摘要:

84 FLURSCHEIM : THE RELATION BETWEEN THEX.-The Relation between the Strengths of Acidsand Buses, and the Qzcuntitative Distribution ofA@nity in the Molecule. Part 11.By BERNEURD FLURSCHEIM.IN Part I (Trans., 1909, 95, 718)* it has been shown how thehitherto inexplicable influence which many substituents exerciseon the dissociation constants of acids and bases can be approxi-mately foreseen i f the electropolar nature of the substituent istaken into consideration, and also the amount of chemical forcerequired for its linking and the steric effect exercised by it on theelectrolytic equilibrium. Mention was also made of the factthat all known constants of amines are in harmony with thetheory, with the exception of the chloro- and bromo-anilines andpaminophenol. The latter compound and p-anisidine will bedealt with in Part 111; the present paper is concerned with thehalogen-substituted anilines, and, in view of conflicting valuesgiven by different authors, also with the toluidines. Further, agraphic method has been devised by which the superposition of thethree factors can be better illustrated than by the tabular arrange-ment previously given.Lastly, an analysis of the constitution ofsome derivatives of triphenylcarbinol, etc., is intended todemonstrate how these views may be applied with advantage tothe elucidation of some disputed problems.1.-The Dissociation Constants of p-Toluidine, m-Toluidke,pChloroaniline, m-Chloroaniline, p-Bromoaniline, and m-Bromo-aniline.The following values have been hitherto obtained :p-Toluidine .........1'56 x lodg (at 25", kw=1.18 x 1O-l4) (Bredig, Zeitsch.physikal. Chem., 1894, 13, 303); 1 ' 1 3 ~ l O - ~ (at 25",kw=1*18 x (Farmer and Warth, Trans, 1904, 85,1713) ; 4.5 x 10-lo (at 15") (Veley, Trans., 1908,93,2122) ;2.2 x (at 25") (Denison and Steele, Trans., 1906, 89,999, 1386).m-Tolnidine ...... 5.9 x 10-lo (at 25") kw=1'18 x (Bredig, Zoc. cit.) ;2-9 x 10-lo (at 25") kw=1-18 x lO-l4) (Farmer and Wltrth,Zoc. c i t . ) ; 3.9 x 10-lo (at 14") (Veleg, Zoc. cit.).p-Chloroaniline . . . 1 '49 x 1 0-lo (at 25") (Farmer and Warth) ; 1-24 x 10-l1 (atlo") (Veley).* In Part I, page 727, line 11 from below, the passage " the strength of linkingsis more affected . . . ." should read "the strength of linkings is less affected .. . ."This principle has been correctly applied in the tables. Also page 729, line 3," OmO0158 " should read '' 0*00149." Some printers' errors have been correctedin the list of " Errata.STRENGTHS OF ACIDS AND BASES. 85m-Chloroaniline,p-Bromoaniline ,m-Bromoaniline ,.. 6-58 x (at 10") (Veley).,..,.2'07~10-~~ (at 18") (Veley) ; 1*04~10'~~ (at 25") (Farmer9.5 x 10-l' (at 19") (Veley).and Warth).All these constants have been determined by hydrolysis, eitherby electrical conductivity (Bredig), or by an indicator (Veley),distribution (Farmer and Warth), and velocity of migration(Denison and Steele). I n addition, hydrolytic values have beendetermined for some of these bases electrolytically by Walker(Zeitsch.physikal. Chem., 1889, 4, 319), and colorimetrically byLellmann and Gotz (Annalert, 1893, 274, 139), but no constant,has been calculated. According t o Walker, the relative strength,beginning with the weakest, is : m-chloroaniline, pchloroaniline ;p-toluidine, aniline, m-toluidine, and, according to Lellmann andGiitz : m-chloroaniline, m-bromoaniline, pchloroaniline, p-bromo-aniline; aniline, ptoluidine. After due allowance has been madefor the effect of the differing temperatures chosen by Veley, hisseries would be : mchloroaniline, p-chloroaniline, m-bromoaniline,p-bromoaniline ; aniline, m-toluidine, p-toluidine. The series ofFarmer and Warth is : pbromoaniline, p-chloroaniline ; m-tohidine,aniline, p-toluidine ; and that of Bredig : aniline, m-toluidine,ptoluidine.If this mass of contradictory evidence is sifted in the light ofthe present theory, m-toluidine should be stronger than aniline(compare Part I, tables).Similarly, m-bromoaniline should bestronger than m-chloroaniline, for the same reason that mbromo-benzoic acid is weaker than m-chlorobenzoic acid (compare Part I,tables). The relative strength of the met% and para-halogen-substituted compounds is, however, theoretically not quite so simplydeduced. It is well known that many substituents exercise astronger polar influence from the par* than from the me&position, notwithstanding the greater number of intervening atoms,which, in an open chain, reduce the polar effect of a substituent.This can only be due to a direct neutralisation of residual affinitybetween the para-atoms, as has been assumed in the benzeneformula of Claus.The strength of this diagonal bond is, however,variable, for it depends on the amount of affinity which the carbonatoms of the nucleus have to offer t o the substituents. I n para-monosubstituted anilines, the diagonal bond between the sub-stituted carbon atoms is the weaker the more unsaturated thesubstituting atom is, that is, the more affinity it can neutralise.An independent proof for this has been given by means of thedirecting influence on introduction of a substituent ( J . p . Chern.,1905, [ii] 71, 502). Whereas steric considerations would lead oneto expect that the ratio of para- to ortho-compound would b86 FLURSCHEIM : THE RELATION BETWEEN THEgreater when bromobenzene than when chlorobenzene is nitrated,the reverse has been observed.It might be argued that this isdue to the greater polarity of chlorine, which might inhibit theformation of an ortho-compound; but this view is excluded by thefact that other strongly negative groups, such as NO, and CO,which are mainly substituted in the meta-position, always yieldmore ortho- than para-di-derivatives as by-products. The onlyexplanation that remains is therefore to assume that an unsaturatedsubstituent, like chlorine, by making a great demand on theaffinity of the carbon atom t o which it is linked, primarily weakensthe diagonal bond with the par%atom to a greater extent thanthe normal bonds with the ortho-atoms, with the result that thefree affinity on which substitution depends is more increased inthe par& than in the ortho-position; the reverse happens whenan oversaturated atom, such as quinquevalent nitrogen in thenitro-group, is linked t o the nucleus, which it cannot bind asstrongly as the hydrogen atom that it has displaced.Moreover,since chlorine has a, stronger para-substituting power, in similarconditions, than bromine, it must reduce the diagonal exchange ofaffinity t o a greater extent, that is, it must be a little more stronglylinked to the nucleus, a deduction which is in agreement withother facts and views briefly outlined in a recent preliminary note(Proc., 1909, 25, 261), also with the constants of chloro- andbromo-substituted aliphatic acids (Part I, tables).I f it follows, however, as a necessary deduction from observedfacts, that the strength of the diagonal bond is variable, itremained an open question whether the transmission of a polareffect from atom to atom also varies with the amount of affinitybound by their linking.The a 5 i t y va.lues of the chloro- andbromo-anilines are capable of supplying an experimental solution.For none of the meta- or para-compounds is there a steric factorto be considered. The quantitative factor would tend to makep-nitroaniline a stronger base than the meta-isomeride (Part I,tables) ; nevertheless, p-nitxoaniline, where the strong negativeinfluence is transmitted by a strong diagonal bond, is four timesweaker than m-nitroaniline.On the other hand, taking thequantitative factor alone, the para-halogen-substituted anilineswould be weaker than the meta-isomerides. From analogy t o thenitroanilines, the polar factor would have the same effect if thetransfer of polarity were independent of the strength of thediagonal bond. If, however, that transfer showed a variationparallel to that of the bond, it is conceivable that with a weakeningof the diagonal linking, as in p-chloroaniline, a point may bereached where the diagonal influence becomes smaller than thSTRENGTHS OF ACIDS AND BASES. 87difference between the polar effects in the y- and &positions in anopen chain; in that case the polar factor becomes smaller for thepara- than for the met*position, and this difference may againconceivably be so great that it outweighs the quantitative effect inthe opposite direction. The result would be that p-chloro- andbromo-aniline would be stronger bases than their isomerides.Thesame considerations enable one to foresee the relative strength ofp-chloro- and pbromo-aniline in either case. I f the polar influencetransmitted through a bond is independent of the strength of thelatter, chlorine, being a little more strongly linked and also morepolar, would, in the para-position, weaken aniline more than wouldbromine; in the reverse case, the very fact that chlorine is morestrongly linked, would, by weakening the diagonal bond, alsoreduce its polar effect, so that p-chloroaniline might become astronger base than p-bromoaniline.Moreover, if the polar factor out-weighed the quantitative factor as regards the relative strengthof the meta- and para-isomerides, it would have to do the samewith regard to that of the para-compounds among each other. Inother words, p-chloroaniline not only might, but would, be strongerthan p-bromoaniline if pchloroaniline were stronger than m-chloro-aniline; the sequence of values of Lellmann and Gotz, and ofVeley, would therefore be impossible.To decide these important points, it was necessary to devise amore trustworthy method for the determination of the affinityvalues of very weak bases. The vastly differing results quotedabove show that no such method existed. It is well known thatvalues based on electrical determinations of hydrolysis become lessaccurate for very weak bases, whereas the colorimetric methodsdepend greatly on physiological factors, and can claim but a quali-tative usefulness.A good distribution method, however, whichwould yield values in ageement with those obtained by the con-ductivity method for stronger bases, where the latter method istrustworthy, could also be relied on to give accurate results for veryweak bases, where the conductivity method fails. Such a method,simple and suitable also for organic laboratories, would be that dueto Farmer and Warth (Zoc. c i t . ) . The results published by theseauthors for m- and ptoluidine, however, differ considerably fromthose obtained by Bredig by the conductivity method (ZOC.cit.).This has been ascribed to association. Having had some experienceof the difficulties affecting the quantitative determinationof volatile amines, the author thought that the incorrect resultsof Farmer and Warth might be due either to actual experimentalerror in the determination of the amines, or to the too highconcentrations used, which again may have been necessitated b88 FLURSCHEIM : THE RELATION BETWEEN THEthe difficulty of accurately estimating small quantities of theamine. As may be seen in the experimental part, this was foundto be the case, and the introduction of an accurate method ofdetermining the amine gave results in agreement with the deter-minations by conductivity where such were available, and closelyagreeing with each other in all the other cases.The followingvalues were obtained, a t 25O and for k,=1*18: mtoluidine,5.48 x 10-10; p-toluidine, 1-48 x 10-9; m-chloroaniline, 3.45 x 10-11;m-bromoaniline, 3.82 x 10-11; p-chloroaniline, 9.9 x 10-11; p-bromo-aniline, 8.8 x 10-11. The relative values for m- and p-toluidine andthose for mchloro- and m-bromo-aniline agree with the theory.The relative values for the meta- chloro- and bromo-compounds onthe one hand, for the para-compounds on the other, constitute, onthe basis of the present theory, an experimental proof that atom$transmit their polarity to each other in proportion t o the quan-titative strength of the bond by w h k h they are linked. Lastly,the relative values for p-chloro- and bromo-aniline also agree withthe theory.2.--GraphicaZ Illustration of t h e Three Factors zohiclb Determinethe Uissociation Constant.When a radicle is introduced two or three times successively inthe same position, the magnitude of the effect on each introductionis generally not the same.This is in accordance with thetheoretical postulate that all three factors, if they differ from 1,must vary with each substitution. When two atoms A and Bare linked, by partly transferring the polarity of each to theother, they reduce the difference in their specific polarities (compareProc., Zoc. cit.). If a second atom B is then linked to A, thedifference of polarity being now less than it was for the first B,the polar effect of the second B on A ihust be smaller than thatof the first B.Similarly, since the force with which atoms arelinked is the result of an equilibrium ( J . pr. Chem., 1907, [ii],76, 185; Proc., Zoc. cit.), that equilibrium capnot be displaced somuch by the second atom as by the first. The steric factor, onthe other hand, shows the reverse change. The behaviour ofdi-ortho-substituted when compared with mono-ortho-substitutedcompounds, and that of tertiary, secondary, and primary aliphaticacids on esterification leave no room for doubt that the stericeffect is relatively greater for each subsequent introduction of thesame substituent in the same position.All this has been duly considered in the tables given in Part I,but it can, of course, be much more accurately representedgraphically, as exemplified by the accompanying figures.ThSTRENGTHS OF ACIDS AND BASES. 89logarithms of the factors and the total effect are plotted asordinates, and the total number of substituting groups as abscissae ;the logarithms of the factors, when added, give the logarithm ofthe total effect exercised by a substituent. This total is thequotient of the dissociation constant of the substituted by that ofthe unsubstituted compound. The individual factors, althoughthey cannot, of course, be determined with mathematical accuracy,Sztbstitwtion of Hydroxyl in Bcnzoic Acid.Substitution of Chlorine in Acetic Acid. Substitution of NO, in, Beiazoic Acid.can still be approximately arrived at, especially as regards theirrelative values, by conforming to the three postulates just men-tioned, and by comparing a great number of compounds, andgenerally conforming to the principles laid down in Part I.As the curves for ammonia show, the hitherto inexplicable effectof methyl in first raising, then lowering, the constant is readilyaccounted for.For trichloroacetic acid, the older value b90 FL~RSCHEIM : THE RELATION BETWEEN THEOstwald (K=121) has been adopted, since the curves obtainedwith the constant given by Drucker (K<40) left no doubt that thisvalue is too low, a conclusion which is supported by comparisonswith other chlorinated acids. (Owing to the exigencies of space,the different figures are on different scales.)3.-The Constitution and Relative Stability of Some QuaternaryBases, Salts, and Ions.The constitution of numerous coloured organic salts is still amuch discussed point, the question being generally whether the saltsand ions have the same constitution as the corresponding base, orwhether the ionisation of the latter has been accompanied byintramolecular rearrangement.In many cases, at least in solution,differences of constitution have been established ; but in othersonly the inconclusive evidence afforded by the colour of thecompounds has been available. The present theory suggests thefollowing deductions.A linking can be broken by ionisation if the amount of affinityavailable for its formation is relatively small (see Part I), or if therespective atoms are of pronounced and opposite polarity.Now theformer of these conditions is common to all organic ‘‘ halochromic ”bases, both in their normal and pseudo-forms. I n triphenylcarbinol.for instance, the aliphatic carbon atom of the benzenoid form is to agreat extent saturated by the residual affinity of the three benzenenuclei (Thiele) ; little affinity is therefore left for the hydroxyl,which becomes ionisable (Walden). In the quinonoid form, thehydroxyl group would be attached to a carbon atom saturated bythe great residual affinity of the atoms a t the end of a chain ofcontiguous ethylenic linkings (compare pentadiene, Thiele), andtherefore also weakly bound and ionisable. Hence it is evidentthat when such a compound is dissolved in an ionising solvent,the great mobility of the electric charge must cause an equilibriumin which ions of either form are present.is determined mainly by the polarity of the atom linked to thepositive corpuscle in either case, in the sense that the electronprefers the atom most strongly heteropolar or least isopolar toitself.Which of the two isomeric forms separates as a solid fromsuch a solution depends on the product:The constantiE, = Cquinonoid ion/cbenzenoid ion(1). k3 x k,k2If it is greater than 1, the quinonoid form separates, and viceversa. In this expression k, and k, are the dissociation constantssolubility of undissociated benzenoid formsolubility of undissociated quinonoid form- x . . STRENGTHS OF ACIDS AND BASES. 91of the quinonoid and benzenoid forms respectively.These dependon the quantitative polar and steric factors, and their relativemagnitude can therefore be ascertained by means of the presenttheory. It is seen that, whereas in the ion both forms aresimultaneously present, the solid salt or hydroxy-compound may,a priori, correspond with either one of them.When the quinonoid form of two compounds, I and 11, givesa base of alkaline strength (oxonium, azonium, etc.), and thereforepractically non-hydrolysed salts, it can be shown that the relativedegree of hydrolysis of their benzenoid salts, with strong acids andfor equivalent dilutions, very approximately corresponds with theequation :(2). . . . . . Chydrololysed I-- Chydrolysed 11 = &,, x k , ,The tendency toward hydrolysis therefore is also a functionof all the three factors, as the following few examples maydemonstrate.(a) The Polar Factor.-The dimethylamino-group is much moreelectropositive than methoxyl.I n consequence, k, is much greaterfor p-dimethylamino-substituted triphenylcarbinols than for thecorresponding methoxy-derivatives, and the former are hydrolysedto a much less extent than the latter. For the same reason,N-methylquinolinium salts are more stable than benzopyriliumsalts. Since, for polar reasons, k, for a hydroxide or acetate, etc.,is invariably much lower than for a chloride, sulphate, etc., whereasfor the oxonium-, azonium-, etc., form, k, is of the alkaline order forthe hydroxide as well as for all the salts, and since k, is independentof the anion, prcduct (1) leads one to expect that the solidhydroxide, etc., will be benzenoid in many cases where the chloride,etc., are quinonoid.( b ) The Quantitative Factor.-An unsaturated substituent inthe para-position raises the quantitative factor of k,, as shown bythe formula:An independentsuch cases groupslabile and reactiveproof for this is afforded by the fact that inattached to the methane-carbon atom becomeeven where ionisation and a quinonoid changeare excluded.Thus phenylisoamylcarbinol can be distilled at 1 3 2 O(Grignard, Ann. Univ. Lyon, 1901, No. 6, page 1), whereas its p-di-methylamino-derivative gives off water at 1 20° (Sachs and Weigert,Ber., 1907, 40, 4365), on account of the weakened linking of thehydroxyl group.When, accordingly, methoxyl is introduced intoevery para-position in triphenylcarbinol, each successive substitutio92 FLURSCHEIM : THE RELATION BETWEEN THEmeans, for the respective nucleus, a corresponding rise of k,, and,through the polar factor, also of k,. By equation (2), the suc-a3I o 11 i c equilibria.cessive decrease of hydrolysis is therefore approximately geometrical(compare v. Baeyer and Villiger’s ‘‘ Potenzengesetz,” Bey., 1902,35, 3021). Similar considerations apply t o the introduction ofone, two, and three dimethylamino-groups in the para-positions oftriphenylcarbinol (Hantzsch and Osswald, Ber., 1900, 33, 278), orof one and two of these groups in the para-position with respectto nitrogen in an azoxonium or azothionium salt (compareKehrmann, Ber., 1906, 39, 923).( c ) The Steric Factor.-If the ionic equilibrium for fluoresceintrimethyl ether :@ G,H,*CO,MeOMe C,H3<:> C,H,* OM0\/ C6H4-C02MeOMe C,H,<$>C,H, OMe63C6H4-C02Me-- .- OMWC,H,<~>C,H,:OM~ (5I 63is compared with that for the similar compound not containing thecarboxymethyl group, k3 is nearly the same for both, since thesteric and polar influence of the carboxyl group counterbalanceeach other. But k,, depending only on the polar factor, is muchgreater for the fluorescein, which is accordingly less hydrolysed,notwithstanding the presence of the additional negative substituent(Kehrmann, Ber., 1909, 42, 870).It is a disputed point whether these and similar ions (azoxonium,azothionium, etc.) are ortho- or para-quinonoid; it is seen thatthey are both.The relative preponderance of the competingequilibria depends on the respective products k, and k,.If the ionic equilibria for benzopyrilium salts are compared :(A-)CHZCH - CH:QHe3 a3C6H4<o-(!7~ - C6H,<o =CH ;I STRENGTHS OF ACIDS AND BASES. 93Cf3 Cf3i t is seen that for k3 in B both the steric and quantitative factorsare greater than in A ; and the polar factor, and therefore k,, notbeing greatly different for A and B, B is hydrolysed to a lessextent than A (Decker and Fellenberg, Ber., 1907, 40, 3818;Decker and Felser, Ber., 1908, 41, 3002).In the ionican increase ofaccordingly, inequilibrium,the size of the anionthese compounds the+ --- CPh,,raises the steric factor for k,;bromides are better conductorsIc3than the chlorides (Walden).The above ionic equilibrium also facilitates the interpretationof the reactions of these compounds.If they were merely benzenoidin solution, the lability of para-substituting halogen atoms indissociating solvents would be inexplicable ; if a direct migrationof the acidic radicle in the undissociated molecule were assumedto account for it (Gomberg), then triphenylmethyl chloride insulphur dioxide would be transformed into pchlorotriphenyl-methane, since hydrogen is much more mobile than chlorine.According to the theory advanced in this paper, the exchange ofhalogen exclusively occurs in the quinonoid ion, and, the electriccharge being much more mobile than hydrogen, the former onlymigrates to the central atom.It also follows from this that saltsand double salts obtainable from a benzenoid carbinol or halogenidein a non-dissociating solvent must t,hemselves be benzenoid, whatevertheir colour (compare v. Baeyer, Tschitschibabin). The same appliesto the corresponding derivatives of distyryl ketone and similarcompounds, These deductions apply to many other ionic equilibria,for instance : diazonium salts * :H H* The reasons why Cain's formulae have been adopted in this paper are, inaddition to those adduced by Cain (Trans., 1907, 91, 1049, and recent discussionwith Hantzsch), the following :1. The fazt thar; only the normal, but not the iso-derivative, can directly change tothe diazonium form ; this excludes sterecisomerism, and is explained by Cain'sformula94 FLURSCHEIM : THE RELATION BETWEEN THEacridinium salts :e!Ietc.EXPERIMENTALIn order to effect a quantitative estimation of the volatile aminesobtained in the benzene layer by Farmer and Warth’s distributionmethod, it is not feasible to precipitate the amine by hydrogenchloride and then t o collect it.For, apart from partial thermicdissociation on drying, the mechanical losses preclude a sufficientaccuracy, especially when it is remembered that the weight of theamine in the benzene layer, and therefore any experimental error inits determination, is multiplied by 20, after which the weight ofthe amine in the aqueous layer is obtained by subtraction.(a) Determination as Acetates.-By adding a small excess ofacetic anhydride to the benzene layer, and then distilling off the2.The fact that only the isodiazohydroxide, but not the normal one, changes toa nitrosoamine excludes stereoisomerism, and is explained by Cain’s formula.3. The quantitative and polar factors being the same for 8yn- and unli-isomerides,but the steric factor being greater for the syn-, the latter would be the stronger acid.The reverse is, however, the case, notwithstanding the fact that the secondarychange of the undissociated hydroxide, which would shift the electrolytic equilibriumin its favour, is generally more pronounced for the iso- than for the normalcompound.4. An objection against Cain’s formuls has now been removed by the recentdiscovery of azomethane, whereas no aliphatic diazonium compound has yet beenobtained.5.The fact that diazonium salts do not show the characteristic reactions of theethylenic bonds of a quinone is in perfect harmony with Cain’s views ; according touniversal experience, especially as regards benzene substitution, tervalen t nitrogenis more unsaturated than an ethylenic linking, so that bromine, for instance, is firstadded by tervalent nitrogen, whereby the quinonoid configuration disappears, and aperbromide of Chattaway’s formulation is produced. Similarly, hydrogen is firstadded by tervalent nitrogen in the diazonium ion, and the bridge being therebyapened, only a hydrazine, but not a diamine, can result. Oxygen, also, is primarilyadded by the tervalent nitrogen of the diazonium ion, the bridge being broken, anda nitroarnine produced.6.Other formulae that have been put forward seem to be highly improbable.There are steric objections against Euler’s ,formula, whereas Morgan’s seems anunnecessary complication. Cain’s views leave room, of course, for an analogousortho-quinonojd formula ; but since Hantzsch (Ber., 1903, 36, 2069 ; Hantzsch andSmythe, Ber., 1900, 33, 505) has shown that the replacement of o- and p-substituentsin the nucleus of diazo-compounds probably occurs in the isodiazo-form, it need nothave any bearing on the constitution of the normal diazo- and diazoniumcompoundsSTRENGTHS OF ACIDS AND BASES. 95benzene and drying a t looo, the amine may be determined in afairly exact way in some cases, whereas no constant weight isobtained in others.Thus, with p-bromoaniline, the weight of theacetyl derivative was invariably too low.( b ) Determinution as Hydrochlorides.-The benzene was distilledoff in a current of dry hydrogen chloride, and the residue, togetherwith the flask (which had been weighed when dry), heated for anhour in a current of the same gas at looo; before opening theflask, the hydrogen chloride was expelled by dry carbon dioxide.A t first a cork stopper was used, and two tests gave the followingresults :p-Chloroaniline : 0.5774 gave 0.7394 hydrochloride ; calculated,0.7424 ; difference, 0*0030 = 0.4 per cent.p-Chloroaniline : 0-4822 gave 0.61 79 hydrochloride ; calculated,0-6199 ; difference, 0.0020 = 0-32 per cent.Subsequently it was found that, after repeated use, traces ofthe cork dissolved in the benzene under the action of the acid,and a washing flask with ground-in stopper was therefore used.(c) Determination as Picrates.-An experimentally simpler and,in view of reduced thermic dissociation, also better method consistsin heating about 1 gram of picric acid to constant weight, at looo,in a wide-necked 120 C.C.flask. The benzene solution is thenintroduced, the solvent distilled off, the flask heated for aboutforty-five minutes a t looo, and the weight of the amine obtainedby subtraction. The flask is then heated .for another hour, whenthe loss should be less than 0*0010 gram. I f it is more, heatingshould be continued until it is less (per hour), and until the lossbecomes constant (due to thermic dissociation only) ; this constantloss per hour, multiplied by the time of heating, must then beadded to the final weight.m-Bromoaniline : 0.0962 gave 0.0965 after heating for thirtyminutes, and 0.0956 after seventy minutes.p-Anisidine: 0.1166 gave 0.1169 after six hours; in this caseprolonged heating was necessary, whereas nearly always forty-fiveminutes were sufficient, since, probably through traces of oxidation,the mass became coloured and tenaciously retained some benzene.As the anisidine picrate showed no thermic dissociation whatever,the weight became finally constant and was correct, notwith-standing the prolonged heating.Since the picrate method gave results as accurate as could bedesired, the results by that method are alone given in detail, thoseby the hydrochloride method being shortly mentioned for com-parison.For p-anisidine, however (see Part 111), the latter methodwas fonnd to be preferable, there being no oxidation in that case96 FEURSCHEIM : THE RELATION BETWEEN THEDetermination of A finity Values.-In each case specially purepreparations were procured. The values were calculated by theformulze given by Farmer and Warth (Zoc. cit.). The results bythe picrate method do not vary by more than 5 per cent., a limitwhich has been declared by Ostwald to be admissible even for thedirect conductivity method (Zeitsch. physikal. Chem., 1889, 3 1,73).They differ by less than 10 per cent. from Bredig's con-ductivity values, which, in one case, differ by 18 per cent. fromeach other.The letters again signify : F = distribution coefficient ; c1 =initialconcentration of acid ; c2 = total initial concentration of amine;x =hydrolysis ; v = dilution ; s =substance used (in grams) ; T = sub-stance obtained from benzene layer. Where salt is added unders, the hydrochloride of the amine was used; in the other cases, thefree amine and the amount of N-hydrochloric acid correspondingwith c1 were employed.m-To1uidine.-A specimen wasacetylation, nitration, hydrolysis,and reduction :S. r.0.1 623 0.09070-0763 0'0428prepared from p-toluidine byelimination of the amino-group,F. :i::6 Average, 32.S. r . c,. C1. 9. X. k.0.9299 0.0357 0.00648 0-00648 154'3 0.056 5'48 x( salt)Specimen from Kahlbaum, which was redistilled :2'1794 0.0561 0.0152 0'0152 65-8 0-037 5'46 x(salt)1.8753 0.0518 0'0131 0-0131 76.3 0.0397 5-49 x(salt) Average, 5-48 x 10-lo.By Hydrochloride Method:~ = 1 * 5 9 ; ~ = 6 7 ; ~ = 0 ' 0 3 5 3 ; k= 6.10 x lO-]".p-Toluidine (Kahlbaum) :S. r. 11:0'0952 0.0528 31 '08. I'. C> C1' 9. 2, k.2-6247 0.0376 0.0183 0.0183 54.6 0'0207 1'48 x(salt )m-Chloroaniline (Schuchardt) :S. r. F.0.2370 :::: Average, 55.2. 0'33160'3169 0-22793. r. 4. c1. V. z. k.0.7793 0'2423 0-00613 0.00613 163 0'21 3-45 x locJx0'7984 0-2465 0.00626 0-00626 160 0-208 3'45 x lo-"Average, 3-46 x lo-"STRENGTHS OF ACIDS AND BASES. 97By Hydrochloride Xethod:9=1'8143 ; s570.4 ; x=0*142 ; k=3*56 xm-Bromoaniline (Schuchardt) :5. T. 2.162.3 155.5 Average, 158.9 0'1916 0,14930.3156 0-2449S. T. Czs C1' 9. X. k.0.2988 0.1673 0'00174 0-00175 575 0.345 3.73 x0.3397 0,1571 0'00163 0-00163 613.8 0-347 3'92 x 10-l'(anlt) Average, 3.88 x 10-l1.By Hydrochloride Method:~=0'3180 ; v=540*5 ; ~=0'351; k=3*36 x 10-l'.p-Chloroaniline (Schuchardt) :8. r . F. ii:: Average, 64 0.2177 0.14780.2030 0'1379S. T. c2. C1. V. X. k.0.8173 0.1222 0.00498 0.00498 201 0'143 9.9 x lo-"By Hydrochloride Method:(salt)S= 1.9702 ; V = 64.73 ; x = 0.084 ; k= 9.9 =lo-".p-Bromoaniline (Kahlbaum) :S. r. F.0.1929 0.1447 113.8 115.8 Average, 114.8.0.1908 0*1428S. r. C,. C1' V. 2. k.0.3443 0'1141 0.00165 0.00165 606 0.248 8.8 x 10-l1.(salt)By Hydrochloride Method :s=2.0975; ~ = 8 2 * 0 ; ~=0'0975 ; k=9*2 x lo-".It will be noticed that by the picrate method, dilutions varyingfrom 54.6 to 613.5 could be employed, whereas Farmer and Warth'sdilutions were much smaller, varying from 10.0 to 64.1.The author is again indebted to Dr. Senter for kind criticism,FLEET, HANTS.VOL. XCVII

