barnei3,62 who uses a metal packing toinhibit polymerisation during the purification of methacrylic acid.Theaddition of a volatile hydrocarbon having an initial b. p. not more than1 5 O F. above that of the required pure material is advooated by F. M. Archi-bald and C. A. &hen 63 to assist in the purification by distillation of aliphaticpolyoxygenated compounds such as glycerol.(ii) Axeotropic Distillation.Reviews.-A comprehensive study of the subject has been made by B. J.&lair, A. R. Ghgow, junr., and I?. D. R ~ a s i n i . ~ ~ They present the generaltheory and, in the partioulrtr application to hydrocarbons, find that almostall polar organic compounds produae azeotropes with theae compounds.The b. p. depression, and heme the ease of separation, decreases in the orderparaffins, naphthenes, mono-olehs, diolefins, aromatics.They recommendchoice of an azeotrope-forming compound with b. p. 0-30" below that of theclose-cut hydrocarbon fraction to be treated and emphasisc the desirabilityof choosing a material easily separated from the hydrocarbon, as, e.g., byextraction with water. The review includes a list of hydrocarbons separableby this means from petroleum.The theory of azeotropic mixtures is dealt with by V. A. Kireev,6K who68 Id. Eng. Chem. (Anal.), 1941, 18,494. 6o U.S.P. 2,231,241.61 U.S.P. 2,240,764. 6a U.8.P. 2,241,176. U.$.P. 2,228,431.64 J . Res. Nut. Bur. Stand., 1941, 27, 39; Refiner, 1940, 19, 430.es Actu Physicochim. U.R.S.S., 1941, 14, 371F A Y : FRACTIONAL DISTILLATION. 227develops equations correlating composition and vapour preswre.Deducedvalues are found to agree well with published data for many different mix-tures of organic liquids. G. Schouls 66 has derived thermodynamical dis-tihtion relationships with particular reference to rates ~f vaporisation andexplains the constancy of temperature and pressure in azeotropic distillationby the hypothesis, which is in agreement with experimental data, ofdistillation a t constant rates.The behaviour of ternary mixtures on distillation has been fully dis-cussed by W. Reinders and c. H. de Mir~jer,~? who pay particular attentionto the effect upon the ternary systems of azeotropic points among the binarysystems. A general discussion of the theory and practice of distillationwith steam and other vapours is given by G.A. Fester,68 and, among hrtherpublications reviewing general or particular aspects of azeotropy, mentionmay be made of a comprehensive discussion of the subject and its use8 byT. Hannotte; 69 its applications in the dehydration of acetic acid and inmany industrial processes by D. F. Othmer ; ' 0 a general discussion of third-component, or '' entrainer," distillation by D. B. Keye~,~1 who gives eK-amples in hydrocarbon and aqueous systems; a review of the maximumboiling mixtures of chloroparaffins with donor liquids by R. H. Ewell andL. M. Welch; 72 and a mathematical conaideration of entropy changesduring azeotrope formation by A. K. Zhdan0v.~3Ewperimntul Work-Many investigators have devoted their attentionduring recent years to the study of relevant data.E. M. Baker, R. 0. H.Hubbard, J. H. Huguet, and S. S. Michalowski74 have constructed com-position curves from refraotive index and density determinations for thesyatems ethanol-water, ethanol-cellosolve, and cellosolve-water, and Baker,with R. E. Chaddock, R. A. Lindsay, and R. C. Werneq75 publishes reaultsfor the corresponding ternary system. W. M. Langdon and D. B. Keyes 76have obtained vapour-liquid equilibrium data for the ethanol-water systemand also for the isopropyl alcohol-water mixture, in which they find that theazeotrope contains 68.35 mol.% of the alcohol. The latter system has alsobeen studied by J. E. Schumacher and H. Runty7' who have investigatedthe minimum- boiling azeotropes in the mixture nitromethane&?opropy1alcohol-water. Data are given for the ternary system and for the threecorresponding binary combinations.W. D. Bonner and M. B. Williams 78have worked a t pressures down to 160 mm. of mercury on the separation ofwater and alcohol in presence of beneene. Using refractive index as aBull. SOC. chirn. Belg., 1940, 49, 214.6 7 Rec. Tp.au. chim., 1940, 59, 207.6* Rev. Centro Eatud. Ing. Quim., Univ. Nacl. Litoral (8anta FB, Argentine), 1840,No. 15, 97.Chern. Zentr., 1940, 1, 3578. '* Chem. Met. Eng., 1941,48, No. 6, 91; Ind. Eng. Chem., 1941,33,1106.7 1 Ibid., p. 1019.78 J . Ben. Chern. Russia, 1941, 11, 403.Bid., p. 1383.J. PhyshZ Ohem., 1940, 44, 404.78 J . Arner. Chern. rSoc., 1941, 63, 2476.74 Ind.Eng. Chern., 1939, 81, 1260.76 Ibid., 1942, 34, 938. 'T Ibdct., p. 701228 ANALYTICAL CHEMISTRY.method of analysis, they find that the water is most efficiently removed a tlower pressures.Among other binary systems investigated, interesting data have beencompiled by S. Takagi 79 on the b. p.'s of formic acid-water mixtures. Start-ing from samples of higher and lower concentrations than those of theazeotropic mixtures, and carrying out experiments to coiucidenc6 of constantb. p.'s, he obtains results of accuracy within &lo in temperature and h0.1 yoin composition. K. Tuda, A. Oguri, and S. Hukusima find 43.6% byweight (0.65 mol.) of acetic acid in the azeotrope with a-diethylamino-butan-y-01, and P. I. Lebed 81 reports 85% by weight of ethyl alcohol in itsazeotrope with m-xylene. The vapour-liquid equilibria in the three binarysystems formed by acetone, chloroform, and benzene have been studied byW.Reinders and C. H. de Minjer,82 who find that only the acetone-chloro-form mixture possesses an azeotropic point, the composition being 786% ofchloroform and the maximum b. p. 64.5". The same authorss3 have deter-mined the course of the distillation line in the corresponding ternary mixture.H. J. McDonald ** states that ethyl alcohol separates from the boiling ternarymixture with glycerol and benzene in such a manner that its mo1.-fraction isthe same in the vapour as in the liquid phase.AppZications.-The fundamental work of Mair and others, to whichreference is made above, has been applied to the isolation of a number ofpure substances from petroleum.The normal procedure is to subject aclose-cut (approximately 2") fraction to azeotropic distillation with a suitablepolar organic liquid in a very efficient column containing between 50 and 100theoretical plates. Using entrainer liquids such as diethylene glycol mono-methyl ether, Mair and A. J. Streiff 85 have separated the aromatic hydro-carbons and isolated in a pure state naphthalene and various other COM-pounds from petroleum, and A. R. Glasgow 86 has separated high-boilingparaffins from the same source.An interesting application has been described by D. F. Othmer, J. J.Jacobs, junr., and J. F. Levy.87 The continuous nitration of benzene isaccomplished by using nitric acid without any dehydrating agent, the waterof reaction being removed as i t is produced by azeotrope formation with thebenzene.has made a study of the system nicotine-water and appliesthe results to the separation of nicotine from related alkaloids.R. Negisiand T. Isobe 89 have investigated mixtures of water with n- and iso-butylalcohols. They find that the azeotropes contain 57.6 and 67% of the alcoholsrespectively, the b. p.'s being 92.6" and 90°, and claim practically quantitativeseparation of the alcohols from associated hydrocarbons.C. R. Smith7O Bull. Chem. SOC. Japan, 1939, 14, 508.81 J . Physical Chem. (U.S.S.R.), 1940, 14, 277.S2 Rec. Trau. chirn., 1940, 59, 369. 83 Ibid., p. 392.A4 J . Physical Chern., 1941, 45, 706.8 5 J .Res. Nat. Bur. Stand., 1940, 24, 395; 1941, 27, 343.86 Ibid., 1940, 24, 509. 8 7 Ind. Eng. Chem., 1942, 34, 286.88 Ibid., p. 251.J . Pharm. SOC. Japan, 1941, 61, 74.Bull. Chem. SOC. Japan, 1941, 16, 278FAY : FRACTTONAL DISTILLATIOX. 229The advantages of an anhydrous entrainer liquid over steam for certainclasses of material are reviewed by G. A. Fester and A. Collados,gO who proposethe use of a kerosene cut instead of water for the distillation of pyrogalloland phenols in general.An idea of the wide application of azeotropism can be obtained by abrief survey of some patents recently taken out which involve the use of thisprocess. For example, the drying of acetic and other aliphatic acids isaccomplished by entraining the water impurity with propyl acetate andpropyl a1cohol:l diisobutyl ketone,92 a mixture of diisopropyl ketone withethyl isopropyl ket0ne,~3 or butyl a~etate.~4 Procedures for the separationof aromatic, unsaturated, and paraffin hydrocarbons from mixtures witheach other and other substances include the purification of low-boilingaromatics by azeotropically distilling associated hydrocarbons with methylalcohol,95 methyl acetate ,06 acetone ,97 or crot onaldehyde ,98 the separationof paraffins from 0lefil1~,99 and the purification of indene by distillation ofthe oil with pheno1,l glycols,2 and many other organic compounds containinga carboxyl, hydroxyl, amino- or pyridinic nitrogen radical.3 A small quantityof maleic anhydride is found to facilitate the purification of anthracene bydistillation in presence of a polyhydric alcohol, such as ethylene glycol,having a b.p. in the neighbourhood of 2OOO.4 A similar azeotrope-formingsubstance is utilised in the removal of cyclic ethers from acetoneY5 fromwhich water may be removed by distillation with an aliphatic hydrocarbonMethods for the separation and purification of phenol and its derivativesinclude its removal from cycbhexanone by distillation with a compoundcontaining a t least two alcoholic hydroxyl groups, such as diethylene glycol.'Coloured impurities are removed from phenothiazine by distillation withchlorinated diphenyl ether.8 Other interesting applications include thesimultaneous production and purification of aliphatic hydroxy-substancessuch as glycerol by treating a corresponding halogen compound with waterand removing the halogen acid from the reacting zone as the aqueousaze~trope,~ the dehydration of unsaturated aliphatic cyanides with methyleneof b.p. 28-100°.6Anal. Asoc. Qulm. Argentina, 1942, 30, 36.91 A. W. Bright and J. H. Zeigler, U.S.P. 2,199, 982.g2 D. F. Othmer, U.S.P. 2,275,862.@' D. F. Othmer and R. E. White. U.S.P. 2,275,802.95 H. M. Spiers and H. K. Suttle, B.P. 536,172.96 E. Field, U.S.P. 2,279,194.g8 F. W. Sullivan, jun., U.S.P. 2,265,220.OD Phillips Petroleum Co., B.P. 521,092.93 Idem, U.S.P. 2,269,163.9 7 Idem, U.S.P. 2,212,810.K. H. Engel, U.S.P. 2,279,778.Idem, U.S.P. 2,279,780.J . A. C. Yule, U.S.P. 2,213,755.British Celanese Ltd., B.P.539,487; J. E. Bludworth, U.S.P. 2,273,923.J. F. Eversole and A. C. Plewes, U.S.P. 2,259,951.E. Field, U.S.P. 2,265,939.Idem, U.S.P. 2,279,779.* E. C. Britton, F. B. Smith, and R. L. Brown, U.S.P. 2,284,124.@ H. Dreyfus, B.P. 536,428230 ANALYTZOAL UEEMBTRY.chloride,l* the conoentration of aqueous halohydrin solutions,ll and theseparation of hexamethyleneimine from the diamine by distilling it as anazeotrope with wafer.18(iii) Vmuetm and Mohular Distillation.Revietos.-Many publications on this increasingly important subject havebeen made in the last year or two. The principles involved in ordinary,vacuum and molecular distillations are discussed by M. Furter,l3 and mole-cular, or short-path, distillation has been reviewed by several workers,including D. D.Howat,la who discusses thermal efficiency and the degree offractionation, W. F. Withera,15 and H. I. Waterman and C . van Vlodrop.I*S. 3. Detwiler, junr.,17 has issued a supplement to his bibliography on thissub j ecf .Apparatus.