Theoretical Study of theRegioselectivity of the Interaction of 3-Methyl-4-pyrimidoneand 1-Methyl-2-pyrimidone with Lewis Acids.

A density functional theory (DFT) study is performedto determine the stability of the complexes formed between eitherthe N or O site of 3-methyl-4-pyrimidone and 1-methyl-2-pyrimidonemolecules and different ligands. The studied ligands are boron andalkali Lewis acids, namely, B(CH3)3, HB(CH3)2, H2B(CH3), BH3, H2BF, HBF2, BF3, Li+, Na+, and K+. The acids are divided into twogroups according to their hardness. The reactivity predictions, accordingto the molecular electrostatic potential (MEP) map and the naturalbond orbital (NBO) analysis, are in agreement with the calculatedrelative stabilities. Our findings reveal a strong regioselectivitywith borane and its derivatives preferring the nitrogen site in bothpyrimidone isomers, while a preference for oxygen is observed forthe alkali acids in the 3-methyl-4-pyrimidone molecule. The complexationof 1-methyl-2-pyrimidone with these hard alkali acids does not showany discrimination between the two sites due to the presence of acontinuous delocalized density region between the nitrogen and theoxygen atoms. The preference of boron Lewis acids toward the N siteis due to the stronger B–N bond as compared to the B–Obond. The influence of fluorine or methyl substitution on the boronatom is discussed through natural orbital analysis (NBO) concentratingon the overlap of the boron empty p-orbital with the F lone pairsand methyl hyperconjugation, respectively. The electrophilicity ofthe boron acids gives a good overall picture of the interaction capabilitieswith the Lewis base. [ABSTRACT FROM AUTHOR]