Chemical and X-ray studies of a [1,4]diazepino[7,1-a]isoquinolin-2-one, a Schmidt reaction product from 3-ethyl-1,6,7,11b-tetrahydro-9,10-dimethoxy-4H-benzo[a]quinolizin-2(3H)-one

Abstract

The major and minor Schmidt reaction products from 3-ethyl-1,6,7,11b-tetrahydro-9,10-dimethoxy-4H-benzo[a]quinolizin-2(3H)-one (I) are shown to be 4-ethyl-1,4,5,7,8,12b-hexahydro-10,11-dimethoxy[1,4]diazepino[7,1-a]isoquinolin-2(3H)-one diastereoisomers, (II) and (III), respectively. Structure (II) has been confirmed for the major product by X-ray analysis of its hydrobromide which crystallises in the orthorhombic space group Pbca with Z= 8 in a unit cell of dimensions a= 12·412 ± 0·005, b= 20·574 ± 0·010, c= 13·657 ± 0·005 Å; the structure was refined to R 0·078 for 1793 reflections measured by diffractometer. Conversion of the lactam (II) into its diastereoisomer (III) and into the diazacycloundecene (VIII) proceeds through a common intermediate (VI). Hydride reduction of the methiodide (IV) is followed by Hofmann elimination to give an enamine (XI), from which the tetrahydroisoquinolines (XII) and (XIII) are formed. Oxidation of either lactam (II) or (III) by mercuric acetate yields the didehydro- and tetradehydro-compounds (XV) and (XVI); these are hydrolysed rapidly by aqueous mineral acid with decarboxylation to a dihydroisoquinolinium salt (XX) and an isoquinolinium salt (XXI), respectively. The former cyclises in the presence of base to the imidazoisoquinoline (XXII).