N′-substituted N-acyl- and N-imidoyl-thioureas: preparation and conversion of N′,N′-disubstituted compounds into 2-(N,N-disubstituted amino)thiazol-5-yl ketones

Abstract

Known methods were developed to give convenient general procedures for preparing N-acyl-N′-mono and -N′,N′-disubstituted thioureas from acid chlorides, and related N-imidoyl thioureas from imidoyl chlorides. In the products from three acid chlorides and ammonium thiocyanate the acyl isothiocyanates did not appear to be accompanied by the isomeric thiocyanates.Treatment of N-(anilino)benzylidene-N′,N′-disubstituted thioureas with chloroacetone in the presence of triethylamine leads to 5-acetyl-4-phenyl -2-(N,N-disubstituted amino)thiazoles. In contrast, the corresponding N-benzoyl thioureas form only small amounts of these compounds; the main products are the 5-benzoyl-4-methyl isomers, and this unexpected outcome requires a revision of the literature. It is thought that formation of the 5-benzoyl-4-methylthiazoles involves N–C(4) fission of a cyclic intermediate to give an open-chain intermediate in which nucleophilic attack can occur at either the acetyl or the benzoyl group. One of the latter intermediates was generated directly from 2-acetyl-2-bromoacetophenone and N-methyl-N-phenylthiourea, and found to give the 5-benzoyl-4-methyl - and 5-acetyl-4-phenyl-thiazoles as the major and minor products, respectively.