摘要:

280 HOMER AND PURVIS: THE ABSORPTION SPECTRA OFXX1X.-The A bsorption Spectra of Naphthalene andof Tetrame t h y lnaph t ha1 ene.BY ANNIE HOMER and JOHN EDWARD PURVIS.IN a paper on the absorption spectra of the hydrocarbons isolatedfrom the products of the action of aluminium chloride on naphthalene(Homer and Purvis, Trans., 1908, 93, 1319), we described theabsorption spectrum of a substance having the empirical formulaC14H,,. From chemical con5iderations it had been suggested that* Air-dried. t Dried at 100NAPHTHALENE AND OF TETRAMETHYLNAPHTHALENE. 281this hydrocarbon was an alkyl, probably a tetramethyl, derivative ofnaphthalene, and it was thought that a comparison of the absorptionspectrum of this hydrocarbon with that of naphthalene would furnishadditional evidence as to its constitution.Hartley, in his earlier work (Trans., 1881, 29, 1531, showed thatthe absorption spectrum oE naphthalene was characterised by fourbands in the ultraviolet region of the spectrum.In a later paper,Hartley (Trans,, 1886, 47, 685) showed that there were four bands,the positions of which differed from those of the earlier observations.The method employed by Hartley differed from that used by us, anddescribed in the previous paper (Zoc. cit.). For purposes of comparisonit was necessary for us to study the absorption spectrum of naphths-lene under the same experimental conditions as those employed in thestudy of the hydrocarbons under investigation. Our results showedthat for N/LOOO-solutions in alcohol, the absorption curve fornaphthalene, as observed by Hartley in his first paper, showed fourcharacteristic bands.The mean oscillation frequencies of thesebands did not coincide with those given by Hartley, but we did notcomment on the discrepancies at the time of our previous work.The curve for N/lOOO-solutions of the hydrocarbon Cl4H1, alsoshowed four bands, similar in character to the naphthalene bands,although less persistent and further shifted towards the red end ofthe spectrum (Fig. 1).The mean oscillation frequencies of the bands were :For naphthalene, Hartley, first paper ...... 3508 3690 3840 392139 second paper ... 3211 3273 3369 3849previously published).. 3500 3620 3765 3900For CI4Hl6, Homer and Purvis ............... 3434 3562 3680 3776From these results we concluded that the substance C14H16 wasprobably tetramethylnaphthalene, as had been previously suggested(Homer, Trans., 1907, 91, 1103).Since the publication of these results, Baly and Tuck (Trans.,1908, 93, 1902), in their work on the absorption spectra of aromatichydrocarbons,jhave shown that for naphthalene thereare three character-istic bands having mean oscillation frequencies : 1/h = 3125, 1/X = 3220,and 1/X=3700.The bands 1/X 3125 and I/h 3220 only appearin strong solutions or in proportionately greater thicknesses of dilutesolutions. The band 1/A 3700 is a broad band, and corresponds withthe four bands observed by Hartley in his first paper (Trans., 1881,39, 153) and also by us.After reading Baly and Tuck’s paper, it seemed necessary for us tore-examine the absorption spectrum of the hydrocarbon C,,H1,.Forif, as we had previously surmised, the hydrocarbon C14H16 is a tetra-BS Homer and Purvis (no282 HOMER AND PURVIS: THE ABSORPTION SPECTRA OFmethyl derivative of naphtbalene, there should be indications of bandscorresponding with the naphthalene bands, 1/A 3125 and l / A 3230,observed by Baly and Tuck. The absence of such bands would, accord-ing to these observers, point to a difference between the constitutionof naphthalene and of the hydrocarbon C,,H,,.At the time of our previous experiments we had only suf3ticient ofthe hydrocarbon with which to make a N/lOOO-solution. This strengthwas compared with a similar N/lOOO-solution of naphthalene, Thesesolutions gave the four bands already described, and correspondingwith the broad band, 1 / A 3700, of Baly and Tuck.Since then theFIG. 1.Oscillation frequencies.33 34 35 36 37 38 39 40 41 42Full curve : N/lOOO-solution of naphthalene in alcohol.Dash ,, : N/lOOO-solution of CI4H,, in alcohol.hydrocarbon has been made in larger quantity, and we have been ableto compare its iVj’10-solution with a similar solution of naphthalene.The results have been plotted in the accompanying curves (Fig. 2).It will be seen from a glance a t the curves, that for N/lO-solutionof naphthalene there are two bands similar to those obtained byBaly and Tuck. The curve for the hydrocarbon C14H16 also showstwo similar bands, less persistent and further shifted towards thered end of the spectrum than the naphthalene bands.The mean oscillation frequencies of the bands are :Naphthalene, Baly and Tuck ........., .... ... ... ... .. . 3125 3220), N/10-solution, Homer and Purvis ... 3122 3225C14Hlsr N/lO-solution, $ 9 3 ) 9 9 * * I 2638 277NAPHTHALENE AND OF TETRAMETHYLNAPHTHALENE. 283The results of our investigation may be summarised as follows :I. The absorption curves for both N/lOOO- and N/lO-solutions ofthe hydrocarbon CI,HI6 are similar to the curves for naphthaleneThese results are in accordance with our previous suggestion thatthe substance is a tetramethyl derivative of naphthalene.11. Our experiments confirm the observation of Bnly and TuckFIG. 2.Oscillation frequencies.26 28 30 32 34 36Fnll curve : N/IO-solution 04 naphthalene i n clkohol.Dash ,, : N/lO-soZution of C14H,, in alcohol.with regard to the preqence of bands corresponding with l / X 3125and l / h 3220 in naphthalene and its derivative.111. Hartley in his first paper represented the naphthalene curvefor dilute solutions as being characterised by the presence of fournarrow bands. Baly and Tuck from their results consider that thereis only one broad band, 1/X 3700, which corresponds with Hartley’284 BARGER AND EWINS:four bands. The curves obtained by us for N/lOOO-solutions ofnaphthalene, and of its derivative, CI4Hl6, shows four narrowbands. These observations wpport Hartley’s first interpretation ofthe absorption curve of naphthalene.UNIVERSITY CHEMICAL LABORATOKY,CAMBRIDGE

ISSN:0368-1645    

DOI:10.1039/CT9109700280

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

284 BARGER AND EWINS:XXX.-The Alkaloids of Brgot. Part 1%By GEORGE BARGER and ARTHUR JAMES EWINS.IN a previous communication on this subject (Trans., 1907, 91,337), oue of us, in conjunction with F. H. Carr, described thenew amorphous alkaloid ergotoxine, C,,H,,O,N,, and assigned t oTanret’s crystalline ergotinine the formula C,H,,O,N,. Thecrystalline alkaloid was thus proved to be the anhydride of theamorphous one, as was first surmised by Kraft.*The transformation of ergotoxine into ergotinine takes place byboiling with methyl alcohol (Kraft), or with acetic anhydride.When, on the other hand, ergotinine was warmed on the water-bath with very dilute phosphoric acid, Barger and Carr obtainedfrom it the crystalline phosphate of an amorphous base, whichclosely resembled ergotoxine phosphate in physiological action andhad the same melting point; the crystalline form was, however,entirely different. Ergotoxine phosphate crystallises in thin needles(Fig.2), the new phosphate formed rhomb-shaped, triangular, orhexagonal plates (Fig. l), and the difference persisted after thebases had been liberated, dissolved in ether, and again convertedinto their phosphates by precipitation with alcoholic phosphoricacid.We have now found the cause of this difference between the twosalts. When ergotinine is heated with a solution of phosphoricacid in ethyl alcohol, there is formed, not ergotoxine phosphate,but the phosphate of ergotoxine ethyl ester, and it is the lattersalt which crystallises in plates.The hydrochlorides of the twobases are also quite different (Figs. 3 and 4). That the new base* The identity of Kraft’s hydroergotinine (Arch. Pharm., 1906, 244, 336) withergotoxine was recently doubted by Vahlen (Arch. e q . Path. Phnrm., 1908, 60, 42)on physiological grounds, but an analysis of hydroergotinine sulphate by Kraft(Arch. Pharm. , 1907, 245, 644) and a comparative physiological examination byDale (Arch. exp. Path. Phnmt., 1909, 61, 113) leave no doubt that hydroergotinineand ergotoxine are synonymous termsTHE ALKALOIDS OF ERGOT. PART 11. 285is an ethyl ester was shown by analysis, and especially by a deter-mination of the ethoxy-group by Zeisel’s method.It thus follows that ergotoxine contains a carboxyl group, andthat ergotinine is its lactone (or lactam).I n accordance with thisview, ergotoxine is soluble in sodium hydroxide, but ergotinine isnot, nor is the ester-base above referred to. Esterification probablytakes place to some extent when ergotoxine is boiled with alcohol(in the absence of phosphoric acid). We have noticed repeatedlyin converting ergotoxine into ergotinine by boiling with methylalcohol (Kraft’s method) that the yield is far from quantitative;some of the ergotoxine is probably converted by this process intothe very soluble ethyl ester, instead of the crystalline anhydride. Itis, moreover, quite likely that ergotinine itself when boiled withalcohol forms ergotoxine ester to some extent; this behaviour wouldexplain the loss of ergotoxine on recrystallisation which we our-selves and others (Tanret, Meulenhoff) have noticed.The fall inoptical rotatic n shown by alcoholic ergotinine solutions, especiallyon boiling, is also probably due t o the formation of an ergotoxineester.Besides proving the presence of a carboxyl group in ergotoxine,we have been able to establish the presence of a somewhat largerand more characteristic fragment of the complicated molecule ofthe ergot alkaloids. On destructive distillation, both ergotoxine andergotinine yield a small quantity of a crystalline substance, andthis we have been able to identify as isobutyrylformamide,CHMe,*CO*CO*NH,. The yield of this substance is only 5 percent. of the (very costly) alkaloid employed; as we had only afew decigrams of the substance a t our disposal, its identificationwas somewhat troublesome, but was finally rendered certain bydirect comparison with a specimen of isobutyrylformamide syn-thesised for the purpose.A ketonic amide of this type does not appear to have beenpreviously obtained from a natural substance, and we are unableto suggest the mechanism of its formation from the ergot alkaloids.We do not think, however, that either of the oxygen atoms of theamide belongs t o the carboxyl group which we have shown to bepresent in ergotoxine.If this be admitted, we have accounted forfour out of the six oxygen atoms of that alkaloid (or three out ofthe five present in ergotinine). The two remaining oxygen atomsare not present as phenolic hydroxy- or methoxy-groups, becauseergotinine is insoluble in sodium hydroxide, and when examinedby Zeisel’s method yields a negative result.One of the nitrogenatoms probably has a methyl group attached to it, because some286 BARGER AND EWINS:thing like one equivalent of methyl iodide is set free whenergotinine is examined by Herzig and Meyer's method. At leastone of the five nitrogen atoms is tertiary, for a methiodide is slowlyformed. It is remarkable that, in spite of having five nitrogenatoms, the ergot alkaloids are only very feeble mono-acid bases.EXPERIMENTAL.Phosphate of Ergot oxine E't hyl Ester, C34H4004N5* C0,*C,H5,H3P0,.One gram of crystalline ergotinine was suspended in 10 C.C. ofabsolute ethyl alcohor; and 1.1 equivalent of phosphoric acid dis-solved in 5 c .~ . of alcohol was added. On warming on the water-bath for fifteen to thirty minutes, the ergotinine gradually dis-solved ; on cooling, an amorphous solid separated, which witscollected' and crystallised from 90-95 per cent. ethyl alcohol. Inthis way about 0.3 gram of a grey product was obtained, whichFIG. 1. FIG. 2.UPhosphate of ergotoxine ethyl ester. Ergotoxine phosphate.x 65 diameters. x 65 diameters.on recrystallisation from 1 2 C.C. of 95 per cent. alcohol separatedin almost white leaflets (Fig. 2), melting at 187-1880 (bath pre-viously heated to 180°). For the sake of comparison the crystallineform of ergotoxine phosphate is shown in Fig. 2. These and theother figures were drawn from micro-photographs :0.1353 gave 0.2922 CO, and 0*0812 H,O. C = 58.9 ; H = 6.4.C37H450,N,,H3P0, requires C = 58.9 ; H = 6.4 per cent.C3,H,,06N5,H3P.04 ,, C = 57.9 ; H = 6.1 ,,As the phosphate of an ethyl ester of ergotoxine contains only1 per cent,.more carbon than that of the corresponding ergotoxinesalt, a direct deterinination of the ethoxy-group was made by Zeisel'smethod THE ALKALOIDS OF ERGOT. PART 11. 2870.3503 gave 0.1064 AgI.C34H4,0,N,*C02Et,H,P04 requires OEt = 5-97 per cent.The rotation of this salt was also determined in 75 per cent.alcohol. Z = 1 dcni.; c=2*03; ctD + 1 . 5 8 O ; [a], +77*8O. From thephosphate obtained in the manner described, the base was set freeby sodium carbonate, dissolved in ether, and dried with sodiumsulphate.From the ethereal solution of the base obtained in thisway, the hydrochloride and the oxalate were precipitated by addingalcoholic hydrochloric acid and ethereal oxalic acid solutions respec-tively.OEt =5.82.Hydrochloride of Ergo toxine Etlql Ester, C3,H4,0,N,,HC1.The precipitated salt crystallised from 90 per cent. alcohol inlarge plates (Fig. 3), which melted at 206-207° (bath previouslyheated to 190.). For the sake of comparison, crystals of ergotoxinehydrochloride (m. p. ZO5O) are shown in Fig. 4.*The difference in crystalline form existing between salts ofergotoxine and the corresponding salts of the ethyl ester is alsoclearly shown is the case of the oxalates formed by adding anFIG. 3. FIG. 4.Hydrochloride of ernotoxine ethyl ester.x 65 &meters.Ergotoxinc hydrochloride.x 65 diameters.ethereal solution of oxalic acid to the bases dissolved in ether.Both salts melt a t 179-180°, but whereas the ergotoxine oxalateforms elongated, rectangular prisms, the salt of the ester crystallisesin hexagonal leaflets.By warming ergotinine with a solution of phosphoric acid inmethyl alcohol, crystalline salts of ergotoxine methyl ester arereadily obtainable.As in the case of the ethyl ester, this base is* I n the previous paper (Trans., 1907, 81, 350) it was stated that ergotoxine hgdro-chloride forms ‘‘ diamond-shaped plates and very thin and very long, square-endedneedles. ” The plates, however, were an adinixtnre of the hydrochloride of ergotoxineethyl ester288 RARGER AND EWINS:amorphous, thus resembling ergotoxine ; the ester bases differ,however, from ergotoxine in being insoluble in dilute sodiumhydroxide.Salts of Ergotoxine.In addition to the phosphate, the hydrochloride, and the twooxalates of ergotoxine, which were described in the earlier paper,several other salts have been obtained crystalline.They wereprepared in each case by adding a dilute ethereal or alcoholicsolution of the acid to a solution of ergotoxine in ether, until nofurther precipitate wa-s formed. The precipitated salt wz19 driedin a vacuum, and crystallised from warm 90 to 95 per cent. alcohol.Not infrequently the salt separates as a jelly on cooling; in suchcases it is best to dilute the solution, so that nothing separates oncooling, and then to add a few drops of dry ether at intervals.Ergotoxine picrate forms pale yellow, acicular prisms, meltingat 214-215O (bath first heated t o 210O):0.1536 gave 17.2 C.C.N2 (moist) a t 10'5O and 757 mm.Ergotoxine hydrobromide, acicular prisms, melting at 208O :0.1042 gave 0.0260 AgBr. Br=10'6.Ergotoxine sulphate, prisms, melting at 197O :0.1192 gave 0.0358 BaSO,.This appears to be a somewhat impure acid sulphate; thatErgotoxime nitrate forms short, broad prisms, melting atN=13*2.C&&,O6N&6H&&Ns requires N = 13.1 per cent.C,H,,O,N,,HBr requires Br = 11.3 per cent.H,SO,= 12.6.C3,H4,O6N,,H,80, requires H,SO, = 13.5 per cent.prepared by Kraft was the normal one.193-194'.Action of Methyl Iodide o n Ergotinine, Ergotoxine, and ErgotoxineEsters.Ergotinine and allied Gases appear to have one tertiary nitrogenatom.Ergotinine dissolves readily in methyl iodide, but when thesolution is left at the laboratory temperature for some days, it isgradually transformed into a white jelly, readily soluble in alcohol;this jelly doubtless represents the methiodide. Ergotoxine and itsesters behave in a similar way, except that the reaction is morerapid. In no case, however, could a crystalline product be isolated.We give as an example the analysis of the precipitate formed ina solution of ergotoxine methyl ester in methyl iodide; the sub-stance, presumably the methiodide, was washed with dry ether anddried a t loooTHE ALKALOIDS OF ERGOT. PART 11.2890.1300 gave 0.0365 AgI. I= 15.2.C36H4,0,N,,CH31 requires I = 16.2 per cent.Action of Absolute 9Zcohol on Ergotinine.A sohtion of 0.24 gram of crystalline ergotinine in 100 C.C. ofabsolute ethyl alcohol was divided into two portions. A 2-2-dcm.polarimeter tube was filled with one portion of the solution, andkept in the dark at the laboratory temperature for some months.During this time the rotation gradualy decreased,, as shown by thefollowing table :a,. 1. [a],.June 11 th + 1 *76" 2'2 clcm. + 333"June 12th f 1 . 7 1 2.2 2 2 + 324June 14th + l - 6 6 2.2 2 ) + 314June 17th +1%1 2.2 > s + 305July 19th + 1'52 2'2 J > + 290June 28th + 1-61 2-52 2 2 + 305Sept. 13th + 0'62 1 2 ) -!- 258The other portion was heated under a reflux condenser on thewater-bath ; here the change was more rapid :Time in hours.a D .0 +1*76"1 + 1-594 + 1 '41 a+ + 0'67154 + o-al23 + 0'5930 + 0.4837 + 0.371. [ale-2.2 dcm. + 333"2 2 2 + 3312 2 9 + 2942 1) + 2751 2 t + 2541 1 ) + 2461 2 ) + 2001 ? ) + 154In boiling alcoha,,.: solution t-e c .ange is even more rapid. Asaturated solution prepared by shaking a t loo gave:Z=2*2 dcm.; ~=0*2566; aD+1*9l0; [ u ] ~ +338O.After boiling for five minutes, [a], fell to 3 2 7 O , after one hourCrystals of ergotinine, obtained by rapidly cooling a boilingto 300°, after three hours to 2 4 2 O .alcoholic solution, are shown below :FIG. 5.VOL. XCVII.Ergotinine. x 65 diameters..290 EARCIER AND EWINS:Isolation of iEjoButyryIforrnarnide on Destructhe Distillation.of theErgot AIkaloas.The formation of a crystalline sublimate can be observed bycarefully heating a few milligrams of ergotinine or ergotoxine init small tube. The alkaloids melt and decompose, and a minutequantity of a colourless liquid appears in the cold part of the tube;this soon crystallises, and if the operation is carried out underdiminished pressure the substance appears a t once in glisteningleaflets.It was soon found that the substance, once set free, sublimes a tlooo, and cannot be recrystallised from organic solvents withoutgreat loss. I t s purification was therefore carried out by sub-limation under diminished pressure.Ergotinine (in some cases ergotoxine) was heated in quantities of0.5 gram a t a time in a flask of 6-10 C.C.capacity, which was pro-vided with a neck 25 cm. long and 1 cm. wide. Almost the whole ofthe bulb could be immersed in a metal-bath at 220-240O; the lowerpart of the neck, adjoining the bulb, was jacketed with steam, andthe flask was evacuated to 2 mm. pressure. By this means thecrystalline sublimate collected only on the upper part of the neck,above the steam-jacket. It wits contaminated with a little yellowoil, and was purified as follows. The region of the tube wherethe sublimate had condensed was cut off, placed in it test-tube, andthe substance re-sublimed in a boiling water-bath under a pressureof 15 to 20 mm.; it condensed on the upper portion of the test-tube,from which it was removed by means of a glass rod.In this way0.09 gram of pure sublimate was obtained from the base from3 grams of somewhat impure exgotoxine phosphate ; in anotherexperiment, 0.5 gram of pure ergotinine yielded 0.021 gram ofsublimate, or 4.2 per cent.As thus obtained, the substance formed thin, large, glisteningleaflets, melting in a sealed tube a t logo, readily soluble in coldalcohol, but only sparingly so in cold water and in benzene:0.0467 gave 0.0881 CO, and 0.0325 H,O.0.0860 ,, 8.8 C.C. N, (moist) at 19O and 767 Rim. N=12*0.C,H,O,N requires C = 52.1 ; H = 7.8 ; N = 12.2 per cent,The vapour-density was determined by Victor Meyer's method :0.091.3 gave 22-05 C.C. moist air at 17O and 762 mm.C,H,O,N= 115 requires V.D. =57.5.Although the percentage of carbon found is rather low, theAt first we foundC = 51.1 ; H = 7.4.0.1034 ,, 0.1946 CO, ,, 0.0756 H2O. C=51.3; H=8.1.V.D.=53.formula C,HDO,N is established with certaintyTHE ALKALOIDS OF ERGOT. PART 11. 291several per cent. too much nitrogen, until we employed cuprouschloride (compare Haas, Trans., 1906, 89, 570). The same difficultywas experienced by Barger and Carr in determining the nitrogenin ergotinine (Trans., 1907, 91, 343, footnote), and is apparentlydue to the presence of a gem-dimethyl group, resulting in theformation of methane. We have now actually located this dimethylgroup in isobutyrylformamide, where, on analysis by Dumas'smethod, unless cuprous chloride or lead chromate is used, it producesa much larger error than when accompanied by the rest of themolecule in ergotinine.Some of this methane probably alsoescaped combustion in the carbon and hydrogen estimations quoted.The melting point of our substance corresponded closely withthree substances of the formula C,H,O,N described in the literature,namely, butyrylformamide, isobutyrylf ormamide, and lzvulinamide.We first prepared butyrylformamide by the method given below.This substance was found to have a striking resemblance to thesublimate from the ergot alkaloids, and melted a t 1OSo, but onmixing with this substance the melting point was 89-90O. Wenext prepared isobutyrylformamide, which again was quite similarin its properties. It melted at 107-108°, and this time the meltingpoint remained unchanged, when the synthet,ic was mixed with thenatural substance.The melting points may be tabulated thus :1. Butyrylformarnido, 108". Mixture of 1 and 2, 88-89",2. isoBur yrylforinaniide, 107-108". Mixture of 1 and 3, 89-90".3. Sa1)stsnc.e from ergot alldoids, 109". Mixture of 2 arid 3, 107-10s".In addition, the vapours of 2 and 3 readily gave, on gentlewarming, tlie pyrrole reaction with a pinewood splint moistenedwith hydrochloric acid, but 1 gave only a doubtful coloration onstrongly heating.The sublimate from the ergot alkaloids is therefore isobutyryl-formamide, CHMe,*CO*CO.NET,.In addition to this substance we obtained, on destructive dia-tillation of the alkaloids under 2 mm. pressure, a small quantity ofa base boiling a t 88-89O, which was condensed in a tube cooledby carbon dioxide and acetone, and had an odour like pyrrolidine.The substance left in the flask was somewhat volatile under 2 mm.pressure, and crept up the sides of the flask as an amber-coloured,viscid liquid, but could not be distilled.Synthesis of Butyryl and isoButyryEforrnarnide.Moritz (Trans., 1881, 39, 14) prepared butyryl and isobutyryl-cyanide from the corresponding chlorides and silver cyanide.Wefound the yield to be very unsatisfactory, and therefore adoptedClaisen's method (Ber., 1S98, 3 1, 1023), using anhydrous hydrogenu 292 CHATTAWAY AND CHANEY :cyanide. 12.5 Grams of butyryl chloride were added to a solutionof 3-2 grams of hydrogen cyanide in 46 C.C. of dry ether, and tothe well-cooled solution 10 C.C. of pyridine were slowly added.After standing overnight, the pyridine hydrochloride, which ha,dseparated, was removed by filtration. The ethereal filtrate waswashed with 5 per cent. sulphuric acid to remove the pyridine, andthen with water to remove the acid. After drying, the etherealsolution was evaporated, and the residue distilled, when 1 gramof butyrylcyanide was obtained ; the rest of the reaction productconsisted mostly of the bimolecular polymeride. By hydrolysis with85 per cent. sulphuric acid, 0.4 gram of butyrylformamide wasobtained. It was purified by sublimation from a boiling-waterbath under diminished pressure, and melted in a sealed tube a t 108O(Moritz found 105-106°). isoButyrylformamide was prepared inthe same way, and melted a t 107-108°. As stated above, this sub-stance, unlike the normal amide, on heating, readily gives thepyrrole reaction with pinewood. Its melting point is given byMoritz (erroneously) as 125--126O, by Brunner (flfonatsli., 1894,15, 758) as 10G-107°, and by Friinke and Kohn (Monatsh., 1899,20, 887) as l l O o .We desire to acknowledge our indebtedness to Messrs. E. T.Thompson and S. M. Pettet, who have respectivelyc made the micro-photographs and drawings, from which the figures of crystals havebeen prepared.THE WELLCOME PHYSIOLOGICAL R ESEAXCH LABORATORIES,RROCKWELL HALL, HERNE HILL, LONDON, S.E

