3-Hydroxypyrroles and 1H- pyrrol-3(2H)-ones. Part 10. Alkylation of pyrrolones under basic conditions: regiospecific formation of 3-alkoxypyrroles

Abstract

Alkylation of 1 -substituted 1 H-pyrrol-3(2H)-ones 1 in the presence of base generally gives a mixture of O-alkylated 3, C, O-dialkylated 4 and C, C-dialkylated 5 products. The proportion of C-alkylation is increased by the use of a soft alkylating agent (e.g. iodomethane) and a solvent of low polarity (e.g. THF), whereas O-alkylation is favoured by hard alkylating agents (e.g. methyl toluene-psulphonate), and dipolar aprotic solvents (e.g. dimethylimidazolidinone). These latter conditions give a good preparative route to a wide range of 1-substituted and 1,2-disubstituted 3-alkoxypyrroles 3 (65–90% yield). The X-ray crystal structure of 1 -tert-butyl-3-methoxy-2-phenylpyrrole 22 is reported.