Organic Reactions VOLUME IV EDITORIAL BOARD ROGER ADAMS, Editor-in-Chief WERNER E. BACHMANN LOUIS F. FIESER A. H. BLATT JOHN R. JOHNSON HAROLD R. SNYDER ASSOCIATE EDITORS JAMES CASON MILTON C. KLOETZEL WILLIAM S. EMERSON S. M. MCELVAIN H. L. HOLMES ERICH MOSETTIG WALTER S. IDE DAVID TODD NEW YORK JOHN WILEY & SONS, INC. LONDON: CHAPMAN & HALL, LIMITED COPYRIGHT, 1948 BY ROGER ADAMS All Rights Reserved This book or any part thereof must not be reproduced in any form without the written permission of the ptihlisher. PRINTED IN THE UNITED STATES OF AMERICA PREFACE TO THE SERIES In the course of nearly every program of research in organic chemistry the investigator finds it necessary to use several of the better-known synthetic reactions. To discover the optimum conditions for the appli cation of even the most familiar one to a compound not previously subjected to the reaction often requires an extensive search of the liter ature; even then a series of experiments may be necessary. When the results of the investigation are published, the synthesis, which may have required months of work, is usually described without comment. The background of knowledge and experience gained in the literature search and experimentation is thus lost to those who subsequently have occasion to apply the general method. The student of preparative organic chemistry faces similar difficulties. The textbooks and labora tory manuals furnish numerous examples of the application of various syntheses, but only rarely do they convey an accurate conception of the scope and usefulness of the processes. For many years American organic chemists have discussed these problems. The plan of compiling critical discussions of the more im portant reactions thus was evolved. The volumes of Organic Reactions are collections of about twelve chapters, each devoted to a single reac tion, or a definite phase of a reaction, of wide applicability. The authors have had experience with the processes surveyed. The subjects are presented from the preparative viewpoint, and particular attention is given to limitations, interfering influences, effects of structure, and the selection of experimental techniques. Each chapter includes several detailed procedures illustrating the significant modifications of the method. Most of these procedures have been found satisfactory by the author or one of the editors, but unlike those in Organic Syntheses they have not been subjected to careful testing in two or more labora tories. When all known examples of the reaction are not mentioned in the text, tables are given to list compounds which have been prepared by or subjected to the reaction. Every effort has been made to include in the tables all such compounds and references; however, because of the very nature of the reactions discussed and their frequent use as one of the several steps of syntheses in which not all of the intermediates have been isolated, some instances may well have been missed. Never- v Vl PREFACE TO THE SERIES theless, the investigator will be able to use the tables and their accom panying bibliographies in place of most or all of the literature search so often required. Because of the systematic arrangement of the material in the chapters and the entries in the tables, users of the books will be able to find in formation desired by reference to the table of contents of the appropriate chapter. In the interest of economy the entries in the indices have been kept to a minimum, and, in particular, the compounds listed in the tables are not repeated in the indices. The success of this publication, which will appear periodically in volumes of about twelve chapters, depends upon the cooperation of organic chemists and their willingness to devote time and effort to