ISSN:0368-1645    

DOI:10.1039/CT9109700284

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

292XXXI .- TheCHATTAWAY AND CHANEY :Action of Chlorine on Phen y 1 car bamide.By FREDERICK DANIEL CHATTAWAY and NEWCOMB KINNEY CHANEY.THE action of chlorine on phenylcarbamide is of necessity a com-plicated one, since each of the three hydrogen atoms attached t onitrogen in the compound can be exchanged for halogen, which can alsopass into the nucleus by intramolecular rearrangement when thehydrogen of the imino-group connecting the carbonyl and phenylgroups is replaced.The isolation of the various compounds produced is rendereddifficult and in eome cases impracticable by the circumstance that thegroup *CO.NHCI, which is comparatively stable in presence of hydro-chloric acid, a t once breaks down with liberation of nitrogen iTHE ACTION OF CHLORINE ON PHENYLCARBAMIDE.293presence of alkali carbonates, whilst the group *CO*NCl*C,H,, which i jcomparatively stable in presence of the latter, undergoes isomericchange under the influence of hydrochloric acid.Hence, since chlorination has to be effected in acid solution, deriv-atives containing the unsubstituted phenyl residue, although un-doubtedly formed, have not been isolated in a pure state; indeed, onlywhen the phenyl group contains chlorine in all available positions canany considerable number of the N-halogen compounds theoreticallypossible be obtained.The action of chlorine on phenylcarbamide is interesting, as thehalogen passes with great ease at the ordinary temperature, not onlyinto the para- but into both ortho-positions, whilst with acyl anilidesthe final transformation, in which the halogen enters the second ortho-position, is only effected with some difficulty a t a comparatively hightemperature.The N-halogen derivatives obtained are also of more than ordinaryinterest on account of their unexpectedly great stability, for examp:e,2 : 4 : 6-trichlorophenyltrichlorocarbamide can be heated to a tempera-ture approaching 130° without decomposition.A consideration of the properties of the N-chloro-derivativesobtained leads to the conclusion that chlorine enters preferably theamino-group, the hydrogen of the *NH*G,H, group being nextreplaced thus :NH,*CO-NHPh -+ NHCl-CO*NHPh -+NHCl*CO*NClPh -+ NCl,*CO*NClPPh.The entrance of halogen into the nucleus follows the regular coursethe para- and ortho-positions being taken up, until finallyall three areoccupied by halogen.EXPERIMENTAL.Action of Chlorine and of Hypochlorous Acid on Phsnylcarbamide.The N-chloro-derivatives derivable from unsubstituted phenyl-carbamide are undoubtedly formed when chlorine is passed into asolution of phenylcarbamide in glacial acetic acid containing an excehsof sodium acetate, but halogen enters the phenyl group with S U C ~ Areadiness that they have not been isolated.The considerable evolutionof heat which takes place in this action is caused by the entrance ofhalogen into the ring, since only a very slight development of heat iscaused by the replacement of hydrogen in carbamide by halogen.If to a strongly-cooled solution of phenylcarbamide in alcohol thecalculated quantity of N/10 aqueous hypochlorous acid is added, aN-chloro-derivative separates in the form of a somewhat viscid solidThis dissolves easily in chloroform, and is left on evaporation of th294 CHATTAWAY AND CHANEY :solvent as a slightly brown, viscid mass, which, without doubt, consistsmainly of the compound NCl,*CO*NClPh, as it contains almost thotheoretical amount of chlorine attached to nitrogen and is transformedinto a mixture of substituted phenylcarbamides on keeping a solutionin glacial acetic acid for some hours, We have not, however,succeeded in bringing it in to a crystalline condition.SubstitutedN-chloro-derivatives, although crystallising well from chloroform orpetroleum when perfectly pure, can only with great difficulty be madeto crystallise when they contain even slight amounts of impurity,especially when, as in the case of those containing unsubstitutedphenyl groups, they are of low melting point.A similar result was obtained when phenylcarbamide suspended inwater was chlorinated in presence of excem of calcium carbonate.p- Chlorophen ylcl~lorocccrbamide, N HCl* GO* N H C,H,CI,This compound can be prepared by thecareful chlorination of phenyl-carbamide or of p-chlorophenylcarbamide dissolved in glacial aceticacid in presence of excess of sodium acetate.Five grams of p-chloro-plienylcarbamide were dissolved in 250 grams of glacial acetic acid, andfinely powdered, crystalline sodium acetate was added so long as it wasdissolved.This liquid was cooled i n ice to as low a temperature aspossible without crystallisation of the glacial acetic acid, and a slowstream of chlorine passed in. p-Chlorophenylchlorocarbamide separatedin small, colourless needles. The stream of chlorine was stoppedbefore the whole of the p-chlorophenylcarbamide had been cmvertedinto the N-chloro-derivative, and the latter was collected, washed wellwith water and finally with chloroform, and dried in a vacuum overphosphoric oxide. It crystallises from warm chloroform, in which it issparingly soluble, in colourless, fine needles. When heated it remainsapparently quite unchanged until 122O, when it suddenly decomposeswithout previously melting. When treated with hydriodic acid, iodineis quantitatively liberated, and p-chlorophenylcarbamide, identical withthat obtained from potassium cyanate and p-chloroaniline, is formed.It and the other N-chloro-derivatives described in this paper wereanalysed by the method generally applicable to nitrogen chlorides, byadding known quantities to solutions of potassium iodide containingglacial acetic acid and titrating the iodine liberated with N/lO-sodiumt hiosulphat e :0,1083 liberated iodine = 10.4 C.C.N/10 I. C1 as :N@l= 17.02.C7H,0N,CI, requires Cl as :NCI = 1'7.29 per centTHE ACTION OF CHLORINE ON PHENYLCARBAMTDE. 295p-Chlorophertyldichlo~~~r~a~~de, NCla.CO*NH*C,H,CI.This compound separates as a pale yellow solid when the calculatedamount of an aqueous solution of hypochlorous acid i s rapidly addedt o a solution of phenylcarbamide in glacial aoetic acid.It crystallisesfrom warm acetic acid, in which it is readily soluble, in pale yellowneedles, which soften a t about 85' and melt and decompose a tabout 90° :0.1804 liberated iodine = 30.3 C.C. N/10 I.The yellow colour of the compound indicates that in it two chlorineC1 as :NCI= 29.77.C7H,0N,C13 requires C1 as :NCI = 29.6 per cent.atoms are attached to the same nitrogen atom.p-Chlorophenylt~&chZorocarbam~d~, NCl, G0.N C!1* C,H,CI.This compound is formed when chlorine in excess is passed into acooled solution of p-chlorophenyloarbamide in glacial acetic acid inpresence of excess of sodium acetate. The insoluble N-monochloro-derivative first formed slowly dissolves as the passage of the chlorineis continued, and the N-trichloro-derivative is obtained as a paleyellow, viscid liquid by diluting with water, extracting with chloroform,and removing the solvent in a ourrent of dry air.This liquid always gave on analysis a somewhat too low peroentageof chlorine as :NCI, and itlhas never been brought into a orysta.llinecondition.This is probably due to it never having been obtainedperfectly pure, but always mixed with a small amount of the corre-sponding N- trichloro-derivative of 2 : 4-dichlorophenylcarbamide, thepassage of the chlorine having to be continued so long to effect thesolution of the N-monochloro-derivative that transfer of chlorine intothe phenyl group in the ortho-position always takes place to a smallextent.2 : 4-Dichlorophenylrnonochlorocarbamide, NHC1-CO*NH*C,H3CI,.This compound is formed when equivalent amounts of 2 : 4-dichloro-phenylcarbamide and of its N-dichloro-derivative are dissolved in assmall a quantity as possible of warm glacial acetic acid.On cooling,2 : 4-dichlorophenylmonochlorocarbamide separates in needle-shapedcrystals. It crystallises from hot chloroform, in which it is sparinglysoluble, in long, colourless, silky needles. When heated it decomposes at132", giving off bubbles of gas and fusing to a brown mass :0.2215 liberated iodine = 18.7 C.C. N/10 I. C1 as :NCI= 14.96.C7H,0N,C13 requires C1 as :NC1= 14.8 per cent296 CHATTAWAY AND CHANEY :2 : 4-DichZorop~eny~dic~lorocarbanzide, NCI,-CO*NH*C,H 3C12.2 : 4-Dichlorophenyldichlorocarbamide can be prepared either fromphenylcarbamide or from p-chlorophenylcarbamide, and as i t is easilysoluble in chloroform and crystallises well, it can be separated withoutdifficulty from any small admixture of other products which may beformed together with it.It is most readily prepared by dissolving phenylcarbamide in fromtwelve to fifteen times its weight of glacial acetic acid, adding twoequivalents of powdered sodium acetate, and passing chlorine until theliquid is saturated.'J'he liquid should be cooled as far as possibleduring the passage of the gas so that it never becomes even slightlywarm. After filtering off, if necessary, a small quantity of 2 : 4 : 6-tri-chlorophenylmonochlorocarbamide, which is occasionally formed ifthe chlorination has been continued too long, cooled chlorine-wateris added in excess, when the N-dichloro-derivative separates as a yellowsolid or as a yellow liquid which quickly crystallises. To obtain i tdry and free from adhering acid, it is best to add sufficient chloroformt o dissolve it, shaking vigorously, then, after washing repeatedly withchlorine-water, separating, and drying the chloroform solution overfused calcium chloride, to drive off the solvenl in a current of warmdry air, A yellow, crystalline solid separates as the chloroformvolatilises, or if crystallisation does not a t once take place, this can bebrought about by stirring the deep yellowish-coloured oil with a littlepetroleum of very low boiling point.It can be similarly easilyprepared from p-chlorophenylcarbamide or 2 : 4-dichlorophenyl-carbamide, but as these are somewhat difficult to procure it is best t oproceed as described above.It crystnllises well from hot chlcroform, in which it is readily soluble,in pale yellow, four-sided, rhombic prisms. It melts at 7 6 O ; whenheated above this temperature, it remains apparently unchanged upt o 100-105", when it begins to give off gas; the gas evolution is a tfirst veiny slight, but it increases in amount as the temperature risesuntil the neighbourhood of 120" is reached, when slight cracklingexplosions generally occur, due to the evolution and explosion ofvapour of nitrogen chloride :0.3897 liberated iodine= 56.8 C.C.N/10 I-,C7H,0N2C1, requires C1 as :NCI = 25.68 per cent.As this compound shows a yellow colour as intense as that ofnitrogen chloride, it seems probable that both the chlorine atoms notin the nucleus are attached to the same nitrogen atom, since phenyl-carbamide derivatives, which contain only one chlorine atom attachedt o nitrogen, and the dichloro-derivative of carbamide itself, whichCl as :NCl= 25-84THE ACTION OF CHLORINE ON PHENYLCARBAMIDE. 297contains two *NHCl groups, are without appreciable colour. It seemslikely that this and the similarly-constituted derivative of p-chloro-phenylcarbamide are formed by the intramolecular rearrangementof phenyltrichlorocarbamide and p-chlorophenyltrichlorocarbamiderespectively, thus :NCl,*CO*NClPh -+ NCl,~CO*NH*C,H,Cl andNCl,* COD N C1*C6H,Cl -+ NC12* CO NH.C,H,CI 3.2 : 4-Dichloropheny?-s-dichZorocarbc~mide, NHCl*CO*~C1*C,H,C12.If 2 : 4-dichlorophenyldichlorocarbamide is dissolved in chloroformand the solvent allowed slowly to evaporate, tufts of slender, colour-less prisms are deposited. These can be recrystallised from chloro-form, but have never been obtained perfectly pure, as they readilychange into 2 : 4 : 6-trichlorophenylmonochlorocarbamide, from whichthey cannot b completely freed. Different specimens were found tomelt not very sharply about 80-85O, and t o contain amounts ofchlorine as :NCl varying from about 23.5 to 24.5 per cent., thisbeing from 1 to 2 per cent. too low for the pure substance. Thus thecoloured, unsymmetrical N-dichloro-derivative when in solutionappears slowly to become converted into the colourless, symmetricalderivative, which very easily undergoes transformation into 2 : 4 : 6-trichlorophenylmonochlorocarbamide :NC12*CO*NH*C6H3CI, -+ NHC1*CO*NC1*C6H3C1, --tNHCl*CO*NH* C6H2C13.2 : 4 : 6- Trich Zorophe~zyZmonochZo~ocarbamide, NHC1.CO *NH* C6H2C1,.This, on account of its stability and very sparing solubility in glacialacetic acid, is the most easily prepared of all the N-chloro-derivativesof phenylcarbamide. It is formed when ,either phenylcarbamide,p-chlorophenylcarbamide, or 2 : 4-dichlorophenylcarbamide is dissolvedin acetic acid and chlorine passed into the liquid for any considerableperiod. It may be conveniently obtained as follows : Five grams ofphenylcarbamide are dissolved in about 25 grams of glacial acetic acid,and a rapid stream of chlorine is passed into the solution, cooling bywater SO that the temperature does not rise above ZOO.After thechlorine has been passing for an hour or thereabouts, fine colourlesscrystals of 2 : 4 : 6-trichlorophenylmonochlorocarbamide make theirappearance in the liquid, and slowly increase in quantity as thepassage of the gas is continued. When the separated solid no longerappears t o increase in amount, it is collected and washed well withcold glacial acetic acid and afterwards with chloroform. A furtherquantity of a somewhat impure product can be obtained by adding a littl298 THE ACTION OF CHLORINE ON PHENYLCARBAMIDE.water to the filtrate.It crystallises from warm glacial acetic acid, inwhich it is sparingly soluble, in small, very slender, hair-like crystals.When heated it turns brown, and begins to decompose at about 150°,and, if rapidly heated, further melts and decomposes at about155-156O. When dry, it can be kept for a long period at theordinary temperature without decomposition :0.2682 liberated iodine=30.1 C.C. N/10 I. C1 as :NC1= 13.28.C7H,0N,C14 requires C1 as X C l = 12.94 per cent.2 : 4 : 6-TrichlorophenyZcarbamide, NH,*CO~NH*C6H2Cl,.This compound is most easily obtained by replacing the N-halogenatom in 2 : 4 : 6-trichlorophenyimonochlorocarbamide by hydrogen.Five grams of 2 : 4 : 6-trichlorophenylmonochlorocarbamide weresuspended in 20 C.C. of glacial acetic acid, and 2 grams of powderedpotassium iodide added.The iodine liberated was removed as fast asit was formed by adding an aqueous solution of sodium sulphite,When iodine was no longer liberated, a slight excess of sulphitesolution was added, the liquid was warmed for some time on a water-bath, and kept for twenty-four hours. The 2 : 4 : 6-trichlorophenyl-carbamide thus formed was then collected and recrystallised fromalcohol. It separates from boiling alcohol, in which it is moderatelyeasily soluble, in colourless, long, hair-li ke crystals, When heatedrapidly it melts at 250°, and decomposes and evolves gas at a slightlyhigher temperature :C1= 44-24, 0.1422 gave 0.2545 AgCl.C7H,0N,CI, requires GI = 44-42 per cent.2 : 4 : 6-TrichEorophenyZdichZoroca~bam~de, NHCI*CO*NCI* C,H,CI,.This and the N-trichloro-derivative are best obtained from pure 2 : 4 : 6-trichlorophenylcarbamide.Five grams of 2 : 4 : 6-trichlorophenyl-carbamide were dissolved in 500 grams of cold glacial acetic acid, anda rapid stream of chlorine passed in for about ten minutes until thechlorine escaped freely. The clear yellow liquid thus produced wasdiluted with an equal bulk of water and extracted with chloroform.The chloroform solution was thoroughly washed with water, driedover fused calcium chloride, and the solvent driven off by a current ofwarm dry air. A very pale yellowish-coloured oily liquid was thusobtained, which on stirring with a little light petroleum deposited awhite solid in fine granular crystals.This was recrystallised from hotchloroform, in which it is sparingly soluble, and separates in colourless,probably orthorhombic prisms terminated by dome or pyramidal faces.On being beated it remains apparently unchanged up to 128O, when it;begins to decompose with crackling explosions without previouslHARDING AND WEIZMANN : LV-NONYLENIC ACID. 299melting. A t this point chlorine is evolved, and it seems probable thatthe explosions are due to the liberation of the vapour of nitrogenchloride, which explodes as soon as it is formed, setting free chlorine :0.2111 liberated iodine= 27.5 C.C. N/10 I.C7H,0N2Cl, requires C1 as :NC1= 22.99 per cent.The circumstance that this compound is colourless leads to theconclusion that the two chlorine atoms attached to nitrogen are notattached to the same nitrogen atom, as does also its relatively highmelting point.C1 as :NCl=22-93.2 : 4 : 6- TrichloroZ.henyEtri~o~~ocarbccmide, NC12*CO*NC1*C6H2CI,.Four grams of 2 : 4 : 6-trichlorophenplcarbamide were mixed withabout 8 grams of finely powdered sodium acetate and suspended in50 grams of glacial acetic acid. The liquid was kept cool, and a slowstream of chlorine was passsd in for an hour. The solution was thenfiltered, diluted with chlorine water, and extracted with chloroform.The chloroform extract was then repeatedly shaken with a cooledsolution of chlorine water containing a little sodium acetate. Onseparating, drying with fused calcium chlcride,and driving off the chloro-form in a current of warm dry air, a deep yellowish-coloured, viscidliquid was obtained. On dissolving this in warm petroleum of lowboiling point and keeping the solution for some hours, 2 : 4 : 6-tri-chlorophonyltrichlorocarbamide separated in bright yellow, short,glistening prisms.It melts a t 58", and can be heated to 130° without, apparent changeWhen heated above this temperature, bubbles of gas are liberated, andin the neighbourhood of 155O it darkens and completely decomposes :C7H20N,CI, requires C1 as :NCl= 31.02 per cent,0.2209 liberated iodine = 38-55 C.C. N/10 I. C1 as :NCl= 30.90.UNIVERSITY CHEMICAL LABORATORY,OXFORD

