An Unexpected Reaction in a Pomeranz-Fritsch Isoquinoline Synthesis

Abstract

For the purpose of preparing cycleanine (I), an attempt was made to cyclize the Schiff base (VII) by the Pomeranz-Fritsch reaction to 1-(4-bromobenzyl)-6, 7-dimethoxy-8-hydroxyisoquinoline (VIII) but instead of the anticipated substance (VIII), 6, 7-dimethoxy-8-hydroxyisoquinoline (IX) was obtained, formed by the liberation of the p-bromobenzyl group. The structure of (IX) was confirmed by the formation of anhalidine (2-methyl-6, 7-dimethoxy-8-hydroxy-1, 2, 3, 4-tetrahydroisoquinoline) (XI) by reduction of its methiodide (X) with tin and hydrochloric acid.
In connection with the foregoing, it was found that the Bischler-Napieralski reaction starting with N-formyl-3, 4-dimethoxy-5-benzyloxyphenethylamine (XIX) gave 6-benzyloxy-7, 8-dimethoxy-3, 4-dihydroisoquinoline (XX), and that the reduction and debenzylation of its methiodide (XXI) afforded 2-methyl-6-hydroxy-7, 8-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline (XXIII), an isomer of (XI).