George McGillivray

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.

Rate measurements of certain Vilsmeier–Haack reactions. Part 2. The effect of N-substituents in the amide

Rate measurements on the reaction between a series of amide–POCl3 complexes (2a–h) and ethyl 2,4-dimethylpyrrole-3-carboxylate in 1,2-dichloroethane were used to study the effect of N-substituents in amides (1a–h) on the Vilsmeier–Haack reaction. The results obtained are generally consistent with the expected steric and l strain effects with the exception of the morpholide and the two N-substituted piperazides which showed unexpected reactivity; a reason for this exceptional reactivity is suggested. The morpholide is recommended for the benzoylation of pyrroles.

Rate measurements of certain Vilsmeier–Haack reactions. Part 1. The benzoylation of a trisubstituted pyrrole

Rate measurements on the reaction between the NN-dimethylbenzamide–POCl3 complex (1) and ethyl 2,4-di-methylpyrrole-3-carboxylate (2) in 1,2-dichloroethane show that the reaction follows second-order kinetics, first order in each of (1) and (2), for reactions taken to at least 90% of completion. The rate constant remained un-changed for reactions in which an excess of POCl3 was present, or where the concentration of the pyrrole (2) was varied, but became inconsistent when the concentration of the complex (1) was varied. The Arrhenius activation energy was determined and the low value obtained is consistent with a very early transition state. The presence of traces of water was found to have a marked effect on both the rate of the reaction and the yield obtained.

A general method for the preparation of 2-benzylpyrroles by modified borohydride reduction of azafulvenium salts

2-Benzylpyrroles (5a–h) can be prepared in high yield from pyrroles by reduction, with modified borohydride reagents, of the corresponding 1-azafulvenium salts (3a–h) generated in situ in the presence of excess of phosphoryl trichloride. The procedure is compatible with ester groups.