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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.

The mechanisms of two reactions which give isomeric thiazol-5-yl ketones have been elucidated by work with substrates containing pairs of acyl groups and their deuterium-substituted analogues.

A study has been made of the condensations between N-acyl-N′,N′-disubstituted thioureas and α-halogeno ketones [reaction (I)], and between N,N-disubstituted thioureas and 2-bromo-1,3-diketones [reaction (II)]. The mechanistic details were elucidated by using substrates with pairs of (almost) equally reactive but spectrometrically distinguishable acyl groups, e.g., CH3CO and CD3CO. In the presence of added base (triethylamine) both reactions proceed through a common open-chain 1,3-diketone; from this, isomeric products are formed by nucleophilic attack at the alternative carbonyl groups to give cyclic intermediates which then undergo rate-limiting dehydration. If base is not added the media become acidic. Reaction (II) follows its previous course but the relative rates of the stages are reversed. In reaction (I) the initial cyclic intermediate is dehydrated so rapidly that the open-chain 1,3-diketone is not formed, and only one isomer is produced.Both reactions are useful preparatively. For example, by adding or omitting triethylamine a typical reaction (I) was induced to give 1-(5-p-methoxybenzoyl-4-p-nitrophenylthiazol-2-yl)hexahydroazepine (yield 79%) or the isomeric 4-p-methoxyphenyl-5-p-nitrophenyl compound (78%).