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DOI:10.1039/CT9109700084

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年代:1910

数据来源: RSC

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98 CROSSLEY AND WREN : 3 : 5-DICHLORO-0-PHTHALIC ACID.XI.-3 : 5-Dichloro-o-phthalic Acid.By ARTHUR WILLIAM CROSSLEY and GERTRUDE HOLLAND WBEN.IN a recent number of the Berichte (1909, 42, 3529), Villigerdescribed the preparation of three of the four possible dichloro-o-phthalic acids (Cl: C1, 3: 6, 3: 4, 4 : 5 ) by the direct chlorinationof phthalic anhydride. Villiger points out (ibid., p. 3532) that afourth isomeride was described by Crossley and Le Sueur in 1902(Trans., 81, 1533), and regards the acid as 3 : 5-dichloro-o-phthalicacid, although " its constitution has never been controlled."The acid described by Crossley and Le Sueur was prepared bythe direct oxidation with dilute nitric acid of a substance believedto be 3 : 5-dichloroo-xylene. This chloro-derivative (111) was ob-tained a s a by-product in the action of phosphorus pentachloride on(11,)(111.)dimethyldihydroresorcin (I) [the main product being 3 : 5-dichloro-1 : 1-dimethylcyclohexadiene (II)], and this structure was assigned toit because there did not appear to be any reason t o presume that,in the conversion of the hydroaromatic into the aromaticdichloro-derivative, the chlorine atoms would alter their positions,During the reaction, however, a methyl group must have wandered,and this was shown to have migrated t o the ortho-position, becauseon oxidation an acid was obtained which readily gave an anhydride,and also the fluorescein reaction.Villiger is right in saying that, a tthat time (1902), the constitution of the dichloro-acid had not beencontrolled either by an analytical or a synthetical method, but thischeck on the constitution has since been recorded.I n 1904 (Trans., 85, 284) Crossley showed that the dichloro-o-xylem, obtained from dimethyldihydroresorcin, gave, on treatmentwith a nitrating mixture, a dichlorodinitro-o-xylene melting at175--176O, and in 1909 (Trans., 95, 205) Crossley and Renoufshowed that this same dichlorodinitro-o-xylene could be obtainedfrom 3 : 5-(or 4 : 6-)dinitro-o-xylene by reducing the two nitro-groupst o amino-groups, replacing the latter by chlorine atoms, and nitratingthe dichioro-o-xylem so obtained.This series of reactions obviouslyproved that the dichloroxylene obtained from dimethyldihydro-resorcin is identical with that prepared by replacing the nitro-groupsin 3 : 5-dirritro-o-xyieue by chlorine atoms, and hence it must bPOWER AND MOORE: THE CONSTITUENTS OF COLOCYNTH. 993 : 6-dichloro-o-xylene.The properties of the two specimens ofdichloro-o-xylene were not, however, oarefully compared, nor was thedichloroxylene, obtained horn 3 : 5-dinitro-o-xylene, oxidised to thecorresponding phthalic acid, but this has now been completed undersimilar conditions to those previously described, and the results aregiven in the following table :Froni dimethyl-dih ydroresorcin.Dichlorosylene . . . .. . . . . . . . . . . Yellow, refractive liquid ;slight aromatic odour.B. p. 226", m. p. 3-4".Dichlorodinitroxylene ...... M. p. 175-176".Dichlorophthalic acid ...... 51. p. 164" (previous soft-ening) with evolutionof gas.Dichlorophthalic anhydride M. p. 89".Dichlorophthalanil ,.. ... .. . M. p. 150-150 *5".From 3 : 5-di-nitro-o-xylene.Yellow, refractive liquid ;slight aromatic ociour.B. p. 226", In. p. 6-7".M. p. 176".M. p. 164" (previous soft-ening) with evolutionM. p. 89".M. p. 150".of gas.I n all cases the above melting points of the two correspondingseries of substances were checked by the mixed melting-pointmethod.This direct synthesis of 3 : 5-dichloro-o-phthalic acid proves beyonddqubt the correctness of the conclusions as to the constitution of theacid obtained by Crossley and Le Sueur from dimethyldihydro-resorcin.RESEARCH LABORATORY, PHARMACEUTICAL SOCIETY,17, BLOOMSBURY SQUAXE, W.C

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DOI:10.1039/CT9109700098

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年代:1910

数据来源: RSC

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POWER AND MOORE: THE CONSTITUENTS OF COLOCYNTH. 99XIL-The Constitueuts of Colocyntk.By FILEDERICK BELDING POWER and CHARLES WATSON MOORE.UNDER the title of ‘‘ Colocynth ” the various national Pharmacopceinsrecognise the dried, peeled fruit, or the dried pulp of the fruit, ofCitrullus Colocynthis, Schrader. Although this f r u i t has been usedmedicinally for a very long period, and has been the subject of severalinvestigations, no complete chemical examination has hitherto beenmade of it, and the various products described in the literature ashaving been obtained therefrom were either amorphous or of anindefinite nature. It was recorded, for example, many years ago byWalz ( N . Jahrb. Pharm., 1858, 9, 16, 225; 1861, 16, 10) thatcolocynth contains a bitter glucoside, designated ‘‘ colocynthin,” which,although usually forming a yellow, amorphous mass, could be obtainedin a crystalline state by the slow evaporation of its alcoholic solution.H 100 POWER AND MOORE: THE CONSTITUENTS OF COLOCYNTH.This so-called colocynthin, to which the formula C,,H,,O,, wasassigned, was stated to yield, on heating with dilute acids, dextroseand “ colocynthein,” tho latter having been described as an amorphousresin. The same investigator noted the occurrence of a tasteless,crystalline substance, designated ‘‘ colocynthitin,” which was found tobe insoluble in water and cold absolute alcohol, but soluble in boilingalcohol and ether, although its characters do not appear to have beenfurther determined.Henke (Arch. Pharrn., 1883, 221, 200) couldobtain a product corresponding with colocynthin only in the form ofa yellow, amorphous powder, and was unable to confirm the state-ment respecting its glucosidic character.Johannson (Zeitsch. anal.Cliem., 1885, 24, 154) has stated that colocynthin, when heatedwith dilute sulphuric acid, yields colocynthein, elatsrin, and bryonin,”and he recorded some colour reactions which were supposed t odifferentiate these products,Naylor and Chappel (Pha~m. J., 1907, [iv], 25, 117), in a paperentitled : ‘‘ On Cucumis trigonus, Roxb., and Colocynthin,” have com-pared a product obtained by them from the fruit of the above-mentionedspecies of Cucunais, indigenoils to India, with the so-called ‘‘ colocyn-thin” obtained from colocynth by Henke’s method and by a,modification of the latter.It is stated that whilst the productobtained from either the Indian fruit or from colocynth by Henke’sprocess was amorphous, ‘‘ that resulting from the modified processwas most largely deposited on spontaneous evaporation of its solventin pale yellow needles.” They were thus led to conclude, in the firstplace, that ‘‘ colocynthin prepared from CitrulZus Colocynthis may beobtained in a crystalline state, despite the failure of Henke and ofWagner t o induce it to assnme a crystalline form ” ; secondly, thatnotwithstanding the doubts cast by Henke upon its decomposition byacids into colocynthein and a sugar, their results on the contraryconfirm those of Johannson (Zoc. cit.), that colocynthin is capable ofhydrolysis, and that it yields, amongst other products, colocyntheinand elaterin, t o which they may add-and a sugar, dextrose.Thesame authors furthermore state that (‘ colocynth contains a white,crystalline body, agreeing in its general characters with the colocyn-thetin (colocynthitin) of Walz.” There is, however, no evidence thatany of the products prepared and examined by Naylor and Chappelwere pure or homogeneous substances, and their comparison of themwas chiefly restricted to certain colour reactions which are by nomeans characteristic of the substances they are supposed to identify.On the other hand, it may quite safely be assumed that.the productsreferred to were very indefinite mixtures.The present investigation has shown that colocynth contains aconbiderable amount of a-elaterin (Trans., 1909, 95, 1989), whicPOWER AND MOORE: TEE CONSTITUENTS OF COLOCYNTH.101is present in the free state, together with other .compounds whichhave not previously been isolated. A complete summary of the resultsnow obtained, with the deductions from them, is given at the end ofthis paper.EXP E RIM E NTA L.The material employed in this investigation was Turkish colocynth,consisting of the dried, peeled fruit of Citrullus Colocynthis, Schrader.The original weight of this material was 103 kilograms. Afterseparating a8 completely as possible the seeds from the pulp, thelatter was found to weigh 25.6 kilograms, or 24.4 per cent. of thewhole. The seeds amounted to 79.3 kilograms, thus representing75.5 per cent.of the weight of the entire peeled fruit.A small portion (10 grams) of the above-mentioned pulp wassubjected to the test for an alkaloid, when reactions were obtainedindicating the presence of an appreciable amount of such a substance.A. further portion (20 grams) of the ground pulp was extractedsuccessively in a Soxhlet apparatus with various solvents, when thefollowing amounts of extract, dried at looo, were obtained.Petroleum (b. p. 35-50") extracted 0'33 gram = 1.65 per cent.Chloroform ,, 1-06 ,, = 5.30 ,,Ethyl acetate ,, 0.61 ,, = 3.05 ,,Alcohol ,, 0'92 ,, = 4'60 ,,Ether ,, 1'75 ,, = 8.75 ,,- -Total . .. .. . ... . . . 4.67 grains = 23'35 per cent.For the purpose of a complete examination, 24.6 kilograms of theground colocynth pulp were completely extracted with hot alcohol.After the removal of the greater portion of the alcohol, a viscid, dark-coloured extract was obtained, amounting to 6.63 kilograms,DistiZlation of the Extract with Steam.A quantity (2 kilograms) of the above-mentioned extract, represent-ing 7.42 kilograms of the pulp, was mixed with water, and steampassdd through the mixture for several hours, The distillate,which amounted to 4 litres, contained some drops of oil floating onthe surface.It mas extracted with ether, the ethereal liquid beingwashed, dried, and the solvent removed, when a small quantity of anessential oil was obtained. This was a pale yellow liquid, whichpossessed a characteristic odour, and, after some time, deposited asmall amount of a crystalline substance.The amount of this oilwas, however, too small to permit of its further investigation102 POWElt AND MOORE: THE CONSTITUENTS OF COLOCYNTH,Non-volatile Constituents of the. Extruct.After the distillation of the extract with steam, as described above,there remained in the distillation flask a dark-coloured, aqueous liquid(A) and a quantity of a brown resin (B). The latter was collected andrepeatedly washed with water until nothing further was removed, thewashings being added t o the above-mentioned aqueous liquid.Examination of the Aqueous Liquid (A).Isohtion of a New Dihydric AZcohol, Citrullol, C22H3602(OH)2.The aqueous liquid (A), which amounted to 6.5 litreg, was repeatedlyextracted with ether, and the ethereal extracts united, after which aquantity of a colourless, sparingly soluble substance which accompaniedthem was separated by filtration.This substance was almost insoluble in all the ordinary solvents,and appears to have been contained in the aqueous liquid in acolloidal form.It was, however, readily soluble in hot pyridine, fromwhich it crystallised in glistening plates, melting and decomposing at285-290O. The quantity so obtained was 0.9 gram :0.1253 gave 0.3310 CO, and 0,1192 H20.C,,H,,O, requires C = 72.1 ; H = 10.4 per cent.This substance, when dissolved in chloroform with a little aceticanhydride, gave on the addition of a few drops of concentratedsulphuric acid a series of colour reactions similar to those produced byipuranol, C23H380,(0H)2 (Trans., 1909, 95, 249), and it appears,in fact, to be a lower homologue of the latter.A s it does not agreein its properties with any substance of the above formula which hashitherto been described, it is proposed to designate it citrutlol, withreference to the generic name of the plant from which it has beenobtained .It was ascertained that citrullol exhibits no physiological activitywhen administered to a dog in doses of 0.05 gram.Diacetylcitrullol, Cz2H3,0,( CO-CH,),.-This was obtained by heatingcitrullol with acetic anhydride, from which it separated i n glisteningneedles, melting at 167" :C = 72.0 ; H = 10.6.0.1330 gave 0.3378 CO, and 0.1098 H,O. C = 69.3 ; H= 9.2.C26H4206 requires C = 69.3 ; €€ = 9.3 per cent.The ethereal liquid from which the citrullol had been separated byfiltration, as above described, was subsequently evaporated, but ityielded only a resinous product from which nothing definite could beisolatedPOWER AND MOORE: THE COSSTITUENTS OF COLOCYNTH.103Isolation of an Alhloidal Principle.The aqueous liquid, which had previously been extracted with ether,was treated with a solution of basic lead acetate. This produced avoluminous, yellow precipitate, which was collected, washed, and thensuspended in water and decomposed by hydrogen sulphide. Onfiltering the mixture a liquid was obtained which, after acidifying withhydrochloric acid, responded to the ordinary alkaloid reagents. It wasrendered alkaline by means of ammonia, and extracted many timeswith chloroform. The chloroform extracts were united and repeatedlyshaken with dilute (10 per cent.) hydrochloric acid.The acid liquidswere at once brought into a solution of ammonia, and the precipitatedbase extracted by means of chloroform. On the evaporation of thesolvent there was obtained a small amount (about 5 gramsj of a lightbrown product, which was resinous in character, very weakly basic,and possessed an extremely bitter taste. It dissolved sparinglyin dilute acids, and was precipitated from its solutions by the usualalkaloid reagents, including tannin. Neither the free base nor itssalts could be obtained in a crystalline condition. On warming thebase with alkali hydroxides it dissolved, and, on prolonged boiling,ammonia was evolved.When heated with 20 per cent. hydrochloricacid it yieIded ammonia and pyridine, the latter having been identifiedby its odour, and by the formation of its platinochloride.The basic principle was not glucosidic, as no sugar was formed onboiling its acid solutions. It represents one of the physiologicallyactive constituents of colocynth, as doses of 0.1 gram administered todogs produced very drastic purgation.The filtrate from the above-mentioned basic lead acetate precipitatewas treited with hydrogen sulphide for the removal of the excess oflead, and the filtered liquid concentrated under diminished pressure toa small volume. It was then treated with a large volume of strongalcohol, which effected the precipitation of a quantity of inorganicsalts, consisting chiefly of the chloride, sulphate, and nitrate OFpotassium, togsther with a little sugar.The latter yielded d-phenyl-glucosazone, melting at 208--310°. The clear alcoholic liquid wasdecanted from the precipitated material, mixed with purified sawdust,and the thoroughly dried mixture extracted in a Soxhlet apparatuswith chloroform. This removed a small quantity of a brown syrup,whicb, on hydrolysis, yielded a sugar which readily reduced Fehling’ssolution, and from which d-phenylglucosazone, melting at 208-2 loo,was prepared, It is therefore evident that the aqueous liquid con-tained a very small amount of a glucosidic substance, but this coul104 POWER AND MOORE: THE CONSTITUENTS OF COLOCYNTH.not be obtained in a form which would permit of its being moredefinitely characterised.Examination of the Resin (B).Isolation of a-Elaterirt.This resin was a brown solid, which softened below loo', andamounted to 675 grams.It was digested with about 2 litres of strongaloohol, in which i t only partly dissolved. The undissolved portionwas collected, washed first with alcohol, and then with ether, when itwas obtained in small, colourless crystals, melting and decomposing at227-230'. On recrystallising this product from alcohol, it formedsmall, glistening, hexagonal prisms, melting and decomposing at 232O!rhe amount of crystalline substance thus obtained was 80 grams,corresponding with about 1.08 per oent.of the weight of colocynthpulp employed :0.1446 gave 0.3655 CO, and 0.1060 H,O. C = 68.9 ; H - 8.1,@20H2805 requires C = 68.9 ; H = 8-0 per cent.C,,H,*O, ,, C=68*9 ; H=84 ,, ,,Ca8H,,07 ,, C=69*1 ; H=7*8 ,, ,,This substanoe a,grees in crystalline form, melting point, and solu-bility, and in all its chemical properties with a-elaterin, as previouslydescribed by us (Trans., 1909, 96, 1989). Its empirical formulacannot yet be considered definitely established.A determination of its speoific rotatory power gave the followingresult :0.3121, made up to 20 C.C. with chloroform, gave a , - 2'9' in a %durn.tube, whence [a], - 68.9'.The alcoholic solution of the resin (B), from which the a-elsterinhad been separated by filtration as above described, together with thealcoholic and ethereal washings from the latter, was mixed with puri-fied sawdust, the thoroughly dried mixture being then suocessivelyextracted in a Soxhlet apparatus with light petroleum (b.p. 35-509),ether, chloroform, ethyl acetate, and alcohol.Petroleum Extract of the Resin (B),Isohtion of Hentriacontane, C31H64, and a Phytostevol, C,7H,60,This extract was a dark green, waxy solid, and amounted to34 grams. It was dissolved in ether, the ethereal solution beingsuccessively shaken with dilute aqueous sodium carbonate and sodiumhydroxide, which, however, removed nothing. The ether was accord-ingly evaporated, and the residue hydrolysed by boiling with aPOWER AND MOORE: THE CONSTITUENTS OF COLOCYNTH. 105alcoholiu solution of potassium hydroxide, after which the alcohol wasremoved, water added, and the alkaline solution of potassium saltsextracted with ether.The ethereal liquid was mashed, dried, and thesolvent removed, when a small quantity of a crystalline product wasobtained. This was dissolved in 250 C.C. of absolute alcohol, and thesolution kept for some hours, when a small quantity of an almostcolourless substance separated, This was collected and washed withcold alcohol, after which i t was distilled under diminished pressure.The distillate, which rapidly solidified, was crystallised from ethylaoetate, when small, glistening, colourless leaflets, melting a t 68O,were obtained :0,1344 gave 0.4176 CO, and 0.1824 H,O.The substance was thus identified as hentriacontane.The alcoholic solution from which the hntriacontane had beenremoved by filtration was concentrated to a small volume and dilutedwith water, when a quantity of a crystalline substance separated.This was collected and washed with a little ethyl acetate, after whichit was distilled under diminished pressure.The distillate was crystal-lised from a mixture of dilute alcohol and ethyl acetate, when i tformed colourless, glistening leaflets, melting at 160-1 62'. Theamount of substance so obtained was 1.3 grams :C = 84.7 ; H = 15.0.C,,H6, requires C = S5.3 ; H = 14.7 per cent.02205, heated at 115', lost 0.0104 H,O.071493 gave 0.4560 CO, and 0.1590 H20.H,O = 4.7.C27H,,0,H,0 requires H,O = 4.5 per cent.C,7H,,0 requires C = 83.9 ; H = 11.9 per cent.C=83.3 ; H= 11.8.This substance thus agrees in composition with a phytosterol, andit yielded the colour reactions of this class of compounds.It wasfound to be optically inactive, and in this respect appears to differfrom any of the phytosterols which have hitherto been recorded,The acetyl derivative, when crystallised from acetic anhydride,separated in glistening plates, melting a t 175-177'.Examination of ths Ratty Acids.The aqueous, alkaline solution of potassium salts, from which thehentriacontane and phytosterol had been removed by extraction withether, was acidified and again extracted with ether. The etherealsolution was washed, dried, and the solvent removed, when a quantity(12 grams) of fatty acids was obtained which, when distilled underdiminished pressure, passed over between 220' and 250°/15 mm.Tengrams of the mixed acids were converted into their lead salts, andthe latter digested with ether, when the greater portion dissolved.Both the soluble and insoluble portions were decomposed by hydro106 POWER AND MOORE: THE CONSTITUENTS OF COLOCYNTH.chloric acid, and the regenerated fatty acids purified by distillationunder diminished pressure. The soluble portion of the lead saltsyielded 8 grams of liquid acids, whilst the insoluble portion gave 1.5grams of solid acids.The Liquid Acids.-These acids, when distilled under diminishedpressure, passed over between 225O and 235'/15 mm. An analysis anda determination of the iodine value gave the following results :0.1406 gave 0.3964 CO, and 0.1460 H,O.0.5625 absorbed 0.8346 iodine.C = 76.9 ; H = 11.5.Iodine value = 148.4.C,,H,,O, requires C = 76.6 ; H = 12.1 pet cent.ClSHs2O2 ,, C = 77.1 ; H = 114 ,, ,, Iodine value = 181.4.I n order to obtain more definite information respecting the natureof the above mixture, a quantity of it was oxidised according to thomethod described by Lewkowitsch (Chemical Technology and Analysisof Oils, Pats, amd Wax68, 1904, Vol.I., p. 360). This resulted inthe formation of dihydroxystearic acid (m. p. 125-127') and tetra-bydroxystearic acid (m. p. 157-1 60"), the latter in predominatingamount.It may thus be concluded that the liquid acids consisted chiefly of amixture of oleic and linolic acids, the latter predominating.The Solid Acids.-These acids melted at 56-5S0, and, on analysis,gave the following result :0,1430 gave 0.3955 CO, and 0-1636 H,O.Iodine value = 90.1.C = 76.4 ; H = 12.7.C,,H,,O, requires C = 75.0 ; H = 12.5 per cent.C18H3602 ,, C= 76.1 ; H= 12.7 ,) 1,By repeated crystallisation from acetic acid a small amount of anacid melting at 68-69O was obtained, from which a silver salt wasprepared and analysed :0.21 18 gave 0.0576 Ag.From the above results it is evident that the solid acids consisted ofAg = 27.2.C18H,50,Ag requires Ag = 27.6 per cent.a mixture of palmitic and stearic acids.Ether and Chloroform Extracts of the Besin (B).Theywere light-coloured resins, and, with the exception of about 10 gramsof a-elaterin and a little of the previously-mentioned citrullol, nothingdefinite could be isolated from them.When heated with a solution ofsulphuric acid iri dilute alcohol they yielded no sugar, and thereforecontained nothing glucosidic.Both of the above-mentioned extracts were found to possesa avery marked cathartic action, which was doubtless due in part toThese extracts amounted to 169 and 180 grams respectivelyPOWER AND MOORE: THE CONSTITUENTS OF COLOCYNTH. 107the presence of small quantities of the previously described alkaloidalprinciple, as about 3 grams of the latter were obtained from them.The activity of the extracts was, however, not appreciably diminishedby the complete removal of the alkaloidal principle, as they thenproduced drastic purgation when administered to dogs in doses of 0.1gram.Ethyl Acetate and Alcohol Extracts of the Resin (B).These extracts were brown resins, amounting to 85 and 100 gramsThey respectively, and nothing definite could be isolated from them.were not glucosidic, and possessed no purgative action.Examination o f Colocynth Seeds.The material required for the proceeding investigation of the pidp ofcolocynth fruit having rendered available a large quantity of the seeds,it appeared desirable to examine the latter with respect to their moreimportant constituents.A small portion (10 grams) of the crushed seed was tested for thepresence of an alkaloid by treatment with Prollius's fluid, when distinctreactions were obtained with the usual reagente. These reactionswere probably due to the presence of a very small amount of thesame alkaloidal principle as that contained in the pulp of the fruit.Separation of an Enzyme.A quantity (2 kilograms) of the crushed Eeed was extracted bypercolation with cold light petroleum for the removal of the fattyoil, after which the material mas mixed with cold water and themixture kept for several hours.The aqueous liquid was thenexpressed and filtered, and to it a quantity of strong alcohol wasadded. A voluminous, light-coloured precipitate was thus produced,which was collected, washed with a little alcohol, and dried in adesiccator. The product so obtained amounted to 10 grams, and,although containing a large proportion of inorganic material, i treadily hydrolysed P-glucoaides.The Fatty Oil.The amount of fatty oil contained in the seed, a8 determined by theextraction of 50 grams of the ground material in a Soxhlet apparatuswith light petroleum (b.p. 35-50°), was 12.72 per cent.The oil obtained was a clear pale yellow liquid, which was devoidof optical activity. A determination of its constants gave thefollowing results : specific gravity, 2Oo/2O0= 0*92i3 ; acid value, 2.6 jeaponification value, '186.7 ; iodine value, 126.6108 POWER AND MOORE: THE CONSTITUENTS OF COLOCYNTH.Hydrolysis of the patty Oil. holation of c6 Php?OSteTOE, C20H340.A quantity (150 grams) of the oil was hydrolysed by boiling withalcoholic potassium hydroxide, the alcohol removed, water added, andthe alkaline solution of potassium salts extracted with ether.Theethereal liquid was washed, dried, and the solvent removed, when asmall quantity of a crystalline substance was obtained. This wasdistilled under diminished pressure, after which it was crystallisedfrom a mixture of dilute alcohol and ethyl acetate, when i t separatedin colourless, glistening plates, melting at 158--160'. The amountof substance so obtained was 0.3 gram :0.1700 gave 0,5154 CO, and 0.1784 H,O. C=82*7 ; H= 11.3.This substance was evidently a phytosterol, and it yielded theA determination of its0.2473, made up to 20 C.C. with chloroform, gave aD +Oo12' in aThe acetyl derivative, when crystallised from acetic anhydride,C,,H,,O requires C = 52.8 ; H = 11.7 per 1 ent.colour reactions of this class of compounds.specific rotatory power gave the following result :2-dcm.tube, whence La],, + 8.1'.separated in glistening plates, melting a t 167-1 70".The Fatty Acids.The alkaline solution of potassium salts, which had been extractedwith ether as above described, was acidified and again extracted withether, the ethereal solution being washed, dried, and the solventremoved. The fatty acids thus obtained amounted to 87 per cent. ofthe weight of the oil. When distilled under diminished pressure,they passed over between 240' and 245'/15 mm. as a viscous liquid,which solidified on cooling to a soft, nearly colourless mass. Adetermination of the constants of the total acids gave the followingresults :Melting point (complete fusion), 29.5-32' ; specific gravity,5Oo/5O0 = 0.8910 ; neutralisation value, 195.6 ; iodine value 13 1.1.These constants, both for the fatry oil and the total acids obtainedtherefrom, are in fairly close agreement with those recently recordedby Grimaldi and Prussia (Chern.Zeit., 1909, 33, 1239). The last-mentioned investigators had, however, extracted the colocynth seedsby means of carbon tetrachloride, and describe the oil as having areddish-yellow colour with a slight green fluorescence.Summary.The results of the preceding investigation may be summarised asfollows POWER AND MOORE: THE CONSTITUENTS OF COLOCYNTH. 109The material employed consisted of the dried, peeled fruit ofCitrullus Colocynthis, Schrader. The pulp of the fruit, deprived ofits seeds, represented 24.4 per cent.of the whole.On extracting the pulp with alcohol, and subjecting the resultingextract to distillation with steam, a very small amount of a paleyellow essential oil was obtained, From the portion of the extractwhich mas soluble in water, the following substances were isolated :(i) A new dihydric alcohol, C22H3602(OH)Z (m. p. 285-290°),designated as citrullol, which is apparently a lower homologue ofipuranol, and yields a diacetyl derivative melting at 16'7'. (ii) Anamorphous, alkaloidal principle, which is a very weak base, and fromwhich no crystalline derivative could be prepared; it possesses anextremely bitter taste, and represents one of the purgative principlesof the fruit.The aqueous liquid from which the above-mentionedsubstances were isolated contained, furthermore, a quantity of in-organic salts, a Iittle sugar, and a very small amount of an amorphous,glucosidic substance.The portion of the alcoholic extract which was insoluble in waterconsisted chiefly of resinous material, from which, however, a quantityof a-elaterin (m. p. 232'; [a],- 68.9') was isolated (compare Trans.,1909, 95, 1989). After the separation of the latter substance,the resin was extracted with various solvents, when it yielded a smallamount of hentriacontane, C31H,, (m. p. 68') ; a phytosterol, C,7H,,0(m. p. 160-162', optically inactive) ; a mixture of fatty acids, and afurther quantity of a-elaterin, together with a little of the above-described alkaloidal principle, None of the extracts from the resinwere glucosidic.The ether and chloroform extracts possessed markedpurgative properties, even after the complete removal of the activealkaloidal principle.The seeds of the colocynth, which represented '75.5 per cent. of theentire peeled fruit, were found to contain traces of an alkaloidalprinciple, a small amount of an enzyme which hydrolyses /3-glucosides,and a quantity of fatty oil corresponding to 12-72 per cent. of theweight of the seed. The constants of the fatty oil, and of the totalfatty acids obtained therefrom, were determined, and from the oil asmall amount of a phytosterol, C?oH340, was isolated, which melted atl58-l6O0, and had [.ID + 8-19The results of the present research have established the fact thatthe so-called '' colocynthin " and '' colocynthitin," as well as theother products obtained from colocynth by previous investigators t owhich specific names have been attached, consisted of mixtures of avery indefinite character, and that the amount of glucosidic substancecontained in the fruit is extremely small. On the other hand, it hasnow been ascertained that the purgative action of colocynth is due t110 QORTNER: A CONTRIBUTION TO TEEat least two principles, one of which is alkaloidal, although a veryweak base, and apparently incapable of forming any crystalline salts,whilst the other source of activity is represented by some non-basicprinciple or principles contained in both the ether and chloroformextracts of the resin, All the attempts to obtain the last-mentionedactive principle in a more definite form were, however, unsuccessful.No evidence could be obtained of the presence in colocynth ofp-elaterin, which constitutes the physiologically active constituent o€the f r u i t of EcbaZZiunz EZateriunz.I n conclusion, the authors desire to express their best thanks t oDr. H. H. Dale, Director of the Wellcome Physiological ResearchLaboratories, for having kindly conducted the numerous physiologicaltests involved in this investigation.THE WELLCONE CHEMICAL RESEARCH LABOXATORIES,LONDON, E.C

