Carbon Protonation of 2,4,6-Triaminopyrimidines:  Synthesis, NMR Studies, and Theoretical Calculations

• Published in: Journal of organic chemistry 2006-06, Vol.71 (13), p.4910-4918
• Main Authors: NMETH, Balazs, WEBER, Csaba, VESZPREMI, Tamas, GATI, Tamas, DEMETER, Adam
• Format: Article
• Language: English
• Subjects: Carbon - chemistry; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Magnetic Resonance Spectroscopy - methods; Magnetic Resonance Spectroscopy - standards; Molecular Structure; Organic chemistry; Preparations and properties; Protons; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Quantum Theory; Reference Standards; Sensitivity and Specificity
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0605703

Several C(5)-substituted 2,4,6-triaminopyrimidine derivatives and their HBF4 salts were synthesized to study the carbon protonation of the pyrimidine ring. NMR investigations in DMSO-d 6 prove experimentally that, in addition to the usual protonation at N(1), the compounds can be protonated at C(5) as well. We present several new stable cationic σ-complexes in the pyrimidine series, where C(5) protonation predominates over N(1) protonation. Quantum chemical calculations using the B3LYP/cc-pVDZ method were utilized in the gas phase and also in DMSO solvent with the polarized continuum model (PCM) method to rationalize the observed protonation behavior. Results of the calculations accord with the experimental observations and prove that combined steric and electronic effects are responsible for the observed C(5) protonation and for σ-complex stability. We demonstrate that C(5) protonation is a general feature of the 2,4,6-triaminopyrimidine system.