-The performance of laboratory columns packed withRaachig rings, 3erl saddles, and spiral screen gauze at reduced pressure(20 mm. of mercury) for the fractionation of terpenes has been studied byW. D. Stallcup, R. E. Fuguitt, and J. E. Hawkins,l* who conclude that thelast is the most efficient packing yet described for this type of work.E. Kirschbaum l9 has used ethanol-water mixtures to investigate theefficiency of bubble-plate columns a t pressures down to 50 mm. Muchinformation, including pressure-drop data, is presented, together with agraph indicating permissible vapour velocity as a function of other variables.The concentric-tube type of column, which has been critically examined,among other open tube types, by J.H. Westhaver,m has been used in anapparatus described by S. A. Hall and S. Palkin 21 for the efficient fraction-ation of a- and p-pinene at 20 mm. pressure. Two other vacuum stills whichmay be mentioned are an apparatus for the fractional vacuum distillationof small quantites of high-boiling mixtures22 and a 205-1. capacity still,described by the Histology Labomtory of the University of Amsterdam,zasuitable for fractionation, at about 10 mm. pressure, of alcohol, urine, etc.Another development is the modification, by C.E. Watts, J. A. Riddick,and F. Shea?* of the A.S.T.M. standard distillation apparatus to enableboiling ranges to be determined a t reduced pressures.Various devices have been designed to overcome the tendency to frothingduring vacuum distillations. M. Burger, who has also designed a neatlo E. C. Britton and A. R. Sexton, U.S.P. 2,263,436.l1 W. C. B. Smithuysen, U.S.P. 2,188,264; W. Coltof, Can.€'. 394,847.E. I. du Pont de Nemours and Co., B.P. 536,024.Is Milt. Lebensm. Hgg., 1939, 30, 200.Chem. Age, 1941, 45, 309, 323; 1942, 46, 3.l6 J . PTOC. Austral. Chem. Inst., 1942,9,103.l6 Rev. Chim. ind., 1939, 48, 314.Ind. Eng. Chem. (Anal.), 1942, 14, 603.2. Ver. hut. Ing., 1940, No. 3, 69.21 Ind. Eng. Chem. (Anal.), 1942, 14, 807.22 E.Klenk and K. Shuwirth, 2. physwl. Chem., 1941, 207, 260.1 7 Oil and Soap, 1940,17,241.20 Ind. Eng. Chem., 1942, 34, 126.Ohm. WeekbZad, 1941, 38,646. 24 Ind. Eng. Chem. (Anal.), 1942,14,606FAY : FRACTIONAL DISTILLATION. 231continuous vacuum distillation appnratus,z~ dcxribes a valve accessorywhich permits the introduction of a little air through an extra tube.26 I.Levin27 uses the foam level to actuate a relay to achieve the same object,and D. R. Rexford 2* has designed a device in which an air-leak, providedthrough a stop-cook, is operated by EL counterpoised mercury bulb. Thefrequency of this de-foaming cycle may be adjusted between 8 and 20phaaes per minute.Pressure regulating and measiiriirg devices have been described by manywritrerls.An invertedglam filter cell, lacquered 80 that only a wedge-shaped porous surface isexposed, is immersed in mercury to the required depth and connected to alevel-regulating manometer, so that the amount of gas admitted to fheapparatus can be adjusted and controlled. An extremely simple but effec-tive device, constructed from a gaswashing bottle, is described by M. S.Ne~rnan,~O and others who have designed regulators include J. H. Thelin,31who obtains pressure control within O.l.mm. of mercury up t o 200 mm.,B. Ferguson, junr.F2 who employs a magnetically operated capillary leak,C. 13. dc Witt,33 whose apparatus includes a trap and manometer system,and M. J. Cttldwell and H. N. Barham,34 who use a glass valve pressureregulator capable of controlling preasures above or below atmospheric toabout 1 mm.of mercury. E. R. Kline $6 describes a modified McLeod gaugefor the measurement of moderate vacuum (0-05-2 mm. of mercury).A simple receiver, utilising two standard 3-way stop-cocks, which alllowsany required number of fractions to be collected without disturbing thepressure in the still, has been designed by R. S. Tome, E. E. Young, andL. T. Ebyf6 J. B. Cloke3’ has described a vacuum-jacketed receiver,J. W. Patterson and R. W. Van Dolaha8 adaptors for the collection offractions, and A. J. Bailey 39 a still-head, mounted within the flask, for .thelow-preesure distillation of organic mixtures. Miscellaneous publicationsinclude the description of a method of economising in water during prolongeduse of a filter pump,u a trap t o prevent blackflow from suction pumps,4land the preparation, from shellac and pine.tar oil, of a laboratory cement,suitable for vacuum ~ o r k .~ aF. Wittka 43 has dealt in considerable detail with the equipment, describedup t o that time, for laboratory and large-scale molecular distillation. A2B J . Lab. Clin. Med., 1940, 25, 1221. 2o Chemist*Analyst, 1940,&9,20.27 Ibid., p. 89. 28 Ind. Eng. Chm. (Anal.), 1941, 18,95.29 Ber., 1940, 73, 1023.30 Ind. Eng. Chem. (Anal.), 1940, 12, 274.31 Ibid., 1941, 13, 908.33 Chemist-Analyst, 1941, 30, 40.34 Ind. Eng. Chen. (Anal.), 1942, 14, 495.36 Ibid., p. 542.38 Ibid., 1942, 14, 611.40 G. F. Shapley, €‘ham. J., 1942, 148, 71.‘I A. E. Meyer, Ind.Eng. Chem. (Anal.), 1942, 14, 605.42 W. C. Fernehs, “ Inorganic Synthem,” MeGraw-Hi11 Co., No. 67, p. 189.43 Angew. Chem., 1940, 68, 467.An ingenious method is employed by A. Rollett.=3a Ibid., 1942, 14, 104.36 Ibid., 1941, 18, 626. 37 Ibid., 1940, 12, 329.38 Ibid., p. 71232 ANALYTICAL CHEMISTRY.large number of diagrams and an extensive bibliography are provided.Recently, A. J. Bailey44 has described the construction of a simple mole-cular still from two Pyrex micro-belljars and a heated brass plate, theapparatus being suitable for the distillation of such material as lignin.A n improved form of the laboratory molecular still of Main, Shicktanz,and Rose, suitable for the separation of vegetable and animal fats and oils,is given by S. B.Detwiler, junr., and K. S. M a r k l e ~ , ~ ~ a means for the inter-mittent withdrawal of fractions being provided.In publications dealing with accessory equipment, D. D. Howat 14describes low-pressure gauges and compares the relative merits of mercuryand oil pumps, the design, construction, and working of which are alsodiscussed by K. D. Sinelnikov, A. K. Walter, D. N. Ulezko, and A. N. Yam-nitskiLqs s. Eklund4? has made some measurements of ultimate vacuumand the pump speed of molecular pumps and describes a very efficientdesign.Applications.-Certain aspects of this subject have been considered byJ. N. Ray4* in his discussion of recent developments in the study of theconstitution of natural products. Howat 49 gives an extensive review of theliterature on the preparation of vitamins A , D, and E .Vacuum distillation has been applied to the study of Rumanian petroleumby T.Cogciug," who collects various 2' fractions a t 20 112111. pressure; to therecovery of used mineral oils by K. Thomas,51 and to the preparation ofpure lactic acid by G. Genin.52 F. A. Norris, I. I. Rusoff, E. S. Miller, andG. 0. Burr 53 have investigated the effect of vacuum distillation throughpacked columns on the absorption spectra of the methyl esters of highlyunsaturated fatty acids. They conclude that the products obtained aresufficiently representative to be used in isolation and structure work. Useof spiral ~creen and Stedman columns at pressures of the order of 15-20 mm.has been made for the purpose of separating certain constituents of heavycoal-tar naphtha in a pure state.A study of petroleum and tar products by distillation under a cathodicvacuum has been made by several workers.M. Richter 55 has examinedaeroplane-motor fuels and uses the results obtained by distillation in IL200-ml. copper still a t 0*001 mm. pressure to determine the constitutionand assess the performance of lubricants. The absolute identification oflubricating oils by the application of a similar technique is described by R.Petit, Y. Crimail, and R. Duchene.56 Louis 57 uses the method to study4I In&. Eng. Chem. (Anal.), 1942, 14, 177.46 cJ. Tech. Physics (U.S.S.R.), 1941, 11, 879.d 7 Arkiv Mat. Astron. Fysik, 1940, 27, A , No. 21.Proc. Nat. Inst. Sci., India, 1939, 5, 205.Ann. sci.Univ. Jassy, 1940, Sect. 1, 26, 406; 415.4b Ibid., 1940, 12, 348.Chem. Age, 1942, 46, 41, 53.b2 Lait, 1940, 20, No. 197, 412.64 5. W. J. Fay, unpublished.61 2. Ver. deut. Ing., 1941, 86, 33.6s J . Biol. Chem., 1941, 139, 199.6 5 Luftfahrt-Forsch., 1939, 16, 212.O6 Chemie-Induetrie, 1941, 46, 304; Brennstoff-Chem., 1941, 22, 237.6 7 Bull. As8oc. franc. Techn. Pktrole, 1938, No. 45, 31FAY : FRACTIONAL DISTILLATION. 233paraffins and petrolatums. A rather lower pressure to mm.) isemployed by V. A. Korovkina 68 for the investigation of the origin andchemical nature of bituminous products.An interesting application of low-pressure technique, described by C. D.Hurd and R. W. Liggett,59 is the analytical separation of sugars, accom-plished by fractionation of their propionates. Details are given of severalmixtures, and it is concluded that pressures below 0.01 mm. are best. Theaccuracy obtained is about 1-2% for monosaccharides and 2-4y0 fordisaccharides.Far too many pat.cnts have b'een taken out for any attempt to be madehere to give anything like a comprehensivc summary, but a few may bementioned ps having particular points of interest. K. C. D. Hickman hasdeveloped his unobstructed-path still for the distillation under high vacuum(0.001 to mm.) of such materials as hydrocarbons and animal andvegetable oils torecover unsaturated glycerides, sterols, and vitaminfractions.60The same author, with J. G. Baxter,61 has described a method of minimisingoxidation of a fat-soluble oxidisable oil during high-vacuum distillation byaddition of a glyceride oil containing an anti-oxidant. The use of aluminiumpowder as a coating for the vaporising surface of the still, to lessen thedeposition of interfering solid materials, is advocated by J. C. Hecker.62Other stills have been described by G. Burrows 63 and by Distillation Pro-ducts Incorporated.64 One of the latter designs has as an aid to fractiona-tion rotating screens of rods, strips, or wire gauze, and the other utilises thelatent heat of condensation of the distillate for the vaporisation of the fluidoperating the diffusion pump. The same company G5 and other workers 66apply the process to the preparation of hormones, vitamins, and enzymesfrom fish and vegetable oils and extracts. The purification of fatty acids,oils, glycerol, and similar materials is also dealt with in patents by theEastman Kodak Company,67 E. Morlock,68 K. S0ndermann,6~ and othemiOApparatus and processes for the distillation of lubricating oils are describedby J. E. S ~ h u l t z e , ~ ~ R. V. B e ~ k n e l l , ~ ~ and others,73 and a combined oxidationand vacuum distillation apparatus for the production of acetic anhydridefrom acetaldehyde is given by D. C. Hull and C. A. Rlarshall.74 A neatmeans of collecting a number of condensed fractions a t various distances68 Khim. Referat. Zhur., 1940, No. 7, 125.88 J . Amer. C'herrL. SOC., 1941, 63, 2659.6o U.S.P. 2,218,240, 2,221,691, 2,234,166; B.P. 630,367 (with J. C. Hecker).6 1 B.P. 535,100.G3 B.P. 523,754.6 5 B.P. 532,770.6 6 E. W. Fawcett and G . Burrows, U.S.P. 2,156,669.6 7 Fr.P. 845,957; B.P. 524,390; 524,439.6 8 U.S.P. 2,261,939.i o E.g., T. W. Evans, J. R. Scheibli, and G. H. Van de Griendt, U.S.P. 2,234,400.71 U.S.P. 2,217,385, 2,217,386.73 E.g., D.R.-P. 699,900; V. Voorhees, U.S.Y. 2,224,621.7 * U.S.P. 2,283,209.62 U.S.P. 2,269,153.64 B.P. 535,565, 540,603.U.S.P. 2,179,833, 2,224,025.72 U.S.P. 3,2L7,356.H 234 ANALYTICAL CHEMISTRY.from the vapourising surface and providing reflux of the oondensed portionsis the subject bf a patent by C . V. L i t t ~ n . ' ~The separation of o- andp-chlorotoluenes is dealt wibh by P. D. Hammondand R. W. Harri~,7~ who describe an apparatus for the continuous distillationof a 60% o-mixture through an efficient column, u s i n g a high reflux rabio,under an applied pressure not exceeding 200 mm. absolute, and by M. J. P.Bogart and J. S. F. Carter,77 who also describe B method of distilling phenolsand cresols, 78 J. W. J. F.J. W. J. FAY.J. G. N. GASKIN.76 U.S.P. 2,266,063.7 7 U.S.P. 2,240,762.76 U.S.P. 2,240,962.U.S.P. 2,241,110