ISSN:0368-1645    

DOI:10.1039/CT9109700099

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

110 QORTNER: A CONTRIBUTION TO TEEXII1.-A Contribution to the Study of the Oxydases.By Ross AIKEN GORTNER, Ph.D.IN 1883 Yoshida (Trans., 1883, 43, 472) discovered laccase, thefirst of the oxydases to be studied. Later Bertrand (Compt. rend.,1896, 122, 1215) found that another variety of this class waspresent in various examples of the vegetable world, for example,potatoes, bulbs of the dahlia, various mushrooms, such as Russulanigricans, etc. This oxydasc differed radically from laccase in thatit lost its vitality a t 65-70°, and was also able to oxidise aqueoussolutions of tyrosine through various colour stages (from pink torose, violet, and blue-black), ending by a deposition of a black,melanin-like substance, and leaving the supernatant liquid com-pletely decolorised.On account of this power of oxidising tyrosine,Bertrand gave the name tyrosinase t o the oxydase.Many authors* have since that time reviewed and extended theBiedermann (PJiiger’s Archic, 1898, 72, 152) ; Biedermann and Moritz (ibid.,1899, 75, 43) ; Gessard (Ann. hut. Pculezbr, 1901, 15, 593 ; Comnpt. rend., 1903,136, 631 ; 1903, 138, 774; Compt. rend. SOC. Biol., 1902, 54, 1304, 1398) ;v. Fiirth and Schneider (Beitr. C’he-ln. Physiol. Path., 1901, 1, 229) ; Durham (Proc.Roy. Soc., 1904, 74, 310) ; Wilcock (J. PhySioZ., 1906, 34, 207) ; Bouduoy ( Trav.Sci. Univ. Bennes, 1903, 2, 281 ; 1905, 4, 67) ; Gautier (ibid., 1905, 4, 287) ;Weindl (Arch. Enl’ntech., 1907, 23, 632) ; Bertrand and Roseriblntt (Compt. rend.,1908, 146, 304) ; Abd~rhalden and Guggenheim (Zczt8ch.physiol. Chem., 1908, 54,337) ; IVolff (Compt. rend., 1909, 148, 500 ; 149, 467) ; Bncli (Ber., 1909, 42,694 ; Biochem. Centr., 1909, 9, 1, 73) ; Rocques (Compt. rend., 1909, i49, 418)STUDY OF THE OXYDASES. 111original work, so much so that tyrosinases have been found to bevery widely distributed in nature, and to occur not only in manyplants, but also in numerous animal bodies.By far the greater portion of the European work has been donewith the glycerol extracts of Eussula nigricans (Bertrand, Zoc. cit .),Russula queletin (Bertrand and Rosenblatt, Zoc. cit.), Russuladelica (Wolff, Compt. rend,, 1909, 148, SOO), Russula noircissant(Bertrand, Ann. Inst. Pasteur, 1908, 22, 381), etc., but theoccurrence of tyrosinase has been demonstrated in the ink sac of thesquid (Przibram, cited by v.Furth, T’eryleichende chemischePliiysiologie der niederen Tiere, Jena, 1903, p. 372 ; Gessard, Compt.rend., 1903, 136, 631), in the hameolymph of various insects(v. Fiirth and Schneider, loc. cit.), in wheat bran (Bertrand andMutermilch, Ann. Znst. Pasteur, 1907, 21, 833), in the intestinalfluid of meal worms (Tenebro molitor) (Biedermann, Zoc. cit.),in molluscs (Biedermann and Moritz, loc. cit.), in gum arabic andmistletoe (Bonduoy, loc. cit.), and in plants which blacken duringthe process of drying (Gautier, Zoc. cit.), etc., etc.Miss Durham (loc. cit.) states that she obtained evidence of thepresence of tyrosinase in the skins of fetal and newly-born guineapigs and rabbits of black or agouti origin.Inasmuch aa her resultsdepended on the addition of a milligram of ferrous sulphate asan “activator” (no darkening occurring in a tube containing“juices ” and tyrosine but no ferrous sulphate), and, as will beshown later in this paper, a milligram of ferrous sulphate inhibi-tscoloration almost completely-also since her ‘‘ tyrosinase ” (obtainedfrom red guinea pigs) is the only known example of a tyrosineoxidising ferment which oxidises only to the orange stage (allothers progressing to black), and lastly, since the pigment-likesubstances described in her work “are readily soluble in alkalis,”unlike those produced by v. Fiirth and Schneider (Zoc. cit.), andalso by the author from the interaction of tyrosine and tyrosinase,these substances being found to be insoluble even in hot dilutesodium hydroxide or ammonia, it is apparent that her “tyrosin-ase” reaction, if not due to some section of the ferrous sulphate,is certainly due to an agent altogether distinct from that namedby Bertrand “ tyrosinase.” The author has made several att.emptsto confirm her results, but has as yet obtained no trace ofcoloration induced by an oxydase.I n all the literature cited, the tyrosinase was that obtained byextracting with either glycerol or chloroform-water. Gessard( A n n .Inst. Pasteur, 1901, 15, 601) states that the extract maybe made with either chloroform-water or glycerol, but that theglycerol extract keeps best, and has no effect on the results112 GORTNER: A CONTRIBUTION TO THEThe source of the tyrosinase in the experiments described inthis paper varied somewhat, but the major portion of the workis devoted to the description of a new variety of this ferment,which is distinguished by absolute insolubility in water, the activityof which is destroyed by glycerol, by alcohol and ether, or bydrying a t room temperature; further, it does not oxidise resorcinol,orcinol (Wolff, loc.cit.), pyramidone (Bonduoy, Zoc. cit.), or quinol,thus in most of these reactions differing radically from the knowntyrosinases.EXPERIMENTAL.Tyrosinase in t h e Intestinal Fluid of the Meal Worm (Tenebromolitor) .Biedermann (loc. cit.) in 1898’ made a detailed study of themeal worm (Tenebro molitor), and he states that “the middleintestines of three or four hungry worms were triturated withchloroform-water. On allowing the yellow solution to stand over-night with tyrosine, a violebblack coloration was produced, whilstin a solution to which no tyrosine had been added only a slightdarkening wi~s observed.”In a repetition of the work, his results have been confirmedby the author, but it has also been found that the more perfectlythe body solids were removed from the outer surface of theintestine the less rapidly did the coloration with tyrosine proceed,this being true for either hungry or well-fed larva.The body ofthe larva is filled with a white semi-solid folded in many con-volutions. If this solid is exposed to the air, it rapidly changesthrough slate to a dense grey-black, and, as will be shown later,it contains some soluble tyrosinase and a large amount of a new‘‘ insoluble tyrosinase.”The intestinal juice, obtained by removing the intestine andcleansing it as completely as possible from the body-filling, thengrinding with fine quartz in an agate mortar, triturating withchloroform-water, and filtering, does not colour appreciably intwenty-four hours, but later changes through violet to a denseblack solution. The action of the fresh extract on tyrosine isslow, but shows the presence of some small amounts of theoxydase; that the oxidising power is due t o incomplete removalof the body-filling and not to intestinal juices is the present beliefof the author.Soluble Tyrosimase in the Body-Filling of the Meal Worm.Twenty-seven grams of the larva were ground in a mortar withchloroform-water, and the milky liquid was strained througSTUDY OF THE OXYDASEB.113cheese-cloth. The grinding of the residue was repeated until thestrainings were no longer milky, and only the hulls of the larvaremained in the cloth.The milky extract, if kept a short time in the air, rapidlydarkens a t the surface, but remains white where not in contactwith oxygen.The extract was poured into a thin filter paper, and kept,covered with a witch glass, until most of the liquid had filteredthrough, dropping on solid ammonium sulphate in excess ofwhat was required t o produce a saturated solution, this processrequiring some hours.I n this manner the soluble tyrosinaseand the colloidal insoluble tyrosinase, which passed throughthe first filter, were precipitated together as a light grey,voluminous mass.* This was collected, washed with saturatedammonium sulphate solution, dissolved in distilled water andfiltered, reprecipitated with ammonium sulphate, washed with asaturated ammonium sulphate solution, and dissolved in 40 C.C.of 0.05 per cent. sodium carbonate solution, and filtered. Thesolution so obtained was light brownish-grey, and contained thesoluble tyrosinase originally present in the larva. 0.5 C.C. por-tions of this solution were added to zolutions of various reagents,with the results shown in table I. When the tyrosinase solutionhad been previously heated to 90°, no coloration appeared in anytube, excepting in that containing quinol, showing that perhapstwo oxydases were present, tyrosinase being destroyed before 90°,and laccase perhaps surviving the short heating, tyrosinase beingalmost always accompanied by a laccaselike ferment (Bourquelot,Compt. rend., 1896, 123, 315, 423).TABLE I.Action of SoZdEe Tyrosinase from Larva of Tenebro molitor.Total volume, Time,Tube.Reagent. in C.C. in hours. Results.1.2.3.4.6.6.7.8.9.10.-Tyrosine ...............Tyrosine + 0'001 gramQuinol ..................Phenol ..................p-Aminophenol.. .......Guaiacol ...............Phloroglucinol .........Resorcinol ...............Pyramidone ............FeSO,.3333333333i 2247224482424727272Unchanged.Violet-black and prc-cipitate.Unchanged.Deep red.Pink.Brownish-black.Pink,Unchanged.> )9 )* If the filtered liquid is not precipitated, i t very rapidly darkens and soonThe black pigment may be salted out with ammoninm sulphate, becomgs j e t black.and appears as a lustrous, black, amorphous mass.It will be investigated later.VOL. XCVII. 114 GORTNER: A CONTRIBUTION TO THEWhen the precipitation of the filtrate is carried out by theaddition of three volumes of alcohol instead of saturating withammonium sulphate, a grey precipitate is obtained very similar inappearance t o that produced by the ammonium sulphate, butwhen this precipitate is dissolved it shows no tyrosinase properties,and only the laccase-like ferment can be found in the alcoholicmother liquor, showing that apparently alcohol is fatal to thisvariety of tyrosinase.Insoluble Tyrosinase.The residue left on the filter from the filtration of the extract ofcrushed larva (see above) was washed on the filter with chloroform-water during several days.The washing was considered completewhen 10 C.C. of the liquid, which had been in contact with thesolid (total volume=60 c.c.) for sixteen hours, after being filteredthrough double ‘‘ barium ” filters, gave no coloration with tyrosineduring twenty-four hours.The solid so obtJained is a grey, flocculent mass, which, whendried a t 6 5 O , forms 4 to 5 per cent. of the original weight of thelive larva.It contains from 1-0 to 1.5 per cent. of ash, consistingchiefly of iron oxide, and containing no manganese which couldbe detected by the usual tests. The drying process, however,destroys all oxidising activity.The entire insoluble mass, naturally, cannot be called tyrosinase,as a large percentage of it must be other insoluble body products.The insoluble tyrosinase in this preparation is, however, very active.I f the product is washed as above, it may be kept withoutdiminution of activity for months in a tube containing enoughchloroform and water (1CHCI3: 4H@) to cover it completely.When a few drops of this suspension are added to an aqueoussolution of tyrosine, the mixture undergoes a series of colourchanges, ranging through pink, rose, violet, and blue-black to adeposition of a black, pigment-like substance, and leaving thesupernatant liquid completely decolorised.The coloration usuallybegins in from two to four minutes after the addition of tyrosine,and the series of colour changes is complete in a few hours. Ifthe colourless, supernatant liquid is then removed and moretyrosine solution added, the series of cdour changes is repeated.This continual removal and addition of tyrosine solution has beencarried out with one specimen of tyrosinase weighing approximately0.01 gram* for four days, during which the series of colourchanges was repeated seven times.* Where weights of “insoluble tyrosinase used” are given, it means that analiquot portion of the preparation was dried on a water-bath and weighed.Theweights are therefore only an approximationSTlJDY OF THE OXPDASES. 115That the entire series of colour changes is produced from contactwith the insoluble portion and not by a zymogen acting in thepresence of tyrosine to set free soluble tyrosinase, was proved bythe following experiment.A portion of insoluble tyrosinase was added to a saturatedaqueous solution of tyrosine. In a few minutes the solution hadbecome pink, changing shortly to rose. One half of this solutionwas now removed and filtered twice through “barium” filters,the other half remaining in contact with the insoluble tyrosinase.The tubes were then set aside in the dark. In a few hours thecontents of the tube containing the insoluble tyrosinase and tyrosinesolution became changed, first violet, and finally colourless, withthe deposition of a black, pigment-like substance.The filteredportion, on the other hand, remained an unchanged rose colourfor eighteen days, and was then discarded.That the tyrosinase was not present in still unruptured cellswas proved by grinding the insoluble preparation in an agatemortar with fine quartz until no grit was precipitable. This wasthen triturated with water, and filtered. The filtered portion gaveno coloration with tyrosine in twenty-four hours, whilst theinsoluble residue was as active as it was before grinding.Not only does the insoluble preparation oxidise tyrosine easily,but other phenolic compounds are also acted on to produce theseries of colour changes given in table 11:TABLE 11.[Approximately 0.01 gram of insoluble tyrosinase ( + insoluble bodyproducts) was used in each test.Volume of 5 C.C. in each.]Tube. Reagent added.- 1. .....................2. Tyrosine .....................3.4.5.6.7.a.9.10.11.12.13.14.15.Pyrogallol ..................Phloroglucinol ............Resorcinol ..................Quinol ........................Pyramidone ...............Orcinol .....................p-Aminobenzaldehyde ...p-Nitrosobenzaldehyde . , .Ethyl p-aminobenzoate ...p - Aminophenol ............Guaiacol .....................Gum gnaiacum ............2 : 4-IXaminophenol * ...Colour series.Colourless after 72 hours.Pink -+ orange-rose + rose + light red+- violet +- blue-black + insolubleblack precipitate.Colourless after 72 hours.J 9 2 , 9 s? 7 9 7 7 9* 2 9 2 2 27 ) > 7 Y99 7 > ? 9 ,9 2 $ 2 2 ,Y f $ 9 Y 22 1 Y 2 , Y Brown + reddish-brown precipitate.Orange-pink + red +- brownish-red.Rapidly blues.Pink + orange-pink + orange-brown +orange-red + deep red.* An aquecjus solution of 2 : 4-diaminophenol changes colour when exposed to theair, but not nearly so rapidly as when insoluble tyrosinase has been added.1 116 GORTNER: A CONTRIBUTION TO THEI n order to test the effect of salts on the system tyrosine-tyrosinase, 0.001 gram of various salts was added to tubes con-taining approximately 0.01 gram of insoluble tyrosinase and 5 C.C.of a saturated aqueous solution of tyrosine, and the tubes werekept for some time.I n those tubes to which had been added potassium cyanide,mercuric chloride, copper sulphate, uranyl chloride, and ferroussulphate, no coloration was observed during sixteen hours.Theaddition of manganous sulphate, potassium nit7rit>e, barium chloride,potassium oxalate, strychnine, or atropine had no effect on theprogress of the coloration, whilst sodium arsenate, starch, andstarch and pot.assium iodide had a marked effect in that the rosecoloration appeared more rapidly and remained much longer anddeeper in colour than in the case of the untreated solution. Theportion treated with starch and potassium iodide became intensered,* whilst the untreated solution was only light pink.Warmingthe solution to 7 5 O for a short time prevents all coloration when itis subsequently treated with tyrosine, starch, and potassium iodide.Action of Glycerol o n Insoluble Tyrosinase.Various attempts were made to preserve the ferment in glycerolrather than in chloroform-water since Gessard (loc. cit.) recom-mends this method, but in every instance the preparation wasrendered inactive. I n order further to test the effect of glycerol,the author proceeded as follows. One gram of live larva wasground with chloroform-water and filtered through cheese-cloth.To the filtrate (3 c.c.) was added two volumes of glycerol andsolid tyrosine. No coloration appeared in twelve hours. Thesolution was then diluted with water to 36 c.c., and kept for afurther period of twenty-four hours without a trace of colorationappearing; a further dilution to 65 C.C.caused no change inseventy-two hours more. Without the addition of glycerol thecoloration proceeds very rapidly even in the absence of addedtyrosine. Addition of glycerol to the washed insoluble tyrosinaseand keeping the mixture for a few hours caused a total loss ofthe activity of the preparation even when subsequently washedfree from glycerol.Occurrence of a Laccase-like Ferment in the Larva ofTenebro molitor.It was early noticed in the progress of this work that quinol wasrapidly oxidised by the unwashed body-filling of the larva and* No iodine was liberated in 48 hoursSTUDY O F THE OXYDASES, 117not by the washed insoluble tyrosinase.If the washings are heatedrapidly to boiling, the resulting, precipitate collected, and thefiltrate then evaporated a t 30-40°, an oily solid is depositedwhich is very active in oxidising quinol, but does not affect tyrosine.This oxydase is much more resistant to heat than tyrosinase, andmay be heated a t looo for some minutes without losing much ofit% activity. Prolonged heating, however, gradually causes it tolose its oxidising power.The Chromogen occumviryg in t h e Larva of Tenebro molitor.As has been previously stated, the body fluid of the meal worm,when exposed to the action of the air, rapidly darkens under theinfluence of the tyrosinase contained in it and oxygen, to form adense, black solution. The formation of this coloration showsthat a chromogen must be present in the body-filling of the larva,and attempts were made to isolate it.Five grams of the larva were ground with chloroform-water andfiltered through cheese-cloth. The filtrate (150 c.c.) was warmedon a water-bath to 8 5 O to destroy all tyrosinase and to coagulatethe insoluble products, albumen, etc.After a few minutes' heating,the mixture was filtered, and the filtrate precipitated with basiclead acetate, again filtered, and lead removed from the filtrate byhydrogen sulphide. The clear filtrate was evaporated to drynesson a water-bath. The product, so obtained, is a light yellow resin,completely soluble in 0.05 per cent. sodium carbonate (3 c.c.),giving a yellow solution. When three drops of this solution areadded to water, containing insoluble tyrosinase (total vol.2 c.c.),a mixture is obtained giving identical colour changes to thoseobtained from a tyrosine solution, namely, pink, through rose,violet, and blue-black, a black precipitate being finally formed.The amount o'f the chromogen so obtained was very small, butan attempt will be made to prepare larger quantities in the nearfuture. From the evidence a t hand, however, the chromogenappears t o be either tyrosine or a closely allied compound. Nocoloration is produced by the addition of laccase.Occuwence of Tyrosinase in Other Animal Bodies.Two examples of myriopods, Scalopocryptops sexpinosa andJulius canadensis, Newp., were examined for the presence oftyrosinase, and in both instances an abundance of the ferment wasfound.The entire body mas ground with sand in an agate mortar,extracted with chloroform-water, and filtered. This fluid wasdivided into three parts, one containing no added material, oni i a GORTKER: A CONTRIBUTION TO THEtyrosine, and one phenol. I n a few hours the portion containingtyrosine had changed through violet to blue-black, with thedeposition of a black, melanin-like substance. The portion con-taining phenol changed through orange to deep sepia, whilst theuntreated tubes remained colourless. Boiling prevents allcoloration.Tyrosinase was also found to be very abundant in the larva ofCucu jus cZavipes,* changing tyrosine solution through pink to rose,violet, blue-black to melanin, and phenol through rose to light redand crimson.Occurrence of a Quinol-oxidising Ferment in, Vertebrate AnimatTissues.It has long been observed (Baumann and Preusse, Zeitsch.physiol.Chem., 1879, 3, 156) that after the use of phenol theurine assumes a dark colour on exposure to the air (the so-called‘ I carbolic urine ”), from which quinol, quinolsulphonic acid, andquinol-decomposition products may be isolated. The samecoloration occurs after the administration of quinol.The author has observed that this coloration is not peculiar tothe urine, but that extracts of practically all the tissues rapidlyoxidise quinol to intensely coloured solutions. Among the animalsinvestigated were young rats, mice, albino rats, kittens, chickens,etc., and in each instance a rapid oxidation was produced withextracts of the heart, liver, lungs, brain, kidneys, spleen, pancreas,testes, ovary, skeletal muscles, skin, and blood serum; in everycase the coloration being most intense when blood serum wasused.Long-continued boiling causes a gradual loss in oxidisingpower, although a very short heating seems to increase the activity.Different extracts gave different colorations in similar circum-stances, and these changes are shown in table 111. The tissueswere ground with sand, triturated with chlorof orm-water, andfiltered. To the turbid filtrate, quinol was added, and the tube setaside in an oven a t 4OO.f-No coloration was observed in any case in “blank” tubes, orin tubes treated with tyrosine or guaiacol.I n all cases the finalcoloration obtained with quinol was either deep blood-red orreddish-brown verging on black.When quinol was injected subcutaneously in a kitten, and theanimal killed after three to four hours, the post-mortem examina-tion showed a red circle under the skin where the injection was* Identified through the courtesy of Dr. A. D. Hopkins, of the Bureau ofEntomology, The United States Department of Agriculture.t The coloration is decidedly more rapid at 40” than at room temperatureSTUDY OF THE OXYDASES. 119TABLE 111.Time,Tube. Organ. Origin. in hours.1.2.3.4.5.6.7.8.9.10.11.12.13.14.15.16.17.11.19.20.21.22.Skin ............ Young rat ... ........................,) ............,) ) ) ...Spleen ............ , ) ...Kidney ......... ), )) ...Pancreas .........Lungs ............Liver ............) , (boiled). ..Testes ............Muscle .........Brain ...........Bile ...............), ............... ), ......Liver ............ , , ......Brain ............ )) ......Ovary ............ )) ......Blood serum ... ......Pancreas ......... ), ......Spinal cord ...... Grey rat ......Brain ............ ), ......12242424242448484848484848162416161616161616Result.Claret-coloured solution.Deep red solution.Brown solution (had been firstheated to 100").Red solution.Rose ) ) (after 48 hours,red).Rose solution.L&ht pi:k solution.Deep red ,)Pink $ IDeep brown ),Brown Y YBlack 9 )Deep red ) )Reddish-brown solution.Re&ish-bl&k :: Brownish-black y )Bright red $ 9Dull reddish-brown solution.Y Y 1 39 ) $ 9made.The remainder of the under surface of the skin and theflesh were normal in colour, but on exposure to the air the skintissue and the muscles rapidly turned pink. The blood-serum alsosoon became deep red, although, when expressed from the clot, itwas of normal colour.Occurrence of Laccase and Tyrosinase in theGautier (Zoc. c i t . ) found that many plants which blacken duringthe process of drying contain a tyrosine-oxidising ferment. Thecommon Monotropa uniflora, of the north-eastern portion of theUnited States, presents this peculiarity, and an effort was madet o discover whether or not this plant could be used ils a source oftyrosinase.A chloroform-water extract of the crushed plants was pre-cipitated with five volumes of 95 per cent.alcohol. The violet-coloured precipitate so obtained was collected after twenty-fourhours, and redissolved in 0.05 per cent. sodium carbonate solution.The solution was found to have some oxidising power, slowlyoxidising tyrosine to a blue-black insoluble substance. The actionon quinol was very rapid, however, the solution becoming deepred. Boiling destroyed tihe power of oxidising tyrosine, but notIndian Pipe "(Monotrope uniflora)120 A CONTRIBUTION TO THE STUDY OF THE OXYDASES.the power of oxidising quinol, showing that the major portion ofthe oxydase is evidently laccase.Tincture of gum guaiacum israpidly turned blue, whilst guaiacol is turned pink by the actionof the solution,I f the fresh plants are crushed with three parts by weight ofglycerol, and the mixture kept for eighteen hours and then filteredby the aid of the pump, a clear, greenish-blue solution is obtained,which, after a long time, becomes an intense bluish-black.Two drops of this filtrate almost instantly turns tincture of gumguaiacum blue, a.nd oxidises tyrosine, which changes colour throughpink to rose, violet, and finally blue-black. Quinol exhibits, underits influence, colour changes from orange to brown, deep reddish-brown, and finally intense red. When the solution of the oxydasehas previously been warmed to 80°, it is without effect on tyrosinesolution. From these data, it is evident that both tyrosinase andlaccase are present in the plant, but the quantity of tyrosinase issmall compared with that found in certain of the Russula.Summary.1. A new variety of tyrosinase has been discovered and investi-gated.2. This variety is distinguished from the known tgrosinases byits insolubility in water, its loss of vitality in glycerol solutionsand on drying, and by its inability t o oxidise resorcinol, orcinol,etc.3. A chromogen has been found in the larva of Tenebro molitor,giving with tyrosinase colour reactions identical with those givenby tyrosine.4. Tyrosinase has been found in the myriopods Scalopocryptopssexphosa and Julius canadensis, Newp., and also in t.he larva ofCzcczcjus clavipes.5. It has been observed that extracts of almost all animal tissuespossess the power of oxidising solutions of quinol, and that thispower is considerably diminished by prolonged boiling.6. Tyrosinase has been found t o exist together with laccase inthe Monotropa z~niflora.THE CARNEGIE INSTITUTION OF WASHINGTON,COLD SPRING HARBOUI:,LONG ISLAND, NEW YORR, U.S.A

