The mechanism of the Vilsmeier–Haack reaction. Part II. A kinetic study of the formylation of thiophen derivatives with dimethylformamide and phosphorus oxychloride or carbonyl chloride in 1,2-dichloroethane

Abstract

The kinetic order of the reaction of thiophen derivatives with dimethylformamide and phosphorus oxychloride in 1,2-dichloroethane depends on the reactivity of the substrate. Reactions of relatively inert substrates (such as thiophen and the methylthiophens) follows third-order kinetics, first-order in each reagent. On the other hand reactions of very labile substrates (such as 2-methoxythiophen) follow second-order kinetics, the rates being independent of the concentration and the nature of the substrate. The observed kinetics are consistent with a mechanism involving an equilibrium leading to an electrophilic complex, which then attacks the heterocyclic substrate. According to the reactivity of the substrate, the rate-determining step is either the attack of the complex on the aromatic compound or the formation of the complex. The reactions with the complex formed from dimethylformamide and carbonyl chloride follow pure second-order kinetics, first-order in substrate and first-order in complex.