摘要:

J O U R N A L OF THE CHEMICAL SOCIETY, TRANSACTIONS. HORACE T. BROWN, LL.D., F.R.S. J. DEWAR, LL.D., F.R.S. WYNDHAM R. DUNSTAN, M.A., F.R.S. C. E. GROVES, F.R.S. A. VERNON HARCOURT, M. A,, F.R. S. C. T. HEYCOCK, M.A., F.R.S. R. MELDOLA, F.R.S. H. FORSTEE MORLEY, M. A,, D.Sc. A. SCOTT, D.Sc., F.R.S. T. E. THORPE, LL.D., F.R.S. W. A. TILDEN, D. Sc., F. R. S. @hifor# : C. E. GROVES, F.R.S. W. P. WYNNE, D.Sc., F.R.S. Sinb-@;Mtar ; A. J. GREENAWAY. 1899. Vol. LXXV. LONDON: GURNEY & JACKSON,: 1, PATERNOSTER ROW, 1899.I ~ I C H A I ~ ~ CLAY AND BONS, LIAIITM:U LONDON AND BC’YCIAI’.C O N T E N T S. PAPERS READ BEFORE 1.-The Oxidation of Polyhydric By HENRY J. HOBSTMAN JACKSON, B.A., B.Sc. I1 .-D-Ald e bydopropionic Acid, THE CHEMICAL SOCIETY. PAGE Alcohols in Presence of Iron.FENTON, M.A., and HENBY CHO*CH;CH,*C00H. and . 1 b-Aldehydoikobutyric Acid, CHO*C~,*Cri(CH,)*COOH. By WILLIAM H. PERKIN, jun., and CHARLES H. G. SPRANKLING 111.-Cannabinol. Part I. By THOMAS BARLOW WOOD, M.A.; W. T. NEWTON SPIVEY, M.A. ; THOMAS HILL EASTERFIELD, M.A., Ph.D. . 1V.-Characterisation of Racemic Compounds. By FREDERIC STANLEY KIPPING and WILLIAM JACKSON POPE . V.-Crystalline Form of Iodoform. By WILLIAM JACESON VL-PP-Dimethylglutaric Acid and its Derivatives ; Synthesis By WILLIAM H. PERKIN, POPE . of cie- and tram-Caronic Acids. jun., and JOCELYN F. THORPE. . VII. -Sy n t hesis of apP-Trime t h y lglutaric Acid, COOH*CH(CH,)*C(CH,),*CH,*COOH. By WILLIAM H. PERKIN, jun., and JOCELYN F. THORPE . VI1I.-Occurrence of Orthohpdroxyacetophenone in the Volatile Oil of Chione glabra.By WYNDHAM R. DUNSTAN, F.R.S., and THOMAS ANDERSON HENRY, Salters’ Research Fellow in the Laboratories of the Imperial Institute 1X.-Occurrence of Hyoscyamine in the Hyoscyamus mulicus of India. By WYNDHAM R. DUNSTAN, F.R.S., and HAROLD BROWN, Assistant Chemist in the Laboratories of the Imperial Institiite . X.-Preparation of Hyponitrite from Nitrite, through Hydroxy- amidosulphonate. By EDWARD DIVERS, M.D., D.Sc., F.R.S., XI.-Absorption of Nitric Oxide in Gas Analysis. By EDWARD XI1.-Interaction of Nitric Oxide with Silver Nitrate. By . and TAMEMASA HAGA, D.Sc., F.C.S. . . . DIVERS, M.D., D.Sc., F.R.S. . EDWARD DIVERS, M.D., D.Sc., F.R.S.. A 2 11 20 36 46 4s 61 66 72 77 82 83iv CONTENTS. XII1.-Preparation of Pure Alkali Nitrites. By EDWARD DIVERS, M.D., D.Sc,, F.R.S.. . . . 8 . X1V.-Reduction of an Alkali Nitrite by an Alkali Metal. By EDWARD DIVERS, M.D., D.Sc., F.R.S. . * . 8 XV.-Hyponitrites ; their Properties, and their Preparation by Sodium or Potassium. By EDWARDIVERS, M.D., D.Sc., F.R.S. , . I . . . XV1.-Derivatives of Camphoric Acid. Part 111. By FRED- ERIC STANLEY KIPPING, Ph.D., D.Sc., F.R.S. . . XVI1,-a-Retotetrahydronaphthalene. By FREDERIC STANLEY KIPPING, Ph.D., D.Sc., F.R.S., and ALFRED HILL XVII1.-Production of Optically Active Mono- and Di-alkyl- oxyswcinic Acids from Malic and Tartaric Acids. By THOMAS PURDIE, F.R.S., and WILLIAM PITKEATHLY, B.Sc., Berry Scholar in Science . . . X1X.-Determination of the Constitution of Fatty Acids. Part I. By ARTHUR WILLIAM CROSSLEY and HENRY RONDEL LE SUEUR .. . XX.-Some Halogen Derivatives of Acetone Dicarboxylic Acid. Part 1. By FREDERICK W. DOOTSON, M.A. , . XX1.-Action of Chlorosulphonic Acid on the Paraffins and other Hydrocarbons as a means of Purifying the Normal Paraffins. By SYDNEY YOUNG, D.Sc., F.R.S. . XXI1.-Oxidation of Sulphocamphylic Acid. By W. H. PERKIN, jun. . . XXII1.-Researches on Moorland Waters. I. Acidity, By WILLIAM ACKROYD, F.I.C. . . XX1V.-The Nutrition of Yeast. Part I. By ARTHUR L. STERN, D.Sc. . . . . . XXV.-An Isomeride of Amarine. By H. LLOYD SNAPE, D.Sc., Ph.D., and ARTHUR BROOKE, Ph.D. XXV1.-Studies of the Terpenes and Allied Compounds. Nitrocamphor and its Derivatives. 1V. Nitrocamphor as an Example of Dynamic Isomerism. By T. MARTIN LOWRY, B.&.. . . XXVI1.-The Action of Ammonia on Ethereal Salts of Organic Acids. By SIEGFRIED RUHEMANN. . XXVIII.-The Changes of Volume due to Dilution of Aqueous Solutions, By EDWARD BRUCE HERSCHEL WADE, M.A. , XX1X.-Methanetrisulphonic Acid. By ERNEST HAROLD BAGINALL, B.Sc. . . XXX.-Maltodextrin : its Oxidation-Products and Constitution. B~HORACE T. BROWN, LL.D., F.R.S., and JAMES HILLS MILLAR . , PAGE 86 8’7 95 125 144 153 161 169 172 175 196 20 1 208 21 1 246 254 278 286CONTENTS. V XXX1.-Attempts to Prepare Pure Starch Derivatives through their Nitrates. By HORACE T. BROWN, LL.D., F.R.S., and JAMES HILLS MILLAR . XXXI1.-The Stable Dextrin of Starch Transformations, and its Relation to the Maltodextrins and Soluble Starch. By HORACE T. BROWN, LL.D., F.R.S., and JAMES HILLS MILLAR XXXIIL-Position Isomerism and Optical Activity ; the Methylic and Ethylic Salts of Benzoyl- and of Ortho-, Meta-, and Para-toluylmalic Acids.By PERCY FRANKLAND, Ph.D., F.R.S.,: and FREDERICK MALCOLM WRARTON, A. I.C., late Priestley Scholar in Mason University Oollege, Birmingham. XXXIV.-Some Regularities in the Rotatory Power of Homo- logous Series of Optically Active Compounds. By PERCY FRANKLAND, Ph.D., F.R.S. XXXV.-Detection and Determination of Sucrose in the Presence of Lactose. By EDWIN DOWZARD . * XXXV1.-Note on Certain Isomeric Tertiary Benzylthioureas. By AUGUSTUS EDWARDIXON, M.D. . . XXXVI1.-On LGssner’s Benzoylethyloxysulphocarbamic Acid ; and the Formation of Pseudoureas. By AUGUSTUS EDWARD DIXON,M.D. . XXXVIIL-Action of Metallic Thiocyanates on Certain Sub- stituted Carbamic and Oxamic Chlorides; and a New Method for the Production of Thiobiurets. By AUGUSTUS XXX1X.-Formation of a-Pyrone Compounds and their Trans- formation into Pyridine Derivatives.By SIEGFRIED RUHEMANN . . I . XL.-Hydrolysis of the y-Cyanides of Di-substituted Aceto- acetates. By WILLIAM TREVOR LAWRENCE . XL1.-Bromomethylfurfuraldehyde. By HENRY J. HORSTMAN FENTON, M.A., and Miss MILDRED GOSTLING, B.Sc., Bathurst Student of Newnham College . XLI1.-A Reaction of some Phenolic Colouring Matters. By ARTHUR GEORGE PERKIN, F.R.S.E. , . XLII1.-A Method of Studying Polymorphism, and on Poly- morphism as the Cause of some Thermal Peculiarities of Chloral Hydrate, XL1V.-Contribution to the Characterisation of Racemic XLV.-Etherification Constants of Substituted Acetic Acids, By JOHN J.SUDBOROUGH and LORENZO L. LLOYD , . E. DIXON, M.D. . . . . By WILLIAM JACKSON POPE Compounds. By A. LADENBURG . . w . I PAQE 308 315 337 347 371 373 375 388 41 1 41 7 423 433 455 465 467vi CONTENTS. X LV1.-The Rotatory Powers of Optically Active Methoxy- and Ethoxy-propionic Acids prepared from Active Lactic Acid. By THOMAS PURDIE, F.R.S.,and JAMES C. IRYINE, B.Sc. The Com- parative Rotatory Powers of Methylic and Ethylic Ditoluyl- glycerates. By PERCY FRANKLAND, F.R.S., and HENRY ABTON, late Priestley and Forster Scholar in M.ason Uni- versity College, Birmingham . . XLVII1.-Isomeric Fencholenic Acids. By GEORUE BERTRAM COCKBURN, B.A., B.Sc. . . XLIX.-Synthesis of some Derivatives of PP-Dipyridyl from Citrazinic Acid.By W. J. SELL, M.A., F.I.C., and H. JACKBON, B.A., B.Sc. . L.-The Condensation of Oxalic Acid and Resorcinol. By JOHN THEODORE HEWITT and ARTHUR ERNEST PITT . L1.-Synthesis and Preparation of Terebic and Terpenylic Acids. By W. TREVOR LAWRENCE . LI1.-Ethyl A mmoniumsulphite. By EDWARD DIVERS and MASATAKA OGAWA . LII1.-Ethyl Ammonium Selenite and the Non-existence of Amidoselenites (Selenosamates). By EDWARD DIVERS and SEIHACHI HADA. . L1V.-The Action of Certain Acidic Oxides on Salts of Hydroxy- acids. IV. By GEORGE GERALD HENDERSON, D.Sc., M.A., THOMAS WORKMAN ORR, and ROBERT J. GIBSON WHITEHEAD LV.-Derivatives of aa'-Dibromocarnphorsulphonic Acid. By ARTHUR LAPWORTH . LV1.-Crystalline Glycollic Aldehyde. By HENRY J. HORSTYAN FENTON, M.A., and HENRY JACKSON, B.A., B.Sc.. LVI1.-Diortho-substituted Benzoic Acids. Part IV. Form- ation of Salts from Diortho-substituted Benzoic Acids and different Organic Bases. By LORENZO L. LLOYD and JOHN J. SUDBOROUGH . . . LVI.11.-A Kew Compound of Arsenic and Tellurium. By E. C. SZARVASY, Ph.D., and C. MESSINOER, Ph.D. . LlX.-The Combustion of Carbon Disulphide. By HAROLD BAILY DIXON and EDWARD JOHN RUSSELL . LX.-The Action of Nitric Oxide on Nitrogen Peroxide. By HAROLD BAIGY DIXON and JAMES DYSART PETERKIN . LXI.--On the Mode of Burning of Carbon. By HAROLD BAILY DIXON . XLV11.-Position-Isomerism and Optical Activity. PAGE 483 493 501 507 518 527 533 537 542 558 5 75 580 597 600 613 630CONTENTS. vii LXI1.-A Study of the Absorption Spectra of Isatin, Car- bostyril, and their Alkyl Derivatives in Relation to Taut- omerism. By WALTER NOEL HARTLEY, F.R.S., and JAMEB LXIII.-Preparation of Acid Phenylic Salts of Dibasic Acids. By SAMUEL BARNETT SCHRYVER, D.Sc., Ph.D. LX1V.-Corydaline. Part TI. By JAMES J. DOBRIE, D.Sc., M.A., and ALEXANDER LAUDER . LXV.-The Relative Efficiency and Usefulness of various Forms of Shill-head for Fractional Distillation, with a Description of some new Forms possessing special Advan- tages. By SYDNEY POUNU, D.Sc., F.R.S. . LXV1,-The Salts of Dimethylpyrone, and t h e Quadrivalence of Oxygen. By J. N. COLLIE, Ph.D., F.R.S., and THOMAS TICKLE, Salters’ Company’s Research Fellow in the Research Laboratory of the Pharmaceutical Society of Great Britain LXVI1.-Chemical Examination of the Oleo-resin of Dacryodes hexandra.By ANDREW MORE, A.R.C.S. . LXVIIL-Estimation of Boric Acid mainly by Physical Processes. By A. WYNTER BLYTH , LXIX-The Blue Salt of Fehling’s Solution and other Cupro- tartrates. By ORME MASSON, M.A., D.Sc., and B. D. LXX.-The Allotropic Modifications of Phosphorus. By DAVID LEONARD CHAPMAN, B.A. . . LXX1.-Oxidation of Furfuraldehyde by Hydrogen Peroxide. By C. F. CROSS, E. J. BEVAN, and THY. HEXBERG . LXXI1.-Active and Inactive Phenylalkyloxyacetic Acids, By ALEX. MCKENZIE, M.A., D.Sc. . LXXIIL-Some Derivatives of Dimethyldihydroresorcinol. By ARTHUR WILLIAM CROSSLEP . LXXIV.-Condensation of Ethylic Salts of Acids of the Acetylene Series with Ketonic Compounds. By SIEGFRIED RUHEMANN and A. V. CUNNINGTON LXXV.-Action of Hydrogen Peroxide on Carbohydrates in the Presence of Ferrous Salts.By ROBERT SELBY MORRELL, M.A., Ph.D., and JAMES MURRAY CROFTS, B.A., B.Sc.. LXXV1.-The Action of Alkyl Haloids on Hy droxylamine. Formation of Substituted Hydroxylamines and Oxamines. By WYNDHAM R. DUNSTAN, F.R.S,, and ERNEST GOULDINa, B. sc. . . LXXVI1.-The Condensation of Ethylic Acetonedicarboxylate and Constitution of Triethylic Orcinoltricarboxylate. By DAVID SMILE8 JERDAN . * . . . . a J. DOBBIE, M.A., D.Sc. . * . . . STEELE, B.Sc. . s . . PAGE 640 661 6 70 6 79 710 7 18 722 725 734 747 753 771 778 786 792 808viii CONTENTS. LXXVII1.-The Colouring Matter of Cotton Flower8, Gor~yphm herbaceurn. Note on Rottlerin. By ARTHUR QEOEGE PERKIN, F.R.S.E. . . LXX1X.-T he Colouring Matters contained in Dyer’s Broom (Genista tinctoria) and Heather (Calluna vulgarig).By ARTHUR GEORGE PERKIN, F.R.S.E., and FREDERICK GEORGE NEWBURY . . . LXXX.-Researches on the Alkyl-substituted Succinic Acids. Part I. Methods of Preparation. By WILLIAM A. BONE and CHARLES H. G. SPRANKLINB. . . . . By FRANCIS E. FRANCIS, B.Sc., Ph.D., Lecturer in Chemistry, University LXXXI1.-Action of Light and of Oxygen on Dibenzyl Ketone. By EMILY C. FORTEY, B.Sc. LXXXII1.-The Vapour Pressures, Specific Volumes and Critical Constants of Hexamethylene. By SYDNEYOUNG, D.Sc., F.R.S., and EMILY C. FORTEY, B.Sc. LXXX1V.-The Composition and Tensions of Dissociation of the Ammoniacnl Chlorides of Cadmium. By WILLIAM ROBERT LANO, D.Sc., and ALBERT RIGAUT . . . LXXXV.-The Aluminium-Mercury Couple. Part I. Action of Sulphur Chloride on some Hydrocarbons in presence of the Couple, By JULIUS BEREND COHEN and FREDERICK WILLIAM SKIRROW, The Yorkshire College .LXXXV1.-The Aluminium-Mercury Couple. Part 11. The Action of Bromine on Organic Compounds in presence of the Couple, By JULIUS BEREND COHEN and HENRY D. LXXXVI1.-Experiments on the Constitution of Isooamphor- onic Acid. By WILLIAM HENRY PERKIN, jun., and JOCELYN FIELD THORPE . . . . . a * . LXXXVIIL-The cis- and tr~~s-~-Phenylbutane-aala,-tricarb- oxylic Acids, COOH*CH,* CH(C,H,)* CH(COOH)*CH,- COOH. By JOCELYN FIELD THORPE and WILLIAM UDALL . , LXXX1X.-Experiments on the Synthesis of Camphoric Acid. Part IT. By H. A. AUDEN, WILLIAV HENRY PERKIN, jun., and J. L. ROSE . I . . . XC.-The Action of Ethylene Dibromide and Trimethylene Di- bromide on the Sodium Compound of Ethylic Cyanacetate.By H. C. H. CARPENTER and WILLIAM HENRY PEBKIN, jun. XC1.-Influence of Substitution on Specific Rotation in the Bornylamine Series. By MARTIN ONSLOW FORSTER, Ph.D., D.Sc. b . . LXXX1.-Some Derivatives of Dibenzyl Eetone. College, Bristol . . m . . . . DAKIW, The Yorkshire College . . . PAGE 825 830 839 865 871 873 883 887 893 897 904 909 921 953CONTENTS. ix PAQI XCI1.-Studies of the Acids of the Acetylene Series. By SIEGFRIED RUHEMANN and ALFRED V. CUNNINGTON. . . 954 XCII1.-A Contribution to the Chemistry of the Mandelic Acids. By ALEX. MCKENZIE, M.A., D.Sc. . . 964 XC1V.-Non-existence of the so-called Suboxide of Phosphorus. By DAVID LEONARD CHAPMAN and F. AUSTIN LIDBURY. , 973 XCV.--The Chlorine Derivatives of Pyridine.Part 111. The Interaction of Chlorine and Pyridine Hydrochloride. By WILLIAM JAMES SELL, M.A., F.I.C., and FREDERICK WILLIAM DOOTSON, M. A. . 979 XCVI.-Homocamphoronic and Camphononic Acids. By ARTHUR LAPWORTH D.Sc., and EDGAR M. CHAPMAN, Burrough’s Scholar i n the Research Laboratory of the Pharmaceutical Society of Great Britain. . . 986 XCVI1.-The Action of Hydrogen Peroxide on Secondary and Tertiary Aliphatic Amines. Formation of Alkylated Hydroxylamines and Oxarnines. By WYNDHAM R. DUNSTAN, F.R.S., and ERNEST GOULDING, B.Sc. . . 1004 XCVIII. -Amidoamidines of the Naphthalene Series. By RAPHAEL MELDOLA, F.R.S., and PERCY PHILLIP PHILLIPS. . 1011 XC1X.-Condensations of Anhydracetonebenzil and its Ana- logues with Aldehydes.By FRANCIS R. JAPP, F.R.S., and ALEXANDER FINDLAY, M.A., B.Sc. . , 1017 C.-Triphenyloxazolone. By FRANCIS R. JAPP, F.R.S., and ALEXANDER FINDLAY, M.A., B.Sc. . . 1027 GI.-Interaction of Phenanthraquinone, Acetopheuone, and Ammonia. By FRANCIS R. JAPP, F.R.S., and ANDREW N. MELDRUM, B.Sc. . 1032 CI1.-Furfuran Derivatives from Benzoin and Phenols. By FRANCIS R. JAPP, F.R. S., and ANDREW N. MELDRUM, B.Sc. 1035 (3111.-Interaction of Benzoin with Phenylenediamines. By FRANCIS R. JAPP, F.R.S., and ANDREW N. MELDRUM, B.Sc. 1043 CIV.-A Series of Substituted Nitrogen Chlorides and their Relation to the Substitution of Halogen in Anilides and Anilines. By HUGH RYAN, M.A., 1851 Exhibition Scholar of the Queen’s College, Galway . , 1054 CV1.-The Action of Sulphuric Acid on Fenchone.By JAnrEs E. MARSH. . 1058 CVI1.-On a Method for Providing a Current of Gaseous Chloroform mixed with Air in any desired proportion, and on Methods for Estimating the Gaseous Chloroform in the Mixtures. By A. VERNON HARCOURT, M.A., F.R.S., Lee’s Reader in Chemistry a t Christ Church, Oxford . . 1060 By F. D. CHATTAWAY and K. J. P. ORTON. . 1046 CV.-Synthetical Preparation of Glucosides.x CONTENTS. PAGE CVII1.-The Application of Powerful Optically Active Acids t o the Resolution of Externally Compensated Basic Substances. Resolution of Tetrahydroquinaldine. By WILLIAM JACKSON POPE and STANLEY JOHN PEACHEY . . 1066 C1X.-The Application of Powerful Optically Active Acids to the Resolution of Externally Compensated Basic Substances. Resolution of Tetrahydroparatoluquinaldine.By WILLIAM JACKSON POPE and EDMUND MILTON RICH . . 1093 CX.-The Application of Powerful Optically Active Acids t o the Resolution of Externally Compensated Basic Substances. Resolution of Racemic Camphoroxime. By WILLIAM JACKSON POPE . . 1105 CXL-Homogeneity of Dextrolaevo-a-phenethylamine Dextro- camphorsulphonate. By WILLIAM JACKSON POPE and ALFRED WILLIAM HARVEY . I . 1110 CXI1.-A Method for Discriminating between ‘L Non-racemic ” and “ Racemic ” Liquids. By WILLIAM JACKSON POPE and STANLEY JOHN PEACHEY . . * 1111 CXII1.-The Characterisation of “ Racemic ” Liquids, By FREDERIC STANLEY RIPPING and WILLIAM JACKSON POPE . 1119 CXIV.-Asymmetric Optically Active Nitrogen Compounds. Dextro- and Laevo-a-benzylphenylallylmethylammon~um Iodides and Bromides. By WILLIAM JACKSON POPE and STANLEY JOHN PEACHEY . . 1127 CXV.-Tetrazoline. By SIEGFRIED RUHEMANN and H. E. STAPLETON, Scholar of St. John’s College, Oxford . . 1131 CXV1.-Action of Hydrolytic Agents on a-Dibromocamphor. Constitution of Bromocamphorenic Acid. By ARTHUR LAPWORTH . . 1134 CXVI1.-Camphoroxime. Part 111. Behaviour of Camphor- oxime towards Potassium Hypobromite. By MARTIN ONSLOW FORSTER, Ph.D., D.Sc. CXVII1.-Influence of an Unsaturated Linking on the Optical Activity of Certain Derivatives of Bornylamine. By MARTIN ONSLOW FORSTER, Ph.D., D.Sc. . . 1149 CXJX.-The Interact ion of Sodium Hydroxide and Benz- aldehyde. By CHAXLES ALEXANDER KOHN, Ph.D., B.Sc., and WILLIAM TRANTOM, Ph.D., B.Sc. . 1155 CXX.-The Ultra-violet Absorption Spectrum of Proteids in Relation to Tyrosine. By A. WYNTER BLYTH . . 1163 Annual General Meeting . . 1167 . 1141

ISSN:0368-1645    

DOI:10.1039/CT89975FP001

出版商:RSC    

年代:1899

数据来源: RSC

摘要:

/3-&LDEHYDOPROPIONlC ACID, ETC. IT.+- Aldehydopropionic Acid, CHOGH,. CH,*COOH, and P-Aldehydoisobutyric Acid, CHO *CH2* CH(CH,)*COOH. By W. H. PERKIN, jun., and C. H. G. SPRANKLING. SOME time since (Trans., 1896,69, 162), a paper was published by one of us in conjunction with Messrs. W. IT. Bentley and E. Haworth which had for one of its objects the discovery of a method for intro- ducing the group *CH,*CH,*OH into organic substances, a synthetical process which, if it could be easily carried out, would be very valuable as a means of forming ring compounds. It was found that theaction of glycol chlorhydrin, Cl*CH,*CH,*OH, on the sodium compounds of substances like ethylic acetoacetate, ethylic malonate, and their derivatives, did not, except in isolated cases, yield the desired result ; ultimately, however, a method was devised which in the few cases tried gave fairly satisfactory results, and which may be briefly stated in the form of an example thus./3-Bromethyl phenyl ether,C,H,*O*CH,*CH,Br,was prepared by acting on sodium phenoxide with ethylene bromide, and this, when digested with the sodium derivative of ethylic methylmalonate, yielded ethylic y-phenoxyet h ylmeth ylmalona te , C1,H,~O0CH2*CR2*C(CH,)( COOC,H,) 2. The acid corresponding to this ethereal salt, when heated a t looo, losea12 PERKIN AND SPRANXLINQ : &ALDEHYDOPROPIONIC ACID one molecule of carbon dioxide with formation of y-phenoxyethyl- methylacetic acid, C,H,*O*CH,* CH,*CH( CH,) COOH, from which hydrobromic acid eliminates the phenyl group and forms y-bromethyl- methylacetic acid, CH2Br*CH2*CH(CH,)*COOH.This brom-acid when boiled with sodium carbonate, gives the sodium salt of hydroxyethyl- methylacetic acid, OH*CH,*CH,*CH(CH,)*COONa, from which, on - - acidifying, met hy 1 bu tyrolactone QH,.~’~*QH*cH,, is at once 0--co obtained. When this method was tried in more complicated synthetical experiments, it did not work well, partly owing to the number of operations involved, but principally on account of the smallness of the yield obtained in some of these operations. For these reasons, experi- ments were made with a view to discover a more direct method, and ultimately we found in bromacetal, (C,H,O),CH*CH,Br, a subst.ance which seems likely to answer the purpose. Bromacetal reacts readily with the sodium derivative of ethylic malonate, yielding ethylic acetaZmaZonai?e according to the equation (C2H50),CH*CH,Br + CHNa(COOC,H,), = (C,H,O),CH*CH,*CH( COOC,H,), + NaBr. This ethylic salt, which distils without decomposition at 151-154O (16 mm.), yields, on hydrolysis, the corresponding acetrclmalonic acid, (C2H50),CH*CH,*CH(COOH),, and this, when heated with water at 180” is decomposed into alcohol, carbon dioxide, and P-uZdehydopopimic acid, (C2H50)2CH*CH2*CH(COOH)2 + H20 = CHO*CH2* CH2* COOH + 2C2H,*OH + CO,.P-Aldehydopropionic acid is a new and very inter- esting substame, since it is the (‘ half-aldehyde ” of succinic acid and belongs to the class of aldehyde acids of which, so far, very few hum been prepared, Its properties show that it is a true aldehyde, and not a hydroxymethylene compound of the formula CH( OH): CH*CH,* COOH, it therefore, does not belong to the class of substances which Claiseo has investigated with such brilliant results.Aldehydopropionic acid is an almost colourless liquid which reduces Fehling’s solution and gives a violet coloration with a solution of rosaniline hydrochloride decolorised by sulphurous acid. It is slowly oxidised in contact with air, rapidly by nitric acid, with formation of succinic acid, and when reduced with sodium amalgam it yields butyroZactone, O-- CHO*CH2*CH2*COOH = OH*CH,*CH2*CH2*COOH = When boiled with caustic soda solution in a flat basin, aldehydopropionic acid undergoes a most interesting change, yielding small quantities of terephthalic acid, the dihydroterephthalic acid, which may be assumed to be the first product of the condensation, being oxidised to tire-AND &ALDEHYDOISOBUTP RIC ACID.13 phthalic mid by the action oE the air, C H O CH,*CH,*COOH gH*CH,*g*COOH GH-CH :q*COOH COOH* CH,* CH,* CHO = CO0H.C CH,. CH = CO0H.C CH : CH and this is, so far, the only experiment which has been instituted with the object of testing the value of aldehydopropionic acid in conden sation experiments. The action of bromacetal on sodium compounds is probably a general one, since we have found that the reaction proceeds equally well when the sodium derivative of ethylic methylmalonate is substituted for that of ethylic malonate in the above experiments. The ethyl& acetalmthylmahate, (C,H,O),CH* C H,* C( CH,)( COOC,H,), , thus obtained yields acetalmethylmlortic acid, (C,H,O),*CH*CH,*C( CH,)(COOH),, on hydrolysis, and this, when heated with water a t 180°, is converted into @-aldehydoisobutyricacid, CHO*CH,*CH(CH,)*COOH, a liquid acid which, on oxidation, yields methyl succinic acid, COOH.CH, CH(CH,) COOH. Further experiments on the action of bromacetal on the sodium compounds of ethereal salts are in progress. It should be mentioned, in conclusion, that C. Harries (Ber., 1898,31,42) obtained a substancg which is probably the methylal of the half-aldehyde of succinic acid, (CH,O),CH*CH,*CH,*COOH, by the action of sodium hypobromite on levulin methylal, (CH,O),CH*CH,*CH,* CO-CH,, but he does not appear to have further investigated this substance. Action of Bromacetal on, the Sodium Derivative of Ethylic malonncb.Fmmtion of Ethyylic Acetalmalonate, (C2H50)2CH*CH,*CH(COOC2H6)2. Ethylic acetalmalonate is conveniently prepared as follows. Sodium (14.2 grams) is dissolved in absolute alcohol (170 grams) and the solution, while still warm, is mixed with ethylic malonate (100 grams) and bromacetal (80 grams) and the mixture, inclosed in sealed tubes, is heated a t 130-140' for 4 hours; when as much alcohol as possible has been removed from the product by distillation on the water bath, water is added to the residue and the precipitated oil extracted several times with ether. The ethereal solution is washed, well dried over calcium chloride, the ether distilled off, and the residual oil frac- tionated under reduced pressure (15 mm.). More than half passes over below 148' and consists of a mixture of unchanged ethylic malonate and bromacetal, whilst the fraction distilling between 145O and 165O14 PERKIN AND SPRANKLING : 6-ALDEHYDOPROPIONIC ACID contains the ethylic acetalmalonate, The oil boiling below 145O (15 mm.), and which was assumed to contain about 50 per cent.of bromacetal, was again heated in sealed tubes with the caleulated quantity of the sodium derivative of ethylic malonate, the temperature, however, being now allowed to rise to 160'. In this way, practically the whole of the bromacetal was converted into crude ethylic acetdmalonate boiling at 145-165" (15 mm.), and from this fraction the almost pure ethereal salt could be obtained by repeated fractionation as a colourless oilof a peculiar and not unplea- sant odour, and boiling at 151-154' (15 mm.), or at 166-168" (at 26 mm.).Analysis.* 0.1821 gave 0.3714 CO, and 0.1418 H,O. C = 55.62 ; H = 8.65. 0.1640 ,, 0.3360 CO, ,, 0.1282 H20. C=55*87; H=8.67. (C,H50),CH*CH2*CH(COOC,H,), requires C = 56.50; H = 8.69 per cent, Acetcclmaloltic Acid, (C,H,O),CH CH,* CH( COOH),. Acetalmalonic acid is obtained by hydrolysing its ethereal salt with alcoholic potash, but the operation has to be carefully performed, since prolonged boiling with the alkali decomposes the acid with elimination of the group *CH,*CH(OC,H,), and formation of malonic acid. It is not clear how this decomposition takes place, but there can be no doubt as to the formation of malonic acid, since, i n one instance, when a quantity of this acid was obtained melting at 131°, an analysis was carried out with the following results.0.2687 gave 0,3480 CO, and 0.0972 H,O. It was very soluble in water, and when heated decomposed with evolution of carbon dioxide and formation of acetic acid. I f , however, the action of the potash is only allowed to proceed for a short time, hydrolysis takes place normally, and a good yield of aeetalmalonic acid is obtained. After many experiments, we found that the following process gave the best results. Ten grams of the pure ethereal salt is mixed with a solution of 6 grams of pure potash in alcohol, and the mixture heated on the water-bath for 10 minutes, the alcohol is then rapidly driven off on the water-bath and the cold residue mixed with an excess of dilute sulphuric acid and extracted repeatedly with ether.The ethereal solution, after drying and evaporating, deposits a thick oil which shows no sign of crgsfallising, even after standing for some days over sulphuric acid in a vacuum. On * The numbers obtained are slightly low, on account of the oil containing traces of bromine, which it was found imposfiible to remove by fractionation. C = 35.33 ; H = 4-26. CH2(COOH), requires C = 34.63 ; H = 3.86 per cent.AND &ALDEHYDOIE(OBUTYRIC ACID. 15 analysis," it gave numbem agreeing approximately with those required for acstalrnalonic acid. I. 0-1150 gave 0.2040 CO, and 0.0722 H,O. C- 49.15 ; H = 6.97. 11. 0.1779 ,, 0.3177 CO, ,, 0.1200 H,O. C=48.72 ; H=7*47. 111. 0.1974 ,, 0.3529 CO, ,, 0*1227 H,O. C=48.75 ; H=6.91. IV.0.153'7 ,, 0.2719 CO, ,, 0.0915 H20. 0=48*26 ; H=6.61. (COOH),CH- CH,*CH(OC,H5), requires C = 49.05 ; H = 7-27 per cent. S~~satt.-Acetalmalonic acid is very soIuble in water, and if the aqueous solution is neutralised with ammonia, and silver nitrate added, a dense, white precipitate of the silver salt is precipitated, which, after washing first with water and then with alcohol and ether, gave the following results on analysis. 0.2177 gave, on ignition, 0-1092 Ag. Ag=50-16. (C,H,O),CH*CH,* CH(COOAg), requires Ag = 49-79 per cent. Distillation of Acetdmalonic Acid.-When this acid is heated in a fractionating flask, decomposition soon sets in with evolution of carbon dioxide, and the residue, after repeatedly fractionating under reduced pressure, yields a liquid which boils, apparently constantly, at 167-1 61' (15 mm.), and which was at first thought to be acetalacetic acid (C,H,O),CH*CH,*CH,*COOH.The analyses, however, show that thie substance consists, for the most part, of aldehydopropionic acid (p. 16), elimination of alcohol having taken place during the distilla- tion owing, probably, to the unavoidable presence of small quantities of water. 0.2658 gave 0.4740 CO, and 0.1607 H,O. C = 48.63 ; H = 6.71. 0.2514 ,, 0.4372 00, ,, 0.1437 H,o. C= 48.53 ; H= 6.39. COOH*CH,*CH,*CHO requires C = 47.05 ; H = 5.88 per cent. COOH*CH,*CH,*CH(OC,H,), requires C = 54-54 ; H = 9.09 per cent. I n order to confirm this view, the liquid was heated with an equal quantity of phenylhydrazine for 10 minutes at 150' and poured into ether, when, on standing, a white, crystalline substance separated, which, after crystallisation from acetic acid, melted a t 191" and gave the following results on analysis. 0*0601 gave 0.1502 CO, and 0.0350 H,O.0.1258 gave 21.3 C.C. nitrogen a t 19' and 768 mm. N = 19.42. C,,H,,N,O requires C = 68.09 j H = 6.38 j N = 19.85 per cent. This substance, on examination, was found to be identical with the condensation product formed by heating aldehydopropionic acid with * The four analyses given here were carried out with four different preparations of the acid. C = 68-17 ; H = 6-47.16 PERKIN AND SPRANKLING : @-BLDEHYDOPBOPIONIC ACID phenylhydmsine (see below), and thus it is probable that this aldehyde acid was present in the oil obtained by the distillation of acetalrnalonic acid. p-Aldehydopropionic acid, CHO*CH,* CH2* COOH.In order to prepare this substance, acetalmalonic acid is heated with about four times its weight of water at 180-190° for 4 hourg, the solution evaporated on the water-bath, and the residue allowed to stand over sulphuric acid in a well exhausted desiccator for 4 or 5 days. The yellow, oily residue thus obtained, on analysis, gave numbers agreeing approximately with those required for /3-aldehydopropionic acid." I. 0.2084 gave 0.3611 CO, and 0.1127 H20. C= 47-40; H= 6-01, 11. 0.2124 ,, 0.36'75 CO, ,, 0*1132 H,O. C=47*20; H=5*92. 111. 0.1703 ,, 0.2928 CO, ,, 0.0890 H20. C=46.89 ; H=5.82. IV. 0.13'79 ,, 0.2300 CO, ), 0.0806 H,O. C=45*47 ; H= 6.47. V. 0.1576 ,, 0.2649 CO, ,, 0.0909 H,O. C= 45-90; H- 6.40.CHO*CH,*CH,*COOH requires C = 47.05 ; H = 5.88 per cent. /3-AZ&hydopropknic acid is a slightly brownish liquid which dissolves readily in water, freshly prepared, its solution reduces Fehling's solution, and produces a pink colour when mixed with a solution of rosaniline hydrochloride which has been decolorised with sulphur dioxide. When heated at 150° with phenylhydraxine for 10 minutes, condensation readily takes place, and if the product is poured into ether a white, crystalline substance separates on standing, which, after recrystallisa- tion from acetic acid, gave the following results on analysis. 0.0590 gave 10.1 C.C. nitrogen at 18' and 758 mm. This substance, of which a full analysis is given on p. 15, melts at 192O and is evidently the phenylhydrazide of the phenylhydrazone of aldehydopropionic acid, C,H,*NH*N: CH*CH,*CH,*CO*NH*NH.C,H,, which contains 19.85 per cent.of nitrogen. N= 20.00. O d a t i o n of Atdehydopropionic Acid. Fmmatim qj Succinic Acid. When aldehydopropionic acid is left exposed to the air, it darkens in colour and gradually deposits crystals, ultimately being converted into a brown, pasty mass, which in contact with porous porcelain slowly * As this substance would not crystallise, analyses of each preparation were made, and some of these varied as much as 3 per cent. from the theoretical ; we therefore wish it to be distinctly understood that we do not consider that the aldehydo-acid made in this way is pure. All the preparations contained a small amount of ash derived from the tube in which they were prepared ; this was allowed for in the analyses.AND fl-ALDEHYDOI8OBUTYRIC ACID, 17 becomes a nearly colourless, crystalline mass, the sticky, oily impurity being only very gradually absorbed.The crystals were purified by recrystallisation from hydrochloric acid with the aid of animal charcoal, and in this way colourless plates were obtained which melted at 181' and had all the properties of succinic acid. Analysis. 0.1201 gave 0.1786 CO, and 0.0561 H20. C=4056; H=5.18. COOH*CH,*CH,*COOH requires C = 40.68 ; H = 5.08 per cent. This experiment shows that aldehydopropionic acid is slowly converted into succinic acid by the oxygen of the air, and this change takes place very rapidly when oxidising agents are employed. A small quantity of the aldehydo-acid, after being heated to boiling with dilute nitric acid (20 per cent.) for some hours until no further oxidation took place, was evaporated repeatedly on the water-bath with the addition of small quantities of water, until a colourless, crystalline residue was left. This, after recrystallisation from hydrochloric acid, melted at 181-184" and consisted of succinic acid.0.0598 gave 0-0898 00, and 0.0279 H20. C=40*96; H=5*18. COOH*CH,*CH,*COOH requires C = 40.68 ; H = 5-08 per cent. Rducticm of Aldehydoprohic Acid. ?H2* CH,* g! 0-- Five grams of the pure aldehydo-acid were dissolved in water and treated with three times the calculated quantity of 4 per cent, sodium amalgam, carbon dioxide being passed through the liquid and the temperature kept below 10' during the whole operation, in order to avoid, as far as possible, risk of polymerisation or condensa- tion; after separating the mercury, the solution was made strongly acid with sulphuric acid, heated to boiling for half an hour in a reflux apparatus, and then repeatedly extracted with ether.The ethereal solution, when dried and evaporated, deposited a colourless oil, which, after twice fractionating, boiled a t 203 -208'. On analysis, it gave numbers agreeing with those of butyrolactone, which, according t o Fittig and Roeder (Annnlm, 227, 1885, 22), boils at 206'. C,H,02 requires C=56*81 ; H ~ 6 - 9 7 per cent. Rormation of Butyrolactone, 0.1356 gave 0.2760 CO, and 0.0888 H20. C = 55.51 ; H = 7*27. VOL. LXXV. C18 PERKIN AND SYRANKLIBGI : @-ALDEHYDOPROPIONIC ACID Action of Cawtic Soda on P-Aldehpdopropionic Acid.Xyntl~sis of This synthesis, which is explaiaed in the introduction to this paper, was carried out as follows. P-Aldehydopropionic acid (10 grams) was dissolved in an excess of dilute sodium hydroxide and the solution evaporated in a flat glass basin nearly to dryness, water was then added and the solution again evaporated, this operation being con- tinued during three days ; the concentrated liquid, after being acidified and allowed to stand over-night, deposited a small quantity of a brownish powder, which, on examination, was found to be crude tere- phthalic acid. This was purified by dissolving it in dilute sodium carbonate, boiling with animal charcoal until most of the colour had been removed, and then treating the solution at 0' with permanganate until the violet colour remained permanent for 2 minutes; the filtrate from the manganese precipitate was concentrated, and, while still hot, acidified with hydrochloric acid ; the colourlesIs, crystalline precipitate, which separated rapidly, had all the properties of terephthalic acid, It was almost insoluble in water and ether, did not melt at 270°, and on heating in a small test tube it sublimed apparently without melting, The small quantity of acid remaining (about 0.2 gram) was converted intD its methylic salt by Baeyer's (Annalen, 1888, 245, 140) method by heating with phosphorus pentachloride, mixing the product with methylic alcohol, and purifying the crystals which separated, by re- crystallisation from methylic alcohol, with the aid of animal charcoal ; the colourless plates thus obtained were very sparingly soluble in methylic alcohol and melted sharply at 140°, the melting point of the methylic salt of terephthalic acid.A specimen of the methylic salt prepared from pure terephthalic acid was found t o be identical with the synthetical substance in every respect, moreover, an intimate mixture of the two preparations melted sharply at 140'. These experi- ments prove conclusively that the acid formed by the action of sodium hydroxide on P-aldehydopropionic acid is terephthalic acid, and it is un- fortunate that, in spite of a number of experiments, we have been unable to devise a better method for the condensation of the aldehyde, aa the yield of terephthalic acid obtained was certainly not more than 5 per cent.Terephthalic Acid. P-AZdef~~doiaobut~ric Acid, CHOaCH,*CH(CH,)*COOH. The first step in synthesising this substance was to prepare ethylic acetalmethylmalonate, and this was readily accomplished by heating the sodium derivative of ethylic methylmalonate with bromacetalAND &ALDEHYDOISOBUTYRIC AUID, I9 under the conditions already described in tho case of ethylic acetal- malonate. The ethylic malonate employed in these experiments was made by the etherification of pure methylmalonic acid; the quantities of the substances used in the synthesis of ethylic acetal- methylmalonate were, Ethylic methylmalonste 54 grams. Sodium ............. , ..... ,. 7.2 ,, Bromacetal . , , , . . , . . , . . , , . 40 ,, After isolating the product in the way described in the case of ethylic acetalmalonate, the crude oil was submitted to careful fractionation and the fraction 165' (26 mm.), which consisted of nearly pure ethylio acetalmethylmalonate, was analysed with the following result.0.1491 gave 0*3056 CO, and 0*1204 H20. C = 57-20 ; H = 8.97. (C,H,O),CH~CH,~CH(CH,)(COOC,H,), requires C = 5'7.92 ; H * 896 per cent, Acetulmethylrnalonic Acid, (C,H,0),*CH*CH,*CH(CH,)(COOH)2, This acid, which was prepared by the careful hydrolysis of its 0.1965 gave 0.3624 GO, and 0.1404 B20. The silver salt, prepared by precipitating a neutral solution of the ammonium salt with silver nitrate, is a white, amorphous powder, which readily darkens when exposed to light. ethereal salt, is a colourless syrup readily soluble in water. C=50*30 ; H ~ 7 - 9 4 , CloH1806 requires C = 51.28 ; H = 7.69 per cent. 0,2026 gave, on ignition, 0.0980 Ag. CloHloAg,O, requires Ag = 48.19 per cent, Aldehydoisobutyric acid, obtained by heating acetalmethylmalonic acid with water at 180' for 4 hours, and evaporating the liquid on a water bath, is an oil which, after standing for some days over sul- phuric acid in a vacuum, was analysed with the following results." C = 51.53 ; H = 7.28. Ag = 48.37. 0.1933 gave 0.3653 CO, and 0.1238 H,O. CHO*CH,*CH(CH,!*COOH requires C = 51-72 ; H = 6.89 per cent, This substance is very similar to aldehydopropionic acid in its pro- perties, and its constitution is proved by the fact that, when oxidised with nitric acid, it yields methylsuccinic acid ; this, after recrystallisa- tion, melted a t 110-112', and gave the correct numbers on analysis. COOH*CH(CH,)*CH,*COOH requires C = 45.45 j I3 = 6-06 per cent, 0.2142 gave 0.3558 CO, and 0.1238 H,O. C= 45.30 ; H= 6-40, OWENS COLLEGE, M ANCHESTER. * See footnote, p b 16. c 2

ISSN:0368-1645    

DOI:10.1039/CT8997500011

出版商:RSC    

年代:1899

数据来源: RSC

摘要:

