Synthesis Of4-Substituted1,2,3,4-Tetrahydroisoquinolines

In this thesis, synthesis of4-substituted1,2,3,4-tetrahydroisoquinolines by five-step reaction from4-substituted phenylacetonitriles, which empoly deprotonation alkylation, reduction, acylation, Pictet-Spengler cyclization and deprotection has been described.1. Preparation of the key intermediate β-phenethylamines (2a-2p)4-substituted phenylacetonitriles1was used as the starting material for the synthesis. Deprotonation-alkylation of1, followed by reduction of the nitriles to their β-phenethylamines (2a-2p) generated the key intermediate of Pictet-Spengler cyclization (Scheme1). Scheme12. Pictet-Spengler cyclization of N-trifluoroacylated phenethylaminesBy means of N-trifluoroacylated, Pictet-Spengler cyclization and trifluoroacetyl deprotection of β-phenethylamines (2a-2p),4-substituted1,2,3,4-Tetrahydroiso--quinolines (5a-5p) were synthesized (Scheme2). The effect of different substituent R and Ri, R2of N-trifluoroacylated phenethylamines3a-3p on the Pictet-Spengler cyclization to provide the appropriate tetrahydroisoquinoline structures4a-4p was also disscussed. The results indicate that the influence of substituent on the Pictet-Spengler cyclization predominantly depend on withdrawing electron group (R). Ri and R2can also affect the yield. 3. Pictet-Spengler cyclization of N-tosyl phenethylaminesIt was found that when R is electron-donating group (OMe, Me), using N-tosyl phenethylamines in the Pictet-Spengler cyclization will get higher yields than using N-trifluoroacylated phenethylamines (Scheme3). In contrast, the trifluoroacetyl protection of phenethylamines have a better yield than N-tosyl phenethylamines when R is Br.