A Facile Synthesis of 2-Aminobenzoxazoles and 2-Aminobenzimidazoles Using N-Cyano-N-phenyl-p-toluenesulfonamide (NCTS) as an Efficient Electrophilic Cyanating Agent

Abstract

A facile synthesis of 2-aminobenzoxazole and 2-aminobenz­imidazole derivatives employing a nonhazardous electrophilic cyanating agent: N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) with various substituted 2-aminophenols and benzene-1,2-diamine derivatives in the presence of lithium hexamethyldisilazide (LiHMDS) is described. This novel protocol boasts operational simplicity, shorter reaction time, and simple workup.

Key words

2-aminobenzoxazoles - 2-aminobenzimidazoles - electrophilic cynating agent - nonhazardous - N-cyano-N-phenyl-p-toluenesulfonamide

• References and Notes

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• 19 Typical Experimental Procedure for the Synthesis of 2-Aminobenzaxozole from o-Aminophenol (Table 2, Entry 1) To a solution of o-aminophenol (400 mg, 3.67 mmol) and NCTS (998 mg, 3.67 mmol) in THF (6 mL), 1 M LiHMDS in hexane (3.67 mL, 3.67 mmol) was added and stirred at 5 °C to r.t. for 1 h. Then the reaction mixture was poured in ice water and stirred for 15 min. Then extracted with EtOAc, the organic layer was separated. The organic layer was washed with brine solution. Then organic layer was dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtained pure 2-aminobenzaxozole in 90% yield (471 mg).
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• 21 Spectral Data for 1f (Table 2, Entry 6) Mp 136–138 °C; R_f = 0.28 (40% EtOAc–cyclohexane). ¹H NMR (400 MHz, DMSO-d ₆): δ = 6.96 (d, J = 7.65 Hz, 1 H), 7.09 (s, 1 H), 7.12 (m, 2 H), 7.19 (d, J = 7.28 Hz, 1 H), 7.30 (m, 2 H), 7.32 (m, 1 H), 7.36 (s, 2 H, NH₂). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 118.2, 121.1, 124.6, 126.5, 128.2, 132.4, 138.2, 142.8, 144.6, 152.1, 168. ESI-MS: m/z = 211.19 [M + H]⁺. Spectral Data for 1g (Table 2, Entry 7) Mp 168–170 °C; R_f = 0.32 (40% EtOAc–cyclohexane). ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.22 (d, J = 8.4 Hz, 1 H), 6.90 (d, J = 2.4 Hz, 1 H), 6.76 (s, 1 H), 5.24 (br s, 2 H, NH₂), 3.82 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 55.6, 96.8, 115.1, 135.8, 150.8, 158.1, 166.2. ESI-MS: m/z = 165.2 [M + H]⁺.

The same procedure was applied for the synthesis of 2-aminobenzimidazole derivatives (Table 2, entries 8–14). The spectral data were in accordance with those reported in the literature:
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