Study On Preparation And Application Of Important Intermediates In New Process Of Synthesizing Floxacin

The floxacin of FQNS have a lot of similarity in the mother structure, and the old route of their synthesis have many drawbacks such as more steps, time consuming, more foreign matter and poor yield. All of the researchers used the ethyl N,N-dimethylamino acrylate as the most important intermediate in the new synthetic methods of this kind of drugs. Compared with those old route, the new routes have shortened the synthetic route, cut down the consumption of the raw material, decurtated the reaction time, increased the yield of reaction, improve equipment utilization and simpled the postprocessing. This is a kind of economic synthesis methods of floxacin.A lot of previous documents reported some methods of how to synthesize ethyl N,N-di- methylamino acrylate. But in these methods, the raw materials were difficult to get, expensive price or need harsh craft, lower yield. So these methods were not comfortable for industrial production.This thesis studied the preparation and application of important intermediates, ethyl N,N-dimethylamino acrylate, in the new process of synthesizing floxacin. To dimethylamine hydrochloride, ethyl acetate, carbon monoxide as raw materials, ethanol sodium as a catalyst, through the heating and pressurizing to synthesize objective product. Inspect some factors detailedly, the factors included the match of the raw materials, reaction temperature, reaction pressure, different polar solvents and use phase-transfer catalyst and so on. Based on a large number of experimental contrasts, the best experimental conditions are as follows: the solvent is toluene, dimethylamine hydrochloride: ethyl acetate: ethanol sodium = 2:3:2, the reaction temperature is 60℃, and the reaction pressure 20 bar. The yield is 60 percent. Under this, we carried out five amplification experiments. The yields were stable. The products were identified by IR,HPLC-MS and HNMR.This thesis studied the synthesis of floxacin which used tetrafluorobenzoic acid as raw material and ethyl N,N-dimethylamino acrylate as intermediate. Studied the prepare of Levofloxacin, Gatifloxacin, Sparfloxacin et al. The result implied that this new craft is feasible, and it shortened the process, milded the reaction condition, reduced the contamination and increased the yield.In our country, there are no reports of synthesis of N,N-dimethylamino acrylate until now, and there are no factory produce or sell this intermediate. Use this intermediate can greatly reduce the route of synthesizing of the floxacin, and almost all types of floxacin can use this intermediate to reconstruct the texture.So this research has practical significance and application prospects.