ISSN:0365-6217    

DOI:10.1039/AR9434000204

出版商:RSC    

年代:1943

数据来源: RSC

摘要:

INDEX OF AUTHORS' NAMES.ABBASY, M. A., 177.Abraham, E:P., 182, 189, - .190.Abrams, R., 182.Abresch, K., 206, 215.Adamovich, L. P., 205.Adcock, F., 74.Agde, Q., 32.Agte, C., 73.Ajtai, N., 141.Albert, A., 167, 168.Albrecht, G., 95.Alder, K., 101.Alexander, P. P., 75.Allen, C. F. H., 160.Allsebrook, W. .E., 170,Alsberg, C. L., 191.Alter, C. M., 81.Alterthum, H., 73.Alther, H. B., 161, 152.Ambelang, J. C., 169.Amende, J., 114.Anderson, H. H., 64.Anderson, H. V., 35.Anderson, E. W., 194.Anderson, J. S., 60.Anderson, T. F., 200.Anslow, W. K., 192.Anslow, W. P., 107.Aoyame, S., 75.Archer, H. E., 177.Archer, S., 105, 106.Archibald, F. M., 226.Arens, J. F., 163.Arkel, A. E. van, 68, 72,Armstrong, H. E., 30.Annstroaig, M.D., 174.Arndt, F., 114.Arthur, P., 219.Arx, E. von, 148.Asahina, Y., 108.Ashmore, J., 29. 'Astbury, W. T., 84.Auerswald, H., 187.Aumuller, W., 157.73.Bachmann, W. E., 114,123,Bacon, R. F., 82.Baddiley, J., 169, 171.Badger, G. M., 146.Badger, R. M., 92.Bagshawe, B., 207,209.Bahr, K., 102.Bailey, A. J., 217,-231, 232.Bailey, J. R., 226.Baker, B. R., 143, 144.Baker, E. M., 227.125, 133.Baker, R. H., 218.Baker, W., 92, 141, 189.Baker, Z., 186, 187.Balaban, I. E., 142.Bald, J. G., 197.Balenovid, K., 164.Balke, C. W., 78.Ball, G., 166.Bangham, D. H., 36, 37,40, 42, 43.Bannister, F. A,, 82.Bardhan, J. C., 162.Barfoot, W. F., 209.Barham, H. N., 231.Barkenbus, C., 218.Barker, E. F., 87, 91.Barker, F.G., 204.Barnes, C. E., 226.Barnett, J., 151, 152.Barrer, R. M., 43.Barrows, R. S., 165.Barry, V. C., 116.Bartell, F. E., 40.Bartlett, M. K., 177, 178,Basart, J. C. M., 73.Baskervil, W. H., 225.Bateman, L., 96.Bateman, L. C., 127.Bauer, J. E., 198.Bauer, S. H., 62, 90, 92.Bawden, F. C., 197, 198,199, 201, 203.Baxter, G. P., 81.Baxter, J. G., 233.Beach, G. Y., 91.Beall, D., 155.Beard, D., 198, 199, 200,Beard, J. W., 198, 199, 200,Becker, K., 73.Becknell, R. V., 233.Bednarczyk, W., 109.Beeching, R., 31.Beeghly, H. F., 215.Behmenberg, P., 213.Belkevitch, 5. P., 210.Bell, R. P., 62.Bendich, A., 198.Bennett, J. G., 42.Bergel, F., 161, 169, 194.Berger, E., 119.Bergmann, E., 102.Bergmann, W., 169.Bergstriim, S., 152.Bergstrom, IT.W., 165.Berna1,J. D.,33,95,197,201.235179.201.201.Barnheher, O., 162.Bernstein, S., 142.Best,& J., 197.Beutel, R. H., 162.Bianchi, E., 138.Bielanski, A., 21 I.Bielig, H. J., 187.Birch, A. J., 133, 134.Birkinshaw, J. H., 191, 192,Bischler, A., 160.Binchof, E., 208.Biscoe, J., 33, 35.Black, 0. F., 191.Blair, V., 90.Blake, F. G., 190.Blanchard, E. W., 145.Bland, R. E., 217.Blayden, H. E., 32, 33, 34,Blomquist, A. T., 135.Blosjo, H. H., 207.Bludau, H. H., 81.Bludworth, J. E., 229.Bock, R., 69.Bockmiihl, M., 167.Boddy, R. G. H. B.; 43.Bodendorf, K., 107.Bodenham, D. C., 190.Boeseken, J., 107.Baggild, 5. K., 11.Bogart, M. 5. P., 234.Bogataki, G., 208, 211, 214.Bogert, M.T., 136, 143.Bolduan, 0. E. A,, 94.Bone, W. A., 29, 34.Bonner, W. D., 227.Booth, H. S., 63, 64.Boretskaya, T. V., 206.Borg, W. A. J., 176.Borkar, R. S., 163.Borsche, W., 164, 165.Bosshard, W,, 164,Bourne, G., 177, 178, 179.Bowen, E. J., 17.BowIes, 3. A. C., 45.Bozorth, R. M., 88.Bracken, A., 192.Bradley, W., 114.Bradt, W. E., 81.Bragg, (Sir) L., 88, 88.Bragg, L. B., 220, 222, 225.Brammall, A., 30.Braun, C. D., 210.Braun, 5. von, 92.Bray, E. E., 86.Bredereck, H., 119.Bretechneider, H., 141.193.42236Breuer, W., 81.Brewer, R. E., 32.Briggs, H., 35.Bright, A. W., 229.Bright, H. A., 211.Bright, W. M., 90.Brigl, P., 114.Brimm, E., 75.Briscoe, H. V. A., 60.British Celanese, Ltd., 229.British Colloids, Ltd., 142.Britton, E.C., 229, 230.Britton, H. T. S., 44, 45,46, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59.Broche, H., 29.Brockway, L. O., 86,90, 91,Brode, W. R., 91.Bronsted, J. N., 29.Brijsse, W., 224.Bronfenbrenner, I. J., 199.Brooker, L. C. S., 27.Brooks, D. B., 225.Brooks, L. A., 135.Broos, J., 77.Brown, G. B., 173, 174.Brown, H. C., 62.Brown, R. L., 42, 112, 113,Browne, A. W., 54, 65.Browne, (Miss) V. R., 56.Brownlee, G., 1.38, 145.Brihger, G., 78.Bruggen, J. T. van, 193.Bruk, L. E., 210, 213.Brunauer, S., 38.Brunowsky, B., 32, 34.Bruson, H. A., 108, 109.Bryan, W. R., 199.Buchman, E. R., 92, 163.Buerger, M. J., 85.Buttner, E., 170.Bunn, C. W., 96.Burchhardt, V., 152.Burg, A.B., 62.Burger,. A., 146.Burger, M., 230.Burgers, W. G., 73.Burgin, J., 101.Burnop, V. C. E., 125, 126.Burr, G. O., 232.Burrows, G., 233.Bursuk, A. J., 208, 211.Burton, M., 19.Bush, M. T., 193, 219.Businger, A., 146.Butenandt, A., 107, 157,Butz, E. W. J., 132.Butz, L. W., 132.Cain, C. K., 193.Calcott, W. S., 106.Caldwell, M. J., 231.Caldwell, W. T., 169.92.115, 229.159.'DEX OF AUTHORS' NAMES.Calvin, M., 28.Campbell, H. A., 112.Campbell, J. A., 86.Campbell, N. R., 137, 140,141, 142, 144, 160.Cannon, C. G., 31, 42.Cantor, S. M., 110.Carlisle, C. H., 138, 141.Carlson, G. H., 163.Carnes, J. J., 163.Cam, C. J., 122.Carson, J. F., 119.Carter, H. E., 194.Carter, J. S. F., 234.Cassell, H., 36.Catch, J.R., 189.Cbttaneo, C., 184.Cavaglieri, G., 134.Center, E. J., 211.Chaddock, R. E., 227.Chaffee, E., 188, 189, 190.Cham, E., 181, 182, 188,189, 190, 191, 192, 194,196.Chakravorty, 9. N., 152.Chamberlin, E., 162.Chambers, L. A., 198, 200.Chandlee, G. C., 215.Chargaff, E., 198.Charlesby, A, 85.Chattaway, F. W., 144.Chatterjee, D. P., 214.Chaudron, G., 79.Christ, C. L., 95.Christensen, H. N., 185.Christiansen, W. G., 139.Chukavin, M. K., 212.Church, J. nl., 104.Cioranescu, E., 126.Cirulis, A., 65.Clark, A. M., 190.Clark, G. L., 88.Clark, H. K., 89.Clark, R. A., 206.Clarke, W. W., 209.Clauberg, A., 213.Cloke, J. B., 231.Clusius, K., 61, 71.Clutterbuck, P. W., 188.Cobb, J.W., 42.Cobb, L. H., 60.Coburn, A. F., 186.Cockram, C., 29.Cohen, C. A., 226.Cohen, S. S., 201, 203.Cole, W., 123.Colebrook, L., 190.Coleman, G. H., 163.Collados, A., 229.Colonna, M., 164.Coltof, W., 230.Colyer, H., 184.Conn, J. B., 185.Cook, A. H., 164, 189.Cook, J. G., 130.Cook, J. W, 133.Cooke, P. W., 93.Cooksey, D., 6.Coolidge, A. S., 41.Cooper, E. A., 192.Cooper, G. R., 201.Coppens, L., 35.Copper, Q. R., 199.Cornforth, J. W., 128, 135.Cornforth, (Mrs.) R. H.,Cosby, J. N., 225.Cosciug, T., 232.Cottrell, T. L., 110.Coulson, C. A., 18, 92.Coulthard, C. E., 193.Courtois, J., 116.Coyne, F. P., 192.Crafton, H. C., jun., 225.Craigie, J., 197.Crandon, J. H., 178, 179.Cretcher, L. H., 120.Criegee, R., 107.Crimail, Y., 232.Crone, H.G., 42.Crouch, W. W., 162.Crowfoot, (Miss) D., 96, 138,Crowley, G. P., 135.Crowther, A. F.. 160.135.141, 191.Cunningham, T:R., 82, 213,215.CGnen, E. C., 187.Curtius, T., 115.Damaschke, A., 94.Dane, E., 131, 132, 152.Daniel, (Niss) V., 85.Dath, S., 181.Davies, J. S. H., 146, 147.Davis, R. E., 132.Davis, S. B., 136.Davydov, A. L., 214.Dawsey, L. H., 108.Dawson, H. M., 44, 189.De Boer, J. H., 73, 77.De Bretteville, A., 94.Debye, P., 32.De Decker, H. C. J., 88,De Jonge-Bretschneidsr, A.,De Man, T. J., 173.DemjBn, I., 139, 168.De Minjer, C. H., 227, 228.Dennis, L. M., 65.De Passill6, A., 75.Desch, C. H., 68.Detwiler, S. B., jun., 230,De Witt, C. B., jun., 231.Dickinson, R.G., 88.Dienes, M. T., 122.Dietrich, K., 208.Dietz, W., 207.Dill, D. S., 178.Dimov, A. M., 214.89.141.232INDEX OF AUTHORS’ NAMES. 237Dimroth, I<., 147.Dingle, J. H., 198, 200.Distillation Products Inc.,Docken, A. M., 138.Dodd, E. N., 48, 55, 56.Dodds, E. C., 137, 140, 142,Dodds, G. B., 160.D6ring, T., 75.Doering, W. E., 136, 137.Doisy, E. A., 193.Donald, R. M., 225.Donnell, C. K., 169.Dorfman, A., 182.Dornow, A., 162.DOW, R. B., 203.Dreisbach, R. R., 226.Dreyfus, H., 229.Driggs, F. H., 78.Dubos, R. J., 181, 184, 185,186, 187, 188.DuchGne, R., 232.Diirr, H., 81.Du Feu, E. C., 128.DufTendack, 0. S., 10.DufEin, W. M., 146, 189.Dunn, M. S., 95.Du Pont de Nemours &, Co.,Ltd., E.I., 230.Dutcher, 5.D., 191.Du Vigeaud, V., 172, 173,Eastman Kodak Co., 233.Eby, L. T., 231.Edmunds, G., 80.Edwards, F. C., 96.Edwards, (Miss) 0. S., 85.Edwards, R. R., 185.Ehrhart, G., 157.Eisenstein, A., 86.Eisermann, F., 214.Eistert, B., 114.Eklund, S., 232.Elbe, G. von, 108.Elliott, G. H., 126.Emerson, 0. H., 190.Emmens, H., 77.Emmerich, R., 181.Emmett, P. H., 38.Enderby, J., 141.Enders, J. F., 181.Engel, K. H., 229.English, J. P., 134, 169.Engs, W., 101.Erametrii, O., 70.Erxleben, H., 176.Euw, J. von, 150, 154, 155,Evans, E. F., 115.Evans, L. K., 137.Evans, T. W., 233.Evans, W. L., 120.Eversole, J. F., 229.Ewell, R. H., 217, 220, 227.233.146.174.159.Eyles, G. E. S., 212.Eyster, E.H., 87.Fahim, H. A., 146.Fakhoury, N., 36, 40.Fanelli, R., 82.Fankuchen, I., 95, 197, 201.Farquhar, J. P., 92.Fast, J. D., 73.Faust, G. T., 88.Fawcett, E. W., 233.Fay, J. W. J., 224, 232.Fezekas, J. F., 184.Fedorov, A., 212, 214.Feit, W., 70.Feitknecht, W., 44.Feldman, J., 133.Feller, A. E., 198, 200.Fenske, M. R., 219.Ferguson, B., jun., 2 19,23 1.Fernelius, W. C., 71, 231.Fester, G. A., 227, 229.Field, E., 229.Fieser, L. F., 106, 139.Filbert, B. M., 224.Finch, G. I., 85.Finkelstein, H., 200.Finlay, 0. R., 90.Fischer, E., 119, 160.Fischer, F., 29.Fischer, H., 161.Fischer, W., 69, 78.Fish, E. W., 180.Fisher, (Miss) N. I., 52.Fleischer, G., 189.Fleming, A., 181, 188.Fletcher, C. M., 182.Fleury, P., 116.Florey, H.W., 181, 182,188, 189, 190, 191, 192,194.Florey, M. E., 190.Fodor, 0. von, 141, 168.Foldi, Z., 139, 141, 168, 169.Forster, T., 18.Folkers, K., 174, 175.Forbes, G. S., 64.Forgeng, W. D., 78.Forstner, G. E., 192.Forsyth, R. P., 209.Foster, A., 190.Foster, J. W., 188.Foulston, R. B., 209.Fox, F. W., 178.Frampton, V. L., 200.Francis, A. E., 192.Francis, W., 30.Franke, H., 187.Frary, C. G., 64.Frediani, H. A., 208.Freifelder, M., 169.French, D., 96.Freudenberg, K., 110.Freudenberi; W:, 120, 121,122.Frey, H., 149.Friauf, J. B., 88.Fricke, R., 69.Frierson, W. J., 64, 65.Frost, A. A., 108.Frush, H. L., 115.Fry, E. G., 147.Fry, E. M., 116.Fu, Y., 40.Fuchs, H., 66.Fuchs, H. G., 148, 154, 156,Fuhrer, J., 164.Fuguitt, R.E., 230.Fuller, C. T., 48.Furter, M., 230.Gaby, W. L., 193.Gaddis, A. M., 132.Gatzi, K, 114, 119.Gallaway, W. S., 91.Gard, S., 200.Gardner, A. D., 181, 182,190, 196.Gardner, T. S., 119.Garen, V. F., 208.Garner, (Mrs.) E. V., 06.Gates, O., 207.Gaushin, A. A., 210.Geddes, R. L., 225.Geiler, J., 75.Geist, H. H., 216.Genin, G., 232.Genis, M. J., 209.George, R. W., 112.George, W. H., 31.Gerecs, A., 118.German, W. L., 59.Geselle, P., 82, 83.Geuer, G., 208.Giacomello, G., 138.Gibson, G. P., 219.Gibson, J., 32, 33, 34, 42.Gibson, T., 190.GiguBre, P. A., 86, 87.Gilchrist, R., 71.Gillam, A. E., 137.Gingrich, N. S., 86.Giulotti, A., 78.Giunti, M. H., 144.Glasgow, A.R., jun., 226,Glaxo Laboratories, Ltd.,Glister, G. A., 193.Gochfeld, R. V., 212, 214.Goese, M. A., 163.Golberg, L., 137.Goldacre, R., 167.Goldberg, M. W., 124, 131.Goodall, G. D., 141.Goodman, W., 208.Goralnik, A. S., 207.Gordon, A. H., 185, 186.Gordy, W., 91.Ooth, A., 193.Graessle, 0. E., 187.159.228.142238 INDEX OF AUTHORS’ NAMES.Graham, G., 177.Graham, 5. I., 35.Grandjean, P., 152, 153.Gratia, A., 181, 195.Gratton, 5. F., 147.Gray, F. W., 209.Green, (Miss) A. A,, 62.Green, J. W., 112.Green, R. H., 200.Greenwood, M., 192.Gregg, S. J., 38, 40.Gregory, E., 209.Grenberg, E. I., 