A Practical Access to Functionalized Alkyl Sulfinates

Abstract

We describe herein a three-step synthesis of aliphatic sulfinates. This cost-effective method involves the use of 2-mercaptobenzothiazole under mild conditions and exhibits good yields (up to 78% over three steps). This approach provides an access to a wide range of functionalized sulfinates. A good tolerance with respect to diverse functional groups (alkene, alkyne, ether, acetal) was also noted.

Key words

sulfinate salts - mercaptobenzothiazole - sulfinic acids - functionalized alkyl sulfinates - sulfones

• References and Notes

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• 37 It should be noted that BTS was prepared from 2,2′-dithiobis(benzothiazole).
• 38 Alkylation Conditions General Procedure A (for 2b–d,f,g,i,j) To a suspension of NaH (720 mg, 30 mmol, 3.0 equiv) in DMF (35 mL), was added a solution of mercaptobenzothiazole (1.7 g, 10 mmol, 1.0 equiv) in DMF (5 mL). The mixture was stirred at room temperature for 30 min. Alkyl halide (11 mmol, 1.1 equiv) diluted in DMF (2 mL) was then introduced to the yellow solution. The reaction was stirred at 70 °C for 3 h, quenched with water, and extracted with Et₂O. The organic layer was washed five times with brine, dried over MgSO₄, filtered, and concentrated under reduced pressure. The yellow residue was then purified by column chromatography on silica gel to afford the expected compound. General Procedure B (for 2a,e) To a solution of Na (rinsed with heptane, 345 mg, 15 mmol, 1.5 equiv) in dry MeOH (dried over CaH₂, 30 mL) was slowly added mercaptobenzothiazole (1.7 g, 10 mmol, 1.0 equiv). The mixture was stirred at room temperature for 10 min. The alkyl halide (11 mmol, 1.1 equiv) was then introduced to the yellow solution. The reaction was stirred at 60 °C for 3 h, quenched with water, and extracted with CH₂Cl₂. The organic layer was washed with brine, dried over MgSO₄, filtered, and concentrated under reduced pressure. The yellow residue was then purified by column chromatography on silica gel to obtain the desired compound. General Procedure C (for 2h,k–n) Mercaptobenzothiazole (1.7 g, 10 mmol, 1.0 equiv) was dissolved in DMF (11 mL). Alkyl halide (15 mmol, 1.5 equiv) and K₂CO₃ (2.8 g, 20 mmol, 2.0 equiv) were added, and the mixture was stirred at room temperature for 24 h. The reaction was then quenched with water and extracted with Et₂O. The organic layer was washed five times with brine, dried over MgSO₄, filtered, and concentrated under reduced pressure. The yellow residue was then purified by column chromatography on silica gel to afford the expected compound. Compound 2j was prepared according to procedure A starting from 1-(chloromethyl)-4-methoxybenzene (1.5 mL, 1.7 g, 11 mmol, 1.1 equiv). Purification on silica gel (cyclohexane to cyclohexane/ethyl acetate = 95:5) afforded 2j as a white solid (2.5 g, 87%). ¹H NMR (400 MHz, CDCl₃): δ = 7.95–7.88 (m, 1 H), 7.75 (d, J = 7.8 Hz, 1 H), 7.46–7.35 (m, 3 H), 7.34–7.27 (m, 1 H), 6.89–6.82 (m, 2 H), 4.57 (s, 2 H), 3.80 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 166.7, 159.3, 153.3, 135.4, 130.5, 128.1, 126.2, 124.4, 121.7, 121.1, 114.2, 55.4, 37.5. R_f = 0.48 (cyclohexane/EtOAc = 80:20); mp 64 °C. IR: 1610, 1513, 1454, 1424, 1251, 1172, 1026, 1007, 836, 755, 729, 699 cm^-1.
• 39 Oxidation Conditions 2-Alkylthiobenzothiazole (1.0 equiv) was dissolved in CH₂Cl₂, mCPBA 70% (3.0 equiv) was then introduced, and the mixture was stirred at room temperature for 3 h. The reaction was then quenched with a saturated solution of Na₂S₂O₃ and extracted with CH₂Cl₂. The organic layer was washed with brine, dried over MgSO₄, filtered, and concentrated under reduced pressure. The residue was then purified by column chromatography on silica gel to obtain the corresponding sulfone. Sulfone 3j was prepared according to procedure D starting from 2-[(4-methoxybenzyl)thio]benzo[d]thiazole (1.5 g, 5.2 mmol, 1.0 equiv) in CH₂Cl₂ (26 mL) and mCPBA (2.7 g, 15.0 mmol, 3.0 equiv). Purification on silica gel (cyclohexane to cyclohexane/ethyl acetate = 95:5) afforded 3j as a white solid (1.7 g, quant.). ¹H NMR (400 MHz, CDCl₃): δ = 8.25 (ddd, J = 8.3, 1.2, 0.7 Hz, 1 H), 7.94 (ddd, J = 8.1, 1.4, 0.7 Hz, 1 H), 7.64 (ddd, J = 8.4, 7.2, 1.3 Hz, 1 H), 7.57 (ddd, J = 8.3, 7.2, 1.3 Hz, 1 H), 7.20–7.14 (m, 2 H), 6.83–6.73 (m, 2 H), 4.70 (s, 2 H), 3.75 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 165.5, 160.4, 152.7, 137.2, 132.5, 128.1, 127.7, 125.5, 122.4, 118.1, 114.5, 60.5, 55.4. R_f = 0.18 (cyclohexane/EtOAc = 80:20); mp 124 °C. IR: 1513, 1406, 1313, 1250, 1145, 1065, 760 cm^–1.
• 40 Reduction Conditions To a solution of sulfone (1.0 equiv) in EtOH was added NaBH₄(2.0 equiv). The mixture was stirred at room temperature for 2 h, then concentrated under reduced pressure, and triturated with Et₂O. The supernatant was removed using a Pasteur pipette. The white solid was then dried under reduced pressure to afford the corresponding sulfinate. Sulfinate 4j was prepared according to procedure E starting from 2-[(4-methoxybenzyl)sulfonyl]benzo[d]thiazole (1 g, 3.1 mmol, 1.0 equiv) in EtOH (16 mL) and NaBH₄ (237 mg, 6.3 mmol, 2.0 equiv), sulfinate 4j was obtained as a white solid (940 mg, quant.); mp >266 °C. ¹H NMR (400 MHz, CD₃OD): δ = 7.20 (d, J = 8.6 Hz, 2 H), 6.86 (d, J = 8.6 Hz, 2 H), 3.77 (s, 3 H), 3.46 (s, 2 H). ¹³C NMR (101 MHz, CD₃OD): δ = 160.1, 132.0, 126.7, 114.7, 69.9, 55.6. IR: 1513, 1251, 1010, 982, 822, 676, 637 cm^–1.