2-(N,N-disubstituted amino)thiazoles with electron-withdrawing groups at position 5: preparation and investigation of structural features

Abstract

A convenient procedure for preparing N-mono- and N,N-di-substituted cyanamides from cyanogen bromide has been developed. N,N-Disubstituted thioureas, obtained from the cyanamides, were condensed with α-bromo-α-cyano-ketones to give 5-cyano-2-(N,N-disubstituted amino)thiazoles and with α-bromo-ketones to give 2-(N,N-disubstituted amino)thiazoles. Substitution in the latter products afforded 5-trifluoroacetyl- and 5-nitro-2-(N,N-disubstitutedamino)thiazoles; nitration is greatly facilitated by the presence of a 4-aryl group.

The average values of the barriers to rotation of the 2-NR₂ groups (ΔG^‡₂₉₈) in the 5-substituted thiazoles were established by variable temperature ¹H n.m.r. spectrometry to be 57.4 kJ mol^-1(5-NO₂), 56.2 (5-COCF₃), and 51.5 (5-CN). I.r. examinations showed that the 5-trifluoroacetyl compounds adopt one rotational form preferentially; this is probably the carbonyl O,S-syn-conformation.