2-(Tosylamino)benzyltrimethylammonium Halides as Precursors of 2-Substituted Indoles

Abstract

The reactions of 2-(tosylamino)benzyLrimethylammoniUm halides (1) with diiethylsulfonium 2-0x0-2-phenylethylide (6b), dimethylsulfonium 2-ethoxy-2-0x0-ethylide (6c) and diiethylsulfonium cyanometbylide (6d) are useful synthetic routes to 2-substituted indoles (8b-d). The relationship between reaction conditions and selectivity is discussed.Our work on the use of sulfiu. ylides in the synthesis of heterocyclic compoundslJ included the 2-(tosylamino)benzyltrimethylammonium halides (1) (Scheme 1). These compounds bear an electrophilic (cH~N+) and a nucleophilic site (NH-Tos) ortho each other. Thus, they are expected to react with s u f i ylides through a sequence of reactions leading to a fivemembered ring cyclization.Dedicated to Professor Paolo GTiinanger on the occasion of his 7 8 biihday. 2398HETEROCYCLES. Val. 43. No. 11.1996 Comgamdm (1) oan bo proparod eanlly by moana of two simple and e5ciont routes. The first procedure (Scheme la) starts fiom o-aminobenzyl alcohol which, upon treatment with tosyl chloride, gives selectively the corresponding N-2-hydroxymethylphenyl-4-metbylbetlzene~~Lfonamide (2). The N-tosylated benzyl alcohol (2) is converted into the corresponding chloride which undergoes a nucleophilic substitution with trimethylamine leading to la. An alternative route to 1 for instance l b (Scheme 1) requires the alkylation with methyl iodide of N-2-dimethylaminomethylphenyl-4-methyIbenzenesulfonamide (4) prepared fiom N, N-dimethyl-2-aminobenzenemethanamine (3) and tosyl chloride Scheme I a: i o s t o s