ISSN:0368-1645    

DOI:10.1039/CT9109700292

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

HARDING AND WEIZMANN : LV-NONYLENIC ACID. 299xXXII.--hl-Nonylenic Acid.By VICTOR JOHN RARDING and CHARLES WEIZMANN.IN the present communication an account is given of the. pre-paration in large quantities and the means of identification ofAl-nonylenic acid, an acid of considerable technical importance.It was first obtained by Schneegans (Annden, 1885, 227, SO), whoprepared it by the condensation of heptaldehyde and sodiu300 HARDING AND WEIZMAKN : A~-NONYLEKIC ACID.acetate by means of acetic anhydride a t 160-170° for thirty hours.The yield was very poor, and its identification uncertain.Knevenagel (Friedlander : Fortschritte der Teerfarb enfabrikation,7 , 738) has also prepared this acid by the condensation of hept-aldehyde and malonic acid through the agency of piperidine.Theauthors, however, have not been able to obtain large yields by thismethod, the piperidine inducing condensation products of hept-aldehyde with itself similar in character to those obtained bymeans of alkalis. These high-boiling neutral products also occurredwhen other secondary or primary bases, such as diethylamine,ammonia, or aniline, were used as the condensing agent, and itwas only when tertiary bases were employed that good yields of thedesired acid were obtained. The heptylidenemalonic acid whichis first obtained,easily loses carbon dioxide to form Al-nonylenic acid,CH,*[CH2],*CHO+ CH,(CO2H),=H,O +CH,*[CH,],*CH:C(CO,H),,CH3*[CH2],*CH:CH*C0,H.This unsaturated acid, after purification by means of its bariumsalt, boils a t 144O/13 mm., and is obtained as a colourless oil witha characteristic odour.As a means of identification, the authorsrecommend the use of the amide or the p-toluidide, but moreespecially the former, as its preparation in a, pure state is botheasy and rapid. A'-Nonylenamide melts at 126-127O; thep-toluidide a't 73-74O. The dibromo-acid,CH3*[CH,],*CHBr*CHBr*C02H,although it has been obtained as a solid melting at 3 5 O , on accountof the difficulty with which it is prepared, is not suitable as ameans of identification. Al-Nonylenic acid, on reduction withsodium and alcohol, gives nonyl alcohol. I n order to control theconstitution of the unsaturated acid, an alternative method ofpreparation was adopted. This was the condensation of hept-aldehyde and ethyl bromoacetate by means of zinc:CH,*[CH2],*CH0 + Zn + CH,Br*CO,Et --+CH,*[CH2]5*CH(OZnBr)*CH2*C02Et -+CH,*[CH2],*CH(OH)*CH,*C02Et.Ethyl P-hydroxy-n-nonoate, on hydrolysis, gives the correspondingacid as a white, crystalline solid, melting at 57-59O.This acid haspreviously been prepared by Wagner (Ber., 1894, 27, 2736), whoobtained it by the oxidation of hexylallylcarbinol by means ofpermanganate. Wagner gives the melting point of this acid as48-51°, but we do not think there can be any doubt as to theidentity of the two substances. The removal of water from thehydroxy-acid waa accomplished by means of acetic anhydride, HARDING AND WEIZMANN : A1-NONYLENIC ACID. 301method which has been used with such conspicuous success byWallach to produce unsaturated acids containing the ethylenelinking in the aP-position.The identity of the two preparationsof A'-nonylenic acid was proved by means of their amides, a mixtureof the two preparations having the same melting point as theirseparate constituents.EXPERIMENT A L.Al-Nonylenic A cid, CH3*[CH,],*CH:CH*C02H.After many unsuccessful attempts, the following method ofpreparing Al-nonylenic acid was found to give the best results.One hundred grams of malonic acid were dissolved in 160 grams ofpyridine, and to the cold liquid was added 100 gra.ms of hept-aldehyde. The whole was kept at the ordinary temperature forthirty-six hours, and then gently heated on the water-bath for twohours. The product was poured into water, and acidified withhydrochloric acid.The oil was extracted by ether, and well washedwith water. The unsaturated acid was next removed from theethereal extract by means of sodium carbonate solution. Theethereal solution was dried and evaporated, when the very smallresidue which was obtained was found to consist almost entirely ofunchanged heptaldehyde, high condensation products being pro-duced only in very small amount. The sodium carbonate washings,on acidification, extraction with ether, drying, and distillation,yielded 90 grams of Af-nonylenic acid, boiling a t 145-150°/ 12 mm.Analyses of this acid, even on redistillation, always showed adeficiency of carbon, and several methods of purification were tried,of which the following gave the best results. Eighty grams of thedistilled acid were boiled in 95 per cent.alcohol with 127 grams ofpure barium hydroxide. The barium salt which is formedgradually dissolves in much boiling alcohol, from which it separateson cooling as a white, crystalline powder. This, on acidifying withdilute hydrochloric acid and extraction with ether, gave about40 grams of pure Al-nonylenic acid, boiling constantly a t144O/13 mm.:0.1210 gave 0.3097 CO, and 0.1102 H,O.Al-Nonylenic acid is a colourless oil, with the faint odourcharacteristic of acids of this class. It is readily soluble in coldsodium carbonate solution, and instantly decolorises cold alkalinepermanganate. The preparation of Al-nonylenic acid in good yieldwas also attempted by condensing heptaldehyde and malonic acidby the use of piperidine (Kncevenagel, Zoc.cit.), but the yields wereC=69.7; H=10.1.C9H1602 requires C = 69-2 ; H = 10.2 per cent302 HARDING AND WEIZMANN : A~-NONYLENIC ACID,very poor, large amounts of high-boiling condensation products ofheptaldehyde with itself being formed. This is easily shown ifto heptaldehyde alone a few drops of piperidine are added. Theliquid rapidly becomes hot, loses the characteristic odour ofheptaldehyde, and decomposes on distillation. Similar results aregiven by other primary and secondary bases, such as ammonia,aniline, and diethylamine. The condensation of heptaldehyde andmalonic acid by means of dimethylaniline gave, from 100 grams ofheptaldehyde, 30 grams of hl-nonylenic acid and also some con-densation products of high boiling point.These we attribute to thepresence of methylaniline in the dimethylaniline employed.Af-Nonylenyl Chloride.-Nonylenic acid reacts vigorously withphosphorus pentachloride to form Al-nonylenyl chloride, boiling at144O/90 mm. :0.2861 gave 0.2335 AgC1. C1=19.9.The nzethyl and ethyl esters boil respectively at 110°/20 mm. and123O/25 mm.Af-Nonylenanzide, C8H,,*CO*NI12. - This most characteristicderivative of Al-nonylenic acid is very readily prepared by pouringthe acid chloride into concentrated aqueous ammonia,. The amideinstantly separates as a solid, and is collected and purified bycrystallisation from aqueous methyl alcohol or petroleum. Itcrystallises in beautiful pearly leaflets, melting at 126-127O :CgHl,OCl requires C = 29.1 per cent.0.1741 gave 13.9 C.C.N, (moist) at 20° and 752 mm.A*-Nonyleno-p-toluidide is prepared by adding the acid chlorideto a slight excess of p-toluidine and then gently warming. Theyellow, semi-solid mass which is produced is then treated severaltimes with dilute hydrochloric acid and with sodium carbonatesolution. The a'dhering oil is removed by contact with porousporcelain, and leaves the p-toluidide as it white solid, whichcrystallises from light petroleum in small, shining leaflets meltingat 73-74O:N=9.0.CgHIgON requires N=&9 per cent.0.1610 gave 7.6 C.C. N2 (moist) at 19O and 770 mm. N-5.5.C,,H2,0N requires N=5.7 per cent.&E'ydroxy-n-mono& Acid and i t s Ester,CH,.[CH,J,*CH(OH)*C~~*CO,E.This acid is easily and rapidly prepared by condensing hept-aldehyde and ethyl bromoacetate by means of zinc in benzenesolution.Eighty-eight grams of heptaldehyde and 128 grams ofethyl bromoacetate are mixed with twice their volume of benzeneHARDING AND WEIZMANN : A~-NONYLENIC ACID. 303and 52 grams of zinc added. The reaction is started by warmingon the water-bath, but when once commenced is extremely vigorous,and cooling must be resorted to. When the reaction has subsided,the condensation may be completed by heating on the water-bathfor a couple of hours. The viscous product is decomposed by iceand hydrochloric acid, extracted with ether, the ethereal extractwell washed with water, dried, and distilled, when ethyl P-hydroxy-n-nonoate passes over as a colourless, inodorous oil, boiling at145O/13 mm.:0.1381 gave 0.3302 CO, and 0.1287 H,O.C,,H,,03 requires C = 65.3 ; H = 10.8 per cent.When treated with an aqueous solution of hydrogen bromidesaturated at Oo, this hydrosy-ester only gives very small quantitiesof ethyl P-bromo-wnonoate, the hydroxy-group remaining un-affected. 6-Hydroxy-naonoic acid is easily obtained by thehydrolysis of its ester by means of alcoholic potash. The potassiumsalt, which separates in large plates from the alcoholic solutionon cooling, is collected, dissolved in a little water, cooled with ice,and acidified, when 8-hydroxy-n-nonoic acid separates as an oilwhich rapidly solidifies. This is collected, any adhering oil beingremoved by contact with porous porcelain, and purified bycrystallisation from hot water, or from light petroleum, when itmelts a t 57-59O:C=65*2 ; H = 10.4.0.1193 gave 0.2707 CO, and 0.1102 H,O.P-Kydroxy-mnonoic acid crystallises in short needles as a white,inodorous compound.It is readily soluble in cold benzene, alcohol,chloroform, acetic acid, o r ethyl acetate, and is stable towardscold alkaline permanganate. It is instantly soluble in cold sodiumcarbonate solution. When treated with an acetic acid solution ofhydrogen bromide and gently warmed, it yields P-bromo-n-nonoicacid as a heavy oil.C=61*9; H=10.2.C9HI8O3 requires C = 62.1 ; H = 10.3 per cent.Preparation of Al-Nonylenic Acid from P-Hydroxy-n-nonoic A c i d .In order to confirm the constitution of Al-nonylenic acid preparedfrom heptaldehyde a d malonic acid, it was deemed advisable toprepare it from P-hydroxy-n-nonoic acid, using acetic anhydride asa dehydrating agent. Ten grams of crude P-hydroxy-n-nonoic acidwere boiled with 50 C.C.of acetic anhydride for four hours. Theproduct was poured into water, and distilled in a current of steam,when the unsaturated acid passed over slowly. The distillate wassaturated with ammonium sulphate, extracted with ether, and frac304 HARDIKG AND WEIZMAX” : A~-NONYLENIC ACID.tionated under diminished pressure, when the acid (5 grams) wasfound to boil at 181°/60 mm.:0.1315 gave 0.3293 CO, and 0.1237 H,O.C,H,,O, requires C = 69.2 ; H = 10.2 per cent.The acid prepared in this way possessed a sharper odour than thatprepared by the first method, but its identity was proved beyondall doubt by its conversion into the acid chloride and then intothe amide.The amide, when crystallised from petroleum, meltedat 126O, and when mixed with a specimen of Al-nonylenamideprepared from malonic acid, no alteration in the melting point wasobserved.C=65.3; H=10*4.Reduction of Ethjl Al-Non$enate to Nonyl Alcohol.Fifty grams of ethyl nonylenate, prepared from the crude acid,are dissolved in 150 grams of absolute alcohol, and gradually addedto 50 grams of sodium contained in a large flask provided with itreflux condenser, the temperature being kept at 150O. The reduc-tion is very vigorous, and alcohol must be added from time to timeto complete the solution of the sodium. When all the sodium hasdissolved, the product is distilled in a current of steam, the nonylalcohol being extracted by ether and fractionated. The yield is35 per cent. The nonyl alcohol was identified by means of itsphenylurethane.aP-Dibromo-n-nonoic A cid, CH,*[CH,],*CHBr*CHBr*CO,H.This acid is prepared by the addition of bromine to a solutionof Al-nonylenic acid in carbon disulphide until the bromine ceasesto be decolorised. The carbon disulphide is distilled off, the aciddissolved in ether, washed with dilute sulphurous acid, dried, andthe ether evaporated. After a long time in an evacuated desiccator,the yellow oil gradually solidifies to a white, crystalline solid.This is pressed on porous porcelain to remove adhering oil, but theacid is too soluble in all organic solvents to permit of a convenientcrystallisation. It melts a t 3 5 O :0’2125 gave 0.2450 AgBr. Br=49*1.C9H160,Br2 requires Br = 50.6 per cent.It is soluble in dilute sodium carbonate solution, but the solutioxrapidly becomes cloudy, owing to the separation of a-bromo-Al-nonylenic acid.THE UNIVERSITY,MANCHESTER

