Synthesis of Sulfonyl, Sulfonimidoyl, and Sulfoxyl Fluorides under Solvent-Free Mechanochemical Conditions in a Mixer Mill by Imidazole-to-Fluorine Exchange

Abstract

A sustainable, mechanochemical procedure for the synthesis of sulfur(VI) fluorides starting from readily available sulfur(VI) 2-methylimidazoles as stable S(VI) precursors has been developed. The transformation proceeds with potassium bifluoride (KHF 2 ) as the fluorine source in the presence of acetic acid (AcOH) in a mixer mill under solvent-free conditions. The corresponding sulfonyl, sulfonimidoyl, and sulfoxyl fluorides are formed in good to excellent yields. Compared with the solution-based counterpart, the reaction times are shorter. This environmentally benign mechanochemical approach exhibits significant ecological advantages and requires less resources for the optimized purification by simple silica plug filtration.

Mechanosynthesis of sulfonamides via a telescopic, environmentally friendly, and cost-effective process

“…To address solvent-related environmental concerns, we delved into mechanochemistry's pivotal role in green chemistry, offering solvent-free conditions that enhance the efficiency and minimize by-products. 32–34 Despite breakthroughs by Bolm 35 and Iaroshenko, 36 the reliance on expensive metal catalysts prompts our innovative approach (Scheme 1).…”

Mechanochemical Deoxyfluorination of Carboxylic Acids to Acyl Fluorides and Successive Mechanochemical Amide Bond Formation

“…25−32 A ball mill is a mechanochemical apparatus that employs the controlled movement of a ball at a specified frequency to exert mechanical force on a mixture of reagents, thereby expediting the reaction process. Although many mechanochemical reactions, including fluorination 33,34 and difluoromethylation, 35,36 have recently been reported, there is an absence of mechanochemical synthesis methods for acyl fluorides.…”

“…IUPAC has acknowledged mechanochemistry as one of the ten leading technologies in chemistry, responding to the growing need for environmentally friendly processes and sustainable reaction conditions. − A ball mill is a mechanochemical apparatus that employs the controlled movement of a ball at a specified frequency to exert mechanical force on a mixture of reagents, thereby expediting the reaction process. Although many mechanochemical reactions, including fluorination , and difluoromethylation, , have recently been reported, there is an absence of mechanochemical synthesis methods for acyl fluorides.…”

Green and Efficient Protocols for the Synthesis of Sulfonyl Fluorides Using Potassium Fluoride as the Sole Fluorine Source

“…While this method can circumvent the need to handle gaseous toxic reagents like fluorosulfonic acid and anhydrides, challenges such as the restricted accessibility and instability of sulfonyl chlorides, as well as the hazardous use of certain reagents (KHF 2 or HF) with metallic apparatus, impede its application in green processes and scalability. − The relentless pursuit to develop more efficient methods continues using alternative starting materials (sulfonic acids, sulfonates, sulfonyl hydrazides, or sulfonamides , ). Bolm and co-workers introduced a sustainable mechanochemical solvent-free protocol for the imidazole/fluorine exchange using KHF 2 as a fluorine source . Pd-based coupling approaches of aryl halides with 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO) and a fluorinating agent such as Selectfluor or N -fluorodibenzenesulfonimide (NFSI) have been developed. , Our group reported the oxidative fluorination of disulfides or thiols with electrophilic fluorinating reagents, such as Selectfluor, to afford the corresponding sulfonyl fluoride in high yields. , In 2019, Noël and colleagues accessed sulfonyl fluorides through the electrochemical oxidative coupling of thiols and potassium fluoride as the sole fluorine source .…”