Fluorinated enamines of nucleobases as precursors of nucleoside analogues. Synthesis, spectroscopic and structural studies

Abstract

The ¹H and ¹⁹F NMR spectra of N-α-fluoro-β-trifluoromethylenamines and isostructural N-β-fluoro-β-trifluoromethylenamines of nucleobases dissolved in CDCl₃ and DMSO-d₆ have shown distinct differences associated with the conformational conversion between the Z and E stereoisomers. In the E stereoisomer the tetrafluoropropenyl group is rotated relative to the heteroring plane, whereas the Z stereoisomer assumes the most planar structure. The flat conformation of the Z stereoisomer is stabilised by internal hydrogen bonding between C^α–H and the carbonyl oxygen (pyrimidinic bases) or the endocyclic nitrogen (purinic bases). Large variations in the magnitudes of the chemical shifts of C^β–H, C^α–F, C⁶–H and C⁸–H were observed, i.e. the chemical shift increased with increasing polarity and ability of DMSO-d₆ to establish intermolecular hydrogen bonds in competition with intramolecular hydrogen bonds. The (Z)-N⁴-benzoyl-N¹-(1,3,3,3-tetrafluoroprop-1-enyl)cytosine crystals undergo a phase transition at 230 K induced by the tetrafluoropropenyl substituent reorientations. Between 300 and 230 K the molecules are present in two conformations, and below 230 K the molecules gradually assume five conformations, remaining in a stable equilibrium with intermolecular forces, evidenced by single-crystal X-ray diffraction.