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

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.

Microwave-assisted synthesis of 1,2,3,4-tetrahydroisoquinoline sulfonamide derivatives and their biological evaluation

“…In our previous experiments, we have reported the synthesis of 1,2,3,4-tetrahydroisoquinolines, including sulfonamide derivatives using a conventional intramolecular α-amidoalkylation reaction. 21 Herein we aim to use microwave irradiation as an environmentally friendly method for the synthesis of N-methylsulfonyl-1,2,3,4-tetrahydroisoquinoline compounds using SiO 2 /PPA as a heterogeneous catalyst.…”

“…The starting amines 1a and 1b are commercially available. For obtaining of amine 1c, a procedure 21 developed in the Department of Organic Chemistry, University of Plovdiv was applied.…”

“…Comparing the yields of compounds 3 obtained by proposed microwaveassisted intramolecular α-amidoalkylation reaction with the yields of the same compounds obtained by conventional heating in a mixture of acetic : trifluoroacetic acid = 4:1 (v/v) or in a polyphosphoric acid / silica gel system (20 wt % SiO 2 ), 21 we found that the yields of compounds 3b and 3c were higher and the reaction time shorter when using microwave radiation instead of conventional heating in acetic : trifluoroacetic acid in a ratio of 4 : 1 (v/v) at the same temperature (100 °C) ( Table I). It was also found that compared to conventional heating and the use of the heterogeneous PPA/SiO 2 catalyst, the yields of the microwave-assisted intramolecular α-amidoalkylation reaction were comparable for the same reaction time.…”

Silica supported Brönsted acids as catalyst in organic transformations: A comprehensive review

“…Manolov et al [36] synthesized 4-aryl-and 4-methyl-1,2,3,4tetrahydroisoquinoline derivatives by the reaction of aminoacetaldehyde dimethylacetal with different substituted benzenes in polyphosphoric acid, followed by acylation of the obtained amines with different acid chlorides or sulfochlorides using silica supported polyphosphoric acid. The catalyst was completely recoverable and the efficiency of the catalyst remained unaltered even after three to four cycles.…”

“…Scheme 27. Synthesis of 4-aryl-and 4-methyl-1,2,3,4-tetrahydroisoquinoline derivatives using PPA-SiO2 [36]. Anomeric benzoyl groups were also removed in excellent yields (Scheme 32).…”