ISSN:0368-1645    

DOI:10.1039/CT9109700110

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

EXPERIMENTS ON THE WALDEN INVERSION. PART 111. 121XIV.-Experiments on, the Walden Inverszon. Part .HI.Optically Active 6-Hydroxy-p-phenylpropionic Acidsand the Corresponding P- Bromo-B-phenylpropionicAcids.By ALEX. MCKENZIE and HERBERT BROOKE PERREN HUMPHRIES.THE effect, which in certain cases is associated with the electro-negative phenyl group, has been brought out clearly in previouswork on the Walden inversion (McKenzie and Clough, Trans., 1908,93, 811 ; 1909, 95, 777). For example, I-phenylchloroacetic acid,C6H,*CHCl*C0,H, is converted into a mixture of r- and Emandelicacids when aqueous sodium hydroxide is used t o displace the chlorineatom by the hydroxy-group; a mixture of r- and d-mandelic acidsis, however, produced when silver carbonate is substituted for sodiumhydroxide.This behaviour makes the problem of the Walden inversionmore complicated than before, for this reason that, by analogy withprevious work of Walden and others, it was to have been expectedthat sodium hydroxide should have caused the formation of a deztro-rotatory mandelic acid mixture from the laevorotatory chloro-acid, andthat silver carbonate should have caused the formation of a Zaewo-rotatory mandelic acid mixture. The contrast between the inter-conversion of the active lactic acids, CH,*CH(OH)-CO,H, on theone hand, and the interconversion of the active mandelic acids,C,H,-CH(OH)*CO,H, on the other, by the Walden inversion, isvery striking, and must be taken into account in any interpretationregarding the mechanism of the action which may be advanced.The present research is concerned with changes undergone by theoptically active P-hydroxy-P-phenylpropionic acids,C,H,*CH(OH)*CH,*CO,H.One of the objects was to find out if any Walden inversion could bedetected in the course of changes undergone by a compound where thecarboxyl group is not attached directly to the asymmetric carbonatom. Meanwhile this problem has been investigated by E.Fischer andScheibler (Ber., 1909, 42, 1219), who studied the displacement of thehydroxy-group in Z-P-hydroxybutyric acid, CH,*CH(OH)*CH,*CO,H.By the action of phosphorus pentachloride, this :acid was convertedinto d-/3-chlorobutyric acid, from which the original I-hydroxy-acidwas regenerated by displacing the chlorine by means of a number ofdifferent agents.Bearing in mind the possibility of the phenyl group exerting aninfluence entirely diff went from that of the methyl group, we preparedthe optically active P-hydroxy-P-phenylprpionic acids by the resolu122 McKEEjZIE AND HUMPHKIES :tion of the inactive acid with morphine in aqueous solution.Whenthe I-acid is acted on by hydrobromic acid, the resulting bromo-acidis dextrorotatory, and the change is accompanied by a certain amountof racemisation, which is less pronounced when the temperature a twhich the displacement occurs is kept low. The behaviour of thed-hydroxy-acid towards hydrobromic acid is, of course, similar.Phosphorus pentabromide also brings about a change of sign ofrotation by its action on the active hydroxy-acids.When the brominein the active bromo-acids is displaced by the hydroxy-group, either bymeans of silver oxide and water, or by sodium carbonate and wateror by water alone, a change of sign of rotation again occurs. Theparent acid is accordingly regenerated :by HBrl-C6H,*CH(OH)*CH2*C0,H ;y& d-C6H’,*CHBr*CH2*C02Hby waterAg20 or Xu‘azCOs--- -+ l-C,H5*CH(OH)*CH2*C02H.The displacement of the hydroxy-group in the active P-hydroxy-P-phenylpropionic acids by the bromine atom appears t o be a normalaction, since both phosphorus pentabromide and hydrobromic acid actin a similar manner, and since a change of sign also accompanies theaction of hydrobromic acid on the methyl d-ester.There is, therefore, no evidence of the occurrence of a Waldeninversion in any of the changes studied.EXPERIMENTAL.Resolution of Inactive /3-Hydroxy-/3 phenylpropionic Acid.Inactive /3-hydroxy-P-phenylpropionic acid was prepared by theaction of boiling water on inactive P-bromo-P-phenylpropionic acid,which is readily obtained from hydrobromic acid and cinnamic acid(Fittig and Binder, AnnaZen, 1879, 195, 131).The resolution by means of morphine proceeds with exceptionalease.So far as we are able to judge, it is immaterial whethersynthetic or storax cinnamic acid is used as the starting point for thepreparation of the inactive acid.Powdered morphine (61 grams) was added t o a solution of 36 gramsof the hy’droxy-acid in 750 C.C. of boiling water. Crystallieationbegan after the solution was allowed to cool at the ordinary tempera-ture for one hour ; the solution was then stirred occasionally, and leftovernight at the ordinary temperature.About half of the totalmorphine salt separated. The crystals, which melted and decomposedat about 2 0 6 O , were suspended in 50 C.C. of water and the morphineprecipitated by means of a slight excess of ammonia. The addition ofan excess of hydrochloric acid to the filtrate, from which the morphinEXPERIMENTS ON THE WALDEN INVERSION. PART 111. 1%ha3 been separated, caused the gradual separation, in the formof needles, of the Z-acid, which is sparingly soluble in water. Theacid was drained off and, after crystallisation from 300 C.C. of benzene,was pure. The yield amounted to 9 grams.Its melting point and itsspecific rotation did not alter after it had been recrystallised severaltimes from benzene.l-P-Hydrox~-P-pl~elzy~?.opionic acid, C,H,*CH( OH)* CH,. CO,H, issparingly soluble in water and in benzene. It separates in colourlessneedles and melts at 115-1 16' :001925 gave 0.4579 CO, and 0.1032 H,O.C9H,,08 requires C = 65.0 ; H = 6.1 per cent.Its rotation was determined in ethyl-alcoholic solution :C = 64 *9 ; H = 6.0.I = 2, c = 5.153, a: - 1-95', [u]: - 18.99I n order to obtain the enantiomorphously related isomeride, themother liquor, from which the morphine I-salt had been separated, wasconcentrated by evaporation to 150 c.c., when no separation of salttook place. The dextro-acid was then separated in the mannerdescribed above and crystallised from benzene.The yield amountedto 10 grams.d-p-Hydroxy-P-phelzylpropionic acid melts a t 115-1 16O, andresembles its Eisomeride in other particulars :0.194 gave 0.4638 CO, and 0.1051 H,O.C,€€.,,O, requires C = 65.0 ; H= 6.1 per cent.A determination of its specific rotation in ethyl-alcoholic solutionC = 64.9 ; H = 6.0.gave a value in agreement with that of the 1-acid :Z = 2, c=5.194, a? + 1-99', [a]: + 19.2'.Although the inactive acid had not been resolved previously, theactive acids have been obtained by Barkow (Inaug. Diss., Strasburg,1906), working in Erlenmeyer's laboratory, in the course of aninvestigation dealing with the a-halogen-P-hydroxy-/3-phenylpropionicacids. Barkow found that when d-u-bromo-/3-hydroxy-/3-phenyl-propionic acid, C,H,*CH(OH)*CHBr-CO2H, was reduced by sodiumamalgam, it was converted into d-/3-hydroxy-P-phenylpropionic acidwith [a]= + 19' in ethyl-alcoholic solution.Action of H9drobromic Acid on the Active P-H?/drox~-P-p~enyZpropionicAcids.Attempts to resolve inactive P-bromo-P-phenylpropionic acid into itsoptically active isomerides were not promising.The bases employedcaused some decomposition of the bromo-acid into styrene. The activebromo-acids were accordingly obtained from the correspondin124 McKENZIE AND HUMPHRlES :hydroxy-acids, but they underwent partial racemisation in the processof their formation by this method.The I-hydroxy-acid ( 2 5 grams) was covered with aqueous hydro-bromic acid, which had previously been saturated at 0'.The hydroxy-acid dissolved, and the bromo-acid separated. After one hour, waterwas added, the sparingly soluble acid drained off, washed with water,and dried over soda-lime under diminished pressure. The product had[a], + 16.8' for c = 2.059 in ethyl-alcoholic solution. It was a mixtureof the T- and d-bromo-acids, since its melting point was indefinite andits rotation changed on crystallisation. The effect of crystallisingthree times from carbon tetrachloride was to give an acid mixture,which contained more of the inactive form than before, the value for itsrotation in ethyl-alcoholic solution being [aID + 8.5' for c = 2-05.If the fuming hydrobromic acid is shaken with the I-hydroxy-acidfor a few minutes only at the laboratory temperature, the racemisationis less pronounced.In one experiment, for example, the crude bromo-acid, obtained from the I-hydroxy-acid, was crystallised once fromcarbon tetrachloride, and then gave [aJD + 20.6' for c = 2.204 in ethyl-alcoholic solution.When the d-hydroxy-acid was shaken with aqueous hydrobromicacid, saturated at Oo, for two or three minutes at Oo, the crudebromo-acid which separated had [a], - 23.9O for c = 2.974 in ethyl-alcoholic solution.Obviously, therefore, the amount of racemisation could be lessenedby maintaining the temperature low during the action of the hydro-bromic acid. Forty C.C. of aqueous hydrobromic acid (saturated a t 0')were accordingly cooled to - lo', and 8.5 grams of the I-hydroxy-acidadded.The rapid solution of the hydroxy-acid was succeeded by theseparation of a voluminous crop of the bromo-acid. After five minutes,the crystals mere separated, washed with a little water, and dried. Theproduct melted indefinitely at 126-133O, and had [aID +32*2' forc = 2.125 in ethyl-alcoholic solution. It mas crystallised from 65 C.C.of chloroform, and the crop which separated (6 grams) had [a]= f21'.From the mother liquor, two successive crops were withdrawn, thesecond of which (1.1 gram) had [a], +58*3 for c=1.03 in ethyl-alcoholic solution, whilst the residual mother liquor yielded 2 grams ofacid with [alD +96.2" for c=1*107 in ethyl-alcoholic solution. Anestimation of bromine in the latter acid indicated the presence ofcinnamic acid together with the bromo-acid.The pure active bromo-acids have accordingly a value for theirspecific rotation higher than 96*2O, and appear to be more readilysoluble in most solvents than the inactive isomeride.Furtherattempts ko isolate them were not made, since the points of interestEXPERIMENTS ON THE WALDEN INVERSION. PART 111. 125from the point of view of this investigation, could be established by aidof the partly-racemised acids.The d-hydroxy-acid gave similar results t o the above when it wastreated with fuming hydrobromic acid at - 10'.Action of Phosphorus Pentabromide on the 1- Zlydroxy-mid.The E-acid WRS dissolved in a mixture of chloroform and ether andacted on with an excess of phosphorus pentnbromide, the temperaturebeing maintained low.The bromo-acid, obtained after decompositionof the acid bromide with water, gave [.ID + 14.4" fcr c = 2-39 in ethyl-alcoholic solution.Thus phosphorus pentabromide behaves like hydrobromic acid incausing a change of sign of rotation when it acts on the activehydroxy-acid, As is usually the case when a phosphorus halide actson an active hydroxy-acid, the formation of the balogen acid isaccompanied by partial racemieation.Tormation of 1-Bromo-ester from d- Pydroxy-ester.d-P-Hydroxy-P-phenylpropionic acid was converted into its methyester by the Fischer-Speier method. This ester, which had [.ID + 14.1"for c = 4-717 in ethyl-alcoholic solution, was added to an excess offuming hydrobromic acid at - lo", and, after shaking for five minutes,the bromo-ester was separated.It was laevorotatory, giving[.ID - 28.5' for c = 6.654 in ethyl-alcoholic solution.The action of phosphorus pentabromide on the d-hydroxy-ester wasalso examined, the bromination being effected in dry chloroform andat a low temperature. The resulting bromo-ester was again Irevo-rotatory, giving [.ID - 4.6" for c = 3.03 in ethyl-alcoholic solution.Digplncemelit of Bromine in the d-Bromo-acid by t ? ~ IIydrozy-group.A mixture of the dextro- and inactive bromo-acids (0-4 gram) with[.ID +58.3* was added t o water (10 c.c.), and, after five days at theordinary temperature, the solution was heated for a few minutes untilthe odour of styrene had disappeared. The pi-oduct was thenevaporated to dryness at the ordinary temperature under diminishedpressure.The residue gave the value [.ID - 7.7" for c = 2.27 in ethyl-alcoholic solution.A mixture of the dextro- and inactive bromo-acids (0.7 gram) with+ 58.5' was added t o a solution of 0.4 gram of sodium carbonateAfter five days, the small amount of styreneOn acidification with hydrochloric acid, therein 10 C.C. of water.present was removed126 FORSTER AND MULLER: THE TRIAZO-GROUP. PART XI.was no appreciable separation of cinnamic acid. The hydroxy-acidwas extracted with ether, and had the specific rotation [.ID - 5.5' forc = 1 *451 in ethyl-alcoholic solution.Silver oxide, obtained from 1 gram of silver nitrate, was added tothe dextrorotatory bromo-acid (0.7 gram) with [a], + 96.2' and 10 C.C.of water. After twenty-four hours, with occasional shaking, theproduct was treated with hydrochloric acid, filtered, and the filtrateextracted with ether. The resulting hydroxy-acid gave the value[a]= - 1 3 0 7 ~ with c= 1.17 in ethyl-alcoholic solution.In these cases, therefore, using either water alone, sodium carbonateand water, or silver oxide and water, the hydroxy-acid recovered isopposite in sign to t h a t of the bromo-acid used, and of the samesign as the parent hydroxy-acid from which the bromo-acid wasobtained.BIRKBECK COLLEGE,LONDON, E.C

ISSN:0368-1645    

DOI:10.1039/CT9109700121

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

126 FORSTER AND MULLER: THE TRIAZO-GROUP. PART XI.XV. -The Triaxo -group. Part XI. Sub st i t u t edTriaxomalonic m d Phenyltrialxoacetic Acids.By MARTIN ONSLOW FORSTER and ROBERT M~LLER.PURSUING our study of the effect produced by environment on thebehaviour OF the triazo-group, we deal in the present communicationwith substituted triazomalonic acids, for the purpose of comparisonwith the series of monobasic fatty acids already considered in previouspapers (Trans., 1908, 93, 7 2 ; 1909, 95, 191). It has been shownthat the characteristic manner in which triazoacetone is decomposed byalkalis may be deeply modified by exchanging the unsubstitutedmethyl group for ethoxyl, the azidic radicle in triazoacetic ester andits homologues being quite indifferent towards alkali, the attack ofwhich is resisted even by the triazo-acids themselves unless consider-able excess of the agent is employed and the temperature raised to50° or more.From the fact that i n the series quoted, a-triazoiao-butyric acid escaped altogether, it was concluded that the limitingcondition for elimination of t wo-thirds the azidic nitrogen from triazo-acids depends on the association of hydrogen with the carbon atomwhich carries the triazo-group.Accepting ethyl triazoacetate as a standard, the series of substitutedtriazomalonic esters described in this paper may be regarded asderived by replacing one or both atoms of hydrogen with carboxyethylFORSTER AND MULLER: THE TRIAZO-GROUP. PART XI. 127alkyl, phenyl, or triazidic groups, as represented by the followingconstitutional formulz :E t 0 C 0- C N3<g EtO* CO*CN3<C0,E HE thy1 triazoace tate.E tO*CO*CN3<,023, CHEthyl triazomalonate(not isolated).EtO*CO*CN,<C,$t CHEthyl methyltriazomalonate. Ethyl ethyltriazomalonatc.Ethyl phenyltriazomalonate.E t h ylbis triazomalonate.The first point to notice in connexion with the above series is thatthe introduction of a second carboxyethyl group into the niolecule oft riazoacetic ester disturbs so profoundly the equilibrium of thomolecule that ethyl triazomalonate is not capable of separate exist-ence. All attempts to prepare this compound by variations of theoriginal process for obtaining triazo-esters have been fruitless, notfrom want of reactivity between sodium azide and the halogen of thesubstituted malonate, but because under those circumstances in whichdouble decomposition can be brought about, the product immediatelyundergoes profound decomposition, and gives rise to nitrogen, ammonia,and hydrazoic acid, along with a solid nitrogenous compound of highmolecular weight.As soon as the remaining hydrogen atom isreplaced, however, whether by alkyl, phenyl, or the triazo-group,stability returns to the molecule, and the substituted triazornalonicester is sufficiently cohesive not only to withstand the action OF alkali,but actually to undergo hydrolysis, furnishing the substituted triazo-malonic acid.Tn the alkyltriazomalonic acids we have to deal with substancesdirectly comparable with a-triazoisobutyric acid, inasmuch as thetriazotised carbon atom is tertiary.Accordingly they displayunusual resistance towards alkali, which depends for the success of itsattack on the well known power OF substituted malonic acids to loseone molecule of carbon dioxide. Making this alteration in ethyltriazo-malonic acid, for example, leads to a-triazobutyric acid :Consequent on this, there occurs elimination of two-thirds the azidicnitrogen, so that the net result of decomposing ethyltriazomalonic acidwith alkali is propionylformic acid :CH3*CH2*CN3(C0,H)2 + H20 = CH,*CH,*CO*CO,H + 00, + N, + NH,.Proceeding now to consider the effect of the phenyl group, anincrease in the reactivity of the molecule is to be noted, and althoughit has proved possible to hydrolyse the ester to phenyltriazomalonicCH3*CH2*CN3(C0,H), - CO, = CH,*CH2*CHK3*C02H128 FORSTER AND MULLER: THE TRIAZO-GROUP.PART XI,acid, and by the action of ammonia to prepare phenyltriazomalonamide,nevertheless the further breakdown to benzoylformic acid is accom-pIished more readily than the corresponding degradation of the purelyaliphatic molecule :C,H,*CN,(CO,H), + H20 = C,H,*CODC02H + CO, + N, + NH,.This access of reactivity is shown still more clearly by the behaviourof phenyltriazoacetic ester, which we have prepared for comparisonwith triazoacetic ester. Whilst the latter substance may behydrolysed to the acid without risk of eliminating the two-thirdsnitrogen, phenyltriazoacetic ester is so sensitive towards alkalithat the acid cannot be prepared by hydrolysis, but must be derivedfrom sodium phenylchloroacetate by double decomposition with sodiumazide :C,H,*CHCl*CO,Na + NaN, = C,H,*CHN,*CO,Na + NaCl,Ey proceeding carefully it is possible to arrest decomposition ofphenyltriazoacetic acid with alkali at the stage intermediate betweenthe original substance and benzoylformic acid, namely, potassiumphenyliminoacetate :C,H,=CHN,*CO,K --+ C,H,*C( :NH)*CO,K + N,,but this compound readily suffers hydrolysis to potassium benzoyl-formate and ammonia.The instability of phenyltriazoacetic ester isillustrated still better by its behaviour towards ammonia, which con-verts it into phenyliminoacetamide with loss of two-thirds nitrogen andwitbout formation of phenyltriazoacetamide.C,H,*CHN,*CO,*C,H, + NH, =C,H,-C(:NH)*CYO*NH, + C,H,*OH + N,.The latter substance, i n fact, could not be isolated, although the trans-formation of triazoacetic ester [into triazoacetamide by the directaction of ammonia is practically quantitative.Proceeding now to the bistriazo-derivatives, we are confronted withanother illustration of the comparative immunity of the triazo-groupwhen the carbon atom which carries it is tertiary.I n studying theproperties of bistriazoacetic ester (Trans., 1908, 93, 1073), it wasfound that potassium hydroxide readily eliminates hydrazoic acid, andthat even ammonia brings about this change too rapidly to permit theproduction of bistriazoacetamide ; moreover, during the preparation ofthe ester i t mas noticed that the double decomposition between di-chloroacetic ester and sodium azide was accompanied by continuousliberation of hydrazoic and prussic acids, indicating subsidiary changeswhich reduced the yield very much below that required by theory.Bistriazomalonic ester, on the other hand, is a comparatively stablesubstance, and, although exploding with some violence a t lSOo, is muchless dangerous to handle than bistriazoacetic ester.Ammonia convertFORSTER AND MULLER: THE TRIAZO-GROUP. PART XI. 129it into bistriazomalonamide, and although this bhange is accompaniedby elimination of hydrazoic acid, the isolation of a solid amiderepresents a distinct superiority to the behaviour of the bistriazoaceticester. As might be expected, however, the amide is much moresensitive towards concentrated sulphuric acid than.methyltriazomalon-amide and ethyltriazomalonamide, and is completely broken down bypotassium hydroxide, yielding nitrogen and ammonia with prussic andhydrazoic acids.An attempt to produce bistriazomalonic acid by cautious hydrolysisleads us to believe that this substance, like triazomalonic acid, iscapable of existing in solution, but not in the individual state. Anethereal solution was concentrated without heating, but therebyacquired a powerful odour of hydrazoic acid, which remained noticeableduring many days' exposure to reduced pressure; a few crystals ofoxalic acid separated, and the oil, when quite free from hydrazoic acid,gave a nitrogen percentage agreeing fairly well with that of triazo-glycollic acid, this indication being further confirmed by analysis ofthe barium salt. It appears probable, therefore, that bistriazomalonicacid undergoes the following changes in solution :N N;>c<co;H CO H + H,O = H o > ~ ~ * ~ ~ , ~ + CO, + HN,.N3The production of prussic acid during the disruption of the triazo-group appears to be a feature of bistriazo-derivatives exclusively, andwe have searched again for this compound among the products ofdecomposing with alkali those triazo-acids and triazo-esters which havebeen described in previous pBpers, with a negative result ; it is, horn-ever, noteworthy that phenyltriazomalonamide, when warmed withalkali, gives a distinct odour of phenylcarbylamine.It is difficult toexplain the formation of prussic acid from bis triazomalonamide unlessthe production of the substance is preceeded by the loss of carbondioxide, which mould lead t o bistriazoacetamide ; this might beexpected to lose two-thirds the nitrogen of one azidic group, yieldinga highly unstable molecule which mould become resolved into a,mmoniawith hydrazoic, carbonic, and prussic acids :HCN + HN, + CO, + NH,.Such a change appears more probable when it is recalled thatConrad and Bruckner have shown that dichloroacetamide is amongthe products of treating dichloromalonic ester with ammonia (Bey.,1891, 24, 2994).VOL. XCVII. 130 FORSTER AND MULLER: THE TRIAZO-GROUP. PART XI.Much remains to be learned, however, in connexion with thosebistriazo-compounds in which both azidic groups are attached tothe same carbon atom, other points in addition to those mentionedserving to emphasise the characteristic behaviour of such substances.Bistriazomalonic ester, for example, is remarkably stable, and doesnot appear t o undergo alteration with lapse of time, whilst bistriazo-acetic ester develops the odour of prussic acid and deposits, inthe course of a few months, massive, transparent crystals (m.p. 91')containing more carbon, but less nitrogen, than the original material.This rearrangement will be investigated further, as there doubtlessoccurs some change comparable with the triazole formation whichtakes place in the molecule of allylazoimide (Trans., 1908, 93, 1174),and with the production of 1-hydroxy-5-phenyltetrazole from benz-hydroximic chloride and sodium azide (Trans., 1909, 95, 183); therecent observation of Schroeter (Bey., 1909, 42, 2336), who obtaineddiphenyltetrazole from diphenylbistriazomethane, belongs, probably,to the same class of transformation,EXPERIMENTAL.Interaction of Chloromalonic Ester and Sodium Axide.Fifty grams of chloromalonic ester (b.p. 91°/2 mm.) were heatedunder reflux on the water-bath with 25 grams of alcohol, 20 gramsof sodium azide, and sufficient water to maintain the salt insolution; the mixture rapidly became yellow, then dark red, whilebrisk effervescence was set up, the escaping gases being nitrogen,ammonia, and hydrazoic acid. After four hours the liquid wasallowed to cool, and filtered from 3 grams of crystalline material,of which a further quantity about equal to the first was obtained byremoving esters in a current of steam, concentrating the residue t oabout 200 c.c., and then adding dilute sulphuric acid.The substancewas purified by precipitation with sulphuric acid from the solutionin sodium carbonate, followed by successive recry stallisation fromboiling alcohol and ethyl acetate independently, approximately onelitre of the latter solvent being required by 0.5 gram; it crystallisedin minute, colourless needles, became deep red at about 220', anddecomposed completely in the neighbourhood of 240'. Many analyseshave been made, of which the following are typical, without, however,1 evealing the identity of this compound, but they point consistentlyt o a molecule arising by condensation of two or more molecules oftriazomalonic ester :0.2061 gave 0.3577 GO, and 0*0908 H,O.C = 4799 ; H = 4.90,0.1181 ,, 13.2 C.C. N, at 20° and 746.5 mm. N = 12.56.