One-Pot Efficient Synthesis of Sulfonimidamides from Sulfonyl Chloride

Abstract

Sulfonimidamides, featuring a hexavalent sulfur structure, are a class of key compounds with broad application prospects in the fields of pharmaceuticals and agrochemicals. However, their applications have been limited due to the lack of economically effective synthetic methods. Utilizing the cost-effective and readily accessible sulfonyl chloride as the initial reagent, this method involves the sequential formation of intermediates, including sulfinamide and sulfonimidoyl chloride, culminating in the synthesis of the sulfonylimidamide compounds. This approach yields sulfonimidamides in moderate to good yields, thereby offering a viable synthetic route for the expanded application of these important compounds.

Key words

one-pot strategy - sulfonimidamide - sulfonyl chloride - sulfinamide - sulfonimidoyl chloride

Publication History

Received: 13 January 2025

Accepted after revision: 06 March 2025

Accepted Manuscript online:
06 March 2025

Article published online:
11 April 2025

• References and Notes

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• 27 Carbamoyl Transfer Reaction; General Procedure A mixture of 1a (19.0 mg, 0.1 mmol, 1.0 equiv) and triphenylphosphine (PPh₃, 26.2 mg, 0.1 mmol, 1.0 equiv) in DCM (1.0 mL) was stirred at 0 ℃. Then TEA (10.1 mg, 0.1 mmol, 1.0 equiv) and amine (2.0 equiv) were added dropwise to the flask at 0 °C. The reaction mixture was stirred for 5 min before the addition of trichloroisocyanuric acid (TCCA; 23.2 mg, 0.1 mmol, 1.0 equiv) at 0 °C. The resultant mixture was stirred for 30 min. To the mixture was added morpholine (17.4 mg, 0.2 mmol, 2.0 equiv) or amine (0.2 mmol, 2.0 equiv). The resultant mixture was stirred at 0 °C for 10 h. Upon completion, the reaction was quenched with saturated sodium chloride solution (NaCl, 5.0 mL), followed by extraction with DCM three times. The combined organic phases were dried with anhydrous MgSO₄ and concentrated under reduced pressure. Purification of the residue by flash chromatography (petroleum ether/EtOAc = 20:1 to 10:1) gave the product. 4-(N-(tert-Butyl)-4-methylphenylsulfonimidoyl)morpholine (5a) Yellow oil (83% yield); R_f = 0.51 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.69 (d, J = 8.2 Hz, 2 H), 7.27 (d, J = 8.0 Hz, 2 H), 3.70 (d, J = 4.7 Hz, 4 H), 2.92 (t, J = 4.7 Hz, 2 H), 2.42 (s, 3 H), 1.42 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 142.0, 134.0, 129.0, 127.5, 66.6, 54.9, 47.5, 33.0, 21.3. HRMS (ESI): m/z [M+H]⁺ calcd. for C₁₅H₂₄N₂O₂S: 297.1631; found: 297.1637. 4-(N-(tert-Butyl)-4-fluorophenylsulfonimidoyl)morpholine (5b) Colorless oil (71% yield); R_f = 0.42 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.82 (dd, J = 8.7, 5.3 Hz, 2 H), 7.16 (t, J = 8.4 Hz, 2 H), 3.71 (t, J = 4.6 Hz, 4 H), 2.92 (t, J = 4.8 Hz, 4 H), 1.42 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 164.56 (d, J = 260.2 Hz), 133.0 (d, J = 3.0 Hz), 130.0 (d, J = 9.1 Hz), 115.5 (d, J = 22.2 Hz), 66.5, 55.1, 47.5, 33.0. ¹⁹F NMR (376 MHz, CDCl₃): δ = –107.90. HRMS (ESI): m/z [M+Na]⁺ calcd. for C₁₄H₂₁FN₂O₂S: 323.1200; found: 323.1200. 4-(N-(tert-Butyl)-4-chlorophenylsulfonimidoyl)morpholine (5c) Colorless oil (82% yield); R_f = 0.45 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.73(d, J = 8.6 Hz, 2 H), 7.46 (d, J = 8.6 Hz,2 H), 3.71 (t, J = 4.7 Hz, 4 H), 2.92 (t, J = 4.6 Hz, 2 H), 1.42 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 137.9, 135.5, 128.9, 128.6, 66.5, 55.1, 47.5, 33.0. HRMS (ESI): m/z [M+Na]⁺ calcd. for C₁₄H₂₁ClN₂O₂S: 339.0904; found: 339.0909. 4-(N-(tert-Butyl)-4-bromophenylsulfonimidoyl)morpholine (5d) Colorless oil (78% yield); R_f = 0.42 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.69–7.61 (m, 4 H), 3.71 (t, J = 4.7 Hz, 4 H), 2.93 (t, J = 4.6 Hz, 4 H), 1.41 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 136.0, 132.1, 131.6, 129.0, 128.5, 126.4, 66.5, 62.8, 55.2, 47.5, 33.0, 30.1. HRMS (ESI): m/z [M+H]⁺ calcd. for C₁₄H₂₁BrN₂O₂S: 361.0580; found: 361.0582. 