ISSN:0368-1645    

DOI:10.1039/CT9109700299

出版商:RSC    

年代:1910

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STRYCHNINE, BERBERINE, AND ALLIED ALKALOIDS. 305XXXII1.-Strychnine, Berbeqine, and Allied A tkaloidsBy WILLIAM HENRY PERKIN, jun., and ROBERT ROBINSON.I.--St r y c hnine and Brucine.SEVERAL years ago (Trans., 1889, 55, 63; 1890, 57, 992) one of uscarried out a systematic study of the alkaloid berberine, andsucceeded in obtaining a series of degradation products, theinvestigafion of which made it possible to suggest it constitutionalformula for berberine, and this formula, except for slight modifica-tions in minor details, is still accepted as correct. The intention atthat time wslrs to use the experience obtained in order to attackthe problem of the constitutions of several other alkaloids, andafterwards to attempt their synthesis, and a series of experimentson cryptopine" (Proc., 1891, 7, 166) and on other opium alkaloidswere commenced.Owing, however, to the necessity for completing other investi-gations, these researches had, for the time, to be reluctantly putaside.I n recent years the difficult problem of the constitution of brazilinand haematoxylin made it imperative that we should very carefullystudy the constitution and nature of the groupings contained innatural products generally, and particularly in the alkaloids, and,in reviewing the work which had been published on strychnine,brucine, berberine, corydaline, and allied alkaloids, we were ledto certain conclusions as to their constitutions which we think maybe worth recording, and the validity of which we propose to test byexperiment. Although the alkaloids, strychnine and brucine, havebeen the subject of detailed investigations, especially at the handsof Tafel and Leuchs, very few deductions have been made as totheir constitutions.It is well known that strychnine, C21H220,N2,while containing two atoms of nitrogen, is only a mon-acid base,yielding salts, such as the hydrochloride, C2,H,202N,,HCI + l&H20,with only one equivalent of the acid. It is also known that thealkaloid is a tertiary base, and that it does not contain methoxy-groups. When strychnine is treated with alkalis (Loebisch andSchoop, Mowtsh., 1886, 7 , 75; Tafel, A n d e n , 1891, 264, 49), itsuffers hydrolysis with the addition of a molecule of water andformation of strychnic acid (and isostrychnic acid, p.317) :C 2 P 2 2 0 2 N 2 + H 2 O = C 2 P 2 4 O 3 N 2 .Strychnic acid is an imino-carboxylic acid, and a t the same time* Owing to the generosity of Messrs. T . and 13. Smith, of Edinburgh, who havesupplied me with considerable quantities of this very rare alkaloid, this investigatioiiis being continued.-W.H.P., jun.VOL. XCVII. 306 PERKIN AND ROBINSON :a tertiary base, since it yields metallic salts and, when treated withmethyl iodide, is converted into methylstrychnic acid methiodide,C2,H,,0N(MeI)(:NMe)-CO2H (Tafel, Annalen, 1891, 264, 59), andthe presence of the imino-group is further demonstrated by theformation of a nitrosamine, C,,H,,ON(:N*NO)*~,H, when theacid is treated with nitrous acid. These results, together with thefact that strychnic acid is readily converted into strychnine byheat, led Tafel to suggest that the relationship of strychnine tostrychnic acid is probably that represented by the scheme :co N i C,,H,,O<&and is similar to that existing,H,*YONH-COIt can scarcely be doubtedand the non-basic propertiesCO H = NiC,,H220<N~ ,between $-isatin and isatinic acid :A $!6H4.70EH2 CO,H 7that this representation is correct,of the grouping 0CO.N: affords anexplanation of the fact that strychnine, although it contains twonitrogen atoms, is only capable of combining with one equivalentof an acid.Further confirmation of the presence of the grouping=CO*N: in strychnine is obtained from the study of the productswhich are formed when the alkaloid is treated with variousreducing agents.When strychnine is reduced with phosphorusand hydriodic acid, it is converted into a substance, C21H2sON,,called desoxystrychnine (Tafel, Annden, 1892, 268, 245), and thissubstance, the importance of which is emphasised in the followingpages, evidently has the formula (A):tA.1 (R. )since, like strychnine itself, it is a mon-acid base, which, onhydrolysis, yields desoxystrychnic acid (B).This imino-acid has properties very similar to those of strychnicacid, and its whole behaviour indicates that the characteristicgroups N: and *CO*N: of strychnine have undergone no changeduring the reduction to desoxystrychnine. When desoxystrychnineis treated with sodium and alcohol, it yields strychnoline (I), the*CO*N: group becoming *CH2*N:, but electrolytic reduction pro-ceeds further and causes the addition of another two atoms ofhydrogen, and dihydrostrychnoline (11) results (Tafel, Annalen,1898, 301, 324 and 326):(1.) (11.)Lastly, when strychnine itself is reduced electrolytically, it yieldSTRYCHNINE, BERRERINE, AND ALLIED ALKALOIDS.307tetrahydrostrychnine (111), the group *CO*N: being reduced toCH,(OH)NH:, and this readily loses water with formation ofstrychnidine (IV) (Tafel, Annalen, 1898, 301, 303) :NiC,,(111.) (1V. 1One of the most characteristic properties of strychnine is theease with which it is nitrated, since warming with very dilutenitric acid (5 per cent.) converb it into dinitrostrychnine hydrate,C,,EI&O,N,(NO,),,H,O (Tafel, Annalen, 1898, 301, 299).This behaviour, and also the fact that strychnine is very readilysulphonated (Leuchs and Schneider, Ber., 1909, 42, 2681), maybe taken as proof of the presence of at least one benzene ring, andit will be shown later that all the evidence points to there beingonly one such ring in the molecule.There can, furthermore, belittle doubt that this benzene ring forms part of a quinolinenucleus, and, although no known quinoline derivative has so farbeen obtained from strychnine, there is ample indirect evidence ofthe presence of such a nucleus.Tafel (,4nnaZen, 1898, 301, 336) investigated the action first ofdilute and then of strong nitric acid on strychnine, and showedthat, under the conditions he employed, the alkaloid is nitratedand suffers degradation with the formation of dinitrostrychol-carboxylic acid, (NO,),C,H,N(OH),*CO,H, and this importantacid, when heated a t ZOOo, loses carbon dioxide, with the formationof dinitrostrychol, (N02)2CgH3N(OH),.There can be little doubt,as, indeed, Tafel has suggested, that this latter substance is adinitrodihydroxyquinoline, and we are at present engaged in itsinvestigation, not only with the object of proving this point, butalso, at the same time, of determining the relative positions of thesubstituent groups in the quinoline nucleus. Still more conclusiveevidence of the presence of the quinoline nucleus in strychnine hasbeen obtained in the following way. Strychnine combines withmethyl iodide to yield strychnine methiodide, C2,H220,N2,MeI,and this, on treatment with silver hydroxide, or barium hydroxide,yields methylstrychnine, and, since this substance shows all theproperties of a betaine, there can be little doubt that its formationis to be represented by the scheme:MeI:NIC,,H,,O<$O -+ Me0H:N iC,,H220<NH C0,H -+PoMeN i C20H220\NH4'Methy Zutrychnine.Methylstrychnine has all the properties ofVOL.XCVII.a secondary base; it308 PERKIN AND ROBINSON :yields, for example, a nitrosamine, and reacts with methyl iodideto form dimethylstrychnine :9 MeNiC H 022 “MeTafel (BnnaZen, 1891, 264, 43) has already pointed out howremarkably the properties of dimethylstrychnine resemble those ofLT-niethyltetrahydroquinoline :CH2/\/\CH, 1 1 ‘\ / \ P H 2NMe.and dimethylaniline. Like these substances, dimethylstrychnineyields a green nitroso-derivative, and condenses with benzaldehydein the presence of zinc chloride with the formation of the leuco-baseof a green colouring matter, which closely resembles malachite-green and the green colouring matter obtained from N-tetrahydro-quinoline under the same conditions ; furthermore, it combineswith diazobenzenesulphonic acid to yield a yellow azo-dye.Becauseof this behaviour, Tafel draws the conclusion, not only that strych-nine contains a quinoline nucleus, but also that the :NMe groupin dimethylstrychnine and the :NH group in methylstrychnine,and therefore the :N-CO- group in strychnine, is combined by onelinking direct to the benzene ring, and that strychnine must there-fore contain the grouping:AI I\/\N*CO*.The consideration of the properties of strychnidine leads toexactly the same conclusions.This substance is produced, asexplained on p. 307, by the reduction of the CO- group instrychnine to -CH,:NiC,,H2,0<~0 t o N iC,,H,,O<~Hzand this process converts a substance with the properties ofacetanilide into one which again exhibits exactly the behaviour ofdime th y laniline or N-me t h yl t e t rah ydroquinoline towards reagents.The most valuable evidence as to the internal structure of theother portion of the strychnine niolecule is obtained from theconsideration of the properties of an important monobasic acid,C,,H,,O,N,-CO,H, which is produced when strychnine is oxidisedby chromic acid (Hanssen, B e y ., 1884, 17, 2849; 1885, 18, 777and 1917; 1887, 20, 451). This acid is also obtained under thesame conditions from brucine, an alkaloid which contains twSTRYCHNINE, BERBERINE, AND ALLIED ALKALOIDS. 309methoxy-groups and has properties so exactly similar to those ofstrychnine that there can be no doubt that it is dimethoxy-strychnine. Since the two methoxy-groups disappear during theformation of the acid C,,H,j0,N2*C0,H from brucine, it followsthat the benzene ring of the quinoline nucleus in the two alkaloids,brucine and strychnine, is broken down during the formation ofthis acid, evidently in the following manner :C CNow the acid C1,H,,O2N2,CO2H is a derivative of carbazole,because it yields this substance on distillation with zinc dust, andwe therefore arrive at the conclusion that the molecule of strychninemust contain the two residues :It has already been shown that the quinoline nucleus containsa benzene ring,-and therefore, in order-to account for the largenumber of hydrogen atoms in the strychnine molecule, it is neces-sary, as it appears to us, to conclude that not only the pyridinering of the quinoline nucleus, but also the carbazole section of themolecule must be almost completely reduced.Adopting a line ofargument which we have employed on previous occasions (Trans.,1890, 57, 1004; 1902, 81, 238; 1908, 93, 491), we find that thesefacts afford a basis on which it is possible to build up constitutionalformulae for strychnine and its derivatives which, we are convinced,must a t least be very near the truth.The two residues just figured contain C22, and as the formula ofstrychnine is C21H2202N2, it follows that these two residues mustbe fused together in such a way that one carbon atom a t least iscommon to both.It is clear that the basic nature of strychnine isnot due to the nitrogen atom of the tetrahydroquinoline nucleus,because of its union with the CO group; it must therefore be dueto the nitrogen atom of the carbazole residue. I f we now attemptto construct a formula for strychnine on the assumption that thetwo residues are united in such a way that one carbon atom iscommon to both, we have to remember that strychnine is a tertiarybase, and the nitrogen of the reduced carbazole residue musttherefore be rendered tertiary by union with a carbon atom of thequinoline nucleus, whilst the CO group unites with the carbazole31 0 PERKIN AND ROBINSON :nucleus.This would lead to formuke which clearly camnotrepresent the skeleton of strychnine.It s e h s to us that the only possible alternative is to assumethat, in the fusion of the two nuclei, two carbon atoms becomecommon to both,* and that the skeleton, which now contains C30,is completed by the introduction of an additional carbon atombetween the CO group and the basic nitrogen atom,+ yielding, inthe first place:/--\\-// \\-//\/\I 1\/\/ N*CO-CII,N<Further fusion may now take place in two ways, and two only,and leads us to the following alternative expressions for theskeleton of strychnine :/\/\I l l/-\/\/\-/ NC O N \ I \ co \/ \ /* If the two nuclei are fused together in such a way that three carbon atoms arecommon to both, then two additional carbon atoms must be introduced, and weobtain expressioiis such as the following for the skeleton of strychnine :/-\ ;-p 0\/'$'\c/\/\I l lIn such cases the carboxylic group in strychnic acid methiodide would be so farremoved from the iodine atom that the formation of a betaine would appear to be outof the question (p.307).P For, if not, then the only other possible way of uniting the :N*CO* group withthe rest of the molecule, in order to make the basic nitrogen atom tertiary, is theconstruction of a four-carbon ring, which is highly improbableSTRYCHNINE, BERBERIKE, AND ALLIED ALKALOIDS, 31 1Formula I contains a seven-membered ring, and it is veryunlikely that such a ring would be readily produced by theelimination of water from strychnic acid ; on the other hand, suchelimination leading to the formation of a six-membered ring isquite usual, and for this and other reaso-ns we prefer formula 11.If this formula be accepted ils the skeleton of strychnine, therecan be little doubt that desoxystrychnine, C2,H2,0N,, the productof the reduction of strychnine with phosphorus and hydriodic acid(p.306), must be written:Desoz ystr ychniii e.and this formula is in complete agreement with the properties ofthis substance.It exhibits desoxystrychnine as a derivative of tetra-hydroquinoline, accounts for its conversion into desoxystrychnicacid, and for the behaviour of this acid, as well as of desoxy-strychnine itself, towards methyl iodide, nitrous acid, etc.Similarly, the highest product of the hydrogenation of strychnine,namely, dihydrostrychnoline, C,,H2*N2 (p. 306), will be representedby the formula :CH, CH2/\/\CH /\CH, 1 I bH, bH CH2 \/\/ \/ \/\F H YH YH2CH CH,, CH, N-- rBih ydrostrychmline.and the fact that further hydrogenation, without reduction of thebenzene ring, is impossible is well indicated by this structure.On the basis of skeleton formula, 11, it is possible not only toexplain the recent important results of Leuchs (Ber., 1908, 41,1711), Leuchs and Schneider (ibid., 4393; 1909, 42, 2494), andLeuchs and Weber (Ber., 1909, 42, 3703), but also to deduce aconstitutional formula for strychnine which cannot be very farfrom the truth312 PERKIN AND ROBINSON :Leuchs and his collaborators find that strychnine, on oxidationin acetone solution with permanganate, is converted into a keto-dibasic acid, strychninonic acid, which has the composition,NiC17Hls( :N*CO)(CO)(CO,H),.On reduction with sodium amalgam, this acid yields the corre-sponding secondary alcohol dibasic acid, strychninolic acid,Ni ClfHI8( :N*CO)(CH*OH)(CO,H),, and this substance, on treat-ment with dilute potassium hydroxide, is decomposed, yieldingglycollic acid and strychninolone, C19HlS03N2, a substance whichpossesses neither acid nor basic properties.An exactly similarseries of products was also obtained from brucine under the sameconditions.There can be no doubt, that the formulze for strychninonic andstrychninolic acids suggested by Leuchs, which represent theseacids as containing a tertiary nitrogen atom, are correct, and theabsence of basic properties is amply explained by the presence ofthe two carboxyl groups. When strychninolic acid loses glycollicacid under the influence of alkali, the substance produced,strychninolone, is devoid of both acid and basic properties, andit is therefore obvious tha8t, during its formation, mutualneutralisation has taken place between the two carboxyl groupsand basic nitrogen atoms.Since two such atoms are required forthis process, it follows that the section :N-CO*CH,*N$: of theoriginal strychnine skeleton must have lost the grouping *CO*CH,*,and this is therefore the source of the glycollic acid::N*CO*CH,*N: + 2HzO = :NH -+ C?O,H*CH,*OH + HN:.The cause of the non-basic nature of one of the nitrogen atomsin strychnine is thus removed, and the two :NH groups are nowboth basic and free to combine with two carboxyl groups to yielda neutral substance, such as strychninolone.The problem which still remains is to discover the process bywhich the structure : c c\/Ccan be broken up in order to supply two carboxyl groups in suchpositions that they can combine with the two :NH groups toyield two neutral :N*CO* groupings.The following appear to bethe only two ways in which this can be satisfactorily accomplished STRYCHNINE, BERBERINE, AND ALLIED ALKALOIDS. 