Acid halides

This chapter is a comprehensive review of new methods introduced since 1995 for preparations of acid fluorides, chlorides, bromides, and iodides. These are compared to older more traditional procedures. New fluoride salts containing a nucleophilic fluoride ion have been introduced. Acid chlorides can now be converted into fluorides using ammonium perfluorocyclobutane ylide, cobaltocenium fluoride, and thermally labile 1-acyl-4-benzylpyridinium tetrafluoroborates. Deoxo-Fluor™ has been introduced as a safe alternative to DAST. Several alternatives, to the mild but expensive fluorinating reagent cyanuric fluorides, have been introduced including tetramethyl fluoroformamidinium hexafluorophosphate, and nitrogen salts of HF. Acid fluorides have also been obtained by oxidation of alcohols with bromine trifluoride and electrochemical fluorination of aldehydes. The addition of benzotriazole to thionyl chloride reactions has been shown to facilitate the rapid conversion of carboxylic acids into acid chlorides. Oxalyl chloride remains a popular alternative to thionyl chloride. New methods for the conversion of carboxylic acids into acid chlorides under neutral conditions include the use of hexachloroacetone or trichloroacetonitrile with triphenylphosphine. A brief description of solid-supported reagents is also given. An outline of currently available methods for preparation of acid bromides and iodides is described.