THE REACTIONS OF ALIPHATIC ACID CHLORIDES NORMAN 0 . V . SONNTAG Colgate-Palmolive-Peet Company. Jersey City. New Jersey Received November 16. 1962 CONTENTS I . Introduction .................. ......................................... 238 I1. Scope of the revieL1. ....................................................... 239 I11 . Nomenclature ............................................. IV . Reduction of aliphatic acid chlorides ...................... A . The Rosenmund reduction., ............................................ 245 B . Catalytic hydrogenation .............................................. 247 C . Chemical methods of reduction ....................................... 248 1. With sodium amalgam .......................................... 2 . With metal hydrides ................................................ 249 3 . With other reducing agents ........................................ 251 V . Hydrolysis of aliphatic acid chlorides ....................................... 251 VI . Reaction of aliphatic acid chlorides with ammonia, hydroxylamine, and hy- drazine ................................................................... 258 A . Reaction with ammonia .............................................. 258 1. At low temperatures............................................... 258 2 . At high temperatures ................................................ 265 B . Reaction with hydroxylamine and hydrazine.,........................... 266 VI1. Reaction of aliphatic acid chlorides with amines, substituted amines, and re- lated compounds ....................................................... 268 A . Reaction with primary amines ........................................... 269 B . Reaction with secondary amines ........................................ 277 C . Reaction with tertiary amines ....................................... 294 D . Reaction with compounds containing a carbon-nitrogen double bond ... 299 VI11. Reaction of aliphatic acid chlorides with amides and imides ...............302 A . Reaction with aromatic carboxylic amides ........................... 302 B . Reaction with aliphatic carboxylic amides ......................... 305 C . Reaction with sulfonamides ......................................... 309 D . Reaction with ureas and urethans ............................... 310 E . Reaction with miscellaneous amide types ............................ 311 F. Reaction with imides ................................................ 307 IX. Reaction of aliphatic acid chlorides with hydroxy-containing compounds (esterification reactions) ........................................... 312 9. Reaction with alcohols .............................................. 312 B . Reaction with phenols ................................................. 320 C . Reaction with polyhydroxy nds ................................. 321 D . Reaction with hydroperoxid ..................................... 324 X . Reaction of aliphatic acid chlor h carbonyl-containing compounds .... 324 A . Reaction n-ith aldehydes and ketones .................................... 324 B . Reaction with esters ................................................... 328 C . Reaction with acids and salts of acid ................... 330 D . Reaction with acid anhydrides and la ......... 337 E . Reaction with ketenes., ..... ..................... 337 F . Reaction with quinones ................................................. 338 237 238 NORMAN 0. V. SONNTAG XI. Reaction of aliphatic acid chlorides with inorganic compounds involving re- placement of the chlorine atom.. ......................................... 340 A. Replacement of the chlorine atom by the cyano group B. Replacement of the chlorine atom by other halogens.. C. Replacement of the chlorine atom by other groups ....................... 342 XII. Reaction of aliphatic acid chlorides with peroxides and oxides 343 A. Reaction with peroxides.. ........ ................................. 343 B. Reaction with oxides .................................................... 344 XIII. Reaction of aliphatic acid chlorides with hydrocarbons (Friedel-Crafts type of reaction) .............................................................. 345 A. Reaction with aromatic hydrocarbons. ............ B. Reaction with olefins.. ......... C. Reaction with acetylenes.. ..... D. Reaction with saturated hydrocarbons.. XIV. Reaction of aliphatic acid chlorides with heterocyclic compounds (Friedel- Crafts type of reaction). ................................................. 352 XV. Reaction of aliphatic acid chlorides with ethers and epoxides.. .............. 353 XVI. Reaction of aliphatic acid chlorides with halogens and halogenating agents. .. 358 A. Chlorination ............................................................ 359 B. Bromination ............................................................ 361 C. Chloroformylation. ............................................... D. Other halogenations.. ....................... XVII. Reaction of aliphatic acid chlorides with azides XVIII. Reaction of aliphatic acid chlorides with diazo compounds.. ................ 365 A. Reaction with diazomethane (Arndt-Eistert synthesis) B. Reaction with diazoacetic ester and diazoacetone.. ...................... 367 C. Reaction with other diazo compounds.. ................................. 369 XIX. Reaction of aliphatic acid chlorides with metals and organometallic com- pounds. .................................................................. 369 A. Reaction with alkali metals.. ........................................... 369 B. Reaction with other metals ............................. 370 C. Reaction with Grignard reagents.,...................................... 372 D. Reaction with other ..................381 1. Dialkylzinc compounds.. .. ... ........ 381 2. Dialkylcadmium c ..................385 3. Other organometallic compounds.. .................................... 386 XX. Reaction of aliphatic acid chlorides with mercaptans (thioesterification) and other sulfur, arsenic, silicon, phosphorus, and selenium compounds.. ...... 387 XXI. Reaction (non-Friedel-Crafts type) of aliphatic acid chlorides with compounds containing double or triple bonds.,....................................... 393 XXII. Miscellaneous reactions A. Dehydrochlorination. ........................................ 394 B. Pyrolysis.. ......... C. Rearrangement.. .... D. Polymerization.......................................................... 398 E. Miscellaneous ........................................................... 398 XXIII. References. ........................................................ 399 I. INTRODUCTION The aliphatic carboxylic acid chlorides as a class are among the most versatile and reactive of organic compounds. Some of the lower homologs, particularly those containing from two to five carbon atoms, have long been used in the prep- aration of a large variety of chemical compounds in a series of well-known and REACTIONS OF ALIPHATIC ACID CHLORIDES 239 well-understood reactions, such as the esterification of alcohols and the Friedel- Crafts acylation of aromatic hydrocarbons. Recent research has greatly extended the applicability of these materials in new and unprecedented ways. The straight- chain aliphatic acid chlorides containing from eight to eighteen carbon atoms, especially the even-numbered members, have achieved prominence as a conse- quence of recent developments in the field of fatty acid derivatives among which the esters, metallic salts, amides, nitriles, amines, and amine quaternaries have been noteworthy. These derivatives have assumed commercial importance over a period of years. The acid chlorides have received somewhat less attention, in general, than the other types of fatty acid derivatives, probably as a result of their relatively poorer stability and the difficulties encountered in handling them. In spite of these minor disadvantages more and more attention has been focused upon fatty acid chlorides as useful intermediates for the preparation of a huge number of products. The advent of newer synthetic routes to the aliphatic acids, particularly those utilizing inexpensive animal fats and vegetable oils, and the ease with which these acids can be converted into acid chlorides are further fac- tors which enhance the importance of acid chlorides. 11. SCOPEOF THE REVIEW This review covers the chemical reactions of aliphatic carboxylic acid chlorides containing two or more carbon atoms. Straight- and branched-chain, saturated and unsaturated, and mono- and polyfunctional types have been included. The literature has been surveyed through December, 1951. In instances where cer- tain portions of the material have been reviewed elsewhere within the last ten years the attempted coverage has been less complete, and an effort has been made, where feasible, to bring the previously reviewed material up to date. No attempt has been made to include the reactions of aromatic or aromatic-ali- phatic acid chlorides, except for certain examples of the former type where dif- ferences in reaction behavior bring out the variation in general reactivity between these types and aliphatic acid chlorides. The reactions of alicyclic and hetero- cyclic acid chlorides have not been included, nor have those of amino-, alkoxy-, or mercapto-substituted aliphatic acid chlorides. 111. KOMENCLATURE The nomenclature of acid chlorides requires the names of acyl radicals in the several systems of nomenclature, since, regardless of the system, the name for an individual species is “acyl chloride.”