Purine analogues. I. The status of Hückel molecular orbital calculations as predictors of proton shifts, basic strengths, and reactivity

Abstract

A detailed series of n~olecular orbital calculations based on the HMO method lias been made for the various possible ionic species of purine, pyrazolo(3,4-d)pyrirnidine, v-triazolo(4,5-d)pyrimidine, and pyrazolo(3,4-b)pyridine. rt-Electron densities and localization and delocalization energies for nucleophilic substitution have been derived.The results are compared with the observed proton chemical shifts in the conjugate acids of these n~olecules, with the relative rates of nucleophilic piperidinodehalogenations in the neutral molecules, and with the ionization constants.It is concluded that it is possible to reconcile the calculations with experimental results for the various positions within a six-membered ring, but that positions in six-and five-membered rings cannot be directly compared. The electron densities seem to be of little value in correlating the observed ionization patterns of purines and their analogues.Canadian Journal of Chemistry, 47, 1129Chemistry, 47, (1969 Introduction As a consequence of their involvement as determinants of biological processes, the purine components of nucleic acids and their analogues have received much attention from synthetic organic chemists (1, 2) and from quantum chemists (3). However, there is little constructive interaction between the two groups: uncritical applications of molecular orbital (MO) calculations by synthetic chemists (4) often suggest that the calculations have little value, while defences of the value of simple MO treatments (5, 6) often quote irrelevant or incorrect supporting data. In this paper, we seek to show where simple MO calculations on appropriate ionic species of purines and their analogues are of correlative or predictive value, and also to indicate areas where the simple approach gives predictions at variance with experimental facts.We have chosen three areas where detailed comparisons between theory and experiment are possible: calculated n-electron densities and

Pyrazolo[3,4-b]pyridines: Syntheses, reactions, and nuclear magnetic resonance spectra

“…Our interest in synthesis and reactivity of the parent compound and its substitution products arises from promise shown as inhibitors of xanthine oxidases (27). A minor portion of our work has been reported in another study of purine analogues (28), and we have also described the synthesis of the parent system by rearrangement accompanying decarboxylation of pyrazolo[l,5-alpyrimidine carboxylic acids (29).…”

Electronic Absorption Spectra of Some Triazolopyrimidine Derivatives

“…A detailed series of MO studies at the HMO level have been carried out on purines, pyrazolopyrimidines, triazolopyrimidines, and pyrazolopyrimidines [14][15][16]. The aim of such qualitative MO calculation is to ascertain the extent of aromaticity in the studied compounds.…”

Novos derivados do sistema heterocíclico 1H-pirazolo[3,4-b]piridina: síntese e assinalamentos de hidrogênios e carbonos por RMN 1D e 2D

“…A literatura relata que alguns desses derivados se apresentam como novos e promissores antimetabólitos purínicos ou pirimidínicos 4 . Substâncias do tipo 2, foram sintetizadas como análogos mais ativos do alopurinol, 3, utilizado no tratamento clínico da "gota", como inibidor da xantina oxidase 5 e, na quimioterapia de alguns tumores 3,6 , enquanto que o derivado 4, apresenta atividade ansiolítica e anticonvulsivante 7 .…”