Efficient One-Pot Synthesis of 2-Substituted Benzimidazoles from Triacyloxyborane Intermediates

Abstract

An efficient one-pot synthesis of 2-substituted benzim­idazoles via triacyloxyborane intermediates is reported. The mild protocol is efficient and tolerant of acid-labile functional groups.

benzimidazoles - borane-THF - carboxylic acids - tri­acyloxyboranes - diacyloxyboric acids - benzoxazoles

References and Notes

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17

General Procedure for the Formation of Benzimidazoles
To a carboxylic acid (2 mmol) in toluene (10 mL) in an ice-water bath was added dropwise a solution of borane-THF (1 M, 0.70 mmol) in THF. The mixture was stirred at r.t. for 30 min. Benzene-1,2-diamine (0.66 mmol) was added, and the mixture was heated at reflux with stirring for 12 h. After cooling, the mixture was concentrated in vacuo, and the residue was purified by flash chromatography. The physical data of the products in Table  [¹] , entries 1-11, 15, and 16 are consistent with those of reported literatures,^{¹0e,¹¹c,d,¹5} or those of authentic samples. The new compound characterizations are provided below.
tert -Butyl 2-(5-Methyl-1 H -benzo[ d ]imidazol-2-yl)-ethylcarbamate (Table 1, Entry 12)
^¹H NMR (300 MHz, CDCl₃): δ = 7.43 (d, J = 8.1 Hz, 1 H), 7.32 (s, 1 H), 7.04 (d, J = 8.1 Hz, 1 H), 5.40 (br, 1 H), 3.68-3.61 (m, 2 H), 3.12-3.18 (m, 2 H), 2.45 (s, 3 H), 1.40 (s, 9 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 156.7, 152.2, 132.0, 123.7, 114.3, 114.0, 79.9, 38.4, 30.2, 28.4, 21.6. ESI-HRMS: m/z calcd for C₁₅H₂₁N₃O₂ + H⁺: 276.1712; found 2761723. tert -Butyl 4-[(5-Chloro-1 H -benzo[ d ]imidazol-2-yl)-methyl]piperidine-1-carboxylate (Table 1, Entry 13) ^¹H NMR (500 MHz, CD₃OD): δ = 7.53 (d, J = 1.9 Hz, 1 H), 7.47 (d, J = 8.7 Hz, 1 H), 7.20 (dd, J = 1.5, 8.6 Hz, 1 H), 4.15 (d, J = 13.2 Hz, 2 H), 2.83 (d, J = 7.3 Hz, 2 H), 2.76 (br, 2 H), 2.10-2.02 (m, 1 H), 1.66 (d, J = 12.2 Hz, 2 H), 1.44 (s, 9 H), 1.36-1.28 (m, 2 H). ^¹³C NMR (125 MHz, CD₃OD): δ = 156.6, 156.5, 140.4, 137.8, 129.0, 123.8, 116.3, 115.4, 81.0, 44.6, 37.0, 36.4, 33.0, 28.7. ESI-HRMS: m/z calcd for C₁₈H₂₄ClN₃O₂ + H⁺: 350.1635; found: 350.1642.
5-Bromo-2-(thiophen-2-ylmethyl)-1 H -benzo[ d ]-imidazole (Table 1, Entry 14)
^¹H NMR (500 MHz, CD₃OD): δ = 7.72 (d, J = 1.5 Hz, 1 H), 7.47 (d, J = 8.5 Hz, 1 H), 7.41 (dd, J = 1.5, 8.5 Hz, 1 H), 7.32 (dd, J = 1.5, 5.5 Hz, 1 H), 7.04-7.03 (m, 1 H), 6.99 (dd, J = 3.5, 5.0 Hz, 1 H), 4.52 (s, 2 H). ^¹³C NMR (125 MHz, CD₃OD): δ = 155.8, 141.1, 139.4, 138.4, 128.1, 127.6, 126.6, 126.1, 118.7, 117.0, 116.3, 30.3. ESI-HRMS: m/z calcd for C₁₂H₉BrN₂S + H⁺: 292.9748; found: 292.9768.