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. 2013 Feb 1;18(2):1869-80.
doi: 10.3390/molecules18021869.

Silica-supported polyphosphoric acid in the synthesis of 4-substituted tetrahydroisoquinoline derivatives

Stanimir Manolov  1 , Stoyanka Nikolova, Iliyan Ivanov
Affiliations

Silica-supported polyphosphoric acid in the synthesis of 4-substituted tetrahydroisoquinoline derivatives

Stanimir Manolov et al. Molecules. .

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.

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Figures

Scheme 1
Scheme 1
Retrosynthetic scheme for the synthesis of 4-substituted tetrahydroisoquinolines.
Scheme 2
Scheme 2
Synthesis of amines 3.
Scheme 3
Scheme 3
Synthesis of 4-aryl tetrahydroisoquinolines.
Scheme 4
Scheme 4
Synthesis of 4-methyl tetrahydroisoquinolines.
See this image and copyright information in PMC

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