An Unusual and Chemoselective Reduction of Ester Grouping in Nsubstituted-3-acetylindoles by Sodium Borohydride

Abstract

Treatment of 3-acetylindoles 1(a-e) with ethyl chloroacetate in the presence of K2CO3 and tetrabutylammoniumbromide (TBAB) as phase transfer catalyst in DMF, resulted in the formation of the corresponding N-substituted derivatives, ethyl 2-(3-acetyl-1H-indol-1-yl)acetate 2(a-e) which on reaction with NaBH4 yielded, unexpectedly, ethanol derivatives, 1-(1-(2-hydroxyethyl)-1H-indol-3-yl)ethanone 3(a-e) by the unusual and chemoselective reduction of ester grouping in preference to the acetyl group. Alternative synthesis of the latter was achieved by the treatment of 1(a-e) with 2-chloroethanol under phase transfer catalytic conditions (PTC). 1(a-e), on treatment with benzenesulphonyl chloride, under PTC conditions, yielded the corresponding N-benzenesulphonyl-3- acetylindoles 7(a-e), which on reduction with NaBH4 in methanol afforded the corresponding hydroxy derivatives Nbenzenesulphonyl-( α-hydroxyethyl)indoles 8(a-e). These reactions throw light on the ease of reduction of the 3-acetyl group on indoles with NaBH4. Keywords: 3-acetylindole, N-benzenesulphonyl-3-acetylindole, chemoselective, reduction, NaBH4-MeOH, borohydride, zinc chloride, ketones, esters, Acetylindole