STUDIES IN THE DIPHENYL SERIES by JOSEPH LAVERIE, B.Sc., A.R.I.C. A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy in the Faculty of Science of Glasgow University. JUNE, 1949. ProQuest Number: 13870131 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 13870131 Published by ProQuest LLC(2019). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 The author wishes to express his thanks to Professor W.M. Gumming, O.B.E., D.Sc., P.R.I.C., M.I.Chem.E., F.R.S.E., and to Dr. I.V. Hopper, B.Sc., Ph.D., A.R.C.S.I., F.R.I.C., for their supervision, interest and encouragement throughout the course of this research. He also wishes to thank the Governors of the Royal Technical College, Glasgow, for the research facilities granted to him. STUDIES IN THE DIPHENYL SERIES. PAGE SUMMARY ......................................... 1 GENERAL INTRODUCTION ........................... 8 Nomenclature . ................. 8 Methods of preparation of Diphenyl Derivatives • • .12 A Symmetrical Diphenyls • • • . .13 B Unsymmetrical Diphenyls • • 16 m i I INTRODUCTION . 21 A Anils ............ •••••••21 Mechanism of Anil Condensations • • . 2 3 Anils of the Benzidine Series • • • • 27 Reaction of Benzoin with Primary Aromatic Amines • • • • 28 The Ortho Effect • 29 Anils of Sulphonie Acid Salts • • • • 30 g Nltrosyl Chloride ••..,... 32 THEORETICAL SECTION ...................... 33 A (A) ANIL CONDENSATIONS OF SOME BENZIDINE DERIVATIVES . 33 Anil Formation ....................... 33 ii PAGE EFFECT OF NUCLEAR SUBSTITUENTS (a) The Nttro Group *..•••• 35 (b) The Methyl Group .............. 37 (c) The Methoxyl Group 38 DISCUSSION OF EXPERIMENTAL RESULTS Reactions of Acetophenone and Benzophenone with Benzidine • . • • • • 39 with o-Tolldine • • • • 40 with o-Dianisidine • • 40 Effect of the Methyl Groups . • • • . 4 1 Effect of the Methoxyl Groups » . • 42 (B) REACTION OF THE BENZIDINE BASES WITH BENZOIN . • . 43 (C) REACTIONS OF BENZIDINE SULPHONIC ACID SALTS WITH BENZALDEHXDE. (1) Die odium Benzidine 2:2,**Disulphonate • • • • • 44 (ii) Dianiline Benzidine 2:2 ^Disulph- onate # 44 (iii) Sodium Benzidine 3~Sulphonate • 45 (D) ANIL CONDENSATIONS OF 2-NITROBENZIDINE. (t) Acetophenone • ••♦.... 45 (2) Salicylaldehyde ................ 46 iii PAGE (E) BENZALDEHYDE ANILS . 47 m-Anlsldine ..••••.. -47 o-Tolldine • ••••••«• *48 o-Dianisidine ..................... 48 B THE NITROSYL CHLORIDE TETRAZOTISATION OP BENZIDINE . 4fl EXPERIMENTAL SECTION. A N:Nf-Bis(t-phenyleth3rtlidene)benzidine • • . 52 N:N*-Bis( 1 -phenylethylidene)-o-tolidine . 54 o-Dianisidine - Acetophenone Reaction • • • . 55 N 2N*-Dibenzohydrylidenebenzidine • • • • • 56 O-Tolidine - Benzophenone Reaction • • • • *58 o-Dianisidine - Benzophenone Reaction • • . - 59 N:Nf-Didesylbenzidine ............ ....60 NjfcT-Didesyl-o-tolidine ........61 NtN'-Didesyl-o-dianisidine • • • • . .62 Diaodium Benzidine 2:2,-Dlsulphonate - Benzal­ dehyde R e a c t i o n ............ 