Isoquinoline ring Pomeranz-Fritsch

This reaction was first and concurrently reported by Pomeranz and Fritsch in 1893. It is the synthesis of isoquinolines via an acid-promoted electrophilic cyclization of benza-laminoacetals prepared from aromatic aldehydes and aminoacetals. Therefore, this reaction is known as the Pomeranz-Fritsch cycUzation, Pomeranz-Fritsch isoquinoline synthesis, Pomeranz-Fritsch reaction," Pomeranz-Fritsch ring closure, Pomeranz-Fritsch ring synthesis, or Pomeranz-Fritsch synthesis. ... 

Of the well-known methods to prepare isoquinolines, including the Pictet-Spengler and Bischler-Napieralski cyclisation, the Pomeranz-Fritsch reaction is the only direct generally accepted method for the construction of the fully unsaturated isoquinoline ring system. 

The Pomeranz-Fritsch synthesis of isoquinolines from the acetals (286) often gives oxazoles as by-products. Isoquinoline formation is favoured by the presence of electronreleasing groups in the benzene ring and suppressed when the ring is deactivated. Nitroaryl-methylene compounds (286 X = NOz), for example, give only oxazoles (equation 102). 

The Pomeranz-Fritsch synthesis [Eqs. (1) and (2)]1 is the only isoquinoline synthesis involving a simple two-step sequence from common starting materials. Furthermore, it is one of the few methods which can be used to prepare isoquinolines substituted in the 7- and 8-positions. The first step, Schiff base formation [Eq. (1)], takes place readily, but the ring closure [Eq. (2)] is difficult. The yields vary markedly with the concentration of H2S04 and are generally low. Frequently the reaction fails completely. Most of the work described in this chapter was undertaken to circumvent these problems and to realize the potential promise of the synthesis. 

Electrophilic cyclisation, in which the heterocyclic ring is formed in the manner of the Pomeranz-Fritsch isoquinoline synthesis, offers a potential route to benzoisoquinolines. Cyclisation of the N-2-... 

Tetrahydroisoquinoline ring from glycosamines Pomeranz-Fritsch-type isoquinoline ring closure... 

Numerous classical isoquinoline syntheses utilize intramolecular SeAr reactions for the construction of the hetero ring. Among them are the Bischler-Napiehaiski synthesis, the Pictet-Gams and Pictet-Spengler syntheses, and the Pomeranz-Fritsch synthesis. 

Polysulfides s. Trisulfides Pomeranz-Fritsch isoquinoline ring closure 27, 940 Position shift (s. a. Interchange, positional, Migration, Rearrangement)... 

Benzylideneaminoacetoaldehyde acetals prepared from benzaldehydes have been key intermediates of a well-established method for isoquinoline synthesis known as the Pomeranz-Fritsch reaction (Scheme 16, route a) [49,50], Intramolecular cycliza-tion of this type of imines under acidic conditions provided isoquinolines, where the two-carbon substituent on the nitrogen atom was transformed into a part of the isoquinoline ring. For the synthesis of 8-fluoroisoquinohne, the application of the standard procedure gave a low yield of the desired product (3 % in two steps from 2-fluorobenzaldehyde) [51]. However, in the modified procedure using ethyl chloro-formate, trimethyl phosphite, and titanium tetrachloride for the cyclization step [52] provided 6-fluoroisoquinoline from 4-fluorobenzaldehyde in 34 % overall yield (Scheme 17) [25],... 

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