A Convenient Preparation of Heteroaryl Sulfonamides and Sulfonyl Fluorides from Heteroaryl Thiols

Abstract

Heteroaromatic thiols may be oxidized to the sulfonyl chloride at low temperature (-25 degrees C) by using 3.3 equiv of aqueous sodium hypochlorite. The reaction is rapid, avoids the use of chlorine gas, and succeeds with substrates that have previously been found to afford little or none of the sulfonamide product with other procedures. The method allows the preparation of the sulfonyl fluorides, which are stable enough to be purified and stored, making them potentially useful monomers in parallel chemistry efforts.

Heterocyclic pentafluorophenyl sulfonate esters as shelf stable alternatives to sulfonyl chlorides

“…6 Recently, Wright and Hallströ m described a very convenient procedure, where NaOCl was used as the oxidant. 7 They were confronted with the same problems of instability, and chose to react the sulfonyl chlorides directly with amines. Subsequently, they sought to convert the sulfonyl chlorides to a shelf stable entity that would react similarly.…”

“…The following procedure is adapted from Wright and Hallströ m. 7 To a mechanical stirred mixture of 2 M HCl (76 mL) and CH 2 Cl 2 (100 mL) cooled to À5 C (internal temperature) was added a cold (5 C) sodium hypochlorite (w10% solution, 1.55 M, 65 mL, 100 mmol, 3.3 equiv) at such a rate that the temperature was maintained below 0 C. Thiol 1a-d (30 mmol) was added in small portions while maintaining the internal temperature at À10 C to À5 C. The mixture was stirred for 15-20 min at À10 C to À5 C after the addition was complete. Excess chlorine was quenched by adding cold (0 C) 1 M Na 2 SO 3 or 1 M Na 2 S 2 O 3 until the yellow greenish color of the mixture disappeared and iodide paper (KI/starch) no longer gave a fast coloration.…”

4‐Cyano‐2‐Methoxybenzenesulfonyl Chloride

“…Numerous methods have been developed for this transformation using a variety of inorganic oxidants, [15][16][17][18] and both organic 15,18,19 and inorganic chloride sources. 16,17 After exploring various methods with limited success, we discovered that a zirconium(IV) chloride promoted oxidative chlorination of 3 was a convenient procedure to prepare sulfonyl chloride 4 on multi-gram scale.…”

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

“…[5][6][7][8][9] Although this methodology is relatively general, issues associated with the use of excess oxidant and/or aqueous acid have prompted the development of alternative methods. 10,11 We describe here an oxidation/substitution sequence that is mild and minimizes both the amount of oxidant required and the aqueous component. Recently, the direct oxidative conversion of thiols into sulfonamides with H 2 O 2 -SOCl 2 was reported by Bahrami and et al…”