Kinetics and mechanism of N-substitution of indoles and carbazoles in Vilsmeier–Haack acetylation

Abstract
The rate constants of acetylation of several pyrroles, indoles, and carbazoles by the Vilsmeier–Haack reagent (NN-dimethylacetamide–carbonyl chloride) have been measured in 1.2-dichloroethane at 25 °C. Most substrates undergo N-substitution and the data strongly support a mechanism involving rate determining direct attack on the nitrogen atom. The order of susceptibility to the electrophile for positions 1–3 of the indole nucleus is C-3 > N-1 > C-2. Differences in behaviour towards N-substitution of pyrrole, indole, and carbazole are discussed in terms of loss of resonance energy in the transition states.

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