20 WOOD, SPIVEY, AND EASTERFIELD: CAWNABINOL. PART I. 111.-Cannabinol. Part I. By THOMAS BARLOW WOOD, M.A. ; W. T. NEWTON SPIYEY, M.A. ; THOMAS HILL EASTERFIELD, M.A., Ph.D. IN a paper communicated to the Society in 1896 (Trans., 1896, 88, 539) the authors, under the name of “cannabinol,” described a physiologically active substance which they had isolated from (‘ charas,” the exuded resin of Indian hemp. From the constancy of composition of a number of preparations of this substance obtained from different samples of “charas,” it was believed to be a definite chemical compound of the formula C18H,,02 ; this conclusion seemed to be justified by the determination of the molecular weight, and by the examination of several derivatives. Since then, the authors have further examined cannabinol, and have found that it is a mixture of at least two compounds having similar physical characters.One of these, of the formula C21H2602, has been isolated, and it is proposed to retain the name cannabinol for this compound. During the progress of this investigation, a note on oxycannabin by Messrs. Dunstan and Henry appeared in the Proceedings of the Society (Proc., 1898, p. 44), in which the formulae C,,H,,,NO, and C18H,0Ac were assigned to oxycannabin and acetylcannabinol respectively. From the description of these substances, there can be no doubt that they are identical with those we have obtained, but the results of our analyses correspond with the formulae Cl,H,,NO, for oxy- cannabin and C2,H2,02*C,H,0 for acetylcannabinol. These formulae are confirmed by molecular weight determinations, and by analyses of many derivatives. Dunstan and Henry (Zoc.cit.) state that, on oxidising cannabinol with nitric acid, normal butyric acid is formed ; we can confirm this statement, with the addition that larger quanti- ties of normal valeric and caproic acids are produced at the same time. As the present paper deals mainly with the substances produced by the breaking down of the cannabinol molecule, the authors have only described such of its reactions as suffice to show that it is a true chemical compound. An account of the reactions of cannabinol, together with a more complete examination of several of the com- pounds described below, will shortly be brought before the Society. When crude cannabinol (the red oil obtained by fractionating alcoholic charas extract under diminished pressure) is treated with nitric acid under certain conditions, it yields a yellow, crystalline eubstance, the analysis of which corresponds with the formula C,,H15N20, (Proc., 1898, p.SS), but determinations of the molecular weight show that a higher formula is required. As it has acidicWOOD, SPIVEY, AND EASTEBFIELD: CANNABINOL. PART I. 21 properties, salts were prepared and analgsed, and their composition proves that the formula is C1,,H,,N30,, which agrees with the molecular weight determinations. It is readily reduced by boiling with hydriodic acid and phosphorus, yielding the hydriodide of a base ; the latter has not as yet been isolated, owing to the readiness with which it oxidises.As the formula C21H23N,0S represents the trinitro- derivative of a compound, C,,H,,O,, the presence of the latter in crude cannabinol is probable, and this is definitely proved by the isolation of the acetyl derivative, C,,H,,O,- C,H,O, from a crude cannabinol. After the separation of the crystalline acetyl derivative from the products obtained by the acetylation of crude cannabinol, an oily residue was left amounting to more than threequarters of the acetyla- tion product, and from it by treatment with acetic anhydride, no other crystalline acetyl derivative could be obtained ; it appears to contain the acetyl derivatives of one or more substances with a lower percentage of carbon than C,,H,60,. (( Crude cannabinol ” is, therefore, a mixture of cannabinol, C,,H,,O,, with one or more compounds probably of lower molecular weight.The fact that cannabinol forms an acefyl derivative proves that it contains a hydroxylic group, and the failure of all attempts to obtain an ethereal salt from the trinitro-compound referred to above, makes it probable that the acidity of the latter is not due to the presence of a carboxyl group, but to the influence of the nitro-groups on the hydroxyl group. On oxidising the trinitro-derivative by boiling it for several hours with fuming nitric acid, and pouring the product into water, a yellow, flocculent precipitate was deposited ; this was filtered off, and the acid filtrate steam distilled ; the distillate was found to contain normal butyric, valeric, and caproic acids. The normal butyric acid waa identified by its calcium salt, the normal valeric and caproic acids by their anilides.By direct oxidation of crude cannabinol with nitric acid, the same fatty acids were obtained, and caproic acid was also obtained when potassium permanganate or chromic mid mixture was employed. The yellow, flocculent precipitate, on crystallisation, gave a mixture of oily acids containing nitrogen, and a pale yellow, crystalline com- pound, the oxycannabin of Bolas and Francis (Chem. News, 1871, 24, 77); to this they gave the formula C,oH,oN,O~, but the results of their analyses agree equally well with the authors’ formula C,,H,,NO,. Dunstan and Henry, in their note (Proc., Zoc. c k ) , state that oxy- cannabin ‘‘ does not dissolve in aqueous alkalis unless warmed with them in a closed tube.By acidifying the resulting solution, an acid is precipitated which is at present under investigation. Oxycannabin would, therefore, appear to be a laotone.” The present authors find,22 WOOD,. SPIVEY, AND EASTERFIELD : CANNABINOL. PART I. however, that oxyoannabin dissolves in aqueous oaustic soda if boiled with it for a few minutes, and that unaltered oxycannabin is precipi- tated on aoidification. They have proved it to be a lactone by the preparation and analysis of salts of the corresponding oxy-acid, but this oxy-acid has not been isolated, since it is at once re-converted into the lactone when set free from its salts. I n fact, its tendency to undergo thi8 change is so great that, on treating the silver salt with ethylic iodide, the lactone is obtained instead of the ethylic salt.On oxidation with dilute nitric acid a t 185O, oxycannabin yields a sparingly soluble nitro-lactonic acid of the formula CloH8NO4- COOH together with a very soluble tribasic acid, C,H,NO,. On reduction, oxycannabin yields a compound, C,,H,,NO,, which corresponds to the reduction of a nitro-group in oxycannabin to an amido-group. On this evidence, the authors propose for oxycannabin the name nitrocannabino-lactone, and for the reduction product the name amidocannabino-lactone. The amido-lactone is readily diazotised, and an attempt was made to prepare caanabino-lactone directly from it by Friedlander’s method, but it was found more convenient to prepare iodocannabino-lactone, C$,HlII02, by adding potassium iodide to the diazotised solution, and to reduce this with sodium amalgam in alkaline solution.The oily canna- bino-lactone, C,,H,@,, thus obtained, was converted into colourless crystalline, cannabino-lactonic acid, C,,H,,O,, by boiling it with an alkaline solution of potassium permanganate ; this action corresponds to the oxidation of a methyl group to a carboxyl group. On reduction with hydriodic acid and phosphorus, the lactonic acid yields a dibasic acid of the formula C1,H1204, thus affording confirmation of its lactonic nature. From the fact that a methyl group, both in cannabino-lactone and in its nitro-derivative, is oxidised to a carboxyl group, and from the behaviour of nitrocannnbino-lactone on reduction, and subsequent diazotisatim, the presence of a benzene nucleus in cannabino-lactone is probable, In order to confirm this, and, further, to ascertain the structure of the lactone ring, the lactonic acid was fused with caustic potash; in this way, isophtbalic acid was obtained, and identified by conversion into its methylic salt.However, when cannabino-lactone wa8 fused with potash, metatoluic acid was formed, together with iso- phthalic acid. The formation of these two acids definitely proves the presence in cannabino-lactone of a benzene nucleus, with two side chains in the meta-position relatively to each other, one of these chains being a methyl group. The second side chain must evidently contain the lactone ring, and on the assumption that i t is a y-lwtone, which from i t s great stability is probable, there appear toWOOD, SPIVIGY, AND EASTERFIELD: CANNABINOL PART I.23 be only three possible formulm, namely, t h e of the thcee metatolyl- butyrolactones, ( 3 3 3 - V6H4 CH3* 7BH4 ‘=3* I. QH- CH2* QH2 11. QH2* CH* QHz 111. FH2* CH2* FH 0--co 0-- co 0---co Syntheses of these three lactones are at present in progress, with a The following table shows the relationships of the compounds view to deciding which of them is identical with cannabino-lactone. described in this paper. Cannabinol, C2,H2,02. Acetylcannabinol, C,,H,,O,* COCH,. Trinitrocannabinol, C21H,,(N02)3* 0,. Cannabino-lactone, (1) CH,* C6H4<ye>C0 (3). Nitrocannabino-lactone (oxycannabin), (1) C H 3 > C , H 3 < 3 ~ ~ ~ 0 Amidocannabino-lactone, (1) c H 3 > C 6 H 3 < ~ ~ ~ c o (3).Iodocannabimlactone, (1) cHf>C6H,<~~DC0 (3). Cannabino-lactonic acid, (1) COOH. C6H4<Ef2>C0 (3). NO2 NH2 Nitrocannabino-lactic acid, (1) c 0 ~ ~ ~ f 3 H 3 < ! ! ~ 9 c 0 (3)* Carboxyphenylbutyric acid, GOOH* C,H4* C,’H,* COOH (3). EX P E RI M ENT A L. T&itrocannabinoZ, C21H23(N02),02.-This compound is produced on adding fuming nitric acid (5 c.c.), drop by drop, to a well cooled solu- tion of crude cannabinol (8 grams), dissolved in glacial acetic acid (18 c.c.), the temperature being kept down by immersing the flask in icecold water. After standing for several days, the crystals are col- lected; the yield is 20 per cent. (1.6 grams) of the crude cannabinol used. The compound is easily soluble in benzene, phenol, alcohol, and ether ; it is also readily soluble in hot, but only sparingly in cold, glacial acetic acid, which is the most convenient solvent for its recrystallisa- tion.It crystallises in bright yellow plates, which, when quickly heated, melt at 160° (uncorr.) with some decomposition. Four preparations were analysed A and B, purified through the ammonium salt. C. Five times re- crystallised from glacial acetic acid. D. Sample C, once recrystallised from alcohol.24 WOOD, SPIVEY, AND EASTERFIELD: CANNABINOL. P U T I. 0.1417 gave 0-2935 CO, and 0.0678 K O . A* { 0.1235 ,, 10 C.C. moist nitrogen a t 18' and 760 mm. B. 0.1676 ), 0.3480 CO, and 0.0835 q0. 0°1860 )) 0.3855 CO, ,, 0.0913 H,O. c* { 0-1440 ,, 11.5 C.C. moist nitrogen at 21' and 756 mm. D. 0.1527 ,, 0.3180 CO, and 0.0750 H,O.Calculated for Found. C,,H,N30*. A. B. C. D. C- 56.6 per cent. ............ 56.5 56.6 56.5 56.8 H= 5.2 ,, ............ 5.3 5.5 5.4 5.5 N= 9.4 ), ............ 9.3 - 9.0 - The molecular weight was determined by the freezing point method In benzene (i) 0.5220 gram, dissolved in 20 grams of benzene,lomered (ii) 0-95 13 gram, dissolved in 20 grams benzene, lowered the freezing In phenol (iii) 0.4733 gram, dissolved in 20 grams phenol, lowered (iv) 1.0023 grams, dissolved in 20 grams phenol, lowered the freezing in benzene and in phenol. the freezing point by OW312". point by 0.570". the freezing point by 0*410". point by Oo9000. Calculated for Found. C2IH*SNSO,. (i). (ii). (iii). (iv). Molecular weight = 445.. ....... 409 409 427 412 &&.-The compound has acidic properties, forming salts of potas- sium, sodium, ammonium, and silver, all of which are bright yellow, crystalline compounds sparingly eoluble in water, easily in alcohol. They are best crystallised by diluting their hot alcoholic solutions with water. The potassium and sodium salts are explosive, the silver salt is not.Sodium Sak-The most soluble of all the salts examined, the saturated solution at 15' containing 1 part of salt in 120 p r t e of solution. It is prepared by dissolving the acid in excess of alcoholic soda solution and diluting with water. Two samples were analysed. 0.2130, at 160°, lost 0-0290 H20 and gave 0-0255 Na,SO,. Na -. 3.9 ; 0.1545 gave OgO205 NaaO,. Na = 4.3. H20 = 13.6. NaC21H,2N30, + 4H,O requires Na = 4.3 ; H20 = 13.4 per cent. Potassium salt, prepared in the same way as the sodium salt, 0.1210 lost no weight at 150°, and gave 0-0220 K2S0,.0*1300 gave 0.230 K2S04 ; K = 7.9. quires for solution 2000 parts of water at 15O, and 500 at 100'. K = 8.2. KC2,H,2N,0, requires K = 8.1 per cent,WOOD, SPIVEY, AND EASTERFIELD: CANNABLNOL. PART I. 25 Ammoniwna salt may be prepared by dissolving the acid in boiling ammonia solution, when the salt crystallises out on cooling, or by dis- solving the acid in excess of alcoholic ammonia and diluting with water. It requires for solution 1600 parts of water at 15", and 200 at looo. 0811'70 gave 0.2330 CO, and 0*0605 H,O. C=54.3 ; H=5*7. 0.1312 0.4190 0.1320 0.1595 ,, 13.3 C.C. moist nitrogen a t 18" and 758 mm. N=11*7. ,, on distillationwith soda,NH, = 9*7c.c.N/10 HC1.NH,= 3.9. ,, 0.2640 CO, and 0.0690 H,O. C = 54.5 ; H = 5.8. ,, 17.0 C.C. moist nitrogen at 19' and '750 mm. N= 12.1. NH,*C,,H,,N,O, requires C = 54.5 ; H = 5.6; N = 12.1 ; NH, = 3.7 per cent. Silver salt, prepared either by adding silver nitrate solution to the solution of the sodium salt, or by boiling the alcoholic solution of the acid with excms of silver carbonate. A. Was prepared from the sodium Balt and recrystallised from alcohol. B. From the acid and silver carbonate. C is B recrystallised. 0*1900 gave 0.3180 GO,, 0.0715 H,O, and 0.0362 Ag. C = 45.6 j A* 0.1829 gave 11.2 C.C. moist nitrogen at 16' and 766 mm. N = 7.2. B. 0*1580 ,, 0.2673 CO,, 0.0586 H,O and 0.0295 Ag. C=46*1 ; H=4'1; Ag=lS.8. 0*1850 gave 0-3090 CO,, 0.0675 H,O ,, 0.0357 Ag.C= 45.5; (3. { H=4.1; Ag=19.3. 0.2600 gave 16.2 C.C. moist nitrogen a t 18Oand 758 mm. N= 7-2. AgC2,H,,N,O8 requires C = 45.6 ; H = 4.0; N = '7.6; Ag= 19.4 per cent. Reduction of Tv.initrocarnnabirnoZ.-Trinitrocannabinol is reduced by boiling with hydriodic acid and phosphorus in acetic acid solution; 3.7 grams of trinitrocannabinol were dissolved in 50 C.C. of glacial acetic acid, and boiled for 13; hours with 25 C.C. of hydriodic acid sp. gr. 1-6, and 4 grams o€ yellow phosphorus; the almost colourless solution was then filtered from the excess of phosphorus, and distilled down to one-third its volume, The pale yellow crystals of hydriodide which were deposited on cooling were collected, washed with acetic acid, and dried in a vacuum over solid potnsh. Attempts to isolate the base failed, as when set free from the hydriodide it is at once oxidised, with formation of coloured products. The hydriodide was analysed, and gave the following numbers, C = 41.2 ; H = 5.2 ; I = 41.3 ; N = 5.0 per cent.Tbe authors do not feel justified in making any statement as to the constitution of the product of reduction until they have isolated the base and made a further examination. AcetyZcanmbimZ, C21H2502*CO*CH8.-Crude cannabiaol is readily H=4.2; Ag=19*1.26 WOOD, SPIVEY, AND EASTERFIELD : CANNABINOL. PART I. aoetylated by boiling it with acetic anhydride or with acetic chloride, After distiIling off the exces8 of wetic anhydride and rectifying the residue under diminished pressure, an oil, lighter in colour and more mobile than the original crude cannabihol, is obtained ; this some- times, on standing, but, better, by dissolving it in alcohol and cooling the solution to Oo, deposits a white, crystalline substance, which can be purified by crystallisation from alcohol, light petroleum, or acetic acid ; it melts at 75', and is evidently identical with the ' acetylcannabinol, C,8H230A~,' mentioned by Dunstan and Henry (loc.cit.). Analysis indicated as the simplest formula C1,H,,02 (Proc., 1898, 66), but determination of the molecular weight and the results of saponification show that the higher formula, C23H2803, must be adopted (Proc., 1898, 153). The following samples were analysed. A. Recrystallised from alcohol. B. Four times recrystallised from alcohol. C, Recrystal- lised from light petroleum and then from acetic acid.C = 78.4 ; H = 7.9. As { 0.1118 ,, 0.3208 CO, ,, 0.0820 H,O. C=78*3 ; H=8*1. 0.1250 ,, 0.3595 00, ,, 0,0914 H,O. C = 78.4 ; H= 8.1. B' { 0.1290 ,, 0.3692 00, ,, 0.0928 H,O. C! = 78.1 ; H= 8.0. C. 0.1860 ,, 0.5315 CO, ,, 0.1330 H,O. C= 77.9 ; H= 8.0. C,,H,,O, requires C = 78.3 ; H = 7.8 per cent. C2,H,,O2* CO*CH3 requires C = 78.4 ; H,O = 8.0 per cent. C18H,,0Ac (Dunstan and Henry) requires C = 80.5 ; 3 = 8.7 per cent. The molecular weight was determined by the freezing point method, in glacial acetic acid and in benzene. In glcceictl acetic acid.-(i) 0.2043 gram, dissolved in 20 grams of glacial acetic acid, caused a depression of 0.123'. (ii) 0.5052 gram, dissolved in 20 grams of glacial acetic acid, caused a depression of 0.3 10'.I n benzm.*--(iii) 0.1 877 gram, dissolved in 17.04 grams of benzene, caused a depression of 0.140'. (iv) 0.3032 gram, dissolved in 17.04 grams of benzene, caused a depression of 0.240'. 0.1537 gave 0.4420 CO, and 0.1101 H,O. Calculated for Calculated for Found. C15H1802. C,,H,,O,*CO*CH,. (i). (ii). (iii). (iv). Mol. wt. = 230 352 324 318 385 365. The percentage of acetyl was determined by mponifying the com- pound, either by boiling with alcoholic potash, or by heating with it in a sealed tube a t 130'. Water was added to the product, * For the molecular weight determination in benzene solution, we are indebted to the kindness of Mr. H. Jackson, R A , , Downing College.WOOD, SPIVEY, AND EASTIGRFIELD: CANNABINOL, PART I. 27 and, after the alcohol had been boiled off, the aolultion WRS made strongly acid with phosphoric acid, and steam distilled until the dis- tillate no longer had an acid reaction. The distillate was then titrated with semi-normal caustic soda solution. 1.6 gave acetic acid equivalent to 8.85 C.C.N/2 NaOH solution. 9.0 9 , Y, 7, 52.4 C.C. ?) Calculated for Calculated for C16H1130?2 C,H2,0,*CO*CH,. Found. Acetyl= 18.7 per cent. 12.2 11.9, 12.5. Cannabinol, C2,H2,0,. The residues left in the distilling flasks in the above acetyl determi- nations were extracted with ether. The ethereal solution was dried over calcium chloride, the ether distilled off, and the residue distilled under diminished pressure, when practically the whole passed over a t 285O under 80 mm. pressure; the distillate was an almost colourless oil, which, on cooling, set to a transparent resin.A second preparation was made, and both were analysed. 0.1880 gave 0,5587 CO, and 0.1445 H,O. C = 81.5 ; H= 8.5. 0.1715 ,, 0.5100 CO, ,) 0.1300 H20. C=81*1 ; H=8*4. C2,H2,02 requires C = 81.3 ; H = 8.4 per cent. The molecular weight was found by the freezing p'oint method in 0.5876 gram, in 20 grams of glacial acetic acid, gave a depression 0.6250 gram, in 20 grame of glacial acetic acid, gave a depression glacial acetic acid solution. of 0 * 3 80'. of 0.390O. Calculated for C21H2602' Found. Mol. wt. = 310. 310, 313. The compound is optically inactive. Oxidation of Z'rinitrocanna6inol with Nitric Acid. One hundred and twenty grams of trinitrocannabinol was dissolved in 300 C.C. of hot, Fuming nitric acid, and gently boiled for 5 hours in a reflux apparatus, more acid being added from time to time, until in all 700 C.C.had been used. On pouring the product into water, 70 grams of a yellow, waxy precipitate separated, and from this 35 grams of nitrocannabino-lactone (oxycmnabin) were obtained on treatment with alcohol, The fiNrate from the above yellow precipitate28 WOOD, SPIVEY, AND EASTERFIELD : CANNABINOL. PART I. smelt strongly of valeric acid, and contained normal caproic, valeric, and butyric acids, possibly also propionic acid, together with non- volatile acids. Substantially the same products were obtained by the oxidation of crude cannabinol with nitric acid. Examination of the Vohtile Fatty Acids. The volatile acids were removed from the above-mentioned acid mother liquor by steam distillation, and the distillate neutralised with sodium carbonate and evaporated to dryness ; on acidifying with dilute sulphuric acid and extracting with ether, 12 grams of the mixed acids were obtained. These were fractionated with the follow- ing results.105-150°= 2-2 grams. 