313&'\/\C/ YO,H I I ' \/\F\P \P\ N H Q $! $! -+c:C CO,Hc : ? NHC0,H.C--C\/CICO,H\ -3NH 7 $!02HF)NH-c\/CCc c (7 cI f now the hydrogen atoms and the carboxyl and other groupsin strychninonic acid, NiC,:H,,(:N*CO)(CO)(CO,HZ,, are filled intothe first formula of scheme I, it will be found that the completeexpression must contain one double linking, whereas, if the sa'meprocess is carried out in the case of scheme 11, two double linkingswill be found to be necessary. This difference is due to the factthat, in developing scheme I from the skeleton formula of strych-nine, one closed ring suffers fission, whereas in the case of scheme I1two closed rings suffer disruption314 PERKIN AND ROBINSON :I f we consider, in the first place, the development of a formulafor strychninonic acid on the basis of the first skeleton formulaof scheme 11, we arrive at expressions of the types:CH CH,' I ' I\/\/c\/co y 7 p 2 HC 0 N-CH*[ CH2],* C0,H\/CH2CH, CH2/\/\ /\ I I FH YH2and CHCH :CH*C02HIt can be shown in several ways that such formulae cannotrepresent strychninonic acid, and the same is true of any otherformulae built up on the basis of the first skeleton formula ofscheme 11, but only one reason for this need be given here.Strychninonic acid is obtained from strychnine by a simple per-manganate oxidation, and it must therefore be possible to recon-struct the formula of strychnine in a comparatively simple mannerfrom that of strychninonic acid, I f we select formula I, andattempt to construct from it a formula for strychnine, we arriveat the expression:C!H CH,/\/\c/\c"I I 6 hH2CH2 \/\/ \/ .\ / \ 7 Y*OHYH,CO N-CH CH,which cannot be correct, because oxida'tion with permangitnatewould attack the double linking combined with the benzene ring,and it would therefore be impossible to obtain from this expressionthe formula for strychninonic acid from which it was derived, andthe same line of argument applies equally to all other formulaederived from the first skeleton formula of scheme 11.Whilst, then, scheme I1 is out of the question, careful con-sideration shows that scheme I leads t o the following expressions forstrychninonic acid and strychnine STRYCHNINE, BERBERINE, AND ALLIED ALKALOIDS.315g CH, CO,H CH, C H ,/ \ (‘(b’. I CO,H CH I CH, CH I CH2fYH $932.C O N--CH CH, CO N--CH CH,d\/\A/ \ / \ 7 7H YH,\/ \/CH, CH*OH\/ ‘\\/CH, COStrychrtinonic acid.cStrychnine.which seem to us to be in every way satisfactory, since theyaccount in a comparatively simple manner for all the knownreactions of these substances. From the several possibilities wewere led to select the positions assigned to the double linkings inthe strychnine formula for various reasons, and of these the follow-ing need only be discussed. I f the formula assigned to strych-ninonic acid is correct, the formation of this acid by the oxidationof strychnine clearly points to one of the double linkings occupyingt.he position marked a.The position b was selected for the seconddouble linking, because this linking must be situated in a, stableportion of the molecule, otherwise it would also suffer oxidationunder the conditions employed in the preparation of strychninonicacid, and experience of heterocyclic systems has shown that thedouble linkings in nuclei, such m :/\ -y 7- /\ -y y- or co N- OH-C N-are not readily oxidised. St.rychninonic acid is a keto-dibasicacid, and there can be little doubt that the keto-group is producedby the oxidation of a secondary alcohol group; in other words,the molecule of strychnine contains a :CR(OH) group (compareLeuchs, Ber., 1908, 41, 1711), and the difficult problem remainingto be solved is that of assigning the correct position to this group.It cannot occupy the position 9, because this would makestrychninonic acid a derivative of benzoylacetic acid, and f and eseem also t o be out of the question, for the reason that hydroxy-groups in these positions would be y- and 6- to one of the carboxylgroups in strychninonic acid, md this acid does not appear tohave any tendency to yield a, lactone.So far no definite experi-mental evidence is available to enable us to select with anycertainty either of the remaining positions d or e, but we hav316 PERKIN AND ROBINSON :chosen c as the rbsult of a comparison of strychnine with quinineand other natural products in which a similar grouping occurs.This argument, based on lactone formation, might appear toapply also to a hydroxyl group in the position c, but theexamination of a model shows that a hydroxyl group in thisposition is too far removed from the carboxyl group to makelactone formation probable.The formula which we have suggested for strychninonic acidleads to the following expressions for strychninolic acid andstrychninolone :CH, CO,HI I FH bHCH,/\A/ CO,H\/\P\/\A\/ \/7 FH SH,CO N-CH,CH,CH, CH-OHandCH2J’lrychninolic mid. Strychninolone.and these also appear to agree in a satisfactory manner with theproperties of these substances so far as they have been investigated.A possible objection to the formula assigned to strychninoloneis the stability of this substance towards oxidising agents, whichmay not be considered compatible with the presence of the :CH*OHgroup, but, in our opinion, this argument does not carry muchweight.It has already been pointed out (p.309) that brucine is di-methoxystrychnine, and the positions of the methoxy-groups inthe benzene nucleus seem to be fixed by the observation of Leuchsand Weber (Ber., 1909, 42, 3709) that brucinolone is readilyoxidised by nitric acid, with elimination of the methoxy-groups andformation of a quinone which crystallises in red needles, andyields a q u i d on reduction with sulphurous acid. Since ano-quinone would hardly be produced under these conditions, it isprobable that f i e substance is a p-quinone of the constitution :CH*OH8 $: YHC;H,CO-CH-CH CH2\/CHSTRYCHNINE, BERBERINE, AND ALLIED ALKALOIDS. 317and its formation is a strong indication that the methoxy-groupsoccupy the position assigned to them in the fallowing formula forbrucine :Me0 CH,CHC CH CH,\/\A/\/\M e O r f: QH YH,CON-CH CH,Brmine.One other very interesting point in connexion with strychnineand brucine which we have already mentioned (p.305) is thebehaviour of these alkaloids on hydrolysis. When strychnine isdigested with sodium methoxide or barium hydroxide, it yieldsstrychnic and isostrychnic acids :N ~ c , , H , , o ~ ~ ~ -+ NX,,H,,O<~; CO H ,and these isomeric acids are converted by the action of heat intothe isomeric alkaloids , strychnine and isostrychnine.Brucineexhib?ts an exactly similar behaviour. Strychnic and isostrychnicacids resemble each other so closely in all their reactions that itmight at first sight appear that they were simply stereoisomericmodifications of the same substance. The conversion of these acidsinto the isomeric strychnines is, however, scarcely in accordancewith this view, and it is far more probable that the isomerism isdue to a difference in the position of one of the double linkings inthe molecule, probably in the sense represented by the formulze:CH, CH/\/\AC CH CH, \A/ \/\/\N H f.’H 5!H2C0,HN-CH CH,\/’ \/CH, CH*OHCH, CHCO,H &-CH, CH,CH, CH*OH\/ \/S’tyycknic acid. so Sty y c h ic nc id.If the formulae suggested for strychnine a nd brucine be examinedwith the view of discovering some reason for the extremely poisonou318 PERKIN AND ROBINSON :nature of these alkaloids, it would seem that the only section towhich this property can be ascribed is the grouping (C) :t:/\ -7 7-co N-(C. 1 (D.)containing the two nitrogen atoms.Schotten (Ber., 1888, 21,2244) has called attention to the fact that a-ketopiperidine(a-piperidone) (D) has poisonous properties of the same kind aathose exhibited by strychnine and brucine, and it is not a t allimprobable that the introduction of the second nitrogen atominto this molecule may have the effect of much intensifying thesepoisonous properties.We are at present engaged in synthesising substances containingthe above di-nitrogen group, and propose to have these examinedin order to find out whether they have poisonous properties similarto those of strychnine and brucine.11.-Berb erine, Corydatine, and A Zlied AIlcaloids.The constitution of berberine, C2,,H1,0,N, is generally acceptedas being represented by the formula:0-CH,and this formula is based on the investigation of the long seriesof products which result from the degradation of the molecule byoxidation with permanganate (Trans., 1889, 55, 63; 1890, 57,992).The position of the methylenedioxy-group * is determined by thefact that hydrastic acid (I) and o-aminoethylpiperonylcarboxylicanhydride (11) are found among the products of this oxidation :C0,H/)c)>cH2 Co"a(/ TR-COf)O>CH, CH,*CH,\/O ()CO,HMe0M~O/\CO,H(1.1 (11.1 (111.)* It is unfortunate that this group should have been wrongly placed in theoriginal papers.-W.H. P., junSTRYCHNINE, BERBERINE, AND ALLIED ALKALOIDS. 319On the other hand, the fact that hemipinic acid (111) is producedin considerable quantities during the oxidation of berberine doesnot definitely fix the positions of the metho,xy-groups, since theformula for berberine :0-CH, /\A CH I Iwould also account for the formation of hemipinic acid onoxidation.On carefully considering this matter, it appeared to us that theonly ox7dation product of berberine which is able to afford definiteinformation as to the position of these methoxy-groups is berberal(Trans., 1890, 57, 1000 and 1062). This substance, on hydrolysis,yields $-opianic acid and o-aminoethylpiperonylcarboxylic an-hydride, and conversely it may be synthesised by simply heating$-opian ic acid and o -aminoe t hy lp ip er on y 1 car b o x y li c anhydride a t180O. When this experiment was described (Zoc.cit., p. 1079),this important synthesis was assumed to take place according tothe equation :and it was suggested (p. 1002) that the constitution of berberalmust be represented thus:Me0M~O/\CHO 1 ICO~N~CH,~CH) ,-- cq;>c€€,.\/ \/The formula, for berberine itself, given at the commencementof this section, was largely based on this constitutional formula forberberal. $-Opianic acid was first obtained as the result of theseexperiments on the oxidation of berberine, and, as it is difficultto prepare in any quantity by this process, and no other methodof preparation has yet been discovered, the mechanism of itscondensation with basic substances has not been investigated indetail.If, however, the formule of $-opianic acid is compared withthat of opianic acid, it will be seen that they are both o-aldehydo320 PERKIN AND ROBINSON :acids, and differ only in the positions of these groups relative tcthe methoxy-groups :Me0 Me0MeO/\CHO MeO/\CO,H!,)CO,H (,!CHO '+-Ottiaiiic acid.Opianic acid.and as this is the only difference in constitution, it may be safelyassumed that they will behave in an exactly s i m h r manner whentaking part in reactions characteristic of o-aldehydo-acids.Important evidence in support of this view has already beenobtained, since it was shown in the earlier papers (Trans., 1890,57, 1081) that opianic acid condenses with w-aininoethylpiperonyl-carboxylic anhydride to yield a substance :which has properties exactly similar to those of berberal, and wastherefore named isoberberal.During recent years opianic acid hasbeen the subject of detailed investigation, and the results whichhave been obtained necessitate a modification of our views as tothe constitution of isoberberal, and conseque.ntly of berberal andof berberine itself. Liebermann (Ber., 1886, 19, 2284; 1896, 29,175) has shown that opianic acid reacts with aniline in the coldto yield anilino-opianic acid, and expressed the opinion that,during this process, the opianic acid reacts as a derivative ofhydroxyphthalide in accordance with the equation :Me0 Me0 CO'M ()/\A + NH2*C,H, = 1 I 0\/\/CH *NH*C,H, V\PCH*OHand from the study of this and many other similar condensations,it is clear that, in condensations of opianic acid with basic sub-stances, it is always the carbon atom of the aldehyde group whichis attached to the nitrogen atom in the final product.There canbe little doubt that a similar process takes place when opianicacid reacts with w-aminoethylpiperonylcarboxylic anhydride to yieldisoberberal, and the constitution of this substance is therefore notthat originally assigned to it (p. 319), but must be modified to:Me0 COMeO(\/ '0 ,COf)O>c.,yCH*N*CH,*CH,\ A / / V0woBerbera1.STRYCHNINE, BERRERINE, AND ALLIED ALKALOIDS. 321Furthermore, since +-opianic acid is so exactly similarly con-stituted to opianic acid, and exhibits in all its reactions so closean analogy with this acid, it cannot be doubted that, when itcondenses with basic substances, it also reacts in it similar manner.It follows, therefore, that in the formation of berberal by thecondensation of +-opianic acid with o-aminoethylpiperonylcarboxylicanhydride, the aldehydic carbon atom of the +-opianic acid becomescombined with the nitrogen atom, and the constitution of berberalmust therefore be represented by the formula:Kerberal.and not by that originally assigned to it (p. 319).*This new expression is in complete agreement with the propertiesof berberal, and its acceptance involves the alteration of theposition of the methoxy-groups in the old berberine formula(p.318), so that the .constitution of the alkaloid must now bewritten (compare p. 319):O-CH,Berberine.* The actual mechanism of the condensation of opianic acid or +-opianic acid withbasic substances is probably not so simple as that suggested by Lieberrnann (loc.cit.). Whes the syntheses of berberal and isoberberal were described (Trans., 1890,57, 1080 and 1082), it was proved that in both cases the first step is the formationof the salt of the acid with the base. Thus, for example, +-opianic acid combineswith w-aminoethylpiperonylcarboxylic anhydride to form the salt,/CHO CO-- 0( Me0)2C6H2 I \C6H2' b H , ,\CO*O*NH2*CH2* CH2/ \O/which, when heated at 180°, yields berberal.Most probably aldoltakes place during this change, followed by rearrangement according,GO-0 co---\CII(OH)*NH*CH,*CH,( Me0)2C6H'2' \/ >CC.~<,">CH~formation firstt o the scheme :\C H /"\ co co---CH-N*CH,*CH~'(MeO)&6H2< >o I 6 Z\O/CHP.The synthesis of isoberberal takes place in an exactly similar manner, and it isvery probable that all such condensations between opianic acid or +opianic acid andbasic substances proceed on similar lines322 STRYCHNINE, BERBERINE, AND ALLIED ALKALOIDS.The formation of berberal by the oxidation of berberine is noweasy to understand, and evidently takes place according to thescheme :O--QH,/\. 0I /0-CH, /\A I 1/\/,\/CO$ / I /\/"02" co -+Me01\/\cH(oH)-N CH,\/ Me0 I \/'(-3%l f e d \/\CH=N ' ;i' CH,Me0CH2(OH)0-y H 2/\aI I -+ / \// \ / ? O Y 0 1M"o\/\ I /\/I I 0 N CH,Me0 CH CH,The salts of berberine are derived from the hydroxyl formulagiven above (compare J.Gadamer, Arch. Pharm8., 1905, 243, 31),but there is reason t o believe that the alkaloid itself exists in thecorresponding aldehyde modification. Gadamer (Chem. Zed., 1902,26, 291) has shown that, when berberine sulphate is treated withbarium hydroxide, it yields a brownish-red, strongly alkaline solu-tion, which doubtless contains the hydroxy-modification of berberine.If, however, this solution is mixed with excess of sodium hydroxide,a yellow modification of berberine is obtained, which apparentlyhas the properties of an aldehyde, and Gadamer has named thismodification b erb erinal. The constitution of this modification,based on the new formula for berberine which we have proposed,will be the following : -0-QH,/)OCH 1 /\/\A/ Meou NHCH, ? IMe0 C H O W(3%Berberinal.Berberinal yields an oxime, reacts with magnesium alkyl iodideswith formation of homologues of berberine (Freund and Beck, Ber.DECOMPOSITION OF DIMERCURAMMONIUM NITRITE HP HEAT, 3.231904, 37, 3336 and 4673), and, when treated with a large excessof alkali, is reduced t o dihydroberberine and simultaneouslyoxidised to hydroxyberberine, the aldehyde grouping being con-verted into -CH,(OH) and -CO,H in the manner chmacteristic ofaromatic aldehydes.The proposed modification of the positions of the methoxy-groupsin the berberine formula receives further confirmation from theconsideration that berberine occurs along with hydrastine inhydrastis canadensis, and the close relationship between thesealkaloids becomes very striking if the new formula for berberinalis placed by the side of that of hydrastine:0-CH, /\d CH I I0-CH, /\oBerberinal. Hydrastine.These alkaloids are, indeed, so closely related as to suggest thathydrastine is either formed in the plant from berberine, or thatthey are both derived from some common parent.THE UNIVERSITY,MANCHESTER

