Pictet-Spengler reaction for the synthesis of tetrahydroisoquino

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

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540604, 546141, 548411, 548482, C07D21702, C07D22120, C07D20944, C07D20970

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058080716

ABSTRACT:
A commercial scale process for the production of tetrahydroisoquinolines and related heterocyclics by reaction, in mildly acidic conditions, of aryl N-sulfonylethylamines in the presence of a suitable Lewis acid, and a compound capable of in situ generation of formaldehyde. The process is further characterized by formaldehyde being generated by the reaction of the Lewis acid upon the formaldehyde generating agent, instead of being present as an initial reactant. The process further avoids the presence of initial water which destroys the Lewis acid before it can act upon the formaldehyde generating agent.

REFERENCES:
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Saito, N., et al., A Facile Synthesis of 1,2,3,4-Tetahydroisoquinolines through Cyclization of O,N-Acetals.II. these os o Isoquinolinequinone Antibiotics Chem. Pharm. Bull., 37(6) 1493-1499 (1989).
Whaley, W.M., et al., The Pictet-Spengler Synthesis of tetrahydroisoquinolines and Related Compounds, Organic Reactions, Chap. 3, pp. 151-159 (1951).
Remers, W.A., et al., Synthesis of Indoles from 4-Oxo-4,5,6,7-tetrahydoindoles. II. Introduction of Substituents into the 4 and 5 Positions J. Org. Chem. 36(9) 1232-1240 (1971).
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