Theoretical Investigation of Reaction Pathways of 3-Methyloxadiazolinium Ion and 1,2,3-Oxadiazoline: Correlation with Experimental Findings

Quantum mechanical calculations were used to investigate the stability of the 3-methyloxadiazolinium ion and 1,2,3-oxadiazoline and to determine the most probable thermal decomposition pathway of the oxadiazoline. Ab initio RHF calculations were carried out at the 3-21G and 6-31G* basis set level to obtain the optimized SCF energies and geometries of these molecules, as well as that of the protonated 4,5-dihydro-2,3-oxadiazolidine. Only the N2-protonated oxadiazoline was found to be stable; the N1- and O-protonated oxadiazolines underwent immediate decomposition. Calculations on the oxadiazolinium ion confirmed experimental results regarding the most likely site of nucleophilic attach on the molecule. Sequential bond-stretching of the N-O, N-C, and O-C bonds of the optimized oxadiazoline molecule revealed that breakage of the N-O bond leading to diazomethane and formaldehyde was energetically the most favorable pathway at all levels of theory (energy of activation (E(a)) of 18.8 kcal/mol at the MP2/6-31G* level). This result is consistent with the experimental finding of methylation of DNA guanine by N-(2-hydroxyethyl)-N-nitrosomethylamine [C-14]-labeled in the ethyl group, which has been postulated to involve the oxadiazoline as the methylating agent. Breakage of the N-C bond led to nitrogen gas and acetaldehyde as products with an E(a) of 25.2 kcal/mol, while the stretching of the O-C bond led to the production of nitrous oxide and ethene with an E(a) of 28.8 kcal/mol. Breakage of the N-O bond in the N2-protonated oxadiazoline occurred with an E(a) of 40.0 kcal/mol, the least energetically favorable process. Optimized geometries and energies for the reactant, transition state, and product molecules were obtained at post Hartree-Fock using MP2 and QCISD, as well as the density functional code, DGauss. Comparison of the optimized geometries of the transition states from the three different bond-breakage processes revealed minor differences in these structures at the various levels of theory.