Studies On Synthesis And Activity Screening Of Hydantoin And 5,5-Dimethyl Hydantoin

Hydantoin is one of five-membered heterocyclic ring compounds and its derivatives are used widely in the fields of medicine, pesticide, printing, resin and organic synthesis . Early in 1875 at Urech had prepared hydantoin , but it has not been able to arouse people's interest, until the sixties, with the progressive-depth research, it was discovered that a lot of excellent properties of hydantoin derivatives, the widely uses of hydantoin and its derivatives were recognized by people. The literature reports indicated that hydantoin derivatives have many kinds of physiologic activities, each kind of different substitution hydantoin and its derivatives have the widespread pharmacology activeness and application. Exist because of its structure, as well as many functional groups have a greater reactivity of the different groups to replace hydantoin and its derivatives can be used for a variety of fields such as chemistry and chemical engineering, medicine, agriculture etc . The pharmacological effects of hydantoin derivatives have reported at anti-bacterial, anti-inflammatory, lowers blood sugar, sodium ion channel blockers, inhibit the generation of uremic toxins. So far, domestic reports about hydantoin derivatives used as a drug is less than abroad . Such as: sterilization, the maternity area, diabetes, the renal failure, the anti-inflammatory and antibacterial immune enhancement and so on.1-Methyl hydantoin is a kind of hydantoin derivatives and also the principal effective component of Rana temporaria chensinensis .Its structure has been identified. Anti-inflammatory, anti-low serum albumin levels, the elimination of the role of reactive oxygen and free radicals, the treatment of rheumatoid arthritis are reported about pharmacological activity of 1-methyl hydantoin . In this laboratory in previous studies, with pharmacological experiments confirmed that 1-methyl hydantoin extracted from Ranae temporaria chensinensis has strong anti-asthmatic effect, the same anti-asthmatic activity with aminophylline, slightly lower than codeine, but the toxicity is far smaller than these two.Based on previous studies, this study conducted a research about anti-asthmatic activity of hydatoin derivatives, selected hydantoin and 5,5-dimethyl hydantoin which have good anti-asthmatic activity less toxicity, and this study innovated the synthetic route for both compounds . At the screening in the selection of anti-asthmatic activity we choose mouse model similar to clinical cough . We make a scientific evaluation of antitussive efficacy of hydantoin,1-bromo-3-chloro-5,5-dimethylhydantoin,1,3-dibromo-5,5-dimethylhydantoin,1,3-dichloro-5,5-dimethylhydantoin,1-benzylhydantoin and 5,5-dimethyl hydantoin which is confirmed in the following experiment using guinea pig model .After anti-asthmatic activity screening, this study combined with the needs of industrial production has set up chemical synthesis process of hydantoin and 5,5-dimethyl hydantoin. Through screening of 2 chemical synthesis routes ,this study design the synthesis routeof 5,5 - dimethyl hydantoin by the method of Liquid-phase synthesis. We use the 2-amino-iso-butyric acid and cyanate as main raw materials, synthesis 5,5-dimethyl hydantoin by heat treatment under acid condition. The structures of the final compound is ensured by TLC, melting point,the ultraviolet spectrum, the infrared spectrum. We determined the contents of 5,5- dimethyl hydantoin by the method of HPLC, the purity of crude product is about 96%, the yield is 90%,the purity of product puritied is 98%. This technology possess many characteristics: convenient operation, bland reaction conditions, shorter route, fine security, and the yield and purity are more high. Therefore, this technology suits to industrialization production.This study design the synthesis route of hydantoin by the method of Liquid-phase synthesis. We use the glycine ethyl ester hydrochloride and cyanate as main raw materials, synthesis hydantoin by heat treatment under acid condition. The structures of the final compound is ensured by melting point,the ultraviolet spectrum, the infrared spectrum, the nuclear magnetic resonance hydrogen spectrum and the carbon spectrum. We determined the contents of hydantoin by the method of HPLC, the purity of crude product is about 98%, the yield is 78%,the purity of product puritied is 99%. This technology possess many characteristics: convenient operation, more bland reaction conditions, fine security, and the yield and purity are more high. Therefore, this technology suits to industrialization production.At present, the synthesis technology of hydantoin and 5,5-dimethyl hydantoin has been reported, however there is no literature report about the synthesis technology which is the same with this study . The results of this research provide a feasible method and the reliable theory basis for the further study on hydantoin and its derivates.