the preparation of the chapters. They have manifested their interest already by the almost unanimous acceptance of invitations to con tribute to the work. The editors will welcome their continued interest and their suggestions for improvements in Organic Reactions, CONTENTS CHAPTER PAGE 1. THE DIELS-ALDER REACTION WITH MALEIC ANHYDRIDE—Milton C. Kloetzel 1 2. THE DIELS-ALDER REACTION: ETHYLENIC AND ACETYLENIC DIENOPHILES— H. L. Holmes 60 3. THE PREPARATION OF AMINES BY REDUCTIVE ALKYLATION—William S. Emerson 174 4. THE ACYLOINS—S. M. McEhain 256 5. THE SYNTHESIS OF BENZOINS—Walter S. Ide and Johannes S. Buck . . 269 6. SYNTHESIS OF BENZOQUINONES BY OXIDATION—James Cason 305 7. THE ROSENMUND REDUCTION OF ACID CHLORIDES TO ALDEHYDES—Erich Mosettig and Ralph Mozingo 362 8. THE WOLFF-KISHNER REDUCTION—David Todd 378 INDEX 423 vii SUBJECTS OF PREVIOUS VOLUMES VOLUME ACETOACLTIC ESTER CONDENSATION AND RELATED REACTIONS I ALIPHATIC FLUORINE COMPOUND •» II ALKYLATION OF AROMAMC COMPOUNDS BY IH* JRH DI L-CKA*IS MLIHOD III AMINATION OF HETEROCYCI ic BASi SBY ALKALI AMIDI S I ARNDT-FlSTERr REACTION I AROMATIC ARSONIC AND ARSINIC ACIDS II AZLACTONES III BlARYLS II BUCHERER REACTION I CANNI77ARO RLACTION II CHLOROMrTIIYLATION Or AROMATIC COMPOUNDS I CLAISEN RrARRANGEMENTl II CLEMMrNSLN REDUCTION I CURTIUS RLACTION III CYCLIC KETONLS II DIRECT SULFONAIION 01 AROMAIIC ITYDROCAUBONS AND Tin m HAr OGI N DI RIVATIVES III iiiLBS REACTION I JB RiES REACTION I HorMANN REACTION III JACOBSEN REACTION I MANNICII REACTION I PERIODIC ACID OXIDATION II PERKIN REACTION AND RELATED REACTIONS I PREPARATION or KETENL^ AND KETENE DIMERS III REDUCTION WTTH ALUMINUM ALKOXIDI S II REFORMATSKY REACTION I REPLACEMENT or AROMATIC PRIMARY AMINO CROUP BY HYDROGEN II RESOLUTION OF ALCOHOLS II SCHMIDT REACTION III SUBSTITUTION AND ADDITION REACTIONS OF THIOCYANOGFN III WILLGERODT REACTION III viii CHAPTER 1 THE DIELS-ALDER REACTION WITH MALEIC ANHYDRIDE MILTON C KLOETZEL DePauw University * CONTENTS PAGE NATURE OF THE REACTION 2 Table I Dienophiles in the Diels-Alder Reaction 4 Reaction Mechanism 8 Reversibility of the Reaction 9 Stereochemical Selectivity of the Reaction 10 Side Reactions 12 SCOPE AND LIMITATIONS OF THE REACTION 14 Reaction with Acychc Compounds 15 Reaction with Ahcychc Compounds 22 Reaction with Aromatic Compounds 28 Wholly Aromatic Systems 28 Table II Equilibrium Mixtures from Polycyclic Hydrocarbonb and Maleic Anhydride m Boiling Xylene 28 Aromatic-acyclic and Aromatic-ahcychc Systems 32 Reaction with Heterocyclic Compounds 35 Diene Analysis 39 EXPERIMENTAL CONDITIONS AND PROCEDURIS 40 With Butadiene 41 With l-Phenyl-l,3-butadiene 41 With l,2~Diphenyl~l,3-pentadiene 42 With Cyclopentadiene 42 With 9-Methylanthracene 42 With 1,2-Benzanthracene 42 With Isoeugenol Methyl Ether 42 With Furan 43 SURVEY OF THE DIELS-ALDER REACTION INVOLVING MALEIC ANHYDRIDI 43 Table III Adducts from Acychc Compounds 44 Table IV Adducts from Ahcychc Compounds 47 Table V Adducts from Aromatic Compounds 50 Table VI Adducts from Heterocyclic Compoundb 53 Table VII Adducts from Dienophiles Related to Maleic Anhydride 54 * Present address, University of Southern California, Los Angeles, California 1 2 ORGANIC REACTIONS NATURE OF THE REACTION The Diels-Alder reaction (diene synthesis) consists in the addition of a compound containing a double or triple bond (usually activated by additional unsaturation in the apposition) to the 1,4-positions of a conjugated diene system, with the formation of a six-membered hydro- aromatic ring. The following additions of various diene systems to dienophiles are typical examples of the Diels-Alder reaction. XH 2 ^CH XCH ^ CHO 2 •V . V\ . r T v^ j, . > ^^ + x/ + CWH Diene Dienophilo Adduct A noteworthy feature of the Diels-Alder reaction is the great variety of the compounds which may serve as the dienophile. With a few excep tions, the compounds that have been employed as dienophiles fall into one of the following categories. 