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An influence of a basic side chain moiety on the tautomer ratio between the enamine and methylene imine forms in azole condensed quinoxalines
Author(s) -
Kurasawa Yoshihisa,
Matsumoto Yuko,
Ishikura Aiko,
Ikeda Kazue,
Hosaka Tomoyoshi,
Takada Atsushi,
Kim Ho Sik,
Okamoto Yoshihisa
Publication year - 1993
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570300545
Subject(s) - quinoxaline , chemistry , enamine , tautomer , trifluoroacetic acid , medicinal chemistry , moiety , methylene , imine , stereochemistry , organic chemistry , catalysis
The reaction of 7‐chloro‐4‐(2‐cyano‐2‐hydroxyvinyl)tetrazolo[1,5‐α]quinoxaline 2a with 4‐aminopyridine, p ‐toluidine or p ‐aminophenol gave 7‐chloro‐4‐(4‐pyridylcarbamoylmethylene)‐4,5‐dihydrotetrazolo[1,5‐α]‐quinoxaline 7a , 7‐chloro‐4‐( p ‐tolylcarbamoylmethylene)4, 5‐dihydrotetrazolo[1,5‐α]quinoxaline 8a or 7‐chloro‐4‐( p ‐hydroxyphenylcarbamoylmethylene)‐4,5‐dihydrotetrazolo[1,5‐α]quinoxaline 9a , respectively. The reaction of 7‐chloro‐4‐(2‐cyano‐2‐hydroxyvinyl)‐1,2,4‐triazolo[4,3‐α]quinoxaline 2b with 4‐aminopyridine, p ‐toluidine or p ‐aminophenol afforded 7‐chloro4‐(4‐pyridylcarbamoylmethylene)‐4,5‐dihydro‐1,2,4‐triazolo‐[4,3‐α]quinoxaline 7b , 7‐chloro‐4‐( p ‐tolylcarbamoylmethylene)‐4,5‐dihydro‐1,2,4‐triazolo[4,3‐α]quinoxaline 8b or 7‐chloro‐4‐( p ‐hydroxyphenylcarbamoylmethylene)‐4,5‐dihydro‐1,2,4‐triazolo[4,3‐α]quinoxaline 9b , respectively. The reaction of compound 2a with 2‐aminopyridine or 3‐aminopyridine provided 7‐chloro‐4‐(2‐pyridyl‐carbamoylmethylene)‐4,5‐dihydrotetrazolo[1,5‐α]quinoxaline 10 or 7‐chloro‐4‐(3‐pyridyl‐carbamoylmethylene)‐4,5‐dihydrotetrazolo[1,5‐α]quinoxaline 11 , respectively. Compounds 7a,b (4‐pyridylcarbamoyl) predominated as the enamine tautomer A in a trifluoroacetic acid solution, while compounds 8a,b ( p ‐tolylcarbamoyl) and compounds 9a,b ( p ‐hydroxyphenylcarbamoyl) coexisted as the enamine A and methylene imine B tautomers in a trifluoroacetic acid solution. Moreover, the ratio of the enamine tautomer A elevated in an order of compound 11 (3‐pyridylcarbamoyl), compound 10 (2‐pyridylcarbamoyl) and compound 7a (4‐pyridylcarbamoyl), reflecting an order of the increase in the pKa values of the aminopyridine side chain moieties. In general, the ratio of the enamine tautomer A was higher in the basic carbamoyl derivatives 7–11 than in the neutral ester derivatives 3a,b . From these results, the basic side chain moiety of the tetrazolo[1,5‐α]quinoxalines 7a‐11 or 1,2,4‐triazolo[4,3‐α]quinoxalines 7b‐9b was found to increase the ratio of the enamine tautomer A in trifluoroacetic acid media.