Structure-reactivity correlation for the kinetics of the formation reaction of 4-(substituted phenyl)-1,4-dihydropyridines

Abstract

Quantitative structure-reactivity correlations for the kinetics of the Hantzsch synthesis of 4-(substituted phenyl)-1,4-dihydropyridines in the reaction between ethyl m- and p-substituted 2-benzylideneacetoacetate and the enamine (ethyl 3-aminocrotonate) was studied. The reaction kinetics was followed spectrophotometrically. It was found that the reaction correspond to second-order kinetics. Quantitative structure-reactivity correlations of log k were obtained with the corresponding substituent constants (s, s+, sI and s + ) using the Hammett and extended Hammett equation (dual substituent parameter, DSP, equation). They showed linear relationships with positive values of reaction constants (r). The obtained data were processed by linear regression analysis. It was confirmed that Michael addition of the enamine to benzylidene represented the slow step of the reaction with a high positive charge at the benzylidene molecule. MO calculations were performed and they were in agreement with the conclusions derived from the structure-reactivity correlations. .

Proučavan je kvantitativan odnos strukture i reaktivnosti za kinetiku Hančove sinteze supstituisanih 4-fenil-1,4-dihidropiridina u reakciji etil-m- i p-supstituisanih 2-benziliden-acetoacetata i enamina. Kinetika ispitivane reakcije je praćena spektrofotometrijskim metodom. Zapaženo je da je reč o reakciji drugog reda. Kvantitativne korelacije strukture i reaktivnosti koje izražavaju logaritam određene konstante brzine reakcije (log k) u zavisnosti od odgovarajućih konstanti supstituenata (s, s+,sI i s +) određene su za Hametovu (Hammett) i proširenu Hametovu jednačinu (DSP-jednačinu). Pokazale su linearnu zavisnost sa pozitivnim vrednostima nagiba, odnosno reakcione konstante (r). Time je potvrđeno da Majklova (Michael) adicija enamina na benziliden predstavlja spori stupanj u reakciji sa izraženim pozitivnim naelektrisanjem na molekulu benzilidena. MO proračuni su takođe urađeni i njihovi rezultati su bili u skladu sa zaključcima izvedenim iz korelacija strukture i reaktivnosti. .