1. CH=CHA. 2 A « CHO, COH, COCH, COCH, COCl, COCH, COCH, CN, NO, 2 2 3 2 2 5 3 6 5 2 CH, CHOH, CHX, CHNH, CHCN, CHCOH, CHNCS, 6 5 2 2 2 2 2 2 2 2 OCOCH, SCHCH, SOR, X, H. 3 6 4 3 2 DIENE SYNTHESIS I S 2. CHCH=CHA. 6 5 A - CHO, COH, COCH, COCH, COCH, COCH. 2 2 3 2 2 5 3 6 6 3. CH=CA. 2 2 A = COCH, CN, COCH, X. 2 2 6 3 4. ACH=CHA. A - COH, COCl, COCH, COCH, COCH, COCH, X. 2 2 3 2 2 6 3 6 6 5. Quinones. 6. AC^CA. A - COH, COCH, COCH, COCH, CH, H. 2 2 3 2 2 5 6 5 6 6 The more reactive dienophiles usually contain the C=C—C-O or the C=C—C=O system. Other unsaturated groups, such as CN, NO , 2 or SO2, promote the addition. In some instances even substances with isolated double bonds have been found to add dienes, but these sub stances usually require more drastic reaction conditions. Ketenes do .not react with dienes in the Diels-Alder fashion.1-4 Among those substances that have been employed most frequently as dienophiles are maleic anhydride and other closely related dicarboxylic acid derivatives (which are discussed in this chapter), a,/3-unsaturated carbonyl compounds and acetylenic compounds (which are discussed in Chapter 2), and quinones and other cyclic ketones (which will be dis cussed in Volume V). In Table I are listed some other compounds which have been employed successfully as dienophiles. 1 Allen and Sheps, Can. J Research, 11, 171 (1934). 2 Farmer and Farooq, J. Chem. Soc, 1938, 1925. 3 Smith, Agre, Leekley, and Prichard, J. Am. Chem. Soc, 61, 7 (1939). 4Brooks and Wilbert, J. Am. Chem. /Soc, 63, 870 (1941). 4 OBGANIC REACTIONS TABLE I DlENOPHILES IN THE DiELS-ALDEB. REACTION Dienophile i Reference Dienophile Reference Acrolein 5-21 I Ethylenetetraearboxylic acid Crotonaldehyde 6, 12, 15, 16, and ester 51 20-23 Azodicarboxylic ester 52, 53 Cinnamaldehyde 6,24 Acrylonitrile I 54 Acetylethylene (methyl vinyl ketone) 25 /3-Naphthol (keto tautomer) 55 Ethylideneacetone 9 Nitroalkenes 29,56-59 Benzoylethylene (vinyl phenyl ketone) 26 ^^-Unsaturated sulfones 56 Benzalacetone and Cyclopentadiene 60-63 benzalacetophenone 27, 28 1,3-Cyclohexadiene 64 Dibenzalacetone 29 I Styrene 58,65 l-Cyclopenten-3-one and Indencs 44, 65-69 derivatives 30-33 Acenaphthylene 69 l-Cyclohexen-3-one 34 Allyl compounds 70 st/m-Diacctylethylene 35, 36 Vinyl haHdes, esters, and st/m-Diaroylethylenes 27, 29, 37-41 sulfides 56,71,72 Acrylic acids 8, 10, 18, 42 Di- and poly-chloroethylenes 71,73 Crotonic acid and crotonyl 4-Vinyl-l-cyclohexene 74 chloride 8,43 1-Methyl- 1-cyclopentene 66 Cinnamic acids and esters 24, 27, 44r-47 Unsaturated bicyclic com 3,4-Dihy dro- 1-naphthoic pounds (such as dicyclo- acids and esters 48, 49 pentadiene) 75,76 Coumarin 46 Ethylene 77, 78 /3-Aroylacrylic acids 27, 50 Aikylidene-malonic, -acetoacetic, and -cyanoacetic esters 51 5 Diols and Alder, Ann,, 460, 98 (1928), 6 Diols, Alder, Liibbert, Naujoks, Querberitz, Rohl, and Segeberg, Ann., 470, 62 (1929). 7 Diels, Alder, Petersen, and Querberitz, Ann., 478, 137 (1930). 8 Alder, Stein, Liebmann, and Holland, Ann., 514, 197 (1934). 9 Diels and Alder, U. S. pats. 1,944,731-2 [C. A., 28, 2016 (1934)]. 10Lehmann and Paasche, Ber., 68, 1146 (1935). 11 Kasansky and Plate, Ber., 68, 1259 (1935). 12 Arbuzov, Ber., 68, 1435 (1935). 13 Lehmann, Ber., 69, 631 (1936). 14 Dupont and Dulou, Compt. rend., 202, 1861 (1936). 15 Arbuzov, Zinov'eva, and Fink, J. Gen. Chem. U.S.S.R., 7, 2278 (1937) [C. A., 32, 507 (1938)]. 16Chayanov and Grishin, Colloid J. U.S.S.B., 3, 461 (1937) [C. A., 32, 6226 (1938)]. 17 Chayanov, /. Gen. Chem. U.S.S.B., 8, 460 (1938) [C. A., 32, 7905 (1938)].