Study On Synthesis Of Imidazole-4(5)-substituted Series Compounds

In this paper, imidazole-4(5)-substituted series compounds were synthesized by usi-ng imidazole etc. as raw materials, and the products were characterized.The mixed acid as the nitration reagent,4-nirtoimidazole was synthesized by the reaction of the mixed acid and imidazole, the yield was91.2%. The optimal reaction conditions were as follows:n(imidazole):n(95%of fuming nitric acid):n(20%of fu-ming sulfuric acid)=1.0:1.4:3.5, the mixed acid was dropwised at60℃, the temperatu-re was rased to80℃and continue stirring for1.5h.The4-methyl imidazole was synthesized by the reaction of methylglyoxal, ammo-nia and formaldehyde, the yield was70.7%. The optimal reaction conditions were as follows:n(methylglyoxal):n(formaldehyde):n(ammonium oxalate)=1.0:1.1:1.3, pH was about3, the reaction was at60℃for2.5h.4,5-diiodo-1H-imidazole was synthesized by the iodination of imidazole and iodi-ne under alkaline conditions.1H-imidazole-4-iodo was synthesized by deiodination wit-h potassium sulfite. Firstly, n(imidazole):n(iodine):n(sodium hydroxide)=1.0:2.5:5.0, t-he reaction was at room temprature for3h, the yield was84.4%. Secondly, n(4,5-diiodo-1H-imidazole):n(potassium sulfite)=1:7, the reaction was at100℃for8h, th-e yield was71.4%.Benzimidazole was synthesized by cyclization reaction of o-phenylene diamine an-d formic acid. When n(o-phenylene diamine):n(formic acid)=1.0:1.5, the yield was80.7%.4,5-imidazoledicarboxylic acid was synthesized by oxidation reaction of benzi-midazole and hydrogen peroxide.5g benzimidazole was dissolved in40mL concent-rated acid,45mL30%of hydrogen peroxide was dropwised at100℃, the reaction was at140℃for1h, the yield was84.9%.1H-imidazole-4-carboxylic acid was synt-hesized by decarboxylation reaction of4,5-imidazoledicarboxylic acid.5g4,5-imida-zoledicarboxylic acid was added to170mL acetic anhydride, the reaction was at110℃for7.5h, the yield was69.8%.Ethyl1H-imidazole-4(5)-carboxylate was synthesized by conventional esterification or the reaction with thionyl chloride. For the former method:5mL concentrated sul-furic acid as catalyst,5g1H-imidazole-4-carboxylic acid and50mL ethanol was sti-rred at reflux temperature for16h and the yield was71.0%. For the latter method:6mL thionyl chloride was carefully dropwised to the mixture of5g1H-imidazole-4- carboxylic acid and50mL ethanol. The reaction mixture was stirred at reflux temper-ature for6h and the yield was78.6%.4-hydroxymethylimidazole was synthesized by reduction reaction of lithium alumi-num hydride and ester. The optimal reaction conditions were as follows:2.8g Ethyl1H-imidazole-4-carboxylate and0.9g lithium aluminum hydride was stirred at room temperature for1h, the yield was65.9%.