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DOI:10.1039/CT9109700305

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年代:1910

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DECOMPOSITION OF DIMERCURAMMONIUM NITRITE HP HEAT, 3.23Ry PRAFULLA CHANDRA RAY and ATUL CHANDRA GHOSH.THE preparation of dimercurammonium nitrite has been alreadydescribed at some length (Trans., 1902, 81, 644), and evidence hasbeen adduced in support of the view that it is a derivative ofammonium nitrite.The solution of sodium mercuric nitrite, from which it is obtainedby the action of ammonia, does not contain mercury as cation,but as part of a complex anion; it does not, therefore, undergo thehydrolysis so characteristic of oxylic mercuric salts, and has presumablya non-oxylic constitution. Two samples of the salt were prepared, anddried a t 95' for analysis :VOL. XCVII. 324 RAY AND GHOSH: DECOMPOSITION OFFound : Hg= (I) 84.74; (11) 84.61. N = (I) 6.33 ; (11) 6.16,NHg,N02,&H,0 requires Hg = 85.29.N = 5-97 per cent.Method of Experiment.-From 0.2 to 0.6 gram of salt was placed ina small bulb, the drawn-out stem of which was connected with aSprengel pump. A preliminary trial proved that the salt commencedto decompose, although very slowly, a t about 140°, and that even at210’ a portion of it remained undecomposed. The bulb was thereforecautiously and gradually immersed in a bath of molten sodium andpotassium nitrates, mixed in about equal proportions (m. p. 21s’).The temperature mas slowly raised to 260°, when no more gas wasevolved, the ‘‘ click ” in the fall-tube remaining persistent. Raisingthe temperature to 280’ made no difference i n this respect. The gaswhich was evolved was found to consist of a mixture of nitrous oxide,nitrogen, and oxygen ; nitrous fumes were not noticed ; in fact, themercury in the fall-tube was not in the least tarnished, nor couldeven a trace of nitric oxide be detected.I f , however, the bulb wassuddenly plunged in a bath previously heated to 2 2 5 O , the mode ofdecomposition was slightly different. Mercury in the shape of finedust was at once deposited on the glass, and in the gaseous mixturenitric oxide could be recognised.The nitrous oxide was removed by alcohol, and sometimes byrepeated shaking with cold water, until no more absorption tookplace. The oxygen was in some instances removed by alkaline pyre-gallate, but generally by means of phosphorus. The residue in thebulb was of a greyish-yellow colour; it consisted mainly of mercuricoxide with a small proportion of mercuric nitrate.This was provedby boiling the mixture with a solution of sodium hydroxide. Thefiltrate indicated the presence of nitrogen in the form of nitrate.Metallic merciiry, both as a mirror and in fine globules, was depositedin the stem of the bulb. More than a dozen experiments wereperformed, the resdts of- some of which are tabulated below :Total 0“Free” N as N as in the H ~ a s Hg as “Frec”N. N,O. Hg(NO,),. Oxygen. salt. Hg(h0,)p HgO. Hg.I. 3’21 1.55 1.21 0-21 6.82 5-64 57‘20 19-4511. 3-17 1-48 1-32 0.17 - 9.43 55.31 20.55- 6 .OO 62-65 16’68V. 3.73 1.52 0.72 0% - 5-14 83’31 16’84- - - 111. 3-43 1-44 1‘10 0‘22 -IV. 3’53 1‘60 0‘84 0 ‘34I n those experiments in which nitric oxide was obtained, thenitrogen was distributed as follows :“ Free ” N.N as N,O. N as Hg(NO,),. N as NO.I. 2.54 1 ’03 2 ’31 0.0911. 3’23 2 ‘24 0’29 0 ’42111. ‘L.ti9 I .06 0.95 0.3DIMERCURAMMONIUM NITRITE BY HEAT. 325Discussiorn of Resuh.--It has already been pointed out that thehalogen derivatives of the mercurammonium group (NHg,-) may beregarded as non-oxylic in constitution, since they decompose under theaction of heat according to the equation :2NHg2X = N, + 2Hg + 2HgX,*where X = C1 or Br.series should decomposelas follows :and that the mercurous nitrite thus formed, being unstable a t thistemperature, would yield its own products of decomposition (compareRBy and Sen, Tram., 1903, 83, 491).We have repeated theexperiment on the decomposition of mercurous nitrite. The initialtemperature of decomposition has been found to be almost the sameas that of dimercurammonium nitrite, namely, 1 40°, and it is completedat 247O. I n order to protect the mercury in the Sprengel pump frombeing soiled, a glass spiral, packed with glass beads and moistenedwith sodium hydroxide solution, mas interposed, as in some of theprevious experiments (compare Trans., 1905, 87, 180). The gaseousproduct which was collected was found to be nitric oxide. Moreover,had dimercurammonium nitrite decomposed according to the equationgiven above, exactly half the nitrogen would have been given offas “free” nitrogen, but it varies from 3.2 to 3.7 per cent. Theformation of nitrous oxide is rather remarkable. The reactionevidently seems to proceed in three or four directions simultaneously,which may be expressed by the following equations :From analogy, one would naturally expect that the nitrite of the2NHg,N02 = N, + 2Hg + 2HgN02,. . . . . . . NHg,NO, = N, + 3Hg0 (1)NHg,NO,=N,O+HgO+Hg (2)NHg,N0,=N2+2Hg+0, (3)3NHg2N02 = Hg(NO,), + 3N, + 5Hg. . . . (4).(compare NH,NO, 5 N, + 213,O) . . . . . .. . . . . .We are at present engaged in studying the decomposition ofdimercurammonium nitrate, in the hope that further light may bethrown on these points.CHEMICAL LABORATORY,PRESIDENCY COLLEGE, CALCUTTA.* RAY, “ Studien uber die Konstitution der Dinierkuramnioiiium Sake ’’ (Zeitsch.anorg. Chem., 1902, 33, 193; also, Sen, ibid., 197).2

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326 RAY: THE DOUBLE NlTRITES OF MERCURY AND THEBy PRAFULLA CHANDRA RAY.IN a previous communication a general method of preparation ofthe double nitrites of mercury and the alkali metals has been described(Trans., 1907, 91,2031). Recentlyit has been found that this methodis equally applicable to the preparation of the corresponding mercuriccalcium, mercuric strontium, and mercuric barium nitrites. For instance,if a solution of calcium nitrite is added to a perfectly clear solution ofmercuroso-mercuric nitrite, ( HgN02)2,4Hg(N02)2, almost immediateturbidity is caused, due to the separation of metallic mercury i n a finestate of division. The explanation already given (Zoc. cit.), namely,that '' the process of dissociation is accelerated because of the tendencyof one of the products of dissociation, namely, mercuric nitrite, tounite with the alkali nitrite," adinits of further amplification.It isthe tendency t o form complex ions that is really the rnotay of thereaction. A solution of potassium mercuric nitrite, K2Hg(N02),,contains mercury, not as a cation, but as part of a complex bivalentanion, Hg(N02),.* Hence, such a solution behaves as a neutral one,and can be diluted ad injinitzcrn without undergoing the hydrolysis, socharacteristic of the oxy-sal ts of mercury, for example, mercuricnitrate. This also explains the eingular behaviour which I noticedsome twelve years ago (Zeitsch. anorg. Chem., 1896, 12, 367), namely,that carbamide does not precipitate the mercury from the solution,or a solution of sodium sulphate give the characteristic precipitate ofturpeth mineralMethod of Prepamtion.-The light yellow solution of the doublenitrites is evaporated under diminished pressure over sulphuric acid.As a rule, crystallisation of the salts does not take place, buta syrupy liquid is obtained, which, on being stirred with a rod,solidifies entirely, with the formation of mealy crystals and liberationof heat. I n fact, the characteristic behaviour of supersaturatedsolutions is noticed. As the crystals were very soluble, they werewashed with the minimum quantity of water, and dried by pressurebetween folds of bibulous paper. If the salts are preserved in a,stoppered bottle without being well dried, they slowly decompose, withevolution of nitrous fumes ; but if they are kept in the open bottlein the desiccator, they remain perfectly stable (compare mercuricDer Quecksilbernitrit=komplex " (Diss., Breslau, 1906).* Hans Pick, " Beitrage zur Characteristik des Nitrit-ionsMETALS OF THE ALKALINE EARTHS.327nitrite, Trans., 1904, 85, 524). The compounds described belowcontain five molecules of water of crystallisation.Mercuric Calcium Nitrite.Found : Hg = 38-21 ; Ca = 7.96 ; N = 10.98.N = 10.90 per cent.Hg(NO2),,Ca(N0,),,5H2O requires Hg = 38-9 1 ; Ca = 7.78 ;Mewxwic Strorthunz Nitrite.Found : Hg = 44.58 ; Sr = 13.08 ; N = 11-17.N = 10-57 per cent.3 Hg(N02)2,2Sr(N0,),,5LI,0 requires Hg = 45.31 ; Sr = 13.18 ;Mercu& Bayium ATitrite.Found : Hg = 39.88 ; Ba == 19.80 ; N = 10.55.3Hg(N02)2,2Ba(N0,),,5H,0 requires Hg = 42.13 ; Ba = 19.24 ;N = 9.84 per cent.The preparation of the last two salts was repeated, but the com-position was practically constant.The low percentage of mercuryand the proportionately high percentages of barium and of nitrogenin the last one are probably due to the substance being invariablycontaminated with traces of mother liquor containing excess ofthe nitrites of the latter metal.On comparing the whole series of double nitrites, it is of interest t onote that the power of mercuric nitrite to unite with the nitrites ofthe alkali metals is the greater the less the atomic weights of thelatter, Thus, mercuric nitrite can combine with four molecules oflithium nitrite and with three molecules of potassium nitrite, althoughit also forms characteristic stable compounds vith two molecules ofeither sodium or potassium nitrite. On the other hand, it com-bines molecule for molecule with calcium nitrite. Again, onemolecule of mercuric nitrite can combine with only two-thirds of amolecule of strontium or barium nitrite. Cryoscopi:: determinationsof the molecular weights of the above salts have been undertakenwith the view of throwing light on their constitution, the results ofwhich I hope to communicate shortly.CHEMICAL LABORATORY,PREhIUENCY COLLEGE, CALCUTTA