209.Grieneisen, H., 78.Griffith, M., 31, 35, 41, 42.Griswold, J., 220.Groll, H. P. A., 101, 103.Gross, S . T., 88.Grosse-Oetringhaus, H.,224.Grtinfeld, E.I., 137.Giinther, P. L., 82, 83.Guinim, A,, 34.Gulland, J. M., 170.Gurovich, R. E., 218.Gutman, S. M., 212, 313,Qye, W. E., 192.Gyorgy, P., 172.Habitz, P., 207, 210.Hackett, J. W., 213.Hligg, G., 55.Hanig, W., 81.Hague, E., 172.Hague, J. L., 211.Haimerl, H., 61.Haines, R. B., 192.Hale, C. H., 208.Hall, S. A., 219, 230.Halmos, I., 168.Ham, E. J. ten, 176.Hammond, P. D., 234.Hammond, R. P., 70.Hamner, H. L., 215.Hampson, G. C., 89.Hamre, D. M., 193.Hann, R. M., 111, 116, 118,119, 120, 121.Hannotte, T., 227.Hanze, A. R., 113.Hargreaves, A., 94.Herker, D., 95.Harkins, W. D., 41.Harkness, R. W., 217.Harman, R. W., 56.Harmsen, G. W., 219.Harris, G. C.M., 182.Harris, L. J., 177, 180, 191,Harris, R. W., 234.Harris, 8. A., 174, 175.Harrison, R. W., 186, 187.Hart, A. B., 61.Hartley, F., 109.Hartlief, G., 200.Hartmann, M., 164.214.194,Hrtskins, W. T., 118, 119,Hastings, J. M., 90.Haward, R. N., 43.Hawkins, J. E., 230.Haworth, R. D., 141.Haworth, W. N., 110, 121.Haxby, R. O., 6.Hays, J. T., 163..Hazlewood, 0. A. D., 152.Hearne, G., 101, 103.Heatley, N. G., 181, 182,Hecht, H., 67.Hecker, J. C., 233.Hegner, P., 156, 167.Heilbron, I. M., lG4, 189.Heilman, D. H., 181, 180,HeiLner, G., 166.Hendricks, S . B., 88.Henle, G., 186.Henle, W., 198, 200.Heppell, D. H., 210, 214.Herb, R. G., 6.Hdrenguel, J., 79.Herrell, W. E., 181, 186,Hershberg, E. B., 106.Hertz, J., 179.Hettche, H.O., 184, 188.Heukeshoven, W., 59.Heyne, G., 73.Hickling, G., 30.Hicks, D., 35.Hieber, W., 65, 66.Hieronimus, O., 166.Hilberath, F., 218.Hildebrsnd, J. H., 61, 86.Hildebrand, W., 158.Hill, J. H., 193,Hill, W. L., 88.Himwich, H. E., 184.Hirst, W., 31, 35, 41, 42.Hixson, A. W., 217.Hoagland, C. L., 197, 200,Hoar, T. P., 211, 212.Hoard, J. L., 73, 89, 90.Hobby, 0. L., 188,189,190.Hobday, G. I., 142.Hockett, R. C., 117, 122.Hoehn, W. M., 162, 164.Hofmann, K., 172,173, 174.Hofmann, U., 32, 72.Holiday, E. R., 189.Holmes, D. W., 123.Holmes, F. O., 197.’Holzmiiller, W., 204.Roman, D. M., 193.Hoogerheide, J. C., 187.Hooper, I. R., 194.Hopkins, W. A,, 192.Horiuti, J., 60.Homer, L., 161.Horning, E.S., 182, 193.120, 121.188.187.187.201.Horton, L., 29.HOSS, O., 131.Hofchkiss, R. D., 181, 184185, 186, 187, 188.Howard, F. L., 225.Howat, D. D., 230, 232.Howe, P. R., 180.Hromatka, O., 170.Hubbard, R. 0. H., 227.Hudson, C. S., Ill, 116,116, 118, 119, 120, 121,122.Huckel, E., 18.Huttig, 0. F., 74, 81.Hufferd, R. W., 217.Huggins, M. L., 86.Hughes, E. W., 87, 95.Huguet, J. H., 227.Hukusima, S., 228.Hull, D. C., 233.Hunt, A. H., 179.Hunt, H., 227.Hurd, C. D., 233.Hurd, D. T., 73.Hurd, L. C., 75.Huse, G., 93, 94.Ignatieva, L. A., 204.Illingworhh, J. W., 59.Iltgen, A., 172.Imperid Chemical In-dustries, Ltd., 146, 147.Ingalls, T. H., 177.Ingle, D. J., 147.Isbell, H. S., 116.Ishido, B., 177.Ishii, R., 211, 215.Isimaru, G., 212.Ismet, A., 187.Isobe, T., 228.Ives, D.J. G., 52.Iwadare, K., 110, 114.Jackson, E. L., 115, 118.Jackson, J., 110.Jackson, (Miss) P., 58.Jacobs, 5. J., jun., 228.Jaeger, (Mrs.) R., 146.Jahr, I(. F., 59.Jakubowiez, W., 102.James, L. H., 210.Jander, G., 69, 67.Janke, W., 108.Jarrett, M. E. D., 52, 53,64.Jaschinowski, R., 103.Jeffrey, 0. A., 96.Jeger, O., 105.Jennings, M. A., 181, 18%Jensen, H., 147.Jodl, R., 32, 34.Johamsen, T., 63.Johnson, C. M., 209.Johnson, T. B., 169.Johnson, W. S., 133.Sonee, C. M., 177, 178.188, 191, 192, 194INDEX OF AUTHORS' NUES. 239Jones, F. T., 119.Jones, H., 193.Jones, J. I. M., 142.Jones, L. R., 193.Jones, W. E., 133.Jordan, L., 81.Joseph, T.L., 206.Joshel, L. M., 132.Julian, P. L., 161.Jura, G., 41.Kalina, M. H., 206.Kahanson, G., 199.Kameda, T., 44.Kanamori, Y., 212.Kanula, V., 70.Kanvinde, C. K., 163.Kaplan, H., 164.Karimullah, 169.Karlson, P., 162.Kassler, I., 212.Kassler, R., 74.Katzin, B., 147.Katzman, P. A., 193.Kaufmann, W., 70.Kwche, G. A., 201.Keefer, C. S., 190.Keggin, J. F., 59.Kelly, S., 177.Kemp H., 206, 215.Ken all, E. C., 147, 164.Kenner, a. W., 169, 170.Kereeatesy, J. C., 174.Kermack, W. O., 165.Kerschbawn, E., 138.Kerst, D. W., 6, 7.Keyes, D. B., 227.Kharasch, M. S., 140, 142.Kiebler, N. W., 29.Kieffer, G. L., 9LKiehl, 8. J., 56.Kilmer, Q. W., 174.King, J. G., 31, 35.King, L.E., 130.Kinzel, A. B., 82.Kireev, V. A., 226.Kirin, I. S., 212.Kirkptrick, E. C., 135.Kirkwood, 5. G., 89.Kirschbaum, E., 230.Kis&ngar, L. W., 169.Kistiakowsky, G. B., 61.Kleedorfar, A., 138.Klein, K., 218.Klein, M., 182.Klein, R., 194.Klemm, W., 63.Klenk, E., 230.Kline, E. R., 231.Klinger, I?., 205, 210, 212.Kloetzel, M. C., 133.Klug, H. P., 91.Knight, C. A., 202.Knowles, H. E., 209.Koch. H., 218.K l e i m ~ , M., 140, 142;Koch, W., 205, 206, 207,Kocholaty, W., 193.Kodicek, E., 180.Koebner, A., 124, 126, 133.Kogl, F., 172, 173, 176.Koelsch, C. F., 109, 163.Koeppel, C., 224.Kijthnig, M., 119.Koha, E. J., 119.Kolthoff, I. M., 44, 56.Komzak, A., 164.Kondakov, N., 101.Kondrat 'ev, V., 108.Konigsberg, M., 110, 112,Kornfeld, E.C., 169.Korovkina, V. A., 233.Korschun, A., 181.Kothare, A. N., 163.Kovacs, E., 140, 143.Krcloek, F. C., 80.Krantz, H. A., 217.Krath, E., 205.KreitmtLnn, L., 164.Krishnamurti, P., 34.Krishnan, K. S., 22.Kroll, W., 76, 79.Kronrad, J., 64.Kuhn, R., 171, 172, 187.Kuna, M., 119.Kurz, P. F., 107.Kushner, S., 125.Kuwada, S., 239.Kyoguka, K., 153.Ladenburg, A., 92.Lagally, H., 65.Lane, J. F., 146.Lanford, 0. E., 56.Langdon, W. M., 22Langsdin, J. B., 198.Lanman, T. H., 177.Lardon, A., 152, 163, 164.Larsen, E. M., 71.Lassieur, A., 206.Laubengayer, A. W., 64,Lauffer, M. A., 198, 200,Lawitsan, C. C., 8.Lauritsen, T., 8.Lavin, G. I., 201.Lawrence, C. A., 133.Lawrence, E. O., 6.Lawson, E.J., 152.Lawson, W., 137, 140, 142,Lea, D., 201.Lebed, P. I., 228.Lebedev, P. S., 216.Lecky, H. S., 217, 220.Lederer, E., 172.Ledinghaa, J. C. G., 197.Leech, J. G. C., 30.Leffler, M. T., 164.213.113.73, 90.201, 203.146.Lenette, E. H., 197.Lennard-Jones, J. E., 18.Lessing, R., 31.Levene, P. A,, 119,201.Levin, I., 231.Levine, P., 136.Levite, M., 136.Levy, J., 101.Levy, 5. F., 228.Lewis, G. N., 28,L e a , N. B., 47,53.Lewis, R. N., 163.Lewis, W. B., 8.Lialikov, J. S., 210.Liebhafsky, H. A., 73.Liebig, J., 90.Lifschutz, H., 10.Liggett, R. W., 233.Lilliendahl, W. C., 78,LincoIn, R. M., 169.Lindsay, R. A., 227.Lindwrtll, H. G., 160, 161,Link, K. P., 112.Linnell, W. H., 109, 143,Linstead, R.P., 125, 126,Lipmann, F., 168, 185.Lipson, H., 33, 85.Little, R. B., 187.Litton, C. V., 234.Lloyd, D. 3., 77.Lochte, H. L., 162.Lockwood, J. S., 190.Low, O., 181.Logemann, W., 166, 158.Long, C. N. H., 147.Long, H. H., 221.Long, L., 146.Long, R. W., 61.Longtin, B., 225.Longuet-Higgins, H. C., 62.Longwell, B. B., 152.Lonsdale, (Mrs.) K., 82, 86.Loring, H. S., 197, 198,201,Louis, 232.Lovell, R., 188.Low, B., 191.Lowry, H. H., 30, 31.Lu, C. S., 87.Lund, C. C., 178, 179.Lundell, G. E. F., 64, 209.Lundstedt, 0. W., 81.Luria, S. E., 200.Lythgoe, B., 169, 170, 171.Ma, T. S., 169.Maasmn, G., 210.MacArthur, I., 84.McBain, J. W., 94.0McBain, W., 94.MacCallmp, W. G., 197.MacClement, W. D., 197.165.146.136, 137.203.Lothrop, w.c., 92240 INDEX OF AUTHORS’ NAMES.McClenahan, W. S., 117.McCoy, H. N., 70.McCreath, D., 118.McCullough, J. D., 96.McDermott, W. C., 219.McDonald, E., 187.McDonald, H. J., 228.McElvain, S. M., 163.McFadyen, J. S., 163, 165.McFarlane, A. S., 197.MacGillivry, C. H., 88.McGinnis, (Miss) N. A., 133.McKey, H. A. C., 62.McKenzie, B. I?., 154.Maclay, W. D., 115, 116,McLeaxi, I. W., 198.MacLeod, C. M., 187.McMurray, H. L., 25.McNeil, D., 171.Macovski, E., 120.McQuillin, F. J., 128.Macura, H., 224.Illaggs, F. A. P., 37, 41, 42.Mahadevan, C., 34.Mahoney, 5. F., 226.Mair, B. J., 226, 228.Maltaev, V. F., 207.Mann, F. C., 186.Maim, F. G., 160.Mann, W. B., 6.Mannich, C.’, 160.Manske, R. H.F., 94.Marchlewski, L., 109.Marion, L., 94.Markelova, M. N., 212.Marker, R. E., 152.Markley, K. S., 232.Marsh, 5. K., 69, 70.Marshall, C. A., 233.Marshall, C. E., 30.Marshall, E. K., 190.Martin+ A. J. P., 185, 186.Martin, R. H., 127, 129.Marvel, C. S., 135, 136.Masi, O., 206, 209.Mason, C. W., 78.Mason, H. L., 152, 154.Matthies, H., 80.Matuszak, A., 219.Maurer, K., 171.Maxwell, M., 167.May, (Miss) E. L., 163.Meehan, F. T., 36.Meek, F. H., 44, 50.Megson, M. J. L., 30.Mehl, J. W., 201.Meisenheher, J., 101.Meldahl, H. F., 155.Melkonian, G. A., 171.Melville, D. B., 172, 173,Menze1,’A. E. O., 193.Metzger, H. J., 195, 190.Meyer, A. E., 231.Meyer, E., 219.120.174.Meyer, K., 188, 189, 190.Meyer-Delius, M., 124, 126,Meystre, C., 159.Michael, S.E., 192.Michaelis, R., 193.Michalowski, S. S., 227.Micheel, F., 110.Milas, N. A., 107.Miller, B. F., 182, 186, 187.Miller, E. S., 232.Miller, G. L., 202.Milner, G., 42.Minto, R. E., 200, 213.Mirick, 0. S., 187.Mischonsniky, S . , 2 13.Mitchell, D. T., 135.Mohlau, R., 160.Moeller, T., 45, 50.Moers, K., 73.Mohamed, A. F., 36.Moltschanova, R. S., 214.Monnier, R., 124.Monroe, E., 89.Montgomery, E. M., 111,Moody, F. B., 112.Moor, E., 164.Moore, D. H., 198.Moore, W. J., 95.Morgan, (Sir) G. T., 192.Morlock, E., 233.Morrell, W. E., 61.Morrison, A. L., 161, 104.Morton, A. A., 226.Mosallam, S., 40.Moss, A. R., 194.Mott, R. A., 32.Mowat, J.H., 163.Moyer, A. W., 174.Mozingo, R., 135, 174, 175.Much, H,, 187.Muchina, Z. S., 214.Muhlschlegel, H., 114.Miiller, E., 165.Mueller, J. H., 181.Miiller, P., 156.Muir, R. D., 193.Muller, P., 131.Mulliken, R. S . , 23.Murray, P. D. F., 180.Nadkarny, V. V., 163.Nagata, T., 205.Nagelschmidt, G., 35.Naigovzen, A. M., 208.Naray-Szabo, S. von, 91.Negisi, R., 228.Neisser, K., 158.Nenitzescu, C. D., 126.Nesin, S., 184.Ness, A. B., 125.Ness, A. T., 120, 121.Nesty, G. A., 135.Neurath, H., 199,200, 201.Newell, W. C., 216.127.119.Newkirk, A. E., 73.Newman, M. S., 231.Nicholas, S. D., 192.Nickolls, C. L., 219.Niederl, J. B., 143.Niekerk, J. N. van, 94.Niemann, C., 163.Niezoldi, O., 210.Nisikawa, M., 139.Norris, F.A., 232.North, H. B., 154.Novelli, A., 144.Novikova, L. N., 209.Nudenberg, W., 132.Nummedal, J., 207.Nusbaum, R. E., 213.Oaks, H. H., 81.O’Daniel, H., 94.Ogston, A. G., 200.Oguri, A., 228.Ohle, H., 171, 172.Okamoto, G., 60.Oldenberg, O., 108.Oldershaw, C. F., 217.Opponheimer, E. H., 197.Order, R. B. van, 160.Orr-Ewing, J., 181.Osborn, H. T., 198.Othmer, D. F., 227, 328,Owen, L. N., 110.Oxford, A. E., 191, 192, 194.Pabst, A., 91.Pacsu, E., 112, 113.Palkin, S., 219, 230.Panizzon, L., 163.Papadimitriou, I., 122.Parker, B. F., 198.Parkinson, D. B., 6.Parsons, C. L., 47, 48.Partale, W., 114.Partington, J. R., 61.Partridge, H. M., 45.Pascher, F., 101.Passino, H. J., 105.Patterson, J.W., 231.Patterson, L. A., 135.Paul, H., 159.Pauling, L., 24, 27, 59, 8G,Pavlish, A. E., 209.Peak, D. A., 133, 141.Pearce, D. W., 70.Pearson, A. R., 29.Pearson, D. E., 135.Peat, S., 119.Pedersen, K. O., 200.Peniston, Q. P., 110.Penney, W. G., 87, 91.Pepper, K. W., 30.Percival, E. G. V., 110.Perlman, D., 136.P6teri, E., 139.Petit, R., 232.229.91INDEX OF AUTHORS’ NAMES. 