Electrophilic substitution of imidazo[2,1-b]thiazoles

Abstract

Fifteen imidazo[2,1-b]thiazoles containing a range of substituents at position 6 have been used in studies of electrophilic substitution at position 5. Acid-catalysed deuteriation, was examined quantitively and, by making certain assumptions, values for the rate constants (k₁) of the deuteriation process were obtained. A 3-methyl group increases k₁ by a factor of ca. 3; for different 6-substituents the k₁-values are in the order Me > Bu^t∼ C₆H₄OMe-p > Ph. Bromination occurred preferentially at position 5 even with substrates containing 6-substituents (e.g., 2-thienyl) which themselves have a reactive nucleus. Although 6-alkyl-5-nitrosoimidazothiazoles are unstable and cannot be prepared by the standard method (sodium nitrite and acetic acid), the 6-t-butyl compounds were obtained by a procedure in which the work-up involves very mild treatment. The 5-formyl derivatives show extensive mesomerism, and in solution they adopt the conformation having the carbonyl oxygen syn to N(4). In one compound, the 4,6-dimethyl-5-carbaldehyde, the anti rotamer is present as the minor component. Imidazo[2,1-b]thiazoles are easily converted into 5-trifluoroacetyl compounds and 5-thiocyanates.