The pyridinium–dihydropyridine system. I. Synthesis of a series of substituted pyridinium ions and their 1,4-dihydro reduction products and a determination of their stabilities in aqueous buffers

Abstract

Fourteen pyridinium salts, substituted at the 1- and 3-positions, have been prepared and their stabilities determined in aqueous acetate and tris(hydroxymethyl)aminomethane (Tris) buffers. The 1,4-dihydro derivatives of eleven of these have been prepared and characterized and their stabilities likewise determined. The pyridinium ions are stable in acidic solution but undergo either ring attack or amide or ester hydrolysis under basic conditions, whereas the dihydropyridines undergo covalent hydration in acid solution. For only four pairs of compounds and one buffer system (Tris) are there pH-ranges in which the pyridinium and dihydropyridine forms are simultaneously stable (less than 10% decomposition in 24 h). These compounds have a carbamoyl or acetyl group at the 3-position and either a methoxymethyl, acetonyl, or carbamoylmethyl group at the 1-position. The acetic acid catalyzed rates of hydration of the 1-alkyl-3-carbamoyl-1,4-dihydropyridines are correlated by σ* values with a ρ* of −2.00, consistent with protonation being the rate-controlling step.