241Petrow, V. A., 165.Pfankuch; E., 201.Pfenninger, F., 139.Pmner, J. J., 164.Phelan, J. J., 208.Phillips, A. J., 81.Phillips Petroleum Co., 229.Philpot, F. J., 193, 194.Piazza, J., 218, 226.Pickel, F. D., 163.Pickels, E. G., 198, 199,301.Pierce, J. E., 226.Pierce, J. G., 198.Piersma, H. D., 185.Pigott, E. C., 207.Pikl, J., 161.Pilgrim, F.J., 163.Pinkney, P. S., 135.Pinsl, H., 208, 214.Piontelli, R., 78.Pirie, N. W., 197, 198, 199,Pittmrtn, F. K., 70.Pizzarello, R. A., 120.Plankenhorn, E . , 1 10.Plentl, A. A., 143.Plewes, A. C., 229.Plyler, E., 87.Pocza, J., 91.Podbielniak, W. J.,218,222.Pompeo, D. J., 219.Pons, L., 172.Poole, G. M., 210.Porter, H. C., 41.Posternak, T., 152.Powell, C. F., 11.Powell, G., 110.Powell, H. M., 93, 94.Prelog, V., 163, 164.Press, J., 152, 163.Preston, E., 43.Price, D., 163.Price, R. W., 219.Price, W. C., 198.Prillinger, F., 138.Pringsheim, E. G., 187.Prins, D. A,, 155,156, 159.Prokofiev, V. K., 204, 211.Prytz, M., 44, 47.Przemetzky, V., 126.Pugh, L. H., 196.Pugh, W., 58, 77.Purdie, D., 160.Quandel, K., 208.Quarendon, R., 29.Quill, L.L., 71.Quirke, T. T., 88.Rachele, J. R., 172.Raistrick, A., 30.Raistrick, H., 188, 191, 192,Raiziss, G. W., 169.Rake, G., 193.Ralston, 0. C., 41.201, 203.193.Ramage, G. R., 133.Ramler, E. O., 218.Rammelkamp, C. H., 181,Ramsden, H. E., 122.Randall, D. I., 106.Randall, M., 225.Rapson, W. S., 130.Rautenstrauch, C., 132.Ray, J. N., 232.Rsyleigh, (Lord), 83.Razouk, R. I., 36, 40, 41.Rebentisch, W., 82, 83.Redel, J., 105.Reeves, R. F., 161.Reggel, L., 64.Reich, H.; 152.Reichstein, T., 114, 119,148, 149, 150, 151, 152,153, 154, 166, 156, 157,158, 159.186, 188.Reid, R. D., 188.Reinartz, F., 108.Reinders, W., 227, 228.Reithel, F. J., 193.Resuggan, J.C. L., 142.Rsxford, D. R., 231.Reynolds, D. D., 120.Rhymer, P. W., 50.Rice, F. O., 108.Richards, A. R., 218, 220.Richardson, E. M., 163.Richter, M., 232.Richtmyer, N. K., 118, 119,121, 122.Riddick, J. A., 230.Riener, T. W., 108, 109.Rihl, S., 69.Riley, D. P., 35, 36.Riley, H. L., 32, 33, 34, 42,52, 53.Rilliet, A., 164.Rimini, E., 108.Rimlyand, S. S., 205.Rinderknecht, H., 194.Riott, J. P., 207.Ritchie, B., 168.Rittner, E. S., 88.Rivas, A., 209.Rivers, T. M., 198, 199, 200,Roberts, E. C., 193.Robertson,J.M.,85,91,95,97.Robinson, F. A., 142.Robinson, F. L., 66.Robinson, G. M., 160.Robinson, H., 195.Robinson, H. J., 184, 187.Robinson, J. R., 200.Robinson, (Sir) R., 114,124,125, 126, 127, 128, 129,130, 132, 133, 134, 135,137, 140, 145, 160, 189,192.Robinson, R.A., 44, 46, 48,55, 68, 59.201.Robinson, W. O., 48.Roblin, R. O., 169.Robson, J. M., 146.Rodebush, V. H., 108.Rodin, G. I., 209.Rogers, B. A., 207.Rogers, E. F., 121.Rogers, M. T., 86.Rollefson, 0. K., 19.Rollett, A., 231.Rose, A., 221, 225.Rose, H., 90.Rosendahl, F., 218.Rosenheim, A., 68.Ross, A. F., 202.Ross, s., 94.Rossini, F. D., 219, 226.Roswell, C. A., 218.Roushdi, I. M., 146.Rouzaut, R., 225.Rubbo, S. D., 167.Ruer, R., 46.Ruggli, P., 146.Ruhkopf, H., 110.Rundle, R. E., 96.Ruschig, W., 157.Ruska, H., 201.Rusoff, I. I., 232.Russell, R. G., 70.Russell, R. S., 81.Ruzicka, L., 105, 155, 156.Ryan, A. E., 177, 178.Rydon, H.N., 126.Saffer, C. M., 137.Sahama, T. G., 70.Salditt, F., 36.Salmon, M. R., 110.Saloman, A., 169.Salzer, W., 143, 166.Samuel, G., 197.Sanders, A. G., 181.Sandor, J., 37.Sanna, G., 161.Sargent, H., 92.Sasagawa, Y., 139.S a m , A. M., 200.Savelli, J. J., 224.Saweris, Z., 40.Saxer, E. T., 206, 213.Scattergood, A., 112.Schaaf, E., 103.Schaeffer, G. W., 62.Schaffer, E., 107.Scheibli, J. R., 333.Scherrer, P., 32.Schiedt, B., 171.Schieltz, N. C., 88, 96.Schindler, W., 149.Schinle, R., 114.Schlenk, W., 102.Schlesinger, H. I., 62.Schliessmann, O., 206, 212.Schmidt, F. C., 76.Schmidt, G., 201.Schmidt, J., 132242 INDEX OF AUTHORS’ rums.Schmidt-Thorn& J., 157Schmitt, T., 160.Schmitz, A., 101.Schnakenberg, C.W., 95.Schoenbach, C. E., 181,186,Schonberg, A., 1.16.Schoental, R., 184.Schopf, C., 1G6.Schomaker, V., 86, 87, 91,Schong, P., 212.Schouls, G., 227.Schportenko, P. I., 208.Schiirenberg, H., 32.Schulman, J. H., 88.Schultze, G. R., 218.Schultze, J. E., 233.Schumacher, J. E., 227.Schumann, W., 103.Schumb, W. C., 70, 88.Schwartz, W., 211.Schwarz, R., 71.Schwenk, M. E., 189.Seabright, C. A., 64.Sebba, F., 77.Seddon, E., 43.Sedletzky, I. D., 32, 34.Seidman, L. R., 186.Seijo, E., 130.Semgder, F. W., 101.Serini, A., 138, 158.Seshan, P. K., 22.Sevast’yanov, N. G., 89.Sexton, A. R., 230.Seyfried, W. D., 224.Seyler, C. A., 30, 31, 35, 43.Shaikmahamud, H. S., 143.Shand, W., 87.Shapley, G. F., 231.Sharma, V.R., 143.Sharp, D. G., 198, 199, 200,Shamah, P. C., 86.Shea, F., 230.Shea, J., 209.Shedlovsky, T., 198.Sheehan, J. T., 122.Shen, C.-C.; 225.Shepherd, M., 225.Sheshukov, 101.Shinka,i, S., 206.Shkotovrt, S. N., 211.Shoppee, C. W., 166, 156,Short, W. F., 141, 142, 193.Shoupp, W. E., 6.Shiner, R. L., 217.Shuer, A. M., 225.Shunk, C. E., 128.Shuwirth, K., 230.Sidgwiok, N. V., 47, 53.Siedler, P., 79.Silverman, L., 207, 208.Simons, 5. H., 105, 106,158.02, 93.201.158.218.Sinelnikov, K. D., 232.Singer, L., 216.Sinha, R. P., 35.Sinkel, F., 72.Skell, P., 194.Sklar, A. L., 23.Skrapski, A., 211.Skrimshire, U. E. H., 193.Slater, S. N., 127, 134.Sla-sky, M. M., 10.Sloman, H. A., 79.Slotta, K.H., 159.Smadel, J. E., 197, 108:199, 200, 201, 202.Smart, J. S., jun., 81.Smekh, V. H., 208.Smeykal, K., 161.Smith, A. A,, jun., 81.Smith, C. R., 228.Smith, F., 110, 118.Smith, F. B., 229.Smith, G., 191, 192.Smith, K. M., 197, 201.Smith, L., 217.Smith, S., 189.Smithells, C. J., 73, 75, 80.Smithuysen, W. C. B., 230.Snyder, H. R., 217.Sobieski, M., 211.Sobolev, N. N., 204.Sondermann, K., 233.Sonn, A., 165.Sorokina, N. N., 213.Yottysiak, J., 76.Spiith, A., 103.Spencer, E. L., 193.Spielman, M. A., 138.Spiers, H. M., 229.Spinks, J. W. T., 225.Spivey, E., 42.Jpooner, E. T. C., 197.spoor, N. L., 60.Sprague, J. M., 160.Spring, F. S., 101, 108, 147.Springall, H. D., 123.3purr, H., 92.Spurr, R. A., 87.3reenivasaya, M., 203.Stack, M.V., 165.Itackelburg, M. von, 206.stage, H., 218.Stahlberger, E, 163.Itainthorpe, K. R., 66.Stallman, H., 66.Standfimb, A. F. B., €93.Itrtnley, W. M., 197, 198,200, 201, 202.Itansfield, J. M., 102.Itsudinger, H., 139.Itecher, O., 63.Steele, G. J., 208.Stegdr, L., 164.Steiger, M., 154.Sperl, Rb, 210.Jpuhr, w. P., 200.Stailcup, w. D., 280.Steinruck, K., 138.Stengel, E., 208.Stepando, B. N., 110.Stepanov, A. V., 110.Stephens, W. E., 6.Sterling, C., 209.Stevens, 5, R., 162.Stevens, T. S., 163, 166.Stevenson, A. C., 125.Stevenson, D. P., 86, 91.Stewart, T. D., 102.Stockstrom, E., 147.Stokes, A. R., 33.Stokes, 3. L., 186.Stopes, M. C., 30, 31.Story, L. F., 170.Stosick, A.J., 89.Strauch, J., 29.Straumanis, M., 65.Streiff, A. J., 228.Btr6beh3, R., 171.Struve, W. S., 114.Stuart, A. H., 144, 146.Stuart-Harris, C. H., 192.Studar, F. J., 76.Studer, S., 124.3tukanovskhje, G. I., 213.Suchenko, K. A., 215.3uckftil1, F., 110.Suhrmann, R., 71.IuIlivan, F. W., jun., 329.Sullivan, J. D., 209.Jussman, S., 107.Sutherland, G. B. B. M., 87.Sutherland, L. H., 225.Suttle, H. K., 229.Ivedberg, T., 200.Iventitskii, N. S., 210, 213.Svesknikov, A. T., 206.Swanger, W. H., 71, 81.Sykes, G., 193.Iynge, R. L. M., 185, 186.Szaruas, P., 141.Szekeres, H., 168.3zpilfoge1, S., 163.radra, w., 1/16.Cagaki, S., 228.klley, E. A., 120.rallmm, R. c., 144,145.ramamushi, Y., 163.Canasescu, I., 120.ranghe, L.J., 112.Cawara, K., 215.Caylor, A., 33.raylor, A. R., 198, 199,200, 201.raylor, E. M., 30.raylor, H. S., 22.Cei, L. J., 29.Feller, E., 38.bmiremko, T. P., 207.Cenney, A. H., 217.Ceuffert, W., 92.Chanheiser, G., 205, 210.Chelin, J. H., 231MDEX OF AUTHORS’ N-S. 243Thiele, J., 141.Thiemer, H., 81.Thode, H. a,, 217.Thomas, D. Q., 125.Thomas, K., 232.Thomson, M. L., 190.Tideswell, F. V., 31.Tinker, J. M., 106.Tipson, R. S., 119, 120.Tischenko, D. V., 101.Tiselius, A., 200.Tishler, M., 185, 195.Todd, A. R., 132, 169, 170,Tonnis, B., 172.Tollens, B., 120.Tomsicek, O., 56.Topham, A., 169, 170.Torok, T., 204.Tome, R. S., 231.Treibs, W., 108.Treloar, R. L. G., 43.Trenner, N. R., 185.Trombe, F., 78.Truesdale, E.C., 80.Tucker, N. P., 82.Tuckett, R. F., 43.Tuda, K., 228.Turk, A., 219.Turner, H. G., 35.171.Ubbelohde, A. R., 95,Ulezko, D. N., 235.Urey H. C., 108.Usatenko, J. I., 210.Vaisberg, Z. M., 214.Valatin, T., 118.Van de Griendt, G. H., 233.Van Dolah, R. W., 231.Vargha, L. von, 110, 140,Vaughan, E. J., 205, 209,Veinberg, G. J., 215, 216.Verbeek, J. H., 176.Vickerstaff, T., 101.Vigo, S., 204.Vita, A., 212.Vlodrop, C. van, 230.Volkova, L. V., 207.Volquartz, K., 29.Voorhees, V., 233.Voss, E., 63.Vyvapaeva, Z. A., 213.143.210, 214.Wada, I., 215.Wahl, M. H., 108.Waisbrot, S. W., 112, 114,115, 119.Waksman, S. A.. 181, 182,193, 195, 196.Welker, J., 126, 146.Walking, F. O., 217.Wall, M.J., 202.Wallis, E. S., 142, 146, 162.Walpole, A, L., 136.Walter, D., 208.Walter, K., 232.Walton, E., 138.Walton, W. L., 135, 136.Wantz, F. E., 161.Ward, J. L., 194.Ward, S. M., 200.Warren, B. E., 33, 36.Wartenberg, H. von, 75.Waser, J., 93.Waterman, H. I., 230.Watson, L. M., 225.Watts, C. E., 230.Wazer, J. R. van, 61.Weatherhead, (Miss) A. P.,Weber, B., 188.Weber, K., 120.Weidlich, H. A., 124, 126,Weihrich, R., 210, 211.Weiland, P., 181.Weindenbaum, B., 102.Weindling, R., 190.Weinheber, M., 58.Weinmayr, V., 106.Weinstein, L., 186.Weisblat, D. I., 112, 113,Weiss, K. L., 211.Welch, L. M., 227.Welford, G., 46, 59.Wellcome Foundation, Ltd.,Welleba, H., 138, 141.Wells, B. B., 147.Wells, W.H., 6.Welsch, M., 182, 195.Welshans, L. M., 321.Wendt, G., 102.Wentzel, K., 207.Werner, R. C., 227.Wertz, E., 107.Wessely, F. von, 138, 141.Westhaver, J. H., 230.Wettstein, A., 157.Weygand, F., 129.Weygand, P., 152.Wheeler, R. V., 29, 30, 31,Whetstone, R. R., 136.Whistler, R. L., 96.White, E. C., 193.White, H. C., 165.White, R. E., 229.White, R. V., 135.Whitmore, F. C., 104, 225.Wibaut, J. P., 163.Wiberg, E., 63.Wichers, E., 71.Wieland, H., 151, 152.Wiesner, B. P., 193.165.127.114.145.34.Wiggins, L. F., 121.Wilds, A. L., 123, 128,Wiley, R. H., 135.Wilken, J., 213.WiIker, B. L., 188.Wilkins, E. T., 31, 35.Wilkins, W. H., 182, 191,Willard, H. H., 211.Willems, J., 205.Willenz, J., 127.Willgerodt, 164.Williams, G. W., 57.Williams, M. B., 227.Williams, R., 190.Williams, T. I., 194.Willmore, C. B., 63.Wilman, H., 85.Wilson, A. J. C., 85.Wilson, (Miss) B. M., 49,Wilson, C. V., 160.Wilson, E. J., 116.Wilson, U., 188.Windaus, A., 101.Winkelmam, E., 103.Winnek, P. S., 169.Winslow, E. H., 73.Wintersteiner, O., 152, 193.Withers, W. F., 230.Wittka, F., 231.Wohler, F., 90.Wohl, A., 103.Wolbach, S. B., 180.Wolf, D. E., 174, 175.Wolfe, J. K., 121.Wolfrom, M. L., 110, 112,113, 114, 115, 119.Womack, E. B., 160.Wood, W. B., 190.Woodruff, H. B., 182, 188,Woodward, (Miss) I., 91,Woodward, R. B., 134,Wooster, N., 35.Wooster, W. A., 32, 34,Work, T. S., 165.Worley, F. P., 56.Wolz, H., 107.Wragg, W. R., 165.Wright. T. A.. 68.131.194.57.195, 196.95.137.35.Wygkoff, R. ‘W.Wydler, E., 124.198, 199.G.,Yamasaki, K., 152.Yamnitskii, A. N., 232.Yazima, T., 215.Young, A. E., 45.Young, E. E., 231.Yudkin, J., 177.197244 INDEX OF AUTHORS’ NAMES.Zarogathyta, E. N., 213.Zeigler, J. H., 229.Zemplen, G., 118.Zervas, L., 121, 122.Zeutzius, J., 212.Zhdanov, A. K., 227.Yule, J. A. C., 229.Zafito, G., 206.Zagorulko, A. J., 205.Zttjic, E., 138.Zanko, A. M., 205,208,209.Zhdanov, G. S., 89.Ziegler, K., 102, 103.Ziering, A., 143.Ziskin, M., 108.Zittle, C. A., 186.Zophy, W. H., 114

ISSN:0365-6217    

DOI:10.1039/AR9434000235

出版商:RSC    

年代:1943

数据来源: RSC

摘要:

INDEX OF SUBJECTS.Absorptiomet,er, photo-electric, use of, inAcceleration tube, 5.Acetals of hexoses and pentoses, 11 1.Acetamide, N-bromo-, reaction of, withAcetic acid, azeotropic mixture of, withdehydration of, 227, 229.lead salt, as reagent in carbohydratemetallic salts, normal and basic, 50, 51.phenyl ester, conversion of, intoreaction of, with metallic hydroxides,Acetic anhydride, preparation of, fromAcetone, equilibrium of, with benzene3 : 4-Acetone-1 : 6-anhydro-8-d-galacto-Acetylbenzilyl chloride, reaction of, with3-Acetyl- Aa-dihydro thiopyran, C-methyl-Acetylursolic acid, methyl ester, bromin-Acids, aliphatic, drying of, 229.fatty, unsaturated, methyl esters, absorp-ionisation of, 58.weak, reaction of, with metallic hydrox-steel analysis, 205.tetramethylethylene, 103.a-diethylaminobutan-y-01, 228.reactions, 11 7.p-hydroxyacetophenone, 106.50.acetaldehyde, 233.and chloroform, 228.py-ranose, 118.alkylanilines, 161.ation with, 133.ation of, 105.tion spectra of, 232.ides, 50.Acridine, spectrum of, absorption, 25..4cridines, 167.Acridines, amino-, dissociation constants of,Acrylonitrile, reactions of, 108.Actinomyces, antibiotics formed by, 195.Actinomyces antibioticus, actinomycinsfrom, 195.Actinomycetin, 195.Actinomycin A and B, 195.3-Acyloxindoles, 161.Adenine, synthesis of, 170.Adrenal cortex, steroid hormones of,Btioporphyrin-1, structure of, 95.Alcohols, polyhydric, 119.Aldehydes, spectra of, absorption, andstructure, 25.Alfalfa mosaic virus, 202.Allyl alcohol, reaction of, with benzene,in presence of hydrogen fluoride, 106.Allyl bromides, detection of, 104.d-Altrosan, reaction of, with periodic acid,118.167.145, 147.Aluminium, determination of, in steel,Aluminium chloride, reaction of, with205.pure, preparation of, 81.fluorides, 63.hydride, non-volatile, 63.hydroxide, precipitation of, 48.Amino-acids, structure of, 95.Ammonia, Nessler’s test for, 58.Amplifier, 9.a- and 8-Amyrin acetates, bromination of,Analysis, X-ray, 85.Analytical chemistry, 204.Anethole, dernethylation of, 137, 140.Aniline, p-iodo-, compound of, with8-trinitrobenzene, 93.Animal viruses, 198.Anthracene, crystals, moIecular vibrationsin, 86.purscation of, 229.spectrum of, absorption, and structure,25, 28.Anthrwite, anisotropy of, 36.Antibiotios, 182.tetramethyl-ammonium sulphite, 67.105.as fungicides, 184.chemotherapeutic value of, 183.formed by bacteria, 180, 184.formed by fungi, 180, 188.Antimony, determination of, in steel, 206.Antiseptics, definition of, 182.d- Arabinose dimethylacetal, 11 1.Arsenic, determination of, in steel, 206.pure, preparation of, 75.Arsenic trioxide, polymorphism of, 88.Arsenious acid, ionisation of, 68.Aryldiazonium chlorides, reaction of, with2-Arylindoles, 160.Aspergillic acid, 193.Aspergillus, antibiotics from, 193.Aspergillus clauatus, clavacin from, 193.Aspergillus JEavus, aspergillic acid from,Aspergillus fumigatus, antibiotics from,Auric oxide, precipitation of, 48.Aurintricarboxylic acid, ammonium salt,bicycloAza-alkanes, dehydrogenation of,Azeotropic mixtures, theory of, 226.Azeotropy, 227.Azomethane, spectrum of, absorption, andBaciUua brevis, antibiotics from, 181, 184.acrylonitrile, 109.193.193, 194.as reagent for aluminium, 205.164.structure, 25.24246 INDEX OF SUBJECTS.Bacteria, antibiotics formed by, 180, 184.Bacteriostatics, definition of, 182.Benzaza-anthrones, 166.Benzazafluorenones, 166.Benzene, distillation of, mixed withequilibrium of, with acetone and chloro-nitrartion of, 228.orbitals in, 19, 23.oxidation of, to phenol, 107.reaction of, with allyl alcohol in presenceof hydrogen fluoride, 106.wi thisobutylene, with hexene, and withpropylene in presence of hydrogenfluoride, 106, 106.Benzene, o-dichloro-, distilletion of, mixedwith diethylbnmne, 220.s-trinitro-, compound of, with p-iodo-aniline, 93.Benzenesulphonic acid, methyl ester,dehydration of, 226.p-tolyl ester, conversion of, into 2-hydr-alty-5-methyldiphenyl~ulphone, 106.Benzole, determination of, in wash oil,224.Benzophenoneoxime, rearrangement of, t obenzanilide, 106.Benzoylcarbinol, physiological action of,146.Benzylidene d-arabitols, 121.1 -Benzyltetrahydrowoquinolineg, 165.Beryllium, determination of, in steel, 206.pure, preparation of, 79.Beryllium borohydride, structure of, 62.salts, basic, 46.Beryllium-Padon, neutrons from, 8.Betatron, 7.Biochemistry, 17 7.Biotin, and its derivatives, 172.from egg-yolk and liver, 176.Bis~-hydFoxyphenylmethane, derivatives,Bi s -p-h ydr oxyphen ylpropmes, alkylated,Bismuth sesquioxide, polymorphism of,Bituminous products, origin and nature of,Bone, fractures of, effect of vitamin-C onBorohydrides, structure of, 62.Boron, determination of, in steel, 200.pure, preparation of, 73.Boron carbide, crystal structure of, 89.fluorides, structure of, 90.Bromination in aI1yI position, 104.Bromine, isotope, radioactive, use of, inexohange readions, 6 1.Bushy stunt yirus, 200, 201.Butadiene, molocules, orbitals of, 18.n- and iso-Butyl alcohols, equilibrium of,with water, 228.tert.-Butyl alcohol, reaction of, withm-xylene in presence of hydrogenfluoride, 106.ethylene dichloride, 220.form, 228.estrogenic activities of, 144.estrogenic aotivities of, 144.8 8:233.healing of, 179.iaoButylene, chlorination of, 101.hydrogen fluoride, 105.reaction of, with benzene in presence ofCadmium salts, action.of alkalis on, 49.Cmsium, pure, preparation of, 71, 76, 77.Calcium, as reducing agent, 76.determination of, in cast iron, 206.Calycanine, etructure of, 94.Carbohydrates, 109.Carbon, determination of, in steel, 206.neutrons from, 8.preparation of, from sucrose, 72.structure of, effect of heat on, 41.Carbon black, orystallography of, 35.Carbon tetraohloride, structure of, 86.Carbonaceous materials, physical chemis-Carbonates, precipitation of, 56.Csrbonisation, crystallography of, 33.p-Carotene, orbitals in, 19.Catalytic hydrogenation, catalysts for,Cellobiose, synthesis of, 119.Cellobiotol, prepamtion of, 119.Cellosolve, equilibrium of, with ethylalcohol and with water, 227.Centrifuges, high-speed, for study ofviruses, 198.Cerium, pure, preparation of, 79.charcorzl, adsorbent area and heat ofwetting of, 37.etructure of, 36.Chlorination, in allyl position, 101.Chlorine azide, 64.Chloroform, equilibrium of, with acetoneand benzene, 228.All-Cholenic acid, 151.Chromic acid, ionisation of, 58.Chromium, determination of, in steel, 207.pure, preparation of, 75.Chromium salts, bsic, 46.Cinchoninic acid, 3-nitro-, 164.Citrinin, 192.Clarain, 31.Clavacin, 193.Claviformin, 19 1.Cloud chamber, 11.Coal, adsorptive properties of, 35.try of, 20.119, 127, 128.bituminous, crystallography of, 34.bright and dull, 31.carbonisation of, structural changescoking, 32.cornpremed, electrical resistance of, 37.elastic and rheological properties of, 42.elastic constants of, 37.metamorphic development of, 29.petrology of, 30.physical chemistry of, 29.X-ray crystallography of, 32.structure of, effect of heat on, 41.viscosify of, 43.crystallography of, 33.during, 42.Coalificetion, 30.Coal-tar spirits, analysis of, 224INDEX OF SUBJECTS.247Cobalt, determination of, in steel, 208.Cobalt ammines, e x c h g e of hydrogen in,Collagen, formation of, in relation toColour, theories of, 26.Columns, laboratory, 216, 217, 230.choice of, 820.hold-up factor in, 222.packing efEciency in, table of, 223.pure, preparation of, 74.with deuterium, 60.vitamin-C, 179.packed, 217.plate, 217.Condenser, spiral, for distillation, 219.Copper, determination of, in steel, 208.pure, preparation of, 81.Copper earbonyl, 66.chromite, as catalyst, 128.Corticosterone, and 17-fi-hydroxy-, 148.Counters, coincidence method with, 10.Geiger-Muller, 9.Counter-telescope, 1 1.Counting of particles, 9.Cresols, distillation of, 234.Crotonic wid, methyl ester, brominationof, 105.Crotononitrile, reaction of, with acrylo-nitrile, 109.Crystallography, 84.Crystals, dynamics of, X-ray study of,Cucumber viruses, 200, 201.Culture media for growth of bacteria andCupric azide, 65.isocyanic acid, germanium salt, 64.Cygnides, aliphatic, dehydration of, with$-it~oCyanine, spectrum of, absorption,Cyanoethylation with acrylonitrile, 108.Cyclotron, 6.SpiroDecane, naphthalene from, 136.Dehydrocorticosterone, and 1 'I-p-hydroxy -,9- and 11-Dehydroprogesterones, 166.Deoxycorticosterone, and 1 7-p-hyd~oxy-,17-isoDeoxycorticosberone acetate, 149.Deuterium, exchange of, with hydrogenin complex ammines, 60.Deuterium compounda, physical pro-perbies of, and of hydrogen compounds,61.fluoride, physical properties of, and ofhydrogen fluoride, 6 1.X-ray, 85.86.fungi, 183.methylene chloride, 229.and structure, 28.complex, 55.148.synbhesis of, 15 1.148.synthesis of, 149.Diacetone dulcitols, 120.2 : 3 : 4 : 5-Diacetone Z-fucitol, 121.trane-1 : 2-Diacety1ethylene7 diene con-2 : 5-Dialkylpyridines, 162.densations with, 131.Diamond, lattice constants of, 86.1 : 6-3 : 4-Dianhydro-j3-d-ta,iopyrmoee, 118.Diazomethane, reaction of with ddehydo-spectrum of, absorption, and struofure,synthesis of, 82.sugars, 114.25.Dibenz-1 : 5-naphthyridine, 165.Dibenzylidene dulcitokt, 120.1 : 2 : 3 : 4-Dibenzylidene d-aorbibol, 121.Diborane, structure of, 82.Diisobutylene, reaction of, with tchenein presence of hydrogen fluoride,106.Dienmatrol, 137, 142.a-Diethylaminobutan- y-ol, azeotropic mix-Diethylbenzene, distillation of, mixed2 : 2'-Diethylstilbene, 4 : 4'-dihydroxy-,Diethylmalonio acid, diseociation con-stants of, 53.DicycEohexenylacetylene, cydieation of,136.Dihydrostilbcestrol, 140, 141.3.: ll-Diketosetiocholanic mid, methyl3 : ll-Diketo-A4-aetiocholenio acid, methyl3 : ll-Diketocholaraio acid, methyl ester,a-Diketones, oxidation of, 107.2 : 3 : 4 : 5-Dimethylenc rl-mnnnitol, 121.Dimethylgallium borohydride, 63.Diphenyl, 4 : 4'-dinitro-, crystal stnictureof, 94.a&Diphenylbutadione, aMmgenia ac-tivity of, 146.1 : l-Diphenyl-2 : 2-dimethylefhylene,bromination of, 102.Diphenylene, structure of, 92.3 : 2-Diphenyloxindoles, 160.Dipropylmalonic acid, dissociation con-Distillation, ezeotropic, 226.ture of, with acetic acid, 228.with o-dichlorobenzene, 220.143.ester, 153.ester, 153.152.stants of, 53.fractional, 216.molecular and vacuum, 230.vacuum, frothing in, prevention of,Distillation apparatus, for chemical re-6-Divinylace t ylene, conversion of, in toDocosanes substituted, intermediates forDura,jn, 31.Dyes, colour of, theory of, 27.E&&, rare, elements, pure, preperationEgg yolk, bio6in from, 172.Electrodes for steel analysis by spazk230.actions, 225.tetrametiiylc~clohexenone, 138.synthesis of, 225.light absorption by, 28.of, 78.separation of, 69.spectra, 204248 INDEX OF SUBJECTS.Electrons, anti-bonding, 19.motion of, in atoms, equations oforbitals of, 13.spin of, 14.Waves Of, 12.Eleotroscope, 8.Elements, preparation of, by " hot-wire "by thermal decomposition of com-methods, 72.pounds, 71.separation of, 69.solid, pure, preparation of, 68.purification of, by distillation, 79.Encephalomyelitis, equine, virus, 200.Entropy, changes of, during azeotropeformation, 227.Enzymes, effect of, on viruses, 202.preparation of, 233.Epicellobiose, 119.Epilactose, 11 9.Equation, Schrodinger, wave, 32.d-Equilenin, synthesis of, 123.dZ-Equilenin, synthesis of, 123.Ethane, bond lengths in, 86.Ethyl alcohol, azeotropic mixture of,with m-xylene, 228.determination of, in liquids and wines,226.equilibrium of, with cellosolve andwith water, 227.Ethylene, longest-wave absorption of,22.molecules, orbitals of, 18.structure of, 91.Ethylene derivatives, involving allylposition, reactions of, 101.dichloride, distillation of, mixed withbenzene, 220.Ethylenic compounds, oxidation of, byhydrogen peroxide in tert.