An Unprecedented and Concise Method for the Synthesis of 1,3-Thiazino-[3,4a][1,3]benzimidazoles via a Three-Component Reaction

Abstract

For the first time, a novel, simple, and highly efficient synthesis of N-aryl-N-[1,3]thiazino[3,4a][1,3]benzimidazol-1-ylidenamines is presented. The one-pot reaction of o-phenylenediamine, aryl isothiocyanate, and methyl acetylenecarboxylate proceeds in toluene-dichloromethane without any catalyst under reflux conditions to produce the title compounds in 60-70% yield. From a mechanistic point of view, the reaction is proposed to occur via two cyclizations and four heteroatom-carbon bond formations.

Key words

benzimidazole - 1,3-thiazine - thiazinobenzimidazole - methyl propiolate - o-phenylenediamine - aryl isothiocyanate - multicomponent reaction

References and Notes

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20

To a magnetically stirred 5 mL flask containing o-pheny-lenediamine (0.11 g, 1 mmol) and CH₂Cl₂ (2 mL as solvent) was added phenyl isothiocyanate (0.14 g, 1 mmol). After 15 min, methyl acetylenedicarboxylate (0.08 g, 1 mmol) in toluene (5 mL) was added to the reaction mixture and stirring continued under reflux. After completion of the reaction (ca. 10 h; monitoring by TLC based on the presence of intermediate 5), the solvent was removed under reduced pressure, and the residue was washed with cold toluene, Et₂O, and EtOAc and crystallized from CH₂Cl₂.
Compound 4a: yield 0.19 g (70%); white powder; mp 220 ˚C (dec.). IR (KBr): 1685 (C=N), 1663 (C=N), 1638 (C=C), 1589 and 1527 and 1473 and (C=C Ar). ^¹H NMR (500.13 MHz, CDCl₃): δ_H = 6.32 (1 H, d, ^³ J _H,H = 7.7 Hz, SCHCH), 7.31 (1 H, t, ^³ J _H,H = 7.5, CH of Ar), 7.35 (1 H, t, ^³ J _H,H = 7.2 Hz, CH of Ar), 7.44 (2 H, d, ^³ J _H,H = 7.6 Hz, 2 CH of Ar), 7.52 (1 H, t, ^³ J _H,H = 7.4 Hz, CH of Ar), 7.55 (1 H, d, ^³ J _H,H = 7.8 Hz, CH of Ar), 7.60 (2 H, t, ^³ J _H,H = 7.5 Hz, 2 CH of Ar), 7.66 (1 H, d, ^³ J _H,H = 7.9 Hz, CH of Ar), 8.17 (1 H, d, ^³ J _H,H = 7.7 Hz, SCHCH). ^¹³C NMR (125.75 MHz, CDCl₃): δ_C = 106.01 (SCH=CH), 108.49 (CH of Ar), 119.62 (CH of Ar), 122.18 (CH of Ar), 124.90 (CH of Ar), 128.22 (2 CH of Ar), 129.17 (C _ipso of Ar), 129.47 (CH of Ar), 129.86 (2 CH of Ar), 132.52 (SCHCH), 134.74 (CH=CHC), 142.41 (C _ipso of Ar), 148 (C _ipso of Ar), 160.38 (N=CS). MS: m/z (%) = 279 (7) [M⁺ + 2], 277 (6) [M⁺], 260 (100), 250 (10), 207 (9), 185 (9), 167 (18), 149 (49), 130 (16), 118 (9), 105 (92), 91 (55), 77 (90), 57 (48). 43 (53). Anal. Calcd for C₁₆H₁₁N₃S (277.34): C, 69.29; H, 4; N, 15.15. Found: C, 69.32; H, 4.2; N, 15.13.
Compunds 4e and 4e′: yield 0.20 g (67%); white powder; mp 230 ˚C (dec.). IR (KBr): 1676 (2 C=N), 1635 (2 C=N), 1591 (2 C=C), 1533 and 1509 and 1464 and (Ar). ^¹H NMR (500.13 MHz, CDCl₃): δ_H = 2.43 (6 H, s, 2 Me), 2.45 (3 H, s, Me), 2.51 (3 H, s, Me), 6.27 (1 H, d, ^³ J _H,H = 7.7, SCHCH), 6.28 (1 H, d, ^³ J _H,H = 7.8 Hz, SCHCH), 7.11 (1 H, d, ^³ J _H,H = 7.9 Hz, CH of Ar), 7.15 (1 H, d,^³ J _H,H = 8.2 Hz, CH of Ar), 7.32 (4 H, d, ^³ J _H,H = 7.3, 4 CH of Ar), 7.34 (1 H, s, CH of Ar), 7.38 (4 H, d,^³ J _H,H = 8.1 Hz, 4 CH of Ar), 7.41 (1 H, d, ^³ J _H,H = 8.2 Hz, CH of Ar), 7.45 (1 H, s, CH of Ar), 7.54 (1 H, d, ^³ J _H,H = 8.2 Hz, CH of Ar), 8.11 (1 H, d, ^³ J _H,H = 7.7Hz, SCHCH), 8.12 (1 H, d, ^³ J _H,H = 7.8 Hz, SCHCH). ^¹³C NMR (125.7 MHz, CDCl₃): δ_C = 21.37 (2 Me), 21.71 (Me), 21.75 (Me), 105.62, and 105.79 (2 SCH=CH), 108.01 and 108.59 (2 CH of Ar), 119.17 and 119.65 (2 CH of Ar), 123.28 (2 CH of Ar), 126.14 (2 CH of Ar), 127.20 (C _ipso of Ar), 127.87 (2 CH of Ar), 128.90 (C _ipso of Ar), 129.30 (C _ipso of Ar), 130.10 (C _ipso of Ar), 130.60 (2 CH of Ar), 132.16 and 132.23 (2 CH of Ar), 132.40 and 132.53 (2 SCHCH), 134.83 (2 CH=CHC), 139.43 (2 C _ipso of Ar), 140.37 and 142.41 (2 C _ipso of Ar), 148.04 (2 C _ipso of Ar), 160.38 (2 N=CS). MS: m/z (%) = 290 (22), 289 (100), 274 (6), 260 (10), 246 (6), 224 (4), 208 (2), 167 (16), 149 (42), 129 (5), 111 (7), 97 (13), 83 (15), 57 (23), 43 (17). Anal. Calcd for C₁₈H₁₅N₃S (305. 40): C, 70.79; H, 4.95; N, 13.76. Found: C, 70.77; H, 4.97; N, 13.74.