Synthesis Of Oxazolidinone Compounds

Oxazolidinones have the widespread use in medicine, agricultural chemicals, the improvement of polymer, the intermediate of organic synthesis and so on. We have synthesized eighteen oxazolidinone compounds by five processes of preparation, and these compounds had been characterized by the element analysis, infrared analysis and nuclear magnetic resonance hydrogen spectrum. Moreover, some compounds have more better biological activity.5-Chloromethyl-2-oxazolidinone was prepared by using epichlorohydrin, sodium cyanate, and magnesium sulfate as raw materials, and water was used as reaction solvent. The optimal conditions are mole ratio of epichlorohydrin, sodium cyanate and magnesium sulfate 1:2:2, reaction temperature 90-95℃, reaction time 1.5h. Solvent dosage is 10mL/ gram epichlorohydrin. The yield of 5-chloromethyl-2-oxazolidinone was more than 65.2%. 5-Chloromethyl-2-oxazolidinone and sodium phenolate were condensated to give 5-phenoxymethyl-2-oxazolidinone after taking off the sodium chloride in yield of 63.0%~78.0%. Dimethylsulfoxide was used as the solvent, and orthogonal experiment to the reaction condition had been carried out. The optimum conditions were reaction temperature 120°C, reaction time 20h, mole ratio of 5-chloromethyl-2-oxazolidinone and sodium phenolate 1:1. 3,5-Dimethylphenol and epichlorohydrin in sodium hydroxide were condensated to give l,2-epoxy-3-phenoxy propane, then the reation of l,2-epoxy-3-phenoxypropane and the carbamate afforded oxazolidinone in the yields of 69.0%~76.0%. The side reaction had been avoided effectively by the uses of the excessive epichlorohydrin and mixed catalysts. N-Substituted-5-acetylaminomethyl-2-oxazolidinone was prepared by use of epichlorohydrin as the raw material, and benzaldehyde as protecting agent of amino. After the process of ammonolysis, acylating and epoxidizing, carbamate was added to react with intermediate to give oxazolidinone. In this article, we used the benzaldehyde protection ammonolysis to avoid effectively the occurrence of the side reaction. 3-Acetylamino-l,2-epoxypropane was prepared by the use of calcium hydroxide as epoxidizing agent. Calcium hydroxide did not destruct the amido bond with low reaction temperature and short time. The yield of epoxidation was high in more than 93.9%. By the method of solid phase organic synthesis, we synthesized 2-oxazolidinone. The target compound was prepared by using ammonia methyl polystyrene resin as solid support. p-Hydrobenzoic acid and the resin were connected by amido bond in condensing agent of DCC, then condensated with epichlorohydrin in potassium carbonate, and reacted with carbamate to give oxazolidinone cycle. Finally, the goal compound was obtained by acidic dissociation.