Niclosamide Ethanolamine Salt Synthesis Process Research

Niclosamide was the only recommended moUuscacide by WHO since 1972, and was widely used to kill oncomelania to prevent and cure of snail fever. At the same time, niclosamide is also a good repellence of tapeworm. When used as moUuscacide to prevent and cure of snail fever, it is 5-8 times effective than sodium pentachlorophenate. More over, it is less toxic to humanbeing. There were few study of the synthesis of niclosamide in our country. Niclosamide we needed primarily relied on importation, and it is expensive. The main purpose of this study is to synthesize niclosamide with domestic material and to reduce the cost of manufacturing it.This study has synthesized niclosamide, using 5-chloro-salicylic acid and 2-chloro-4-nitro aniline as major material. Phosphorus is used to convert 5-chloro-salicylic acid into 5-chloro-salicylic acyl chloride, improving the acylating ability so as to increase the reaction speed and the conversion rate.This article profoundly studies the yield influencing factors. Optimum manufacturing condition can be obtained after having studied four factors: mol ratio of 5-chloro-salicylic acid and 2-chloro-4-nitro aniline, phosphorus consumption, reaction temperature and reaction time,The optimum reaction condition is as follows: Put 1 mol 5-chloro-salicylic acid, 1.11 mol 2-chloro-4-nitro aniline and one-third of 0.51 mol Phosphorous into reactor. Then raise the temperature to 84.5C and slowly added remained Phosphorous into reactor. Keep the temperature for 157 minutes. After reaction finished, cool the mixture with ice water while agitating so as to get crystallizing niclosamide. Filter the mixture when the temperature reaches less than 10C. Wash the cake three times with 70% acetone, one or two times with clean water, faint yellow solid is obtained. Niclosamide powder yielded after dried the faint yellow solid.In this article, separation and purification methods of niclosamide have been studied. The detail is: crystallization in xylene and then filter, wash the cake three times with 70% acetone and 1~2 times with clean water, finally dried the cake.Niclosamide is qualitative analysed and quantified in this article. The melt point of niclosamide is 233C. 3303cm-1, 3270 cm-1. 3243 cm-1, 3199 cm-1, 3100.9 cm-1, 1653.7cm-1, 1610.8 cm-1, 1568.8 cm-1, 1521.7 cm-1, 1348.7 cm-1.1328. 7cm-1, 1283. 5 cm-1, 1217. 9 cm-1, 1414. 1 cm-1 are the principal IR absorption of niclosamide. Niclosamide has been qualified through non-aqueous titration. Weigh some niclosamide and boil with 50ml ethanediol solution of KOH for 150 minutes, then wash the condenser tube with 100ml alcohol and add the washing liquid to the ethanediol solution. Titrate the mixed solution with ethanol solution of acetic acid. According to the saponification consumption of alkali we can calculate the content of niclosamide. The content of the niclosamide synthesized in this study are all above 98%.The process of manufacture niclosamide ethanolamine salt is as follows: dissolve niclosamide in hot acetone, drop one time over-dose ethanol amine slowly into the hot solution, boil the solution for 2 hours, then cool and filter it. Wash the cake with pure acetone, orange colour powder, that is niclosamide ethanolamine salt, can be obtained after dried the cake.