An Efficient One-Pot Synthesis of 1,4-Oxathiane and 1,4-Thiomorpholine Derivatives

Abstract

An efficient one-pot reaction of nitromethane, isothiocyanates, and three-membered heterocyclic rings (oxiranes and aziridines) for the synthesis of 1,4-oxathiane and 1,4-thiomorpholine derivatives is reported. This procedure is carried out in the presence of K₂CO₃ in DMF at 60 °C.

Key words

cyclization - epoxides - heterocycles - multicomponent reaction - ring opening

• References and Notes

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• 21 Typical Procedure for the Preparation of Aryl Hydrazides 5a–l and 6a,b To a stirred mixture of 2 (1.0 mmol), 3, or 4 (1.2 mmol) and K₂CO₃ (1mmol) in DMF (2 mL), nitromethane (1 mmol, 0.061 g) was added over 30 min, and the mixture was stirred for 8 h at 60 °C. After completion of the reaction (monitored by TLC), the mixture was allowed to cool to r.t., poured into H₂O (4 mL), and extracted with CH₂Cl₂ (3 × 3 mL). The combined organic extracts were dried over anhydrous Na₂SO₄, filtered, and concentrated under vacuum. Finally, the residue was purified by column chromatography to afford pure product.
• 22 N-Ts-aziridines 4a and 4b were prepared following literature procedures.²⁰ Representative Analytical Data N-(6-methyl-1,4-oxathian-3-ylidene)benzenamine (5a) Pale yellow oil; yield 0.17 g (82%). IR (KBr): ν_max = 3025, 2967, 1530, 1330, 1323, 1113 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 1.27 (3 H, d, ³ J = 7.4 Hz, Me), 3.46–3.55 (2 H, m, CH₂), 4.63–4.67 (H, m, CH), 4.86 (H, d, ² J = 10.1 Hz, CH), 4.89 (H, d, ² J = 10.2 Hz, CH), 7.10 (2 H, d, ³ J = 6.9 Hz), 7.19 (H, t, ³ J = 7.1 Hz), 7.27 (2 H, d, ³ J = 6.7 Hz). ¹³C NMR (125.7 MHz, CDCl₃): δ = 13.6 (Me), 35.3 (CH₂), 69.3 (CH), 74.7 (CH₂), 118.7 (2 CH), 125.2 (CH), 130.1 (2 CH), 147.8 (C), 165.4 (C). MS: m/z (%) = 207 (2) [M⁺], 175 (37), 130 (45), 118 (52), 98 (71), 77 (100). Anal. Calcd for C₁₁H₁₃NOS (207.29): C, 63.74, H, 6.32, N, 6.76, S, 15.47. Found: C, 63. 85, H, 6.38, N, 6.55, S, 15.40. 2-[-5-(Phenylimino)-1,4-oxathian-2-yl]phenol (5b) Yellow solid, mp 81–83 °C; yield 0.17 g (58%). IR (KBr): ν_max = 3034, 2961, 1551, 1348, 1324, 1130 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 3.46–3.51 (2 H, m, CH₂), 4.64–4.68 (H, m, CH), 4.83 (H, d, ² J = 9.8 Hz, CH), 4.91 (H, d, ² J = 9.7 Hz, CH), 4.82 (H, br, OH), 6.71–6.78 (2 H, m), 7.02–7.06 (2 H, m), 7.09 (2 H, d, ³ J = 7.4 Hz), 7.22–7.30 (3 H, m). ¹³C NMR (125.7 MHz, CDCl₃): δ = 35.4 (CH₂), 69.4 (CH₂), 80.2 (CH), 118.6 (CH), 121.2 (CH), 123.2 (2 CH), 125.2 (C), 127.6 (CH), 128.1 (CH), 130.2 (CH), 131.4 (2 CH), 147.4 (C), 153.9 (C), 164.1 (C). MS: m/z (%) = 285 (1) [M⁺], 208 (17), 192 (53), 152 (65), 134 (79), 107 (100), 77 (63). Anal. Calcd for C₁₆H₁₅NO₂S (285.36): C, 67.34, H, 5.30, N, 4.91, S, 11.24. Found: C, 67.52, H, 5.43, N, 4.75, S, 11.16. N-(5-Phenyl-4-tosylthiomorpholin-2-ylidene)benzenamine (6a) Pale yellow solid, mp 89–91.5 °C; yield 0.34 g (80%). IR (KBr): ν_max = 3012, 2941, 1555, 1521, 1345, 1324, 1108 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 2.26 (3 H, s, Me), 3.40–3.46 (2 H, m, CH₂), 4.23–4.26 (H, m, CH), 4.40 (H, d, ² J = 11.0 Hz, CH), 4.51 (H, d, ² J = 11.0 Hz, CH), 7.11–7.34 (10 H, m), 7.39 (2 H, d, ³ J = 6.7 Hz), 7.81 (2 H, d, ³ J = 6.5 Hz). ¹³C NMR (125.7 MHz, CDCl₃): δ = 24.3 (Me), 35.2 (CH₂), 50.1 (CH₂), 56.4 (CH), 122.4 (2 CH), 127.1 (CH), 127.3 (2 CH), 127.7 (CH), 128.1 (2 CH), 128.8 (2 CH), 129.5 (2 CH), 131.1 (2 CH), 136.3 (C), 139.4 (C), 141.3 (C), 148.7 (C), 164.5 (C). MS: m/z (%) = 422 (1) [M⁺], 390 (26), 272 (45), 169 (63), 118 (51), 103 (74), 91 (100), 77 (86). Anal. Calcd for C₂₃H₂₂N₂O₂S₂ (422.56): C, 65.37; H, 5.25, N, 6.63, S, 15.18. Found: C, 65.53; H, 5.39, N, 6.81, S, 15.07. N-(5-Benzyl-4-tosylthiomorpholin-2-ylidene)benzenamine (6b) Pale yellow solid, mp 94–96 °C; yield 0.40 g (91%). IR (KBr): ν_max = 3012, 2941, 1555, 1521, 1324, 1108 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 2.25 (3 H, s, Me), 2.64 (H, dd, ² J = 11.6 Hz, ³ J = 6.3 Hz, CH), 2.78 (H, dd, ² J = 11.6 Hz, ³ J = 6.5 Hz, CH), 3.38–3.49 (2 H, m, CH₂), 4.20–4.24 (H, m, CH), 4.38 (H, d, ² J = 10.8 Hz, CH), 4.43 (H, d, ² J = 10.8 Hz, CH), 7.11–7.33 (10 H, m), 7.41 (2 H, d, ³ J = 6.6 Hz), 7.83 (2 H, d, ³ J = 6.2 Hz). ¹³C NMR (125.7 MHz, CDCl₃): δ = 24.6 (Me), 34.7 (CH₂), 40.2 (CH₂), 51.3 (CH₂), 57.6 (CH), 121.8 (2 CH), 126.4 (CH), 127.1 (2 CH), 127.3 (CH), 128.3 (2 CH), 128.6 (2 CH), 129.4 (2 CH), 130.6 (2 CH), 135.7 (C), 137.1 (C), 140.5 (C), 149.4 (C), 164.0 (C). MS: m/z (%) = 436 (2) [M⁺], 404 (24), 286 (36), 155 (65), 131 (51), 118 (79), 91 (83), 77 (100). Anal. Calcd for C₂₄H₂₄N₂O₂S₂ (436.59): C, 66.02; H, 5.54, N, 6.42, S, 14.69. Found: C, 66.25; H, 5.67, N, 6.58, S, 14.57.