(C9H1105N2)s requires C = 47.58 ; H = 4.84 j N = 12.33 per centFORSTER AND M ~ ~ L L E R : THE TRIAZO-GROUP. PART XI. 131The substance is very sparingly soluble in boiling water, alcohol,chloroform, and ethyl acetate; it does not reduce ammoniacal silveroxide, and does not give any characteristic coloration when ferroussulphate is added to a very dilute solution in sodium hydroxide, buta solution in cold absolute alcohol, which of necessity contains only aminute portion of the substance, develops an intense violet colorationwith ferric chloride.As regards the preparation of triazomalonic ester, the foregoingexperiment was a failure, because not only is the solid p'roduct quitedistinct from a triazo-compound, but *he volatile oil removed bysteam was found not to contain nitrogen.Another fruitless attemptto obtain the substance consisted in shaking during twenty hours a tlaboratory temperature a suspension of chloromalonic ester (50 grams)in aqueous alcohol containing sodium azide (20 grams) ; the mixturebecame dark red, and pressure was developed, but the odour ofammonia or hydrazoic acid was not perceptible, and the heavy oilwhich remained undissolved consisted of original material.Having found that sodium phenyltriazoacetate may be preparedfrom the chloro-compound by the action of aqueous sodium azide,25 grams of bromomalonic acid were neutralised with sodiumcarbonate, and gently warmed with 10 grams of sodium azidedissolved in water.It soon became evident that double decom-position had occurred, because a test with 40 per cent. potassiumhydroxide gave torrents of nitrogen and ammonia, but on extractingthe acidified solution with ether, and evaporating the solvent underreduced pressure, hydrazoic acid was liberated continuously, leavingan oil which no longer evolved nitrogen when treated with alkali.Methykriaxomcdonic Acid, CH,*CN,(CO,H),.Five grams of methyltriazomalonic ester were shaken with 5 gramsof potassium hydroxide dissolved in 5 C.C.of water until, after abouttwenty minutes, the oil had disappeared, when the liquid wasgradually acidified with 50 per cent. sulphuric acid and extractedwith ether. The residue from the latter solidified in the desiccator,and, after crystallisation from warm benzene, was redissolved in itsown weight of ethyl acetate; on adding benzene in approximatelyequal volume, there separated stellate aggregates of long, transparentprisms melting at 8 7 * 5 O :0.1551 gave 37.0 C.C. N, at 22' and 743 mm.C,H50,N, requires N = 26.4 1 per cent.The acid is very hygroscopic, and dissolves freely in ethyl acetate ;benzene dissolves it only sparingly, however, and it is insolublein petroleum, Concentrated sulphuric acid attacks the substanceN = 26.40.K 132 FORSTER AND MOLLER: THE TRIAZO-GROUP. PART XI.very slowly, whilst stannous chloride in hydrochloric acid liberatesnitrogen immediately.The silver salt was precipitated by silver nitrate from aqueousammonium methyltriazomalonate, and, although colourless when fresh,rapidly darkened on attempting to recrystallise it from warm water ;a small quantity of the dried substance detonated with considerableviolence when thrown on a hot plate.Ethyl MethyZtriaxomaZonate, CH,* CN,( C0,- C,H,),.Fifty grams of methylbromomalonic ester in 30 C.C.of absolutealcohol were heated under reflux during ten hours with 22 grams ofsodium azide in 30 C.C. of water; action being then complete, aconsiderable quantity of water was added, and the precipitated oildistilled under diminished pressure, the principal fraction (32 grams)boiling at 69O/0*6 mm.:0.1328 gave 23.0 C.C. N, at 17" and 749 mm.Ethyl methyltriazomalonate is a colourless liquid having sp. gr.1.11695 at 16'/16O ; it has a faint, agreeable perfume, suggestingacetoacetic ester, and the vapour when inhaled with steam producesan effect on the blood-pressure similar t o that of the esters inthe monobasic series. As already indicated, cold concentratedpotassium hydroxide merely hydrolyses the ester, provided that thealkali is not in great excess and the mixture is not heated; evenon evaporating to dryness, the liberation of gas is very slight,and only a small proportion of nitrogen is removed in the formof hydrazoic acid.Action of SuZphuric Acid.-As in the case of triazoacetic ester, theinteraction with concentrated sulphuric acid is very slow, and only onheating the mixture during a considerable period did the volume ofliberated nitrogen reach the calculated amount :0.2243 gave 26.8 C.C.N, at 1 7 O and 747 mm.C,H,,O,N, requires 2/3N = 13.02 per cent.Behaviour towards Stannous Chloride.-A solution of stannouschloride in hydrochloric acid is without action on the ester untilthe temperature reaches about SO0, when a slow but regulareffervescence sets in, and is completed in about two hours,N = 19.80.C,H,,O,N, requires N = 19.53 per cent.N = 13.62.0,3038 gave 36.6 C.C. N, at 1 9 O and 742 mm. N= 13.51.C8H1,O,N3 requires 2/3N = 13.02 per centFORSTER AND MULLER: THE TRIAZO-GROUP.PART XI. 133Methyltriaxomnlonamide, CH,*CN,(CO*NH,),.Five grams of the ester were shaken during two hours with 15 C.C.of concentrated aqueous ammonia, excess of which was removedin the vacuum desiccator after twelve honrs had elapsed. Thecrystalline nmide W R S dissolved in boiling benzene, of which about400 C.C. mere required per gram, separating in long, lustrous needlesmelting at 13'7.5':0.1330 gave 52.5 C.C. N, a t 1 7 O and 742 mm.Met7L?lltriaxonzaZo~zum~de is readily soluble in warm water, alcohol,and petroleum, but is insoluble in cold benzene. A hydrochloricacid solution of stannous chloride attacks the substance rapidlywithout being heated, and liberates nitrogen. Concentratedsulphuric acid behaves in tt most unusual manner, nitrogen beingevolved only slowly even on raising the temperature to 125",below which there is not any effervescence.A parallel with thisremarkable behaviour has been noted quite recently in the case oftriphenylmethylazoimide (Wieland, Ber., 1909, 42, 3027), thesolution of which in concentrated sulphuric acid must be heatedt c 200' before gas evolution becomes vigorous.N = 64.71.C,€1702N, requires N = 44.58 per cent.Ethyltviaxomalonic Acid, C,H,*CN,(C0,H)2.Exactly the same procedure was adopted as in the case of methyl-triazomalonic acid, and, after crystallisation from hot benzene, theacid was obtained in colourless, rhombic, hygroscopic prisms, meltingand decomposing at 105-107° :0.1632 gave 34.4 C.C. N, at 22' and 766 mm.The acid is attacked readily by concentrated sulphuric acid, andN = 24.12.C,H70,N, requires N = 24.28 per cent.by stannous chloride in hydrochloric acid.Ethyl Ethyltriaxomalonute, C,H,*CN,(C0,*C2H,),.The ester was prepared from 42 grams of ethylbromomalonicester, 15 grams of sodium azide, and 45 C.C.of 50 per cent. alcohol,heating under reflux being continued during eight hours ; theproduct was fractionated under reduced pressure, boiling at83.5O/Oo7 mm. :0.1670 gave 2'7.3 C.C. N, at 22' and 769 mm.The colourless liquid has sp. gr. 1 el16 1 at 16"/16O, and the vapour,N = 18-74,C,HISO,N, requires N = 18.38 per cent134 FORSTER AND MeLLER: THE TRIAZO-GROUP. PART XI.although characterised by a pleasant odour, has the disagreeableeffect on the blood-pressure which has become associated with thealiphatic triazo-esters. Whilst the effervescence brought about bystannous chloride in hydrochloric acid is very vigorous, that inducedby concentrated sulphuric acid is very slow.A distinction from thelower homologue is offered by the behaviour towards concentratedpotassium hydroxide, because on heating the ester with excess of thisagent, violent liberation of nitrogen sets in, followed by ammonia, and,on cooling the liquid, there separate crystals of potassium propionyl-formate, containing 28.2 per cent. of potassium (C,H,O,K requiresK = 27.9 per cent.) ; the phenylhydrazone was prepared, and meltedat 148.5" after crystallisation from dilute alcohol.Ethyltriazomalonarnide, C,H5*CNg(CO*NH2),.The substance was obtained by shaking the ester with concentratedaqiieous ammonia, and crystallised from hot benzene in colourless,rhombic plates me1 ting at 167" :0.1027 gave 36.8 C.C.N, at 20° and 763 mm. N= 41.05.C5H,02N5 requires N = 40.93 per cent.Decomposition with stannous chloride in hydrochloric acid readily gavethe calculated amount of nitrogen, but the remarkable behaviour ofthe lower homologue towards concentrated sulphuric acid wasreproduced by etbyltriazomalonamide, which was not decomposedbelow 125".PhenyZtriazomaZotdc Acid, C,H,*CN,(CO,H),.As appears below, it was not found possible to distil phenyltriazo-malonic ester, even under pressure reduced to 0.56 mm., withoutdecomposition, which took place at 150°, and accordingly theundistilled material was employed as the source of the acid.Severalgrams of the ester were shaken with the calculated amount ofpotassium hydroxide in the form of a 20 per cent. aqueous solutionuntil, in the course of about three hours, a clear liquid resulted; thiswas extracted twice with ether, acidified with t,he calculated amountof dilute sulphuric acid, saturated yith solid ammonium sulphate, andfurther extracted five times with ether. After drying with ignitedfiodium sulphate, the residue from evaporation was submitted t odiminished pressure (20 mm.) during thirty-four hours, when itsolidified and became colourless on porous earthenware. Recrystal-lisation from hot benzene gave spherical clusters of snow-whiteneedles melting a t 99" without decomposition :0.1562 gave 25.8 C.C.N, at 18" and 768 mm. N= 19.28.C,H70,N, requires N = 19.00 per centFORSTER AND MULLER: THE TRIAZO-GROUP. PART XT. 135Phenyltriaxomalortic acid effervesces vigorously with concentratedsulphuric acid, while torrents of nitrogen are liberated by a solutioiiof stannous chloride in hydrochloric acid; 40 per cent. aqueouspotassium hydroxide effects immediate disruption of the triazo-groupin the cold, but alkali of half this concentration requires to be heatedbefore bringing about decomposition, when ammonia and nitrogen areliberated without formation of hydrazoic and hydrocyanic acids. Thealkaline liquid from the foregoing experiment gave an immediateprecipitate with phenylhydrazine after being neutralised with dilutesulphuric acid; this was found to be identical with the phenyl-hydrazone of benzoylformic acid obtained by similar procedure frompbenyltriazoacetic acid, whence it follows that the disruption of thetriazo-group is preceded by removal of carbon dioxide from thedibasic acid.Ethy I Phen?/ltriazomatonate, C,H,*CN,(C0,*C2H5)2.Phenylmalonic ethyl ester was prepared according to the method ofWislicenus (Ber., 1894, 27, 1093 ; Annalen, 1888, 246, 315), whichdepends on elimination of carbon monoxide from phenyloxalic esterobtained by the action of ethyl oxalate on the sodium derivativeof ethyl phenylacetate. W islicenus states that ethyl phenylmalonatetends to decompose when boiled under atmospheric pressure at 285',and therefore distilled it at 170-172'/14 mm.; our specimen boiledat 127-1 29O/0*35-0.4 mm. The bromination of phenylmalonic esterhas been described by Wheeler and Johnson (J. Amer. Chem. Soc.,1902, 24, 6$0), who carried out this operation in sealed tubes, but wefind that phenylbromomalonic ester may he prepared in almostquantitative yield by heating the ester with the halogen under ordinarypressure at 140-150' in bright daylight, the product distillingat 141-142"/0*48 mm.Phenylbromomalonic ester (1 8.5 grams), sodium azide (6 grams),and alcohol (10 c.c.), with sufficient water to maintain the saltdissolved, were left in darkness during three weeks with frequentshaking and occasional warming to about 40' ; water was then added,and the precipitated ester extracted and dried, but an attempt todistil the product was fruitless, owing to the decomposition which wasthreatened on raising the temperature of the bath to 150°, when thepressure rose from 0.56 mm.to 1.5 mm. quite suddenly, and theoperation was therefore discontinued. There was not any indicationof distillation taking place, and i t has not been possible, therefore, toobtain the substance in purified condition.The crude ester is a Flightly yellow, heavy oil with a faint, pleasantperfume ; the decomposition with concentrated sulphuric acid take136 FORS'J'ER AND MULLER: THE TRIAZO-GROUP. PART XI,place readily, and nitrogen is liberated also by a solution of stannouschloride in hydrochloric acid. The aotion of potassium hydroxide hasbeen already described.Phen yltriaxonanlonamide, C,H,- CN,( CO * NH,),.On continued shaking with strong aqueous ammonia, phenyltriazo-malonic ester was transformed into a crystalline solid, which dissolvedin hot water, and separated therefrom in snow-white, fern-like leaflets ;the substance melted a t 1890h:0.1038 gave 29.7 C.C.N, at 23O and 760 mm.C,H,O,N, requires N = 31.96 per cent,Phenyltriaxomalonfcmide is moderately soluble in acetone, ethylacetate, and ethyl alcohol ; it dissolves sparingly in boiling benzene,and is insoluble in boiling petroleum.The action of concentrated sulphuric acid on the amide is mildat first, and becomes brisk only on continued stirring, whilst a, solutionof stannous chloride in hydrochloric acid does not liberate nitrogenuntil a few drops of alcohol have been added to complete contact.When heated with 20 per cent, aqueous potassium hydroxide, thecompound evolves nitrogen freely, accompanied by ammonia, theodour of phenylcarbylamine being also noticeable ; hydrazoic andprussic acids, however, were not produced,N = 32.24.Ethyl Bistriaxomalonate, (N,),C(C0,*C2H5)2'Ethyl dichloromalonic ester was obtained as a by-product in thepreparation of ethyl chloromalonic ester on treating malonic ester withchlorine a t SOo, and boiled at 231-234O.It is noteworthy that,although ethyl dichloromalonate may be preserved during manymonths without showing any signs of having undergone change, themonochloro-compound (b, p. 222-223') became transformed into abrownish-grey, fuming liquid, having a marked odour of hydrogenchloride.Twenty grams of rectified dichloromalonic ester, 20 C.C.of absolutealcohol, and 14 grams of sodium azide dissolved in 40 C.C. of waterwere warmed carefully until the liquid became clear, and left in dark-ness during one month, with occasional shaking and gentle warming.On diluting with water and extracting with ether, a colourless oil wasobtained, half a gram of which was heated in an open tube underatmospheric pressure before submitting the whole specimen to distil-lation; no change was observed to take place while the temperatureremained below 175O, but a t the moment of reaching 180° an explosionof very considerable violence occurred. The main quantity of esteFORSTER AND MULLER: THE TRIAZO-GROUP.PART XI. 137was then distilled under 0.81 mm. pressure, boiling steadily at115-115.5':0.1576 gave 47-6 C.C. N, a t 21° and 764 mm.C7HIoO4N6 requires N = 34-71 per cent.Bistriaxontalonnic ester is a colourless oil with a pleasant perfume ; ithas sp. gr. 19136 at 20° compared with water at the same temperature.The decomposition by concentrated sulphuric acid is extremely violent,and the liberation OF nitrogen with stannous chloride in hydrochloricacid torrential :0.3251 gave with SnC1, 62.6 C.C. N, at 21' and 768 mm. N = 22.3.0.1816 ,, ,, H,S04 36.2 C.C. N, ,, 2 1 O ,, 764 mm. N=22*8.C7H,,04N, requires 2/3N = 23.14 per cent.An attempt to prepare bistriazomalonic acid by hydrolysing theester with 10 per cent.alkali was unsuccessful, owing to the readinesswith which the product undergoes spontaneous loss of hjdrazoic acid.Seven grams were shaken with the calculated amount of the agentuntil dissolved, extracted with ether, and treated with the exactquantity of dilute sulphuric acid, after which ammonium sulphate wasadded and the bistriazomalonic acid removed by four extractions withether. The solvent having been evaporated without heating, it wasnoticed that the residual oil, which remained viscous, acquired adistinct odour of hydrazoic acid, and was filled with bubbles whichceased to appear after many days in the desiccator :N = 34.57.0°1410 gave 43.4 C.C. N, at 23' and 757 mm. N = 34.6.C,H,O,N, requires N = 46.1 6 per cent.The latter formula represents triazoglycollic acid, which is verylikely produced by the removal of carbon dioxide and hydrazoic acidfrom bistriazomalonic acid under the influence of water.After manydays, crystals of oxalic acid were noticed in the oil, which was treatedwith a paste of barium carbonate in order to isolate, if possible,barium triazoglycollate. The aqueous filtrate from barium oxalateand unchanged barium carbonate was evaporated to dryness withoutheat, and triturated with absolute alcohol, the insoluble portion beingthen analysed :C,H,O,N, ,, N=35.8 ,,0*0786 gave 0.0498 BaSO,. Ba = 37.25..The substance effervesced vigorously with concentrated sulphuricC,H,0,N6 Ba requires Ba= 37.13 per cent.acid, and was most probably barium triazoglycollnte138 FORSTER AND MULLER: THE TRIAZO-GROUP.PART. XI.Bistriazomalonamide, (N,),C(CO*NH,),.Agitation with strong aqueous ammonia during one hour trans-formed bistriazomalonic ester into a snow-white, crystalline solid,which was recrystallised from boiling water, being only very sparinglysoluble therein ; the amide separated in transparent, colourless prisms,melting a t 162' with vigorous decomposition :0.0866 gave 47.6 C.C. N, at 2 4 O and 765 mm.C,H,O,N, requires N = 60.89 per cent.The substance is readily soluble in hot acetone and ethyl acetate,crystallisiag therefrom in six-sided plates ; it is moderately soluble incold alcohol, but dissolves very sparingly in boiling benzene andin boiling chloroform. Immediate effervescence occurs on mixing theamide with concentrated sulphuric acid, and becomes very vigorous onwarming ; stannous chloride also liberates nitrogen very freely.Thedecomposition with 40 per cent. potassium hydroxide is mostprofound, giving rise t o nitrogen, ammonia, prussic acid, and hydrazoicacid.Phen yltriaxoacet ic Acid, C,H,* CHN, C0,H.Owing to the readiness with which the triazo-group in phenyltriazo-acetic ester undergoes disruption in the presence of alkali, the acidcannot be obtained by hydrolysis. Five grams of phenylchloroaceticacid were therefore exactly neutralised with sodium carbonate in about30 C.C. of water, apd, after admixture with 2.5 grams of sodium azidedissolved in 20 C.C. of water, allowed to remain during two daysprotected from light ; dilute sulphuric acid having been added, and theliquid extracted six times with ether, the latter was dried with sodiumsulphate and evaporated in a vacuum desiccator without being heated.The residue became solid, and was recrystallised three times frombenzene, which deposited the substance in thin, colourless, rhombicplates melting a t 98.5O :N = 60.88.0.1543 gave 31.4 C.C. N, at 20° and 764 mm.C,H70,N, requires N = 23.73 per cent.The decomposition with concentrated sulphuric acid was very violent,and nitrogen was also liberated immediately on mixing the acid withaqueous potassium hydroxide or a solution of stannous chloride inhydrochloric acid.The silver salt could not be analysed, becausereduction took place on attempting to recrystallise it from warmwater.Ethyl Phenyltrhzoacetate, C6H,*CHN,* C02*C,H,.Early attempts to prepare this ester were conducted on the linesfollowed in the case of triazoacetic ester and its higher homologues,N = 23.41FORSTER AND M ~ L L E R : THE TRIAZO-GROUP.PART XI. 139but the results were unsatisfactory ; when alcoholic phenylchloro-acetic ester is heated under refliix with aqueous sodium azide, theliquid rapidly becomes yellow and evolves gas, and, although the oilyproduct of steam distillation answers to the azide test with con-centrated sulphuric acid, it is too complex R mixture to repay furthertreatment, the presence of by-products being best avoided by thefollowing procedure.Eighty grams of phenylchloroacetic ester (b.p. 135"/17 mm.)were mixed with 100 grams of alcohol and 40 grams of sodium azide(1 mol. = 26.2 grams), water and alcohol being then added alternatelyuntil both ester and salt were dissolved ; after remaining a few weeksin the dark, the liquid was found to have deposited a crop of sodiumchloride, and at the end of two months, when the action was judgedto have been complete, water and solid ammonium sulphate wereadded to precipitate the ester, which was then removed, dried in theusual way, and fractionated with the aid of the Gaede pump :0.2204 gave 38.3 C.C. N, a t 16' and 770 mm.C,,H,,O,N, requires N = 20.49 per cent.Ethyl phenpltriazoacetate is a colourless liquid with a very faintpleasant perfume suggesting roses; only on distilling the ester withsteam does the vapour produce the throbbing sensation at the base ofthe forehead and palpitation of the heart characteristic of thealiphatic triazo-esters.It boils at 93'/0-09 mm., and has sp. gr. 1.1434at 2Oo/2O0; the action with concentrated sulphuric acid is veryviolent.Action of Potassium Hydroside.-Contact with dilute aqueous alkaliwas found to bring about an immediate disruption of the triazo-group,and it was therefore useless t o attempt hydrolysis by this means. Onadding 40 per cent. potassium hydroxide drop by drop to 10 grams ofthe ester dissolved in 40 C.C. of alcohol, the liberation of nitrogen witsperfectly regular, and, after excess of alkali had been added, thereseparated a reddish oil which in the vacuum-desiccator rapidlysolidified ; this product, being sparingly soluble in water, was recrps-tallised from the gently warmed liquid, and was obtained in colourless,nacreous plates :N = 20*08.0.3114 gave 0.1470 K,SO,.K=21*16.0.2577 ,, 16.7 C.G. N, at 19' and 768 mm. N=7.53.C:,H,O,NK requires K = 20.85 ; N = 7.49 per cent.I n the course of twenty-four hours' exposure to air, the substancehad begun to undergo hydrolysis, yielding potassium benzoylformate,and when the salt no longer contained nitrogen, benzoylformic acidwas obtained from it and identified by the melting point ( 6 5 O ) and byconversion into the phenylhydrazone, a specimen of which melted a140 FORSTER AND M~LLER: THE TRIAZO-GROUP. PART XI.160" and contained 11.8 per cent.of nitrogen (C,,H,202N, requiresN = 11 *7 per cent,).Action of Ammonia.-Attempts t o prepare phenyltriazoacetnmideby the action of ammonia on phenyltriazoacetic ester were un-successful, owing to disruption of the triazo-group ; this can, however,be so controlled as to permit the isolation of phenyliminoacetamide.Excess of dry ammonia was passed into a well-cooled solution ofphenyltriazoacetic ester in absolute alcohol ; liberation of nitrogenaccompanied the separation of crystals, which increased during twenty-four hours in t.he ice-chest. Recrystallisation from .benzene, repeateduntil the melting point was constant, gave colourless, monoclinicplates melting a t 144' :0.2070 gave 34.3 C.C. N, a t 20" and 770 mm.C,H,ON, requires N = 18.92 per cent.The substance is readily soluble in alcohol and in benzene, beingprecipitated from the respective solutions by water and by petroleum.When exposed to air it produces ammonia, giving the a-amide ofbenzoylformic acid, m.p. 90'. The acid itself mas obtained bycompleting the hydrolysis.N = 19.21.Trriaxoacetophenone (Pkenacylazoimide), N3*CH2*CO*C6H,.Twenty grams of bromoacetophenone dissolved in 50 C.C. ofabsolute alcohol and mixed with 7 grams of sodium azide in theminimum quantity of water were shaken at intervals during sixteenhours in the ice-chest; being very readily fusible, the crystallineproduct was collected on a filter, cooled with chilled brine, and thenprecipitated by petroleum from a dried ethereal solution :0.1695 gave 38.4 C.C.N, at Z O O and 767 mm.C1,H70N3 requires N = 26.09 per cent.The triazoketone crystallises in colourless, lustrous plated, and meltsat 17O; in the course of a few weeks the pale yellow substance becamedark brown, even when protected from light, and the odour ofhydrazoic acid mas perceptible. An attempt t o distil it under 0.1 mm.pressure was unsuccessful, because a threatening decomposition set inwhen the temperature of the bath had reached 130°, the pressurequickly rising to 4 mm.On adding 20 per cent. potassium hydroxide to an alcoholic solutionof triazoacetophenone, immediate liberation of nitrogen takes placefollowed by ammonia on heating the liquid; a deep red coloration isdeveloped, but the indication of hydrazoic acid is trifling.Anattempt to establish the intermediate production of benzoylform-aldehyde on the lines indicated by W. L. Evans (J. Arner. Chem. Soc.,1906, 34, 115) was unsuccessful, the only material isolated beingN=26*16FORSTER AND MULLER: THE TRIAZO-GROUP. PART XI. 141benzoic acid. Two grams in ether were shaken with one gram oflime and 40 C.C. of water, the mixture liberating gas immediately andbecoming dark brownish-red ; after thirty hours the aqueous liquid wasremoved, extracted three times with ether, and acidified, when furtherextraction removed benzoic, not mandelic, acid.Phenacylazoimide reduces ammoniacal silver oxide in the coldsolution.Action of Sulphuric Acid.-The concentrated agent attacks thetriazoketone with great violence, and flame sometimes accompaniesthe small explosion which occurs when they are mixed drop by drop.By using more dilute acid the action can be moderated, until at25 per cent.the yield of nitrogen may be measured :0.2336 gave 34.4 C.C. N, at 18' and 772 mm.C,H70N, requires 2/3N = 17.39 per cent.To complete the decomposition it was found' necessary to use a bathof hot brine, and on cooling the contents of the flask, crystals ofbenzoic acid separated.Behaviour towards Stannous Chloride.-With a cdld 20 per cent.solution of the matal in hydrochloric acid the decomposition was veryslow, and, even after heating during two hours, the quantity of gas wasdeficient :N=17*27.0.1586 gave 22.9 C.C. N, at 18' and 772 mm. N= 16.95.C,H70N, requires 2/3N = 17.39 per cent.The aromatic product was not identified.The Semicarbaxone.-An alcoholic solution of the triazoketone wasmixed with aqueous semicarbazide acetate, the solid which separatedduring twelve hours being recrystallised from warm dilute alcohol :0.0895 gave 29.6 C.C. N, a t 19' and 773 mm.C,H,,ON, requires N = 38.52 per cent.The substance crystallised in colourless, silky needles, melting at127n5-128.50. The reaction with concentrated sulphuric acid wasvery vigorous.The Bromophenyl?i,yhaxone.-The derivative crgstallised from dilutealcohol in lustrous, yellow needles, melting at 114.5' :0.1079 gave 20.1 C.C. N, at. 19' and 768 mm.N = 38.68.N = 21.64.C,,H,,N,Br requires N = 21 -2 1 per cent.Frinxoacet op henoneoxi me, N, C H, C ( : NOH). C6H5,Triazoacetophenone was suspended in an aqueous solution ofhydroxylamine prepared by exactly neutralising with sodium carbonatea slight excess of the hydrochloride; alcohol was then added until,with gentle warming, a clear solution was produced. After thre142 CHALLENGER AND KIPPlNG :days in the dark, a pale yellow oil had separated, and this, afteradding water, was extracted with ether, dried with sodium sulphate,and freed from solvent in the vacuum desiccator. As in the case oftriazoacetone (Trans., 1908, 93, 84), i t was not found possible tocrystallise the oxime, which mas therefore analysed in liquid form :0.1050 gave 28.4 C.C. N, at 1 8 O and 771 mm. N = 31-70.C,H,ON, requires N = 31.82 per cent.An attempt to produce the p-toluenesulphonyl derivative, whichserved to characterise triazoacetoxime (Zoc. cit.), led to an uninvitingblack tar.ROYAL COLLEGE OF SCIEKCE, LONDON.SOUTH KENSINGTON, S.W

