N-cyclohexylimidazole can be prepared via the procedure of Martinez et al. [1]
Procedure: To a 3-neck flask with a magnetic stir bar and methanol (30 mL) were attached two dropping funnels and a reflux condenser. One funnel contained a mixture of 40% aqueous glyoxal (11.6 mL, 0.101 mol) and 37% aqueous formaldehyde (7.5 mL, 0.101 mol) in 1:1 methanol: water (50 mL). The second funnel contained a mixture of cyclohexylamine (10 g, 0.101 mol) and 28% aqueous ammonia (14 mL, 0.101 mol) in methanol (30 mL). After heating the methanol in the flask to 50 degC, both dropping funnel solutions were added dropwise, simultaneously. The solution was subsequently heated at 75 degC for 3h. Upon cooling the solution to room temperature, the layers were partitioned by addition of diethyl ether (100 mL) and water (100 mL). Product was extracted with diethyl ether (3x50 mL). The combined organic extracts were dried with Mg2SO4, desiccant filtered off, and solvent removed by rotary evaporation. The crude product was purified by column chromatography (1:1 hexanes:EtOAc). N-cyclohexylimidazole was obtained as an off-white solid.
Notes:
- Attempts to purify the product via short-path distillation were unsuccessful as unidentified impurities codistill with the product. N-Cyclohexylformamide was identified as one of the byproducts by GC-MS.
[1] Martinez, R.; Torregrosa, R.; Pastor, I. M.; Yus, M. Isoprene as Lithiation Mediator: Synthesis of 2-Substituted 1-Alkylimidazole Derivatives. Synthesis 2012, 44, 2630-2638