Fluorinated pyrazolinic thiosemicarbazones: selective synthesis and computational analysis

Thiosemicarbazones are a class of iminic organosulfur compounds synthesized by condensation reaction between a thiosemicarbazide and an aldehyde or ketone. Such compounds present a wide range of biological activities, either as sole organic compounds or in association with metallic species. The fluorinated pyrazoline cyclic thiosemicarbazones described herein were synthesized from 4,4,4-trifluoro-1-phenyl-1,3-butanedione and three thiosemicarbazides. The reactions resulted in thiosemicarbazones 1, 2, and 3, with 51, 70, and 71% yields, respectively. which were characterized by elemental analysis, FTIR, 1H and 19F{1H} NMR, mass spectrometry and single crystal X-ray diffraction. The spectral data confirm that the thiosemicarbazones are cyclic the both in solid state and solution, as no evidence of ring-chain tautomerism has been observed. Additionally, single-crystal X-ray diffraction studies revealed that the compounds mentioned above crystallized in centrosymmetric space groups, two of them in monoclinic P21/n and the last one in triclinic P . Theoretical free energies of formation were calculated using the DFT methodology, and the results indicate that the ring isomer is significantly more stable than the chain isomer; thus, no ring-chain isomerism is expected to form, in agreement with the experimental data.