REGIOSELECTIVE FRIEDEL-CRAFTS ACYLATION OF 2,3,4,5-TETRAHYDRO-1H-2-BENZAZEPINE AND RELATED NITROGEN-HETEROCYCLES

It is revealed that NH-protected 2,3,4,5-tetrahydro-1H-2-benzazepine 4 is acylated on C-8 with greater than 95% regioselectivity. This regio selectivity has been applied to the synthesis of 3,4,5-tetrahydro-1H-2 -benzazepin-8-yl)propan-1-one 3a, an inhibitor of acetylcholinesterase (AChE). The regioselectivities of the acylation of the following nitr ogen heterocycles have also been studied: 4-formyl-2,3,4,5-tetrahydro- 1,4-benzoxazepine 6, 2,3,4,5-tetrahydro-1H-2-benzazepin-3-one 7, 2,3,4 ,5-tetrahydro-1H-3-benzazepin-2-one 8, 7,11b,12,13-tetrahydro-5H-isoin dolo[2,1-b][2] benzazepin-7-one 9 and -tetrahydro-5H-isoindolo[1,2-a][ 2]benzazepin-9-one 10. A molecular orbital (MO) calculation on the Lew is acid coordinated substrates has been used for predicting regioselec tivity.