N-butyl-benzo-iso Thiazole Ketone

Transdermal delivery system is a kind of drug delivery system that drugs, which penetrate the skins, absorbed by capillary vessel enter into the body circulation and bring into curative effect. In order to overcome the skin barrier, penetration enhancers are often used to increase the blood drug concentration, so that the skin penetration velocity and concentration of the drugs can reach the curative demand. Therefore, the development and application of penetration enhancer become extremely important.This thesis is about the synthesis of a new penetration enhancer of great efficiency: thiazone. Orthogonal test method was used for studying on the synthesis of thiazone under phase transfer catalysis condition, using sodium saccharin and 1-butyl bromide as reactants, tetra-butyl ammonium bromide (TBAB) as phase transfer catalyst. The main factors and the minor factors were discussed through the experiments.The experimental results indicated that the reaction temperature and the dosage of 1-butyl bromide were the main factors while the reaction time and the dosage of TBAB were the minor factors. The increase of reaction temperature and dosage of 1-butyl bromide could both increase the yield of product in certain scope, but the excess increasing of them might bring in much by-products. Extending the reaction time could not remarkably increase the yield of product. When the molar ratio of TBAB and 1-butyl bromide was above 0.05:1, the increase of TBAB dosage could hardly increase the yield. The optimized parameters were that the feeding of sodium saccharin and 1-butyl bromide was on the theory ratio at 100°C for 10h under the condition that the molar ratio of TBAB and 1-butyl bromide was 0.05:1. Thus the yield was 87.63%, with white dry sheet crystal obtained.A new synthesis technique of thiazone was developed. The feeding of sodium saccharin and 1-butyl bromide was on the theory ratio in the solvent of DMF without any phase transfer catalyst. The experimental results indicated that the yield of product increased at first but decreased afterwards when increasing the reaction temperature, for the excess increasing of temperature brought in the by-products increase. The most appropriate temperature was 100℃.The melting point determination, the IR spectrum analysis and the element analysis of thiazone were carried out. The results match the literature values and the theory values. Besides these, the side-reaction and the separation of impurity were discussed in the thesis, supporting the further research in the future and industrialization.