Synthesis of Benzo[b][1,4]thiazines by Hetero-Diels-Alder Reaction of o-Iminothioquinones

Abstract

The regioselective sulfenylation of N-sulfonylanilines with phthalimidesulfenyl chloride afforded the precursors of transient o-iminothioquinones obtained very easily under mild reaction conditions. These species are efficient electron-poor dienes able to react with several electron-rich alkenes to give, with complete control of the regiochemistry, benzo[b][1,4]thiazine cycloadducts.

Key words

phthalimidesulfenyl chloride - electrophilic aromatic substitutions - o-iminothioquinones - Diels-Alder - heterocycles

References and Notes

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11

A small amount of the bis-sulfenylated derivative (5-10%) was also isolated.

12

The following procedures for the preparation of 3a, by sulfenylation of 2a with sulfenyl chloride 1, and synthesis of thiazine 5e, by cycloaddition of an o-iminothioquinone with p-methoxystyrene (4e), can be regarded as general procedures as well.
Synthesis of N -Thiophthalimide 3a: A solution of PhthNSCl (1; 0.788 g, 3.47 mmol) in anhyd CHCl₃ (10 mL) was added to a solution of N-tosyl aniline 2a (0.890 g, 2.89 mmol) in anhyd CHCl₃ (10 mL). The reaction mixture was stirred at r.t. for 3.5 h, diluted with CH₂Cl₂, washed with a sat. solution of NaHCO₃, and H₂O, and dried over Na₂SO₄. The material obtained after evaporation of the solvent was purified by flash chromatography on silica gel using CHCl₃ as eluent. o-N-Tosyl-N-thiophthalimide 3a was obtained as a white powder (0.390 g, 73% yield). IR (KBr disc): 3193, 2946, 2845, 1784, 1733, 1728, 1337, 1269, 1158, 1051 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 9.48 (s, 1 H, NH), 7.86-7.88 (m, 2 H), 7.73-7.75 (m, 4 H), 7.19-7.21 (m, 2 H), 6.86 (d, J = 2.4 Hz, 1 H), 6.15 (d, J = 2.4 Hz, 1 H), 3.83 (s, 3 H), 3.81 (s, 3 H), 2.36 (s, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 168.2, 164.4, 162.5, 143.8, 143.6, 135.8, 131.9, 104.8, 134.6, 129.5, 128.6, 127.4, 99.0, 95.4, 56.1, 55.7, 21.6. Anal. Calcd for C₂₃H₂₀O₆N₂S₂: C, 57.01; H, 4.16; N, 5.78. Found: C, 57.40; H, 4.11; N, 5.76.
Synthesis of Benzo[ b ][1,4]thiazine 5e: To a solution of sulfenamide 3a (0.250 g, 0.52 mmol) in anhyd CHCl₃ (4 mL), p-methoxystyrene (4e; 0.103 g, 0.77 mmol) and Et₃N (0.053 g, 0.52 mmol) were added in sequence. The solution was stirred at 60 °C for 17 h. The crude product was concentrated and purified by flash chromatography on silica gel (eluent: CH₂Cl₂-PE, 8:2) to give thiazine 5e as a yellow oil (0.200 g, 81% yield). IR (CHCl₃): 3017, 3000, 2913, 2836, 1350, 1247, 1165, 1036 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.50-7.52 (m, 2 H), 7.29-7.32 (m, 2 H), 7.18-7.20 (m, 2 H), 6.79-6.81 (m, 2 H), 7.04 (d, J = 2.4 Hz, 1 H), 6.29 (d, J = 2.4 Hz, 1 H), 5.72 (app t, X part of an ABX system, J = 6.0 Hz, 1 H), 3.82 (s, 3 H), 3.754 (s, 3 H), 3.746 (s, 3 H), 3.04 (AB part of an ABX system, J _AB = 13.2 Hz, 2 H), 2.38 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 158.70, 157.55, 155.86, 143.69, 136.25, 134.81, 131.09, 129.44, 127.56, 127.29, 113.80, 110.7, 105.89, 97.05, 58.21, 55.95, 55.61, 55.15, 31.68, 21.59. MS (rel. int.%): m/z (%) = 471 (100), 316 (98) [M⁺· - tosyl]. Anal. Calcd for C₂₄H₂₅O₅NS₂: C, 61.70; H, 5.80; N, 2.88. Found: C, 61.96; H, 5.75; N, 2.96.