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Synlett
Volumn , Issue 1, 2009, Pages 63-66
Synthesis of 1-methylbenzimidazoles from carbonitriles
Author keywords

Benzimidazoles; Carbonitriles; Cross coupling; Heterocycles
Indexed keywords

EID: 62449216626     PISSN: 09365214     EISSN: 14372096     Source Type: Journal    
DOI: 10.1055/s-0028-1087383     Document Type: Article
Times cited : (28)
References (45)
  • 7
    • 32044452135 scopus 로고    scopus 로고
    • Neier, R, Ed, Thieme: Stuttgart
    • (b) Grimmett, M. R. In Science of Synthesis, Vol. 12; Neier, R., Ed.; Thieme: Stuttgart, 2002, 529.
    • (2002) Science of Synthesis , vol.12 , pp. 529
    • Grimmett, M.R.1
  • 14
    • 62449193118 scopus 로고    scopus 로고
    • 2-Cyclohexyl-1-methyl-1H-benzimidazole (3a) Diamine 1 (244 mg, 2.00 mmol, NaH (80.0 mg, 60% dispersion in mineral oil, 2.00 mmol, and abs. toluene (1.0 mL) were successively added to nitrile 2a (218 mg, 2.00 mmol, The mixture was stirred for 3 h at 120°C in a tightly closed reaction vial, then completely transferred on top of a column (SiO2, and chromatographed (hexane-EtOAc, 1:1; Rf, 0.32) to give the title compound 3a (384 mg, 1.79 mmol, 90, as a light brown solid, mp 102°C (lit.13a 104°C, 1H NMR (500 MHz, CDCl3, δ, 1.30-1.48 (m, 3 H, 1.74-2.03 (m, 7 H, 2.84 (tt, J, 3.5, 11.6 Hz, 1 H, 3.74 (s, 3 H, 7.20-7.31 (m, 3 H, 7.72-7.77 (m, 1 H) ppm. 13C{1H} NMR (125 MHz, CDCl 3, δ, 25.82 (CH2, 26.32 (2 CH2, 29.52 (CH3, 31.46 (2 CH2, 36.33 (CH, 108.80 CH, 119
    • 2 (214.31): C, 78.46; H, 8.47; N, 13.07. Found: C, 78.40; H, 8.55; N, 13.05.
  • 32
    • 62449292520 scopus 로고    scopus 로고
    • 1-Methyl-2-phenyl-1H-benzimidazole (3h) Diamine 1 (6.1 g, 50 mmol, NaH (2.0 g, 60% dispersion in mineral oil, 50 mmol) and abs. mesitylene (10 mL) were successively added to nitrile 2h (5.2 g, 50 mmol, The mixture was heated to reflux for 16 h (inner temp ca. 170°C, oil bath 210°C, After cooling to ambient temperature, the mixture was filtered through SiO2 (1 cm, the residue washed with CH 2Cl2 (5 mL, and the combined filtrates evaporated. The residue was chromatographed (SiO2, hexane-EtOAc, 1:1; R f, 0.34) to give the title compound 3a (6.2 g, 30 mmol, 60, as a light yellow solid, mp 91°C (lit.18b 92-93°C, 13C{1H} NMR (125 MHz, CDCl3, δ, 31.57 (CH3, 109.54 (CH, 119.76 (CH, 122.33 (CH, 122.67 (CH, 128.58 (2 CH, 129.35 (2 CH, 129.63 (CH, 130.16 (C, 136.51 (C, 142.91 (C, 153.70 (C) ppm
    • 18b
  • 33
    • 36349025735 scopus 로고    scopus 로고
    • cataCXium FSulf = dicyclohexyl{2-sulfo-9-[3-(4-sulfophenyl) propyl]-9-fluorenyl}phosphonium hydrogensulfate; for use in Suzuki reactions, see: (a) Fleckenstein, C. A.; Plenio, H. Green Chem. 2007, 9, 1287.
    • cataCXium FSulf = dicyclohexyl{2-sulfo-9-[3-(4-sulfophenyl) propyl]-9-fluorenyl}phosphonium hydrogensulfate; for use in Suzuki reactions, see: (a) Fleckenstein, C. A.; Plenio, H. Green Chem. 2007, 9, 1287.
  • 35
    • 62449339806 scopus 로고    scopus 로고
    • 2-(Biphenyl-4-yl)-1-methyl-1H-benzimidazole (4) A mixture of bromophenyl compound 3i (91 mg, 0.32 mmol, 1.0 equiv, PhB(OH)2 (42 mg, 0.35 mmol, 1.1 equiv, Na2PdCl 4 (1.2 mg, 4.2 μmol, 1.3 mol, cataCXium Fsulf (3.3 mg, 4.5 μmol, 1.5 mol, and K2CO3 (131 mg, 945 μmol, 3 equiv) was placed in a Schlenk tube and twice evacuated and flushed with N 2. Degassed H2O (0.5 mL) and BuOH (0.5 mL) were added, and the resulting mixture was stirred for 16 h at 100°C. Subsequently, the organic layer was separated and the aqueous layer extracted with CH 2Cl2 (5 mL, The combined organic layers were dried (MgSO4, and after filtration, the solvent was evaporated and the residue chromatographed (SiO2, hexane-EtOAc, 1:1, R f, 0.48) to give the title compound 4 82 mg, 0.29 μmol, 92, as a yellow solid, mp 164
