Heterocyclic compounds with bridgehead nitrogen atoms. Part 9. Synthesis in the pyrrolo[2,1,5-de]quinolizine ([2.3.3]cyclazine) series starting from indolizines

Abstract

Pyrrolo[2,1,5-de]quinolizines may be obtained from various 3-substituted derivatives of 5-methyl-2-phenyl- and 2,5-dimethyl-indolizine by base-catalysed condensation of the 5-methyl group with a carbonyl group in the β-position of the 3-substituent. The 1,3-diethoxalyl derivatives of these indolizines were converted, by treatment with sodium ethoxide or methoxide, into mixtures of pyrrolo[2,1,5-cd]indolizines ([2.2.3]cyclazines) and 4-hydroxy-3H-pyrrolo[2,1,5-de]quinolizin-3-ones. Under similar conditions, 5-methyl-2-phenyl-3-pyruvoyl-indolizine gave a low yield of 4-methyl-2-phenyl-3H-pyrrolo[2,1,5-de]quinolizin-3-one. When the 3-substituent was a 2-oxopropano- or 2-oxo-2-phenylethano-hydroximoyl group, cyclisation was effected with potassium t-butoxide in dimethyl sulphoxide, and the resulting 3-hydroxyimino-3H-pyrrolo[2,1,5-de]quinolizines were cleanly converted into the corresponding pyrroloquinolizinones by treatment with silver(I) oxide. 4-Methyl-2-phenyl-3H-pyrrolo[2,1,5-de]quinolizin-3-one was converted into the corresponding thione and thence, by methylation, into a methylthiopyrrolo[2,1,5-de]quinolizinylium salt.