Sterically‐crowded pyrroles

Abstract

Abstract The syntheses in good yields of a considerable number of moderately to severely sterically‐crowded 1,2,5‐trisubstituted pyrroles by means of modifications of the Knorr‐Paal condensation are described. Notwithstanding reports to the contrary, the classical procedure; succeeded in moderately sterically‐crowded cases, e.g. , R 2 = R 5 = Me, R 1 = i‐Pr, Me 2 CHMeCH‐, Me 2 N‐, Ph 2 N‐, 9‐carbazolo, subst. 4‐morpholino, 1‐piperazino, 1‐piperidino, etc. A product‐water azeotroping procedure succeeded in more severely sterically‐crowded cases e.g. , R 2 = R 5 = Et, R 1 = i‐Pr; R 2 = R 5 = Me, R 1 = Me 3 CCH 2 ‐, R 2 = R 5 = i‐Pr, R 1 = PhCH 2 ‐. Highly sterically‐crowded pyrroles, e.g. , R 2 = R 5 = Me, R 1 = t ‐Bu, adamantyl, PhCH 2 CMe 2 ; R 2 = R 5 = Et, R 1 = t ‐Bu; R 1 = R 2 = R 5 = i‐Pr; R 2 = R 5 = t ‐Ru, R 1 = Me, Et, PhCH 2 ‐, were obtained using titanium tetrachloride as a Lewis acid catalyst and as a water scavenger. Infrared spectra of the reacting mixtures provided evidence pertinent to the mechanism of the reaction, which is discussed.