Regioselective Friedel–Crafts acylation of 1,2,3,4-tetrahydroquinoline and related nitrogen heterocycles: effects of NH protective groups and ring size

Abstract

Regioselectivity of the Friedel–Crafts acylation of the following nitrogen heterocycles was studied: 2,3-dihydro-1H-indoles 3, 1,2,3,4-tetrahydroquinolines 4, 2,3,4,5-tetrahydro-1H-1-benzazepines 5 and 1,2,3,4,5,6-hexahydro-1 -benzazocines 6. It was found that though the ratio of regioisomers depends on ring size, it can be controlled by changing the NH protective groups. A molecular orbital (MO) calculation of the Lewis acid co-ordinated substrates gave a rational explanation of the regioselectivity.