Guareschi-Thorpe pyridine synthesis

The Guareschi-Thorpe pyridine synthesis is closely related to the Hantzsch protocol. The primary point of difference lies in the use of cyanoacetic esters. This modification assembles pyridine 23 by the condensation of acetoacetic esters 21 with cyanoacetic esters 22 in the presence of ammonia. A second variation of this method involves reaction of cyanoacetic ester 22 with P-diketone 24 in the presence of ammonia to generate the 2-hydroxypyridine 25. 

Mechanistically, one could envision a process initiated by ester/amide exchange brought about by the cyanoacetic ester with ammonia (22 27). Amide 27 could then 

Guareschi imides are useful synthetic intermediates. They are formed from a ketone reacting with two equivalents of the cyanoacetic esters and ammonia. This transformation is illustrated in the formation of 4,4-dimethylcyclopentenone 30.The synthesis was initiated with the Guareschi reaction of 3-pentanone 27 with 28 to generate imide 29. This product was hydrolyzed to the diacid and esterified. Cyclization of the diester via acyloin condensation followed by hydrolysis and dehydration afforded the desired target 30. 

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Galatsis, P. Guareschi-Thorpe Pyridine Synthesis In Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, 307—308. (Review). 

When using cyanoacetic esters instead of aldehydes, the Guareschi-Thorpe pyridine synthesis assembles pyridines 155 by the condensation of acetoacetic esters 153 with cyanoacetic esters 154 in the presence of ammonia. A variation of this method involves the reaction of cyanoacetic ester 156 with 3-diketone 157 in the presence of ammonia to generate 2-hydroxypyridine 158." The mechanism of this reaction has been studied, and it was initiated by an ester/amide exchange on cyanoacetic ester 156 with... 

Other references related to the Guareschi-Thorpe pyridine synthesis are cited in the Hterature. ... 

This reaction is related to the Guareschi-Thorpe Pyridine Synthesis, Chichibabin Pyridine Synthesis, KrOhnke Pyridine Synthesis, and Petrenko-Kritschenko Piperidone Synthesis. 

Guareschi-Thorpe pyridine synthesis Chichibabin (Tschitschibabin) pyridine synthesis Bohlmann-Rahtz pyridine synthesis Krohnke pyridine synthesis... 

Guareschi-Thorpe condensation. Synthesis of pyridine derivatives by condensation of cyanoa-cetic ester with acetoacetic ester in the presence of ammonia. In a second type of synthesis, a mixture of... 

This reaction is related to the Chichibabin Pyridine Synthesis Guareschi-Thorpe Condensation, and Hantzsch Dihydropyridine Synthesis. 

Early review F. Krohnke, Synthesis 1976, 1-24. Synthetic applications J. N. Chatteijea et al, Indian J. Chem. 15B, 430 (1977) G. R. Newkome etal, J. Org. Chem. 51, 850 (1986) P. Lhotak, A. Kurfiirst, Coll. Czech. Chem. Commun. 57,1937 (1992) T. R. Kelly et al, J. Org. Chem. 62, 2774 (1997). Cf. Chichibabin Pyridine Synthesis Guareschi-Thorpe Condensation Hantzsh (Dihydro)Pyridine Synthesis. 

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