170-180°= 1-2 grams. 150-170' = 0.9 ,, 180-195' = 3.9 ,, Above 195'= 1-85 grams. From the fraction 150--170°, normal butyric acid was isolated by means of its calcium salt, which was purified and analysed, with the following results. 0.0730 lost 0.0037 H20 at 135O and gave 0.0418 CaSO,. H,O = 7.8 ; Ca = 16.9. (C,H,O,),Ca + H,O requires H,O = 7.7. Ca = 17.2 per cent. The vaZeric mid in the fraction 180-195° was separated as the valeranilide which melted a t 60' (uncorr.), and on analysis gave the following results.0.0660 gave 0.1795 GO, and 0.05 15 H,O. 0.1998 ,, 13.6 C.C. moist nitrogen at 205O and 757 mm. N=7% C,,H,,NO requires C = 74-6 ; H = 8.5 ; N = 7.9 per cent. As the anilide of normal valeric acid has not been described, it was prepared from a sample of normal valeric acid boiling a t 185-186', and was found to melt a t 61' (uncorr.). Admixture of the anilide obtained from the fraction 180-195' with the anilide from normal valeric acid did not depress the melting point of the latter. The acid in this fraction is, therefore, normal valeric acid. The fraction boiling above 195' was converted into the anilide which, after many crystallisations from light petroleum, melted at 93' (uncorr.). The analytical numbers were slightly low for a capro- anilide, and lack of material prevented further purification. Normal caproanilide melts at SS', and since it has been shown that the lower acids belong to the normal series, it can hardly be doubted that the acid obtained from this fraction is normal caproic acid.In a similar examination of a much larger quantity of the fatty C = 74.2 ; H = 8.7.WOOD, SPIVEY, AND EASTERFIELD: CANNABINOL. PART I. 29 acids obtained by oxidation of crude cannabinol with nitric acid, the same acids were obtained. Normal butyric acid was identified by its calcium salt, normal valeric acid by its anilide, and caproic acid by its silver salt. The fraction 150-170° was also examined for isobutyric acid (b. p. 155O) by the method used by V.Meyer and Hutzler (Bet-., 1897, 2519), but as no trace of acetonic acid could be detected after oxida- dation with potassium permanganate, isobutyric acid is evidently absent. Caproic acid was also found in the product of the oxidation of crude cannabinol by chromic acid mixture, and by potassium per- manganat e solution. I n each case, the silver salt wag recrystallised until the analytical results were constant. A. From chromic acid mixture oxidation. B. From potassium permanganate oxidation. C. From nitric acid oxidation. C = 32.5 ; H = 4.9. A' { 0.1650 ,, 0-0800 Ag. Ag=48*5. 0.1459 gave 0.1745 CO, and 0.0648 H,O. B. 0.1070 ,, 0.0515 Ag. Ag=48.1. C. 0.2383 ,, 0.1158 Ag. Ag=48*6. C,H,,CO+g requires C = 32.3 ; H = 4.9 ; Ag = 48.3 per cent. X t r o c a n m b i n o - Z a c t m (oxycannabin), The preparationof this substance from trinitrocannabinol has already been described; it can be obtained more conveniently by the following method.Crude cannabinol is dissolved in three times its weight of glacial acetic acid, warmed to looo, and nitric acid (sp. gr. 1 *42) slowly dropped in from a burette in the proportion of 1 C.C. of nitric acid for each gram of cannabinol; the solution is then boiled gently for half an hour, more nitric acid is added, and the boiling continued for 8-10 hours, nitric acid being added whenever the oxidation slackens, 50 grams of crude cannabinol require in all 300-400 C.C. of nitric acid. The product is then poured into water, and the nitrocannabino- lactone separated as before; the yield is 15-20 per cent.of the crude cannabinol used. When purified by repeated cry stallisation from al- cohol, it is obtained in very faintly yellowish needles melting at 178" (uncorr.), and is not changed by sublimation. On exposure to light, it gradually assumes a reddish tinge. It is soluble in alcohol, acetic acid, benzene, and concentrated nitric acid. These properties show that it is identical with the oxycannabin of Bolas and Francis (loc. cit.), and of Dunstan and Henry (Zoc. cit.). Five samples were30 WOOD, SPIVEY, AND EASTERFIELD: CANNABIWOL. PART I, analysed. A. Purified by sublimation. B. Precipitated from the potassium salt. C. Crystallised from dilute acetic acid. D. From alcohol. E. From trinitrocannabinol, and crystallised from alcohol. A. 0.1478 gave 0.3225 CO, and 0.0663 H,O.C = 59.5 ; H= 5.0. B. 0.1313 ,, 0.2852 CO, !, 0*0580 H20. C=59*2 ; H= 4.9. C. 0.1195 ,, 0.2615 CO, ,) 0.0582 H20. C=59*7; H=5*4. 0.1330 ,, 0.2900 CO, ,, 0.0605 H20. C-59.5; H=5.1. D. 0-1615 ,, 8.8 C.C. moist nitrogen at 21' and 772 mm. N = 6.3. ,, 19' ,, 750 ,, nT=6*4, E. 0.1155 ,, 6.5 ,, 0.1415 ,) 8.0 ,, 99 17" ,, 764 ,) N=6*6. requires C = 59.7; H = 5.0; N = 6.3 per cent, 1 ClIH,PO* C20H20N207 (Bolas and Francis) ), C = 60.0; H = 5.0; N = 7.0 ,, CloHl,NO,(Dunstan and Henry) ,, C = 57.7; H = 4.8; N L-- 6.7 ,, The molecular weight was determined by the freezing point method 0.4313 gram, dissolved in 20 grams glacial acetic acid, lowered the in glacial acetic acid. freezing point 0.375'. Mol. wt. calc. for C,,H,,NO, = 221. Found = 225.Nitrocannabino-lactone is insoluble in cold aqueous alkalis, but dissolves on boiling for a few minutes, and is not precipitated on dilution with water; the addition of mineral acids, however, pre- cipitates it unchanged. Potassium saZt.-This salt separates in slender, pale yellow needleg on mixing saturated solutions, in absolute alcohol, of the lactone and caustic potash. Its salts are prepared as follows. 0.1197 gave 0.0375 K2S04. Silver sak.-Prepared by adding silver nitrate to an aqueous 0-1322 gave 0.0409 Ag. Ag==30*9. CllHI2NO6Ag requires Ag = 31.3 per cent, An attempt was made to obtain the ethylic salt by boiling the silver salt with ethylic iodide ; silver iodide separated, but on extracting the product with boiling alcohol, nothing but unaltered nitrocannabin+ lactone was obtained.The lactone was treated with aqueous ammonia, sp. gr. 0.88, and with saturated alcoholic ammonia, both at the ordinary temperature, and in sealed tubes at 100'. In each case, nothing but the unaltered lactone could be recovered. Failing to obtain an amide, an at- tempt was made to prepare the snilide, but this also was unsuccessful. K = 14.1. CllHI,NO,K requires K = 14.0 per cent, solution of the potassium salt.WOOD, WIVEY, AND EASTERFIELD: CANNABINOL. PART I, 31 Oxidadion of Nitrooannabino-lctorw with dilute Nitric Acid.-Nitro- cannabino-lactone (4 grams) was heated with 25 per cent. nitric mid (80 c.c.) at 185" for 8 hours, and the liquid, on stirring, deposited a colourless, crystalline, sparingly soluble acid ; this, after recrystallisa- tion from hot water, melted at 229-230' (uncorr.).The weight of the recrystallised acid was 1.1 grams. Analysis shows that the substance has the formula CllHgN06, which may be derived from nitrocannabino-lactone by the oxidation of a methyl group to a carbosyl group, thus COOH* C , H , ( N O , ) < ~ f ~ C O . This conclusion is strengthened by the fact that nitrocannabinol lactone, on oxidation with potassium permanganate in the cold, yields the same product. A. Was prepared by oxidation with nitric acid. B. With potassium permanga n a t e. 0.1053 gave 0.0360 H,O and 0.2033 GO,. ** { 0.1328 ,, 6.5 C.C. moist nitrogen at 21' and 750 mm. N = 5.5. 0.1725 gave 04612 H,O and 0.3300 GO,. B* { 0*1700 ,, 8.0 C.C. moist nitrogen a t 20' and 765 mm.N = 5 4 . C,,H,NO, requires C = 52.6 ; H = 3.6 ; N = 5.6 per cent. The acid, neutralised with ammonia, was converted into silver salt. 0-1568 gave 0.0472 Ag. CllH8N06Ag requires Ag = 30.2 per cent, This acid must be regarded as the nitro-derivative of the cannrrbino- lactonic acid described below. The nitric acid mother liquor, from which the sparingly soluble acid had separated, was evaporated to dryness, the residue dissolved in a very small quantity of cold water, filtered, again evaporated to dryness and extracted with ether. The syrup left on evaporating the ether gradually deposited crystals which were excessively soluble in water, alcohol, ether, glacial acetic acid, and ethylic acetate, but practically insoluble in benzene, chloroform, and light petroleum.The compound is most satisfactorily purified by recrystallisation from strong hydrochloric acid, when it is obtained as a colourless, crystal- line powder, melting a t 228-230' with much effervescence, but only a slight discoloration. C = 52.7 ; H = 3.8. c1= 52.2 ; H = 3.9. Ag = 30-1. Three preparations were analysed. I. 0.0948 gave 0.0188 H20 and 0.1478 CO,, C -42%; H= 2.2. 0.0760 ,, 3.5 C.C. nitrogen at 2OC and 760 mm. N=5*5. 11. 0.1646 ,, 0.0302 H,O and 0-8552 CO,. C=42*3 ; H=2*0. 111. 0.1775 ,, 0.0325 H,O ,, 0.2754 GO,. C = 42.3 ; H= 2.0. The formula C,H,NO, requires C = 42.3 ; H = 2.0 ; N = 5.5.32 WOOD, SPIVEY, AND EASTERFIELD: CANNABIWOL, PART I. The acid is tribasic, for on titration with N/10 soda and phenol- phthalein, 0,065 gram required 7.5 C.C.for neutralisation. A tribasic acid of the above formula requires 7.65 C.C. A solution of the calcium salt of the acid was prepared by neutralisa- tion with chalk, and from this, nitrate of silver precipitated the silver salt as a primrose-yellow powder, slightly soluble in hot water. The salt is feebly explosive. 0.113 gave 0.004 H20 and 0.079 00,. C = 19.0; H=0.4. 0.1565 ,, 0.1172 AgC1. Ag-56.4. C,H,NO,Ag, requires C = 18.7 ; H = 0.3 ; Ag = 56.2. No attempt has been made to elucidate the constitution of the acid ; it is, however, difficult to account for the formation of a tribasic acid of the formula CgH,NO8 from nitrotolylbutyrolactone unless the acid is a hydroxyglyoxylic acid of the constitution GOOH* C,H,(OH) (N 0,)-CO-COOH. Amidocacnna6ino-Zactm, C,,H,,NH,* O,,-This compound can be ob- tained by the reduction of the nitrolactone by tin and hydrochloric acid, or by hydriodic acid and phosphorus, but the latter is more convenient. Ten grams of the nitrolactone dissolved in 40 C.C.of glacial acetic acid was boiled with 30 C.C. of hydriodic acid of sp. gr. 1.6 and 5 grams of phosphorus for 2 or 3 hours, the colourless solution on cooling deposit- ing crystals of the hydriodide of the base, and a further quantity of the base was obtained by pouring the strongly acid mother liquor into water. On dissolving the hydriodide thus obtained in boiling water, dissociation occurs, and the free base crystallises out on cooling. Amidocannabino-lactone crystallises readily from hot water in long, white needles melting a t 119' (uncorr.), Two preparations were analysed.A. Prepared by hydriodic acid and phosphorus, B. By tin and hydrochloric acid. 0 0.1260 gave 0.3200 00, and 0-0770 H20. 0.1826 ,, 11.5 C.C. moist nitrogen at 2 2 O and 770 mm. N = 7.2. C = 69.3 ; H = 6.8. A. 0.1140 ,, 0.2895 GO, ,, 0.0720 H20. C = 69.2 ; H = 7.0. B. 0.0795 ,, 0.2005 GO, and 0.0500 H,O. C = 68.8 ; H = 7.0. C,,H,,NO, requires C = 69.1 ; H = 6.8 ; N = 7.3 per cent. i The hydriodide was also analysed. 0.1957 gave 0.1420 AgI. C,,H,,O,-NH,,HI requires I = 39-8 per cent. The platinochloride was prepared by dissolving the base in strong hydrochloric acid and adding platinic chloride solution. Two specimens were analysed. I= 39%WOOD, SPIVEY, AND EASTERFIELD: CANNABINOL. PART I. 33 0.1200 gave 0.0296 Pt;.Pt = 24.7. 0.2594 ,, 0,0636 Pt. Pt=24.5. (CllH,,O,~NH,),,H,PtC1, requires Pt = 24.6 per cent. The base was readily diazotised, and an attempt was made t o prepare cannabino-lactone from it by Friedlander's method, but no satisfactory product could be obtained. Cannabino-lactone was, however, easily obtained through the iodo- lactone, whose preparation is given below. lodocannabino-Zactone, CH,. C , H , I e f e C O . -Ten grams of amido- cannabino-lactone was dissolved in 25 C.C. strong hydrochloric acid, 75 C.C. water added, and the solution diazotised by the addition of 4.5 grams of sodium nitrite dissolved in 15 C.C. of water, the tempera- ture being kept within a few degrees of the freezing point. 12.5 grams of potassium iodide in 25 C.C. water was then added, and the mixture heated on the water bath until evolution of nitrogen ceased ; the acid liquor was then poured off, and the solid residue, after treat- ment with solution of sodium thiosulphate to remove free iodine, was repeatedly crystallised from dilute acetic acid.The yield was 10 grams. The iodolactone forms almost colourless crystals melting at 13'f*5' (uncorr'.), insoluble in water, but easily soluble in alcohol and acetic acid ; it sublimes very readily. 0.2370 gave 0.3825 CO, and 010803 H,O. 0.2785 ,, 0.2145 AgI. 1=41*6. C = 44.0 ; H = 3.8. C,,H1,IO, requires C = 43-7 ; H = 3.6 ; I = 42.0 per cent. XiZver XaZt.-A solution of the potassium salt was obtained by saturating alcoholic caustic potash solution with the iodolactone, and after precipitating the excess of lactone by water, silver nitrate was added to the filtrate.Tbe silver salt was precipitated as an amorphous powder which became crystalline on standing. It is soluble in hot water, but cannot be recrystallised without decom- position. 0.2430 gave 0.131 5 AgI. Ag = 24.9 C12H12103Ag requires Ag = 25 *3 per cent. Cannabino-lactom, CH,* C,H,<-~J>CO.-The C H iodolactone is dis- solved in hot alcoholic potash solution and the solution, diluted with water, is reduced with 2.5 per cent. sodium amalgam. No hydrogen is evolved until almost the theoretical amount of amalgam has been added, but it is found advantageous to use a considerable excess of the reducing agent in order to ensure the complete removal of iodine. After the alcohol has been removed by boiling, the alkaline solution is acidified VOL.LXXV. D (1)34 WOOD, SPIVEY, AND EASTERFIELD : CANNABIPI'OL. PART I. by sulphuric acid, and steam distilled until the distillate no longer becomes turbid on adding a strong solution of potassium carbonate. The lactone is obtained by salting out the distillate with potassium carbonate, and extracting with ether ; the oily residue left on evapo- rating the ether distilled almost to the last drop at 290.5' (uncorr.) under a pressure of 768 mm. When purified by redistillation under diminished pressure, it was obtained as a colourless, highly refracting liquid of sp. gr. a t 2Oo/2O0 = 1.0833, and boiling at 126' (uncorr.) (20 mm.). The yield of pure cannabino-lactone from the iodolactone amounts to 86 per cent. of the theoretical.0.1105 gave 0.3055 CO, and 0-0700 H20. The lactone dissolves slowly in aqueous solution of caustic alkalis, and is reprecipitated by carbon dioxide. So great is the tendency to lactone formation that a current of steam slowly removes the lactone from its solution in excess of caustic potash. Cannabino-Zactonic Acid, COOH* C,H,<_sO~>CO.--I 1 *5 grams of cannabino-lactone, dissolved in hot aqueous potash, was treated with 41 -4 grams of potassium permanganste dissolved in 1000 C.C. of water, and the mixture, after being boiled for 9 hours, was d-ecolorised by a few drops of alcohol. The filtrate from the manganese dioxide, when evaporated to 200 C.C. and acidified with hydrochloric acid, deposited 10.6 grams of a pearly-white, crystalline compound, which, after re- crystallisation from hot water, was obtained in long needles melting at 203' (uncorr.).Two samples were analysed. C = 74.9 ; H = 7.0. Cl1HI20, requires C = 75.0 ; H = 6.8 per cent, C H The yield is 88 per cent. of the theoretical. C = 63.8 ; H = 5.2. 0.1371 gave 0.3205 CO, and 0.0635 H,O. 0*1380 ,, 0.3250 CO, ,, 0.0626 H,O. C=64*2; H=5*0. CIIHloO, require8 C = 64.1 ; H = 4.9 per cent, The lactonic acid is soluble in about 85 parts of boiling water, very sparingly in cold water, and easily in alcohol. Potassium 8aZt.-Prepared by adding alcoholic potash to an alcoholic solution of the lactonic acid. 0.2295 gave 0.0825 K,SO,. I< = 16-1. The silver salt was found to contain 33.8 per cent, Ag. Cl,H,04Ag requires 34.5 per cent. Theethylic salt was prepared by boiling the lactonic acid for 5 hours with a 3 per cent.solution of hydrogen chloride in absolute alcohol. After remystallisation from dilute alcohol, it melted a t 1 0 5 O (uncorr.), and, on analyais, gave the following numbers. C,,H9O4K requires K = 16.0 per cent.WOOD, SPIVEY, AND EASTERFIELD: CANHABINOL. PART I. 85 0*0861 gave 0.2095 CO, and 0.0484 H20. C = 66.4 ; H = 6.2. 0.1608 ,, 0.3905 CO, ,, 0.0890 H,O. C=66.2 ; H = 6.1, C,,H,O,* C2H5 requires C = 66.7 j H = 6.0 per cent. Fusion of Cannabino-hetonic Acid with Potash. 4.4 grams of the lactonic acid was fused with 25 grams moist caustic potash a t 286' (in a bath of boiling ,&naphthol). The reaction is completed almost instantaneously at this temperature, but proceeds with extreme slowness a t 220'.The melt, on being dissolved and acidified with dilute sulphuric acid, gave 3.4 grams of a crystalline precipitate, which, after several recrystallisations from dilute alcohol, sublimation, and a further recrystallisation, melted above 300°, and sublimed without decomposition. 0.1133 gave 0,2392 CO, and 0-0400 H,O. The analysis and physical characters agree with those of isophthalic Its methylic salt melted a t 64' (uncorr.), and boiled a t 280-282' The salt, C = 57.6 ; H = 3.9. C,H,O, requires C = 57.8 ; H = 3.6 per cent. acid. (uncorr.) (Baeyer gives 64-65', Annalen, 1873, 166, 340). on analysis, gave the following numbers. 0*1084 gave 0.2445 CO, and 0.0518 H,O. C=61*5 ; H=5-3. 0°1060 ,, 0,2395 C02 ,, 0.0510 H,O. C=61.7 ; H=5.3. C6H4(COOCH,), requires C = 61.9 ; H = 5.1 per cent. Potash Fusion of Cannabino-lactone with Potash. The conclusions to be drawn from the fusion of cannabino-lactonic acid are supported by the potash fusion of cannabino-lactone (0.9 gram) with moist caustic potash (15 grams) a t 300' to 320', which yields metatoluic acid, The reaction took place slowly, and the melt, which was very dark in colour, was dissolved, acidified with sulphuric acid, and extracted with ether, &c., in the usual way. After purifying the product by crystallisation from water and animal charcoal 0.3 gram was obtained. It began to melt a t 108', but was not completely melted until 200'. It was accordingly steam distilled, and the crystals, which separated in the distillate, were now found to melt at 110' (uncorr.). Jacobsen (Bey., 1881, 14, 2349) gives the melting point of metatoluic acid as 110.5'. The mother liquor from which the metatoluic acid had been removed by steam distillation, on being evaporated to dryness, dried at 150°, and then recrystallised from water, gave isophthalic acid, which melted above 300°, and sublimed without decomposition ; this was, no doubt, produced from the metatoluic acid by further oxidation. 0 236 KIPPING AND POPE : CHARACTERISATION OF Reduction of Cannabino-lactontic Acid. The lactonic acid was reduced by heating with hydriodic acid and pbosphorus in a sealed tube a t 190°, and the product, after two recrystallisations, melted a t about 210O. As the limited quantity of the substance did not allow of further purification, it was analysed. The result leaves no doubt that i t is the expected metacarboxy- phenylbutyric acid. (1) COOH- C,H,* C,H,* COOH (3). CllHI2O, requires C = 63.5 ; H = 5.8 per cent, 0.1298 gave 0,3044 CO, and 0.0695 H,O. C = 64.0 ; H= 6.9. UNIVERSITY CHEMICAL LABORATORY, CAMBRIDGE.

