Vitae (Jul 2010)
EXPERIMENTAL AND THEORETICAL STUDY OF SHYNTESIS OF N-ALKYL-NITROIMIDAZOLES.
Abstract
In this work we realized and experimental and theoretical study of the N-alkylation of nitroimidazoles.The N-alkyl-2-methyl-nitroimidazoles correspond to biologically active molecules, obtained by reactionof 2-methyl-5-nitroimidazole and different alkyl halides. This reaction showed the formation of a mixtureof isomeric products in different proportions, denominated like N-alkyl-2-methyl-4-nitroimidazole andN-alkyl-2-methyl-5-nitroimidazole, respectively. The reaction suggestes the formation of a tautomericequilibrium, which generates two nucleophilic sites susceptible to electrophilic attack by the alkyl halide.The local nucleophilic reactivity of the nitroimidazole ring is determined using local reactivity indices suchas the Fukui function and the electrostatic potential, besides the electronic localization function (ELF). TheFukui function was integrated for each atom using partition schemes based on analysis of Mulliken chargesand natural bond orbital (NBO). Finally the reaction profiles were assessed. The results show a minordifference in the local reactivity. Nevertheless a significant difference in energy barriers is observed explainingthe formation of an isomeric product over another. These results agree quite well with the experimental data.
