Convenient One-Pot Synthesis of Sulfonamides from Thiols and Disulfides Using 1,3-Dichloro-5,5-dimethylhydantoin (DCH)

Abstract

A convenient synthesis of sulfonamides from thiols and disulfides is described. In situ preparation of sulfonyl chlorides from thiols is accomplished by oxidation with 1,3-dichloro-5,5-dimethylhydantoin (DCH) under Nbenzyl-trimethylammonium chloride and water. The sulfonyl chlorides are then further allowed to react with excess amine in the same reaction vessel.

A continuous flow investigation of sulfonyl chloride synthesis using N-chloroamides: optimization, kinetics and mechanism

“…This is supported by others, observing the formation of disulfide when using a 0.15 molar ratio of thiol to DCH ( 2 ). 26 Regardless of the pathway followed, the overall mass balance for the reaction is shown in Scheme 5b. Veisi et al introduced the use of tetra-butylammonium chloride (BnMe 3 NCl) as a method to increase the reaction rate of oxidative chlorination, 20,50 and Ho et al demonstrated that NH 4 Cl also increases the rate.…”

“…24 DCH ( 2 ) is reported using AcOH/H 2 O/MeCN, 25 and BuMe 3 NCl/H 2 O/MeCN. 26 TCCA ( 3 ) is described using BnMe 3 NCl/H 2 O/MeCN, 20,27,28 and K 2 CO 3 /H 2 O. 29 N -Chloroamides 1–3 are all colorless solids at room temperature.…”

Synthesis, Radiolabeling, and in Vitro and in Vivo Evaluation of [18F]ENL30: A Potential PET Radiotracer for the 5-HT7 Receptor

“…However, this approach yielded in sufficient amounts of ( 10 ) that could be used in a subsequent coupling step with another key intermediate 3-(2-fluoroethoxy)­benzenesulfonyl chloride ( 14 ). ,,, The synthesis of ( 14 ) is detailed in Scheme . Notably, in the final step in the synthesis of 14 , the need for S -deprotection was circumvented and allowed direct oxidation of sulfur. , In summary, the reference synthesis was completed in 13 steps, ending up with an overall low yield of approximately 0.2%.…”

“…Notably, in the final step in the synthesis of 14, the need for Sdeprotection was circumvented and allowed direct oxidation of sulfur. 39,40 In summary, the reference synthesis was completed in 13 steps, ending up with an overall low yield of approximately 0.2%.…”

7.28 Oxidation of Sulfur, Selenium, and Tellurium

“…98 Sulfenamides or sulfonamides can be produced by the use of a copper catalyst in air or under dioxygen atmosphere in the presence of amines. 99 Commercially available TCCA 100 or 1,3-dichloro-5,5-dimethylhydantoin (DCH) 101 is used in combination with the chlorinating agent BnMe 3 NCl to convert thiols to sulfonyl chloride and, subsequently, to sulfonamides using various amines in organic solvents. A more environmentally benign and cheaper oxidation of thiols or disulfides to sulfonamides is provided by TCCA in water followed by the addition of K 2 CO 3 and the proper amine.…”