Studies on the syntheses of heterocyclic compounds. Part CCCLXXXV. Pschorr reactions of 1-(2-aminobenzyl)- and 1-(2-aminophenethyl)-1,2,3,4-tetrahydroisoquinolines (total synthesis of thalicsimidine)

Abstract

In order to obtain dienones coupled between the 8a- and 2′-positions, 1-(2-amino-4,5-dimethoxybenzyl)-1,2,3,4-tetrahydro-6,8-dimethoxy-2-methylisoquinoline (IIIa) and the corresponding 5,6,7-trimethoxy-(IIIb) and 6-hydroxy-7-methoxy-(IIIc) derivatives were subjected to the Pschorr reaction. Compound (IIIb) afforded thalicsimidine (XIXa); compound (IIIc) gave 3-nitropredicentrine (XIXb) and the (2-hydroxybenzyl)isoquinoline (IIIj), together with the normal product (predicentrine)(XIXc) and the diosphenol-type compound (Ib) in poor yield. However, Pschorr reactions of 1-(2-amino-3,4,5-trimethoxyphenethyl)-(IIId) and 1-(2-amino-4-benzyloxy-3,5-dimethoxyphenethyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinoline (IIIn) gave abnormal products, 1′,2′,3′,4′-tetrahydro-5,6,6′,7,7′-pentamethoxy-2′-methylspiro[indan-1,1′-isoquinoline](XXXIa) and its 6-benzyloxy-analogue (XXXIb).