Additions of Acetonitrile and Chloroform to Aromatic Aldehydes in the Presence of Tetrabutylammonium Fluoride

Abstract

Addition reactions of acetonitrile to aldehydes afford βhydroxynitriles which can be converted into amino, carboxyl or other functional groups in organic chemistry. Cyanomethylation has been performed by deprotonation of a nitrile compound followed by addition to an aldehyde or a ketone. Depending on the reaction conditions, α,β-unsaturated nitriles are given as in aldol-type condensations. There have been some reports describing various methods of cyanomethylation. Addition reactions of a trichloromethyl group to aldehydes give trichloromethyl carbinols which can be converted into α-amino, α-hydroxy and α-thio acids. The reaction can be carried out by base-mediated addition of the trichloromethyl group to an aldehyde or ketone as the same manner as in cyanomethylation. Reagents of trichloromethylation are made of a CCl3 − source such as chloroform, tetrachloromethane and (trimethylsilyl)trichloromethane and bases such as n-butyl lithium, potassium t-butoxide, potassium hydroxide, and DBU. When strong bases are used, a carbene could be generated in some cases. Tetrabutylammonium fluoride (TBAF) is a typical desilylation agent for breaking oxygen-silicon or carbon-silicon bonds and plays a role as a base or a nucleophilic fluorination reagent. Recently, we have found an equivalent of TBAF can oxidize benzaldehyde to benzoic acid. During the studies on solvent effects in the oxidations of aromatic aldehydes with TBAF, we observed cyanomethylation and trichloromethylation with certain aldehydes. In this paper, we described cyanomethylation and trichloromethylation, as well as competition with oxidation.