Structure–activity relationship of dihydroimidazo-, dihydropyrimido, tetrahydrodiazepino-[2,1-b]-thiazoles, and -benzothiazoles as an acylation catalyst

Cyclic isothioureas 1, 2, 3, and 4 were synthesized through a four-step procedure from the corresponding ortho-bromoanilines 10 via Pd- or Cu-catalyzed cyclization–benzothiazole formation. Nonbenzo analogues 7, 8, and 9 were synthesized by a condensation reaction of cyclic thioureas 15 and α-bromoacetophenones 14. Investigations of the acylation reactions of 1-phenylethanol with acid anhydrides in the presence of these cyclic isothiourea catalysts revealed their structure–activity relationships. Remarkable electronic effects resulting from substituent(s) on a benzo or phenyl moiety and the influence of the size of the annulating ring were observed. Introduction of an electron-donating substituent(s) enhanced the reaction rate. A few substitution effects on chiral catalysts of type 3 and 7 were also studied.