Cinnolines. Part XV. Methylation of methoxy- and alkyl-cinnolines and -4(1H)-cinnolones

Abstract

The effects of substituent methoxy-groups upon the methylation of 4(1H)-cinnolone and upon the quaternisation of cinnoline with methyl iodide have been examined by isolation of the products and by n.m.r. measurements. 3-Methoxy-4(1H)-cinnolone gives only 3-methoxy-1-methyl-4-cinnolone whereas 5-, 6-, 7-, and 8-methoxy-4(1H)-cinnolones yield mainly the 2-methylcinnolinium-4-olates with some of the 1-methyl-4-cinnolone. Treatment of 3-methoxycinnoline with methyl iodide gives the 1-methyl salt and 2-methyl-3-cinnolone, several 4-methoxycinnolines form the corresponding 2-methyl salt and 1-methyl-4-cinnolone, and 5-, 6-, 7-, and 8-methoxycinnolines give 2-methiodides as major products. 3-Alkyl substituents (Me, Et, Buⁿ, CH₂Ph) in the cinnoline ring do not prevent predominant quaternisation at N-2 but 3,4-dibenzylcinnoline yields mainly the 1-methiodide. In the case of 3,4-diphenylcinnoline, however, the 2-methiodide is the major product, as predicted by Lund. Some alkylcinnolinium salts were identified by reduction to indoles or indolines. Indolines were conveniently prepared by hydrogenation of indoles in acetic acid in the presence of perchloric acid and palladium–charcoal catalyst.