Syntheses of 1, 2, 3, 4-Tetrahydroisoquinolines from N-Sulfonyl-phenethylamines and Aldehydes

Abstract

N-Sulfonylphenethylamines (6—9) have been readily condensed with formaldehyde under mild acidic condition to the corresponding N-sulfonyl-l, 2, 3, 4-tetrahydroisoquinolines (14—17) in excellent yields. Condensation of sulfonamide (10) with formaldehyde under similar condition gave a mixture of two cyclization products (18 and 19). In the case of similar condensation of 3, 4-disubstituted-N~sulfonamides (11 and 12) with formaldehyde, 6, 7-disubstituted products (20 and 21) were obtained alone. Similar reaction of sulfonamides (6, 11 and 12) with aliphatic aldehydes or aromatic aldehydes also afforded the corresponding N-tosyl-l, 2, 3, 4-tetrahydroisoquinolines (22—27). Furthermore, l-benzyl-N-tosyl-l, 2, 3, 4-tetrahydroisoquinolines (31 and 37) were similarly synthesized from sulfonamide (12 or 13) and phenyl acetaldehyde (30 or 36). Birch reduction of (37) afforded the racemic form (33) of natural N-nororientaline, which was previously isolated by us from the leaves of Erythrina X bidwillii (Leguminosae). © 1977, The Pharmaceutical Society of Japan. All rights reserved.