ISSN:0368-1645    

DOI:10.1039/CT8997500020

出版商:RSC    

年代:1899

数据来源: RSC

摘要:

36 KIPPING AND POPE : CHARACTERISATION OF IV.-Characterisution of Racemic Compounds. By FREDERIC STANLEY RIPPING and WILLIAM JACKSON POPE. WE have previously shown (Trans., 1897,71,989) that the results of the study of a number of externally compensated substances indicate that only one method is a t present of really practical use for characterising solid racemic compounds, that, namely, which is based on the deter- mination of the crystalline forms of the optically active and externally compensated materials ; and, in accordance with this conclusion, we defined crystalline racemic and pseudoracemic compounds from a purely crystallographic standpoint (Zoc. cit., 993). But the crystallographic constants of an organic substance are not always determinable with ease and completeness ; hence the establishment of other criteria of racemism is a matter of considerable importance.Now, Liebisch has shown (AnNaZen, 1895, 286, 140) that a com- parison of the densities of the optically active and externally compen- sated compounds affords a very simple method for the determination of racemism (compare Walden, Ber., 1896, 29, 1692) ; unfortunately, however, the results of the experimental determination of a difference between two density constants, especially when this difference is very small, as it frequently may be, can hardly be considered so conclusive as those derived from the much more complex series of constants constituting the crystallographic properties. This diffieulty of ascertaining, except by crystallographic. deter- minations, whether certain substances are really racemic on the one hand, or merely pseudoracemic or externally compensated mixtures onRACEMIC COMPOUNDS.31 the other, has led to attempts being made to devise simpler methods for the determination of racemism. Thus, Ladenburg (Bev., 1894, 27, 3065) formulates ‘‘ eine allgemeine Methode, um Gemenge enantio- morpher Korper von racemischen Verbindungen zu unterscheiden. Sobald es gelingt, die in Frage stehende Substanz, die wenigstens einen kleinen Ueberschuss der einen drehenden Modification enthalten muss, durch Behandlung mit inactiven Korpern in Fractionen von verandertem Drehungsvermogen zu verwandeln, liegt stets eine Verbindung vor.” Now this method, if really applicable, should prove of great value, but inasmuch as Ladenburg adduces no experimental evidence sup- porting its validity as a means of discrimination, but uses it without further inquiry in order to decide as to the racemic nature of externally compensated coniine, the conclusions based on its use cannot be regarded as in any way decisive.Moreover, the method is arrived at by means of a curiously fallacious piece of reasoning, for, just before the above quotation, Ladenburg writes : ‘‘ es ist, wie ich glaube, eine bisher ausnahmlos bestitigte Thatsache, dass enantiomorphe Eorper stets die gleiche Loslichkeit besitzen und daher auch in Verbindung mit inactiven Stoffen nicht durch Krystnllisation oder partielle Fallung getrennt werden konnen.” Now there seems not the least justification, experimental or theoretical, for the deduction which Ladenburg draws from the fact of the equal solubility of the two enantiomorphously related substances, namely, that a mixture of unequal quantities could not be separated by crystallisation or partial precipitation.There is, in fact, no evidence that an inactive non-racemic mixture has the same solubility as either of its active components and if its solubility be greater, then, on concentrating a solution containing such a non- racemic mixture together with excess of one enantiomorph, a t constant temperature, that excess would crystallise first, leaving material of lower specific rotation in solution ; a continuation of this process would ultimately afford a mother liquor containing an inactive non-racemic mixture. The solution would then go on depositing dextro-and lsvo- material in equal proportion as evaporation proceeded, casual dis- turbances of equilibrium such as always occur in a crystallising solution being, of course, disregarded.Obviously, therefore, any arguments based upon our present knowledge of the laws governing solubility should have led Ladenburg to a conclusion diametrically opposed to that a t which he actually arrived. The question of the racemic nature of externally compensated coniine has lately been again considered, and Kuster (Bey., 1898, 31, 1847), arguing from the solubility products of the various isomerides, con-38 ICIPPING AND POPE : CHARACTERISATION OF dudes that a large part of the inactive substance exists in solution in a racemic condition. Although this conclusion may be true, yet, inasmuch as no case has been investigated in which the solubility values indicate that no racemism occurs in the solution, or in the solid state, as the case may be, Kuster's method cannot be accepted.A hypothesis founded upon one set of phenomena often gives valuable indications as to the direction in which work should be done in con- nection with the examination of a second set of phenomena, but these are merely indications, and require experimental verification before the hypothesis can be extended so as to cover the new ground. The cases dealt with by Kuster are instances in which the ordinary solubility laws applying to two mutually inactive soIutes are not followed ; when a case is found amongst externally compensated substances in which the solubility determinations indicate the non-existence oE a racemic compound in solution, Kuster's method will become of practical value.Until then, however, it must be classed with Ladenburg's method as an untried one. In order to ascertain the accuracy or otherwise of Ladenburg's argument, we have examined three cases experimentally ; those, namely, of sodium ammonium tartrate, sodium potassium tartrate, and potassium hydrogen tartrate. Sodium Ammonium Dextro- and Lawo-turtrates. An externally compensated mixture of dextro- and lwo-sodium ammoninrn tartrates is known to be non-racemic a t ordinary tempera- tures, but becomes racemic a t and above 27' (van't Hoff and Deventer, BeT., 1886, 19, 2148); below this temperature, the salt separates from solution as a mere mixture of the two tartrates.Now, if Ladenburg's rule be applicable, on crystallising the sodium ammonium salt of racemic acid with an excess of sodium ammonium dextrotartrate below 2 7 O , the successive fractions should have the same specific rotation ; but, as a matter of fact, the behaviour of the mixture on crystallisation is that which would be expected from our interpretation of the laws governing the equilibrium of such solu- tions. In a, preliminary experiment, an intimate mixture of 25 grams of aodium ammonium dextrotartrate with 5 grams of the corres- ponding lzevotartrate was made; it was found to have the specific rotation [ u ] ~ = + 15.60' in a 5 per cent. solution, instead of the calculated value [u] = + 15-76', The mixture was dissolved in cold water and set aside to evaporate; after several days, a fraction (1) sepa- rated and was collected, washed with cold water, and dried in the air.The mother liquor and washings were mixed and set aside to crystallise,KACEMIC COMPOUNDS, 39 wheh a further separation (2) was obtained; this was removed as before, the mother liquors evaporated to dryness, and the residue collected, During the experiment, the laboratory temperature never rose above 15"; the weights and rotations of these fractions were as follows. Weight. [.ID Total material 30 g. c 15-60' E'irst fraction, (1) 8 g . + 23.51 Second ,, (2) 13 g. + 20.27 Third ,, (3) 8 g. 0 Instead of all the .three separations having the same specific rot-ation as the original mixture, as required by Ladenburg's rule, the first two fractions consisted almost entirely of dextrotartrate, whilst a 5 per cent.aqueous solution of the residue in the mother liquor had no observable rotation in a 200 mm. tube. In order to trace this process of separation more carefully, and thus obtain further data, the following experiments were made. A mixture of 26.1 grams of sodium ammonium dextrotartrate, with an equal weight of the salt obtained from racemic acid, was made ; this mixture, having a specific rotation of [ aID = c 11.82", was dissolved in water and allowed to crystallise spontaneously at the ordinary laboratory temperature, which never rose above 18O, namely, 9' below the tem- perature at which a racemic compound begins to separate. As the various deposits were obtained, they were separated by means of the filter pump (but not washed free from mother liquor) and examined, the fractionation proceeding in accordance with the following scheme (next page).The weigh are given in 6 and 6 give .is, w, and the specific rotations a, of the various fractions columns 2 and 3 respectively of Table I (p. 41), columns respectively the excess of dextro- over inactive salt in 100 parts of t h e various fractions, and the actual weights in grams of the excess of dextro-salt in these fractions. The weight of salt recovered from the 52.2 grams dissolved was Xu, ~ 5 1 . 2 5 grams; the weighted mean specific rotation of all the fractions is Swa/Xzu= + 12-20', and if the weight of salt taken, namely, 52.2 grams be substituted for Zw, the mean specific rotation &~a/52*2 = + 1148O is obtained.The mixture of salts actually had the specific rotation [a JD = c 11-82' so that within the limits of the experimental errors unavoidably incurred in so long a series of fractionations, the whole of the salt used is accounted for. The specific rotation of sodium ammonium dextrotartrate, Na(NH4)C4H406 + 4H,O, is [alp = + 23*64O, and the first large deposit of 32.1 grams contained26'1 grams. d-Na(NH4)C4H40,,4H20. 26'1 grams. i-Na(NH4)C4H406,4H,0. Dissolved. I I Mother liquor. - Crystals. I f- I 3.2-i g. 19.25 g. Crystals. I Mother liquor. C. I M. L. +- > +--+----- I I------- I 1 6.8 g. C l , M. L. I I hi 4 '85 8. I I +- 12'3 g. C. I M. L. I--+ I Zl 2.5 g. 9.8.g. C. I M. L. --+- I I z26*1 Q. 13 3!7 g.h2 3-25 g. I h, 1.7 g. '1 I" P. m, 1-15 g. k2'4*6 g. k, i . 9 g.RACEMIC COMPOUNDS. 41 TABLE I. 1. Fraction. 2. W. grams. 4 -85 3.25 1 '70 1 -50 4-60 3.9 2.5 6 '1 3.7 4 '15 3 '5 11 '6 BW = 51'25. 3. a. + 23 '23 + 23-23 + 21 $5 + 23-47 + 23'12 + 23 *02 + 22.51 + 10.51 0 + 15.52 +5'41 - 22'40 4. wa. -1-112'67 + 75-50 3- 36 '64 + 35-20 + 106.35 -l- 89% + 56 '27 + 64.11 0 + 64.41 + 62.76 - 78-40 5. Percentage excess of d-salt. + 98.26 + 98.26 + 90'36 + 99.28 + 97 '80 + 97 '38 3-95'22 + 46 '46 0 -l- 65.65 - 94-75 + 22-88 6. Weight of excess of d-salt. D. + 4'766 + 3.194 +1-550 +1*488 3- 4'499 + 3,798 + 2.381 +2*712 + 2.724 + 2.655 0 - 3.316 Bwa= f625.29. BD= + 26.451. Zwa- -- +11-98" Bwa - + 12.20". BW 52'2 28.25 grams of sodium ammonium dextrotartrate and 3.85 grams of the isomeric laevo-salt ; this corresponds with 24.4 grams of the sodium ammonium dextrotartrate with 7.7 gramsof the inactive mixture, so that nearly the whole of the 26.1 grams of the dextro-salt originally taken was deposited in the first crop of crystals.After the next separation, ml, from the mother liquor, 27.1 grams of the dextrotar- trate had separated in addition to inactive material ; consequently, the mother liquor was strongly laevorotatory, and the next separation, m2, was a laevorotatory one. Practically, all the excess of the dextro- rotatory salt was contained in the first fractions, h,, h,, h,, kl, k,, k,, and I,, which consisted almost entirely of this salt, but still contained small quantities of the inactive material, partly because the crystals mere not washed, and partly, no doubt, because of occluded mother liquor, which is often present in noticeable quantity, The further changes during crystallisation will be understood from the tabulated results.In a recent paper (Trans., 1897, 71, 999), we have shown that ex- ternally compensated camphorsulphonic chloride (Trans., 1893,63,560) and camphorsulphonic bromide (Trans., 1895, 67, 359) are probably pseudoracemic ; consequently, they behave, on cry stallisation, like non-42 RIPPING: AND POPE : CHARACTFAISATION Ol? racemic compounds and the ethylic acetate solutions of a strongly dextrorotatory mixture of the sulphonic chlorides deposits, on evapra- tion, part, or the whole, of the excess of the dextro-compound ; after the solution has thus become nearly or quite inactive, further crystal- lisation affords deposits which sometimes contain fin excess of one or other isomeride, a behaviour which is obviously very similar to that of the sodium ammonium tartrates.Sodium Potassium Dextrotartvate a d Racemate. Having shown by the foregoing experiments that Ladenburg's method does not hold in the case of non-racemic sodium ammonium dextro- and lavo-tartrates, namely, in the only test case on which the method has yet been worked out, we thought it advisable to apply the same method to a case in which a crystalline racemic com- pound undoubtedly exists, in order to ascertain whether the fractional separation occurs in a manner essentially different from that observed in the case of a non-racemic mixture, Sodium potassium dextrotartrate is isomorphous with the corre- sponding sodium ammonium salt and, at temperatures between - 6' and +4l0, forms a racemic compound with the isomeric lsvotartrate (van't Hoff and Deventer, Zed.physik. Chem., 1895, 17, 505); it therefore forms a racemic compound a t ordinary temperatures. The optically active substances have the composition NaKC,H,06 + 4H20, whilst the composition of the racemate is NaKC,H,O, + 3H20. A mixture of 47.4 grams of sodium potassium dextrotartrate with 44.4 grams of the racemate (molecular proportions) was dissolved in water and fractionally crystallised as before ; the scheme given on the next page shows how the various fractions were collected. Table I1 (p. 44) gives the weights, w, and the specific rotations, a, for the D-line ; columns 5 and 6 give the values corresponding with those in Table I.The specific rotation of the anhydrous dextrotartrate, KNaC4H40,, is + 29-67' (Landolt) ; that of the mixtupe of 47-4 grams of hydrated dextrotartrate with 44.4 grams of the racemic salt is, therefore, [.ID = + 11*41°. The weighted mean specific rotation of all the separated fractions is whilstRACEMIC COMPOUNDS. 63 I44 KIPPING AND POPE : CHARACTERISATION OF 1 Fraction. 2. w. grams. 9 -15 10.40 7 -45 4.45 8 *70 7 -8 12 -2 3.3 3-4 6 *7 8.7 9.0 TABLE 11. 3. a. + 22 '08" + 21 -77 + 21 '56 + 21.25 + 17 '50 + 21 -35 +4'58 - 20.00 + 10.00 + 1-35 0 0 4. wa. + 202.0 + 226 '6 + 160 '6 + 94.6 + 152.2 + 166.5 4- 55.9 - 66.0 + 34.0 +9.0 0 0 6. Percentage excess of d-salt.+ 99'73 + 98 '33 + 97'38 + 95-98 +79'22 t 96'43 + 31 *90 + 45.17 +6*10 0 0 - 90'34 6. Weight of excess of d-salt. D. +9*125 I- 10 '230 + 7'255 -t- 4.271 + 6 -891 +7'523 + 3 *364 + 1 -536 + 1 '408 - 2'981 0 0 Zw = 91'25. ZWU= + 1035'4. 3 3 = + 11 -34". tW ZD= 3- 47'622 t ~ = 5 3 * 5 a 4 . E= + 11-28". The agreement between the quantities and specific rotations of the material taken, and the quantities and specific rotations of the fractions recovered, is hence highly satisfactory. From an inspection of Table 11, it is seen that the successive fractions separating from the solution decrease in specific rotation, that is t o say, they contain decreasing quantities of the dextrotartrate in excess of the racemate, and ultimately the mother liquors contain nothing but pure racemate.The table also shows the following curious facts : the fractions h, k, and I contain 48.66 grams of the dextrotartrate as such, whilst material corresponding with only 47.4 grams was used; the difference of 1.26 grams, therefore, musf, be ascribed either to experimental error or to the fact that part of the racemate used was resolved, and the dextrorotatory component de- posited here. That the latter alternative is the true one is shown by the mother liquor becoming laevorotatory. Consequently, on crystal- lising the latter, the first deposit, ml, is strongly Iaworotatory, con- taining 90.34 grams of lzevotartrate to each 9.66 grams of racemate; 2.98 grams of lsvotartrate crystallised as such in ml, whilst the solution only contained 1.26 grams excess of this salt.I n the end, therefore, 50.38 (47*4 + 2.98) grams of dextrotartrate had separatedRACEMIC COMPOUNDS. 45 from solution as such, or about 3 grams more than had been used ; it follows, therefore, that a partial resolution of the racemate had occurred, about 6 grams being so resolved. The good agreement of the sums of the weights of salt separated from the solution and the mean rotation of the fractions, on the one hand, with the weight of salt and the mean specific rotation which should have been obtained, on the other hand, is proof that we are not here being misled by experimental error. The interesting work of Purdie on the resolution of lactic acid into its optically active components (Trans., 1893, 63, 1143) affords a case, similar to the above, of the resolution of a racemic compound. Racemic zinc ammonium lactate crystallises with 3H,O, and when its supersaturated solution is sown with a crystal of either of the optically active isomerides, that particular isomeride separates in crystals containing 2H,O ; this resolution is similar t o that which has occurred in fractions 1, and ml of our mixture.We are thus led to the following conclusion : a racemic compound may, under certain conditions, be resolved into its optically active components by simple crystallisation, at temperatures at which the racemic compound is more stable than the mixture of the two optically active salts. A comparison of Tables I and I1 shows that the fractional crystal- lieation has followed much the same course in the case of the racemic compound as in that of the non-racemic mixture ; the separation of the racemic compouEd from the dextrorotatory one is, however, not quite so sharp as in the separation of the non-racemic mixture. Pota8sium Hydrogen Dextrotartrate and Racemate, KHC,H,O,.In the foregoing cases, the inactive mixture or compound is more soluble than either of the active components; it seemed desirable, therefore, to investigate a case in which the contrary is true. Such a case was found on examining the behaviour of the potassium hydro- gen tartrates. On crystallising a mixture of equal quantities of the dextrotartrate and of the racemate, by allowing the hot solution to cool, it was found that the mother liquor contained a salt of much higher specific rotation than that of the mixture deposited; by repeatedly recrystallising the deposit, the specific rotation of the material in the successive mother liquors remained nearly constant, and of very much higher value than that of the crystalline separations. Owing to the sparing solubility of these two salts, they had to be dis- solved in dilute ammonia for the rotation determinations. The results need not be quoted in full, because they were in so many respects similar to the preceding cases, and the experimental error was greater.46 POPE : CRYSTALLIME FORM OF IODOFORM. The examination of these three cases shows that Ladenburg’s method does not constitute a means of discriminating between cases in which a solid racemic compound is formed, and those in which a mere inactive mixtiure is obtained; a scrutiny of Tables I and I1 will show that this method gives practically the same results with a well-deflned racemic compound as with a non-racemic mixture. It may possibly be objected that, although inactive sodium am- monium tartrate does not exist as a solid racemic compound at ordinary temperatures, it may exist as a racemic compound in soh- tion ; to make this assumption unsupported by experimental evidence is, however, unjustifiable, and can only be regarded as an expression of opinion. CHEMISTRY DEPARTMENT, CHEMISTRY DEPARTMENT, UNIVERSITY COLLEGE, GOLDSMITHS’ INSTIrUTE, NOTTINGH AM. LONDON, S.E.

ISSN:0368-1645    

DOI:10.1039/CT8997500036

出版商:RSC    

年代:1899

数据来源: RSC

摘要:

46 POPE : CRYSTALLIME FORM OF IODOFORM. Form of Iodo form. By WILLIAM JACKSON POPE. UP t o the present, no geometrical measurements with any pretensions to accuracy have been made on crystals of iodoform, the only available data consisting of two angles measured by Rammelsberg (Kryst.-phys&%. Chm., 1882,2,321) ; these measurements cannot, however, be credited with much value since Rammelsberg remarks of his crystals that '' die Flachen sind ziemlich matt." Considerable difficulty is found in obtaining well developed crystals of iodoform using the ordinary organic solvents such as alcohol or benzene. Iodoform is, however, fairly soluble in acetone, and on allowing the cold solution t o evaporate spontaneously at n uniform temperature, magnificent, transparent, six-sided tablets of iodoform separate ; in order to obtain the best results, the acetone should be as free from water as possible.Even when pure, almost odourless iodoform is used, blacken- ing occurs round the sides of the vessel, and gome product, probably iodacetone, is formed during the evaporation which excites to tears, and powerfully affects the mucous membrane. The crystals, which may readily be obtained of a centimetre in dia- meter, and several millimetres in thickness, are uniformly developed, and the faces give very perfect reflections on measurement. The dominant form is c (1 1 l}, the pyramid (100, 22T) being very much smaller ; the prisms p (rl0) and 9n (21i) are rarely observed and are always small (see Fig. 1). The crystals are very hard and brittle, freePOPE ! CRYSTALLINE FORM OF IUDOFORM.47 Mean. from striations, and have no noticeable cleavage ; they show a six-sided internal growth of hexagonal symmetry when allowed to grow rapidly. The normal hexagonal optic axial interference figure is seen on 00110- scopic examination through the faces of c { 11 l} ; the double refraction is strong and negative in sign. Rammelsberg (Zoc. cit.) determined the angles cr (1 11 : 100) = 52' 0' and rr (221 : 100) = 4 6 O 30', gives the axial ratio u : c = 1 : 1.108, and only observed the forms c ( l l l } and r (100, 221). Crystalline system.-Hexagonal. a : c = 1 : le1O84. a = 93' 41'. Forms observed c (11 l}.. ............ .(0001} (ioo,22i}.. .... ...{ i o i i } p (110) ............ .,.{2110) {21i] ............ ...( olio) - - Calculated, FIG.1. The following angular measurements were obtained. Angle. c r = l l l : 100 rr= 100 : 012 r~ = 221 : GO1 I.r=T_00 : 010 pr=llO : 010 rr =22T : 100 W= 2 2 i : zoo Cplll : 1E rm= 100 : 211 Number of measurements. 38 16 47 15 22 34 19 13 18 Limits. 51'55'- 52" 7' 85 58- 86 6 7550- 76 6 93 54- 94 3 46 43- 47 2 46 20 - 46 25 133 32 -133 41 89 57- 90 4 37 54- 38 9 51 "59'5 0' 86 2 0 76 0 30 93 58 10 46 57 30 4.6 23 40 133 36 10 90 0 20 38 2 0 - 86" 2'20'' 76 020 93 57 40 46 58 50 46 24 0 133 36 0 90 0 0 38 010 After cautious melting under acover slip on a microscope slide, iodoform crystallises readily, giving broad, individual crystal flakes, the surfaces of which are parallel to c (111) ; the optic axis of negative double re- fraction emerges normally to the film surface. It is interesting to note that a large proportion of compounds of simple constitution crystallise in systems of high symmetry, such as the cubic or hexagonal. It may also be remarked that, whilst the molecule of carbon tetriodide has partial cubic symmetry and crystal- lises in the cubic system, the molecule of iodoform has partial hexagonal48 PEHKIN AND THORPE : fl&DIMETEYLGLUTARIC symmetry and crystallism in the hexagonal system. Many other similar analogies could be quoted, and although complications due to polymorphism frequently occur, it may be stated that a knowledge of the chemical constitutions of simple compounds often allowg of a safe prognosis of the crystalline form which those compounds assume. CHEMICAL DEPARTMENT, CENTRAL TECHNICAL COLLEGE, LONDOX.

ISSN:0368-1645    

DOI:10.1039/CT8997500046

出版商:RSC    

年代:1899

数据来源: RSC

摘要:

48 PEHKIN AND THORPE : fl&DIMETEYLGLUTARIC ~I,-$B- Dimethylglutaric Acid und its Derivatives ; Synthesis of cis- and trans- Caronic Acids. By WILLIAM H. PERKIN, jun., and JOCELYN F. THORPE. CARONE, C,,H160, one of the most important ring ketones in the terpene series, is formed when dihydrocarvone hydrobromide is treated with alcoholic potash, hydrogen bromide being eliminated, a decompo- sition which, according to G. Wagner," may be formulated in the following manner. CH- CH, CH* CH, /\ A H2C GO / \ I I H2C H,C CH, = I ( C W , I \ I / \i/ co + HBr. \/ H2C C--CH QH (CHd2CBr CH Dihydrocarvone hydrobromide. Carone. This view of the constitution of carone was considered probable by Baeyer, who, in order to confirm this formula, carried out a number of important experiments on carone, during the course of which he, in conjunction with Ipatieff, investigated the behaviour of this sub- stance on oxidation with permanganate (Bey., 1896, 29, 2796).It was found that, although carone is very stable towards perman- ganate at the ordinary temperature, it is moderately readily oxidised at looo, with formation of two isomeric dibasic acids, C,H,(COOH),, melting at 176' and 2 1 2 O , which were named caronic acids. The former of these, which is produced in much the larger quantity, readily yielded an anhydride melting at 54-56' when boiled with acetyl chloride, but the other acid was not affected by this treatment. * Compare Raeyer (Ber., 1896, 29, 5 and 2796).ACID AND ITS DERIVATIVES. 49 A careful examination of these acids led Baeyer and Ipatieff to the conclusion that the caronic acids were stereoisomeric modifications of dimethyltrimethylenedicarboxylic acid.c(cH3)2 A / \ '('I3[,), /\ COOH. 6-17 -COOH H-Q -C-H, H H COOH bOOH and that these were formed by the oxidation of carone at indicated by the dotted lines in the formula trans-Caronic acid. cis-Caronic acid. CH*CH, the points That these acids have the same structure and are stereoisomeric seemed probable from their behrtviour towards hydrobromic acid at looo, under which conditions both are converted into terebic acid with disruption of the trimethylene ring (Zoc. cit., p. 2801). Br(&CH3)2 GOOH* CH-CH*COOH + HBr = COOH. CH2* CH* COOH (?(cH3)2 + HBr. 0- I = CO CH,. CH* COOH No mention is, however, made of any attempt to convert the one modification into the other.In studying this important work, it seemed to us that it would be most interesting t o find some means of synthesising the caronic acids, and of thus placing their constitution beyond doubt. This was ultimately accomplished in the way described in this paper. Some time since, it was shown by Goodwin and Perkin (Trans., 1896, 69, 1475), that ethylic dimethylacrylate condenses with the sodium derivative of ethylic malonate with formation of ethylic d-imetb y lpropanetricarboxylate, (COOC2H,),CW* C(CH,),* CH,* C00C2H,, and from this, by hydrolysis and elimination of carbon dioxide, pp-di- methylglutaric acid, GOOH* CH2* C(CH,),* CH,* COOH, was prepared. The yield of acid obtained in this way is small, but by substi- VOL. LXXV E50 PERKIN AND THORPE : &?~-DIMETHYLGLUTARRTC tuting ethylic cyanacetate for ebhylic malonate in the condensation with ethylic dimethylacrylate, we now find that the yield of condensation product, which consists of a mixture of some ethylic a-cyano-PP-dimethyG glutarate, COOC,H,* CH(CN)*C(CH,),* CH,.COOC,H,, with much of the hydrogen ethylic salt, COOH. CH(CN)*C(CH,),* CH,. COOC,B ,, is more than 80 per cent. of the theoretical, and, as these ethereal salts, on boiling with 50 per cent. sulphuric acid, are quantitatively converted into PP-dimethylglutaric acid, it is now an easy matter to prepare this acid in quantity. When the anhydride of dimethylglntaric acid is treated with phos- phorus pentabromide and bromine, and the product poured into absolute alcohol, ethylic bromodimethyllglzctarat~, COOC,H,- CHBr* C(CH,),*CH,* COOC,H,, is produced, together with large quantities of the hydrogen ethylic salt of the same acid, COOH.CHBr*C(CH,),* CH,. COOC,H, ; that the latter should be produced in such quantities is certainly remarkable, andra possible explanation of its formation is given in the experi- mental part of this paper. When ethylic bromodimethylglutarate is digested with alcoholic potash, hydrolysis and elimination of hydrogen bromide .takes place simultaneously, and it mixture of acids is ob- tained which, by conversion into the ammonium salts and treatment with alcohol, as recommended by Baeyer and Ipatieff (Zoc. cit., 2978), is easily separated, and found to consist of large quantities of trans- carmic acid, some lactone acid of hydroxydimethylglutaric acid (see below), and traces pf ois-caronic acid.This synthesis of the caronic acids may be represented in the following way. C(CHJ2 /\ gives COOH. UH-CH* COOH. / \ COOC,H,* CHBr OH,* COOC,H5 Hydrogen ethylic bromodimethylglutarate, COOH* CHBr*U(CH,),*CH,* COOC2H5, on treatment with alcoholic potash, is quantitatively converted into trans-caronic acid, apparently without even traces of the cis-modifica- tion being formed. The synthesis of a trimethylene compound in the manner represented above is remarkable, but a few similar cases have been observed, as, for example, in the formation of acetyltrimethylene by the action of alkalis on acetylpropyl bromide, CH,*CO*CH2A(?H2 = UH,* C0*CH<FH2 + HBr. CH,Br CH2 The synthetical caronic acids have been very carefully investigated, and it is shown in the experimental part of this paper that their pro.ACID AND ITS DERIVATIVES, 51 perties agree in a11 respects with those of the acids obtained by Baeyer and Ipatieff from carone, so that there cannot be any doubt as to the identity of the acids produced by these different methods.One additional point of interest has been discovered, namely, 'that tram-caronic acid is converted into the anhydride of ciscaronic acid by the action of acetic anhydride at 220°, a transformation of the tram- into the cia-modification which was required to clearly show that these two acids are stereoisomeric. Furthermore, it is shown in this paper that aqueous sodium car- bonate hydrolyses the hydrogen ethylic salt of bromodimethylglutaric acid, COOH* CHBr*C(CH,),* CH,* COOC,H,, in a manner quite different from alcoholic potash, with formation of the lactone of a-hydroxy- PP-dimethylgh?ark mid, CooH* C'C(CH3)2* CH2, a beautifully c r p b-- 60 talline substance which melts at 112' and is isomeric with the caronic acids.When ethylic bromodimethylglutarafe, COOC,H,* CHBr- C(CH,),* CH,* COOC,HB, is digested with diethylaniline, hydrogen bromide and ethylic bromide are eliminated and an ethereal salt is obtained, which, on examination, has been found to consist of the ethylic salts of tram-caronic acid, and of the lactone of hydroxydimethylglutaric acid. EX PER I M E NTAL. Condensation of Ethyl& DimethyZacryZate with the Xodiuna Derivative of Ethylic Cyanacetate.PP-Dimethylglutaric acid, COOI€*CH,*C(CH,),*CH,* COOH, the acid which is the starting-point in the aynthesis of the caronic aids, was first prepared by Goodwin and Perkin (Trans., 1896, 69, 1476), who obtained it by the following series of reactions. Ethylic dimethylacrylate was, in the first place, digested with the sodium derivative of ethylic malonate in alcoholic solution, when con- densation took place with formation of ethylic dimethylpropanetri- carboxy late, (COOC,H,),CH, + (CH,),C:CH* COOC,H, = (COOC,H,),CH* C( CH,),. CH2-COOC,Hv This ethereal salt, on hydrolysis, yields the corresponding tribarsio acid, which, at 200°, loses carbon dioxide with formation of P/3-dimethyl- glutaric acid, GOOH. CH,* C(CH,),* CH,*COOH, and from this the anhydride is readily prepared by treatment with acetic anhydride.The yield of the original triethylic salt is unfortunately not good, and $ 252 PERKIN AND THOBPE : &~-DIMETHITLGLUTARIC seldom reaches more than 40 per cent. of the theoretical ; indeed, the average yield is scarcely more than 28 per cent. Until quite recently, we have prepared all the dimethylglutaric anhydride required for this research by the method devised by Goodwin and Perkin. A few months since, however, we discovered that the yield may be very greatly im- proved by substituting ethylic cyanacetate for ethylic malonate in the condensation with ethylic dimethylacrylate, the yield of condensation product ,being increased to at least 80 per cent. by this means.* Ethylic a-cyano-#l-dimethylglutarate, COOC2H,: CH(CN)*C(CH,),*CH,* COOC,H,, has been prepared in large quantities by the above proces8, the details of preparation being the following. Sodium (23 grams) is dissolved in alcohol (300 grams), the solution of sodium ethoxide mixed with ethylic cyanacetate (1 13 grams), ethylic dimethyl- acrylate (129 grams) is then added, and the whole heated in a reflux apparatus on the water bath.The sodium derivative of ethylic cyano- acetate, which a t first separates.as a white, crystalline powder, slowly dissolves, and the liquid darkens and gradually sets to an almost solid cake of the sodium derivative of the condensation product, the reaction being finished in about 24 hours. Water is now added, and the oily con- densation product extracted with ether in the usual way; the ethereal solution, after washing with water and drying over calcium chloride, deposits a thick oil which, after two distillations under reduced pres- sure, passes over constantly a t 190' (30 mm.), and consists of pure ethylic cyanodimethylglutarate.0.2614 gave 13.5 C.C. nitrogen at 20' and 750 mm. The yield of this substance produced in the above reaction is about 15 per cent. of the theoretical. The principal product formed in this condensation is the acid ethylic salt of the substance just mentioned, that is, ethylic hydrogen a-cyano-pp- dimeth&Zutwate, COOH- CH(CN) C(CH,),* CH,* COOC,H, ; this is obtained on acidifying the mother liquors of the eondensation product mentioned above and extracting with ether. After thoroughly washing the ethereal solution, drying over calcium chloride and evapo- rating the ether, a thick oil is left, which was not snalysed, since, for reasons stated below, it cannot be purified by distillation, and it showed no signs of crystallising.The yield of this substance formed is no less than 60-70 per cent. of the theoretical. N=5*S0. C12Hl,N0, requires N = 5.81 per cent. * This immensely increased yield is not confined to this condensation, since it has been found that a similar result is obtained when other unsaturated ethereal salts, such as ethylic crotonate, ethylic methylacrylate, &c., are employed, and the products formed in this way are at present being investigated by one of us.ACID AND ITS DERIVATIVES. 53 It is very difficult to understand why this acid ethereal salt should be produced in such large quantities; its formation is certainly not due to the presence of water, as several careful experiments which were made with specially dried alcohol gave, in every case, the same yield, When distilled under ordinary pressures, this acid ethereal salt is readily decomposed, with elimination of carbon dioxide and formation of ethylic y-cyano-P/l-dimethyZhtyrate, CN* CH,* C(CH,),- CH,*COOC,H,, which is a mobile oil distilling without decomposition at 244O.0.2783 gave 21.8 C.C. of nitrogen at 20' and 735 mm. C,H,,O,N requires N = 8-28 pet cent. When digested with concentrated hydrochloric acid in a reflux appa- ratus, it rapidly dissolved, and on cooling and mixing with an equal bulk of water, a mass of crystals separated, which, on examination, was found to consist of the imide of dimethylglutaric acid.N=8*66, This substance is produced by the hydrolysis either of ethylic a-cyanodimeth ylglutarate or hydrogen ethylic cyanodimethylglutarate, the process in the two cases being somewhat differently conducted. When the first or neutral ethylic salt is employed, the pure substance (60 grams) is heated with methyl alcoholic potash (50 grams) for 2 hour#, the solution evaporated until free from alcohol, acidified, and extracted with ether, After evaporating the ether, the residue, which probably consists principally of cyanodimethylglutaric acid, is digested in a reflux apparatus with concentrated hydrochloric acid for 3 hours, when, on evaporating, the whole become4 filled with colourless needles of the imide ; these are collected with the aid of the pump and recrys- tallised from water, In the case of the hydrogen ethylic salt, it is only necessary to boil with an equal volume of concentrated hydro- chloric acid for 3 hours, in order to get directly an almost quantita- tive yield of the imide, care being taken to so moderate the reaction as to avoid loss from the evolution of carbonic anhydride, which is apt to become very vigorous.PP-Dimethylglutarimide crystallises from water in long, colourless needles, which melt a t 144", and a t a higher temperature distil unchanged. It is very sparingly soluble in cold water, readily in hot water, and is almost insoluble in dry ether. 0.3034 gave 26 C.C. nitrogen at 17' and 750 mm. N = 9 *82. C7H,,N02 requires N = 9.93 per cent.58 PERKlN AND THORPE : fl&DIMETB[YLCtLUTARIC This imide is quantitatively converted into PP-dimethylglutaric acid (m.p. 1 0 1 O ) on heating in a closed tube with concentrated hydrochloric acid for 5 hours at 20O0, or by heating with dilute rsulphuric acid (50 per cent.) for 3 hours on a sand bath, the acid being readily obtained from the products of hydrolysis by extraction with ether in the usual may. This anhydride has already been obtained from the acid by treatment with ace& anhydride (Trans., 1896,69,1475), but the process used in the production of the acid and conversion of this into the anhydride has subsequently been much improved, and very large quantities have been prepared for the purposes of this research by the following method, Ethylic cyanodimethylglutarate, as well as the acid ethylic salt, which is always the chief product in the condensation of ethylic cyanoacetate with ethylic dimethylacrylate, are boiled with an equal volume of 50 per cent.sulphuric acid for 12 hours on the sand bath. The exact; end point of the reaction is difficult to determine, owing to the fact that the sulphuric acid converts a large proportion of the dimethyl- glutaric acid into anhydride, and this, like the unhydrolysed ethylic d t ' s , floats on the surface of the aqueous liquid as on oil; we found, however, that 12 hours was sufficient to ensure complete hydrolysis. The product, when cold, is extracted several times with ether, the ether distilled off, and the residue, without further purification, mixed in the same flask with an equal bulk of acetic anhydride, and boiled for 3 hours on a sand bath, using a reflux condenser.After distilling off most of the acetic anhydride under the ordinary pressure, the orude dimethylglutaric anhydride which remains is purified by fractionation under reduced pressure, when almost the whole passes over at 181' (25 mm.) as a colourless oil, which, on cooling, solidifies to a hard, crystalline cake. The yield of pure anhydride obtained in this way was over 90 per cent. of theory calculated from the et hylic cyanodimethylglutarate, or about 73 per cent. calculated from the ethylic cyanoacetate originally used in the condensation. Action of Bromine on Dimetl$gZoctaric Anhydq*ide.--In investigating this reaction, dimethylglutaric anhydride was treated with phosphorus pntsbromide and bromine, and the bromo- or dibromo-acid bromides thus produced were converted into methylic or ethylic salts by the action of methylic or ethylic alcohols.Et h y 1 ic a- b rmo- PP-dime thglgZu t arate, COOC,H,- CHBr*C(CHJ2* CH,- COOC2H5,ACID AND ITS DERIVATIVES. 55 was prepared from dimethylglutaric anhydride (13 grams) by mixing it with phosphorus pentabromide (50 grams), and heating the mixture in a reflax apparatus on the water bath until the reaction was com- plete ; bromine (16 grams) was then gradually added, and a8 soon as the vigorous evolution of hydrogen bromide had ceased the whole was heated on the water bath until colourless, and the product poured into well-cooled absolute alcohol.After being allowed to stand for some hours, water was added, when a heavy oil was precipitated which was extracted with ether, and the ethereal solution, after washing well with sodium carbonate solution, was dried over calcium chloride and evaporated. The nearly colourless heavy oil thus obtained, on fractiona- tion, distilled constantly at 181O (20 mm.), and consisted of pure ethylic bromodimethylglutarate. 0.1820 gave 0.0669 AgBr. Br = 27.23. C1,H,,BrO, requires Br = 27.11 per cent. Hydrogen EthyZic XaZt of a-Bromo-pp-caimethyZgZzctaric Acid, COOH. CHBr*C(CH,),- CH,* COOC,H5. This is precipitated in considerable quantity when hydrochloric acid is added to the sodium carbonate washings obtained as ex- plained in the last paragraph. It is a heavy, colourless oil which distils without decomposition at 240' (35 mm.).0.1932 gave 0.0771 AgBr. C,H,,BrO, requires Br = 29.97 per cent. The formation of this acid ethylic salt in the proportion of about 20 per cent. of the total product of bromination is not due t o the presence of water in the alcohol used, as is shown by the fact that exactly the same amount was formed in an experiment in which extra precautions were taken to eliminate, as far as possible, every trace of water. It seems to us probable that, from the examination of a number of similar cases, some acid bromides have the power of decom- posing alcohol in such a way as to form the free acid and ethylic bromide, thus : R'COBr + HO*C,H, = R*COOH + C,H5Br. It is also possible that the position of the bromine atom may account for the di5culty with which this hydrogen ethylic salt is further etherified, as an experiment which we made with the object of converting the hydrogen ethylic salt into the neutral ethereal salt, by means of alcohol and hydrogen chloride, showed that very little etherifica tion had taken place, Br = 29.80.Methylic a-bromo-PP-~i~ethylgluta~~ate, COOCq* CHBr*C(CH,),* CH,* COOCH,, s obtained when the bromo-acid bromide of dimethylglutaric acid,56 PERKIN AND THORPE : ,!~@-DIMETHYLGLUTARIC prepared as explained above, is poured into well cooled methylio alcohol, It is a mobile liquid boiling at 173' (20 mm.). Laotone of a-Hy&roxy-PP-dimethylglzctccric Acid, COOH*QH* C(CH,),- QH, O--- co This interesting substance, which is isomeric with the caronic acids, was prepared as follows.The hydrogen ethylic salt of bromodimethylglutaric acid (20 grams) wa8 dissolved in dilute sodium carbonate and boiled in a reflux apparatus on a sand bath, care being taken that the solution always had a distinctly alkaline reaction. As soon as a small quantity of the liquid gave no precipitate with hydrochloric acid, the whole was acidified, saturated with ammonium sulphate, and repeatedly extracted with ether ; the dried ethereal solution, when evaporated, gave a hard, crystalline mass which, on being left in contact with porous porcelain for some days, became quite colourless and melted at 80-looo. I n order to purify this crude product, and especially with the object of determining whether it contained any trans-caronic acid (p.59), the lactone was dissolved in a slight excess of ammonia, evaporated on the water bath, and the well dried ammonium salt warmed with absolute alcohol, when the whole dissolved readily, showing that no tram-caronic acid was present. Ether was then added to the alcoholic solution until a slight turbidity wae produced, and the fine, transparent prisms of the pure ammonium salt deposited on standing were collected, washed, and converted into the acid, which was further purified by repeated recrystallisation first from benzene and then from water, Analysis. 0.1643 gave 0.3225 CO, and 0.0932 H,O. C = 53.53 ; H = 6.30. This lactone melts at 112O, and when heated in a small retort distils without change. It is readily soluble in ether, acetone, ethylic acetate, and hot benzene, moderately in chloroform, and almost insoluble in light petroleum.C7H,,0, requires C=53.16 ; H= 6-33 per cent. Action of Alcoholic Potash on Ethylic a-Bromo-&3-dimethylglutwat%. Porrnation of cis- and trans-Caronic Acide. C(CH,), A COOH*CH-CH* COOH. In this interesting experiment, the brom-ethereal salt (1 5 grams) was digested in alcoholic solution with caustic potash (15 grams) forACID AND ITS DERIVATIVES. 57 10 houw, and the product, after being freed from alcohol by evapora- tion on the water bath with the addition of water, was dissolved in water, acidified, and extracted several times with ether. On distilling off the ether, a syrupy mass was obtained, which became partially solid on standing ; this was dissolved in a little water and saturated with hydrogen chloride, when the crystalline solid, which slowly separated after being collected and dried on a porous plate, melted indefinitely between 170° and 200O.This crude substance was dis- solved in ammonia, evaporated to dryness, and the residual solid ammonium salt ground up with cold absolute alcohol; a small quantity passed into solution, but most of it remained undissolved .* The insoluble salt was collected, washed with absolute alcohol, dissolved in a little water, acidified and extracted with ether ; the ethereal solution, on evaporating, deposited a solid acid which even before recrystal€ising melted at 210-21 2O, and after recrystallisiog from water a t 213O. This substance is trans-cmronic acid. The alcoholic filtrate from the insoluble ammonium salt of tram-caronic acid, on being mixed with ether and allowed to stand, deposited a small quantity of crystalline Rolid ; this, after collecting, acidifying, and extracting with ether, yielded an acid melting a t 176O, which, doubt- less, consisted of cis-caronic acid (m.p. 176O), but the quantity was too small for analysis. In this hydrolysis, therefore, both the caronic acids appear to be formed, but the tran8-modification in far larger quantity than the cis-modifi cat ion. On evaporating the solution after the precipitation of the cis- and trans-caronic acids to dryness with ammonia, and dissolving the residue in alcohol, an oily ammonium salt was precipitated on the addition of much ether, which, on long standing, became solid ; from this, on acidifying, a considerable quantity of the lactone of hydroxy- dimethylglutaric acid was obtained, melting a t 112'.Action of Potacsh om the Hydrogen, Ethylic Salt of a-Bromo-PP-dhethpl- glutcvric Acid. This hydrolysis, which gives by far the best yield of trams-caronic acid, was conducted as follows. Equal weights of the brom-ethereal salt and caustic potash were heated together in alcoholic solution in a reflux apparatus for 3 hours, and after evaporating the alcohol, acidifying, and extracting with ether, exactly as explained in the last experiment, a hard, solid, crycltalline cake was obtained; this, on being crystallised once from water, melted at 213O, and consisted of pure trans-caronic acid. On treating this acid and its mother liquors * This salt is th.e acid ammonium salt of trans-csronic acid, and has the formula C,H,,NO, (Baeyer, Ber., 1896, 29, 2800).58 PERKIN AND THORPE : @@-DIMETHYLGLUTARIC with ammonia and alcohol, as explained above, we were not able to extract even traces of the cis-modifioation or of the lactone of hydroxydimethylglutaric acid.It is remarkable that hydrogen ethylic bromodimethylglutarate should behave so differently from the normal ethylic salt on treatment with potash under the same conditions, and that-in the latter case, besides trans-caronic acid and traces of the cis-modification, such con- siderable quantities of the lactone of hydroxydimethylglutaric acid should be produced. The formation of trans-caronic acid from the hydrogen ethylic salt seems to us to prove that this salt has the formula COOH- CHBr-C(CH,),* CH,* COOC,H5, given to it on p.50, and that elimination of hydrogen bromide takes place before hydrolysis. If this ethereal salt had the alternative formula, COOC,H,* CHBr*C(C H,),* CH,* COOH, the elimination of hydrogen bromide would be expected to take place between the bromine atom and the hydrogen atom of the carboxyl group, and the lactone of hydroxydimethylglutaric acid would be formed ; this, however, ia not the case. Action of Diethylaniline on Ethylic BromodimethylgZutcwate.- As it has frequently been found that diethylaniline is a very valuable reagent for removing hydrogen bromide from organic substances, it was thought that interesting results might be obtained if its behaviour were investigated in the present instance.Accordingly, 50 grams of ethylic bromodimethylglutarate was boiled in a reflux apparatus with 75 grams of pure diethylaniline for 2 hours, and after cooling, the nearly solid product was treated with dilute hydrochloric acid, and the oil which separated extracted with ether. The ethereal solution was dried, evaporated, and the residual oil fractionated a great many times, first under reduced and then under the ordinary pressure. It was thus separated into two fractions which boiled at 241' and at about 265-275". The oil boiling at 241', on analysis, gave the following numbers. 0.1345 gave 0.3032 CO, and 0.1087 H,O. C = 61.48 j H = 8.98. C,,H,,O, requires C = 61 -68 ; H = 8.41 per cent. Since this oil, on hydrolysis, yielded tmms-caronic acid, it is evidently the ethereal salt of this acid. The fraction 265-275', which was not analysed, gave, on hydrolysis, the lactone of hydroxydimethylglutaric acid, and is evidently the ethereal salt of this lactonic acid.These two substances were ob- tained in about equal quantities.ACID AND ITS DERLVATIVES. 59 C(CH3h trans-Ccuronic mid, COOH* &)?* COOH. H H The synthetical acid has proper ties identical with those described by Baeyer and Villiger (Bef*., 1896, 29, 2800) as characteristic for the acid from carone. It is sparingly soluble in cold water, but readily in hot water, and separates from its hot solution in prisms which melt at 213O. It is very sparingly soluble in ether, benzene, and cold water, and almost insoluble in chloroform and light petroleum.CvH1,04 requires C = 53.16 ; H = 6-33 per cent. 0.1504 gave 0.2913 CO, and 0.0888 H,O. The silver salt is precipitated as a white, crystalline powder when 0*2660gavo0*2177 CO,, 0*0547H20and0*1538Ag. C = 22.33; H = 2-29; C = 52.82 ; H = 6.56. silver nitrate is added to a neutral solution of the ammonium salt. Ag 3: 57.82. C7H,04Ag, requires C = 22.57 ; H = 2.15 ; Ag = 58.06 per cent. tram-Caronic acid does not give an anhydride when digested with acetic anhydride, but when heated with acetic anhydride at 220' it yields the anhydride of cis-caronic acid (p. 6 1). That it is a saturated acid is shown by the fact that its solution in sodium carbonate does not reduce permanganate. Conversioa of trans-Cwonic Acid into Terebic Acid, 60. CH,* CH- COOH' O--- p%), It was stated in the introduction to this paper that one of the most remarkable reactions of trans- and cis-caronic acid discovered by Baeyer, was the transformation of these acids into terebic acid by the action of hydrobromic acid at looo, and it was consequently of im- portance to show that the synthetical acids behaved in the same manner under the same conditions. About 0.5 gram of pure synthetical tram-caronic acid was heated with about 5 C.C. of concentrated hydrobromic acid (saturated a t Oo) for 5 hours at looo; the hydrobromic acid was then removed by evaporation on the water-bath, and the residue recrystallisedj from water ; the colourless, cubic crystals melting a t 174' thus obtained gave the following numbers on analysis.0.1422 gave 0.2757 CO, and 0.0802 H,O.C = 52.87 ; H = 6.26. C$H1,,O, requires C = 53.16 ; H= 6.33 per cenf,60 ~fl-DIMETEYLCtLUTARIC ACID AND ITS DERIVATIVES. Terebic acid has the same empirical formula and the same melting point as cis-caronic acid, but in other respects these acids possess very different properties, and there can be no doubt that the acid obtained in the above experiment was terebic acid, and not unchanged cis- caronic acid, for the following reasons (compare Baeyer, Ber., 1896, 29, 2799). This acid yields an ammonium salt which differs from the ammonium salt of cis-caronic acid in that, besides having a different crystalline form, its solution in alcohol is not precipitated by ether. It gives, with silver oxide, a silver salt which is readily soluble in water and crystallises in needles, and on boiling with baryta water it yields the characteristic crystalline barium salt of diaterebic acid.Finally, a small quantity heated in a test tube gave the odour of pyroterebic acid, (?(CH3)2 = COOH* OH,* CH:C( CH3), + CO,, O-- bO*CH2* CH* COOH and the residue, dissolved in soda, instantly reduced permanganate, a behaviour not shown by cis-caroniclacid, which, under these conditions, is simply converted into its anhydride, Conversion, of trans-Caronic Acid into cis-Caronic Acid. This conversion, which had not previously been observed, may be readily accomplished in the following way. trans-Caronic acid is mixed with three times its weight of freshly distilled acetic anhydride, and the mixture heated in a sealed tube for 6 hours a t 220'. The dark brown product is then freed from the excess of acetic anhydride by distillation, the residue dissolved in boiling water, digested with animal charcoal, filtered, and evaporated to a small bulk ; on cooling, large, glistening, colourless crystals separate, which melt a t 176', and consist of pure cis-caronic acid.0.1602 gave 0.3108 CO, and 0*0900 H,O. C=52*91 ; H=6*24. C7Hlo04 requires C = 53-16 ; H = 6.33 per cent. / \ cis-Cmonic acid, HC--QH , is very sparingly soluble in cold water, but readily in hot water, and crystallises from water most beautifully in brilliant, glistening plates with bevelled edges. It is sparingly soluble in dry ether and in light petroleum, and practi- cally insoluble in chloroform ; it dissolves readily in sodium carbonate, and this solution does not decolorise permanganate. When heated above its melting point, cis-caronic acid is rapidly ctonverted into it8 6OOH COOHSYNTEESCS OF C@~-TRIMETHY LGLUTARIC ACID, 61 anhydride. The ammonium salt of cia-caronic acid is readily obtained by dissolving the acid in excess of aqueous ammonia and evaporating the solution on a water bath. The crystalline residue differs most sharply from the ammonium salt of the trans-acid in being readily soluble in absolute alcohol ; from its alcoholic solution, it is precipitated by ether in the form of slender needles. When cis-caronic acid is heated with hydrobromic acid, under the conditions given in detail in the corresponding experiment with the truns-acid (p. 59), it is con- verted into terebic acid melting at 174'. It will be seen from this short description of the properties of cis- caronic acid that the synthetical acid is identical with the acid obtained by Baeyer (Zoc. cit.) from carone. /T.*)' Anhydride of cis-Curonic mid, Hq----QH.-This anhydride is Go-0-00 formed either when cis-caronic acid is distilled, or when trans-caronic acid is heated at 220' with acetic anhydride, but it is best prepared by boiling cis-caronic acid with acetyl chloride until hydrochloric acid ceases to be evolved, evaporating, and crystallising the residue from dry ether, when lustrous plates are obtained which melt at 56'. There can be no doubt that this is the anhydride of the &-acid, because it is, as Baeyer found (Zoc. cit., p. 2799), quantitatively con- verted into the acid on boiling with water. The authors wish to state that this research was carried out with the aid of a grant from the Eoyal Society Research Fund, and that they are indebted to Mr. F. H, Lees for making most of the analyses given in this and the succeeding communication. OWENS COLLEGE, M ANCHESTER.