ISSN:0368-1645    

DOI:10.1039/CT9109700126

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

142 CHALLENGER AND KIPPlNG :XVI. - Organic Derivatives of Silicon. X I I . *Dibenzylethylpropylsilicane and Sulphonic AcidsDerived fi.orn It.By FREDERICK CHALLENGER, B.Sc., and FREDERIC STANLEY KIPPING.WHEN the study of organic derivatives of silicon was commenced byone of us, the principal object in view was the preparation of anoptically active compound containing one asymmetric silicon group.After a short experience of the behaviour of silicon derivatives, theplan which seemed to cffer the best prospect of success was t osyn thesise some asymmetric silico- hydrocarbon, SiR,R,R,R,, whichcould afterwards be sulphonated, and then to resolve the dl-sulphonicacid which would be thus obtained.I n pursuance of this plan, phenylmetbylethylpropylsilicane,SiPhMeEtPr, and phenylbenzylethylpropylsilicane, SiPhEtPr*CH,Ph,were first prepared; but on attempting to sulphonate these compounds,the phenyl group was eliminated as benzene and tertiary silicols wereformed (Kipping, Trans., 1907, 91, 221).I n the case of the phenylbenzyl derivative, this unexpectedbehaviour did not necessitate any change in the original scheme, as itwas found that a sulphonic acid could be obtained from the benzyl-ethylpropylsilicol, CH ,Ph*SiEtPr*OH, which was produced from thesilico-hy drocar bon.Further investigation showed, however, that this sulphonic acid wasderived from the oxide, (SiEtPr-CH,Ph),O, and therefore containedtwo asymmetric silicon groups ; t h i s fact, of course, upset the original* Parts X and XI, Tram, 1909, 95, 302 and 489 respectivelyORGANIC DERIVATIVES OF SILICOX.PART XII, 143plan, but at the same time opened out an alternative one, for if thedl-sulphonic derivative of benzylethylpropylsilicyl oxide which was thusobtained proved to be the dE and not the internally compensated com-pound, it might be resolved into its optically active components. Thesepossibilities were ultimately realised, and in later investigations theresolution of the homologous sulphonic acid derived from benzylethyl-i8obutylsilicyl oxide, (C,H,*SiEt CH,Pb),O, was also accomplished(Kipping, Trans., 1907, 91, 234; Luff and Kipping, Trans., 1908,93, 2090).These acids, which owe their optical activity to the presence of lwoasymmetric silicon groups, are the only active silicon compounds whichso far have been described; they hold this position, not because theoriginal object has been abandoned, but because all attempts to attainit resulted in failure.Thus, during the progress of the experiments referred to above, twoother asymmetric silico-hydrocarbons, namely, benzylmethylethyl-propylsilicane, SiMeEtPr- CH,Ph, and benzylethyl propylbobutyl-silicane, C,H,*SiEtPr*CH,Ph (Kipping, Trans., 1907, 9 1, 717 ;Kipping and Davies, Trans., 1909, 95, 69), were prepared andsulphonated, and many attempts were made to resolve the dl-acidsthus produced, Although, however, the externally compensatedcharacter of the acids could hardly be open to queetion, no definiteevidence of their asymmetry was obtained on fractionally crystallisingtheir salts with active bases.Our knowledge of asymmetric substances is still so incomplete thata reason for these repeated failures can hardly be suggested with anyconfidence.It seemed possible, however, that by preparing a com-pound in which the groups combined with the silicon atom were morewidely different than those in the two acids under discussion, thechances of being able to accomplish a resolution would be increased.Now as most of the readily available alkyl and aryl halogen com-pounds had already been utilised in the preparation of the fourasymmetric silico-hy drocarbons referred to above, the simplest way ofobtaining a new asymmetric sulphonic acid of the desired characterseemed to be to prepare a silico-hydrocarbon containing two benzylgroups and two different alkyl groups, and then to convert this corn-pound into an asymmetric acid by sulphonating one of the benaylgroups.The present paper contains a record of the experiments which haveled to the production of such an acid, namely, dibenzylethylpropyl-silicanemonosulphonic acid, CH,Ph*SiEtPr*CH,*C,H,*SO,H ; thedisulphonic acid, SiEtPr(CH2*C,H,-Su,H)2, derived from the samesilico-hydrocarbon has also been obtained.l)ibenxyZethyl~ropyZs~~cane, SiEtPr(CH,Ph),, was prepared by tli144 CHALLENGER AND KIPPING :interaction of benzylethylpropylsilicyl chloride (Kipping, Trans., 1907,9 1, 722) and magnesium benzyl chloride ; a simpler method, whichwas afterwards adopted, consisted in preparing dibenzylethylsilicylchloride directly from etbylsilicon trichloride and then treating thisproduct with magnesium propyl bromide.The compound thus obtained, like all those silico-hydrocarbonswhich contain a benzyl group, is readily attacked by chlorosulphonicacid at the ordinary temperature, and under suitable conditions ityields a monosulphonic acid, which, however, is invariably accompaniedby a disulphonic acid, It would seem that in both cases only one ofthe possible structural isomerides is formed in appreciable quantities,namely, the para-derivative.The isolation of these two sulphoriic acids was by no means a simpletask, but it was at last accomplished by two methods, namely, by frac-tionally crystallising the mixture of strychnine salts, or of Z-menthyl-amine salt8, prepared from the product of sulphonation.Thedisulphonic acid, which has the symmetrical constitution given above,and is consequently of little interest, has not been examined muchfurther than was necessary for establishing its composition. Itsstrychnine salt is more soluble in water than the salt of the mono-sulphonic acid, and decomposes from about 226'. Its 1-menthylaminesalt is practically insoluble in light petroleum, and melts at 205-20S0.The ammonium, sodium, and barium salts are crystalline.The strychnine and the 1-menthylamine salts of the dkmonosulphonicacid are not resolved during the prolonged course of fractional crystal-lisation which is necessary in separating them from the derivatives ofthe disulphonic acid.The strychnine salt crystallises well, andmelts at 199'.The 1-menthylamine salt,CH,Ph 'SiEt Pro CH,*C,H,*SO,H, C10H21N, 2 H,O,crystallises from moist light petroleum in lustrous plates, and is verysimilar in properties to the corresponding salts of the monosulphonicderivatives of benzylmethylethylpropylsilicane and benzylethylpropyl-isobutylsilicane. This fact was by no means promising, and seemed toindicate that attempts to resolve the new dZ-acid would be just asunsuccessful as those already recorded in the case of the acids justmentioned. Fortunately, however, the great uncertainty of conclusionsbased on analogy in dealing with asymmetric compounds was againillustrated, as, after a few failures, the acid was easily resolved into itsoptically active components.An account of the resolution experiments and of the propertiesof the active acids will be given in the near futureORGANIC DERIVATIVES OF SILICON.PART XII. 145EXPERIMENTAL.Prepurution of Dibenxylet?~ylsiZicyl Chloride, SiEtCl(CH,Ph),.Ethylsilicon trichloride (1 mol., 250 grams), diluted with about sixtimes its volume of dry ether, and magnesium powder (1 atom) areplaced together in a large flask, which is provided with a tap-funnel, astirrer, and a suitable outlet tube.A little benzyl chloride (2-3 c.c.) and a small quantity of anethereal solution of magnesium benzyl chloride (prepared in a test-tube) are now added, and the flask is gently warmed. I n a short timea reaction sets in, accompanied by the separation of magnesiumchloride, and, as soon as this reaction becomes fairly vigorous, the flaskis immersed in melting ice and the stirrer is started.Benzyl chloride(2 mols.) is then run in drop by drop, an operation which occupies abouttwo and a-half hours; when the whole of it has been added, thecontents of the flask are heated under a reflux condenser during threeto four hours. After cooling the product, the granular precipitate ofmagnesium chloride is separated by filtration in absence of moisture(compare Kipping, Trans., 1907, 91, 216) and is washed several timeswith dry ether; on evaporating the combined ethereal filtrate andwashings, there remains a yellow liquid, which fumes in moist air.This liquid is first roughly fractionated under 100 mm.pressurefrom an ordinary distillation flask. Very little passes over below1 6 5 O , but between this temperature and 210' a fairly large fraction iscollected. The thermometer then rises quickly to 2 3 8 O , and anotherlarge fraction distils from 238' to 390'. Distillation may be continuedup to 320°, or even higher, but this fraction has been only superficiallyexamined; the dark green liquid which then remains in the flask issometimes pasty, owing to the presence of magnesium chloride.By systematically fractionating the liquid boiling between 165' and210', using a long-necked flask with a rod-and-disk column, benzyl-ethylsilicon dichloride (Kipping, Trans., 1907, 9 1, 720) is obtained asan oil boiling a t 168-170°/100 mm.The rest of the originaldistillate when similarly fractionated yields a liquid passing overbetween 246' and 251°/70 mm., almost the whole of which, however,boils constantly at 249'. The yield of this product is 40-50 per cent.of the theoretical. The fractions boiling at about 300'/40 mm. containa small quantity of tribenzylsilicyl chloride which separates incrystals on cooling. The formation of this substance is probably dueto the presence of silicon tetrachloride in the ethylsilicon trichloridewhich was employed, and not to the displacement of an ethyl by abenzyl group; from a longer experience of silicon compounds itis concluded that such displacements, at one time thought to bepossible (Robison and Kipping, Trans., 19OS, 93, 440), do not occur.VOL. XCVII.148 CHALLENGER AND KIPPING :The liquid boiling at 249O/70 mm. consists of dibenzylethylsilicylchloride. It was analysed by decomposing it with dilute ammonia andtitrating the neutral solution with silver nitrate ; 1 C.C. = 0.003509gram C1 (Hipping, Trans., 1907, 91, 217) :0.9788 required 35.9 C.C. AgNO,.C1,HI9ClSi requires C1= 12.9 per cent.Dibenxylethglsilicyl chloride is an almost colourless oil, possessing,especially when freshly distilled, a fine bluish-violet fluorescence,which is probably due t o traces of impurity. It has an aromatic,pungent odour, fumes in moist air, and is rapidly decomposed bywater, giving dibenzylethylsilicol, which passes spontaneously intodibenzylethylsilicyl oxide (m. p. 56') when it is kept over sulphuricacid for a week or two.c1= 12.8.DibenxylethylpropyZg~Z~cane, SiEtPr(CH,Ph),.Dibenzylethylsilicyl chloride (1 mol., 170 grams) is mixed with anethereal solution of magnesium propyl bromide (l& mols.), and theether is distilled off.Very little, if any, action takes place until mostof the ether is removed, when a slight separation of magnesium chloro-bromide is observed. The mixture is then heated for about twohours at 140-180°, at the end of which time it is cooled and treatedwith water. The oil which separates is extracted with ether andfractionated under 90 mm. pressure.Distillation begins at about 250°, the thermometer quickly risingt o 262O. Most of the product then passes over between 262' and270°, and only a small quantity of high boiling residue remains in theflask.After further fractionation, pure dibenzylethylpropyhilicane,boiling at 262-265'/90 mm., is obtained. The yield is 70 to 80 percent. of the theoretical :0.1417 gave 0.4166 CO, and 0.1181 H,O.(A)" 0.2244 gave 0.0464 SiO,. Si= 9.7.(B) 0.1202 ,, 0.0253 SiO,. Si=9.89.C,,H,,Si requires C = 80.68 ; H = 9.2 ; Si = 10.05 per cent.The first samples of dibenzylethylpropylsilicane were prepared bythe interaction of benzylethylpropylsilicyl chloride and magnesiumbenzyl chloride. Benzylethylpropylsilicyl chloride ( 1 mol., 20 grams)is added to an ethereal solution of magnesium benzyl chloride(1% mols.), and, as no sign of a reaction occurs at this stage, theether is distilled off and the residue is heated a t about 140' duringone to two hours.The pasty mass of oil and magnesium chlorideis cooled and treated with water. and the oil extracted with ether.When the crude product is distilled under 100 mm. pressure, itC=80.17; H=9.24.* A and B were different preparationsORGANIC DERIVATIVES OF SILICON. PART XII. 147begins to boil at about 210°, and from this temperature to 240'a little dibenzyl passes over; the thermometer then rises rapidlyto 260°, and the silico-hydrocarbon begins to distil. From the liquidcollected between 260' and 280°, dibenzylethylpropylsilicane isobtained by further fractional distillation :0,1948 gave 0.5790 CO, and 0.1628 H,O.0.4567 ,, 0.0945 SiO,. Si = 9.73.C19H,,Si requires C = S0.68 ; H = 9.2 ; Si = 10.05 per cent.Although the yield by this method was very satisfactory, the taskof preparing benzylethylpropylsilicyl chloride, even in an approxi-mately pure condition, is far more troublesome than that ofpreparing pure dibenzylethylsilicyl chloride ; for this reason,practically the whole of the silicane used in this investigation wasobtained by the method described on p.146.DibenzyZeth?/l~opylsiEicane is a colourless liquid with a beautifulviolet fluorescence. It has a pleasant aromatic odour, and is lighterthan water.C= 81.06 ; H = 9.3.It is miscible with most organic solvents.Xulphonation of DibenzyEethylprop~Isilicane.Knowing from previous experience (Kipping, Trans., 1907, 91,223) that sulphuric acid is not a satisfactory sulphonating agentin the case of the silico-hydrocarbons, chlorosulphonic acid was usedin the sulphonation of dibenzylethylpropylsilicnne, and, as it seemedvery likely that both benzyl groups might be attacked, chloro-sulphonic acid (18 mols.), dissolved in a large volume of chloroform,was gradually added to the well-cooled silicon compound, also inchloroform solution.When nearly two-thirds of this solution had beenrun in, a test portion of the product was poured into water and thechloroform mas boiled off; repeating this test at intervals during theaddition of the chlorosulphonic acid, the aqueous solutions of theproduct gradually altered in character. At first they containedvisible drops of unchanged silico-hydrocarbon ; later on, however,they were clear and apparently free from oil while hot, but becamewhite and opaque when cooled, or they were white and opaque whenhot but became quite clear on cooling,Thinking that solubility in water was sufficient evidence thatsulphonation was complete, and as it was very important not touse too large a quantity of chlorosulphonic acid, the addition of thisreagent mas generally stopped as soou as a sample of the productgave a clear solution in hot or cold water.Further investigationshowed, however, that this test was not trustworthy, and that evenwhen the sulphonation product gave a perfectly clear solution inwater (after removiug the chloroform by steam distillation), theL 148 CHALLENGER AND KIPPING :solution might nevertheless contain considerable quantities oi un-changed silico-hydrocarbon; it was also found that when even thetheoretical quantity (1 mol.) of chlorosulphonic acid was employed, aconsiderable quantity of disulphonic acid was formed.In these circumstances various proportions of chlorosulphonic acidwere tried, and the following method of preparation was finallyadopted.A solution of the hydrocarbon (b.p. 262--266O/90 mm.) inchloroform (6 vols.) is cooled in ice, and a solution of chlorosulphonicacid (1% mols.) in chloroform (12 vols.) is added to it drop by dropwhile a rapid stream of dry carbon dioxide is passed through themixture. Hydrogen chloride is evolved almost immediately, and theliquid soon assumes a red colour, which darkens slightly as the.process continues.After keeping the mixture at Oo for a short time, it is poured on ice,and, from the very slowly settling emulsion thus obtained, thechloroform is separated by steam distillation.If the distillation is continued after all the chloroform has beenremoved, oil continues to pass over in small quantities during two orthree hours.This oil is more quickly separated by extracting withether ; it consists almost entirely of unchanged dibenzyletbylpropyl-silicane, but sometimes contains relatively very small quantities ofdibenzylethylsilicyl oxide (m. p. 56O), a fact which seems to show thatthe not very highly purified samples of the silico-hydrocarbon used inthe preparation of the, sulphonic acid contained small quantities ofdibenzylethylsilicol.The almost colourless aqueous solution of the sulphonic acid, whichhas been exhaustively extracted with ether, does not show thepeculiar behaviour referred to above, which, therefore, must beattributed to the presence of the silicane.It is very remarkable,however, that the silicane should dissolve in an aqueous solution ofthe sulphonic acid.Isolation of the Sulpiionic Acids.Many difficulties were met with in attempting to isolate thesulphonic acids produced in the manner described above. Theammonium salt was first prepared and freed from mineral salts by themethod previously used in other cases (Kipping, Trans., 1907, 91,225), but the crude salt was a syrupy or pasty substance, and couldnot be obtained in crystals. Prom the crude ammonium salt, manysalts of organic bases were obtained by precipitation ; of these, thestrychnine salt alone gave crystalline deposits from suitable solvents,and consequently this base was first employed for the purpose in viewORGANIC DERIVATIVES OF SILICON.PART XII. 149I n later experiments, when the properties of the sulphonic acids wereknown, I-menthylamine was used instead of strychnine, but as thereis little to choose between the two methods, they are both described.Method I.-The aqueous solution of the product of sulphonation isneutralised with sodium carbonate and treated with a concert tratedsolution of strychnine hydrochloride. The precipitate which is firstproduced dissolves on stirring, and, after some time, the solutionacquires the appearance of raw white of egg, but on adding morestrychnine hydrochloride a yellow oil is precipitated.'I! he almostclear supernatant liquid is decanted, and the oil is then stirred with alittle more of the solution of strychnine hydrochloride, after which itis extracted five or six times with boiling water and, lastly, with hot8 per cent. aqueous acetone.The remaining oil is then dissolved in alcohol, the solution dilutedwith about half its volume of water, and cooled i n ice ; the crystallinedeposit which is thus obtained is further purified by repeated crystal-lisation from aqueous alcohol, and finally from anhydrous ethyl acetatecontaining a trace of acetone. This product is the strychnine salt ofdl-di benzyleth y lpropylsilicanemonosulphonic acid.The aqueous extracts of the crude strychnine salt, and also thoseobtained with 8 per cent.aqueous acetone, deposit white, ashestos-likeneedles, together with a considerable proportion of oil. Afterseparating the crystals by the aid of the pump, the oil is againextracted twice with hot water, by which means a further quantity ofthe crystalline compound is obtained. The insoluble oily residue thenconsists principally of the strychnine salt of the monosulphonic acid,and is treated accordingly,The salt which is soluble in hot water is dissolved in acetone, whichcontains a very small proportion of water, and the solution is allowedto evaporate spontaneously. The substance which is then deposited,after having been recrystallised from methyl alcohol, consists of thestrychnine salt of dibenzylethylpropylsilicanedisulphonic acid.Nethod 11.-The aqueous solution containing the sodium salts ofthe sulphonic acids is treated with excess of a solution of I-menthyl-nmine hydrochloride, and the precipitated oil is washed with water ;this oil is then repeatedly extracted with boiling light petroleum(b.p. 40-60O). From these extracts the crude Z-menthylsmine saltof dI-dibenzylethylpropylsilicanemonosulphonic acid is deposited inlustrous plates on cooling and stirring well with a little water. Thissalt, however, still contains some Z-menthylamine salt of ihe di-sulphonic acid, from which it is separated by repeated recrystallisationfrom moist light petroleum. I n these operations, petroleum of verylow boiling point gives the best results, because, although the pureZ-menthylamine salt of the disulphonic acid is insoluble even in ligh150 CHALLENGER AND KIPPING :petroleum boiling at 60--80°, it dissolves to a considerable extent inpresence of the salt of the monosulphonic acid.That portion of the precipitated oil which is insoluble in lightpetroleum is dissolved in a small quantity of methyl alcohol, andtreated with ethyl acetate until the well-stirred solution becomesvery slightly turbid.If kept over sulphuric acid, nodular masses ofthe I-menthylamine salt of dibenzylethylpropyIsilicanedisulphonicacid are deposited. From the mother liquors, a further amount of theZ-menthylamine salt of the dl-monosulphonic acid can be obtained byeva.porating them and extracting the residue with light petroleum.St~yclmine dl-Di6enz?lIetl&yt~To~yIs~~~canemo~o~u~~onate,This salt separates from aqueous alcohol or aqueous acetone inhydrated crystals, which melt below 100' and contain 3 moleculesof water:0.9135 of air-dried salt lost 0.0686 H,O.C,,H,,O,N,SSi,3H,O requires H,O = 7.2 per cent.When the hydrated salt is dissolved in ethyl acetate it quicklyseparates again in colourless needles, which still contain water ofcrystallisation and lose weight at 100'.When heated, these do not soften until 160°, but resolidify above thattemperature, and then melt at 199O, the melting point of the anhydroussalt .H,O=7*5.The anhydrous salt was nnnlysed :0,1592 gave 0.4044 CO, and 0.0970 H,O.0,8305 ,, 0.0717 SiO,.Si = 4-06.The anhydrous salt is only very slightly soluble in dry ethylacetate, but dissolves readily in acetone, ethyl or methyl alcohol,chloroform, or toluene. It crystallises in leaflets from benzene, inwhich, however, it is very soluble. Short, stout, prismatic needles areobtained from a mixture of ethyl acetate and acetone. Lightpetroleum and ether have no solvent action.The specific rotation of the anhydrous salt was determined in 98per cent. methyl-alcoholic solution :0.8771, made up to 25 c.c., gave, in a 2-dcm. tube, Q - 0.58'; whenceI n spite of the fact that the isolation of this strychnine salt is onlyaccomplished after a very laborious series of crystallisations fromtwo solvents, the preparation melting at 199' is not a resolutionproduct of the dl-monosulphonic acid, as will be shown later.Conclusive evidence that the salt is really derived from dibenzyl-C = 69.3 ; H = 6.7.C,,H,,O,N,SSi requires C = 68.9 ; H = 6.94 ; Si = 4.09 per cent.[a], -8.26'ORGANIC DERIVATIVES OF SILICON.PART XII. 151ethylpropylsilicanemonosulphonic acid is afforded by the results ofanalyses of several other compounds prepared in the course of thisinvestigation.Strychnine DibenxyZe~hyZ~opyZs~Z~canedisuZphona~e.The pure preparations of this compound, isolated in the manneralready described, consist of a white, gritty powder, which turns brownat 226O and melts completely a t 2314 above which temperature itrapidly decomposes.Under the microscope it is seen to consist of short, rather ill-defined, prismatic needles :0.1894 gave 0.4559 CO, and 0.1170 H20.C = 65.63 ; H= 6.86.0.1780 ,, 0,4293 CO, ,, 0.1098 H,O. C=65*78 ; H=6.86.C,lH70010N,S,Si requires C = 65.8 ; H = 6.35 per cent.Owing to the slight solubility of the salt in 98 per cent. methylalcohol, the specific rotation was determined in 90 per cent. methyl-alcoholic solution :0.6162, made up to 25 c.c., gave, in a 2-dcm. tube, Q - 0.75"; whenceAlthough the strychnine salt of the disulphonic acid might beexpected to have a higher specific rotation than that ([a]D -8.26') ofthe salt of the monosulphonic acid, it seemed probable that the verygreat observed difference might be due to the different proportionsof water in the methyl alcohol employed in determining the twovalues.This conclusion was confirmed by determining the specific rotationof strychnine dibenzylethylpropylsilicanedisulphonate in methylalcohol containing 36 per cent.OF water :0.5298, made lip to 25 c.c., gave, in a 2-dcm. tube, a - 0 . 9 5 O ; whenceThe salt is very sparingly soluble in cold methyl or ethyl alcohol,but "is moderately soluble in the hot solvents, and also in boilingwater ; in ethyl acetate, acetone, benzene, and light petroleum it ispracticaily insoluble, but it dissolves freely in chloroform and inLqueous acetone. The crystals deposited from aqueous solutions meltat about l l O o , and. are doubtless hydrated, as, when dried a t loo",their melting point rises to 226-231'.[a], - 15*21°.[a], -32.4'.l-Jfenthylamine dl-BibenxylethyipropyZsiZicanernonosu1phortccte.This salt crystallises from moist light petroleum in high1 lustrousplates containing 2 molecules of water of crystallisation.Thehydrated salt liquefies at temperatures far below looo, but whe152 CHALLENGER AND KIPPING :kept over sulphuric acid it is completely dehydrated, and then meltsat 99':1.3661 lost 0.0855 H,O. H,O = 6.26.C,,H,70,NSSi,2H,0 requires H,O = 6.55 per cent.The equivalent of the anhydrous salt was determined by boilingwith excess of N/50-sodium carbonate and then titrating with hydro-chloric acid, using litmus as indicator. This method gave the value5 16.4, that required by theory being 5 17.8.The molecular weight of the anhydrous salt was determined by thecryoscopic method in benzene solution :Substance.Solvent . E. M. w.0.795 gram 17 *6 grams 0 -12 1875The calculated value is 517.8.The molecular weight was also determined by the ebullioscopicmethod in methyl-alcoholic solution :Substance.0.089 gram0.207 ,,0.348 ,,0.723 ,,1'006 ,,Solvent. E. M. w.70.0 grams 0.035 3050.075 3320.130 3220.260 3340.360 336These results correspond with those given in benzene and in methyl-alcoholic solutions respectively by the I-menthylamine salt of benzTl-methylethylpropylsilicanesulphonic acid (Ripping, Trans., 1907, 9 1,737), and as the salt is doubtless highly ionised in the latter solvent,the observed values are such as might have been expected.The specific rotation of the anhydrous salt was determined inmethyl-alcoholic solution :0.707, made up to 25 c.c., gave, in a 2-dcm.tube, a - 0.76' ; whenceI-MentTylamine dl-di6enxyletT~yZ23rop~Is~licanenzonosuIp?~onate is in-soluble in water, but dissolves freely in all organic solvents. It maybe recrystallised from aqueous alcohol and from aqueous acetone, butby far the most suitable solvent is petroleum of low boiling point;from this liquid the hydrated salt separates almost completely oncooling, but if the solution is boiled for some time, water is expelled,and the solution of the anhydrous salt does not deposit crystals untilit has been stirred with water.[.ID - 13.4'.Metallic Salts of dl-DibenzyZethyZpl.oioyZsiZicarnemonosuZ~~oitic Acid.The sodium salt was prepared by decomposing the pure Z-menthyl-amine salt with a slight excess of sodium carbonate and distilling offthe liberated base in steam; the very great frothing which occurs iORGANIC DERIVATIVES OF SILICON.PART XII. 153the latter operation may be overcome by dropping alcohol continuouslyinto the liquid.On neutralising the residue with a few drops of acetic acid andevaporating, a soapy mass separates from the cold concentrated solution,but on adding water again and leaving the solution at the ordinarytemperature, the salt is deposited in crystals; it is fairly readilysoluble in cold water, and extremely so in alcohol. It is precipitatedfrom its aqueous solution by sodium hydroxide, carbonate, or acetate.The ammoniuum salt was obtained from the pure strychnine saltas a sticky mass on evaporating its aqueous solution.It is morereadily soluble in water than the sodium salt, and its solution frothsreadily.The barium salt was precipitated in flocculent, oily masses when asolution of the sodium salt was treated with a solution of bariumchloride. It is only sparingly soluble in cold water or alcohol, butdissolves fairly readily in warm aqueous alcohol.I-Mmthylamine Dibenxylethy~ropylsilicanedisulphornote.This salt crystallises from a mixture of ethyl acetate and methylalcohol in nodules, which contain water of crystallisatioo, but which,when anhydrous, melt at 205-208O.The anhydrous salt is readily soluble in ethyl and methylalcohols, but is insoluble in water, acetone, ethyl acetate, lightpetroleum, or benzene..Metallic Salts of the Disulphonic Acid.The ammonium salt of the disulphonic acid was prepared by treatinga warm alcoholic solution of the strychnine salt with excess ofammonium hydroxide; on evaporation of the filtered solution itremained as a yellow solid, which mas purified by recrystallisationfrom a mixture of ethyl acetate and methyl alcohol. It was thusobtained in lustrous plates, readily soluble in the common alcoholsand in cold water, but insoluble in ethyl acetate, acetone, or lightpetroleum.The equivalent of the compound was determined by boiling thesalt with excess of N/5O-sodium carbonate, and then titrating thesolution with acid. The results obtained were 239.4 and 237.4, thetheoretical value being 3 3 8 -4.The sodium salt forms stellate crystals, and is readily soluble inwater, fairly so in alcohol. I n benzene, ethyl acetate, or acetone itis insoluble.The barium salt was precipitated as a granular powder on adding asolution of barium chloride to a neutral solution of the ammoniu154 FRANKLAND AND TWISS: THE INFLUENCE OF VARIOUSsalt.aqueous alcohol :It is sparingly soluble in water, and crystallises well from0.3594 gave 0.1445 BaSO,. Ba = 23-67.C19H,,0,S,SiBa requires Ba = 23.76 per cent.The authors are indebted to the Government Grant Committee ofthe Royal Society for a grant in aid of this research.UNIVERSITY COLLEGE,NOTTINCHAM

ISSN:0368-1645    

DOI:10.1039/CT9109700142

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

154 FRANKLAND AND TWISS: THE INFLUENCE OF VARIOUSXVII, - The Injuence of Varioz~s Substituents on theOptical Activity of Taytrarnide. Part III. Halogen-substituted Anilides.By PERCY FARADAY FRANKLAND and DOUGLAS FRANK TWISS.IN a previous communication (Trans., 1906, 89, 1852) we havegiven a list of the molecular rotations of the known tartramidederivatives, including the anilide and toluidides. In extension ofthis work we are now recording the results obtained with the chloro-anilides and bromoanilides of tartaric acid, since it is of interest !ostudy further the effect of substituents in the benzene ring of theanilide radicle, Previous investigations on asymmetric substancescontaining the benzene ring substituted in the different possiblepositions (for a list of papers see A.W. Stewart’s Xtereochernist~y,p. 95 ; Betti, Gaxxetta, 1907, 37, i, 62 ; and Pickard and Littlebury,Trans., 1907, 91, 300) have elicited the general result that therotation of the isomerides stands in the order para --+ meta -+ ortho,exceptions being comparatively rare (compare Goldschmidt and Preund,Zeitsch. physikal. Chem., 1894, 14, 394 ; also Frankland and Barrow,Trans., 1909, 95, 2031). The bromoanilides and chloroanilidesdescribed in this paper form no exception to the general rule, as isshown by the table given later.I n a previous communication on the ethyl and methyl esters of the0-, m-, andp-toluoyltartaric acids (Frankland and Wharton, Trans., 1896,69, 1309 and 1583), it was also pointed out that the relative rotationsof the ortho-substituted and of the unsubstituted aromatic compoundsrespectively appear to depend on both the centre of gravity of thechain attached to the asymmetric atom, and also on ,the increase inmass of the chain.If the loss in leverage is not compensatedsufficiently by the increase in mass, the rotation af the substituteSUBSTITUENTS ON THE OPTICAL ACTIVITY OF TARTRAMIDE. 155molecule will be less than that of the unsubstituted; this was thecase with the substitution of methyl in the ortho-position in benzoyl-tartaric esters.In the case of the anilides of tartaric acid, the substitution ofmethyl, bromine, or chlorine in the ortho-position lowers the molecularrotation; in the meta-position, the substitution of methyl causes aslight diminution, but the heavier chlorine or bromine an increasein the molecular rotation.This result is in all probability due mainlyto the effect of the superior mass of the bromine and chlorine atoms,but u a y also be assisted to some extent by the negative character ofthese atoms, as explained later,The following table gives the values for the molecular rotations (inpyridine solution) of the chloroanilides and bromoanilides, togetherwith those already published for the toluidides and the anilide, thelatter being included for the sake of comparison."I? [MI? [MI? [MI?dianilide. ditoluidide. dibromoanilide. dichloroanilida. + 739" ortho +667" + 652" + 709"para +793 + 886 + 838meta i-730 + 867 + 824A remarkable fact shown by these numbers is that, whilst thereplacement of the ortho-hydrogen atom by methyl causes a loweringin the molecular rotation, replacement by the heavier substituentchlorine causes a much smaller decrease, and even the bromine atomhardly lowers the rotation of tartranilide more than the methyl group.Again, it is noteworthy that in the series toluidide -+ bromoanilide -+ chloroanilide, the difference between the values of the meta- andpara-isomerides becomes less.This effect, together with the onepreviously mentioned, is possibly due to the increase in the negativecharacter of the substituent ; we would suggest that the negativesubstituent in the meta-position of the benzene ring is attracted(probably by one of the hydrogen atoms in the tartaric acid nucleus)in such a direction that the resulting distortion increases the asym-metry, whilst with the negative atom in the para-position the differentlydirected attraction causes such distortion that the asymmetry isdecreased.Thus the more negative the substituent, the more closelywill the rotations of the meta- and para-isomerides approximate toone another. That this explanation is at least a reasonable one isseen by constructing a graphic formula of the most compact configura-tion of the molecule, with the bonds drawn to the correct angles andto lengths in accord with Traube's atomic volumes. I n such a formulathe chain C*CH.CO*NHPh of the moleculeNHPh*CO*CH(OH)*C€€(OH)*CO"RPhwill be found to form an almost closed ring, the hydrogen attache156 FRANKLAND AND TWISS: THE 1NFLUENCE OF VARIOUSt o the one asymmetric carbon atom falling near the benzene ring andactually between the meta- and para-positions of the chain attachedto the other asymmetric atom.Any attraction between this hydrogenatom and a halogen atom in the para-position of the benzene ring Tillcause an increased compactness of the molecule, and so lessen theasymmetry. On the other hand, an attraction between this hydrogenand a negative atom in the meta-position will lead to a distortionoutwards; from the tartaric nucleus, and so cause an outward displace-ment of the CO*NH*C,H,X chain, with a corresponding increase inasymmetry.A halogen atom in the ortho-position would probably be so farremoved from the hydrogen of the other asymmetric atom that theattraction would be much less ; nevertheless, the experimental resultsseem to indicate that even this has an appreciable effect in increasingthe asymmetry.I n connexion with this hypothesis it is of interest to compare therotation of the m-iodotartranilide * with that of the other meta-substituted tartranilides.Di- Dichloro- Dibromo- Di-iodo-Dianilide.toluidide. anilide. anilide. snilide.[MI? (in pyridine solution) 739" 730" 824" 867" 888"YYY-Increase in rotation .. , ... . , . - 9" 9 4" 43" 21"Increase in mass (for onechain) . . . . . . . , . . . . . . . . . . . . . . 14 20 -5 44.5 47The increase in [MI, is greatest for one of the smallest changes inmass, and it is remarkable that it is between the neutral methyl andthe negative chlorine. For the increase in optical activity betweenthe chloro- and bromo-anilide, the mass-increase is the cause, t h einferior negativity of the bromine atom reducing the [MI, and sogiving rise t o a smaller increment in activity. Again, the diminishednegativity of the iodine atom would be the reason for the greatestincrease in mass (47) being attended, nevertheless, by the smallestincrement in activity.I n the preparation of the compounds described in this paper, greatcare was taken to ensure a pure product.Each substance, wherepossible, was prepared in two ways (from the free acid and from themethyl ester), and the product mas in each case recrystallised until ofconstant specific rotation.The majority of the rotations weremeasured in approximately 5 per cent. solution in dry pyridine at 20".Concentration was found to have little influence on the optical activity.The substances were all crystalline solids of high melting point(185-276').* Prepared by Mr. Norton in this laboratory ; this, with other iodoanilides,will form the subject of a future communicationSUBSTITUENTS ON THE OPTICAL ACTIVI~ Y OF TARTRAMJDE. 157EXPERIMENT A L.Tartarodi-p- bromoanilide.This was prepared by heating together powdered tartaric acid andp-bromoaniline (Kahlbaum) in theoretical proportions a t 150-1 60'for fifteen hours. After extracting with boiling dilute hydrochloric acidand with water, the residue was repeatedly crystallised from a mixtureof alcohol and pyridine (7 : 3 by volume).The following figures shorn the rotation observed in pyridine solu-tion :D [a]y.[ M];O". d 20"/4". I (dms.). $0". P.4.902 1.0004 1'998 + 18.95" + 193.4" + 886"The substance was also prepared by heating together theoreticalproportions of methyl tartrate and p-bromoaniline to 130-140" for tenhours. After similar purification to that described above, the productgave the following rotation in pyridine solution :4.908 1 -0003 1.998 + 18'95" + 193.2" -I- 885"The rotation in methyl alcohol is not snited f o r exact measurementon account of the low solubility of the substance ; the result, however,indicates a distinctly lower rotatory power than that in pyridinesolution :0.1355 0'792 3.899 + 0.76" + 181 -1" + 839"The specimens of bromoanilide prepared by the above methods hadthe same melting point, namely, 264' with decomposition; thesubstance forms slender crystals (elongated flat plates), which becomematted together so as to give rise to a tough white solid resemblingpaper.It is insoluble in water, sparingly soiuble in most of theordinary solvents, but readily so in pyridine :0,2429 gave 12.68 C.C. N, (moist) a t 11-8' and 754 mm. N = 6-12,C,,H1,0,N2Br2 requires N = 6.12 per cent.Tartarodi-m-bromoan~lid~.As with the para-compound, thia was prepared by the twoindependent methods. The tartaric acid and m-bromoaniline(Kahlbaum) were heated t o 150-160° for ten hours, and the methyltartrate and base to 130-140' for the same period. The product ismore soluble in alcohol than the para-compound, and, after extractionwith dilute hydrochloric acid, was purified by recrystallisation fromthis solvent158 FRANKLAND AND TWlSS: THE INFLUENCE OF VARIOUSThe following numbers give the rotation observed in pyridiiiesolution :(a) Preparation from tartaric acid and m-bromoaniline :P.d 20"/4". I (dms.). a?. [.Iy. 1 [M12,0".4'817 0.3995 1.998 -I-18'22" -1-189'4" f 867"( b ) Preparation from methyl tartrate and m-bromoaniline :The rotation of the specimen prepared from tartaric acid was also4.835 0,9994 1.998 -F 18 -28" + 189'3" + 867"measured in methyl-alcoholic solution :0.9862 0.7981 3.899 + 4'74" + 154.5" + 707"The m-bromoanilide crystallises in small, hard, flat plates, which0.2716 gave 14.3 C.C.N, (moist) a t 13O and 753 mm.melt at 220' with slight decomposition :N = 6.14.Cl,Hl,0,N,Br2 requires N = 6.12 per cent,Turturodi-o- bromoanilide.This substance was prepared only from tartaric acid and o-bromo-aniline, the mixture of methyl tartrate and o-bromoaniline undergoingextensive decomposition on heating. Approximately theoreticalproportions of tartaric acid and o-bromosniline (from reduction ofo-bromonitrobenzene : Fittig and Mnger, Ber., 1874, 7, 1179) wereheated to 150-160' for twenty hours. The resultant mass m a spurified bF treatment similar to that in the previous cases, and, finally,repeatedlyrecrystallised from a mixture of alcohol and water (3 : 2 byvolume) with simultaneous decolorisation by animal charcoal.The optical activity was measured in pyridine and in methylalcohol :(a) I n pyridine :P.d 20"/4". I (dms.). a209 [.]y. [ M]y.6'604 1.0076 0.999 + 9'46" + '1 42'3" 4- €52"4'572 0.9989 0.999 6 *53 143 '1 656(a) In methyl alcohol :3'363 0.8076 0.999 i- 3-21" + 118.3" + 542"0'9402 0.7964 2.993 2.71 120.9 554The o-bromoanilide consists of colourless, thin, rectangular needles,which melt at 193" without decomposition; i t is very soluble inpyridine and in hot alcohol, and sparingly so in hot water :05?410 gave 12.9 C.C. N, (moist) at 17.5" and 745 mm. N= 6.04.C,,H,,O,N,Br, requires N = 6.12 per centSUBSTITUENTS ON THE OPTICAL ACTIVlTY OF TARTRAMIDE. 159Tart aioodi- p-chloroanilide.The method of preparation was similar to that of the correspondingbromoanilide ; the substance was purified by recrystallisation from nmixture of 1 volume of pyridine to 3 of alcohol.Preparation from tartaric acid, in pyridine solution :21.d 20"/4". Z (dms.). ,20' D * [a]:Oo. [ M]Eoo.4.605 0-9939 1'998 + 20.77" + 227 *lo + 838"Preparation from methyl tartrate, in pyridine solution :5.015 0.9957 0.999 + 11-34' + 227 *3" 4- 839"The rotation in methyl-alcoholic solution was much lower than thatobserved in pyridine, although the low solubility increases theprobability of error in the specific rotation :0.1749 0.7943 3.899 +1*06" + 196" 3- 722"The p-chloroanilide forms needle- shaped crystals, melting and0.2035 gave 13.6 C.C. N, (moist) at 1 2 . 6 O and 748 mm.decomposing at 276' :N = 7.75.C16H1404N2C12 requires N = 7-59 per cent.~artarodi-m-chloroanili~~.The reaction, both in the case of the preparation from the acid andm-chloroaoiline (Kahlbaum), as well as in that from the ester and base,appeared to proceed less rapidly than in the production of m-bromo-anilide, and involved heating for sixteen hours.After the usualpreliminary treatment, the product was recrgstallised from a mixtureof 1 volume of water with 3 of alcohol.The specimen from tartaric acid and m-chloroaniline gave thefollowing rotation in pyridine solution :P. d 20"/4". I (dms.). a?. [M]Eoo.1.746 0.9829 2.993 11 '42 222.3 820whilst that from methyl tartrate and the base gave the followingfigures :4-966 0.9953 0.999 +11*03" + 223.4" 4-824"4.865 0.9949 0.999 $10 80" + 223 -4" + 824"The rotation in solution in methyl alcohol was as follows :1.504 0.7971 2.993 + 6 -54" +182.3" + 673"~a~tarodi-m-chEoroaniEide crystallises in thin, fibrous needles, whichmelt and decompose slightly a t 21 3 O 160 OPTICAL ACTIVITY OF TARTRAMIDE.0.2035 gave 13.7 C.C.N, (moist) at 13' and 735 mm. N = 7-66.CI,H,,0,N2CI, requires N = 7.59 per cent.As in the case of the corresponding o-bromoanilide, the preparationof this substance was attended with more difficulty than that of themeta-compound ; the mixtures had t o be heated for twenty hours, andthe yields were inferior to those obtained in the case of any of theother anilides. The yield from the ester was particularly poor, thecrude product being a black, pasty mass. For the recrystallisation amixture of one part of water to two of alcohol was employed.The following are the rotations obtained in pyridine solution :(a) Specimen prepared from tartaric acid :P. d 20"/4". I (dms.). C P 0 . [a];O'. [MI];?4.881 0.9944 0.999 + 9 32" + 192-2" + 709"1.392 0,9816 8.993 7 -89 192.9 712(6) Specimen from methyl tartrate :5.060 0.9940 0.999 + 9 *65" + 192.1" -k 709"The optical activity mas measured also in methyl alcohol :1524 0.7980 2.993 + 5 -98" + 164'3" + 606"The o-chloroanilide crystallised in long, narrow plates, melting atIt is sparingly soluble in hot water, but very soluble in pyridine 185".and in hot alcohol :0.2067 gave 13-75 C.C. N, (moist) at 14" and 748 mm.CI,H,,0,N2C1, requires N = 7.59 per cent.N= 706'7.UNIVERSITY,BIRMINGHAM

