AN INFLUENCE OF A BASIC SIDE-CHAIN MOIETY ON THE TAUTOMER RATIO BETWEEN THE ENAMINE AND METHYLENE IMINE FORMS IN AZOLE CONDENSED QUINOXALINES

The reaction of ano-2-hydroxyvinyl)tetrazolo[1,5-alpha]quinoxaline 2a with 4-aminopyridine, p-toluidine or p-aminophenol gave ylene)-4,5-dih ydrotetrazolo[1,5-alpha]-quinoxaline 7a, hylene)-4,5-dihydrotetrazolo[ 1,5-alpha]quinoxaline 8a or -chloro-4-(p-hydroxyphenylcarbamoylmethyle ne)-4,5- dihydrotetrazolo[1,5-alpha]quinoxaline 9a, respectively. The reaction of hydroxyvinyl)-1,2,4-triazolo[4,3-alpha]quinoxaline 2b with 4-aminopyridine, p-toluidine or p-aminophenol afforded -4,5-dihydro-1 ,2,4-triazolo-[4,3-alpha]quinoxaline 7b, )-4,5-dihydro-1,2,4-triazolo[ 4,3-alpha]quinoxaline 8b or )-4,5-dihydro-1,2,4-triazolo[4,3-alpha]qui noxaline 9b, respectively. The reaction of compound 2a with 2-aminopyr idine or 3-aminopyridine provided 2-pyridyl-carbamoylmethylene)-4,5-di hydrotetrazolo [1,5-alpha]quinoxaline 10 or 7-chloro-4-(3-pyridylcarba moylmethylene)- 4,5-dihydrotetrazolo[1,5-alpha]quinoxaline 11, respect ively. 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) coexist ed as the enamine A and methylene imine B tautomers in a trifluoroacet ic acid solution. Moreover, the ratio of the enamine tautomer A elevat ed in an order of compound 11 (3-pyridylcarbamoyl), compound 10 (2-pyr idylcarbamoyl) and compound 7a (4-pyridylcarbamoyl), reflecting an ord er of the increase in the pKa values of the aminopyridine side chain m oieties. In general, the ratio of the enamine tautomer A was higher in the basic carbamoyl derivatives 7-11 than in the neutral ester deriva tives 3a,b. From these results, the basic side chain moiety of the tet razolo[1,5-alpha]quinoxalines 7a-11 or 1,2,4-triazolo[4,3-alpha]quinox alines 7b-9b was found to increase the ratio of the enamine tautomer A in trifluoroacetic acid media.