A versatile synthesis of pyrazolo 3,4-c isoquinoline derivatives by reaction of 4-aryl-5-aminopyrazoles with aryl/heteroaryl aldehydes: the effect of the heterocycle on the reaction pathways

Bogza, S.L.; Kobrakov, K.I.; Malienko, A.A.; Perepichka, I.F.; Sujkov, S.Y.; Bryce, M.R.; Lyubchik, S.B.; Batsanov, A.S.; Bogdan, N.M.

Abstract

The reaction of 4-(3,4-dimethoxyphenyl)-5-aminopyrazoles 7A-D with aromatic and heterocyclic aldehydes in strong acidic media (trifluoroacetic or formic acid) has been studied. The initial azomethine derivatives 8 undergo cyclization similar to the Pictet-Spengler condensation to form the intermediate 4,5-dihydroisoquinolines 9 which readily dehydrogenate giving 5-aryl(heteroaryl)-pyrazolo[3,4-c]isoquinoline derivatives 10 as the final products. Whereas for benzaldehyde and its derivatives this one-pot synthesis presents a convenient general route to 5-aryl-pyrazolo[3,4-c]isoquinolines 10, in the case of heterocyclic aldehydes the product structure varies markedly with the structure of the aldehyde used: (i) 3-pyridyl-, 3-quinolyl-, 3-thienyl-, and 1,2,3-thiadiazolyl-5carboxaldehydes give 5-heteroarylpyrazolo[3,4-c]isoquinolines; (ii) 1-methylbenzimidazolyl-2-carboxaldehyde gives only intermediate azomethine 8Dh, which does not cyclize; (iii) 1-R-3-indolylcarboxaldehydes(R = H, CH3, CH2Ph) eliminate the heteroaryl fragment resulting in 5-unsubstituted pyrazolo [ 3,4- c] isoquinolines 11. Thienyl-2carboxaldehyde reacts by both pathways ( i) and ( iii) depending on the reaction conditions. The single crystal X-ray structures for 10Dj, 10Cd and 11D provide confirmation of the different types of products formed in these reactions. Mechanisms which explain these transformations are presented.

Citation

Bogza, S., Kobrakov, K., Malienko, A., Perepichka, I., Sujkov, S., Bryce, M., …Bogdan, N. (2005). A versatile synthesis of pyrazolo 3,4-c isoquinoline derivatives by reaction of 4-aryl-5-aminopyrazoles with aryl/heteroaryl aldehydes: the effect of the heterocycle on the reaction pathways. Organic and Biomolecular Chemistry, 3(5), 932-940

• Journal Article Type: Article
• Publication Date: 2005
• Journal: Organic and Biomolecular Chemistry
• Print ISSN: 1477-0520
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 5
• Pages: 932-940
• Public URL: https://durham-repository.worktribe.com/output/1603511