Mild and Convenient Synthesis of Benzodithiazoles by Oxidative Cyclization of Bis(thiobenzanilides)

Abstract

Benzodithiazoles were prepared by oxidative cyclization of bis(thiobenzanilides). The reactions were performed at room temperature under mild conditions and rely on the use of N-benzyl-DABCO tribromide.

Key words

benzodithiazoles - thioamides - organic ammonium tribromides - cyclization - C–S bond formation

• References and Notes

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• 14 General Procedure A for the Synthesis of 6a–f To a cold suspension of 1,3-benzenediamine 4 (1.0 equiv, 18.5 mmol) and Et₃N (5.1 mL, 37 mmol, 2.0 equiv) in dry CH₂Cl₂ (50 mL), a CH₂Cl₂ solution (10 mL) of benzoyl chloride 5a–g (2.0 equiv) was added dropwise. The reaction mixture was stirred at 20 °C for 12 h and subsequently poured into 100 mL of H₂O. The organic layer was separated, washed with an aq solution of NaHCO₃ and with H₂O (30 mL), and dried by Mg₂SO₄. The solution was filtered and concentrated under reduced pressure.
• 15 N,N′-(1,3-Phenylene)bis(4-methylbenzamide) (6a) Starting with 4 (2.00 g, 18.5 mmol, 1.0 equiv), Et₃N (5.1 mL, 37 mmol, 2.0 equiv), 4-methylbenzoyl chloride (4.8 mg, 37 mmol, 2.0 equiv), CH₂Cl₂ (25 mL), following General Procedure A, 6a was isolated (3.5 g, 55%); mp 257–259 °C. ¹H NMR (300 MHz, DMSO-d ₆): δ = 3.37 (s, 6 H, CH₃), 7.29–7.37 (m, 5 H), 7.51 (dd, J = 7.9, 1.8 Hz, 2 H), 7.92 (d, J = 8.2 Hz, 4 H), 8.34 (t, J = 3.2 Hz, 1 H), 10.2 (s, 2 H, NH). ¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 20.7 (2-CH₃), 112.9, 115.9, 127.7, 128.4, 128.8 (CH), 132.0, 139.3, 141.5 (C), 165.3 (CO). GC–MS (EI, 70 eV): m/z (%) = 344 (67) [M⁺], 119 (99), 91 (44), 65 (13). HRMS (EI, 70 eV): m/z calcd for C₂₂H₂₀N₂O₂ [M]⁺: 344.1519; found: 344.1522.
• 16 General Procedure B for the Synthesis of 7a–f The amide starting material (0.5 mmol) and Lawesson’s reagent (0.5 mmol) were refluxed in toluene (30 mL) for 1 h. Upon cooling, the solvent was evaporated using a rotary evaporator. The crude mixture was purified by column chromatography (silica gel, CH₂Cl₂–hexane = 1:1) to obtain the deep yellow colored compounds 7a–f in high yields (76–82%).
• 17 N,N′-(1,3-Phenylene)bis(4-methylbenzothioamide) (7a) Starting with 6a (1.00 g, 1.0 equiv), Lawesson’s reagent (0.80 g, 1.0 equiv), toluene (25 mL), following General Procedure B, 7a was isolated (1.34 g, 92%). ¹H NMR (300 MHz, DMSO-d ₆): δ = 2.39 (s, 6 H, CH₃), 7.29 (d, J = 8.1 Hz, 4 H), 7.49 (t, 3 H), 7.69 (d, J = 7.6 Hz, 4 H), 8.35 (s, 1 H), 11.74 (s, 2 H, NH). ¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 20.8 (2-CH₃), 120.1, 122.2, 127.5, 128.3, 128.5 (CH), 139.4, 140.1, 140.9 (C), 197.4 (CS). GC–MS (EI, 70 eV): m/z (%) = 377 (76) [M⁺], 343 (67), 240 (43), 226 (93), 135 (70); HRMS (EI, 70 eV): m/z calcd for C₂₂H₂₀N₂S₂ [M]⁺: 377.1140; found: 377.1138.
• 18 General Procedure C for the Oxidative Cyclization of Thiobenzanilides To a stirred solution of thiobenzanilide 7a–f (1.0 equiv) in CH₂Cl₂–CCl₄ (1:1, 10 mL), N-benzyl-DABCO tribromide (2.0 equiv) was added. The reaction mixture was stirred for 30–90 min at 20 °C (TLC control). The solvent was removed under reduced pressure, and the residue was subjected to column chromatography (CH₂Cl₂–hexane, 1:1) to obtain products 8a–f.
• 19 1,4-Bis[4-methylphenyl]benzo[1,2-d:4,5-d]bisdithiazole (8a) Starting with 7a (200 mg, 1.0 equiv), N-benzyl-DABCO tribromide (450 mg, 2.0 equiv), CH₂Cl₂–CCl₄ (1:1, 10 mL), following General Procedure C, 8a was isolated as a yellow solid (138 mg, 70%); mp 221–223 °C. ¹H NMR (300 MHz, DMSO-d ₆): δ = 2.38 (s, 6 H, CH₃), 7.31 (d, J = 8.1 Hz, 4 H), 7.98 (d, J = 8.4 Hz, 5 H), 8.03 (s, 1 H). ¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 26.3 (CH₃), 124.8, 125.1, 132.2, 134.8 (CH), 135.3, 141.4, 146.6, 158.6, 172.2 (C). GC–MS (EI, 70 eV): m/z (%) = 372 (100) [M⁺], 186 (16), 138 (43). HRMS (EI, 70 eV): m/z calcd for C₂₂H₁₆N₂S₂ [M]⁺: 372.0749; found: 372.0751.