Synthetic studies on indoles and related compounds. XV. An unusual acylation of ethyl indole-2-carboxylate in the Friedel-Crafts acylation.

The Friedel-Crafts reaction of ethyl indole-2-carboxylate (1a) with acyl chlorides or acid anhydrides in the presence of Lewis acids was investigated in order to establish a preparative procedure for the corresponding ethyl 3-acylindole-2-carboxylates (4). Although monoacylation occurred successfully, the products were generally a mixture of ethyl 3-, 5-, and 7-acylindole-2-carboxylates (4, 5, and 6). The ratio of the yields of these three products varied greatly depending on reaction conditions and reagents used. A tendency that the 3-acylindole (4) was obtained as a main product was observed when a Lewis acid other than aluminum chloride was used as a catalyst and/or an acyl chloride derived from a weaker acid was employed, whereas a tendency for formation of the 5- and 7-acylindoles (5 and 6) was observed when aluminum chloride and/or an acyl chloride derived from a stronger acid was used. As to the 5-and 7-acylindoles (5 and 6), the yields of the former (5) were always much higher than those of the latter (6). The result indicates that ethyl 3- and 5-acylindole-2-carboxylates can be regioselectively prepared from a common substrate (1a) by changing the reaction conditions or reagents.