Protonation of the Pyrimidine Ring at the C(5) Position:  Formation of a Stable Cationic σ-Complex

Abstract

NMR studies showed that, in addition to the expected N(1) protonation, 2,4,6-pyrimidinetriamine, N,N,N',N',N",N"-hexamethyl- (1) could also be protonated at the C(5) position in water, leading to an equilibrium between the C(5) and N(1) protonated forms. Analysis of the NMR titration data gives 6.87 and 6.89 for the pK(a) of the C(5) and N(1) protonation equilibria. Moreover, the reaction of 1 with chloroacetyl chloride leads to a novel 1,1-bis(pyrimidin-5-yl)-2-chloroethene type derivative (4) that is, peculiarly, fully monoprotonated at the C(5) position in either of the pyrimidine rings, forming a stable cationic sigma-complex.

Carbon‐protonation of the pyrimidine ring: The story of a small molecule NMR problem

“…Elemental analysis and MS experiments showed that the anion is chlorine (1). We could rationalize the chemical formation of compound 16 and explained the observed carbon protonation by means of geometrical and electronic factors (1).…”

“…Therefore, by excluding accidental isochrony, the rotation of these dimethylamino groups should be fast in unit A and slow in unit B on the NMR chemical shift timescale. Based on the foregoing symmetry considerations, the 12H-intensity minor and major 1 H methyl signals at ␦ 2.78 and ␦ 2.79 can be assigned to the Me 2 N(4,6) …”

“…This compound was obtained quite unintentionally in a routine acylation reaction and its structure, as revealed by NMR, has opened up unexpected new vistas of the protonation of pyrimidines. Although the scientific results and implications of this project were documented thoroughly in a recent publication (1), some intriguing and instructive elements of the discovery process have remained untold. For example, although our previous work (1) gives the data and the reasoning necessary to substantiate our scientific results, it makes no mention of structures that were, in fact, temporarily regarded by us as the likely structures before arriving at the correct structure.…”

“…Although the scientific results and implications of this project were documented thoroughly in a recent publication (1), some intriguing and instructive elements of the discovery process have remained untold. For example, although our previous work (1) gives the data and the reasoning necessary to substantiate our scientific results, it makes no mention of structures that were, in fact, temporarily regarded by us as the likely structures before arriving at the correct structure. Those aspects of the project, together with other plausible hypotheses that were rejected and/or refined along the way, have scientific and didactic values in their own right but are obviously off-key from the standpoint of a pure research journal.…”

“…For more on the chemical and experimental details of this project the reader is referred to Ref. (1).…”