Pyridine-Mediated Synthesis of 1,3-Diazetidin-2-ones (Aza-β-lactams): Novel Investigations on Isocyanate-Carbodiimde Reaction

Abstract

The reported cycloaddition reaction of isocyanates and symmetric carbodiimides is reinvestigated in the presence of pyridine. The Huisgen zwitterion generated by the 1:1 addition of pyridine to arylsulfonyl isocyanate is trapped by dialkyl carbodiimide to obtain symmetrical 1,3-diazetidin-2-ones via a novel intramolecular rearrangement.

Key words

1,3-diazetidin-2-one - aza-β-lactam - carbodiimide - arylsulfonyl isocyanate - pyridine

References and Notes

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22

To a magnetically stirred solution of pyridine (160 mg, 2 mmol) and p-toluenesulfonyl isocyanate (400 mg, 2 mmol) in CH₂Cl₂ (5 mL) was added dicyclohexyl carbodiimide (410 mg, 2 mmol) in CH₂Cl₂ (2mL). The reaction mixture was stirred for 12 h in r.t. After completion of the reaction, the solvent was removed under reduced pressure, and the residue was purified by column chromatography over silica gel (Merck 230-240 mesh) using a hexane-EtOAc (20:1) mixture as eluent. The product was recrystallized from Et₂O to obtain product 11a as colorless crystals, mp 110-112 ˚C, 0.17 g, yield 42%. IR (KBr): ν_max = 1866 (C=O), 1648 (C=N), 1532 and 1439 (Ar), 1317 and 1151 (SO₂) cm^-¹. Anal. Calcd (%) for C₂₁H₂₉N₃O₃S (403.53): C, 62.51; H, 7.24; N, 10.41. Found: C, 62.55; H, 7.25; N, 10.42%. MS (EI, 70 eV): m/z (%) = 322 (88), 279 (14), 248 (21), 220 (19), 197 (28), 155 (66), 123 (17), 91 (100), 69 (15), 55 (43), 41 (7). ^¹H NMR (500.13 MHz, CDCl₃): δ = 1.09-1.96 (20 H, m, 20 H of 2 Cy), 2.45 (Me), 3.68 (2 H, br, 2 NCH), 7.33 (2 H, d, ^³ J _HH = 7.8 Hz, 2 CH of Ph), 7.85 (2 H, d, ^³ J _HH = 7.8 Hz, 2 CH of Ph). ^¹³C NMR (125 MHz, CDCl₃): δ = 21.55 (Me), 25.01 (2 CH₂), 25.18 (4 CH₂), 30.89 (4 CH₂), 54.65 (2 NCH), 126.74 (2 CH of Ph), 129.49 (2 CH of Ph), 138.55 (C _ipso -SO₂), 143.65 (C _ipso -Me), 154.88 (C=O), 157.05 (C=N).
Crystal Data for 11a
C₂₁H₃₃N₃O₃S (CCDC 824721): M _W = 407.57, orthorhombic, space group 2ac, a = 21.8645 (18) Å, b = 9.7928 (9) Å, c = 10.0106 (9) Å, α = 90.00, β = 90.00, γ = 90.00, V = 2143.4 (3) Å^³, Z = 4, D _c = 1.263 mg/m^³, F(000) = 880, crystal dimension 0.26 ¥ 0.18 ¥ 0.07 mm, radiation, Mo Kα (λ = 0.71073 Å), 1.86 ≤ 2θ ≤ 25.00, intensity data were collected at 298 (2) K with a Bruker APEX area-detector diffractometer, and employing ω/2θ scanning technique,
in the range of -21 ≤ h ≤ 26, -11 ≤ k ≤ 11, -9 ≤ l ≤ 11; the structure was solved by a direct method, all nonhydrogen atoms were positioned and anisotropic thermal parameters refined from 2014 observed reflections with R (into) = 0.1497 by a full-matrix least-squares technique converged to R = 0.1334 and Raw = 0.3306 [I > 2 σ(I)].
Compound 11c
Colorless crystals, mp 109-111 ˚C, 0.18 g, yield 46%.
IR (KBr): ν_max = 1874 (C=O), 1659 (C=N), 1532 and 1439 (Ar), 1363 and 1150 (SO₂) cm^-¹. Anal. Calcd (%) for C₂₀H₂₇N₃O₃S (389.51): C, 61.67; H, 6.99; N, 10.79. Found: C, 61.66; H, 6.71; N, 10.82. MS (EI, 70 eV): m/z (%) = 389 (2) [M⁺], 368 (18), 313 (21), 292 (26), 240 (37), 197 (22), 155 (87), 111 (57), 91 (87), 57 (100), 43 (54). ^¹H NMR (500.13 MHz, CDCl₃): δ = 1.12-1.96 (20 H, m, 20 H of Cy), 3.68 (2 H, br, 2 NCH), 7.54 (2 H, t, ^³ J _HH = 7.4 Hz, 2 CH of Ph), 7.61 (1 H, t, ^³ J _HH = 7.1 Hz, CH of Ph), 7.97 (2 H, d, ^³ J _HH = 8.6 Hz, 2 CH of Ph). ^¹³C NMR (125 MHz, CDCl₃): δ = 25.01 (2 CH₂), 25.17 (4 CH₂), 30.90 (4 CH₂), 54.70 (2 NCH), 126.68 (2 CH of Ph), 128.89 (2 CH of Ph), 132.80 (CH of Ph), 141.42 (C _ipso -SO₂), 154.77 (C=O), 157.34 (C=N).