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The Preparation of 3,4-Dihydroisoquinolines and Related Compounds by the Bischler-Napieralski Reaction

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

Published Online: 15 MAR 2011

DOI: 10.1002/0471264180.or006.02

Organic Reactions

Organic Reactions

How to Cite

Whaley, W. M. and Govindachari, T. R. 2011. The Preparation of 3,4-Dihydroisoquinolines and Related Compounds by the Bischler-Napieralski Reaction. Organic Reactions. 6:2:74–150.

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

Abstract

The frequent occurrence of the isoquinoline nucleus in alkaloids has led to considerable interest in the synthesis of isoquinolone derivatives. Many methods have been developed, but only three have enjoyed popularity. One of them, the Bischler-Napieralski reaction is discussed in this chapter. The reaction consists in the cyclodehydration of beta-phenethylamides to 3,4-dihydroisoquinolines by heating to high temperatures with phosphorus pentoxide or anhydrous zinc chloride. Yields were not given for the original reaction, but later studies proved that the yields were low. Modifications using lower temperatures and milder condensing agents improved the reaction. The most important variation was introduced by Picet and Gams, which eliminates the dehydrogenation step. The classical synthesis of papaverine by Pictet and Gams is discussed.

Keywords:

  • Bischler Napieralski reaction;
  • 3,4-dihydroisoquinolines;
  • cyclization;
  • ring closure;
  • side reactions;
  • condensing agents;
  • related compounds