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DOI:10.1039/CT9109700326

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年代:1910

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328 COHEN AND MARSHALL:XXXVL-The Constitution of the Arnidines. A New&kthod fay' Determining khokcukw Symmet?y.By JULIUS BEREND COHEN and JOSEPH MARSHALL.H. VON PECHNANN (Bey., 1895, 28, 869) made the observation thatthe amidine (I) prepared from benzanilide iminochloride and p-toluidinemas identical, so far as could be shown by comparison of melting pointsand other physical properties with the amidine (11) obtained frombe n zoyl-p- t oluid ide i minochloride and aniline.* *C,N,*NH-CPh :N-C,H,. C1,H,*NH*CPh:N*C7H7.The product obtained by the ethylation of this substance was shownto be a mixture of two ethyl derivatives in equal quantities, and thesewere separable by mechanical means. This fact may indicate, eitherthat the original amidine is a mixture of equal quantities of the sub-stances represented by (I) and (II), or that it has a varying structurecaused by the oscillation of the hydrogen atom marked" in theformula between the two nitrogen atoms,I n cases where the two bases differed in character from each other,von Pechmann obtained quite different results.Using ( a ) methyl-benzamide iminochloride and aniline, and ( b ) benzanilide iminochlorideand methylamine, he obtained, as before, the same product in each case,hut methylation of t h i s substance produced only one methyl derivative.This was found to be identical with the amidine obtained by combiningmethylbenzamide iminochloride with methylaniline, indicating thatthe amidine prepared either by method (a) or ( b ) had the constitutionrepresented by (111), and that a substance with the formula (IV) wasnot produced at all.CH,*N:CPh*XH*C,H,.CH,*NH*CPh:N*C,H,.(1.1 (11.1(111.) (IV-)The present investigation was undertaken with the view of deter-mining whether the introduction of optically active groups into theamidine would afford a more delicate means of distinguishing betweenthe products of the two reactions in the event of their being indistin-guishable by other means, The optically active base used in most ofthe experiments was I-menthylamine, as being easily obtainable in largequantities (Tutin and Kipping, Trans., 1904, 85, 69). The benzoylderivative of menthylamine was converted into the iminochloride andallowed t o react with the second base, and the amidine obtained inthis way was compared with that prepared from the iminochloride ofthe benzoyl derivative of the second base arid menthylamine.ThTHE CONSTITUTION OF THE AMIDINES. 329other bases used were aniline, 0-, m-, and p-toluidine, and ethylamine.It was found that in all cases the pairs of amidines had exactly thesame specific rotations, melting points, and other physical properties.I t was also shown, by ethylation of some of the amidines, that theywere single substances and not mixtures, as only one ethyl derivative wasformed in each case. These ethyl derivatives were also sgnthesised,and it was proved that the constitution of the amidine containingphenyl and menthyl groups is represented by (V), and that containingethyl and menthyl groups by (VI).C,H,*NH*CPh:N*C,,H,,.C,H,*NH* CPh : N* C,,H,, .w. 1 (VI.)These experiments confirm the observation that marked differencein character of the radicles causes the formation of one and the sameproduct in the two reactions, and there is no indication of anyequilibrium mixture, as in the case where the radicles are of the sametype. It is interesting t o note that the hydrogen atom is in all casesattached to the nitrogen atom in the less basic group.It was then thought that it would be of interest to prepare anamidine in which the two bases were enantiomorphous. I n such a case,according to von Pechmann, a mixture of two substances would beobtained of the types (VII) and (VIII).NHR*CPh:NK. NHR* CPh: NR.- + f(TII.) (VIII.)These should be produced in equal quantities, and hence any opticalactivity due to (VII) would be counterbalanced by that due t o (VIII),and the product should be inactive, This was found to be the case,the bases used being d- and I-bornylamines, which are easily obtainedby Forster’s method (Trans., 1898, 73, 390) from the correspondingcamphors.Ethylation of the amidine produced one inactive ethylderivative. It was conceivable that if the amidino were a mixtureof two substances represented by formula? (IX) and (X) :(Z)C,,H,7*NH* CPh:N*C,,Hl7(d) (I)C,,Hl7*N:CPh*N H*C,,H,,(d)(IX. ) (X. 1it might be possible by crystallising it with an optically active acid toobtain fractions which would, after removal of the acid, be active.The amidine was combined with Reychler’s d-camphorsulphonic acid,and the salt crystallised several times from hot light petroleum, Thespecific rotations of various fractions were then determined, but theywere found to be practically identical.After removal of the acid, therecovered amidine was inactive. Similar experiments were carriedout with the ethyl derivative, but no resolution of the amidine couldbe detected.It is proposed t o extend to other classes of compounds this metho330 COHEN AND MARSHALL:of examining molecular symmetry by introducing enantiomorphousradicles into different positions in the molecule. We are at presentengaged in determining the space formula of quinquevalent nitrogenby the aid of this method.EXPERIMENTAL.Phen$menthyZbenxccmidine, C,,H,,*N C( U,H,)*NH*C,H,, was pre-pared by boiling in light petroleum the iminochloride obtained from5 grams of benzanilide with 7.5 grams of Z-menthylamine.Thementhylamine hydrochloride which separated was collected, the lightpetroleum removed, and the gummy residue extracted with dilutehydrochloric acid. To the filtered acid solution, sodium hydroxidewas added, and the amicline extracted with ether. It was crystallisedfrom alcohol, and formed fine needles melting a t 110-111' :0.5072 in 20 C.C. chloroform gave, in a 2-dcm. tube, uD - 7.40";The same compound was obtained by boiling the light petroleumsolution of the iminochloride from 5 grams of benzoylmenthylamidewith 3.6 grams of aniline, The hydrochloride of the amidine whichseparated was collected, washed with a little more ether, and decom-posed with sodium hydroxide.The compound obtained after recrgs-tallisation from alcohol melted at 110-lll", and a mixture of thissubstance with that obtained in the previous experiment had the samemelting point :0.5104 in 20 C.C. chloroform gave, in a 2-dcm. tube, a,, - 7.44';0,2054 gave 15 C.C. N, a t 15' and 750 mm.The hydrochZoq*ide, prepared from both specimens, melted a t 224",and formed long needles when crystallised from dilute alcohol. It wasonly slightly soluble in cold, but fairly so in hot, water.The platinichloride was precipitated in a crystalline condition byadding platinic chloride to a dilute alcoholic solution of the hydro-chloride.whence [u]? - 146'.whence [u]F - 146'.N = 8-61.C,,H,,N, requires N = S.39 per cent.It melts at 213' :0.5504 gave 0,0998 Pt.M.W. of amidine = 333.C23H3,,N2 requires M.W. = 334.Ethyzatioiz of Pheny~menthy~benz~~a~d~~ae.2.3 Grams of the pure amidine were heated on the water-bath forten hours with an excess of ethyl iodide, the latter being then distilled.The residue, consisting of the hydriodide of the ethylated amidine,crystallised, and was decomposed with sodium hydroxide. After twTHE CONSTITUTION OF THE AMIDINES. 331crystallisations from alcohol, 1.9 grams of pure substance wereobtained in beautiful square plates, which melted at 66-67". Thesubstance was perfectly homogeneous :0.3596 in 25 C.C. chloroform gave, in a 2-dcm. tube, a, - 11-2s";0.6260 in 25 C.C.chloroform gave, in a 0.302-dcm. tube, aD - 2.95";This amidine was also produced by treating benzoylmenthylamideThe characteristic plates, melting at0.4611 in 25 C.C. chloroform gave, in a 2-dcm. tube, [a], - 14.47' ;0.2164 gave 14.55 C.C. N, at 15O and 749 mm.The hgdrochloride was not obtained in the crystalline condition, butonly as a sticky mass, soluble in water. ' The hydriodide crystallises inprisms, melting at 220'. The- platinicldoride was precipitated from anaqueous solution of the hydrochloride, and melted at 151" :whence [ u ~ ~ " -392O.whence [a]F -391".iminochloride with ethylaniline.66-67", were obtained :whence [alga - 392O.N = 7.92.C2,H,,N, requires N = 7-73 per cent.0.5756 gave 0*09SO Pt. M.W.of amidine = 368.C,,H,,N, requires M.W. = 362.Phenylmenth ylethylbenxamidine.For purposes of comparison, the amidine from benzanilide imino-chloride and ethylmenthylnmine was prepared, It crystallised fromalcohol, in which it was much less soluble than the preceding substance,in needles melting a t 1 5 7 O :0.7436 in 25 C.C. chloroform gave, in a 2-dcm. tube, a, - 3-6O;whence [a]? - 60.5".0.1645 gave 11 C.C. N, at 20" and 762 mm.The hydrocldmide was insoluble in cold water, and crystallised fromN = 7.73.C,,H,,N, requires N = 7.73 per cent.alcohol in needles melting at 28090- Z'olylmenthylbenza~aidine, C, oH,,*N: C( C,H,)*NH* C,H7.This substance, prepared from benzoyl-o-toluidide iminochloride andmenthylamine, was isolated as the hydrochloride by saturating withdry hydrogen chloride the light petroleum solution from which theprecipitated menthylamine hydrochloride formed in the reaction hadbeen separated.The precipitated gummy mass was crystallised fromalcohol and decomposed with dilute aqueous sodium hydroxide. Theamidine crystallises from alcohol in needles melting at 106-107° 332 COHEN AND MARSHALL:0.3391 in 25 C.C. chloroform gave, in a 2-dcm. tube, aD -2.85';This amidine was also prepared from benzoylmenthylamide imino-chloride and o-toluidine, the hydrochloride of the amidine separatingfrom the light petroleum almost quantitatively :0.6264 in 25 C.C. chloroform gave, in a 2-dcm. tube, aD -5.26O;0.2064 gave 13.9 C.C. N2 at 11' and 750 mm.The hydrochZoride crystallises f corn alcohol in small, rectangularThe platinichlode mas obbained as a crystalline powder :0.5654 gave 0.1005 Pt.C24H32N2 requires M.W.= 348.m-~~Zylment~~yZ6enxamidine was isolated in a similar manner to theo-tolyl derivative from benzoylmenthglamide iminochloride andm-toluidine. The base crystallises from alcohol in needles, and meltsat 89-90' :0.6268 in 25 C.C. chloroform gave, in a 2-dcm. tube, a,, - 7-13";The amidine from benzoyl-m-toluidide and menthylamine had the0.6118 in 25 C.C. chloroform gave, in a 2-dcm. tube, a, - 6.98';0.2090 gave 14.4 C.C. N, at 13.5' and 751 mm.The hydrochloride crystallises from alcohol, and is only very slightlyThe platinichlwide forms very small needles, which melt a t 217' :0.5603 gave 0.0991 Pt.C2,H,,N, requires M.W.= 348.p-Z'olyZmenthyZbenxamidine, isolated in the usual wag! from benzoyl-menthylamide iminochloride and p-toluidine, crystallised from alcoholin stout prisms, which melted at 63-68' even after severalrecrystallisations :0.6252 in 25 C.C. chloroform gave, in a 2-dcm. tube, a, - 6.55';Repeated crystallisation had no effect on this value. Whenprepared from benzoy 1-p-toluidide and menthylamine, the same ratherindefinite melting point was observed :0-6231 in 25 C.C. chloroform gave, in a 2-dcm. tube, aD - 6.54';whence [a]:' - 105O.whence [.IF - 105'.N=8*13.C,,H,,N2 requires N = 8.05 per cent.plates, melting at 218', and is scarcely soluble in water.M.W. of amidine =- 344.whence - 142'.same melting point :whence [a]F - 143'.N=8*18.C,,H,,N, requires N = 8.05 per cent.soluble in hot water. I t melts at 232'.M.W.of amidine = 346.whence [=IF - 131'.whence [a]r -131'THE CONSTITUTION OF THE AMIDIKES. 3330.2069 gave 13.9 C.C. N, a t 15" and 747 mrn.C,,H,,N, requires N = 8.05 per cent.The hydrochloride crystallised from alcohol in small needles meltingat 2 2 5 O , and the pkatinichkoride, obtained as a crystalline precipitate,melted at 208' :N = 7.94.0.2700 gave 0.0474 Pt. M.W. of amidine = 350.C2,.H,,N2 requires M.W. = 348.Menth?/ZethyZbenxamiine, C, ,H,,*N: C( C,H,)*NH4J2H5.This substance was prepared by treating tt light petroleum solutionof ethylamine (2 mols.) with the calculated quantity of benzoylmenthyl-amide iminochloride.The ethylamine hydrochloride was collected,and, after removal of the light petroleum, the gummy residue wasboiled with dilute sulphuric acid. The clear solution of the sulphatewas treated with a concentrated aqueous solution of potassium iodide,and the precipitated iodide mas separated and decomposed with sodiumhydroxide. The amidine solidified after removal of the ether used inits extraction, but all attempts at recrystallisation were unsuccessful.The substance melted at 65-67", It was purified by conversion intothe iodide, which was again decomposed. No alteration in the meltingpoint could be observed :0.6282 in 25 C.C. chloroform gave, in a 2-dcm. tube, aD - 5.63";The amidine was also prepared from ethyl benzamide irninochloride0.6240 in 25 C.C.chloroform gave, in a 2-dcm. tube, uD -5.57";0.2133 gave 16.9 C.C. N, at 13" and 750 mm.The hydrochloride was only obtained as a sticky mass, whichThe hydriodide, which was much lesswhence [u]F - 11 2'.and menthylamine, and this specimen had the same melting point :whence [.IF - 11 2O.N = 9.49.C,,H,,N, requires N = 9.80 per cent.was very soluble in water.soluble, was not obtained in a crystalline condition.M.W. of amidine = 280.The platinicliioride formed microscopic plates, melting at 218' :0.4816 gave 0.0968 Pt.C1,H,,N2 requires M.W. = 286.Four grams of this amidine were boiled for ten hours with ethyliodide, and, after distilling off the excess of alkyl iodide, the hydriodideof menth yldiethylbenxainidine which remained was recrys tallised fromwater and then converted into the amidine.On crystallisation fromalcohol, t h i s formed small, rectangular plates, melting at 31-32' :0.4756 in 25 C.C. chloroform gave, in a 2-dcm. tube, uD - 6-53';whence [u]T - 172O334 COHEN AND MARSHALL:This substance was quite homogeneous, and proved to be identicalwith the amidine prepared from benzoylmenthylamide and diethyl-amine :0.4709 in 25 C.C. chloroform gave, in a 2-dcm. tube, a,, - 6.47O ;The hydrochloride was not crystalline, but the hydriodide crystal-lised from water in fine needles, which melted at 1 5 5 O . Theplatinichloride melts a t 180'.Before the enantiomorphous bornylamines were selected for use inthe final experiments, several attempts were made to prepare otherenan tiomorphou s bases.d-Dihydrocarv ylamine was prepared From d-carvone by reductionof the oxime with sodium in alcoholic solution (Wallach, Ber., 1891,24, 3984), and the laevo-base was obtained from d-limonene by wayof the nitrosochloride and I-carvoneoxime. The benzoyl derivativeswere prepared, but it was found that during the reaction of phosphoruspentachloride with these substances, hydrochloric acid is added on tothe molecule, and hence the use of an unsaturated base was out of thequestion.As the enantiomorphous carvones are easily obtained, it wasthought that the carvomenthylamines prepared by the same methodsfrom each of these carvones would answer our purpose.Accordingly,some time was spent in attempts to obtain these bases in quantity.Baeger's method (Ber., 1893, 26, 822) was first tried, but as veryunsatisfactory yields were always obtained, the mebhod wasabandoned.Attempts were made to reduce dihydrocarvylsmine to tetrahydro-carvylamine by Sabatier and Senderens' method, but, althoughreduction took place to some extent, the reduced product was inactive.Next, 2-amino-1 -methylcycZohexane was prepared from 1-methylcyclo-hexan-2-one, obtained from o-cresol (Sabatier and Mailhe, C m p t .rend., 1905, 140, 350), and an attempt mas made to resolve thisbase by fractional crystallisation of the d-cttmphorsulphonate.Nosatisfactory results mere obtained.The active benzoylderivative melts a t 139', and the inactive substance at 144'.whence [.IF - 172'.Finally, the two bornylamines mere prepared.d- Bovny I-1-bom ylbenxnmidine.The iminochloride of benzoyl-l- bornylamide was prepared in theusual way, and treated with a light petroleum solution of d-horoyl-amine. The amidine was isolated and crystallised from alcohol, fromwhich it separated in small prisms (often in stellate clusters), meltinga t 93-94'THE CONSTITUTION OF THE AMIDINES.335The substance was optically inactive. It agreed in every respectwith the amidine from benzoyl-d-bornylamide iminochloride and2-bornylamine :0.2013 gave 12.4 C.C. N, a t 1 2 ~ 5 ~ and 731 mm.C27H4,,N2 requires N = 7.1 4 per cent.The hydrochloride crystallises from ether in long needles, whichmelt a t 297". It is very soluble in alcohol. The platinichloridemelts a t 215'.The sulphate was obtained as fine needles from dilutealcohol, and melted at 138'. The hydyiodide is insoluble in water,crystallises easily from absolute alcohol, and melts at 262".The d-camplhorsui'phonate was prepared by mixing molecularproportions of the amidine and acid dissolved in ether and alcoholrespectively. The salt was crystallised several times from lightpetroleum, and melted at 205-206" :1.0353 in 25 C.C. alcohol gave, in a 2-dcm. tube, uD + 1-34'; whenceThe salt was further recrystallised, but the melting point was notaffected, and a determination of the specific rotation gave 16.4'. Asecond crop of crystals had a slightly lower melting point, and aspecific rotation of 15.4'.A quantity of the salt was mixed with ice-water, cold ether andcold sodium hydroxide solution added, and the ethereal solution of theamidine was immediately polarimetrically examined. No rotationcould be observed,N=7.15.[a]? + 16.2'.Eth y lut i o n of d - Boi-ny l-l -born y 1 bensamidine .The amidine was heated in a sealed tube with light petroleum andexcess of ethyl iodide for eight hours in a boiling-water bath. Oncooling, the hydriodide of the ethylamidine crystallises in fine needles,melting at 257-258', and these were recrystallised from a mixtureof benzene and light petroleum and decomposed by sodium hydroxide.The amidine melted at 93-94', and a mixture of this with theoriginal amidine had a melting point of 91-93".0.1997 gave 12.4 C.C. N, at 14' and 711 mm.The hydrochloride crystallises from alcohol in needles, meltingThe d;cccmpl~olr.suZpAonnte was prepared as before and recry stallised ;0.9987 in 25 C.C. alcohol gave, in a 2-dcm. tube, uD + 1.27'; whenceThe amidine recovered from this fraction of the salt was inactivefIt was inactive :N = 6.96.C29H44N2 requires N = 6.67 per cent.at 298'it melts a t 204-206':[uyr + 16.1336 JONES : SILVER AMALGAMS.as was also that obtained from the other fractions which wereseparately examined,The authors have to thank Mr. M7. H. Perkins for help in thepreparation of the first amidine described in this paper.THE UNIVERSITY,LEEDS

ISSN:0368-1645    

DOI:10.1039/CT9109700328

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

336 JONES : SILVER AMALGAMS.XXXVI1.-Silver Am algains.By HENRY CHAPMAN JONES.SILVER amalgams are of interest, not only because they are membersof the general class of amalgams, but also because some occur inNature, and because of the specific gravity of some of them beingmuch higher than that of mercury. The remarkable contractionthat takes place when the two metals combine was stated by Joule(Journ. Chem. SOC., 1863, 16, 383) to be “referable no doubt tothe assumption of the solid state by the mercury, the specific gravityof which comes out a t 16.5 from these (Joule’s) experiments.”This high value for the specific gravity of solid mercury does notappear to have been confirmed.The silver amalgams that have so far been examined have beenof very irregular compositions when viewed as compounds, andas they have been prepared by bringing the two metals togethereither directly, or by allowing an excess of mercury to precipitatesilver on itself from a salt solution, it is hardly possible that theamalgams obtained were homogeneous.The object of this paper is to indicate a method by which a seriesof silver amalgams may be obtained of definite molecular com-position (within the errors of experiment) and in a really homo-geneous condition; and, further, t o give some of the properties oftwo of them.Tho method consists, in short, in the preparation of a doublesalt, or a molecular mixture of salts, of the two metals withsubsequent reduction in the cold to the metallic condition.Whenmercuric chloride acts on either silver or mercury, or an amalgamof the two metals, each atom of either metal combines with amolecule of mercuric chloride.I f , then, the chlorine is removed,and this is easily done by means of ferrous oxalate, the metals aloneremain. I n this way amalgams may be obtained in which themetals exist in the proportions indicated by the formulze AgHg,AgHg,, AgHg,, AgHg,,, AgHggl, AgHg,, and the author hasactually prepared these six amalgams, although not all of them iJOKES : SILVER AMALGAMS. 337quantities suitable for examination. If the product of the actionof mercuric chloride on metallic silver, that is, the double chloride,AgHgCl,, is treated with an excess of sodium sulphite solution, halfthe silver and three-fourths of the mercury will be dissolved, andthere will remain an amalgam of the composition represented by theformula Ag,Hg.This, by treatment alternately with mercuricchloride and ferrous oxalate, gives another series of amalgams inter-mediate between the members of the series given above, namely,Ag,Hg, AgHg,, AgHg,, AgHg,,, etc.Preparation of the Amalgams.Some details concerning this have already been published ( J .SOC. Chein. Ind., 1893, 12, 983). A granular sample of metallicsilver reacts most readily with mercuric chloride-such preparationsas are obtained by the reduction of silver salts by means of zincin acid solutions, or by dextrose in the presence of alkali hydroxide.But metallic silver so obtained I have never found to be pure.I fdried at looo, it invariably loses something on ignition, 0.12, 0.74per cent., and so on in different cases, although the product waswell washed with dilute nitric acid and ammonia. Silver obtainedby reduction with ammonium sulphite, if properly washed anddried a t 100*, loses nothing on ignition, but such silver is flakyand crystalline rather than granular, and reacts less readily thanthe other. It is preferable, in using ammonium sulphite, to heatthe mixture quickly in small portions, and so obtain the metal morefinely divided than by the usual slow process.Metallic silver and mercuric chloride will interact in manydifferent liquids, or in no liquid, by simply shaking them togetherand allowing them to remain. I have always used water, but,judging from the analogous reaction with mercuric bromide, itmight be possible to find a medium that would expedite the change.Mercuric bromide reacts very slowly in water, the salt being verysparingly soluble; but in benzene, in which the salt is soluble topractically the same extent, the velocity of the reaction is veryremarkably increased, whilst in acetone, which very freely dissolvesthe mercuric bromide, the change does not appear to be so rapidas in benzene.Light petroleum dissolves much less of the mercuricsalt than water does, yet under otherwise the same conditions thechange will appear complete in light petroleum in a time that inwater has sufficed for little more than a superficial reaction.The reduction of the chloride by means of ferrous oxalate takesplace practically at once.The reagent is obtained by pouring onevolume of a saturated solution of ferrous sulphate into six volumesof a saturated solution of potassium oxalate. The large excess o338 JONES : SILVER AMALGAMS.the potassium oxalate is to make sure of keeping the iron salts insolution. The action of mercuric chloride on an amalgam soprepared, for the purpose of adding more mercury to it, is farmore rapid than the action on metallic silver, presumably becausethe amalgam is more finely divided. I f a double (or mixed)chloride of silver and mercury contains metallic silver (anunattacked residue, for example), it will not give a constant weighta t looo, as metallic mercury is liberated by the silver andcontinuously volatilised.The AnzaZ~ccn~ AgHg.-In bulk, as dried over sulphuric acidwithout the aid of heat (in a steam-oven such an amalgam lostmercury at a rate equivalent to 0.47 per cent.per hour), thisamalgam appears as a grey, non-adherent powder, which can beeasily burnished into a metallic film. It consists of roundedparticles, generally about 0.003 mm. in diameter. Some are ovaland up t o 0.005 mm. long, and ot.hers are as small as 0.002 mm.As diffused in cedarwood oil for microscopic examination, theparticles have a marked tendency to adhere in rows, often branched,Y-shape, but the individual particles are quite distinct, and thereis no appearance of a want of homogeneity. The silver mercurouschloride from which it was obtained was in similar roundedparticles, but more varied in size, and on the whole rather smaller.These differences are probably accidental, and it seems almostcertain that on the reduction of the chloride to the amalgam theseparate particles retain their individuality.The specific gravityof the amalgam, taken in water at 20° and compared with watera t 20°, was 12.8055. When pumping out the air, there appearedto be a continual evolution of gas, as if the amalgam decom-posed the water. A second estimation with more stringent methodsto remove air gave 12.8099. A determination in xylene showedthat t.hese figures are not low, and therefore that if the a.malganidoes act on the water the result is not sufficient to vitiate thedetermination. The calculated specific gravity, assuming no con-traction when the two metals combine, is 12-29.Evidently, there-fore, in the amalgam obtained as described, there is contractionon combination, but not nea-rly so much as in the crystallineamalgam which Joule obtained by placing mercury in silver nitratesolution. Such a preparation, which had approximately thesame composition, had a specific gravity of 14.68, and anothersample, obtained by adding more mercury and squeezing out asmuch as possible by a high pressure, gave 13.44. Other observershave found specific gravities for silver amalgams up to about 14.The Amalgam. AgHg3.-When the amalgam AgHg is acted onby mercuric chloride, the resulting chloride (empirically AgHg,Cl,CHATTAWAY AND MASON : HALOGEN DERIVATIVES, ETC.339is not distinguishable when viewed in bulk from the double chlorideAgHgC1, ; it is a white, soft-looking powder. When microscopicallyexamined, it is a t once clear that the characteristic structure ofthe double chloride, AgHgCl,, which persists in the amalgamAgHg, produced from it by reduction, has now gone-the particlesare disintegrated. They are smaller, 0*001 mm. in diameter or less,and irregular in shape. This chloride is easily reduced, and thedried amalgam, AgHg,, appears in bulk as an adherent powder.If allowed to fall froin the side of the bottle, it retains the shapeof the bottle, much as undried sea-sand does. If rubbed with theside of a knife it crunches, and the bright metallic scale so producedappears, on magnification, to have globules of mercury exudingfrom it. If pushed up into a fold of wash-leather with a tooth-brush handle, a large proportion of clean' mercury globules canbe pressed through the leather. When stirred into cedarwood oiland examined microscopically, it appears as crumbling, coherent,homogeneous masses, not separable into individual grains. Themasses have no appearance of liquidity, their outlines are irregularand angular, especially the smaller detached particles, and thepoints tend to be blunt rather than spiky.It is not proposed t o continue this investigation, but Dr. J. C.Philip hopes to examine the physical properties of some of theseamalgams, and t o study the influence of the medium on the velocityof the reaction between mercuric halides and metallic silver.ROYAL COLLEGE OF SCIENCE,SOUTH KENSINGTON

