Iodine-Promoted Synthesis of Thioamides from 1,2-Dibenzyl­sulfane and Difurfuryl Disulfide

Abstract

Thioamides can be generated at 100 °C in high yield through the reaction of 1,2-dibenzyldisulfane with difurfuryldisulfide using iodine as oxidant and DMSO as solvent. The protocol is metal- and additive-free, providing a convenient and economical way for the synthesis of various kinds of thioamides under mild conditions.

Key words

thioamide - metal-free - iodine - disulfide - synthesis

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• 17 General Procedure for the Preparation of 3Iodine (0.25 mmol, 63.4 mg) and 1,2-dibenzyldisulfane (0.5 mmol, 123.4 mg) was added to a solution of 1-methylpiperazine (1.2 mmol, 119.1 mg) in DMSO (0.5 mL), and the reaction mixture was stirred for 8 h at 100 °C. The solvent was removed under vacuum, and the residue was purified by flash silica gel column chromatography with PE–EtOAc (1:1) as eluent to afford the product 3a.(4-Methylpiperazin-1-yl)(phenyl)methanethione(3a)Yield 200.4 mg, 91%. Purified by column chromatography with PE–EtOAc (1:1) as eluent and obtained as a yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.34 (m, 3 H), 7.28 (t, J = 5.9 Hz, 2 H), 4.51–4.37 (m, 2 H), 3.67–3.51 (m, 2 H), 2.69–2.56 (m, 2 H), 2.41–2.35 (m, 2 H), 2.33 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 200.6, 142.9, 128.6, 128.4, 125.8, 55.2, 54.3, 51.8, 49.1, 45.6. MS (EI): m/z = 220.1 [M⁺]. HRMS (EI): m/z calcd for C₁₂H₁₆N₂S [M]⁺: 220.1034; found: 220.1030.Morpholino(phenyl)methanethione (3c)Yield 175.3 mg, 85%. Purified by column chromatography with PE–EtOAc (4:1) as eluent and obtained as a yellow solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.35–7.32 (m, 3 H), 7.31–7.21 (m, 2 H), 4.49–4.35 (m, 2 H), 3.96–3.79 (m, 2 H), 3.59 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 200.9, 142.5, 128.9, 128.5, 125.9, 66.7, 66.5, 52.5, 49.6. MS (EI): m/z = 207.1 [M⁺]. HRMS (EI): m/z calcd for C₁₁H₁₃NOS [M]⁺: 207.0718; found: 207.0714. N-Butylbenzothioamide (3i)Yield 141.0 mg, 72%. Purified by column chromatography with PE–EtOAc (10:1) as eluent and obtained as a yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.98 (s, 1 H), 7.63 (d, J = 7.4 Hz, 2 H), 7.38 (t, J = 7.3 Hz, 1 H), 7.28 (dd, J = 9.3, 4.7 Hz, 2 H), 3.70 (dd, J = 9.3, 4.4 Hz, 2 H), 1.65 (dd, J = 13.7, 6.8 Hz, 2 H), 1.43–1.32 (m, 2 H), 0.93 (t, J = 7.3 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 198.8, 141.7, 130.9, 128.3, 126.7, 46.6, 30.0, 20.3, 13.8. MS (EI): m/z = 193.1 [M⁺]. HRMS (EI): m/z calcd for C₁₁H₁₅NS [M]⁺: 193.0925; found: 193.0920. N-(1-Phenylethyl)benzothioamide (3m)Yield 140.0 mg, 58%. Purified by column chromatography with PE–EtOAc (10:1) as eluent and obtained as a yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.87 (s, 1 H), 7.66 (d, J = 7.4 Hz, 2 H), 7.43–7.26 (m, 8 H), 5.93–5.77 (m, 1 H), 1.64 (d, J = 6.9 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 198.1, 142.0, 141.5, 131.1, 128.9, 128.5, 127.9, 126.8, 126.6, 55.2, 20.3. MS (EI): m/z = 241.1 [M⁺]. HRMS (EI): m/z calcd for C₁₅H₁₅NS [M]⁺: 241.0925; found: 241.0920.
