A Facile Synthesis of 1-Arenesulfonylazetidines through Reaction of 1-Arenesulfonylaziridines with Dimethylsulfoxonium Methylide Generated under Microwave Irradiation

Abstract

A simple, efficient and general method has been developed for the synthesis of 1-arenesulfonylazetidines through a one-pot reaction of 1-arenesulfonylaziridines with dimethylsulfoxonium methylide, generated under microwave irradiation, using alumina as solid support.

Key words

azo compounds - ring expansion - sulfur - ylides - heterocycles

References and Notes

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General Method for the Synthesis of 1-Arenesulfonyl-azetidines: The pertinent aziridine (1 mmol), trimethylsulfoxonium iodide (3 mmol) and KOH (3 mmol) were loaded on neutral alumina (0.5 mmol) solid support. This mixture was irradiated with microwaves for the specified time (Table [1] ). Only a single product (as shown by TLC) was formed. The reaction was quenched by addition of cold H₂O. The product was extracted with EtOAc and purified by simple crystallization or through column chromatography on silica gel.cis -2-Methyl-3-phenyl-1-(4-toluenesulfonyl)azetidine (3f): white crystalline solid; mp 105-106 °C; yield: 79%. IR: 1333, 1164 (SO₂) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.65 (m, 5 H), 7.32 (s, 4 H), 4.26 (q, J = 7 Hz, 1 H), 3.93 (distorted d, J = 6 Hz, 2 H), 3.41 (m, 1 H), 2.39 (s, 3 H), 0.98 (d, J = 7 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 127.2-137.4 (ArC), 63.02 (d), 53.47 (t), 38.17 (d), 21.42 (q), 17.02 (q). Anal. Calcd for C₁₇H₁₉NSO₂: C, 67.77; H, 6.31; N, 4.65. Found: C, 67.10; H, 6.40; N, 4.51. MS (FAB): m/z = 302 [MH⁺].2-Hexyl-1-(4-toluenesulfonyl)azetidine (3g): viscous oil; yield: 79%. IR: 1333, 1164 (SO₂) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.65 (d, 2 H), 7.32 (d, 2 H), 3.42-3.77 (complex m, 3 H), 2.38 (s, 3 H), 1.84 (complex m, 2 H), 1.18-1.32 (m, 10 H, aliphatic), 0.81 (t, J = 7 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 128.26-143.80 (ArC), 66.35 (d), 47.50 (t), 36.02 (t), 31.70 (t), 29.66 (t), 28.59 (t), 24.13 (t), 22.66 (t), 21.42 (q), 14.09 (q). Anal. Calcd for C₁₆H₂₅NSO₂: C, 65.08; H, 8.47; N, 4.74. Found: C, 64.88; H, 7.80; N, 4.30. MS (FAB): m/z = 296 [MH⁺]. 2-(4-Chlorophenyl)-1-(4-toluenesulfonyl)azetidine (3h): white crystalline solid; mp 108-109.5 °C; yield: 72%. IR: 1333, 1160 (SO₂) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.51 (m, 4 H), 7.31 (s, 4 H), 4.89 (t, J = 8 Hz, 1 H), 3.77 (dd, J = 6, 8 Hz, 2 H), 2.40 (s, 3 H), 2.25 (m, J = 8 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 127.83-139.14 (ArC), 65.11 (d), 47.43 (t), 25.89 (t), 21.41 (q). Anal. Calcd for C₁₆H₁₆NSO₂Cl: C, 59.72; H, 4.97; N, 4.35. Found: C, 59.72; H, 5.08; N, 4.07. MS (FAB): m/z = 322 [M⁺].2-(4-Bromophenyl)-1-(4-toluenesulfonyl)azetidine (3i): white crystalline solid; mp 118-119 °C; yield: 71%. IR: 1330, 1164 (SO₂) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.51 (m, 4 H), 7.28 (s, 4 H), 4.78 (t, J = 8 Hz, 1 H), 3.78 (dd, J = 6, 8 Hz, 2 H), 2.38 (s, 3 H), 2.25 (m, J = 8 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 127.83-139.14 (ArC), 65.15 (d), 47.43 (t), 25.89 (t), 21.42 (q). Anal. Calcd for C₁₆H₁₆NSO₂Br: C, 52.45; H, 4.37; N, 3.82. Found: C, 52.22; H, 4.44; N, 3.14. MS (FAB): m/z = 366 [M⁺].2-(4-Methylphenyl)-1-(4-toluenesulfonyl)azetidine (3j): white crystalline solid; mp 110-111 °C; yield: 71%. IR: 1334, 1163 (SO₂) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.42 (m, 4 H), 7.02 (m, 4 H), 4.87 (t, J = 8 Hz, 1 H), 3.77 (dd, J = 6, 8 Hz, 2 H), 2.40 (s, 3 H), 2.33 (s, 3 H), 2.28 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 123.3-140.29 (ArC), 65.83 (d), 47.27 (t), 25.83 (t), 21.4 (q), 21.38 (q). Anal. Calcd for C₁₇H₁₉NSO₂: C, 67.77; H, 6.31; N, 4.65. Found: C, 67.11; H, 5.95; N, 3.96. MS (FAB): m/z = 302 [MH⁺].

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The reaction vials were placed in the MW reactor supplied with a safety valve for release of overpressure.

35

After the set temperature of 90 °C is reached, the power regulates itself to maintain the reaction temperature.