Standard Article

The Pictet-Spengler Synthesis of Tetrahydroisoquinolines and Related Compounds

  1. Wilson M. Whaley*,
  2. Tuticorin R. Govindachari

Published Online: 15 MAR 2011

DOI: 10.1002/0471264180.or006.03

Organic Reactions

Organic Reactions

How to Cite

Whaley, W. M. and Govindachari, T. R. 2011. The Pictet-Spengler Synthesis of Tetrahydroisoquinolines and Related Compounds. Organic Reactions. 6:3:151–190.

Author Information

  1. University of Illinois

  1. *

    Present address: University of Tennessee, Knoxville. Tennessee.

  2. Present address: 25, Thanikachalam Chetty Road, T. Nagar, Madras, India.

Publication History

  1. Published Online: 15 MAR 2011

Chemistry Terms

Choose one or more boxes to highlight terms.


The Pictet-Spengler reaction, in its simplest form, consists in the condensation of a beta-arylethylamine with a carbonyl compound to yield a tetrahydroisoquinolone and is a special example of the Mannich reaction. The condensation of phenethylamine with methylal in concentrated hydrochloric acid to form 1,2,3,4-tetrahydroisoquinoline was achieved in 1911 by Pictet and Spengler. Their reaction has been applied to the synthesis of other ring systems. The theory that proteins are the parent substances of alkaloids was tested by Pictet, who heated casein with methylal and hydrochloric acid, obtaining a mixture of pyridine and isoquinoline bases. Most of the products were not definitely identified.


  • Pictet-Spengler synthesis;
  • tetrahydroisoquinolines;
  • cyclization;
  • aromatic nucleus;
  • carbonyl component;
  • side reactions;
  • condensing agents;
  • carbolines;
  • experimental conditions