    • +].
  • 36
    • 62449170311 scopus 로고    scopus 로고
    • cataCXium FBu = (9-butyl-9-fluorenyl)dicyclohexylphosphonium tetrafluoroborate; for use in Sonogashira reactions, see ref. 24a
    • cataCXium FBu = (9-butyl-9-fluorenyl)dicyclohexylphosphonium tetrafluoroborate; for use in Sonogashira reactions, see ref. 24a
  • 37
    • 62449280125 scopus 로고    scopus 로고
    • 1-Methyl-2-[4-(phenylethynyl)phenyl]-1H-benzimidazole (5)28 A suspension of bromophenyl compound 3i (91 mg, 0.32 mmol, 1 equiv, phenylacetylene (38 mg, 0.38 mmol, 1.2 equiv, Na 2PdCl4 (1.5 mg, 5.1 μmol, 1.6 mol, cataCXium FBu (3.6 mg, 7.2 μmol, 2.3 mol, and CuI (1.5 mg, 7.8 mmol, 2.5 mol, in i-PrNH2 (1.0 mL) was stirred under an inert atmosphere for 16 h at 100°C. Subsequently, all volatile materials were removed in vacuo, the residue dissolved in CH2Cl2 (5 mL, and washed with H 2O (2 x 3 mL, The organic layer was dried (Na2SO 4, and after filtration, the solvent was evaporated. Chromatography of the residue (SiO2; hexane-EtOAc, 2:1; Rf, 0.29) gave the title compound 5 (81 mg, 0.26 mmol, 84, as a light yellow solid, mp 152°C (lit.28 153-155°C, 1H NMR 500 MHz, CDCl
    • +].
  • 42
    • 0000279636 scopus 로고
    • Angew. Chem. 1994, 106, 2473.
    • (1994) Angew. Chem , vol.106 , pp. 2473
  • 43
    • 62449244801 scopus 로고    scopus 로고
    • E)-1-Methyl-2-[4-(2-phenylethenyl)phenyl, 1H-benzimidazole (6) A mixture of bromophenyl compound 3i (60 mg, 0.21 mmol, 1 equiv, freshly distilled styrene (44 mg, 0.42 μmol, 2.0 equiv, Pd(OAc)2 (5.0 mg, 21 μmol, 0.1 equiv, Ph3P (14 mg, 51 mmol, 0.24 equiv, Et3N (85 mg, 0.84 mmol, 4.0 equiv, and abs. DMF (3.0 mL) was stirred for 16 h at 100°C under an inert atmosphere. Subsequently, all volatile materials were removed in vacuo, the residue dissolved in CH2Cl2 (5 mL, and washed with H2O (2 x 3 mL, The organic layer was dried (Na2SO 4, and after filtration, the solvent was evaporated. Chromatography of the residue (SiO2; hexane-EtOAc, 2:1; Rf, 0.27) gave the title compound 6 (31 mg, 0.10 mmol, 48, as a light yellow solid, mp 150°C. 1H NMR (500 MHz, CDCl3, δ, 3.86 s
    • +].
  • 45
    • 62449207736 scopus 로고    scopus 로고
    • 2-[4-(Cyclohexylamino)phenyl]-1-methyl-1H-benzimidazole (7) A suspension of Pd(OAc)2 (3.0 mg, 11 μmol, 5.0 mol, and rac-BINAP (7.0 mg, 11 μmol, 7.5 mol, in abs. toluene (1.5 mL) was stirred for 5 min at 23°C under an inert atmosphere. Bromophenyl compound 3i (60 mg, 0.21 mmol, 1 equiv, CyNH2 (27 mg, 0.27 mmol, 1.3 equiv, and NaOt-Bu (34 mg, 0.36 mmol, 1.7 equiv) were added, and the resulting mixture was stirred for 16 h at 85°C. Subsequently, it was diluted with CH2Cl2 (5 mL) and washed with sat. NaHCO3 solution (5 mL, The organic layer was dried (MgSO4, and after filtration, the solvent was evaporated. Chromatography of the residue (SiO2; hexane-EtOAc, 1:2; R f, 0.44) gave the title compound 7 (42 mg, 0.14 mmol, 65, as a light yellow solid, mp 145°C. 1H NMR 500 MHz, CDCl3, δ, 1.13-1.29
    • +].

* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.