The acidities of exocyclic amino groups in Heteroaromatic systems
Creators: name: Harris, Madeleine Gibson
Publisher: name: University of British Columbia
Year: 2010

description: The acidities of 37 amino-substituted heterocyclic compounds have been determined using measurements of degree of ionization in DMSO/ water/0.011 M hydroxide ion and recently developed extrapolative procedures which are based on the Bunnett-Olseh (B.O.) and the Marziano-Cimino-Passerini (M.C.P.) methods. The compounds studied include 19 aminopyridines and pyrimidines and 18 derivatives of the biologically important nucleotide bases, cytosine, adenine and guanine. The UV/vis spectra of the neutral and anionic forms of the amino-pyridines and pyrimidines are well separated so that in evaluating the ionization ratios, changes of the spectra with medium composition were accounted for by measuring at the wavelength of maximum anionic absorption in each solution and by assuming that eA- and eHA vary linearly with HN . For the majority of the nucleotide derivatives, the neutral and anionic spectra were closely overlapping although different in shape. The ionization ratios were best evaluated by using the area under the spectral curve; spectral changes with solvent composition were accounted for by an adaptation of the method described above. Ionization ratios evaluated by the area method agreed well with those calculated by other methods as long as the anionic area was at least one and one-half times as great as the neutral area (or vice versa). The aminopyrimidines and purines define a new acidity function Hp . This function covers the range from water to 87.6 mole % DMSO and was established using 15 aminopyrimidines and purines. When Hp plotted against mole % DMSO, it rises less steeply than HN. This has been attributed to less extensive derealization of charge in the aminopyrimidine anion relative to that of an aniline (usually a nitroaniline) ionizing at the same solvent composition. The B.O. pKHA values of unsubstituted 2- and 4-aminopyridine, 2- and 4-aminopyrimidine and 2-amino-s-triazine, ranging from 23.50 to 14.91 are well-correlated by a Hammett plot using a values recently established for aza substituents and assuming the additivity of aza substituent effects, p. 4.99. The B.O. pKHA values of five substituted anilines, ranging from 25.50 to 23.13, fall close to this plot. All ten compounds are accommodated by a straight line, p value 5.10, which suggests that the aminoheterocycles may be considered to be aza-substituted anilines. It appears that the sensitivity of aniline and diphenylamine acidity to substituent effects is greater than previously believed. The findings in this work suggest that transmission of substituent effects through a heterocyclic and a benzene nucleus are equal and that an aza group may be regarded as a normal ring substituent. From the acidities of substituted aminopyridines and pyrimidines it appears that, to a first approximation, aza groups do not perturb the effects of other substituents on the same nucleus, although there may be a small resonance interaction between a +R group, such as chloro, and an aza group lying para to it. The same conclusion was reached from examination of the basicities of these compounds.