Synthesis and reactions of 2,3,5,6-tetrahydro-2,5-ethano-3-benzazocin-4(1H)-one and a thieno-extended analogue: X-ray structure of 3-methyl-2,3,5,6-tetrahydro-2,5-ethano[1]benzothieno[3,2-d]azocin-4(1H)-one

Abstract

5,6,7,8,9,10-Hexahydro-6,9-methanobenzocyclo-octen-11-one (3) was prepared through condensation of o-xylene-α,α′-diyl dibromide with N-cyclopentylidenepyrrolidine and converted by Beckmann rearrangement of its oxime (4) into 2,3,5,6-tetrahydro-2,5-ethano-3-benzazocin-4(1H)-one (6). 2,3-Bis(bromomethyl)benzo[b]thiophene was converted similarly into a mixture of 1,4,5,6-tetrahydro-2,5-ethano[1]benzothieno[2,3-d]azocin-3(2H)-one (15) and the isomeric lactam (19). Lactam (6) was N-methylated and both the parent lactam (6) and the N-methyl derivative (23) were reduced with lithium aluminium hydride to the saturated products (24) and (25), respectively. Conversion of lactam (6) into the corresponding thiolactam (26) with phosphorus pentasulphide followed by alkylation of the latter compound gave an N-(29) or S-alkylated derivative, (27) or (28), depending on the reagent and reaction conditions. Similar reactions are reported also for lactams (15) and (19). The 4(1H)-one structures of compounds (15)–(22) are based on an X-ray analysis of 3-methyl-2,3,5,6-tetrahydro-2,5-ethano[1]benzothieno[3,2-d]azocin-4(1H)-one (20). We also report syntheses of 2-azido-5,6,7,8,9,10-hexahydro-6,9-methanobenzocyclo-octen-11 -one (33) and 3-nitro(and 1,3-dinitro)-6,7,8,9,10,11 -hexahydro-7,10-methanocyclo-octa[b][1]benzo-thiophen-12-one, (36) and (37), respectively.