• 18 General Procedure for the Preparation of 6Iodine (0.25 mmol, 63.4 mg) and difurfuryl disulfide (0.5 mmol, 113.9 mg) was added to a solution of 1-methylpiperazine (1.5 mmol, 153.8 mg) in DMSO (0.5 mL), and the reaction mixture was stirred for 10 h at 100 °C. The solvent was removed under vacuum, and the residue was purified by flash silica gel column chromatography with PE–CH₂Cl₂ (1:1) as eluent to afford product 6a.Furan-2-yl(4-methylpiperazin-1-yl)methanethione (6a)Yield 117.8 mg, 56%. Purified by column chromatography with PE–CH₂Cl₂ (1:1) as eluent and obtained as a yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.37 (s, 1 H), 6.97 (d, J = 3.4 Hz, 1 H), 6.38 (dd, J = 3.2, 1.7 Hz, 1 H), 4.26 (s, 2 H), 3.85 (s, 2 H), 2.49 (s, 4 H), 2.28 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 185.8, 152.4, 142.8, 118.2, 112.0, 45.3, 38.8. MS (EI): m/z = 210.1 [M⁺]. HRMS (EI): m/z calcd for C₁₀H₁₄N₂OS [M]⁺: 210.0827; found: 210.0822.Furan-2-yl(pyrrolidin-1-yl)methanethione (6c)Yield 67.3 mg, 37%. Purified by column chromatography with PE–CH₂Cl₂ (10:1) as eluent and obtained as a yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.42 (s, 1 H), 7.25–7.18 (m, 1 H), 6.39 (dd, J = 3.1, 1.5 Hz, 1 H), 3.93 (dd, J = 15.4, 7.3 Hz, 4 H), 2.04–1.90 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 180.5, 153.0, 143.7, 118.8, 112.1, 54.9, 53.5, 26.9, 23.8. MS (EI): m/z = 181.1 [M⁺]. HRMS (EI): m/z calcd for C₉H₁₁NOS [M]⁺: 181.0561; found: 181.0556. N-Butylfuran-2-carbothioamide (6f)Yield 80.6 mg, 44%. Purified by column chromatography with PE–CH₂Cl₂ (10:1) as eluent and obtained as a yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.92 (s, 1 H), 7.44 (s, 1 H), 7.36 (d, J = 3.5 Hz, 1 H), 6.48 (dd, J = 3.0, 1.4 Hz, 1 H), 3.81 (dd, J = 13.1, 7.0 Hz, 2 H), 1.72 (dt, J = 14.9, 7.4 Hz, 2 H), 1.44 (dt, J = 14.7, 7.4 Hz, 2 H), 0.98 (t, J = 7.3 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 182.3, 152.3, 143.6, 117.6, 113.1, 44.8, 30.4, 20.2, 13.8. MS (EI): m/z = 183.1 [M⁺]. HRMS (EI): m/z calcd for C₉H₁₃NOS [M]⁺: 183.0718; found: 183.0713. N-(1-Phenylethyl)furan-2-carbothioamide (6j)Yield 124.1 mg, 54%. Purified by column chromatography with PE–CH₂Cl₂ (10:1) as eluent and obtained as a yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.08 (s, 1 H), 7.44–7.33 (m, 6 H), 7.29 (t, J = 7.0 Hz, 1 H), 6.46 (dd, J = 3.3, 1.6 Hz, 1 H), 5.91 (p, J = 7.0 Hz, 1 H), 1.68 (d, J = 6.9 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 181.2, 152.2, 143.7, 141.5, 128.9, 127.9, 126.6, 118.1, 113.24, 53.4, 20.5. MS (EI): m/z = 231.1 [M⁺]. HRMS (EI): m/z calcd for C₁₃H₁₃NOS [M]⁺: 231.0718; found: 231.0713.