ISSN:0368-1645    

DOI:10.1039/CT8997500048

出版商:RSC    

年代:1899

数据来源: RSC

摘要:

SYNTEESCS OF afl&TRIMETHY LGLUTARIC ACID, 61 VIL-Synthesis of apB- Trimethylglutan'c Acid. COOH- CH(CH8)*C(CH,),* CH,. COOH. By W. H. PERHIN, jun., and JOCELYNF. THORPE. OF the four theoretically possible trimethylglutaric acids, two only, up to the present, have been prepared synthetically, namely, the U ~ U ~ - acid, COOH. C(CH,),* CH,* CH(CH,)*COOH, by Auwers and Victor Meyer (Ber., 1890,23,293) from ethylic u-bromisobutyrate and 6' mole- cular '' silver, and the +acid, COOH. C(CH,),* CH(CH,)*CH,m COOH,62 PPRKIN AND THORPE: SYNTHESIS OF which was prepared by us (Trans., 1897, 71, 1187), by the reduction of the corresponding trimet hylglutaconic acid, COOH- C(CH,),* C(CH,):CH* COOH. The remaining two acids are app ...... COOH*CH(CH,)*C(CH,),*CH,*COOH, and apa COOH.CH(CH,)*CH(CH,)*CH(CR,)*COOH. Of these, the first has a special interest, for the following reason. By the oxidation of camphoric acid with permanganate at the ordi- nary temperature, Balbiano (Bey., 1894, 27, 2133 ; 189'7, 30, 1908), obtained an acid of the formula C,H,,05, to which he assigned the constitution COOH. C(CH,)* C(CH,),* CH. COOH. 1-0- I This acid, on reduction, yielded a lactonic acid of the probable formula CH(CH,)*C(CH,),* He COOH, and this, by further reduction with hydriodic acid, was converted into an acid, C,H1,O,, which Balbiano considered to be upp-trimethyl- glutaric acid, because, on oxidation, it yielded aa-dimethylsuccinic acid. Assuming that this acid is app-trimethylglutaric acid, its formation from camphoric acid is important, as affording evidence that the latter contains the group C*C(CH,).C(CH,),* C-C, a conclusion which, to- gether with results obtained from the great amount of work which has been done on camphoronic acid, throws much light on the constitution of camphoric acid (compare Trans., 1898, 73, '797).It thus became an important matter to be certain that the formula Balbiano assigned to his acid is correct, and for this resson we have, ever since the publication of his paper, been endeavouring to synthesise upp-trimethylglutaric acid, and it is only quite lately that we have been able to accomplish this. I n the first place, we found, as the result of a great many experi- ments, that it seems to be impossible to introduce a methyl group into etb ylic dimethylpropanetricarboxylate, 60--- 8 (COOC,H,),C&* C(CH,),* OH,.COOC,H,, at the point marked *, by the action of sodium ethoxide and methylic iodide. Arguing from analogy to other mono-substitution products of ethylic malonate, this experiment should have yielded an ethereal salt which would have given a&3-trimethylglutaric acid on hydrolysis@&TRIMETHY LGLUTARIC ACID. 63 and elimination of carbon dioxide, but, although tried under very varied conditions, no trace of this acid was obtained. It was then thought possible that the ethylic trimethylpropanetri- carboxylate, (COOC2H5),C(CH3)*C(CH3),* CH,* COOC,H,, which should have resulted from the above experiment, might be formed by the condensation of ethylic dimethylacrylate with the sodium derivative of ethylic methylmalonate, but the experiments made in this direction did not yield a trace of the de,sired compound, and many other syn- theses, which need not be mentioned here, also gave negative results.Ultimately, we discovered the following synthesis, which is so easily carried out that large quantities of c@p-trimethylglutaric acid can now be obtained in a short space of time. The method consists in heating together ethylic dimethylacrylate and the sodium derivative of ethylic cyanacetate in alcoholic solution until the condensation to the sodium derivative of ethylic cyanodi- methyZyZutarate, which probably has the formula, COOC,H,* C(CN)Na* C(CH,),* OH2* COOC2H5, is complete (see p. 52). The crude product is then directly treated with methylic iodide, when an almost quantitative yield of ethylic cyanotrimethylglutarate, COOC,H,* C(UH3)(CN)* C(CH,),* CH,* COOC,H,, is obtained.This, on hydrolysis with methyl alcoholic potash or hydrochloric acid, yields the beautiful, crystalline imide of a&3-trimethylglutaric acid, which, when heated with hydrochloric acid, at 200°, is converted quantitatively into aPP-trimethylglufaric acid. A direct comparison of the acid thus synthesised with that obtained from camphoric acid was rendered possible by the kindness of Professor Balbiano, who sent us a sample of the acid which he was the first to prepare. Both acids melted a t S7", and on treatment with acetyl chloride yielded the same anhydride melting a t 82", and from this by the action of aniline an anilic acid was prepared which in both cases melted a t 150-151", so that there can be no doubt as to the identity of the synthetical acid and Balbiano's acid.I n experimenting with a/3P-trimethylglutaric anhydride, it was found that, not only does it crystallise from water unchanged, but that it actually crystallises with water of crystallisation, in prisms melting at 61°, and without being converted into the acid. This is certainly a very unusual property of an anhydride, and the only somewhat similar case which we have been able to find is that of the p-lactone of dimethylmalic acid, (CH,)2?--?H0 ''OH, which, GO-064 PERKIN AND THORPE: SYNTHESIS OF as Baeyer and Villiger (Ber., 1897,30, 1955) have shown, crystallises with lH,O. We are at present engaged in investigating other condensations between unsaturated ethereal salts and a-cyano-ethereal salts, and also on the action of halogen compounds on the sodium derivative of ethylic cyanodimethylglutarate, and we are especially interested in the ethereal salt which this sodium derivative yields on treatment with ethylic bromacetate, because, if Baeyer's formula for isocam- phoronic acid be correct, this should lead to a synthesis of this very important acid, Ethylic a-Cyano-al-pp-trimethylglutarate, COOC,H,* CH(CN)*C( CH,),.CH( CH,)*COOC,H,. I n order to prepare this substance, ethylic dimethylacrylate is digested in alcoholic solution with the sodium derivative of ethylic cyanacetate, as explained on page 52, and after heating for 15 hours excess of methylic iodide is added and the boiling continued until the liquid has a neutral reaction ; water is then added, and the oily product extracted with ether.The ethereal solution, after washing well with water, drying over calcium chloride, and evaporating, deposits a thick oil which, after twice fractionating, boils constantly a t 181' (25 mm.), and consists of pure ethylic cyanotrimethylglutarate. 0.22 gave 11.8 C.C. nitrogen at 23' and 750 mm. C13H21N04 requires N = 5.50 per cent. The yield of this pure ethereal salt obtained in this condensation is about 68 per cent. of the theoretical, and it is remarkable that, in this case, only traces of an acid ether'eal salt are formed, whereas, as explained on p. 52, if the condensation is worked up before the treat- ment with methylic iodide the principal product is the acid ethereal salt.N= 5-94, This substance is formed when ethylic cyanotrimethylglutarate is hydrolysed either with methyl alcoholic potash or with concentrated hydrochloric acid j in the former case, the product often consists of the acid amide, a white, deliquescent solid which, however, can readily be converted into the imide by boiling for a short time with concen- trated hydrochloric acid. apb-Trimethylglutarimide is sparingly soluble in cold, but readily in hot water, and crystallises in long needles closely resembling PP-dimethylglutarimide (p. 5 3) in appear- ance. It melts a t 126'.~z~~~~-TRIMETHYLGLUTARIC ACID, 65 0.1163 gave 9.4 C.C. nitrogen at 32' and 765 mm. N = 9-20. C,H,,NO, requires N -c 9.03 per cent. is obtained as a beautiful, crystalline precipitate when dilute ammonia is carefully added to a, warm solution of the imide and silver nitrate, Ag = 41.53.C,HI,O,NAg requires Ag = 41 *22 per cent. 0.0874 gave 0.0363 Ag. a&3-TrirnethyZgZzctaric acid, COOH. CH(CH,)*C(CH,),* CH,* COOH. This acid is best prepared from the imide just described by heating it with three times its weight of concentrated hydrochloric acid in a sealed tube for 5 hours a t 200'. The product is evaporated to dryness on the water bath, and the residue extracted with ether j after drying over calcium chloride, the ethereal solution deposits the acid in an almost pure condition on evaporation. For the analysis, the acid was crystallised from water, from which it separates in glistening plates melting at 88'. 0.1316 gave 0.2675 CO, and 0.0960 H,O.C = 55.43 j H = 8.23. C8H,,0, requires C = 55.17 j H = 8005 per cent. which is the most characteristic derivative of aPP-trimethylglutaric acid, is readily prepared by digesting the pure acid for a short time with excess of acetyl chloride, and then evaporating to dryness on the water bath. The crystalline residue, which consists of the almost pure anhydride, crystallises from a mixture of ethylic acetate and light petroleum in prisms which melt a t 82'. 0.1445 gave 00.3248 GO, and 0.0991 HzO. C,H,,03 requires C = 61-54 ; H = '7.67 per cent, This anhydride is quite insoluble in cold dilute sodium carbonate solution, and is only very slowly converted into the acid even on boiling. If this anhydride is boiled with a large quantity of water, and the clear solution, rapidly poured off from the oily drops, is allowed to cool, a small quantity of the anhydride crystallises out in needles (I) ; the same substance is produced on melting the anhydride under hot water and stirring vigorously until it becomes solid (11).The pro- duct in both cases melts a t 61", and consists of the anhydride with half a molecule of water of crystallisation. The following are the results of the analyses of specimens of I and 11. C = 61.34; H = 7.62. VOL, LXXV. F66 DUNSTAN AND HENRY: OCCURRENCE OF ORTHOHYDROXY- I. 0.2322 gram, after drying on a porous plate for 3 hours, lost 11. 0.4712, heated at 50° until constant, lost 0.0242. C,H1,O3 + 4H20 requires H,O = 5.4 per cent. The water of crystallisation is given off rapidly on gently warming, and slowly over sulphuric acid in a vacuum desiccator ; the residue then melts at 82', the melting point of the dry anhydride, 0.01 34 gram at 50'. H,O = 5.8 per cent. H,O = 5.15. app- Trimeth y l g h t armilic Acid, C,H,*NH*CO*CH(CH,)*C(CH,)2*CH,*COOH(?). On the addition of aniline to a solution of the anhydride in benzene, this compound separates after some time as a white, crystalline precipitate, After being purified by recrystallisation from dilute methylic alcohol, from which i t separates in long needles, it melted a t 150-151', and, on analysis, gave the following result. 0.2515 gave 12.2 c,c. nitrogen a t 21' and 752 mm. N = 5.47. C,,H,,NO, requires N = 5.60 per cent. Our thanks are due to Messrs. F. Howles and F. H. Lees, for much valuable help in connection with this and the preceding research, and we wish also to state that the very considerable expense which these experiments have entailed has been largely met by grants from the Royal Society Research Fund. MANCHESTER. OWENS COLLEGE,

ISSN:0368-1645    

DOI:10.1039/CT8997500061

出版商:RSC    

年代:1899

数据来源: RSC

摘要:

66 DUNSTAN AND HENRY: OCCURRENCE OF ORTHOHYDROXY- VIII.-Occurrence of Orthohydroxyacetophenone in the Volatile Oil of Chione glabra. By WYNDHAX K. DUNSTAN, F.R.S., and T. A. HENRY, Salters’ Research Fellow in the Laboratories of the Imperial Institute. SOME years ago, one of us (Dunstan, Proc. Roy. Xoc., 46, 211) showed that the strong fecal odour of the wood of Celtis reticulosa is due to the presence of skatole, the substance to which the odour of human excrement is due. Through the interest of Mr. ThiseltonDyer, the Director of Kew Gardens, other plants having strong odours were then examined, but no definite information as to their constituents could be obtained, owing to the small quantity of material available for examination. Amongst these plants was a small specimen of the wood of Chione glahra, which had been sent t o Hew by Mr.J. H. Hart, F.L.S., Superintendent of the Royal Botanic Gardens, Trinidad, with the suggestion that an examination of its constituents should beACETOPHENONE IN THE VOLATILE O ~ L OF CHIONE GLABRA. 67 undertaken, as the plant is reputed to possess valuable properties as a medicine and, in particular, is stated to be a powerful aphrodisiac. The bark and wood emitted a strong, unpleasant odour, chiefly aromatic, but partly fcecal. This was proved to be due to an oil which was volatile with steam, and although its chief physical and chemical properties were ascertained, the constitution of its principal constituent could not be determined owing to insufficiency of material. A further supply of the wood was afterwards obtained from the collections of the Imperial Institute.This was part of a large log which had been sent previously for exhibition at the World’s Fair a t Chicago. Now, however, it has completely lost its characteristic odour, owing to the escape of the volatile oil, and it proved to be quite useless for our purpose. Through the kind offices of Rlr. Hart, the Trinidad Government undertook the collection of a fresh quantity of the wood, which has made i t possible for us to complete the inquiry by identifying the odorous constituent of the tree, and in fact, proving its identity with the substance prepared synthetically in the laboratory. The genus Chime of the Natural Order RubiaceaE! includes plants which are confined almost exclusively to the West Indies.The species Chime glabra, which is indigenous t o Grenada, is a large flowering tree, known in the island as “Violette,” a name which probably has reference t o the aromatic smell of the flower. Through the kindness of Mr. E. J. Millard, F.C.S., we have received from Grenada a dried specimen of the stem, leaves, and flowers of this tree. The somewhat aromatic, somewhat fcecal, smell is associated with the bark and wood, especially with the .former j on exposure to air, it gradually disappears. The results of the chemical investigation described in the subsequent part of this paper show that the volatile oil, which exhibits in a concentrated form the remarkable odour of t-he wood, ie composed of two substances, the one a yellow oil boiling at 160° under 34 mm.pressure, and solidifying a t low temperatures t o a crystalline mass ; the other, a colourless, crystalline substance melting a t 82”. The former, which is the chief constituent, we have proved to be orthohydroxyacetophnone, OH* C,H,* CO*CH,, and is identical with the compound prepared synthetically. The crystalline substance, which is present in very small quantity, has all the proper- ties of an alkyl derivative of the oil ; the amount of substance obtained, however, was insufficient to enable us to complete the examination, The faecal odour of the fresh wood, wbich seems rather more pro- nounced than that of the constituents we have isolated from the oil, suggested the possibility that the plant might also contain a minute quantity of skatole or some other derivative of indole; but although the volatile oil contains traces of some nitrogenous substance, we have not been able to isolate any indole derivative from it.It is, however, F 268 DUNSTAN AND HENRY: OCCURRENCE OF ORTHOHYDROXY- interesting, and possibly significaht from the biological standpoint, to observe that derivatives of orthohydroxyacetophenone may, by processes involving condensation and elimination of water, pass into compounds belonging to the indole group ; the production of indoxyl from orthacetylamidoacetophenone has, indeed, been accomplished by von Baeyer and Bloem (Ber., 1884, 17, 963), and it is not difficult to conceive that the conversion may occur without difficulty and by shorter steps in the plant. The precursors of skatole and other indole derivatives in plants are a t present unknown, but the occurrence of derivatives of *acetophenone in the vegetable kingdom and particularly in Chione gkabra, whose wood emits a fecal odour, indicates at least one possible direction in which search might be made, Besides those whose names we have already mentioned, we are greatly indebted to Miss L.E. Boole, F.I.C., who conducted much of the preliminary examination of the constituents of this plant. Extraction ox the Volatile Oil. The volatile oil was separated from the wood and bark by cutting these into fine shavings and distilling with steam; the distillate obtained was then shaken with ether, and the ethereal solution dried over calcium chloride and distilled. After removal of the ether, there remained a dark-coloured oil which distilled with some decomposition under the ordinary pressure ; it was, therefore, distilled under reduced pressure, when a fraction boiling from 160' to 165', under a pressure of 34 mm., was obtained.With the small quantity of material available, it was not possible to obtain a fraction of more definite boiling point. Combustions of the liquid gave the following results. 0.0737 gave 0,1926 CO, and 0.0352 H20. C = 71.2 ; H= 5.29. 0.0607 ,, 0.1586 CO, ,, 0.0320 H20. C = 71-21 ; H =5*76. C8H,02 requires C = 70.57 ; H = 5.88 per cent. The relative density of the oil is ct? = 0.850 15'/4". It is slightly soluble in water, and has a peculiar and somewhat unpleasant odour, chiefly aromatic, but partly fecal. An aqueous solu- tion of ferric chloride produces a deep purple coloration, and bromine water a faintly yellow, crystalline precipitate.The oil dissolves in alkaline solutions, and such solutions, on evaporation, leave a crystal- line salt or metallic derivative; the potassium and sodium salts crys- tallise in yellow plates which quickly decompose on exposure to air ; .acids regenerate the oil from them.ACETOPHENONE IN THE VOLATILE OIL OF CHIONE GLABRA. 69 Action of various Beagents on the Oil. Action of Acetic Anhydride.-The liquid was mixed with acetic an- hydride and warmed. The viscous oil precipitated on the addition of water t o the product was removed by shaking with ether, the ethereal solution dried, and the ether removed by distillation. The crystalline residue of acetyl derivative obtained on standing was then recrystttllised from methylic alcohol until the melting point was con- stant at 88".A combustion gave the following result. C,H70*C,H302 requires C = 67.4 ; H = 5.61 per cent. 0.1331 gave 0.3254 CO, and 0.0776 H,O. The substance is, therefore, a monacetyl derivative of the original liquid, and the existence of one hydroxyl group is thus proved. Action of Hydroxylcmine and PhenyZhydraxine.--When an aqueous solution of hydroxylamine is added to the oil suspended in water and the mixture gently warmed, a red, resinous substance separates; this dissolves in boiling water, and the solution deposits colourless needles as it cools. These, after recrystallisation, melt at 112", and have all the properties of an oxirne of the original substance.C = 66.66 ; H= 6.4. 0.1841 gave 0.4242 CO, and 0.1016 H,O. OH*C,H,*NOH requires C = 63.4 ; H = 5.96 per cept. A phenylhydrazone was also obtained by the action of a 10 per cent, solution of phenylhydrazine on the liquid suspended in water ; after 24 hours, this mixture deposited a greenish-yellow oil which soon became crystalline. On recrystallisation, the hydrazone melted at 108O. The production of an oxime and hydrazone indicate the presence of one ketonic group in the original substance. Action of Bromine.-When bromine water is added to the oil suspended i n water, a colourless precipitate forms immediately, and on standing becomes crystalline ; after recrystallisation from hot alcohol, it melts somewhat indefinitely at 108", or, after prolonged heating at a lower temperature, at 95'.-We are funable, at present, t o represent its composition by any formula derivable from that of the parent sub- stance, Combustions and two determinations of bromine by Carius' method gave the following results. C = 62.8; H= 6.12. C. 32.6 per cent. H. 2.52 per cent. 32-3 ), 2.04 ,, 46.2 ,, 32.96 ), 2.09 ,, 32.89 ,, 2.26 ), Br. 45.64 per cent. It will be seen that these values for carbon, hydrogen, and bromine do not agree with those required for a mono- or dibromo-derivative.70 DUNSTBN AND HENRY: OWURRENCE OF ORTHOEYDROXY- C8H70,Br requires c = 44.6 ; H = 3.2 ; Br = 37.2. C8H,02Br, ,, C = 32.6 ; H = 2.04 ; Br = 54.4. When the bromine derivative is reduced with tin and hydrochloric acid, it yields a small quantity of a phenolic substance giving a bromine derivative melting at 86". It is possible that the solid bromo-deriva- tive is a mixture of one or more simple bromine derivatives, but this is not very probable, since its composition seems t o be constant when prepared under various conditions, and its melting point is very definite.Action of -Fused Potash.-When the oil is boiled for some time (in a vessel fitted with an upright condenser) with 10 per cent. potash solution, it merely passes into a metallic derivative, and can be re- covered by acidifying the solution; and even when heated with alkaline solutions in sealed tubes at 125', it is not decomposed. When fused with excess of potash, the potassium salt of the oil floats for a time on the excess of potash, but is subsequently completely decomposed, forming a dark brown mass.When this is dissolved in water, acidified, and the mixture distilled, a. solution containing phenol is obtained ; this was identified by means of its tribromo-derivative. When the acid liquid left after distillation was extracted with ether, it furnished a crystalline substance which, after recrystallisation from hot water, melted at 1514 and gave all the reactions of salicylic ucid m. p. 155'). Action of Nitric Acid.-The residue from the Carius' estimations of bromine in the bromo-derivative was examined, and found to contain oxalic acid and a yellow, crystalline substance; the quantity of the latter, however, was too small to admit of satisfactory identification, but since it dyed silk yellow and did not dye cotton, and gave the chloropicrin reaction, there can be little douht that it; was pkric ucid.These observations as to the chemical behaviour of the volatile oil of Chione glabra prove that its chief constituent is orthohydroxy- acetophenone [OH : CO*CH, = 1 : 21. The facts may be conveniently summarised here. 1. The parent substance has a composition represented by the formula C8H,0,. 2. One of the hydrogen atoms can be replaced by the acetyl group, indicating the presence in the parent substance of one hydroxyl group. 3. The oil forms a monoxime, having a composition represented by the formula C8H,02N. 4. Fusion of the oil with potash furnished salicylic acid and phenol, the latter as the result of secondary action,ACETOPHENONE IN THE VOLATILE OIL OF CHIONE QLABRA.71 The formation of all these substances is readily explained on the assumption that the chief constituent of the oil is orthohydroxy- acetophenone, OH* c6H4*co*cH3. This compound has been described by Tahara (Beg.., 1892, 25, 1306) and by Feuerstein and Kostanecki (Ber., 1898, 31, 710-719). The latter chemists described ortho- hydroxyacetophenone (obtained by the action of alcoholic soda on phenacylidenflavene) as a yellow oil of peculiar odour, distilling at 218O, giving a purple red colour with ferric chloride solution, and forming a yellow, crystalline, sodium salt. Tahara prepared the com- pound by the decomposition of orthomethoxybenzoylacetic acid. The acetyl derivative melted at 89O, and the phenylhydrazone at 107O. We have prepared oxthohydroxyacetophenone from nitrocinnamic acid, by the following series of reactions.Orthonitrocinnamic acid, N02*C6H4*CH: CH* COOH, was converted successively into dibromonitro- phenylpropionic acid, N0,*C6H4*CHBr*CHBroc!00H ; orthonitro- propiolic acid, N0,*C6H,*CiC*COOH ; orthonitrophenylacetylene, NO,*C,H,GCR; orthamidophenylacetylene ; NH,*C6H,*CiCH; ortho- amidoacetophenone, NH2*C6H,* CO*CK, ; and, finally, by diazotising into orthohydroxyacetophenone, OH*C6H,*C@CH3. These compounds, with the exception of the last, have been prepared by Baeyer and Bloem (Ber., 1880, 13, 2259), and we have made use of the methods of preparation and purification described by these chemists. The orthohydroxyacetophenone thus prepared had all the characteristics of ithe oil distilled from Chione gkabra, and furnished derivatives having the same physical constants ; thus the bromine derivative and the oxime melted at 108' and 112' respectively.Orthomethoxyccceto~heco~e.-'l'he quantity of colourless, crystalline substance left as a residue in the distillation of the crude chione oil was too small toadmit of an extended examination, but since it was decomposed by boiling with hydriodic acid, giving a volatile iodide, with the production of an oil having the properties of orthohydroxy- acetophenone, it is probably an ether, possibly the methyl ether of this substance, The minute amount of this constituent present in the volatile oil has made it impossible for us more certainly to identify it.* SCIENTIFIC DEPARTMEN'I', IMPERIAL INSTITUTE, LONDON, S.W. * Since the work described in the present paper was completed, the following account of the volatile oil of Chione gla6ra has appeared (Paul and Cownley, Pham. J O Z C T ~ . , [iv], 7,51). The material examined was obtained from the Windward Islands. '' From the aromatic odour of the bark, it was conjectured that it might contain a volatile oil, and on examination with that object we succeeded in isolating a volatile oil amounting t o about 1.5 per cent. by weight.. '' This volatile oil is of 8 pale yellow colour, and has n specific gravity higher than

