Sterically‐crowded pyrroles

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., R2 = R5 = Me, R1 = i‐Pr, Me2CHMeCH‐, Me2N‐, Ph2N‐, 9‐carbazolo, subst. 4‐morpholino, 1‐piperazino, 1‐piperidino, etc. A product‐water azeotroping procedure succeeded in more severely sterically‐crowded cases e.g., R2 = R5 = Et, R1 = i‐Pr; R2 = R5 = Me, R1 = Me3CCH2‐, R2 = R5 = i‐Pr, R1 = PhCH2‐. Highly sterically‐crowded pyrroles, e.g., R2 = R5 = Me, R1 = t‐Bu, adamantyl, PhCH2CMe2; R2 = R5 = Et, R1 = t‐Bu; R1 = R2 = R5 = i‐Pr; R2 = R5 = t‐Ru, R1 = Me, Et, PhCH2‐, 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.