N,N-Disubstituted 2-aminothiazole-5-carbaldehydes: preparation and investigation of structural features

Abstract

Methods for preparing N,N-disubstituted 2-aminothiazoles have been investigated. 4-Substituted N,N-dimethyl-, N-benzyl-N-methyl-, and N-methyl-N-phenyl-amines were prepared and converted by Vilsmeier formylation into 2-amino-5-carbaldehydes which were examined by i.r. and ¹H n.m.r. spectrometry. The aldehyde group adopts the carbonyl O,S-syn-conformation. With the N,N-dimethyl and N-benzyl-N-methyl compounds the barrier to rotation of the amine group (ΔG^‡) is 50–55 kJ mol^–1 and is insensitive to the nature of the 4-substituent. The amine group of the N-methyl-N-phenyl compounds has a marked preference for one orientation. This was shown by a crystallographic study of 4-t-butyl-2-(N-methyl-N-phenylamino)thiazole-5-carbaldehyde to have the phenyl group directed towards the sulphur atom of the thiazole ring.

The results of the physical methods overlap in establishing the importance of a mesomeric interaction between the functional groups of 2-aminothiazole-5-carbaldehydes.