Pomeranz-Fritsch Reaction – a heterocycle formation reaction

In 1893, C. Pomeranz and P. Fritsch independently described a new synthesis of isoquinoline. This was prepared by heating a benzalaminoacetal generated through the condensation of benzaldehyde and 2,2-diethoxyethylamine in concentrated sulfuric acid.

Over the course of that decade, the authors used this technique to create a broad range of structurally diverse isoquinolines. From then on, the acid-catalyzed cyclization of benzalaminoacetals (Schiff bases) to give substituted isoquinolines has been known as the Pomeranz-Fritsch reaction.

Two of the more important modifications are:

  1. the Schlittler-Muller modification, where a substituted benzylamine is condensed with glyoxal hemiacetal to provide the corresponding C1-substituted isoquinoline

  2. the Bobbitt-modification, where hydrogenation of the benzalaminoacetal and subsequent acid-catalyzed cyclization of the resulting amine generates a tetrahydroisoquinoline

Mechanism of the Pomeranz-Fritsch reaction

Review available Thermo Scientific products for the Pomeranz-Fritsch reaction: