Novel 2-Amino-4-Aryl-Substituted-and 2-Amino-4,5-Disubstituted-Thiazoles

A series of new 2-amino- or 2-allylamino-4-aryl-substituted thiazoles have been prepared from the corresponding α-brominated acetophenones via reaction of the latter with thiourea or allylthiourea in HCCl3:C2H5OH(abs) in a one-pot sequence. The brominated ketones were, in turn, obtained by direct bromination of the parent ketones. Purification of the thiazoles was most easily achieved by sublimation. A few N-acetyl derivatives of the 2-aminothiazoles were prepared by reaction with acetic anhydride in glacial acetic acid. One suberone derivative, namely 2-allylamino-8,9–dimethoxysubero [1,2-dl]thiazole, was synthesized, but the starting material 7,8-dimethoxysuberone was not known. Preparation of the latter ketone was initiated by conversion of 3,4-dimethoxyacetophenone with sodium hydride in diethyl carbonate to the corresponding β-keto ester. The respective enolate was generated from this keto ester, and upon treatment with ethyl 3-bromopropionate, led to, after neutralization, 5-(3',4'-dimethoxyphenyl)-5-oxopentanoic acid. Reduction of the carbonyl group in this keto acid with hydrogen over Pd/C followed to give 5-(3,4-dimethoxyphenyl) pentanoic acid which was cyclized with 115 % polyphosphoric acid near 75 °C to give 7,8-dimethoxysuberone