Calculated tautomeric equilibria and X-ray structures of 2-substituted N-methoxy-9-methyl-9H-purin-6-amines
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Density Functional Theory calculations of nine 2-substituted N-methoxy-9-methyl-9H-purin-6-amines in the amino and imino tautomeric forms, as well as the complexes of the same with dimethyl sulfoxide (DMSO), were performed using two functionals (BP86 and B3LYP) and two basis sets (SV(P) and def2-TZVP). Solid-state structures of two of the compounds were obtained from single-crystal X-ray diffraction techniques. It was found that the inclusion of both an explicit hydrogen-bonding partner (DMSO) as well as continuum solvation effects, and vibrational corrections to energy, were necessary for qualitative and reasonable quantitative agreement with observed tautomeric ratios. The solution-optimized geometries and X-ray structures were found to be in good agreement. NMR spectroscopy confirmed the dependence of the tautomeric ratios on hydrogen-bonding abilities, in addition to the dipole moment of the solvent in question. Natural Bond Orbital charges on the N-7 nitrogen, as well as the tautomeric ratios were used to explain the observed reactivities of the compounds toward N-7 alkylation.
KeywordsDensity functional theory Tautomeric equilibria X-ray structures Purinamines
The Norwegian Research Council is greatly acknowledged for a PhD scholarship to H.R. (grant 171323/V30), as well as for partial financing of the Bruker Avance instrument used in this study. The authors are grateful to NordForsk (project “CRYSTENG”) for networking and mobility support. The work of T.T. was supported by Estonian Science Foundation grant no. 8255.
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