Study On Chemical Synthesis Of Canthaxanthin

Cantharidin is a carotenoid that exists in organisms and plays an important role.Cantharidin has been widely used as an additive in various industries because of its good coloring effect and health care.At present,some domestic enterprises also use their own technology to synthesize cantharidin,but there are always some problems,such as low product content and too many structural analogues.The purpose of this paper is to improve the existing synthesis process of cantharidin.In order to find a greener and simpler method for the synthesis of high purity cantharidin.The common synthesis methods of cantharidin are carbon chain extension and?-carotene one-step oxidation.The synthesis of cantharidin by carbon chain extension method needs to protect the carbonyl group on benzene ring,while the synthesis of?-carotene by this method does not need carbonyl protection and the production process is very mature.Cantharidin can be synthesized by one step oxidation of?-carotene.This method has the advantages of short reaction route and mild conditions.Therefore,this paper combines the two methods and adopts the synthesis route as follows:Tetraethylmethylenediphosphonate?C15phosphate??-carotene?cantharidin.In this paper,only two important and difficult parts of the whole route,the synthesis of Tetraethylmethylenediphosphonate and the synthesis of cantharidin,were completed and verified by ~1H nuclear magnetic resonance spectroscopy(~1H NMR)and mass spectrometry(MS).The main contents are as follows:(1)The synthesis of Tetraethyl methylenediphosphonate was carried out by the reaction of sodium diethyl phosphite with dichloromethane.The method is divided into three steps:the first step is the synthesis of sodium diethyl phosphite in petroleum ether solution.The molar ratio of diethyl phosphite to sodium ethanolate was 1?0.9,and the reaction time was 2 hours at 25?for 30?.The second step is the monosubstitution reaction of sodium diethyl phosphite with dichloromethane at 20?for 24 h,and the third step is the further substitution reaction with dichloromethane to give tetraethyl methylene diphosphonate at 35?for 72 h.After the reaction,the solution was refined.The target product was obtained by distillation.After final distillation,the purity of the positive product was 95.1%and the yield was 70.2%.(2)The canthaxanthin was prepared directly from?-carotene as raw material and by one-step oxidation method.The method dissolves?-carotene with chloromethane,and then adds a elemental iodine/potassium iodide system with a molar ratio of 1:4 to it as a catalyst,with sodium chlorate as oxidant,and the reaction during 4 hours under the condition that the molar ratio of?-carotene and sodium chlorate is 1:10-1:13,the solution is pH=4,and the temperature is 30?,The antioxidants were added to the reaction solution,and the coarse products obtained after washing were recrystallization in the chloroform-ethanol system,and then the isomerization was carried out,and the target products were finally obtained.The purity of the final product was 97.1%,the inverse ratio was 8:92,and the yield was72%.This synthetic route not only avoids the problem of excessive accumulation of by-products in pure carbon chain extension method and needs functional group protection,but also combines the advantages of one-step oxidation,which has certain reference significance for the production of cantharidin in China.