Thermodynamic Parameters of Elementary Steps for 3,5-Disubstituted 1,4-Dihydropyridines To Release Hydride Anions in Acetonitrile.

Abstract

A series of 3,5-disubstituted 1,4-dihydropyridine derivatives including the derivative with two chiral centers, 6H (R2 = CH3, CH2Ph), as a new type of organic hydride source were synthesized and characterized. The thermodynamic driving forces (defined as enthalpy changes or standard redox potentials) of the 6 elementary steps for the organic hydrides to release hydride ions in acetonitrile were measured by isothermal titration calorimetry and electrochemical methods. The impacts of the substituents and functional groups bearing the N1 and C3/C5 positions on the thermodynamic driving forces of the 6 elementary steps were examined and analyzed. Moreover, the results showed that the reaction mechanism between the chiral organic hydride and activated ketone (ethyl benzoylformate) was identified as the concerted hydride transfer pathway based on the thermodynamic analysis platform. These valuable and crucial thermodynamic parameters will provide a broadly beneficial impact on the applications of 3,5-disubstituted 1,4-dihydropyridine derivatives in organic synthesis and pharmaceutical chemistry.