TY - JOUR
T1 - A versatile synthesis of pyrazolo[3,4-c]isoquinoline derivatives by reaction of 4-aryl-5-aminopyrazoles with aryl/heteroaryl aldehydes
T2 - The effect of the heterocycle on the reaction pathways
AU - Bogza, Sergei L.
AU - Kobrakov, Konstantin I.
AU - Malienko, Anna A.
AU - Perepichka, Igor F.
AU - Sujkov, Sergei Yu
AU - Bryce, Martin R.
AU - Lyubchik, Svetlana B.
AU - Batsanov, Andrei S.
AU - Bogdan, Natalya M.
PY - 2005/3/7
Y1 - 2005/3/7
N2 - 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 l,2,3-thiadiazolyl-5-carboxaldehydes give 5-heteroarylpyrazolo[3,4-c] isoquinolines; (ii) l-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-2-carboxaldehyde 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.
AB - 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 l,2,3-thiadiazolyl-5-carboxaldehydes give 5-heteroarylpyrazolo[3,4-c] isoquinolines; (ii) l-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-2-carboxaldehyde 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.
UR - http://www.scopus.com/inward/record.url?scp=15244338794&partnerID=8YFLogxK
U2 - 10.1039/b417002d
DO - 10.1039/b417002d
M3 - Article
C2 - 15731881
AN - SCOPUS:15244338794
SN - 1477-0520
VL - 3
SP - 932
EP - 940
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 5
ER -