ISSN:0368-1645    

DOI:10.1039/CT9109700154

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

THORPE : THOMSEN MEMORIAL LECTURE. 161THOMSEN MEMORIAL ;LECTURE.DELIVERED ON FEBRUARY 17TH, 1910.By SIR EDWARD THORPE, C.B., LL.D., F.R.S., Past-President of theChemical Society.AMONG the Danes whose names are inscribed as men of science onthe eternal bead-roll of fame, that of Julius Thomsen stands pre-eminent-linked indeed with that of 'Oersted. It is significant ofthe position which Thomsen acquired in physical science, and ofthe respect which that position secured for him in the eyes of hiscountrymen, that his statue should have been erected during hislifetime and placed in the vicinity of that of Oersted in the court-yard of the Polytechnic High School of Copenhagen. Thomsen, infact, played many parts in the intellectual, industrial, and socialdevelopment of Denmark.To Europe in general he was mainlyknown as a distinguished man of science. By his fellow-citizens hewas further recognised as an educationist of high ideals, actuatedby a strong common sense and a stern devotion to duty; as anable and sagacious administrator ; as a successful technologist andthe creator of an important and lucrative industry based upon hisown discoveries; and as a man of forceful character, who broughthis authority, skill, and knowledge of men and affairs to the serviceof the communal life of Copenhagen.Thomsen was a municipal councillor of that city for more thana third of a century. He occupied a commanding position on theCouncil, and was invariably listened to with respect. The gas,water, and sewage works of Copenhagen are among the monumentsto his civic activity.From 1882 up to the time of his death hewas a member of the Harbour Board of the port. I n these respectsThomsen sought to realise Priestley's ideal of the perfect man-thathe should be a good citizen first and a man of science afterwards.Hans Peter Jurgen Julius Thomsen was born in Copenhagen onFebruary 16th, 1826. He was educated a t the church school ofSt. Peter in that city, and subsequently a t von Westens Institute.I n 1843 he commenced his studies a t the Polytechnic, and in 1846graduated there in Applied Science, and became an assistant toProfessor E. A. Scharling. Of his earliest years comparativelylittle is known. Thomsen, always a reserved and taciturn man,talked little about himself even to his intimate friends-and leastof all about the days of his youth.It was known to a few thatthese days had not been smooth. Those who were 'best informedVOL. XCVII. 162 THORPE : TEOMSEN MEMORIAL LECTURE.were conscious that to these early struggles much of that dour andresolute nature which formed a distinguishing trait in his characterwas due, Thomsen, indeed, began life as a fighter, and a fighterhe remained t o the end of his four-score years.I n 1847, he became assistant to Forchhammer, passing rich, likeGoldsmith’s pedagogue, on &40 a year. Georg Forchhammer, whoseearliest work dates back to the period when Berzelius was in hisprime, was an active and industrious investigator of the old school,mainly in inorganic chemistry, and more particularly on problemsof chemical geology and physiography. He was a frequent visitorto this country, and was well known to early members of theBritish Association.Although doubtless influenced, in commonwith all teachers in Northern Europe, by the example and methodsof Berzelius, such influence as he himself was able to exert diedwith him. Forchhammer attracted few pupils, and created no school,and Thomsen probably derived no inspiration or acquired anystimulus from this association. For a time Thomsen supplementedhis scanty income by teaching agricultural chemistry at thePolytechnic. In 1853 he obtained a travelling scholarship, andspent a year in visiting German and French laboratories. Heprobably owed this scholarship in great measure to his first con-tribution to the literature of chemistry, namely, his memoir,(( Bidrag ti1 en Thermochemisk System ” (contributions to a thermo-chemical system), communicated to the Royal Society of Sciencesof Copenhagen in 1852, and for which he received the silver medalof the Society and a sum of ten guineas to enable him t o procurea more accurate apparatus. I n this memoir he sought to developthe chemical side of the mechanical theory of heat, doubtless underthe influence of Ludwig Augustus Colding, an engineer in theservice of the Municipality of Copenhagen, and a pioneer, likeMayer, in the development of that theory.Indeed, the Danes nowclaim for Colding, who had made experiments on the relationbetween work and heat as far back as 1842, but whose labours werepractically ignored by his contemporaries, the position which theGermans assign to Mayer (see Mach’s ‘( Development of the Theoryof Heat”).I n 1861 Thomsen further developed his ideas in amemoir on the “ General Nature of Chemical Processes, and on aTheory of Affinity Based Thereon,” published in the Transactions ofthe Danish Academy of Sciences. I n this paper he laid theroundations of the chief scientific work of his life.I n 1853 Thomsen patented a method of obtaining soda fromcryolite, so-called ‘‘ Greenland,” or ice-spar, a naturally occurringfluoride of sodium and aluminium, A12F,,GNaF, found largely,indeed, almost exclusively, in Greenland, and particularly a THORPE : THOMSEN MEMORIAL LECTURE.163Ivigtut. It derives its mineralogical name from its ice-likeappearance and ready fusibility even in the flame of a candle. Itseems to have been first brought to Europe in 1794, and to havebeen described by Schumacher in the following year. Klaprothfirst showed that it contained soda, and its composition was furtherestablished by Vauquelin, Berzelius, and Deville.Thomsen’s process consists in heating a finely divided mixture ofcryolite and chalk in a reverberatory furnace, whereby carbondioxide is expelled and calcjum fluoride and sodium aluminateare formed. The roasted mass is lixiviated with water, so asto dissolve out the sodium aluminate, which is then treated withcarbon dioxide. Alumina is precipitated, and sodium carbonateremains in solution. The aIumina is either sold as such, or con-verted into sulphate (so-called ‘‘ concentrated alum ” or “ alum-cake ”), and the sodium carbonate is separated by crystallisation.Both products are obtained in a remarkably pure condition, and thecryolite-soda, yields excellent “ caustic.”Thomsen’s process, although simple enough in principle, requiresconsiderable skill and pains in its practical execution, and most ofthe manufacturing details were worked out by him, or under hisdirection.Success largely depends upon the maintenance of aproper temperature ; the decomposition begins below a red-heat, butrequires to be finished at that temperature, and care must be takento avoid fusion or even sintering of the mass.In 1854 Thomsenobtained tho exclusive right of mining for cryolite and of workingup the mineral in Denmark for soda and alumina. Actual manu-facturing operations were begun on a small scale in 1857, and in thefollowing year Thomsen planned the present large facbry a tOeresund, near Copenhagen, which was opened on his thirty-fourthbirthday. The importance of this industry to Denmark may beseen from the circumstance that during the fifty years of itsexistence the firm have paid the Danish Government nearlyS300,OOO for the concession. Other factories were started inGermany, Bohemia, and Poland, but met with little success. ThePennsylvania Salt-manufacturing Company at Natrona, nearPittsburg, eventually obtained the right to work up two-thirds ofall the cryolite mined in Greenland.From the start Thomsen tooka large share in the management of the Oeresund works, and byhis energy, foresight, and skill placed the undertaking on a soundcommercial basis.Although Thomsen died a rich man, mainly as the result of theindustry he created, in the outset of his career as a, teacher and atechnologist his means were very straitened. He came of poorparents, of no social position or influence, and they were unable toM 164 THORPE : THOMSEN MEMORIAL LECTURE.further his inclinations towards an academical career. I n 1854 heapplied unsuccessfully for a position as teacher of chemistry a t theMilitary High School in Copenhagen. During three years-from1856 to 1859-while still engaged in developing his cryolite process,he acted as an adjuster of weights and measures to the Municipalityof Copenhagen.It was a poorly paid position, but it kept thewolf from the door. A t about this period he betook himself toliterature, and published a popular book on general subjects con-nected with physics and chemistry-somewhat in the style ofHelmholtz’s well-known work-entitled ‘‘ Travels in ScientificRegions,” which had a considerable measure of success. He was,however, not altogether unknown even at this time as an author,since in 1853 he had collaborated with his friend Colding inproducing a memoir on the causes of the spread of cholera and onthe methods of prevention, which attracted much attention at thetime of its appearance.I n 1859, whilst engaged in the Oeresund factory, he againapplied to the authorities for a position as teacher a t the MilitaryHigh School, and succeeded in obtaining an appointment to alectureship in physics, which he held until 1866.During his tenureof this office he devised his polarisation battery, which receivedmany awards at International Exhibitions and was used for a timein the Danish telegraph service.I n 1859-60 he was “vicarius” for Scharling at the University,and in 1865 became a teacher, and in the following year Professorof Chemistry and Director of the Chemical Laboratory, a positionwhich he retained-active to the last-until 1901, when he retiredin his seventy-fifth year of age.Before his connexion with the University, he founded a d edited,from 1862 to 1878, in association with his brother, August Thomsen,the Journal of Chemistry and Physics, one of the principal organsof scientific literature in Denmark.I n 1863 he was elected a member of the Commission of Weightsand Measures, and was instrumental in bringing about the adoptionof the metric system and the assimilation of the Danish system t othat of the Scandinavian Kingdom.I n 1883 Thomsen became Chancellor of the Polytechnic HighSchool of Copenhagen-a position which he held for ,about nineyears. During this period he entirely changed the character andspirit of the school, and stamped it with the impress of his earnest-ness and industry. Under his direction, new buildings were erectedand arranged in accordance with the best Continental and Americanmodels.Thomsen’s administration was in marked contrast to thatof his somewhat easy-going predecessor, but it is doubtful if i THORPE : THOMSEN MEMORIAL LECTURE. 165brought him popularity in the school. The students respected andeven feared him, but his cold and unsympathetic nature evokedno warmer feeling. It was said of him by one who knew himintimately that he never learned to draw the young to him, tocreate in them an interest for his work, to form a school. Thomsenwas a homely man, but not even in his home, says the sameauthority, was it possible for him to change his active, earnest,strenuous disposition-what his friends called his fighting character.But if he was always the serious master of the house, he was alsoits obedient servant.I n reality he was a man of deep feeling, andwas not without power to give that feeling expression in words,sometimes in verse, and occasionally even in music.It was while occupying the position of Director of the ChemicalLaboratory of the University that Thomsen executed the thermo-chemical investigations which constitute the experimental develop-ment of the ideas he had formulated in his memoir of 1861. Theresults of these inquiries were first made known in a series ofpapers published from 1869 to 1873 in the Transactions of the RoyalDanish Society of Sciences, and from 1873 onwards b,y the Journalfiir Praktische Chemie. The papers were republished in collectedform in four volumes (1882-1886) by a Leipzig house under thetitle of Thermochemische Untersuchungen.A summary of thisexperimental labour, which extended over a third of a century,was subsequently prepared by Thomsen, and published in 1905 inDanish under the title of Thermokemiske Resultater.I n this work he reviewed the whole of the numerical andtheoretical results, to the exclusion of the greater portion of theexperimental details. A translation of this volume by MissKatharine A. Burke, entitled Thermochernistry,” renders itreadily accessible to English readers. Miss Burke has supple-mented the original work by a short account, taken from theThermoc7bem’sche Unt ersuchungen, of the experimental methodsemployed, thereby rendering the whole more intelligible to thestudent.Moreover, in the English edition a partial attempt hasbeen made to translate Thomsen’s deductions into the language ofmodern theory based on the conception of ionisation, which, ofcourse, was not known to science at the time the ThermochemisclieUntersuchungen was published.It is impossible within the limits of such a notice as this to dealin detail with the immense mass of experimental material whichthis work embodies, and I shall not attempt, therefore, to do morethan to offer a generalised statement, based mainly upon theadmirable account of Thomsen’s work given by Professor Bronstedto the Chemical Society of Copenhagen on the occasion of th166 THOltPE : THOMSEN MEMORIAL TJECTURE.meeting held on March 2nd, 1909, t o commemorate Thomsen’sservices to science.The conception of affinity as a cause and determining conditionof chemical change is traceable in some of the earliest cfforts toco-ordinate and explain chemical phenomena.It certainly existedlong prior to the time of Boyle, and was a t the basis of everyphilosophical system after his period. TT7e need only mention thenames of Bergman, Wenzel, and Berthollet to indicate this fact.But to Thomsen belongs the credit of being the first t o make theattempt to measure the relative value or strength of affinityquantitatively, and to express it numerically in definite termswhich admitted of exact comparison. Thomsen’s theory of affinity,as enunciated by him in his 1851 paper, was based upon his con-viction that affinity could be measured quantitatively by estimatingthe amount of heat evolved in the chemical process.We are notimmediately concerned to show whether the theory is right orwrong, or in what respect it fails. The point is that the enunciationof this principle upwards of half a century ago constituted animportant step forward, inasmuch as it sought t o estimate affinityin relation to a quantity which can be fixed by experiment, and iscapable of expression by numbers.I n this and in the subsequent paper of which mention has beenmade already, he thus defines his conception of thermochemistry,and discusses, for the first time, its laws.“The force which unites the component parts of a chemicalcompound is called affinity. I f a compound is split up, whetherby the influence of electricity, heat, or light, or by the additionof another substance, this affinity must be overcome. A certainforce is required the amount of which depends on the strength ofthe affinity.“ I f we imagine, on the one side, a compound split up into itscomponent parts, and on the other side these parts again unitedto form the original compound, then we have two opposite processesthe beginning and end of which are alike.It is therefore evidentthat the amount of the force required to split up a certain compoundmust be the same as that which is evolved if the compound inquestion is again formed from its component parts.‘I The amount of force evolved by the formation of a compoundcan be measured in absolute terms; it is equal t o the amount ofheat evolved by the formation of the compound.(( Every simple or complex action of a purely chemical nature isaccompanied by evolution of heat.‘(By considering the amount of heat evolved by the formationof a chemical compound as a measure of the affinity, as a measurTHORPE : THOMSEN MEMORIAL LECTURE.167of the work required again to resolve the compound into itscomponent parts, it must be possible to deduce general laws for thechemical processes, and to exchange the old theory of affinity,resting on an uncertain foundation, for a new one, resting on thesure foundation of numerical values.”As has been proved by later theoretical and experimental investi-gations, the theory of thermochemical affinity is not absolutelycorrect a t ordinary temperatures.But, on the other hand, it hasbeen shown that a comparatively large number of processes areapproximately in unison with it. Not only do they agree quali-tatively, that is to say, that heat is evolved during the process, butalso in the fact that the results which newer and more exactmethods for estimating affinity have produced, agree numericallywith what would be required by the thermochemical theory. Wemeet here with a fundamental phenomenon which Thomsen deservesgreat credit for having first pointed out, but the explanation ofwhich could not be given at the time he indicated it. It can bedemonstrated theoretically that the lower we reduce the tempera-ture and the nearer we get to the absolute zero, the more nearly isthe condition for the theory fulfilled, so that at the absolute zerothe theory would be found to be an exact law of nature. I f it werepossible to work a t such low temperatures it would be found thatthe evolution of heat, or the evolution of energy by the chemicalprocess, would be an exact measure of the affinity of the process,and that under this condition the theory of Thomsen would be theaccurate expression of it natural law.But under ordinary conditions this is not so, for in reality anever-increasing number of endothermic processes are found tooccur, that is, processes which proceed with the absorption of heat.Thomsen tried a t first to explain these phenomena in such a wayas to keep them within his system, and he drew a distinctionbetween a purely chemical process running conformably to histheory and a physico-chemical process which did not fall withinthe law.But he was- gradually convinced that his theory couldnot be maintained in its entirety. It is to his credit that he didnot seek to uphold an untenable principle, or try to defend it asdid Berthelot, who almost to &is dying day maintained the validityof the principle in spite of all facts.These ideas have, in the words of Ostwald, been the scientificconfession of faith of chemists throughout half a century. Theyhave had the greatest influence on scientific thought in everybranch of chemistry. It is on the basis of them that we havearrived a t a theory of affinity which at the present moment isbeing developed into one of the most perfect chemical theories168 THORPE : THOMSEN MEMORIAL LECTURE.Lastly, it is due to these ideas that the experimental material hasbeen produced which during all time will place the name of JuliusThomsen in the first rank of men of science.To go through this material in detail is, as I have said, impossiblehere.It may be stated generally that practically every simpleinorganic process has been investigated calorimetrically byThomsen, or can be calculated by means of the calorimetric datafurnished by him. I n the case of organic substances, data have beengiven for estimating the heat of combustion of a large number ofcompounds. All these estimations were made by Thomsen per-sonally, according to a pre-arranged plan, and in systematic suc-cession during a period of more than thirty years. They comprisemore than 3500 calorimetrical estimations.It has been truly saidthat this work is unique in the chemical history of any country.Among the results of Thomsen’s thermochemical inquiries whichhave special value for physical chemistry is his investigation of thephenomena of neutralisation, in which he shows that the basicityof acids can be estimated thermochemically, and that it can in thisway be proved whether or not a point of neutrality exists. Hisobservation that the heat of neutralisation is the same for along series of inorganic acids, such as hydrochloric acid, hydro-bromic acid, hydriodic acid, chloric acid, nitric acid, etc., supportsthe theory of electrical dissociation, inasmuch as this requires thatthe heat of neutralisation of the strong acids must in all cases beindependent of the nature of the acid, because the process ofneutralisation for all of them is the combination of the ion of’hydrogen in the acid with the ion of hydroxyl of the base to formwater.These investigations also led to the important thermo-chemical result that the heat of neutralisation of acids (or the heatof their dissociation) cannot be considered as a measure of thestrength of the acids.Another important result is the proof by experiment of theconnexion which exists between the changes of the heat-effect withthe temperature and the specific heat of the reacting substances.The first law of thermodynamics requires the relation indicatedwhere U is the heabeffect, T the by Kirchhoff : d-T =C, -Cz, dUtemperature? and C, and C2 are the heat capacities of t,he twosystems before and after the reaction, and Thomsen showed byinvestigation of the heat of neutralisation, the heat of solution, andthe heat of dilution, that this relation was satisfied For thepurpose of his inquiry, the specific heats of a large number ofsolutions of salts were estimated by an ingenious method, andwith an exactness hitherto unattainedTHORPE : THOMSEN MEMORIAL LECTURE.169Of no less importance are Thomsen’s thermochemical investi-gations on the influence of mass. I n the year 1867 Guldberg andWaage published their theory of the chemical effect of mass.Butthey had only verified the theory to a small extent and in par-ticularly simple cases. They had not investigated the completehomogeneous equilibrium, because at that time no method existedfor experimental investigation of such homogeneous equilibrium.Thomsen showed that the estimation could be made thermo-chemically. By allowing, f o r instance, an acid to act on a saltof another acid in an aqueous solution, the latter acid will bepartly replaced by the first, which will form a salt. By mixing,for instance, a solution of sodium sulphate and nitric acid, thereis formed sodium nitrate and sulphuric acid, but the process willnot proceed to completion. I f we have estimated the heat ofneutralisation of the two acids with sodium hydroxide, the differencebetween these two heat-phenomena will give the amount of heatcorresponding to the total decomposition of the sodium sulphate,and the heat found experimentally by mixing the two solutions willtherefore show to what degree the transformation has taken place.It would be possible to estimate thermochemically the amount ofthe four substances in solution, and thereby, by varying the con-centration or the proportion between the initial quantities ofsubstances, to calculate whether the Guldberg-Waage theory on theeffect of mass was confirmed in this case.Thomsen applied this method to a large number of differentacids and bases, and was enabled thereby to prove the agreementwith the law of the influence of mass in all the cases which heexamined.He found particularly that the proportion of theone acid which remained combined with the base wits constantwith mixtures of constant proportion. On this basis he propoundedthe term avidity, which he defined as the tendency of the acid tounite with the base, and he showed that the avidity was independentof the concentration, and only to a small extent varied with thetemperature. The term avidity has since acquired great importance,particularly since other and more exact methods for its estimationhave been found. Concurrently with this, its meaning has beenmade clear by the theory of electrolytic dissociation.On the basis of these estimations, Thomsen drew up the firsttable, based on experiments, of the relative strength of the acids,and the numbers in this table have been found to agree with theresults obtained by examining the electrical conduct.ivity of theacids.It is worth noting that Thomsen not only produced the experi-mental proof of the correctness of the Guldberg-Waage theory o170 THORPE : THOMSEN MEMORIAL LECTURE.the effect of mass soon after the appearance of this theory, butalso that he was the first to acknowledge and adopt it.It isremarkable that this work of Thomsen received so little attention,although it appeared in a widely circulated German journal, andit was not until ten years later that the law of the effect of masswas generally recognised, as the result of the work of Ostwald andvan’t Hoff.Although Thomsen’s title to scientific fame rests mahly uponhis thermochemical work, his interests extended beyond this par-ticular department of physical chemistry.IIe worked on chloralhydrate, selenic acid, on ammoniacal platinum compounds, and onglucinum platinum chloride, on iodic acid and periodic acid, onhydrogen peroxide, hypophosphorous acid, and hydrogenium. Heearly recognised the importance of MendelBeff’s great generalisation,and contributed to the abundant literature it produced. His paperof 1895, ((On tho Probability of the Existence of a Group ofInactive Elements,” may be said to have foreshadowed thediscovery of the congeners of argon. He pointed out that inperiodic functions the change from negative to positive value, orthe reverse, can only take place by il passage through zero orthrough infinity; in the first case, the change is gradual, and inthe second case it is sudden.The first case corresponds with thegradual change in electrical character with rising atomic weight inthe separate series 01 the periodic system, and the second casecorresponds with a passage from one series to the next. It thereforeappears that the passage from one series to the next in the periodicsystem should take glace through an element which is electricallyindifferent. The valency of such an element would be zero, andtherefore in this respect also it would represent a transitional stagein the passage from the univalent electronegative elements of theseventh to the univalent electropositive elements of the first group.This indicates the possible existence of a group of inactive elementswith the atomic weights 4, 20, 36, 84, 132, the first five numberscorresponding fairly closely with the atomic weights respectivelyof helium, neon, argon, krypton, and xenon (Zeitsch.anorg. Chem.,1895, 9, 283; Jourm. Chem. Soc., 1896, 70, 11, 16). He subse-quently made known the existence of helium in the red fluoritefrom Ivigtut.As evidence of Thomsen’s manipulative ability and his powerof accurate work may be mentioned his determination of the atomicweights of oxygen and hydrogen, and incidentally of aluminium.For the atomic weight of hydrogen he obtained the value 1.00825when 0 = 16, which is practically identical with that of Morley andNoyes. He further made most accurate estimations of the relativTRORPE : THOMSEN MEMORIAL LECTURE.171densities of these gases, and of the volumetric ratios in which theyenter into the composition of water. His value for the atomicweight of aluminium is nearly identical with that adopted in thelast Report of the 1nterna.tion;tl Committee on Atomic Weights.Thomsen maintained his interest in thermochemical problems upto the end, and was a keen and clear-sighted critic of the workwhich appeared from time t:, time during the later years of hislife. This interest occasionally gave rise to controversy, and someof his latest papers were wholly polemical.Thomsen was a pronounced atomist, and t o him a chemicalprocess was a change in the internal structure of a molecule, andthe chief aim of chemistry was to investigate the laws whichcontrol the union of atoms and molecules during the chemicalprocess.He considered that chemistry should be treatedmathematically as a branch of rational mechanics. But no oneinsisted more strongly than he how little we really know of thescquestions. I n summarising his tlicoreticnl ideas in the TAewn o-Eemische Resiiltcitcr, he says, “ An almost impenetrable darknesshidzs from us the inner structure of molecules and the true natureof atoms. We know only the relative number of atoms withinthe molecule, their mass, and the existence of certain groups ofatoms or radicles in the molecule, but with regard to the forcesacting within the molecules and causing their formation or destruc-tion our knowledge is still exceedingly limited.” He fully realisedthat his own work was only the foundation on which the futureelucidation of these questions must rest.“ H e worked,” saysBronsted, “ in the conviction that what we somewhat vaguely callthe affinity of the atoms-their interaction, their attraction, andvarying effect, etc.-follows the general laws of mechanics, and that,as lie worded it, the principle that ‘might is right,’ holds good inchemistry as in mechanics. ‘On this foundation he hoped to beable to evolve the laws for the statics and dynamics of chemicalphenomena, even although the true nature of the action isunknown.”Thomsen’s merits as an investigator received formal recognitionfrom nearly every country in the civilised world.As far back as1860 he was elected one of the thirty-five members of the DanishRoyal Society of Sciences of Copenhagen, and from 1858 until hisdeath he was its President. I n 1876 he became an HonoraryForeign Member of the Chemical Society of London. On theoccasion of the fourth centenary of the foundation of the Universityof Upsala (created in 14$7), he received the degree of Doctor ofPhilosophy honoris causa. I n 1879 he was made an honorary M.D.of the University of Copenhagen. Two years later he was made i172 THORPE : THOMSEN MEMORIAL LECT’C’RE.Foreign Member of the Physiographical Society of Lund, and in1888 he was elected a member of the Society of Science andLiterature of Gothenburg. I n 1885 he became a member of theRoyal Society of Sciences of Upsala, and in 1886 of the StockholmAcademy of Sciences.I n 1883 he and Berthelot were together awarded the DavyMedal of the Royal Society-a fitting and impartial recognition onthe part of the Society of the manner in which the two investigators,whose work not infrequently brought them into active opposition,had jointly and severally contributed to lay the foundations ofthermochemistry .I n the same year Thomsen wits made a member of the Accademiadei Lincei of Rome, and in the following year he was elected intothe American Academy of Arts and Sciences in Boston, and of theRoyal Academy of Sciences of Turin. I n 1887 he was made amember of the Royal Belgian Academy.I n 1886-87 and again in 1891-92 he was Rector of the Universityof Copenhagen. I n 1888 he became Commander of the Dannebrog,and in 1896, and on his seventieth birthday, he was made GrandCommander of the same order. On the same occasion the Danishchemists caused a gold medal t o be struck in his honour. I n 1902he became a Privy Councillor (Geheime Konferenz raad). I n thesame year he was elected a Foreign Member of the Royal Societyof London.He died on February 13th, 1908, full of years as of honours,and was buried on the eighty-third anniversary of his birth andon the jubilee of the opening of the Oeresund factory. His wife,Elmine Hansen-the daughter of a farmer on LangeIand-pre-deceased him in 1890.I desire to express my acknowledgments to Director G. A.Hagemann, of Copenhagen, and t o Professor Arrhenius, ofStockholm, for their assistance in obtaining information concerningThomsen’s personal history. I a,m also much indebted to ourFellow, Mr. Haralcl Faber, for his kindness in making for mea transhtion of Professor Bronsted’s accoiint of Thomsen’s scientificwork, on which my own r6sum6 is mainly based