ISSN:0368-1645    

DOI:10.1039/CT9109700336

出版商:RSC    

年代:1910

数据来源: RSC

摘要:

CHATTAWAY AND MASON : HALOGEN DERIVATIVES, ETC. 339XXXV IT I. - Hul og e n Deriva t iues of 2Lfal on m i l i d e , E t h y 1Mcdonanilate, and iLIulonccnilic Acid.By FREDERICX DANIEL CHATTAWAY and FREDERICK ALFRED MASON.COMPOUNDS of this nature are a t present almost unknown, althougha knowledge of their properties is necessary before the action ofhalogens on the parent substances can be followed and beforeone of the least studied cases of intramolecular rearrangement canbe further investigated.The scanty literature dealing with the subject leaves theimpression that compounds of this class are difficult to prepare bya direct method, whereas the exact reverse is the case.The halogen derivatives of malonanilide and of ethylVOL XCVII. A 340 CHATTAWAF AND MASON : HALOGEN DERlVATIVES OFmalonanilate are produced together when malonic ester in someexcess is heated for a short time with the corresponding aniline, andcan easily be separated, owing to the sparing solubility of theanilides in all ordinary solvents.The best results are obtainedwhen about one gram-molecule of the aniline and one and a-halfgram-molecules of malonic ester are employed; if less ester is used,some aniline, which is troublesome to remove by crystallisation, isleft, whilst if more ester is taken, the products remain partlydissolved in the excess which has to be distilled off, a brownish-coloured product, which needs much purification, being obtained.About 10 to 15 grams of aniline is a convenient amount to use inone operation.The aniline and ester are heated together in a flask attachedto a long tube, which serves as a condenser, and the rate of boilingof the mixture is r.egulated so that the alcohol formed mainlyescapes while the malonic ester is returned to the flask.The yields are generally good, no appreciable decompositionoccurring, the loss arising only from the necessary separation andpurification.The halogen-substituted malonanilic acids are also very easilyobtained by hydrolysing the substituted malonanilic esters : thecrude products from which the substituted malonanilides have beenseparated suffice for this purpose.The esters can be hydrolysed by heating for a short time withaqueous sodium or potassium hydroxide, or even by heating for alonger time with water alone, but it is preferable to suspend themin a dilute solution of sodium carbonate and to pass steam throughthe liquid until the ester disappears. This method has theadvantage that if any aniline remains admixed with the crudeester or is formed during hydrolysis, it passes over with the steam.The acid is separated from the sodium salt in a crystalline state,after concentrating the solution if necessary, by adding a slightexcess of hydrochloric acid.When heated, the malonanilic acids decompose quantitativelyinto carbon dioxide and the corresponding substituted acetanilide,thus, for example :C6H4BroNH*CO*CH2*C0,H = CO, + C,H4Br*NH*CO*CH3.EXP E RIM EN TA L.pp-DichZoromaZonanilide, C6H4C1*NH*CO*CH,*C~*NH0C6H4~~.This compound, together with ethyl p-chloromalonanilate, isproduced when p-chloroaniline is heated with ethyl malonate.Amixture of 12 grams of p-chloroaniline and 25 grams of ethyMALONANILIDE, ETHYL MALONANILATE, AND MALONANILIC ACID 341malonate was gently boiled for thirty minutes, the alcohol formedbeing allowed to escape. The semi-solid mass left on cooling wasshaken with four times its bulk of alcohol, and the dichloromalon-anilide which remained undissolved was collected and recrystallisedalternately from alcohol and acetic acid. It is fairly soluble inboiling alcohol or acetic acid, and separates from either in small,slender, colourless needles, which, when dry, form a felted mass.The yield of pure product obtained thus is about 20 per cent.ofthe theoretical yield from the amount of aniline used.pp-Dichloromalonanilide melts and decomposes a t 261O :0,2474 gave 0.2206 AgC1. Cl= 22.06.C,,Hl20,N2C1, requires C1= 21.95 per cent.Ethyl p-Chlorom,alonanilate, CGH,C1*NH*CO*CH2*C0,*C2H6.This compound was obtained as a white, crystalline powder byslowly adding water to the filtrate from which dichloromalonanilidehad been separated. It was purified by repeatedly crystallising i tfrom hot alcohol, in which it is very easily soluble, and from whichit separates in short, colourless prisms, melting at 97O. It is veryreadily soluble in all common organic solvents, but only verysparingly so in water:0.2146 gave 0.1285 AgC1. C1= 14.81.C,,H,,O,NCl requires C1= 14.68 per cent.p-Chloromalonanilic A cid, C,H,C1*NH-CO*CH2*C02H.This compound was prepared by suspending ethyl pchlcro-malonanilate in twenty times its weight of water containing rathermore than the equivalent amount of sodium carbonate and passingsteam through the liquid until the ester had disappeared.Onadding hydrochloric acid in slight excess to the cooled product,the acid separated in thin, colourless plates. It was purifiedby recrystallisation either from hot water, in which it is mod-erately soluble, or from hot alcohol, in which it is readily so. Itseparates from either solvent in glistening, colourless, flattenedprisms or plates. On heating, it melts and decomposes, and evolvescarbon dioxide at about 16F',* leaving a residue of pure p-chloro-acetanilide, which, after solidification, re-melts a t 175O :* The melting points of this and the other substituted malonanilic acids describedin the paper represent the temperatures a t which the substances melt and rapidlydecompose with gas evolution when quickly heated.The ternpcratures a t whichthis melting takes place vary considerably with the rate of heating. Decompositionoccurs to some extent before these temperatures are reached, and if the acids areslowly heated, they appear to melt at lower temperatures.A A 342 CHATTAWBY AND MASON: HALOGEN DERIVATIVES OF0.2123 gave 0.1439 AgCl. C1= 16.77.C,H,O,NCl requires C1= 16.61 per cent.2 : 4 : 2/ : 4f-TetrachloromalolzaniZ~~e,C,H,Cl,*NH*CO*CH,*CO*NH*C,H3C12.This compound was obtained, together with ethyl 2 : 4-dicliloro-malonanilate, by boiling for about forty-five minutes a mixture of16 grams of 2 : 4-dichloroaniline and 24 grams of ethyl malonate.The tetrachloromalonanilide was separated as described under thecorresponding dichloro-compound, and purified by recrystallisationfrom boiling acetic acid.It is very sparingly soluble in boilingalcohol, and moderately so in boiling acetic acid. It crystallises incolourless, long, flattened needles or prisms, melting at 214O :0.2558 gave 0.3748 AgC1. C1= 36.25.C,,H,,O,N,Cl, requires C1= 36.19 per cent,Ethyl 2 : 4-Bic7~ZoromaZonaniZate, C,H3Cl,-NH*CO*CH2*C02*C2H,.This compound separated on cautiously adding water to thealcoholic filtrate from which the tetrachloromalonanilide had beenseparated.It was several times recrystallised alternately fromboiling acetic acid and alcohol, in both of which it is readilysoluble. It crystallises in colourless, flattened prisms, meltinga t 8 1 O :0.2527 gave 0.2620 AgC1. C1= 25.65.C,,Hl1O3NC1, requires C1= 25.69 per cent.2 : 4-Dic7~ZoromaZonaniZic A cid, C,H,Cl,*NH-CO*CH,*CO,H.This compound was prepared exactly as described under p-chloro-malonanilic acid. It is sparingly soluble in hot water, readilyso in boiling alcohol, and crystallises from the latter in colour-less, slender, flattened prisms. It melts and evolves carbon dioxideat about 1 6 4 O , and leaves a residue of pure 2 : 4-dichloroacetanilide :0.2896 gave 0.3337 AgCl.C,H,O,NCl, requires C1= 28.60 per cent.C1= 28.50.2 : 4 : 6 : 21 : 4/ : 6~'-Hexac?doromaZonanibide,C6H,C13*NH*CO*CH,*CO*NH*C6H2C13.2 : 4 : 6 : 2' : 4' : 6~-Hexachloromalonanilide, together with ethyl2 : 4 : 6-trichloromalonanilate, was prepared by gently boiling foran hour a mixture of 20 grams of 2 : 4: 6-trichloroaniline and 40grams of ethyl malonate, allowing the alcohol formed to escape.About 20 grams of unchanged malonic ester were then distilleMALONANILIDE, ETHYL MALONANILATE, AND MALONANLLIC ACID 343off.The residue was boiled with about 200 C.C. of alcohol, and thehexachloromalonanilide, which is practically insoluble in alcohol,was filtered off from the hot liquid. After washing repeatedlywith boiling alcohol, the white, crystalline residue was several timescrystallised from boiling acetic acid, in which i t is sparingly soluble,and from which it crystallises in colourless, very slender, hair-likeneedles.It turns brown, melts, and evolves gas at about 306O:0.1911 gave 0.3545 AgCl. C1=45.89.C1,H,O,~,C1, requires C1= 46.17 per cent.Ethyl 2 : 4 : 6-TrichloromtzlonaniEate,C,H,CI,*NH* CO*CI3,*CO2*C2H5.This was obtained by adding water to the alcoholic filtrate fromthe hexachloromalonanilide and repeatedly crystallising the esterthus separated from boiling alcohol. It is easily soluble in hotalcohol, and crystallises in colourless, slender prisms, melting at141O :0.3361 gave 0.4643 AgCI. C1= 34.17.C,,H,,O,NCl, requires C1= 34.26 per cent.2 : 4 : 6-T~ichZoroniaZonan~Z~c A cia?, C,H,C~,~~~*C'O~CH,~CO,H.This was prepared exactly as were the previously described acids.It Wacs repeatedly crystallised from boiling alcohol, in which it ismoderately easily soluble. It crystallises from alcohol in colourless,slender prisms, and from boiling water, in which it is sparinglysoluble, in small, fine, colourless needles. When heated, it meltsand evolves carbon dioxide at about 172O, forming 2 : 4 : 6-trichloro-acetanilide :0.1643 gave 0.2495 AgCl.CIz37.57.C,H,03NC13 requires C1= 37-66 per cent.pp -Dib romomdonan&de, C,H,Br- NHo CO*C~,*C~*NH*C,~,Br.Each bromine compound was prepared and isolated in a mannerresembling that described under bhe corresponding chlorine com-pound, so that it is only necessary to record their distinctivepeculiarities.pp-Dib romonzaZonan&de is sparingly soluble in boiling akohol,and moderately so in hot acetic acid.It crystallises from eithersolvent in colourless, slender needles, melting at 268O. I f kept a tthis temperature, some decomposition takes place, the fused sub-stance turning brown and giving off bubbles of gas. The otherhalogen-substituted malonanilides behave similarly :0.2865 gave 0-2598 AgBr. Br = 38-59.C,,R,,O2N,Br2 requires Br = 38.80 per cent344 CHATTAWAY AND MASON: HALOGEN DERIVATIVES OFEthyl p-Br omomaZonadut e, C6H4Br~~H~C'O~CH20C020C,H,.Ethyl p-bromomalonanilate crystallises from alcohol, in which itis easily soluble, in colourless, short, rhombic prisms, melting at 99O :0.2715 gave 0.1788 AgBr.Cl1Hl2O3NBr requires Br = 27.94 per cent.Br = 28.03.p-Bromomalonanilic A cid, C,H,Br*NH*CO*CH,-CO,H.This compound is sparingly soluble in boiling water, but readilyso in hot alcohol.It crystallises from water or alcohol in colourless,flattened, slender prisms. It melts at 169O, carbon dioxide isevolved, and p-bromoacetanilide is formed :0,1750 gave 0.1271 AgBr. Br = 30.91.CgHs03NBr requires Br = 30.98 per cent.2 : 4 : 21 : 4f-TetrabrommaZonaniZide,C,H3Br20NH*CO*CH2*CO*~H*c6€~3Br2.This compound crystallises from boiling acetic acid, in which itis moderately soluble, in colourless, long, flattened ueedles or prisms,melting at 233O :0.2092 gave 0.2769 AgBr. Br = 56-33.C1,Hl,02N2Bra requires Br =56-11 per cent.EthgZ 2 : 4-BibromomaZonanilate,C6H3Br,oNH*C 0 CH2*C0,* C2H5.This compound crystallises from alcohol, in which it is easily0.2431 gave 0.2496 AgBr.Br=43*69.soluble, in colourless, slender, flattened prisms, melting a t 86O :CllH1103NBr2 requires Br = 43-80 per cent.2 : 4-DibromdonaniZic A cid, C6H3Br2*NH*CO*CH2*C02H.2 : 4-Dibromomalonanilic acid is sparingly soluble in water, buteasily so in alcohol. It crystallises from alcohol in colourless,flattened prisms. When heated, it melts, and evolves carbon dioxideat 174O, 2 : 4-dibromoacetanilide being formed :0.2880 gave 0.3195 AgBr. Br =47*21.C,H,03NBr2 requires Br =47*44 per cent.2: 4: 6 : 21: 41: 6~-HexabromomaZonartilide;C,H2Br,*NH~CO~CH2-CO~NH*C,H2Br3.This anilide is so sparingly soluble in all ordinary solvents thatit can only be recrystallised in very small amount from boilingacetic acid.A few tenths of a gram only are dissolved by a litrMALONANILIDE, ETHYL MALONANILATE, AND MALONANILIC ACID 345of boiling acetic acid. It separates from this solvent in colourless,very small, hair-like needles. It can be recrystallised from boilingnitrobenzene, but the product obtained is not quite pure, and veryconsiderable loss from decomposition occurs. It melts and evolvesgas a t 331O:0.1314 gave 0.2041 AgBr.C,,H,O,N,Br, requires Br = 65.90 per cent.Freund (Ber., 1884, 17, 782) obtained a compound to which heassigned this constitution by dissolving malonanilide in glacialacetic acid, and adding bromine in slight excess to the warmedsolution drop by drop. The liquid on cooling deposited a thickcrop of needles, which, after several recrystallisations from aceticacid, melted at 145--146_O.This substance, on heating in a sealedtube with fuming hydrochloric acid at 200°, yielded a, compoundwhich he regarded as symmetrical tribromoaniline, and from thisobservation he deduced its constitution.Freund's compound, however, differs so entirely in its properticsfrom the compound described above, which itself possesses all theproperties that would be expected from a consideration of thoseof the other members of the class described in this paper, thatit cannot have the constitution assigned by him to it.Br = 66.10.Ethyl 2 : 4 : 6-TribromodonaniZate,C6H2Br3-NH*CO*CH2*C0,*C,H,.Ethyl 2 : 4 : 6-tribromomalonanilate is readily soluble in hotalcohol, and crystallises from it in colourless, slender prisms, meltingat 177O:0.1458 gave 0.1854 AgBr. Br=54*11.C,,H,,03NBr, requires Br = 54.02 per cent.2 : 4 : 6-TribromomuZonaniZic A cid, C,H,Br3*NH*CO*CH,*C0,H.2 : 4 : 6-Tribromomalonanilic acid crystallises from alcohol, inwhich it is moderately soluble, in small, colourless needles. If theacid is rapidly heahd, it melts and evolves carbon dioxide a tabout. 201°, 2 : 4 : 6-tribromoacetanilide being produced. If slowlyheated, however, it decomposes below this temperature withoutmelting, carbon dioxide as before is given off, whilst 2 : 4 : 6-tri-bromoacetanilide, which, if the temperature be raised, melts sharplyat 232O, is left in the tube:0.2000 gave 0.2699 AgBr. Br = 57-43.C,H,O,NBr, requires Br = 57.66 per cent.UNIVERSITY CHEMICAL LABORArORY,OXFORD

ISSN:0368-1645    

DOI:10.1039/CT9109700339

出版商:RSC    

年代:1910

数据来源: RSC