63 Dianiline Benzidine 2:2v-Diaulphonate ~ Benzal- dehyde Reaction . .64 Benzidine 3“Sulphonic Acid .......64 Sodium Benzidine 3-Sulphonate - Benzaldehyde Reaction • , . 6 5 iv PAGE 2-Nitrobenzidine - Acetophenone Reaction • . 66 2~Nitrobenzidine - Salicylaldehyde Reaction . 67 m-Anisidine • •••••• . • • • 6 8 N-Benzylidene~m-anisidine • •••••• 69 N-Benzylidene-m-anisidine Picrate • . • 69 N:N*~Dibenzylidene-o~tolidine •••••• 70 HjN’-Dibenzylidene-o-dianisidine • • • • • 71 NjN^Dlbenzylidene-o-dianisldine Dipicrate • .73 B THE NITROSYL CHLORIDE TETRAZOTISATION OF BENZIDINE . • . 74,76,77 PART II HISTORICAL SECTION. THE STEREOCHEMISTRY OF DIPHENYL DERIVATIVES. 80 The Kaufler Hypothesis ••••••••81 Optical Activity of 6 :6,-Dinitrodiphenic Acid 83 The Theory of Restricted Rotation • • • 88 , 90 Racemisation of Active Diphenyls • • . 95 INTRODUCTION Aminodiphenyls .............. 106 2:2,~Dibromobenzidine •••••«.• 109 Substituents in Positions Other than the 2 :6*2 %i6 ' • . • t13 PAGE 2 :2,-Dlbromo-6:6,~dimethyrbenzidine • • . 117 2:2,-Dibromo-5:5,-dimethyrbenzldine • • . 119 2:2,-Dibromo-3;3f-dimethyrbenzidine . • . 120 Ultra-Violet Light Absorption . • • 120 METHODS OF PREPARATION....................... 123 (a) The Formation of Hydrazo Compounds • • 124 (b) The Benzidine Rearrangement . • . • 132 THEORETICAL SECTION. NITRO C O M P O U N D S .......................... 141 AZO, HYDRAZO, AND AZOXY COMPOUNDS . 145 (a) Derived from 3-Bromo-5~nitrotoluene 145 (b) Derived from 4-Bromo-2-nitrotoluene 146 (c) Derived from 2-Bromo-6-nitrotoluene 147 (d) Otherwise Derived ...... 151 THE DIBROMODIMETHYLBENZIDINES (a) P ^ ’-Dibromo-S^-dimethylbenzidine 153 (b) 2:2,-Dibromo-5:5,~dimethylbenzidine 155 (c) 2 :2*-Dibromo-3:3*-dimethylbenzidine 156 Structural Evidence •.. ............... 158 Resolutions ......... 162 EXPERIMENTAL SECTION. (A) SYNTHESIS OF 2:2*-DIBR0M0-6: 6 * ~ DIMETHYLBENZ ID INE . 171 3~Bromo-5-nitro~2-amino toluene . 172 vi PAGE 3-Bromo-5-nitrotoluene ....... 173 3:3,-Dibromo-5:5f-&imethylazo'benzene • • .174 3:3l-Dibromo-5:5,-dimethylhydrazobenzene . 177 2 :2*-Dlbromo-6 :6^dimethylbenzidine • • . 179 Action of Hydrogen Chloride on 2:21-Dibromo- 6:6*-dimethylbenzidine . 186 N :N1-Diacetyl-2:21-dibromo-6:61-dimethyl- benzidine • • 186 2 j 21-Dibromo-6:61-dimethyldiphenyl-4:4 *- bl s jazo- (1) -naphthol- (2 )J • . 187 N :N ’-Dibenzylidene-P :21-dibromo-6 j 61 - dimethylbenzidine • • .188 Reduction of 2:2 *-Dibromo-6:6’-dimethyl­ benzidine . 189 NsN’-Diacetyl-m-tolidine . • • . , . .190 (B) SYNTHESIS OF 2:21-DIBR0M0-515 1 «*DI1£ETHYLBENZID- INE . 191 2-Nltro-4-aminotoluene ..... 192 4~Bromo-2-nitrotoluene ....... 194 S ^ - D i b r o m o ^ ^ ’-dimethylazobenzene • . 196 5:5* -Dibromo-2:21 -dime thy lhydrazobenz ene • 198 P^-Dibromo-S^-dimethylbenzidine . , 200 2 :2*-Dibromo-5:51-dimethylbenzidine dihydro­ chloride • 203 vii PAGE N :N1-Diaoetyl-2:21-dibromo-5:51-dimethyl­ benzidine • . 