Synthesis and Crystallographic Characterization of 1-((2-(2,4-Difluorophenyl)oxiran-2-yl)methyl)-1H-1,2,4-triazole: A Crucial Intermediate for the Synthesis of Azole Antifungal Drugs

摘要

Preparation of oxirane 3 was accomplished in two steps. 1H-1,2,4-triazole was reacted with 2,4-difluoro-alpha-chloroacetophenone 1 in presence of K2CO3 in refluxing toluene to provide compound 2. Compound 2 was treated with trimethylsulfoxonium iodide (TMSI) in aq. NaOH and toluene to provide oxirane 3. Oxirane 3, previously isolated as an oil, was crystallized from (DCM/MeOH) and characterized by X-ray crystallography: triclinic, space group P - 1, a = 7.3225 (15), b = 7.5833 (15), c = 9.856 (2) angstrom, alpha = 91.908 (12), beta = 100.824 (11), gamma = 103.800 (11)degrees, V = 520.28 (18) angstrom(3), Z = 2. The molecule has a stepped conformation with nearly parallel triazole and phenyl rings. Lack of classical hydrogen-bond donors leads to packing dominated by weaker interactions, including C-H center dot center dot center dot N, C-H center dot center dot center dot F and F center dot center dot center dot F contacts.