Synthesis of difluoroaryldioxoles using BrF₃

Abstract

A novel synthesis of different aromatic and heteroaromatic difluorodioxole derivatives has been developed. The starting materials were catechols, which, after treatment with thiophosgene, formed at 0 °C the respective thiodioxoles. The latter were reacted for a short time with commercially available bromine trifluoride, producing potentially biologically important difluoroaryldioxoles in moderate to high yields.

Fluorodesulfurization of Thionobenzodioxoles with Silver(I) Fluoride

“…Here, conversion of catechols into thionobenzodioxoles using thiophosgene 11 or 1,1′-thiocarbonyldiimidazole (TCDI) 12 is followed by a desulfurative fluorination reaction involving HF and NIS 13 or DBH, 14 Fluolead, 15 and BrF 3 (Figure 1B). 16,17 We have previously described the fluorination of thionoesters with AgF in MeCN, 18 and Schoenebeck has recently demonstrated the fluorination of thiocarbamoyl fluorides using AgF. 19,20 Here, we report the use of AgF for the direct desulfurative fluorination of thionobenzodioxoles.…”

“…7, 149.7, 146.3, 142.0, 134.4, 119.8, 105.2, 35.5, 34.6, 31.7, 30.0 [1,3]dioxol-5-yl)ethyl)carbamate (10i). 16 Following General Procedure 1, tert-butyl (3,4dihydroxyphenethyl)carbamate (344 mg, 1.36 mmol) was dissolved in CH 2 Cl 2 (60 mL) with DMAP (423 mg, 3.5 mmol). Thiophosgene (0.15 mL, 2.0 mmol) was added dropwise, and the solution was stirred for 16 h at rt.…”

“…As an alternative approach to difluorobenzodioxoles, the desulfurative fluorination of thionobenzodioxoles has been reported. Here, conversion of catechols into thionobenzodioxoles using thiophosgene or 1,1′-thiocarbonyldiimidazole (TCDI) is followed by a desulfurative fluorination reaction involving HF and NIS or DBH, Fluolead, and BrF 3 (Figure B). , …”

Thiophosgene

“…(C) In 2011, Rozen's group 6 reported a novel methodology for preparing aromatic difluoromethylene dioxides 8 from deactivated or mildly deactivated aromatic rings (5,6) using bromine trifluoride (BrF 3 ). In order to introduce the fluorides without radical side reactions, they rationalized the inclusion of sulfur as a soft base using cyclic thiocarbonates 7 as intermediates, which were obtained by the reaction of aromatic derivatives with thiophosgene in 90-95% yields.…”

“…It can be used to prepare isothiocyanates which serve as important scaffolds to provide compounds such as thioureas, thiazoles 1,2 or thiocarbamates. 3 Besides, thiones, 4 oxadiazolones, 5 thiocarbonates, 6 chlorothioformates, 7 and heptathiodicarbonates 8 can be synthetized with the employment of this reagent.…”