4-(N-(tert-Butyl)-4-iodophenylsulfonimidoyl)morpholine (5e) Colorless oil (63% yield); R_f = 0.45 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.84 (d, J = 8.2 Hz, 2 H), 7.53 (d, J = 8.2 Hz, 2 H), 3.71 (t, J = 4.7 Hz, 4 H), 2.93 (t, J = 4.6 Hz, 4 H), 1.41 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 137.6, 136.7, 129.0, 99.9, 66.5, 55.2, 47.5, 32.9. HRMS (ESI): m/z [M+H]⁺ calcd. for C₁₄H₂₁IN₂O₂S: 409.0441; found: 409.0449. 4-(N-(tert-Butyl)-3-bromophenylsulfonimidoyl)morpholine (5f) Colorless oil (51% yield); R_f = 0.42 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.96 (d, J = 1.9 Hz, 1 H), 7.74 (d, J = 7.8 Hz, 1 H), 7.66 (d, J = 7.9 Hz, 1 H), 7.37 (t, J = 7.9 Hz, 1 H), 3.72 (t, J = 4.7 Hz, 4 H), 2.95 (t, J = 4.7 Hz, 4 H), 1.43 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 138.9, 134.6, 130.3, 129.9, 125.9, 122.6, 66.5, 55.2, 47.5, 33.0. HRMS (ESI): m/z [M+H]⁺ calcd. for C₁₄H₂₁BrN₂O₂S: 361.0580; found: 361.0583. 4-(N-(tert-Butyl)-3-Chloro-2-fluorophenylsulfonimidoyl)morpholine (5g) Colorless oil (67% yield); R_f = 0.56 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.83 (d, J = 7.9 Hz, 1 H), 7.55 (d, J = 7.8 Hz, 1 H), 7.18 (d, J = 7.9 Hz, 1 H), 3.72 (t, J = 4.7 Hz, 4 H), 3.13 (t, J = 4.7 Hz, 4 H), 1.40 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 154.3 (d, J = 258.5 Hz), 134.0, 130.1, 124.0 (d, J = 5.05 Hz), 123.2, 123.0, 66.5, 55.6, 46.9, 32.9. ¹⁹F NMR (376 MHz, CDCl₃): δ = –107.80. HRMS (ESI): m/z [M+Na]⁺ calcd. for C₁₄H₂₀ClFN₂O₂S: 357.0810; found: 357.0814. 4-(N-(tert-Butyl)-2-fluorophenylsulfonimidoyl)morpholine (5h) Colorless oil (56% yield); R_f = 0.56 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.97–7.93 (m, 1 H), 7.52 (t, J = 6.3 Hz, 1 H), 7.48 (t, J = 7.7 Hz, 1 H), 7.17 (dd, J = 10.4, 8.2 Hz, 1 H), 3.73 (t, J = 4.7 Hz, 4 H), 3.13 (q, J = 5.1 Hz, 4 H), 1.41 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 158.8 (d, J = 255.5 Hz), 133.8 (d, J = 8.0 Hz), 132.0, 123.9 (d, J = 4.0 Hz), 117.3 (d, J = 23.2 Hz), 66.7, 55.5, 46.9, 32.9. ¹⁹F NMR (376 MHz, CDCl₃): δ = –106.17. HRMS (ESI): m/z [M+Na]⁺ calcd. for C₁₄H₂₁FN₂O₂S: 323.1200; found: 323.1201. 4-(N-(tert-Butyl)-3-methylphenylsulfonimidoyl)morpholine (5i) Yellow oil (74% yield); R_f = 0.55 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.60 (s, 2 H), 7.36–7.28 (m, 2 H), 3.70 (t, J = 4.7 Hz, 4 H), 2.92 (t, J = 4.8 Hz, 4 H), 2.43 (s, 3 H), 1.43 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 138.5, 136.6, 132.3, 128.3, 127.6, 124.6, 66.5, 54.9, 47.5, 33.0, 21.4. HRMS (ESI): m/z [M+H]⁺ calcd. for C₁₅H₂₄N₂O₂S: 297.1631; found: 297.1628. 4-(N-(tert-Butyl)-2-methylphenylsulfonimidoyl)morpholine (5j) Colorless oil (57% yield); R_f = 0.54 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.91–7.89 (m, 1 H), 7.39–7.36 (m, 1 H), 7.28 (t, J = 8.0 Hz, 2 H), 3.71 (t, J = 4.7 Hz, 4 H), 3.13–3.11 (m, 4 H), 2.73 (s, 3 H), 1.39 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 137.7, 133.0, 131.4, 129.5, 127.5, 125.7, 66.7, 55.2, 47.5, 46.5, 33.0, 21.6. HRMS (ESI): m/z [M+H]⁺ calcd. for C₁₅H₂₄N₂O₂S: 297.1631; found: 297.1625. 4-(N-(tert-Butyl)-4-trifluoromethyl-phenylsulfonimidoyl)morpholine (5k) Colorless oil (45% yield); R_f = 0.55 (PE/EA = 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.94 (d, J = 8.1 Hz, 2 H), 7.76 (d, J = 7.9 Hz, 2 H), 3.72 (t, J = 4.7 Hz, 4 H), 2.95 (t, J = 4.5 Hz, 4 H), 1.44 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 140.5, 133.4, 127.9, 127.4, 125.6 (q, J = 4.0 Hz), 124.8, 122.1, 66.4, 55.3, 47.5, 33.0, 30.1. ¹⁹F NMR (376 MHz, CDCl₃): δ = –362.12. HRMS (ESI): m/z [M+H]⁺ calcd. for C₁₄H₂₁F₃N₂O₂S: 351.1349; found: 351.1351.