Evidence for the Intermediacy of Wheland–Meisenheimer Complexes in SEAr Reactions of Aminothiazoles with 4,6‐Dinitrobenzofuroxan

Abstract

Reactions of DNBF with a series of 2-aminothiazoles (1 a-f) to afford thermodynamically stable C-bonded sigma-adducts have been investigated in acetonitrile. A most significant finding emerged on recording NMR spectra immediately after mixing of equimolar amounts of DNBF and the unsubstituted 2-aminothiazole (1 a) in Me2SO: namely, that the formation of 9 a is preceded by that of a short-lived intermediate species X. From the 1H NMR parameters characterizing this intermediate, as well as the dependence of its lifetime on the experimental conditions-the presence of excess DNBF over 1 a increases the lifetime of X while an excess of base (1 a) accelerates its conversion into 9 a--it is convincingly demonstrated that the structure of X combines the presence of a positively charged Wheland complex moiety (with regard to the thiazole ring) with that of a negatively charged Meisenheimer complex moiety (with regard to the benzofuroxan system). So far, only one intermediate of this type (noted WM) has been successfully characterized, in the reactions of DNBF with 1,3,5-tris(N,N-dialkylamino)benzenes. Among the key features supporting the intermediacy of X along the reaction coordinate leading to 9 a is the fact that the reactions of DNBF with 1 a in the presence of an alcohol (MeOH, EtOH, nPrOH) produce new adducts arising from the addition of an alcohol molecule to the thiazole moiety of WM-1 a. Reflecting the presence of three chiral centres, these species are formed as mixtures of several diastereomers that could all be characterized in their racemic forms in ethanol. These findings generalize the previous report on the formation of Wheland-Meisenheimer carbon-carbon complexes in homocyclic series.