Silica-Supported Polyphosphoric Acid in the Synthesis of 4-Substituted Tetrahydroisoquinoline Derivatives

Stanimir Manolov,Stoyanka Nikolova,Iliyan Ivanov

doi:10.3390/molecules18021869

Abstract

We report herein an application of an α-amidoalkylation reaction, as an alternative efficient synthesis of 4-aryl- and 4-methyl-1,2,3,4-tetrahydroisoquinoline derivatives. The amides required for this purpose would result from reaction of aminoacetaldehyde dimethylacetal with different substituted benzenes in polyphosphoric acid, followed by acylation of the obtained amines with different acid chlorides or sulfochlorides. We compared the cyclisation step using conventional (milieu of acetic-trifluoracetic acid = 4:1) and solid supported reagents (SiO2/PPA), as recovered, regenerated and reused without loss of its activity catalyst. We found that in comparison to conventional methods, the yields of the reaction are greater and the reaction time is shorter.

Highlights

Very rare natural 4-aryl-1,2,3,4-tetrahydroisoquinoline alkaloids have been isolated from Crinum powellii var. alba and other Crinum species [1]
In 1970, Brossi et al [1] isolated from Crinum powelli an alkaloid with a 4-aryl-1,2,3,4-tetrahydroisoquinoline structure named cherylline
In our previous investigations we report application of polyphosphoric acid (PPA) as a cyclisation agent for the construction of tetrahydroisoquinoline ring systems

Summary

Introduction

Very rare natural 4-aryl-1,2,3,4-tetrahydroisoquinoline alkaloids have been isolated from Crinum powellii var. alba and other Crinum species [1]. Very rare natural 4-aryl-1,2,3,4-tetrahydroisoquinoline alkaloids have been isolated from Crinum powellii var. Alba and other Crinum species [1]. Due to the uniqueness of the structure and potential medicinal properties of the 4-arylisoquinoline derivatives [2,3,4,5], many synthetic routes for these compounds [6,7,8,9,10,11,12,13,14,15] and especially cherylline have been reported. In 1970, Brossi et al [1] isolated from Crinum powelli an alkaloid with a 4-aryl-1,2,3,4-tetrahydroisoquinoline structure named cherylline. Some of them are valuable medicines with centrally stimulating, Molecules 2013, 18 thymoleptic, and antiarrhythmic actions [2,17]. Others are calcium antagonistic [18], and exhibit broad spectrum of activity such as antibacterial [19], antiplasmodial [3,4,16,20,21], estrogen agonist/antagonist activity [22], and serotin (5-HT) re-uptake [23]

Methods

Results

Conclusion