Preparation of 2-Substituted Benzimidazoles and Related Heterocycles Directly from Activated Alcohols Using TOP Methodology

Abstract

A one-pot procedure for preparing 2-substituted benzimidazoles directly from activated alcohols in good to excellent yields using a new Tandem Oxidation Process (TOP) is reported. The use of this methodology to prepare 2-substituted benzoxazoles and 2-substituted benzothiazoles is also described.

Key words

2-substituted benzimidazoles - 2-substituted benzoxazoles - 2-substituted benzothiazoles - tandem oxidation procedure - one-pot

References

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10

Representative Experimental Procedure:
Activated manganese dioxide (Aldrich 21764-6, 0.653 g, 7.50 mmol) was added to a mixture of benzyl alcohol (0.054 g, 0.50 mmol), N-methyl 1,2-phenylenediamine (0.15 mL, 1.25 mmol), HCl in Et₂O (2 M, 0.04 mL, 15 mol%) and 4 Å molecular sieves (0.5 g) in dry toluene (12 mL). The mixture was stirred at 105 °C for 18 h. The mixture was cooled to ca. 50 ºC, hot filtered through Celite^®, and the residue washed with excess CH₂Cl₂. The combined organic fractions were concentrated in vacuo and the residue purified using column chromatography on silica (petroleum ether-EtOAc, 3:1) to give 1-methyl-2-phenylbenzimidazole (1a, 0.094 g, 90%) as a brown solid, R_f = 0.3 (petroleum ether-EtOAc, 2:1); mp 96 °C, lit.¹² mp 94-95 °C. The spectroscopic data obtained were consistent with those reported in the literature.¹²