RESUMEN

The reactions of 2-aminothiazole (1a), 4-methyl-2-aminothiazole (1b), and 4,5-dimethyl-2-aminothiazole (1c) with superelectrophilic 4,6-dinitrobenzofuroxan (DNBF) have been studied in acetonitrile and a 70/30 (v/v) H2O/Me2SO mixture. While exhibiting a somewhat higher nitrogen basicity than that of anilines, 1a and 1b do not react as nitrogen nucleophiles, affording exclusively anionic C-bonded sigma-adducts (C-1a and C-1b) through electrophilic S(E)Ar substitution of the thiazole ring by DNBF. Only in the case of the 4,5-dimethyl derivative 1c a N-adduct, N-1c, was obtained. On the basis of 1H-15N correlations, it is demonstrated that this adduct, N-1c;1c,H+, is derived from DNBF addition at the exocyclic amino group and not at the endocyclic nitrogen center of 1c. Rate constants have been determined in the two solvents for the formation of the adducts, revealing a reactivity sequence which accounts well for the finding that 1a and 1b behave preferentially as carbon rather than nitrogen nucleophiles. The enaminic character of these thiazoles is assessed through an estimation of the pKa values for their C-protonation in aqueous solution as well as through a positioning of their reactivity on the nucleophilicity scale recently developed by Mayr et al. (Acc. Chem. Res. 2003, 36, 66). With N values of the order of 6.80 and 5.56, 1b and 1a have a carbon nucleophilicity comparable to that of N-methylindole and indole, respectively.