Hydrogen-bond basicity pKHB scale of six-membered aromatic N-heterocycles

Abstract

Using 4-fluorophenol as a reference hydrogen-bond donor, equilibrium constants, K_f, for the formation of 1∶1 hydrogen-bonded complexes have been obtained by FTIR spectrometry for 65 six-membered N-heteroaromatics of widely differing structures, in CCl₄ at 298 K. The pK_HB scale shows that most N_sp² bases are weaker hydrogen-bond bases than many oxygen bases. This scale extends from the hypobasic pentafluoropyridine, illustrating the electron-withdrawing field effect of fluoro substituents, to push–pull 4-NR₂-pyridines, illustrating the resonance effect of the 4-NR₂ substituents which donate electrons in the order NH₂ < piperidino < NMe₂ < NEt₂ < pyrrolidino. A spectroscopic scale is constructed from the IR frequency shift Δν(OH) of methanol hydrogen-bonded to N-heteroaromatics. The thermodynamic pK_HB scale correlates with the Δν(OH) scale, but 2-substituted pyridines deviate markedly. These deviations are attributed to, and allow the semi-quantitative determination of: (i) steric effects, most important in 7,8-benzoquinoline; (ii) lone pair–lone pair repulsions, most important in 1,2-diazines; and (iii) lone pair–bond pair repulsions, most important in 2,6-difluoropyridine. IR spectra show the fixation of 4-fluorophenol to the nitrile nitrogen of 2-, 3- and 4-cyanopyridines, to the carbonyl oxygen of 3-COOMe, 3-COPh and 4-COMe-pyridines, and to the ether oxygen of 2-methoxypyridine, in addition to the fixation to the pyridine nitrogen. A cyclic complex, with both NH· · ·O and OH· · ·N hydrogen bonds, is formed with 2-amino- and 2-methylamino-pyridines.