The substituent effect of π-electron delocalization in N-methylamino-nitropyridine derivatives: crystal structure and DFT calculations

The crystal and molecular structures of 3-(N-methylamino)-2-nitropyridine, 5-(N-methylamino)-2-nitropyridine and 2-(N-methylamino)-5-nitropyridine have been characterized by X-ray diffraction. To perform conformational analysis, the geometries of the compounds as well as their conformers and rotamers were optimized at the B3LYP/6-311++G(3df,3pd) level. The resulting data were used to analyze the π-electron delocalization effect in relation to the methylamino group rotation in ortho-, meta- and para-substitution positions. Quantitative aromaticity indices were calculated based on which we estimated the electronic structures of the analyzed compounds. The substituent effect of the methylamino and nitro groups was also characterized by related descriptors, i.e., charge of the Substituent Active Region (cSAR(X)) calculated based on the Hirshfeld charges and Substituent Effect Stabilization Energy (SESE). It has been shown that all the used parameters were found to be mutually interrelated with much better correlations for the meta- and para- than the ortho-derivatives. The rotation of the methylamino group relative to the aromatic fragment has an effect on the change in delocalization of the π-electrons of the pyridine ring. Relations between cSAR(NHCH3) and cSAR(NO2) show almost identical sensitivity of the substituent effect in meta- and para-substituted derivatives, whereas in ortho-substituted analogs, different kinds of intramolecular interactions have been revealed. Furthermore, the analyzed dependency of SESE values on the torsional angle of the methylamino group indicates that an increase in the electron-attracting power of the substituent leads to a decrease in energy.