Mechanism of the Isotopic Exchange Reaction of the 5‐H Hydrogen of Uracil Derivatives in Water and Nonprotic Solvents

The mechanism of the isotopic exchange reaction of the 5-H hydrogen of uracil and its methyl derivatives in water and organic solvents has been studied. The key intermediate of the reaction is a C-5 tautomer of uracil in which the carbon atom at the 5-position has two hydrogen atoms, its hybridization is changed from sp 2 to sp 3 , and the aromaticity of the pyrimidine ring is lost. We have used 1 H NMR spectroscopy to follow the kinetics of the hydrogen/deuterium exchange reaction. In aqueous media a general base catalysis was observed and for exchange in organic solvents we have proposed a reaction mechanism that involves the participation of solvent molecules. The reaction rates determined by NMR can be rationalized by density functional computations. We have shown that the hydrogen-to-deuterium exchange reaction is much faster in some suitable nucleophilic solvents than in water. These findings could be used for the tritium labeling of pyrimidine nucleic acid bases.

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