Study On Synthesis Of Novel Imidazole Derivatives

Imidazole compound is a very important kind of heterocycles being the core fragment ofdifferent natural products and biological systems. Due to their special molecular structure,these compounds have been widely applied such as in medicine, pesticides, organicluminescent materials because of its good biological activity and optical property. In thispaper, Kojic acid was used as raw material, through benzyl protection, oxidation andcyclization, in the end one novel imidazole derivatives12and fifteen novel compounds13a-owere synthesized, at the same time synthesis conditions of intermediate products5-benzyloxy-2-hydroxymethyl-pyran-4-one14,5-benzyloxy-4-oxo-4H-pyran-2-carb-aldehyde18and the target products were optimized, and better synthesis conditions were obtained.Structures of all products were elucidated on the basis of IR,¹H NMR,¹³C NMR and MS. Themain results are showed as follows.1,5-benzyloxy-2-hydroxymethyl-pyran-4-one14was synthesized by Kojic acid andbenzyl bromide under alkaline condition. The molar ratio of Kojic acid, benzyl bromide andalkali was fixed to1:1.2:1.2, sodium carbonate, sodium hydroxide and sodium hydrideeffecting the reaction yield was studied, the optimum synthesis conditions were obtained suchas the best base being sodium carbonate, the reaction temperature being70℃and the reactiontime being1hour, the yield was up to88%.2, IBX16was prepared by2-iodobenzoic acid, potassium bromate and2mol/L sulfuricacid at65℃, through post treatment reacted with acetic acid and acetic anhydride at85℃toform DMP17.3,5-benzyloxy-2-hydroxymethyl-pyran-4-one14was oxygenated by different oxidationagents such as manganese dioxide, PCC and DMP to5-benzyloxy-4-oxo-4H-pyran-2-carbald-ehyde18. The yield of DMP oxidation was the best achieving to85%. The reaction conditionswere studied such as methylene chloride being solvent, the molar ratio of5-benzyloxy-2-hydroxymethyl-pyran-4-one and DMP being1:1.1, the reaction temperaturebeing25℃and the reaction time being1hour.4, One novel2,4,5-trisubstituted imidazole12was achieved by5-benzyloxy-4-oxo-4H-pyran-2-carbaldehyde18, benzyl19, ammonium acetate20, L-prolineas catalyst through one-pot synthesis. Fifteen novel1,2,4,5-tetrasubstituted imidazoles13a-o were prepared by5-benzyloxy-4-oxo-4H-pyran-2-carbaldehyde18, benzyl19, ammoniumacetate20, primary amine21, L-proline as catalyst also through one-pot synthesis. The bettersynthesis condition was gained such as the molar ratio of benzil,5-benzyloxy-4-oxo-4H-pyran-2-carbaldehyde, ammonium acetate and4-toluidine being fixedto1:1:1:1, anhydrous methanol as solvent, reaction temperature being65℃, the reaction timebeing48hour and15mol%L-proline as catalyst.