Crystal and molecular structure of 5-trifluorothymine, a metabolite from human urine: Role of fluorine in stacking and hydrogen bonded interactions

The crystal structure of the metabolite from urine, 5-trifluorothymine [5F3T] has been determined by single crystal X-ray diffractometric methods. Crystals of 5F3T are monoclinic, space group P21/c with cell dimensions a = 6.7468(2), b = 15.0740(6), c = 13.4405(6), β = 90.412(2), V = 1366.88(8), Z = 8 (two molecules per asymmetric unit). Crystal structure of 5F3T was determined with 3039 independent data and refined by full-matrix least squares methods to a final reliability factor of 0.047. Molecules of 5F3T are connected by dimeric type of NH⋯O hydrogen bonding linking molecules related by a center of inversion into an extensive layer of dimeric molecules. These layers are stacked on top of each other at a stacking distance of 3.280 Å with a head-to-head stacking of the fluorine atoms on top of each other with no hydrogen bonding involving the fluorine atoms.

Graphical abstract5-Trifluorothymine [5F3T] is a metabolite found in human urine. It could also be synthesized by cyclizing the ureidoamides to 5-trifluoromethyl-5,6-dihydrouracil by reflexing in hydrochloric acid. The crystal structure of 5F3T reveals an extensive network of linear molecule connected by dimeric NH⋯O bonds stacked on top of each other stabilized by non-bonded interactions involving fluorine atoms, which do not take part in the hydrogen bonding network.Figure optionsDownload full-size imageDownload as PowerPoint slide