Pomeranz—Fritsch synthesis

Poly (vinyl pyrrol idones) polymerization, 1, 271 Polyviologens synthesis, 1, 286 Pomeranz-Fritsch synthesis isoqutnolines, 2, 428 6, 218 Pongapin synthesis, 4, 710 Poranthericine, 4, 494 ( )-Porantherine synthesis, 2, 377 Porphin, 4, 386 structure, 4, 378 Porphin, mcso-aryltri-p-tolyl-synthesis, 4, 230 Porphin, mcso-tetraalkyl-synthesis, 4, 230 Porphin, mcso-tetraaryl-synthesis, 4, 230 Porphin, mcso-tetraferrocenyl-synthesis, 4, 230 Porphin, meso-tetraphenyl-synthesis, 7, 767 Porphobilinogen biosynthesis, 1, 100... 

Through a slight modification the Pomeranz-Fritsch synthesis can be made particularly useful for the preparation of 1,2-dihydroisoquinolines. The imine is first reduced with sodium borohydride in 98% ethanol to the corresponding benzylamine, prior to cyclization, by treatment with 6 M hydrochloric acid. When electron-donating groups (such as a methoxyl) are present in the aromatic unit of the benzylamine, the ring-... 

An advantage of the modified Pomeranz-Fritsch synthesis is that the 1,2-dihydroisoquinolines can be reacted in situ with electrophiles, yielding 1,4-dihydroisoquinolinium salts that react with nucleophiles at C-3 (see Section 3.3.3). Such a single pot procedure can be used to form complex 1,2,3,4-tetrahydroisoquinolines. 

A modification of the Pomeranz-Fritsch synthesis <1983JCXI3344> is used in the preparation of thieno[2,3- l-pyridine and its 2-substituted derivatives. An aryl aldehyde undergoes condensation with aminoacetaldehyde dimethyl acetal giving a Schiff base which cyclizes to form an imine product. The imine is treated with ethyl chloroformate followed by triethyl phosphate to form an intermediate carbonate-phosphonate, which then cyclizes to the thienopyr-idine product (Scheme 22) <2004S1935>. Very low product yields (2-17%) are obtained for alkyl- and phenyl-substituted thieno[2,3- ]pyridines however, the unsubstituted product and 2-halogenated derivatives give moderate yields (28-44%). 

Pomeranz-Fritsch Synthesis. Isoquinolines are available from the cyclization of benzalaminoacetals under acidic conditions. 

Numerous modifications to the Pomeranz-Fritsch synthesis of isoquinolines have been studied over the years without much success.42 Some of these cyclizations, had they been successful, would have generated 1,2-dihydroisoquinolines it is possible, at least in some cases, that the overall sequence failed because the conditions of cyclization were too harsh for the 1,2-dihydroisoquinolines formed to survive. 

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. 

The second route [Eqs. (18) and (19)] involves the condensation of a benzylamine with glyoxal semiacetal. This was devised by Schlittler and Muller41 as an improvement on the Pomeranz-Fritsch synthesis.1... 

Hirsenkorn, R. Short-cut in the Pomeranz-Fritsch synthesis of 1-benzylisoquinolines short and efficient syntheses of norreticuline derivatives and of papaverine. Tetrahedron Lett. 1991, 32,1775-1778. 

Arylaldehydes react with aminoacetaldehyde acetals to give isoquinolines Pomeranz-Fritsch synthesis) ... 

The Pomeranz-Fritsch synthesis is normally carried out in two stages. Firstly, an aryl aldehyde is condensed with aminoacetal to form an aryl aldimine. This stage proceeds in high yield under mild conditions. Secondly the aldimine is cyclised by treatment with strong acid hydrolysis of the imine competes and reduces the efficiency of this step and for this reason trifluoroacetic acid with boron trifluoride is a useful reagent. ... 

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. ... 

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. 

---