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TCI Practical Example: Synthesis of Primary Sulfonamides Using tBuONSO

We are proud to present the synthesis of the primary sulfonamide using tBuONSO and p-tolylmagnesium bromide. tBuONSO is a reagent for the synthesis of primary sulfonamides with organometallic reagents such as Grignard reagents and organolithium reagents.

Used Chemicals

• (tert-Butoxyimino)-λ⁴-sulfanone (= tBuONSO) [U0150]
• p-Tolylmagnesium Bromide (19% in Tetrahydrofuran, ca. 1mol/L) [T1700]
• THF (anhydrous)

Procedure

p-Tolylmagnesium bromide (ca. 1 mol/L, 4.4 mL, 4.4 mmol) was added to a solution of tBuONSO (400 mg, 2.96 mmol) in anhydrous THF (12 mL) at -78 °C and the mixture was stirred at the same temperature for 1 hour. The suspension was warmed to room temperature and stirred for overnight. After that, methanol (1 mL) was add to the reaction mixture and the solvent was removed under reduced pressure. The residue was purified by column chromatography (ethyl acetate:hexane = 0:1 - 1:4 on silica gel) to give 4-methylbenzenesulfonamide as a white solid (407 mg, 80%).

Experimenter’s Comments

The reaction mixture was monitored by UPLC.

Analytical Data

4-Methylbenzenesulfonamide

¹H NMR (400 MHz, CDCl₃); δ 7.70 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.27 (brs, 2H), 2.33 (s, 3H).

Lead Reference

• Primary Sulfonamide Synthesis Using the Sulfinylamine Reagent N‑Sulfinyl‑O‑(tert-butyl)hydroxylamine, t‑BuONSO
  • T. Q. Davies, M. J. Tilby, D. Skolc, A. Hall, M. C. Willis, Org. Lett. 2020, 22, 9495.