204 2:21-Dibromo-5 j 51-dlmethyldiphenyl-4: 4 * - bis[azo-(1)-naphthol-(2 )] . • 205 N : N * -Dibenzylidene-2:2 * -dibromo-5 *• 51 - dimethylbenzidine • • • 206 Reduction of 2:21-Dibromo-5:5*-dimethylben­ zidine . • 206 (C) SYNTHESIS OF 2 :2*-DIBR0M0-3:3'-DIMETHYLBENZIDINE 208 2:6-Dinitro-4-aminotoluene ...... 209 2:6-Dinltrotoluene • • . • . *211 2-Nitro-6-aminotoluene • • . • • • • .214 2-Bromo-6-nitrotoluene • • • • • • . .215 3:3'-Dibromo-2:2'-dimethylazoxybenzene • • 217 3:3'-Dibromo-2:2,-dimethylhydrazobenzene . .219 2 :2*-Dibromo-3:3'-dimethylbenzidine and 3:3*-Dlbromo-2:2 *-dimethylazobenzene . 220 2:2*-Dibromo-3:3 *-dimethylbenzidine Bihydro- chloride * . 223 N :N1-Diacetyl-2 :2*-dibromo-3:31-dimethyl­ benzidine . 223 2:2'-Dibromo-313 1-dimethyldlpheny1-4:4 *- bis[azo-(1)-naphthol-(2)J . 224 viii PAGE N : N1 -Dibenzylidene-2:21 -dibromo-3: 31 - dimethylbenzidine • . 225 Reduction of 2 :21-Dibromo-3:3‘-dimethyl­ benzidine • • • 226 (D) MISCELLANEOUS EXPERIMENTS. 3-Nitro-4-aminotoluene ...............228 4-Bromo-3-nitrotoluene *...•• .229 2:2,-Dibromo-5:5,-dimethylazobenzene • • 230,233 2 :2’-Dibromo-5:5 f-dimethylazoxybenzene • . 234 3^Nitro-2-amlnotoluene .......236 2-Bromo-3~nltrotoluene •••»••• 238 Reduction of 2-Bromo-3~nitrotoluene • • . 239 AZOXY DERIVATIVES. 3:31-Dibromo-5:5*-dimethylazoxybenzene • 241,243 5;5,-Dibromoira:2f-dimethylazoxybenzene . 243 3:3,-Dibromo-2:2,-dimethylazoxybenzene • 244 3-Bromo-5-methylazobenzene •••••• 244 2-Nltro-4:6-diaminotoluene . • . • . 246 2:4-Dibromo-6-nitrotoluene • • . 246 3:513 * s 51 -Tetrabromo-2:2 l**dimethylazobenzene 248 2-Bromo-*4-nltrotoluene ••••••• 250 2’“Bromo-4«aminotoluene ....... 250 Nitration of 2-Bromo**4~aminotoluene . 251 ix PAGE (E) RESOLUTION EXPERIMENTS 2 :2*-Dibromo-6 ^ ‘-dimethylbenzidine • • 254 2:2*-Dibromo-5^‘-dimethylbenzidine * • . 258 2:21-Dibromo-3s3’-dimethylbenzidine • • 263 BIBLIOGRAPHY . 267 1 SUMMARY Since this thesis is concerned mainly with a study of optical activity of diphenyl derivatives, the various methods of preparation of diphenyl derivatives are given in the General Introduction. The thesis is divided into two parts: Part I is concerned mainly with the reactions of certain benzidine bases with ketones and Part II, the major portion, with diphenyl derivatives of interest from the point of view of optical activity. In this summary, pages to which cross reference has been given contain the main conclusions of this thesis. Part I is subdivided into three sections: the Introduc­ tion, the Theoretical Section and the Experimental Section. The Introduction gives an account of previous relevant work, experimental and theoretical, and furnishes a background to the actual work undertaken. The latter, together with cer­ tain theoretical aspects, is discussed in the Theoretical Section. Part I was undertaken in order to provide further information on a subject briefly referred to by Reddelien (page 57 ) namely, the reactions of aromatic ketones with benzidine bases. At the same time, it was intended to gain 2 some information on the prospects of optical resolution of appropriately substituted benzidine derivatives by means of the