New Antifungal 1,2,4-Triazoles with Difluoro(substituted sulfonyl)methyl Moiety.

Novel Synthesis of Difluoromethyl‐Containing 1,4‐Disubstituted 1,2,3‐Triazoles via a Click–Multicomponent Reaction and Desulfanylation Strategy

“…Highresolution mass spectra (HR-MS) were recorded under electron impact conditions using a MicroMass GCT CA 055 instrument and recorded on a MicroMass LCTTM spectrometer. Compounds 1, [13] 3e-k, [17] 3l-n [18] were synthesized according to literature procedures. (2) A solution of the ethyl 2,2-difluoro-2-(phenylthio)acetate (1) …”

“…The synthetic pathway for compound 2 is outlined in Scheme 2. The ethyl 2,2-difluoro-2-(phenylthio)acetate (1) was readily prepared by the reaction of ethyl bromodifluoroacetate and thiophenol according to the literature, [13] and the intermediate 1 could easily be reduced by LiAlH 4 to give corresponding alcohol 2. It should be mentioned that the reaction time of the reduction should not exceed 10 min, otherwise, the hydrodefluorination takes place and a mixture of 2 and the defluorinated compound is obtained.…”

Facile synthesis of α,α-difluoroalkyl aryl thioethers and their oxidative desulfurization–fluorination to trifluorides

“…4.2.1.4. Ethyl 2,2-difluoro-2-(4-methylphenylthio)acetate (5d) [11]. The reaction was carried out in a 3.0 mmol scale with ethyl 2-(4-methylphenylthio)acetate (4d) in 3 days at room temperature or as an alternative 22 h at 45 8C.…”

“…Lequeux et al reported the homolytic cleavage of the S-CF 2 bond of sulfanyldifluoromethylphosphonate using AIBN/n-Bu 3 SnH in the presence of various olefins to provide unsaturated difluoromethylphosphonate adducts [9]. Moreover, these authors and Eto et al used a,adifluoroalkyl aryl thioethers as building blocks for the synthesis of acrylthionucleosides [10] and 1,2,4-triazoles with a difluoro substituted sulfonylmethylene unit [11]. Furthermore, Yagupolskii and co-workers oxidized difluorinated sulfides to sulfoxides and converted them to aryl-(N-trifluoromethylsulfonylimino)thiodifluoroacetic acids in order to check their optical properties [12].…”

Strong Antifungal Activity of SS750, a New Triazole Derivative, Is Based on Its Selective Binding Affinity to Cytochrome P450 of Fungi

“…In order to enhance the in vitro and in vivo antifungal activities of this compound against pathogenic fungi, including strains less susceptible to FLC, we introduced fluorine atoms into antifungal triazoles; our research focused on discovering new azoles with a gem-difluoromethylene moiety (2). The introduction of fluorine into an organic molecule causes dramatic changes in biological activity, mainly because of the high electronegativity of fluorine, the strong carbon-fluorine bond, and the increased lipid solubility because of its relatively low molecular weight.…”