-butylalcohol, 107.Flavazole, 17 1.Fluorescein, spectrum of, absorption, andcolour, 28.Fluorine, bond lengths in, 86.Formamidine, use of, in pyrimidinesynthesis, 169.Formic acid, b.p. of mixtures of, withwater, 228.gadolinium salt, structure of, 91.Fractionating columns, 216, 230.choice of, 220.hold-up factor in, 222.number of plates in, 219.packed, 217.packing efficiency in, table of, 223.plate, 217.Freon, use of, to raise sparking potential,Frothing, prevention of, in distillation,d-Fructose dimethylacetal, 112.Fumaric acid, ethyl ester, oxidation of, 107.Fumigacin, 193.Fumigatin, 194.6.219, 230..Fungi, antibiotics formed by, 180, 188.Fungicides, antibiotics as, 184.Furfurylideneacetone, condensations with,Fusain, 31.130.in lignite and peat, 30.Gadolinium, pure, preparation of, 79.d-Galsctosan, preparation of, 118.reaction of, with periodic a i d , 118.d-Galactose diethylthioacetal, 113.d-Galaheptulose, 115.Gallium, pure, preparation of, 77.Gallium alums, structure of, 91.borohydride, 62.Gases, separation and purification of,Gastric disease, vitamin-C' in, 177.Gauges, low-pressure, 232.Generators, electrostatic, ti.Geranylamine hydrochloride, structure of,Germanam, 7 1.Germanic acid, ionisation of, 58.Germanium, preparation of, 71.Gliotoxin, 190.d-Glucose O-methyl-S-ethylthioacetal, 114.6 -/3-d-Glucosidodulci tol, preparation of,Glycerol, preparation and purification of,a-Glycol groups, oxidation of, 115.Glycollic acid, strontium d'-methoxy-Glycosans, 1 17.formation of, from /3-phenylglycosides,Glycylglycine, crystal structure of, 95.Gramicidin, 181, 184.l-Gulomethylitol, preparation of, 119.225.96.d-Glucoheptulose, 1 15.119.229.d-hydroxymethyl ester, 116.119.bacteriostatic action of, 186.H 1, 187.Hafnium, preparation of, 73.separation of, from zirconium, 70.Halogenation in allyl position, 101.Heat of wetting, surface area measure-ments from, 40.Helvolic acid, 194.n-Heptane, distillation of, mixed withmethylcyclohexrtne, 220.Hernia, post-operative, prevention of,179.Hexa-acetyl 1 -chloro -uZdehyd o-d -galac -toses, isomeric, 112.Hexa-acetyl keto-d-glucoheptulose, 11 5.Hexa-acetyl l-methoxyuldehydo-d-galac-tose, 112.Hexa-acetyl l-thioethoxy-aldehydo-d-glu-cose, 113.trune-Hexahydrochrysene diol, Estro-genic activity of, 143.Hexamethylbenzene, compounds of, withpicryl halides, 94INDEX OF SUBJECTS.249Hexamethyleneimine, separation of, fromthe diamine, 230.Heuane, determination of, in mixtureswith heptane and pentane, 224.cycZoHexanone, oxidation of, 108.cycZoHexene, bromination of, 105.reaction-of, with benzene in presence ofwith N-bromophthelimide, 103,Hexenes, isomeric, separation and identifi-cation of, 225.Hexaestrol, 137, 140.Hexosans, preparation of, 118.High-tension apparatus, 5.Hippuric acid, condensation of, withoxindole-3-aldehyde, 161.Holmium oxide, separation of, fromother rare earths, 70.dl-D-Homoequilenin, synthesis of, 124.Homopiperonal, reaction of, with /I43 : 4-di h y dr ox yphen yl ) e t h ylam ine, 1 6 6.Hormones, adrenal cortex, 145, 147.Hydrazine, bond lengths in, 86.Hydrocarbons, aromatic, alkylation of, byhydrogen fluoride, 106.preparation of, 233.alkyl halides, 106.by olefins, 105.purification of, 229.halides of chlorine of, 61.bility of, 55.tion, and its complex salts, 56.ture of, 91.mixed, separation of, 224.Hydrochloric acid, isotope exchange withHydrocyanic acid, mercuric salt, solu-potassium salt, hydrolysis of, in solu-isoHydrocyanic acid, methyl ester, struc-Hydroferricyanic acid, 55.Hydroferrocyanic acid, 55.Hydrofluoric acid, molecular rearrange-ments with, 106.physical properties of, and of deuteriumfluoride, 61.reactions catalysed by, 105, 106.Hydrogen, atoms, energy states andspectrum of, 13.light absorption by, 14.determination of, in steel, 215.molecules, energy states and spectrumof, 16.orbitals of, 15.Hydrogen azide, structure of, 87.peroxide, bond lengths in, 86.Hydrogen-ion concentrations, table of,Hydropyridyl ketones, dehydrogenationHydroxides, amphoteric, 48.Hyperol, crystal structure of, 87.Indene, purification of, 229.Indium, pure, preparation of, 81.Indole, 5-hydroxy-, 161.Indoles, 160.oxidation with, 107.for hydroxide precipitation, 45.of, 164.precipitation of, 43.Indolylglyoxal hydrates, 161.Influenza virus, A, 198.Infusible white precipitate, 58.Iodine, isotope, radioactive, use of, inexchange reaction, 62.purification of, 82.Ions, basic, 45.Ionisation of acids, 58.Ionisation pulses produced by disintegra-Iron, cast, determination in, of carbon,catalytic, surface area measurements of,pure, preparation of, 74.separation of, from aluminium, 205.Isotopes as indicators of reaction mechan-Ivory nuts. See Phytekpas macrocarpa.a-Keratin, structure of, 84.3-Keto-A11-aetiocholenic acid, methyl ester,3-Keto-A 4:11-choladienic acid, 152.ll-Ketocholanic acid, methyl ester, 152.3-Keto-All-cholenic acid, 152,1 l-Keto-3-#l-hydroxysetiocholanic acid,methyl ester, 153.l-Keto-7-methoxy-2-methyl-1 : 2 : 3 : 4-tetrahydrophenanthrene, condensa-tion of, with As-n-pentenylmagnesiumbromide, 126.Ketones, reaction of, with acrylonitrile,with formaldehyde and methylamine,spectra of, absorption, and structure,25.a/3-unsaturated, catalytic hydrogen-2-Ket0-A~:~-octalin, conversion of, intoKetoses, preparation of, 115.Lactic acid, preparation of, 232./I-Lactoglobulin, crystal structure of, 95.Lactose, synthesis of, 119.Laevoglucosan, preparation of, 118.reaction of, with periodic acid, 118.Lanthanum, pure, preparation of, 79.Lead, determination of, in steel, 209.Light, absorption of, picture of, 14.plane-polarised, absorption of, 17.Lignin, X-ray crystallography of, 34.Lignite, 30.Liquids, drops, microfractionation of,226.Lithium, neutrons from, 8.pure, preparation of, 77.Liver, toxicity of helvolic acid to, 194.Lubricants, constitution and perform-Lubricating oils, distilhtion of, 233.d-Lyxotrihydroxyglutardialdehyde, 1 10.tion particles, 8.206.38.ism, 60.152.109.166.ation of, 126.oxidation of, 107.cis-9-methyl-2-decalone, 134.ance of, 232.identification of, 232260 INDEX OF SUBJECTS.Maleic anhydride, reaction of, withMalonic acid, metallic salts, 52, 53.reaction of, with metallic hydroxides,Manganese, determination of, in steel, 207,Mannich reaction, 166.cl-Mannosan, reaction of, with periodicMaatitis, bovine, treatment of, withMelibiotol, preparation of, 119.Mercuric oxide, use of, in acidimetry, 50.Mercuric salts, reaction of, with alkalis,propylene, 10 1.52.209.acid, 118.tyrothricin, 187.49.with ammonia, 57.Mercury, structure of, 86.Mesityl oxide, reaction of, with acrylo-Metals, degassing of, 81.pure, preparation and properties of,preparation of, electrolytically, 77.purification of, by sintering and vacuumelectrolytically, 81.Metallic hydroxides, amphoteric, 48.basic strengths of, 50.precipitation of, 43.reaction of, with weak acids, 50.Metanethole, 141.Methacrylic acid, purification of, 226.Methane, dichlorodifluoro-.See Freon.dZ-Methionine, structure of, 95.Methoxymethyl diglycollaldehydes, 11 6.2.Methoxynaphthalene, reduction of, to8-tetralone, 135.Methyl bromide, isotopic exchange re-actions of, with inorganic bromides,61.a-Methyl-d-arabofuranoside, reaction of,2-Methyl-Ae-butylene, chlorination of, 101.cis-9-Methyl-2-decalone, 134.cis- and trans-%Methyl- I-decalones, 134.Methylspirodecane, methylnaphthalene2 : 5-Methylene d-mannitol, 121.Methylcyclohexane, distillation of, mixedwith n-heptane, 220.mixed with toluene, 2 17.2 -Me thylc ycl ohexanone, condensation of,with furfurylideneacetone, 130.2-MethylcycZohexen-3-one, butadiene ad-dition to, 132.a-Methyl-d-hexopyranosides, reaction of,with periodic acid, 115.cia- and trans-8-Methyl- l-hydrindranones,125.a-Methylmannopyranoaide, oxidation of,with lead tetra-acetate, 127.4-Methyl mannose, 118.nitrile, 109.68.fusion, 80.nitro-, equilibrium of, with isopropylalcohol and water, 227.isocyanide, structure of, 91.with periodic acid, 116.from, 136.a-Methyl-d-pentopyranosides, reaction of,with periodic acid, 115.4-Methyl-3-vinylpyridine, 162.Milk concentrates, biotin from, 172.Minim, crystal structure of, 88.Mixtures, binary, for testing fractionatingternary, distillation of, 227.Molybdenum, determination of, in steel,pure, preparation of, 75.Molybdic acid, 69.C O l ~ S , 220.209.Naphtha, coal-tar, separation of con-Naphthacene, spectrum of, absorption,Naphthalene, pure, from petroleum, 228.reaction of, with propylene in presencespectrum of, absorption, and structure,stituents of, 232.and structure, 26, 28.of hydrogen fluoride, 106.25.Naphthyridines, 165.Neodymium, pure, preparation of, 79.Nessler's solution, 58.Neutrons, energy spectra of, 11.aources of, 7.Nickel, determination of, in steel, 240.pure, preparation of, 74, 81.Raney, 8s catalyst, 119, 127.Nicotiana glubkosa, sensitivity of, toNicotine, equilibrium of, with water, 228.separation of, from' other alkaloids, 228.Niobic acid, 59.Niobium, determination of, in steel, 212.preparation of, 73.pure, preparation of, 78, 80.Nitrogen, determination of, in steel, 215.structure of, 86.Nitrogen organic compounds, heterocyclic,Nitrogen monoxide, structure of, 87.Nitrogen-nitrogen bond, length of, 86.Nitrous oxide.See Nitrogen monoxide.z-Norequilenin, 124.dl-Norleucine, structure of, 95.z-Norcestrone, synthesis of, 126.Notatin, 192.Nucloic acids of viruses, 201.viruses, 199.160.oxides, structure of, 86.Octa-acetyl aldehydo-maltose, 110.Octahydropyridocoline, 104.CEstrogens, synthetic, 146.CEstrono, synthesis of, and its ieomerides,Oils, crude, fractionation of, 226.mineral, used, recovery of, 232.Olefins, oxidation of, 108.Organic chemistry, 98.Organic oompounds, heterocyclic, 160.mechanics,. 