ISSN:0368-1645    

DOI:10.1039/CT8997500066

出版商:RSC    

年代:1899

数据来源: RSC

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72 DUNSTAN AND BROWN : OCCURRENCE OF HYOSCYAMINE IX. -Occurrence of Hyoscyarnine in the Hyoscyamus muticus of India. By WYNDHAM R. DUNSTAN, F.R.S., and HAROLD BROWN, Assistant Chemist in the Laboratories of the Imperial Institute. Hyoscyamus muticus is a species of henbane which occurs in certain districts of India, and has long been used in Indian medical practice, as a particularly virulent drug. The nature of its alkaloid, however, has never been determined. The following account of the plant is abbreviated from that given in Hooker’s Flora Indica. H. muticus is found in the West Punjab, in Scinde, and in Cabul, westward to Egypt. Cauline leaves, petioled, ovate or oblong, entire or toothed, lower flowers pedicelled, calyx striate, pubescent, teeth short, triangular, not acute in fruit, corolla 1 to If inches, lurid yellow or nearly white.Stem, 1 to 3 feet. Leaves, 4 to 7 inches, pubescent, or some- what woolly, petiole 4 t o 3 inches. Lower pedicles in fruit, 4 to 1 inch. Calyx, 8 inch, in fruit, 1 by Q inch, funnel-shaped, ribbed, somewhat reticulate, villous, or ultimately glabrous ; teeth short, triangular, not spreading. The medicinal effects of this drug appear to resemble those of ordinary henbane ; when administered in comparatively large doses, i t acts as a powerful excitant, leading to what have been described as paroxysms of mania, whence the synonym Hyoscyarnus insanus. There is some reason to believe that it has been employed in the preparation of certain extremely potent kinds of the Persian ‘ I Benj ” and in some varieties of the Indian ‘‘ Bhang,” which, however, is usually prepared from Indian hemp.Since there is a t present a considerable demand for atropaceous drugs and their alkaloids, it seemed desirable to examine Capsule, 4 inch in diameter. Seed, & inch in diameter. that of water. It gave a mass of acicular crystals on being cooled to about -20’. The oil gave no crystalline compound with sodic bisulphite, nor could evidence be obtained of methyl salicylate. It gave a semi-solid mass on treatment with a con- centrated solution of caustic soda. I t is readily soluble in dilute caustic soda, and reprecipitated by acids apparently unaltered. It is slightly soluble in water, its aqueous solution gives a purple-blue coloration with ferric chloride. The volatile oil is evidently a phenol.“There are several volatile oils having somewhat similar properties to those above described, but the quantity of oil obtained was too small to admit of the further examination which its peculiarity appears to deserve. ”IN THE HYOSCYAMUS MUTICUS OF INDIA. 73 the alkaloid of this plant, which is fairly abundant in the districts of India in which it is found, and might possibly prove to be worth exporting. Extraction and Estimution of the AZkaloid. The sample, which weighed nearly two pounds, was collected in Scinde, a t the instance of the Reporter on Economic Products to the Government of India, and consisted of both stems and leaves of the plant; these were separated as far as possible, but there remained a mixture of fine stems and broken leaf. 300 grams leaf.Total weight, 900 grams ... 310 ,, stem. These three portions were extracted separately, in order to deter- mine the proportion of alkaloid in each. The material was air-dried at a low temperature, finely powdered, and then exhausted by percolation with cold alcohol, the percolate being evaporated under reduced pressure until nearly the whole of the alcohol had been removed. The semi-solid residue was then extracted with dilute hydrochloric acid (0.5 per cent.), gently warmed, and well shaken ; after subsidence, the acid liquid was poured off and the treatment repeated until the alkaloid was completely removed. The acid solution, after filtration, was shaken with small quantities of chloroform in order to remove the chlorophyll, then made slightly alkaline by the addition of dilute ammonia, and the alkaloid extracted by successive shakings of the alkaline liquid with chloroform; on dis- tilling off the chloroform under reduced pressure, a gummy, alkaloidal residue was obtained having a slight odour recalling that of pyridine.A small quantity of alkaloid remained in the alkaline liquid, and could not be removed by agitation with chloroform ; it was, however, subsequently isolated and examined. By percolation with cold alcohol, the following percentages of alkaloid were found. I n the plant (stem and leaf), 680 grams yielded 0.7 gram of alka- loid, or 0.1 per cent. (nearly pure). I n the stem only, 310 grams yielded 0.46 gram of alkaloid (nearly pure), which is 0.15 per cent. I n the broken leaf and fine stems, 250 grams yielded 0.14 gram of alkaloid (nearly pure), which equals 0.056 per cent.i 290 ,, mixture of leaf and stem, Examination of the AZkaZoid. In order to identify the alkaloid or alkaloids present, the impure amorphous residues were converted into the aurichloride, which was74 DUNSTAN AND BROWN : OCCURRENCE OF HYOSCYAMINE examined by fractional crystallisation, as described in a previous paper on the alkaloids of #copoh CarmioZica (Dunstan and Chaston, Ph. J., [iii], 20, 461) ; this was obtained as a yellow, pulverulent precipitate, which was recrystallised from hot water acidified with hydrochloric acid. The alkaloid from the mixed stem and leaf yielded two large fractions of auric chloride melting at 154-1 56' and, after recrystal- lising, a t 157-158', which is very near the melting point of hyos- cyamine nurichloride.From the mother liquors, containing the excess of auric chloride, two very small fractions of crystals were ob- tained melting at 149-150' and 140-145' respectively ; these were too small to be dealt with separately. The alkaloid from the stem yielded three main fractions of auri- chloride all melting between 154' and 156'. On recrystallising once, three fractions melting at 158', 157.5" and 154-156' were obtained ; by concentrating the mother liquors from these, two small fractions melting at 150-155' and 145-150'were obtained, and, finally, a few crystals melting at 141-145'. The fractions of similar melting points were combined and recrystallised from dilute acid until a constant melting point was attained.In the case of the fractions of higher melting point, two or three recrystallisations sufhced, whereas the lower fractions required the operation to be repeated at least six times before a constant melting point was obtained; by this means, practically the whole of the aurichloride originally taken was obtained in shining leaflets melting a t 159.5'. There only remained two small fractions melting a t 157-158' and the two lowest fractions, at 140-145', which were too small to be separately dealt with, and were consequently retained and afterwards combined with a fraction of similar melting point. It is, therefore, proved that nearly the whole of the aurichloride is that of hyoscyamine, which melts at 160' (Ladenburg).The small. quantity of alkaloid which remained in the alkaline liquid and was not removed by agitation with chloroform was isolated in the following manner (Dunstan and Ransom, Ph. J., [iii], 14,623). The chloroform and alcohol present were removed by distillation under re- duced pressure, the liquid was acidified, and the whole of ths alkaloid precipitated by adding a solution of iodine in potassium iodide; the alkaloidal periodide was collected, washed, and then decomposed by a small quantity of a solution of sodium thiosulphate, the liquid made alkaline with dilute ammonia, and the alkaloid extracted with chloroform. The small quantity of alkaloid thus obtained was con- verted into the aurichloride, but this could not be recrystallised and was mixed with the lowest melting fractions (above referred to) for further treatment.IN TEE HYOSCYAMUS MUTICUS OF INDIA.75 Analysis of the Aurichloride. The pure aurichloride melting at 159*5O, was analysed, the gold, chlorine, and alkaloid, being directly determined. A weighed quantity of the salt was dissolved in water, the gold precipitated as sulphide, ignited, and weighed as metal. After the hydrogen sulphide had been removed from the filtrate by passing a current of air, it was exactly neutralised with soda, and the chlorine determined by titration with centinormal silver nitrate. The filtrate from the silver chloride was concentrated in a vacuum over sulphuric acid, then made alkaline with dilute ammonia, and the alkaloid removed by agitation with chloroform, and the residue obtained on distilling off the chloroform was dried in a, vacuum over sulphuric acid until its weight was constant.I. 0.0636 aurichloride gave 0*0201 Au, and required 42.2 C.C. 11. 0.0424 aurichloride gave 0.0134 Au, and required 27.8 C.C. The two solutions containing the alkaloid from both the above deter- 0.106 aurichloride gave 0.0491 alkaloid = 46-32 per cent. N/100 AgNO, (1 C.C. =0*0003416 Cl). N/100 AgNO,. minations were mixed, and the total amount of alkaloid estimated. Au=31.60 ; C1*22°66. AU = 31.60 ; C1= 22-40. Gold. Chlorine. Alkaloid, Found ............................... 31.60, 31.60 22.66, 22.40 46-32 Calculated for C,7H,3~03,HAuCl, 31.34 22.54 45.96 Another specimen of aurichloride yielded, on ignition, 31 *25 per cent. of gold. From more of the pure aurichloride, the alkaloid was regenerated by the method above described, and after recrystallisation from a mixture of dry chloroform and petroleum, it was obtained in long, silky needles.These were dissolved in absolute alcohol, and the specific rotatory power determined. The solution was lfevorotatory. a=31'. 1=1 dm. ~ = 2 * 0 4 . t-19'. 100 x 31 - 2-04 x 60 whence [ a ] D = - - - 25-32'. Other observers have recorded numbers lying between 20" and 21O. Hyoscyamus muticus as a Commercial Source of Pure hryoscyamine. Having thus ascertained that the alkaloid in Hyoscyamus muticus is chiefly, if not entirely, hyoscyamine, experiments were made to ex- tract the crystalline alkaloid direct from the plant. For this purpose,76 OCCURRENCE OF HYOSCYAMINE, ETC.about 1; lbs. of the plant, both stem and leaf, was finely powdered and the alkaloid extracted by the method already described ; in this way, 0.7 gram of impure alkaloid was obtained as a coloured, gummy residue, which could not be crystallised either from ether or from dilute alcohol. By dissolving in dry chloroform, however, and gradu- ally adding light petroleum, the colouring matter was precipitated, together with a little of the alkaloid, and a nearly colourless solution was obtained, from which, on adding more petroleum and allowing it to stand, groups of small needles were gradually deposited. Several fractions of the crystalline base were thus obtained, and were recrystallised in the same manner. Finally, pure hyoscyamine was obtained in colourless, silky needles melting at 105'.Absence of other Mydriatic Alkaloids.-The small quantity of alka- loid precipitated along with the colouring matter by the first additions of petroleum to the solution in chloro€orm was also examined. The precipitate was extracted with very dilute hydrochloric acid, the solution filtered, and aurichloride added, when a yellow precipitate was produced which quickly aggregated to a resinous mass (fraction A) ; this was removed, and on adding more of the reagent to the filtrate a yellow, pulverulent precipitate was obtained, which did not aggregate on standing (fractiou B). These two fractions were recrystallised separately from dilute acid j from fraction A, two crops of crystals were obtained melting at 154-155O and 156-158' respectively ; and from fraction B, crystals mere obtained melting a t 157-158'.The mother liquors from all these were concentrated in a vacuum, and thus a fsw crystals melting at 146-149' were separated. All fractions of aurichloride insufficient for separate recrystallisa- tion yhich had been obtained in the various experiments made were finally combined into two groups according to their melting points, 165-158O and 140-145O respectively. These were recrystallised as before and virtually the whole of the gold salt was found to melt constantly a t 159.5'. A very small fraction melted a t 158-159', and another from 150--155O, but these were too minute for further re- crystallisation. The following aro the melting points of the auri- chlorides of the chief mydriatic alkaloids : atropine, 136-138', hyos- cyamine, 159-160' j scopolamine or hyoscine, 198-1 99'.There is, therefore, no evidence of the existence in this sample of Hyoscymus muticus of any mydriatic alkaloid than hyoscyamine. We believe that the plant will prove to be an important source of this alkaloid,since it can be isolated from it with far less difficulty than from ordinary henbane (Hyoscyamus niger), which also contains the alkaloid hyoscine, and often atropine in addition. It should, however, be remembered that the nature of the alkaloids contained in atropaceous plants appears to vary with age, mode of culti-PREPARATION OF HYPONITRITE, ETC. 77 Hyoscyamus niger. Biennial. Annual. Atropa Datura belladonna. strarnonima. vation, and other circumstances.Thus, in belladonna, the proportion of hyoscyamine to atropine fluctuates widely with the age of the plant. It is, therefore, desirable that other specimens of Eyoscyamus muticw should be examined, in order to ascertain whether hyoscyamine is invariably the only alkaloidal constituent. It will be convenient to summarise here our present information as to the occurrence of hyoscyamine in various plants. Hyoscymus nQer and albus (hyoscyamine and scopolamine). Eyoscyamus muticus (hyoscyamine). Atropa belladonna (atropine, hyoscyamine, and a little scopolamine). Datum stramonitbm ,, 9 9 9 ) Duboisia myoporoides (hyoscyamine and a little scopolamine). Scopola carniolica (hyoscyamine). Scopola japonica (atropine, hyoscyamine, and scopolamine). Lactzcca sativa and virostc (hyoscyamine). The following percentages of total alkaloid have been recorded. Hyosc yamua ntzctiW. ' Roots. Leaves Seeds., Stem , Entire herb, OS21-0*41 0.15 0'155-0'173 - c 0'30-0'90 { (av. =049) { 2nd ,, 0'045-0*068 and tops 1 o~064-0~070 a:?:af}'" - 0 *16-0'37 0 '058-0 '1 - - - c - 0 '46 - - 0'03 - 0'12-0*20 1st yr. 0*039-0*069 leaves 0 - ~ ~ ~~ ~~ ~~ ~ ~ ~ We are indebted to Mr. E. A. Andrews, Junior Assistant in these Laboratories, for the skilful help he has given in the conduct of this experimental work. SCIENTIFIC DEPARTMENT, IMPERIAL INSTITUTE, LONDON.

ISSN:0368-1645    

DOI:10.1039/CT8997500072

出版商:RSC    

年代:1899

数据来源: RSC

摘要:

PREPARATION OF HYPONITRITE, ETC. 77 X.--Prepamtion o f Hyponitrite from Nitrite through Hydroxyamidosulphonate. By EDWARD DIVEBS, M.D., D.Sc., F.R.S., and TAMEMASA HAGIA, D.Sc., F.C.S. SULPHONATION, followed by hydrolysis, readily converts an alkali nitrite into the unstable hydroxyamidosulphonate, which, in a solution saturated with potassium hydroxide, has all its hydrogen replaced by78 DIVERS AND HAQA: PREPARATION OF HYPONITRITE potassium, and is simultaneously resolved into hyponitrite and sulphite, 2HO*NH-SO,N-a + 4KOH = (KON), + 2KNaS0, + 4H,O. This remarkable change was made known by us in 1889 (Trans., 1889, 55, 760), along with the fact that it afforded a rich source of hyponitrite, since the quantity of the latter formed is equivalent to at least half the nitrite taken.But this, it was pointed out, de- pended on our method of preparing hydroximidosulphonate being employed, and as the description of that method was not published until five years later, the new source of hyponitrite could not be used advantageously by others. Even since then, the method has escaped the notice of seven separate workers on hyponitrites, namely, Thum, W. Wislicenus, Paal and Kretschmer, Tanatar, D. H. Jackson, Piloty, and Hantzsch and Kaufmann, to be at last, however, taken up by Eirschner (Zeit. anorg. Chem., 1898,16, 424). Indeed, it may be said to have been rediscovered by Piloty, who in a paper on ‘‘ an oxidation of hydroxylamine by benzenesulphonic chloride ” (Ber., 1896, 29, 1559), describes the resolution of benzenesulphonic hydroxylamide by potassium hydroxide into hyponitrite and benzenesulphinate, with a yield also of half the calculated quantity of the former salt.As we have each of usvery frequently employed the hydroxyamido- sulphonate method of preparing hyponitrite, and the details requisite in order t o get high yields have not been published, it seems it mill be of service to chemists t o describe the method fully.’ So far as our experience goes, we can be certain of getting a yield of 60 per cent. of the theoretical, and occasionally much more, although we have not succeeded in discovering the cause of this. In what follows, we assume t h a t the convenient quantity of 2 decigram-molecules of sodium nitrite is taken, from which about 17 grams of silver hyponitrite may be obtained.In order to limit the quantity of potassium hydroxide required, which is very large in any case, no more water than is necessary must be used, and except that particular attention must be given to this point, the process begins exactly like that of making hydroxylamine sulphate from nitrite (Trans., 1896, 69, 1665). In a tared, wide-mouthed, round-bottomed flask of 200-250 C.C. capacity, 14.4 grams of 96 per cent. sodium nitrite,t together with sodium carbonate containing 10-6 grams of anhydrous carbonate, are dissolved by heat in enough water to make the total weigh 83.5 grams. Some lead salt * Kirschner’s method is an excellent form of our process, but I prefer that f But preferably, 13.8 grams of pure sodium nitrite, this being now very easy to described in this paper.-E. D.prepare (this vol., p. 85).FROM NITRITE THROUGH HYDROXYAMIDOSULPHONATE. 79 in the nitrite is deposited, but goes into solution when the potassium hydroxide is added and gives no trouble. Sodium carbonate of any hydration may be used, but as, subsequently, more of this salt has to be added, and then should be approximately the monhydrate, it is con- venient to use this form throughout. Such a carbonate, almost pure, is generally found in the "dried"' pure carbonate of commerce. Keeping the flask in active motion in an ice-and-brine bath, sulphur dioxide is passed in until a short time after the temporarily precipi- tated acid carbonate has redissolved, and just when a bit of lacmoid paper in the solution becomes fully red. About 0.1 C.C.strong sulphuric acid is then droppedin. If the temperature is kept below Oo, the conversion of the nitrite into hydroximidosulphonate is com- plete, whereas if it rises much above 0' some nitrilosulphonate would form, and interfere with the result. If higher temperatures have been avoided, the nitrite and carbonate taken in molecular propor- tions, and the sulphur dioxide not used in excess, the solution is ready to be hydrolysed ; but as the salts may not have been in exact propor- tion, and sulphur dioxide may also be present, it is best to blow a strong current of air through the solution a t Oo, so as to expel any sulphur dioxide or nitric oxide that may be present. After this treatment, the solution is brought to about 30°, in order to start hydrolysis, and set aside for a day in a warm place with the flask corked.Complete hydrolysis to hydroxyamidosulphonate with- out further hydrolysis to hydroxylamine is thus secured," and, conse- quently, just the calculated quantity of sodium carbonate (10.8 grams anhydrous) is found to be required, including that for the three or four drops of sulphuric acid added. The approximately monhydrated carbonate, added in fine powder, is briskly shaken with the solution, so as to hinder its caking, the last portions being dissolved by warming the flask. The solution of hydroxyamidosulphonate and sulphate, thus prepared, contains almost exactly half its weight of water, is therefore supersaturated, and is the strongest solution practically obtainable ; it will be found to approach closely 113 grams in weight, so smoothly do the reactions proceed.The solution may * That the production of hydroxylamine is avoided if this detail is attended to, has been proved by shaking the solutiou, after it has been made alkaline, with sodium amalgam, which readily converts hydroxylamine into ammonia, but does not act on the hydroxyamidosulphonste. On testing in this way, no odour of ammonia can be recopised, and moist red litmus paper held in the bottle is barely affected. Kirschner, using potassium hydroximidosulphonate, had to heat t o boiling to effect hydrolysis, which is difficult then to complete without some of the hydroxyamido- sulphonate passing on into hydroxylamine. When the hydrolysis is incomplete, nitrite will be regenerated later on by the alkali ; and when it is carried too far, nitrite will also be formed during the oxidation of the hydroxylamine by the silver (or mercury) oxide.80 DIVERS AND HAGA: PREPARATION OF HYPONITRITE be made weaker, and then concentrated, but the adjustment is troublesome, and the formation of hard cakes of sodium sulphate, which interferes with the proper working a t the next stage of the operation, is difficult to avoid.The contents of the flask are now well drained into a basin, prefer- ably a hemispherical nickel basin, or, lacking that, a stout porcelain one, capable of holding about 500 C.C. Potassium hydroxide, free from chloride, assayed for real alkali and for water, and having not less than two-thirds and not more than 1 mol. of water to 1 of the hydroxide, is required, for i f it were anhydrous it would cause much heating and consequent decomposition of the salts ; generally, the potassium hydroxide purified by alcohol and the more translucent varieties of stick potash contain about the right proportion of water, and dissolve in water without much rise of temperature, From 130 to 165 grams of it, according to its degree of hydration, are quickly crushed in a warm mortar, thrown into the solution in the basin, and incorporated with i.t by means of a pestle.There is marked heating only just at first, which is better met by keeping the basin in water or resting it on snow or pounded ice for a very short time. On stirring in the potassium hydroxide, the solution sets to a stiff paste, if kept cold, quickly becoming thin again on further stirring, but full of an opaque, white precipitate of sulphate.If the basin has been cooled, hardly any gas escapes at first, but gentle effervescence and much frothing occur before long in any case. When the potassium hydroxide has been all ground up and dissolved, the basin is placed under close cover from atmospheric moisture and carbonic acid, and left in 8 warm place for 30 hours ; if kept for more than 50 hours, the quantity of hyponitrite sensibly, but slowly, diminishes. As much even as one-fourth of the hydroxyamidosulphonate may sometimes, in cold weather, still be present, and can be partly destroyed by keeping the basin a t 55-60' for half an hour, although not with noticeable increase of the quantity of hyponitrite, but this heating, with the attendant risk of over-heating, is better omitted, on the whole, Besides undecomposed hydroxyamidosulphonate, the contents of the basin now consist of precipitated sulphate and sulphite, and solution of potassium hydroxide in slightly less than its weight of water (almost exactly KOH : 3H,O), together with the potassium hypo- nitrite, It is, apparently, only t o secure this concentration of the potassium hydroxide, a practically saturated solution, that hardly less than 10 mols.of it to 1 of hydroxyamidosulphonate have to be used, More of it may be added without effect, good or bad, unless the solu- tion of the salts is weaker than is here recommended, for in that case additional potassium hydroxide must be used to bring the concentra- tion to the right point.FROM NITRITE THHOUCH HYDROXYAMIDOSULPHONATE.81 Treatment with a silver salt is the only way of separating the hyponitrite from the other salts, and for this purpose the presence of the alkali is essential, together with large dilution when precipitating. The best way is to use the silver solution exceedingly dilute, because this checks the precipitation of silver oxide and sulphite until some time after all the hyponitrite has separated. Now the necessity for large dilution, and the advantage of still larger dilution, remove the only objection that can be raised t o the use of silver sulphate instead of silver nitrate, and since it is generally important to feel assured that no trace of nitrate or nitrite can have been carrieddown with the hyponitrite, the sulphate should have the preference, although the nitrate can almost certainly be used with as good results.A cold saturated solution contains only 5 or 6 grams of the sulphate to the litre, and is most easily prepared by boiling excess of the salt with water and pouring the solution into an equal volume of cold water. Whichever salt is used, the contents of the basin are first washed into a very capacious precipitating vessel, and the highly dilute silver solution is poured in until it ceases to produce any more black precipitate. When this is at all abundant, as it sometimes is in cold weather, an hour’s interval is given for subsidence of most of it, the still dark solution is decanted, and the precipitate washed by decantation before rejecting it.With or without this interruption, the addition of the silver solution is continued until the bright yellow hyponitrite suddenly appears, and so long after as the joint precipita- tion of brown oxide can be easily checked by stirring. When the point is reached where the oxide only redissolves slowly and no longer gives place to a yellow one of hyponitrite, no more silver solution should be added. If much more were added, there would be permanent precipitation of silver oxide, which is apt to be accompanied by silver sulphite. The quantity of silver sulphate required may be as much us 40 grams, which means 7 or 8 litres of solution; if silver nitrate be used, about 44 grams will be wanted, dissolved in 4 litres, or more, of water. Half-an-hour after precipitation, the solution is to be poured off, even though still a little turbid, and the precipitate washed by decantation, for there is a very slow deposition of a mirror of metallic silver from the sulphite solution, which goes on for days, I n order to separate the hyponitrite from the metallic silver and its oxide, and perhaps chloride, it has to be dissolved in dilute acid and reprecipitated.If every trace of nitrite is t o be kept out of the hyponitrite, nitric acid can hardly be used, because I find that it always contains some nitrous acid, and it is, therefore, necessary to use aulphuric acid. Since the hyponitrite must be kept in solution as short a time as possible, it is advisable to have the acid not very VOL. LXXV. G82 ABSORPTlON OF NITRIC OXIDE IN UAS ANALYSIS.dilute, in order to reduce the volume of liquid t o be filtered, But high dilution is better, because the stability of hyponitrite falls off rapidly with increasing concentration ; moreover, if the sul- phuric acid is not dilute enough, silver sulphate will separate; a 1 per cent. solution of the acid, well cooled in ice, is suitable, some 5 litres of it being required. The precipitate should be treated with the acid in portions a t a time, not all together; and, as far as possible, the undissolved precipitate should be kept off the filter until the last. For so long a filtration a Lunge filter-tube-extension of the funnel is more suitable than the filter pump, the filtrate being allowed to fall directly into excess of sodium carbonate solution. Working with these precautions, the silver hyponitrite can be dissolved and reprecipitated, even in hot weather, with hardly any appreciable loss. Having replaced the alkaline mother liquor by water, dilute sul- phuric acid is cautiously added, until, after stirring up the precipitate well, the solution is no longer alkaline, and some of it, when filtered, is found to contain a trace of the silver hyponitrite ; this is best ascer- tained by adding one or two drops of sodium carbonate solution to about 100 C.C. of it, which shoula cause a permanent, yellow, very slight, opalescence. The precipitate, thoroughly washed by decantation and dried on a filter a t the ordinary temperature in a desiccator, in the dark, and then a t looo, will give 78 per cent. silver (calc. 78-26). But in order to preserve the bright colour of the salt and its entire freedom from nitrite, all work on it should be done with very little exposure to bright daylight. The weight of silver hyponitrite obtained from the quantity of sodium nitrite employed should be not less than 17 grams. IMPERIAL TOKYO UNLVERSITY, JAPAN.

ISSN:0368-1645    

DOI:10.1039/CT8997500077

出版商:RSC    

年代:1899

数据来源: RSC