The reactivity of vinyl compounds as alkylating agents

The reactions of 4-(p-nitrobenzyl)pyridine (a trap for alkylating agents with nucleophilicity similar to that of DNA) with the vinyl compounds acrylonitrile, acrylamide, acrylic acid, and acrolein, which can act as alkylating agents of DNA, were investigated. The following conclusions were drawn: (1) vinyl compounds show an alkylating capacity on 4-(p-nitrobenzyl) pyridine. The sequence of the alkylating potential was found to be acrylonitrile > acrylamide > acrylic acid > acrolein (alkylation with acrolein was not observed after 3 weeks). The formation of adducts with acrylonitrile was approximately 10- and 100-fold faster than with acrylamide and acrylic acid, respectively, which is consistent with its highly carcinogenic and mutagenic activity. (2) 4-(p-Nitrobenzyl)pyridine alkylation reactions by vinyl compounds occur through an enthalpy-controlled Michael addition mechanism. The values for the free energy of activation for these reactions with 4-(p-nitrobenzyl)pyridine were: Δ†G° (37 °C) acrylonitrile, 98 ± 1 kJ mol ^-1; acrylamide, 105 ± 2 kJ mol ^-1; acrylic acid, 109 ± 1 kJ mol ^-1. (3) Application of Hammett treatment to the kinetic results revealed that these alkylation reactions occur through nucleophilic attack, being moderately accelerated by electron-withdrawing groups.