Rate measurements of certain Vilsmeier–Haack reactions. Part 3. The reactivities of various pyrrole substrates

The rates of reaction of six pyrrole substrates with the Vilsmeier–Haack reagent derived from NN-dimethylbenzamide (and in some cases from N-benzoylmorpholine or NN-diethylbenzamide) and phosphoryl chloride were measured. The deactivating effect on substitution at the 5-position of a groups when present at the 2-and 4-position. This net activation of the substrate was lost when the bulkier Vilsmeier–Haack complex derived from NN-diethylbenzamide was used. The presence of a methyl or benzyl group at the 1-position of the pyrrole resulted in an unexpected and very marked deactivation of the substrate. A highly specific orientation of reagent and substrate in the transition state is suggested to account for this effect.