Novel Synthesis of 2-Aminobenzimidazoles from Isoselenocyanates

Abstract

An efficient one-pot procedure for the synthesis of 2-aminobenzimidazoles from isoselenocyanates and various substituted diamines is described. Precipitation of elemental selenium from the reaction mixture greatly simplifies the purification procedure and also allows it to be re-used for preparation of isoseleno­cyanates. A possible mechanism for the formation of 2-aminobenzimidazoles is proposed.

Key words

2-aminobenzimidazoles - isoselenocyanates - cyclization - selenium recycling

References and Notes

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11

Typical Procedure for Compound 2e A mixture of 1-isoselenocyanato-4-methoxybenzene (1e; 0.212 g, 1 mmol) and phenylene-1,2-diamine (0.108 g, 1 mmol) were suspended in CHCl₃ (20 mL). The reaction was carried out at r.t. After 10 min the reaction was ceased, and the reaction mixture was concentrated under vacuum. The residue was washed with a mixture of hexane and EtOAc (hexane-EtOAc = 20:1) to obtain 1-(2-aminophenyl)-3-(4-methoxyphenyl) selenourea (2e) as a yellow solid (0.313 g, 98% yield). ^¹H NMR (400 MHz, DMSO-d ₆): δ = 9.63 (s, 1 H), 9.34 (s, 1 H), 7.26-7.29 (m, 2 H), 6.96-7.02 (m, 2 H), 6.87-6.90 (m, 2 H), 6.74 (dd, 1 H, J = 1.2, 8.0 Hz), 6.56 (dt, 1 H, J = 1.6, 7.6 Hz), 4.89 (s, 2 H), 3.74 (s, 3 H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 178.8, 157.0, 143.9, 132.5, 128.2, 127.4, 127.0, 124.4, 116.4, 115.9, 113.5, 55.2. HRMS (EI): m/z calcd for C₁₄H₁₅N₃OSe: 320.0302; found: 320.0317.

12

Procedure for Controlled Experiment
1-(2-aminophenyl)-3-(4-methoxyphenyl) selenourea (2e,
1 mmol) was suspended in DMF (20 mL) with magnetic stirring. The reaction was carried out at 70 ˚C. A light-avoiding control and a nitrogen-atmosphere control reaction were set up at the same time. The reaction was monitored by TLC. 2-Aminophenylselenourea was totally converted into 3e after 4 h in normal and light-avoiding control. The reaction in nitrogen atmosphere was prolonged to 36 h, but only trace of 3e was found.

13

Typical Procedure for Compound 3e
A mixture of 1-isoselenocyanato-4-methoxybenzene (1e; 0.212 g, 1 mmol) and phenylene-1,2-diamine (0.108 g, 1 mmol) was suspended in DMF (20 mL). The reaction vessel was heat to 70 ˚C with magnetic stirring. Tracing by TLC, the reaction completed when selenourea 2e disappeared. The reaction mixture was then cooled to r.t. and filtered to separate solid selenium. The solid selenium was washed by EtOAc (10 mL). The combined filtrate was concentrated under vacuum, and the residue was purified by column chromatography on silica gel (hexane-EtOAc = 1:1). A white solid N-(4-methoxyphenyl)-1H-benzo[d]imidazol-2-amine (3e, 0.215 g, 90% yield), was then obtained. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 10.79 (s, 1 H), 9.15 (s, 1 H), 7.65 (d, 2 H, J = 8.8 Hz), 7.26 (s, 2 H), 6.95-6.96 (m, 2 H), 6.91 (d, 2 H, J = 9.2 Hz), 3.73 (s, 3 H). ^¹³C NMR (100 MHz, DMSO-d ₆ + CDCl₃): δ = 154.1, 151.7, 138.0, 133.9, 119.8, 119.5, 114.0, 112.2, 55.1. ESI-MS: m/z = 240 [M + H]⁺.