12.stilbestrol type, 137.125.spectra of, absorption, and wavZNDEX OF SUBJECTS.261Palladium ammines, exchange of hydrogenPapilloma virus, Shupe, 199, 200, 201.P a r a m , separation of, from olefins, 229.Particles, emission, detection of, 8.Patulin, 192.Peat, 30.Penatin, 193.Penicillamine, 189.Penicillic acid, 19 1.Penicillin, 188.Penicillin B, 193.Penicillium cibeinum, citrinin from, 192.Penicillium ckzvifom, claviformin from,PepaiaiUim cyclopium, penicillic acid from,PeaiciUium gliocladium, antibiotic from,Penkillium notatum, antibiotics formedin, with deuterium, 60.chemotherapeutic value of, 190.191.191.190.by, 188.notatin from, 193.penicillin from, 181.Penicillium patulum, patulin from, 192.Penicillium puberulum, penicillic acidPeniciUium spinulosum, spinulosin from,Penta-acetyl 1 : l-dichloro-aldehydo-d-Penta-acetyl l-deoxy-keto-d-galaheptu.Penta-acetyl aldehydo-d-galactose, 11 2.Penta-acetyl aldeiaydo-dl-galactose, 1 10.Penta-acetyl g8lactOSe dimethylacetal,Penta-acetyl d-galactose ethylhemiacetal,Penta-acetyl keto-d-fructose, 115.Pentacene, spectrum of, absorption, and12- and iso-Pentanes, separation of, 226.cydoPentanone, oxidation of, 108.2-Pentene, chlorination of, 102.Ah-Pentenylmagnesium bromide, con-densation of, with 1 -keto- 7 -methox y-2-methyl-1 : 2 : 3 : d-tetrahydrophen-anthrene, 126.Peptides, structure of, 95.Perhydro-2 : 2'-diphenic Mi&, 136.Perhydrohexoestrols, 146.from, 191.192.galactose, 112.lose, 115.112.113.structure, 25.~ iO m i m carbonyle, and their derivatives,tetroxide as oxidation catalyst, 107.Osteogenesis, effect of vitamin-C on, 180.Oxidation with hydrogen pepoxide, 107.Oxindole, syntheses with, 161.Oxindole-3-aldehyde, condensation of,Oxindole-3 -glyoxylic acid, e thy1 eater,Oxygen, &termination of, in steel, 215.Oxygen-oxygen bond, length of, 86.Ozone, structure of, 87.66.with hippuric acid, 161.161.'Periodic acid, as reagent in carbohydratePervanadic acid ae oxidation catsly&,Petroleum, distillation products of, 232.isolation of pure compounds from, 228.Rumanian, fractionation of, 232.separation of hydrocarbons from, 226.Phenacylaryhinea, conversion of, intoPhenanthrene, 2 : 7-dihydroxy-, prepar-Pbenazine, a-hydroxy-, bactericidal ac-Phenol, reaction of, with propylene inPhenol, p-nitro-, colour of, 27.Phenols, distillation of, 234.Phenolphthalein, colour of, 27.Phenothiazine, purification of, 229.2-Phenylcinchoninamide, conversion of,into 4-tunino-&-phenylquinoline, 165.Phenylene-bhe, colour of, 27.&Phenylethylamine, 3 : 4-dihydroxy-, re.action of, with homopiperonal, 166.Phenylglyoxylic anilides, reaction of,with phenylmagnesium bromide, 1 GO.1 -Phenyl- 3- (d-erythro-trihydroxypropyl ) -flavazole, 171.3-Phenylpiperidine, and its derivatives,163.2-Phenylquinoline, 4-amino-, 165.Phenyl d-sorbitol, p-hydroxy-, preparationPhosphomolybdic acid, 69.Phosphonitrile chlorides, structure of, 90.Phosphoric acid, collection of, in packedPhosphorus, black, preparation of, 83.Phosphorus pentoxide, polymorphism of,Phosphotungstic acid, 59.Photography, X-ray, divergent-beam, 86.Phthalimide, N-bromo-, bromination by,Phthalocyanine, structure of, 96.Phthalocyanines, thermal expansion of,Phytelepm wz.mrocurlpa, d-mannosan from,Picryl halides, compounds of, with hexa-a- and p-Pinenes, fraotionation of, 230.Pirylene, structure of, 92.Plant viruses, 198.Platinum amminee, exchange of hydrogenin, with deuterium, 60.Polarisation direction of light, 28, 29.Polarograph, in steel analysis, 206.Polychloroprene, structure of, 96.Polyenes, orbitals in, 19.Polygelitol, structure of, 12 1.reactions, 115.as reagent with g i y c m s , 117.108.2-myhdOh3s, 160.ation of, 128.tivity of, 184.presence of hydrogen fluoride, 106.separation and purification of, 239.of, 119.towem, 226.determination of, in steel, 210.88.104.reaction of, with cyclohexene, 103.95.118.methylbenzene, 94252 INDEX OF SUB3ECTS.Porcupine quills, African, a-keratin from,Porphins, thermal expansion of, 95.Potassium, preparation of, 71.pure, preparation of, 77.Potassium mercuri-iodide, reaction of,with ammonia, 57.Potato virus X, 200, 201.Potential, high, production of, 5.Praseodymium, pure, preparation of, 79.Pressure, measuring and regulating devicesProac tinornycin, W5.Progesterone, 37-/3-hydroxy-, 154.isoPropyl alcohol, equilibrium of, withnitromethane and water, 227.Propylarsonic acid as reagent for zir-Propylene, chlorination of, 103.reaction of, with benzene in presence ofhydrogen fluoride, 105.with maleic anhydride, 101.with naphthalene and with phenol inpresence of hydrogen fluoride, 106.Protons, tracks of, emulsions for study of,11.Pseudomonas pyocyanea, pyocyanase from,181, 184.Pumps, 232.suction, prevention of backflow from,231.Purines, 168.Purity, standards of, for metals, 68.Pyridine, mercuration of, 163.sulphonation of, 163.synthesis of, 162.Pyridines, 2-amino-, 162.Pyridine-%-acetic acid, 164.Pyridine-2 -and- 3 -aldehydes, 1 6 3.Pyrimidine, 4 : 6-diamino-, 170.Pyrimidines, 168.Pyocyanase, 181, 184.Pyocyanine, bactericidal activity of, 184.Quinoline, dibromohydroxy-, oxalate, as8-hydroxy-, as reagent for uranium, 214.Quinolines, 164.isoQuinolines, 164.isoQuinoline- 1 -aldehyde, 165.Quinolinealdehydes, 164.Quinones, antibiotic properties of, 192.Quinuclidine, dehydrogenation of, 164.Radioactivity, 5.Rays, cosmic, coincident counters in studyof, 11.X-Rays, analysis by means of, 85.intensity measurements of, 85.Reactions, ionic, electrometric study of,Receivers, for vacuum distillation, 231.d-Rhamnitol, preparation of, 110.2-Rhamnose dimethylacetal, 112.Rhenium, pure, preparation of, 73, 78.84.for, 231.with water, 227.conium, 215.reagent for copper, 208.43.Rhodium carbonyls, and their derivatives,Rib-grass virus, 201.Ribosan, structure of, 119.Rubber hydrochloride, structure of, 96.Rubidium, pure, preparation of, 71, 76,Salicylaldoxime as reagent for copper, 208Salts, basic, soluble, 45.Samarium, pure, preparation of, 79.separation of, from other rare earths,Scandium, pure, preparation of, 78, 79.separation of, from rare earths, 69.Scurvy, wound healing in, in man, 178.dl-Serine, structure of, 95.Silicates, precipitation of, 55.Silicon, determination of, in steel, 21 1.Silver chlorate, crystal structure of, 91.Silver ions, complex, with ammonia andSodium, preparation of, 7 1.Sodium aurite, 48.vanadite, 48.Spectra, absorption, of organic compounds,and wave-mechanics, 12.Spectrograph in steel analysis, 204.Spinulosin, 192.Stannic chloride, reaction of, with tptra-methylammonium sulphite, 67.Starch, structure of, and its iodine com-plex, 96.Stearic acid, sodium salt, structure of, 94.Steel, analysis of, 204.determination in, of aluminium, 205.of antimony, 206.of arsenic, 206.of beryllium, 206.of boron, 206.of carbon, 206.of chromium, 207.of cobalt, 208.of copper, 208.of hydrogen, 2 15.of lead, 209.of manganese, 207, 209.of molybdenum, 209.of nickel, 210.of niobium, 212.of nitrogen, 215.of oxygen, 215.of phosphorus, 210.of silicon, 211.of sulphur, 212.of tantalum, 212.of tellurium, 213.of tin, 213.of titanium, 213.of tungsten, 213.of uranium, 214.of vanadium, 207, 214.of zirconium, 215.65.77.70.purification of, 82.substituted ammonias, 57.Steelometer, 205.Steeloscope, 204INDEX OF SUBJECTS.253Steroids, non-benzenoid, synthesis of,by Robinson-Mannich method, 128.synthesis of, 122.by Diels-Alder method, 131.Stilbene, cwtrogenic activity of, 146.Stilbcestrol, 137, 138.hydrogenat ion of, 14 1.Stills, control of heat input to, 219.molecular, 232.vacuum, 230, 233.Still-heads, 217, 218.Streptothricin, 196.Styracitol, structure of, 121.Sub-atomics, 5.Succinimide, N-bromo-, bromination by,Sucrose, structure of, 116.Sugars, separation of, 233.aldehyde-Sugars, determination of, 110.reaction of, with diazomethane, 114.Sulphides, organic, removal of sulphurSulphites, amphoteric action of, in liquidSulphur, determination of, in steel, 212.Sulphur dioxide, liquid, reactions in, 66.Surface area, measurement of, 37, 38, 40.Tantalic acid, 59.Tantalum, determination of, in steel, 212.pine, preparation of, 71, 73, 78, 80.Tar, distillation products of, 232.Telluric acid, ionisation of, 58.Tellurium, determination of, in steel, 213.Terpenes, fractionation of, 230.d- and t-Tetra-acetyl 1 -deoxy-keto-fruc-Tetra-acetyl 2-deoxy-6-glucoheptonolac-Tetra-acetyl d-galacturonic acid, methylTetrahydroisoquinoline, 166.Tetrahydrothiophen, 3 : 4-diamino-, 174.p-Tetralone, formation of, from 2-methoxy-naphthalene, 135.Tetramethylammonium sulphite, reactionof, with aluminium and stannicchlorides, 67.Te trame thylethylene, reaction of, withN-bromoacetamide, 103.Tetramethylhaematoporphyrin, structureof, 94.Tetramethylcyclohexenone, formation of,from 8.-divinylethylene, 135.desThiobiotin methyl ether, 175.Thiophosphoryl bromofluorides, 63.Thorium, pure, preparation of, 73, 78.Thorium chromates, precipitation of, 54.dl-Threonine, structure of, 96.Thyratron, 9.Tin, determination of, in steel, 213.sulphite in sulphur dioxide, 67.104.from, 175.sulphur dioxide, 66.purification of, 82.pure, preparation of, 80.toses, 114.tone, 114.ester, ethylhemiacetal, 112.pure, preparation of, 77.reaction of, with tetramethylammoniumTitanium, determination of, in steel, 213.Tobacco viruses, mosaic, 197, 200, 201.Toluene, detection of, in mixtures withbenzene and xylene, 224.distillation of, mixed with methylcyclo-hexano, 217.reaction of, with diisobutylene inpresence of hydrogen fluoride, 106.Toluene, o- and p-chloro-, separation of,234.Tomato bushy stunt virus, 197.aa-Trehalose, structure of, 1 16.Tri-p-anisylbromoethylene, estrogenicactivity of, 146.Trimethylamine, additive compounds of,with boron fluoride and its methylderivatives, 62.Trimethylene d-mannitol, 121.Trimethylethylene, oxidation of, 107,Trime thylgallium, 62.Triphenylethylenes, astrogenic, 146.Triphenylmethylethylene, bromination of,Triplumbic tetroxide, crystal structure ofTropane, synthesis of, 163.Tungsten, determination of, in steel, 213.Tungstic acid, 59.Turbostratic systems, 33.mobile and rigid, 34.Tyrocidine, 181, 184.bactericidal action of, 186.Tyrothricin, 18 1, 184.Ulcers, duodenal and gastric, woundhealing in, in relation to vitamin-C,177.Uranium, determination of, in steel, 214..Uranyl ions, baqic, 46.Vaccinia virus, 197, 198, 199, 200.dl-Valine, structure of, 95.Valves, distillation, 219.Vanadic acid, 59.Vanadium, determination of, in steel, 207,pure, preparation of, 75.Vanadium ions, basic, 46.Vanadium dioxide, precipitation of, 48.pentoxide as oxidation catalyst, 107.Vinyl compounds, distillation of, pre-vention of polymerisation during,226.Viruses, 197.pure, preparation of, 73, 76.necrosis, 197, 200.101.88.pure, preparation of, 78.214.effect of enzymes on, 202.inactivation of, 202.properties of, 200.Virus nucleic acids, 201.Vitamins, preparation of, 232, 233.Vitamin-B,, synthesis of, 163.Vitiman-C, effect of, on bone healing, 179.Vitamin-D, synthesis of, 147.on wound healing, 177254 INDEX OF SUBJECTS.Vitrain, 31.Wash oils, determination in, of benzole,Water, distilled, purification of, 225.Wave-mechanics of spectra, 12.Wounds, healing of, effecb of vitamin-G224.on, 177.Xanthine, synthesis of, 170.Xenon, structure of, 86.rn-Xylene, azeotropic mixture of, withethyl alioohol, 228.reaction of, with tert.-butyl alcohol inpresence of hydrogen fluoride, 106.Xylitol, preparation of, 119.d-Xylotrihydroxyglutardialdehyde, 1 10.Ytterbium, separation of, from other rareearths, 70.Zeolites, base-exchange of, with rare-Zinc, pure, preparation of, 80.Zirconium, as reducing agent, 77.determination of, in steel, 215.pure, preparation of, 73, 76.separation of, from hafnium, 70.Zirconium suiphate, basic, 46.earth elements, 70

ISSN:0365-6217    

DOI:10.1039/AR9434000245

出版商:RSC    

年代:1943

数据来源: RSC