ISSN:0368-1645    

DOI:10.1039/CT9109700161

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

FORMATION OF HETEROCYCLIC COMPOUNDS. PART 11. 173XV III.---Formation cf Heterocyclic Comapouncls. Part11. Actim of Buses on the ad-Dib,.omo-deu.ivatilcesoj' Certcrin Diccwboxylic Acids.By HENRY ROXDEL LE SUEUR and PAUL HAAS.THE action of diethylaniline on aliphatic compounds containingbromine, and more especially on the esters of a-bromo-monocarboxylicacids (Crossley and Le Sueur, Trans., 1899,75, 161 ; 1900, 77, 83),is to remove the elements of hydrogen bromide with the formation ofthe corresponding unsaturated compound :R*CH,-CHBr*CO,Et --+ R*CH:CH*CO,Et.This action bas been regarded as quite a general one, and holds goodin the majority of instances. I n the case of ethyl aS-dibromoadipate,CO,Et*CHBr*[CH,],*CHBr.CO,Et, a compound in which the twobromine atoms are separated from each other by four carbonatoms, the action of diethylaniline is quite different.Here it is truesmall quantities of the unsaturated ester, ethyl muconate,CO,Et*CH:CH*CH:CH*CO,Et,are formed, but by far the main product of the reaction is ethyl1-phenylpyrrolidine - 2 : 5 - dicarboxylate (Le Sueur, Trans., 1909,95, 2'76) :This reaction involves the fission of the two ethyl groups in diethyl-aniline, a change which is generally not easily effected, but that thisactually takes place was proved by the isolation and identification oflarge quantities of ethyl bromide resulting from the above reaction.The action of aniline is quite similar to that of diethylaniline, asis shown by the action of aniline on methyl a6-dibromoadipate whenthe correspondiag pyrrolidine ester is produced.The usual actionof aniline on compounds of this type is to replace thebromine atom bythe group C,H,*NH :CO,Et*CHBr*[CH,],,*CHBr*CO,Et -+This great tendency for the formation of a five-membered ringis further illustrated by the action of alcoholic potassium hydroxide ona6-dibromoadipic acid, whereby cis-tetrahydrof uran-2 : 5-clicarboxy licacid is produced :CO,Et*CH(NHPh)* [ CHJn*CH(NHPh)* C0,Et.CO,H*CHBr* QH, CH( CO,H)*FK,CO,H* CHBr CH , --3. O<CH(CO,H)*CH,174 LE SUEUR AND HAAS:the usual action of alcoholic potassium hydroxide, namely, theremoval of hydrogen bromide and formation OF the correspondingunsaturated compound, only taking place to a small extent, as onlysmall quantities of muconic acid were obtained.I n contrast to the above reaction, we may compare the action ofalcoholic potassium hydroxide on py-dibromoadipic acid,CO,H=CH,* CHBr CHBr CH,*CO,H,whereby Rupe (Amden, lS90, 256, 1) obtained an 85 per cent.yieldof muconic acid. I n the bromo-acid employed by Rupe, the twobromine atoms are attached to adjacent carbon atoms, and there istherefore no possibility of the formation of a five-membxed ring, andso the action is the norinal one. The constitution of muconic acid wasdiscussed by Rupe, who concluded that i t is correctly expressed by theformula CO,H*CH:CH*CEI:CH*CO,H ; this conclusion is fully con-firmed by the facts that the acid is obtained from as-dibromoadipicacid and tho ethyl ester from ethyl a6dibromoadipate as described inthe present communication,In order to ascertain i f cyclic compounds analogous to ethylI-phenylpyrrolidino-2 : 5-dicarboxylate would be obtained from thecorresponding bromo-derivatives of other dicarboxylic acids, the actionof aniline and monoethylaniline on these bromo-derivatives wasinvestigated.The action of aniline on ethyl up-dibromosuccinate has been alreadystudied by Gorodetzky and Hell (Ber., 1888, 21, 1796), who obtainedethyl up-dianilinosuccinate, CO,Et*CH(NHPh)*CH(NHPh).CO,Et, asthe main product, together with a small quantity of a yellow compoundwhich they were unable to identify.I t was thought that this yellowsubstance might be the desired cyclic compound containing the ringsystem C6H6*N<y but this was found not t o be the case, andthe compound was identified as the anil of anilinomaleic acid,C'(Bischoff and Walden, AnnaZen, 1894, 279, 139).The action of monoethylaniline on ethyl up-dibromosuccinate wasnext investigated, and in this case the compound obtained was ethylbromomaleate, CO,Et*CBr:CH*CO,:Et, which was obtained in a 74.2per cent.yield. Ethyl ae-dibromosebacate was then substituted for ethylap-dibromosuccinate, and heated with aniline, when it was found thatno cyclic compound had beon formed, but that the action had followedthe normal course, and ethyl a8-dianilinosebacate,C0,Et * CH(NHPh)* [ CH,],* CH( N HPh) *CO,E t,was obtained.By heating an aqueous solution of the lactonc of dihydroxybutaneFORMATION OF HETEROCYCLlC COMPOUNDS. PART 11.175totracarboxylic acid, Lean (Trans., 1900, 77,110) obtained two isomerictetrahydrofuran-2 : 5-dicarboxylic acids, which he regarded as cis- andtrans-modifications :H H H H H H H CO,HOne of these acids melted at 1%3-125', and the other, whichmelted at 93--95O, formed a hydrate melting at 63-64', but Leandid not establish which of these acids was the cis- and which the trans-var i e tp.I n a former communication (Le Sueur, Trans., 1908, 93, 716),the preparation and identification of two as-dihydroxyadipic acidsmere described, and it was shown that the as-dihydroxyadipic acidmelting at 174' is the meso-acid, and the one melting at 146' is theracemic variety. Corresponding with these two hydroxyadipic acidsare two a6-dibromoadipic acids; of these, the one melting at192-193' is the meso-acid, and the other, which melts at138-139', is the racemic acid (compare Rosenlem, Bey., 1904, 37,Now, when meso-as-dibromoadipic acid is treated with alcoholicpotash, the tetrahydrofuran-2 : 5-dicarboxylic acid obtained is the onemelting at 124-1 2 5 O , and from stereochemicsl considerations it willbe seen that this must be the &-variety :2090).H H/ H H \ / .. \ CO,H-C-C-- C-C-CO,H -\ H H /Br BrH HI3 ,6--6, HIneso-a&Dibromoadipic acid, cis-Tet~xhydrofuran-2 : 5-di-in. p. 192-193". carboxylic acid, m. p. 124;125".L\ H H /Br BrH HRaceniic a&dibromoadipiu acid,m. p. 138-139".tl.nns-Tetl.aliydroruupsn-2 : 5-di-carboxylic acid, 111.p. 93-95".It might be argued that the meso-dibromoadipic acid undersuch severe treatment as the action of boiling alcoholic potash hadundergone intramolecular change, and that the acid resulting from itwas the trans- and not the cis-form. In order to settle this point176 LE SUEUR AND HAAS:\ H H /an aqueous solution of the meso-as-dihydroxyadipic acid was heatedin a sealed tube, when the acid lost a molecule of water and gave thetetrahydrofuran-2 : 5-dicarboxylic acid meltiug a t 124-125' :meso-as-Dihydrosyadipic acid, cis-Tetrahydrofuran-2 : 5-di-m. p. 174". carbosylic acid,ni. p. 1%4-125".Finally, if the furan acid melting a t 124-125" is really the cis-acid, then it should form an anhydride, whereas the trans-acidwould not.I n order to investigate this point, the acid melting at124-125O was boiled for several hours with an excess of acetylchloride, when an anhydride, C6HG04, was obtained. This anhydride,on treatment with water, readily regenerated the acid melting at134--125O, which proves conclusively that the acetyl chloride has notcaused an intramolecular change, and that the anhydride reallycorresponds with the tetrahydrof uran-2 ; 5-dicarboxylic acid meltingat 124-125', which latter acid must therefore be regarded as the cis-modification.It is interesting t o note that the above anhydride is ieomeric withthe dilactone obtained by heating racemic as-dihydroxyadipic acid(Trans., 1908, 93, 721). Both the anhydride and the dilactone areformed by the l o ~ s of two molecules of water from their respectivedihydroxyadipic acids, the former being formed in two stages : (1) theloss of a molecule of water from two hydroxyl groups ; (2) the loss ofH H HI I HO* &CO,H -c*co---- Iy 2 1 2 -- heatedHO*C*CO,HI IH H Hliieso-a&Dihydrosy- cis-Tetrahydrofuran-2 : 5-di- Anhydride,ndipic acid.carboxylic acid. m. 1). 128-129".H HICO,H*&*OH IXeatedalone 1--Co*c- I I-+ 0 [CH,], 0 __- If--I--- b* CO--( Watery 2 1 2li €!IHO*C-CO,HRscemic as-dihydroxy- Dilactone,adipic acid. m. p. 134"FORMATION OF HETEROCYCLIC COMPOUNDS. PART 11. 177a second molecule of water from two carboxyl groups, whereas thedilactone is formed by the loss of two molecules of water, eachmolecule of water arising from one hydroxyl group and one carboxylgroup.Ex P ERIMENT A L.Action of Diethylaniline on Ethyl a6-Di6romoadipccte.Ten grams of ethyl as-dibromoadipate (m.p. 66') and 16 grams ofrecently distilled diethylaniline were placed together in a flask attachedto a reflux air condenser and containing a thermometer, the upper endof the condenser being connected to a U-tube immersed in a freezingmixture. The flask and contents were gradually heated to lSO', atwhich temperature the reaction began, and were maintained at185-195' for three hours. During the heating a volatile liquid wasevolved, and was condensed in the U-tube; the total amount of esterheated in this manner was 80 grams.The volatile liquid, after being dried, weighed 15 grams, and boiledat 3S-38-5O :0.1514 gave 0 3644 AgBr.Br = 72-87,The liquid was therefore ethyl bromide, the boiling point of whichis 38.37'.The contents of the flask partly solidified on cooling, and mere addedto dilute hydrochloric acid and the whole extracted with ether; theethereal solution was washSd, dried, and evaporated, and the residuedistilled under 29 mm. pressure :165-185 "... ............ 11 *5 grams 230-255" ............... 11.0 gramsThe fraction b. p. 165-185' slowly deposited long, flat crystals,which, after filtration and drying, weighed 3.3 grams, and, aftercrystallisstion from light petroleum (b. p. 40-60°), melted at 63-64',and consisted of ethyl muconate, the melting point of which is quotedas 63-64" by Ruhemann and Blackman (Trans., 1890, 57, 374) :C=60.31 ; H=7.24.C,H5Br requires Br = '73.39 per cent.210-22s ...............3 -0 ) ) 1 Undistilled resid tic?... 13.5 ,,0,1760 gave 0.3892 CO, and 0.1148 H,O.C,,H1,O, requires C = 60.60 ; H = 7.07 per cent.The fraction b. p. 230-255' consisted for the most part of ethyl1-phenylpyrrolidine-2 : 5-dicarboxylate, as was shown by the fact thatit yielded I-phenylpgrrolidine-2 : 5-dicarboxylic acid on hydrolysiswith 10 per cent. alcoholic potash. The acid which was precipitatedon acidifying the hydrolysed product with hydrochloric acid was crys-tallised from a mixture of acetone and light petroleum, from which i tseparated in oblong plates, which decomposed with evolution of gas a t249'. A mixture of equal parts of this substance and I-phenyl-VOL.XCVII. 178 LE SUEUR AND HAAS:pyrrolidine-2 : 5-dicarboxylic acid (Trans., 1909, 95, 277) decomposedat the same temperature :0,1684 gave 8.6 C.C. N, (moist) a t 13' and 764 mm.C1,H,,O,N requires N = 5 -9 6 per cent.The undistilled residue consisted of a dark thick syrup, which, afterbeing kept f o r several months, showed no signs of solidifying, and fromwhich no pure substance could be isolated.N = 6.07.Action of Aniline on Methyl as-Dibromoadipute.Eighteen grams of methyl as-dibromoadipate and 18 grams ofaniline were heated together in a flask immersed in boiling water forforty hours, and the product worked up and distilled as describedunder the action of diethylaniline on ethyl as-dibromoadipate (p. 177).That portion of the distillate boiling at 225-230°/32 mm.weighed8 grams, and solidified on cooling. It was crystallised from lightpetroleum, when it was obtained in needles, which melted at 88' andhad all the properties of methyl 1-phenylpyrrolidine-2 : 5-dicarboxylate(Trans., 1909, 95, 277). A mixture of equal parts of these twosubstances melted a t 88'. When hydrolysed by boiling with 10 percent. alcoholic potash, it gave 1-phenylpyrrolidine-2 : 5-dicarboxylicacid, which decomposed and evolved gas at 252'.Action, of Monoethylaniline on Ethyl ap-Dibromosuccinate.The ethyl dibromosuccinate was prepared by heating succinic acidwith amorphous phosphorus and bromine in a sealed tube and esterify-ing the resulting bromo-acid with concentrated sulphuric acid andalcohol (Gorodetzky and Hell, Ber., 1888, 21, 1729).Twenty grams (1 mol.) of ethyl a@-dibromosuccinate and 15 grams(2 mols.) of monoethylaniline were heated together in boiling waterfor thirty-five hours ; the resulting product, which partly solidified oncooling, was extracted with much ether, and the insoluble residue ofmonoethylaniline hydrobromide filtered off.The ethereal filtrate waswell washed with water, dried, and evaporated, and the residue distilledunder 32 mm. pressure, when the whole distilled between 149' and 152'.It was re-distilled, and a portion boiling at 148-149O collected foranalysis :022125 gave Oa2981 CO, and 0*0838 H,O. C = 38.26 ; H = 4.38.0-1864 ,, 0.1400 AgBr. Br = 32.13.C,H,,O,Br requires C = 38.24 ; H = 4.38 ; Br = 31.87 per cent.The above substance is therefore ethyl monobromomaleate, theboiling point of which is given as 143O/30-40 mm.(Anschiitz, Ber,,1879, 12,2284)FORMATIOR OF HETEROCYCLIC COMPOUNDS. PART 11. 179Twenty grams of ethyl dibromosuccinate gave 11-2 grams of thepure ester, which corresponds with 74.2 per cent. of the theoretical,so that this reaction affords a very convenient method for preparingethyl mono bromomaleat e.The interaction of monoethylaniline and ethyl ap-dibromosuccinatewas tried under various conditions, such as heating together thetwo substances in alcoholic solution ; heating together a t 180--200c,but in all cases ethyl monobromomaleate mas the only substanceobtained.Action of Andine on Ethyl ap-Dihrornosuccinate.Ten grams of ethyl up-dibromosuccinate (1 mol.) and 14 grams(5 mols.) of aniline were heated together for two hours in a flaskimmersed in boiling water, The contents of the flask partly solidifiedon cooling, and were treated with a large volume of ether and thecrystalline solid collected. This solid, which consisted chiefly ofaniline hydrobromide, was treated with 80 C.C.of warm water, thesolution cooled, and the undissolved residue (0.8 gram) collected andcrystaliised from alcohol, when it was obtained in glistening needles,which melted at 149' and had all the properties of ethyl a/?-dianilino-succinate, the melting point of which is given as 150' by Gorodetzkyand Hell (Ber., 1888, 21, 1797).The ethereal filtrate, on evaporation, left a residue which showedsigns of decomposition on attempting to distil it under diminishedpressure j it was therefore not distilled, but alcohol was added to itwhen a yellow solid slowly separated.This solid was repeatedlycrystallised, first from acetone and finally from a mixture of chloro-form and light petroleum, when it was obtained i n small needlesmelting a t 230' :N== 10.29. 0.1224 gave 10.8 C.C. N, (moist) at 1 8 . 6 O and 769 mm.CI6Hl2O2N2 requires N = 10.60 per cent,This yellow solid is insoluble in ether, light petroleum, oralcohol, and moderately soluble in boiling chloroform or acetone ;it is therefore identical with the ariilinomaleic anil,obtained by Bischoff and Walden (Eoc. cit.).The yield of the above yellow solid was very small, and manyattempts were made t o increase it, but without any substantial irn-provement.Among these attempts may be mentioned : (1) additionof anhydrous sodium acetate to the mixture of ester and aniline;(2) the substitution of aniline hydrochloride for aniline; (3) theN 1130 LE SUEUR AND HAAS:interaction of the ester and aniline in alcoholic solution in the cold ;(4) the interaction of the ester and aniline in the presence ofpotassium hydroxide; (5) heating the ester and aniline at 190'.Action of Aniline on Ethyl a0-Dibromosebacate.The ethyl a6-dibromosebacate was prepared by the action of bromineon tho acid chloride of sebacic acid, and esterification of the resultingbromo-acid chloride by the interaction of this substance and alcohol.Twenty grams (1 mol.) of ethyl a6-dibromosebacate and 20 grams(4 mols.) of recently distilled aniline were heated together for elevenhours in a flask immersed in boiling water.The resulting solid wastriturated with dilute hydrochloric acid, and the undissolved solid(4.5 grams) collected and washed with water. The hydrochloric acidsolution was diluted with a large volume of water, when a solid wasprecipitated ; the whole was extracted with ether, the ethereal solu-tion washed, dried, and evaporated, when 12.5 grams of solid residuewere obtained. This was added to the above 4.5 grams of undissoivedresidue, and recrystallised from alcohol untoil the melting point wasconstant :0.1304 gave 7.5 C.C.N, (moist) at 18.5' and 756 mm.Ethyl ae-dianilinosebacate,N = 6.58.C,,H&,N, requires N = 6.36 per cent.C0,Et *CH( NHPh)*[CH,],-CH( NHPh) CO,Et,melts at 119*5-120*5°, and crystallises from alcohol in fern-likeaggregates. It is insoluble in water, sparingly soluble in ether,alcohol, or light petroleum, and readily so in chloroform, benzene, oracetone.The alcoholic mother liquors from which the above ester hadcrystallised gave a substance which, after recrystallisation, melted at94-100', and on analysis gave the following results :0.1680 gave 0.4378 CO, and 0.1342 H,O. C = 71-07 ; H = 8.87.0.1734 ,, 9.7 C.C. W, (moist) at 16' and 764 mm. N=6.55.C,6H,,0,N, requires C = 70-90 ; H = 8.18 ; N = 6.36 per cent.This substance is therefore in all probability stereoisomeric wittithe ethyl ad-dianilinosebacnte melting at 1 19*5-120*5°, butrepeated recrystallisation failed to give a substance with a definitemelting point.a0-Dianilinosebc6cic Acid.-Thirty-three grams of ethyl a0-dia nilino-sebacate were added to a solution of 20 grams of potassium hydroxidein 150 C.C.of alcohol containing a few C.C. of water, and the wholeboiled for fire hours. The resulting solution was concentrated to halfits volume, and gradually added to a boiling solution of 25 C.C. conFORMATION OF HETEROCYCLIC COMPOUNDS. PART 11. 181centrated sulphuric acid in 125 C.C. of water, when the anilino-acidwas precipitated in a granular form. If the precipitation is carriedout in the cold, then the acid separates in an amorphous form, inwhich condition it is difficult to manipulate. The acid was collected,washed with water, dried, and boiled with SO C.C. of alcohol in orderto remove any non-hydrolysed ester, filtered, and after drying weighed23 grams.It was crystallised from amyl alcohol, from which itseparated in spherical aggregates of small needles, which melt andevolve gas at 210-213O :0.1254 gave 0.3180 CO, and 0.0868 H,O. C = 69.15 ; H = 7-69.0.1707 ,, 10-6 C.C. N, (moist) at 18' and 765 mm. N= 7.21.C,,H,,O,W, requires C = 68.75 ; H = 7-29 ; N = 7.29 per cent.a0-Dictnnilinosebacic acid,CO,H*CH(NHPh)* [ CH21,* CH( NHPh)*CO,H,is insoluble in water, alcohol, ether, chloroform, light petroleum,benzene, or ethyl acetate, and only sparingly soluble in boiling amylalcohol.The silver salt was obtained as a white precipitate on adding asolution of the sodium salt of the acid to a solution of silver nitrate ;it darkened somewhat readily on drying :0*1510 gave 0.0536 Ag.Methyl a0-dianilinose bacate,Ag= 35.5.c22E2604N2Ag2 requires Ag = 36.1 per cent.CO,Me*CH(NHPh)*[ CH,],*CH(NHPh)*CO,Me,wa0 prepared by the interaction of aniline and methyl at9-dibromo-sebacate, as described for the preparation of the corresponding ethylester.It is insoluble in water, ether, or light petroleum, readilysoluble in benzene or chloroform, and crystallises from alcohol, inwhich it is sparingly soluble, in fern-like aggregates of needles meltinga t 133-136':0.1334 gave '7.9 C.C. N, (moist) a t 19' and 768 rnm.C24H3204N2 requires N = 6.79 per cent.N = 6-88.Action of Alcoholic Potassium Hydroxide on meso-a8-Dib~omoadipicAcid.The meso-a8-dibromoadipic acid was separated from the mixture ofracemic and meso-a8-dibromoadipic acids obtained by the action ofbromine on the acid chloride of adipic acid (Trans., 1908, 93, 718) hyextracting the mixed acids with water and crystallising the insolubleresidue of the meso-acid from formic acid until its melting point wasconstant (Rosenlew, Ber., 1904, 37, 2090).Seven and a-half grams of meso-as-dibromoadipic acid (m.p182 LE SUEUR AND HAAS:192-193O) were dissolved in 15 C.C. of hot alcohol, and the hot solu-tion gradually added to a boiling solution of 10.5 grams of potassiumhydroxide in 60 C.C.of alcohol, A vigorous reaction immediately set in,and the mixture was boiled on the water-bath for fifteen minutes,then allowed to cool, and filtered (filtrate = A). The insoluble residuewas dissolved in 15 C.C. of water, the solution strongly acidified withconcentrated hydrochloric acid, and, after some time, a crystallineprecipitate separated ; this was collected and dissolved in dilutepotassium hydroxide solution, and again precipitated by hydrochloricacid, when it was obtained in a crystalline form. The substance hadall the properties of muconic acid, and decomposed without meltingat 272' :0.1608 gave 0.2966 CO, and 0.0678 H,O.C,H,O, requires C ;= 50.70 ; H = 4.22 per cent.The aqueous filtrate from the muconic acid was evaporated to asmall bulk, and repeatedly extracted with a large volume of ether.The ethereal solution was evaporated without previous washing ordrying, and the residue dried and crystallised from a mixture of ethylacetate and light petroleum, when it was obtained in nodularaggregates melting at 124-125' :C= 50.30; H = 4-68.0.1434 gave 0.2344 CO, and 0.0684 H,O.C,H,05 requires C = 45.00 ; H = 5.00 per cent.The molecular weight was determined by dissolving the acid inwater and titrating with N/10-sodium hydroxide, using phenolphthaleinas indicator :0.2040 required 25.6 C.C.N/lO-NaOH, which corresponds with aC = 44-58 ; H = 5.30.dibasic acid of M.W. = 159.4.A dibasic acid, C6Hs05, requires M.W. = 160.The substance is therefore cis-tetrahydrofuran-2 : 5-dicarboxylicacid,H HCO,H C0,HIt readily chars when heated above its melting point, and itssolubilities in various solvents correspond exactly with those of thetetrahydrofuran-2 : 5-dicarboxylic acid melting a t 123-1 25" obtainedby Lean (Zoc.cit.).The alcoholic filtrate A (see above) was saturated with carbondioxide, and the precipitated potassium hydrogen carbonate collected.The filtrate was evaporated to dryness, the residue dissolved in a verFORMATION OF HETEROCYCLIC COMPOUNDS. PART 11. 183emall quantity of water, and the resulting solution acidified withhydrochloric acid and repeatedly extracted with a large volume of ether.The ethereal solution on evaporation left a small residue, which, aftercrystallisation from ethyl acetate and light petroleum, melted at 1'74'and had all the properties of meso-ai3-dihydroxyadipic acid (Trans,,1908, 93, 723).The aqueous mother liquors from the ether extracts were mixedand evaporated to dryness ; the residue obtained was dried, extractedwith alcohol, and ths alcoholic solution evaporated and the residuecrystallised from ethyl acetate and light petroleum, when a furthersmall quantity of the tetrahydrofuran acid melting at 124-125Owas obtained.The amount of tetrahydrofuran acid obtained corresponded with28 per cent.of the theoretical, and the yield of muconic acid was only14 per cent. of the theoretical.The anirnonium salt was prepared by dissolving the acid in alcoholand saturating the solution with ammonia, when the salt was pre-cipitated ; it was collected, and crystallised by dissolving in a smallquantity of water and adding alcohol and ether, when it separatedout in long, transparent prisms.It is readily soluble in water,sparingly so in alcohol, and insoluble in ether :0.1231, boiled with NaOH, gave 0.0213 NH,. N= 14.24.C,H60,(NH,), requires N = 14.43 per cent.Anhydride of cis-Tetrahydrofuran-2 : 5-dicnrboxylic Acid.Twenty grams of acetyl chloride and 2.8 grams of cis-tetrahydro-furan-2 : 5-dicarboxylic acid were boiled together for sixteen hours ina flask attached to a reflux condenser. The acetyl chloride wasremoved by evaporation in a vacuum over 50 per cent. potassiumhydroxide solution, and the resulting solid spread on a porous plate,when 2.5 grams of solid, melting at 97-105', were obtained, This,on extraction with 15 C.C.of dry chloroform, left 1.5 grams of residuewhich melted at 122O, and consisted of the unchanged acid. Thechloroform extract, on evaporation in a vacuum, gave 0.6 gram of asolid, which was crystallised from dry chloroform and light petroleum,when it was obtained in slender needles :0.1022 gave 0.1876 C 0 2 and 0,0414 H,O.The anhydride of cis-tetrahydrof uran-2 : 5-dicarboxglic acid,C = 50.1 ; H = 4.5.C6H60, requires C=50*7 ; H=4.2 per cent.readily volatilises when heated, even on the water-bath, and yields a1% FORMATION OF HETEROCYCLIC COMPOUNDS. PART 11.sublimate of long needles, which melt a t 128-129'. It is readilysoluble in ethyl acetate, cbloroforrn, ether, or acetone in the cold, andis insoluble in light petroleum.It slowly dissolves in cold water,giving a strongly acid solution, which on evaporation gives the;original cis-tetrahydrofuran-2 : 5 - dicarboxylic acid melting at124-125'. When the anhydride is heated with resorcinol and afew drops of sulphuric acid, and the product poured into a solution ofpotassium hydroxide, a green, fluorescent solution is obtained.cis-Tetrahydrof wan-2 : 5-dicarbox yldiani Zide,>o, yH,*CH( CO*NHPh)CH,*CH( CO*NHPh)mas prepared by boiling the acid (0.2 gram) with a large excess ofaniline (2 grams) for seven hours. The product mas poured intodilute hydrochloric acid, and the precipitated solid collected, dissolvedin alcohol, and the solution decolorised by animal charcoal.The solidwhich separated out on cooling was crystallised from alcohol, when itwas obtained in small, thick plates, melting and decomposing at208-2099 The dianilide is readily soluble in acetone or chloroformin the cold, sparingly soluble in hot benzene or cold alcohol, andinsoluble in water :N-9.51. 0.1176 gave 9.4 C.C. N, (moist) at 12O and 766 mm.CI8H,,O,N2 requires N = 9.03 per cent.Pormation of cis-Tetrahydrofuran-2 : 5-dicarbozylic Acid frommeso-as-Dihydroxyadipic Acid.One gram of meso-as-dihydroxyadipic acid (m. p. 174O), obtained byhydrolysis of the meso-as-dibromoadipic acid melting at 192-193O(Trans., 1908, 93, 719), was dissolved in 5 C.C. of water, and thesolution heated in a sealed tube for three hours at 200O. The solutionwas filtered to remove a small quantity of black solid, and the filtraterepeatedly extracted with a large volume of ether. The etherealsolution on evaporation left 0.2 gram of solid which, after dryingand crystallisation from ethyl acetate and light petroleum, melted at124-1 25O ; this melting point was unaltered by mixing the substancewith an equal quantity of cis-tetrahydrofuran-2 : 5-dicarboxylic acid.The substance readily charred when heated above its melting point,and its solubilities in various solvents were identical with those of thecis-furan acid.Action of AZcohoZic Potassium Iiydroxide on Racemicas- Dibromoadipic AcidThe action of alcoholic potassium hydroxide on the racemic as-dibromoadipic acid (m. p. 138-1 39') was investigated in the hopTHE HALF-LIFE PERIOD OF RADIUM; A CORRECTION. 185of obtaining the t~ans-tetrahydrofuran-~ : 5-dicarboxylic acid. Themethod of procedure was exactly as described for the action ofalcoholic potassium hydroxide on the meso-dibromoadipic acid, andmuconic acid and a trace of the cis-tetrahydrofuran acid were obtained,together with a small quantity of residue which could not be crystal-lised. No such residue was obtained from the action of alcoholicpotassium hydroxide on the meso-dibromoadipic acid, and i t is notimprobable that this residue did contain some of the trctns-tetrahydro-furan acid, which, on account of its solubility and reluctance tocrystallise (Lean, Zoc. cit.), could not be isolated.CHEMICAL LABORATORY,ST. THOMAS’S HOSPITAL,LONDON, S.E

ISSN:0368-1645    

DOI:10.1039/CT9109700173

出版商:RSC    

年代:1910

数据来源: RSC