Comparative kinetic studies on the synthesis of quinoxalinone derivatives and pyrido[2,3‐b]pyrazinone derivatives by the hinsberg reaction

Abstract

AbstractKinetic studies on the anelation of quinoxalinone derivatives 3a‐c and pyrido[2,3‐b]pyrazinone derivatives 5a‐c and 6a‐c synthesized by the Hinsberg reaction is reported. o‐Phenylenediamine or 2,3‐diaminopyridine were treated with bifunctional carbonyl compounds such as glyoxylic, pyruvic and benzoylformic acids under different experimental conditions. When pyridopyrazine derivatives were synthesized both position isomers were achieved applying regioselective reactions. Mixture were avoided by looking for special experimental conditions that led unambiguously to only one of the components of the classic “Hinsberg mixture”. Quinoxalinone derivatives 3a‐c were obtained at room temperature in good yields (>90%) using anhydrous methanol or ethanol as solvents. On the other hand, only pyrido[2,3‐b]pyrazin‐3(4H)‐one (5a) was regioselectively attained in aqueous buffer of pH 7 while 3‐methylpyridopyrazinone derivatives were regioselectively separated using anhydrous methanol for one isomer, 5b, and anhydrous chloroform for the other isomer, 6b, at room temperature. Yields were higher than 80%. Reactions with benzoylformic acid did not give good yields and only 2‐phenylpyrido[2,3‐b]pyrazin‐3(4H)‐one (5c) could be obtained using anhydrous chloroform (yield <30%) as the solvent. Steric hindrance exerted by the phenyl group of the benzoylformic acid is supposed to be responsible of our difficulties to obtain 2‐phenylpyrido[2,3‐b]pyrazin‐3(4H)‐one (5c) in good yields applying this technique. The other isomer, 3‐phenyl[2,3‐b]pyrazin‐2(1H)‐one (6c) was always formed together with the former isomer and could not be isolated from the mixture, when other solvents than chloroform were used as the reaction media.