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

作者：Dracinsky Martin^*; Jansa Petr; Chocholousova Jana; Vacek Jaroslav; Kovackova Sona; Holy Antonin

来源：European Journal of Organic Chemistry, 2011, (4): 777-785.

DOI：10.1002/ejoc.201001335

• Nitrogen heterocycles
• Nucleobases
• Reaction mechanisms
• Density functional calculations
• Isotopic labeling
• Deuterium
• Tautomerism
• NMR spectroscopy

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 ob-served 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.

• 出版日期2011-2