Pomeranz-Fritsch reaction

What is Pomeranz-Fritsch reaction?

The Pomeranz-Fritsch reaction was reported in 1893 by Pomeranz and Fritsch, and involves the acid-promoted electrophilic cyclization of benzalaminoacetals derived from aromatic aldehydes and aminoacetals to produce isoquinolines.

This reaction is also known as the Pomeranz-Fritsch isoquinoline synthesis, Pomeranz-Fritsch cyclization, Pomeranz-Fritsch ring closure, Pomeranz-Fritsch ring synthesis, or Pomeranz-Fritsch synthesis.

Pomeranz-Fritsch reaction - general reaction scheme - Pomeranz-Fritsch isoquinoline synthesis - Pomeranz-Fritsch cyclization - Pomeranz-Fritsch ring closure - Pomeranz-Fritsch ring synthesis - Pomeranz-Fritsch synthesis
Pomeranz-Fritsch reaction

= Me, Et, etc. (see list of acronyms)

The Pomeranz-Fritsch reaction is favored by electron-donating substituents on the benzalaminoacetal and usually occurs at the para-position of the electron-donating group, although both para– and ortho-positions are available. When an electron-withdrawing group, such as a nitro group, is present, oxazoles are formed instead of isoquinolines.

Acid promoters used in this reaction include hydrochloric acid, methanesulfonic acid, orthophosphoric acid, perchloric acid, polyphosphoric acid, sulfuric acid H2SO4, triflic acid, trifluoroacetic acid, and BF3 in trifluoroacetic anhydride. However, the traditional Pomeranz-Fritsch reaction gives low yields of isoquinolines, which may be due to steric and electronic effects and partial deactivation of the phenyl ring by the formation of a protonated imino group.

As a result, several modifications of the reaction have been developed, such as the Bobbitt modification, Fischer modification, Jackson modification, and Schlittler-Müller modification. The Fischer modification involves the treatment of benzalaminoacetal with fuming sulfuric acid, while the Bobbitt modification produces tetrahydroisoquinoline derivatives through the hydrogenation of an imine intermediate. The Schlittler-Müller modification involves the use of benzyl amines and glyoxal semiacetal to prepare benzalaminoacetal.

The Pomeranz-Fritsch reaction has also been extended to prepare other types of aromatic heterocycles, such as thieno[2,3-c] and thieno[3,2-c]pyridines by intromolecular cyclization to the thiophene ring.

References

  • Pomeranz, C., Monatsh., 1893, 14, 116
  • Fritsch, P., Ber., 1893, 26, 419
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