A Catalyst-Free Synthetic Route to Thiazolo[3,4-a]benzimidazole Derivatives through a Three-Component Reaction

Abstract

A convenient approach for the synthesis of thiazolo[3,4-a]-benzimidazole derivatives has been developed. Three-component reaction of readily available o-phenylenediamines, aryl isothiocyanate, and 4-chloro-3-oxobutanoate in toluene–dichloromethane without any catalyst proceeds under reflux to afford the title compounds in high yields. The structure of the target molecule was confirmed by X-ray diffraction.

Key words

o-phenylenediamine - aryl isothiocyanate - 4-chloro-3-oxo-butanoate - thiazolo[3,4-a]benzimidazole - multicomponent reaction

• References and Notes

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• 11 A mixture of o-phenylendiamine 1 (1 mmol) and phenyl isothiocyanate 2 (1 mmol) was stirred in CH₂Cl₂ at room temperature for 10 min, after this time 4-chloro-3-oxobutanoate (1 mmol) in toluene (4 mL) was added to the above mixture, and the reaction was stirred at reflux for 1 h. After completion of the reaction (monitored by TLC), compound 3 was separated by column chromatography (silica gel, n-hexane–EtOAc, 10:1). Methyl (Z)-2-{1-(phenylimino)-3H-[1,3]thiazolo[3,4-a][1,3]-benzimidazol-3(4H)-yl}acetate (3a) Yellow crystals, yield 0.27 g (80%), mp 125–128 °C. IR (KBr): 3357 (NH), 1720 (CO₂Me), 1634 (C=N), 1582, 1486 and 1419 (Ar) cm^–1. ¹H NMR (300.13 MHz, CDCl₃): δ = 2.86 (d, AB system, ² J _HH = 15.2 Hz, 1 H, CH), 3.08 (d, AB system, ² J _HH = 15.2 Hz, 1 H, CH), 3.51 (d, AB system, ² J _HH = 11.1 Hz, 1 H, CH), 3.58 (s, 3 H, OMe), 3.73 (d, AB system, ² J _HH = 11.1 Hz, 1 H, CH), 6.62 (d, ³ J _HH = 7.7 Hz, 1 H, CH of Ar), 6.67 (t, ³ J _HH = 7.6 Hz, 1 H, CH of Ar), 6.85 (t, ³ J _HH = 7.6 Hz, 1 H, CH of Ar), 6.88 (d, ³ J _HH = 8.0 Hz, 2 H, 2 × CH _ortho of Ph), 7.05 (t, ³ J _HH = 7.2 Hz, 1 H, CH _para of Ph), 7.30 (t, ³ J _HH = 7.6 Hz, 2 H, 2 × CH _meta of Ph), 7.46 (d, ³ J _HH = 7.5 Hz, 1 H, CH of Ar). ¹³C NMR (75 MHz, CDCl₃): δ = 40.7 (CH₂S), 41.6 (CH₂CO₂Me), 51.8 (OMe), 87.2 (C^3a), 109.0 (CH⁵), 113.2 (CH⁸), 118.2 (CH _para of Ph), 121.3 (2 × CH _ortho of Ph), 123.4 (CH⁶), 123.9 (CH⁷), 129.1 (2 × CH _meta of Ph), 130.9 (C^8a), 143.3 (C^4a), 150.8 (C _ipso -N=C), 154.1 (NCS), 169.6 (CO₂Me). MS (EI, 70 eV): m/z = 340 [M⁺ + 1], 313, 266, 216, 190, 149, 131, 104, 77. Anal. Calcd (%) for C₁₈H₁₇N₃O₂S (339.41): C, 63.70; H, 5.05; N, 12.38. Found: C, 63.69; H, 4.49; N, 12.28. Crystal data for 3a C₁₈H₁₇N₃O₂S (CCDC 1425335): M _W = 339.41, monoclinic, P21/n, a = 10.048(5) Å, b = 8.630(5) Å, c = 18.780(5) Å, α = 90.000(5), β = 91.338(5), γ = 90.000(5), V = 1628.0(13) ų, Z = 4, D _c = 1.385 mg m^–3, F (000) = 712, crystal dimension 0.23 × 0.18×0.15 mm radiation, Mo Kα (λ = 0.71073Å), 2.17 ≤ 2 θ ≤25.10, intensity data were collected at 293(2) K with a Bruker APEX area-detector diffractometer, and employing ω/2θ scanning technique, in the range of –11 ≤ h ≤ 11, –6 ≤ k ≤ 10, –22 ≤ l ≤ 17; the structure was solved by a direct method, all nonhydrogen atoms were positioned and anisotropic thermal parameters refined from 2313 observed reflections with R (into) = 0.0507 by a full-matrix least-squares technique converged to R = 0.0378 and R _aw = 0.1001 [I > 2σ(I)]. Methyl (Z)-2-[1-(3-Bromophenylimino)-3H-[1,3]thiazolo-[3,4-a][1,3]benzimidazol-3(4H)-yl]acetate (3b) Yellow oil, yield 0.26 g (62%). IR (KBr): 3372 (NH), 1727 (CO₂Me), 1633 (C=N), 1578, 1488 and 1411 (Ar) cm^–1. ¹H NMR (300.13 MHz, CDCl₃): δ = 2.93 (d, AB system, ² J _HH = 16.2 Hz, 1 H, CH), 3.31 (d, AB system, ² J _HH = 16.2 Hz, 1 H, CH), 3.49 (d, AB system, ² J _HH = 11.1 Hz, 1 H, CH), 3.62 (d, AB system, ² J _HH = 11.1 Hz, 1 H, CH), 3.77 (s, 3H, OMe), 6.69 (d, ³ J _HH = 7.8 Hz, 1 H, CH of Ar), 6.85 (t, ³ J _HH = 7.8 Hz, 1 H, CH of Ar), 6.97 (t, ³ J _HH = 7.8 Hz, 1 H, CH of Ar), 6.98 (d, ³ J _HH = 7.8 Hz, 1 H, CH of Ar), 7.17–7.28 (m, 3 H, 3 × CH of Ar), 7.76 (d, ³ J _HH = 7.5 Hz, 1 H, CH of Ar). ¹³C NMR (75 MHz, CDCl₃): δ = 40.4 (CH₂S), 40.8 (CH₂CO₂Me), 52.4 (OMe), 87.6 (C^3a), 109.8 (CH⁵), 114.7 (CH⁸), 120.2(CH of Ar), 120.6 (CH of Ar), 122.5 (C _ipso Br), 124.7 (CH⁶), 125.1 (CH⁷), 127.0 (CH of Ar), 130.3 (CH of Ar and C^8a), 142.3 (C^4a), 151.0 (C _ipso N=C), 154.7 (NCS), 171.0 (CO₂Me). Anal. Calcd (%) for C₁₈H₁₆BrN₃O₂S (418.31): C, 51.68; H, 3.86; N, 10.05. Found: C, 51.60; H, 3.78; N, 10.01.