Research On Mechanism Ofα-acetyl-γ-butyrolactone Synthesis And Its Application

a-Acetyl-y-butyrolactone (ABL) is an important drug intermediate and synthon in organic chemistry. As vitamin B1, delay heartache, chloroqhyll, fungicides prothioconazole, anti-convulsant drugs clomethiazole hydrochloride, the antipsychotic risperidone pyrimidine and special medical polymer materials, and are expanded the domestic and overseas markets constantly, the demand of ABL is also increased year by year. So far, there are only two published methods for ABL synthesis. The first one uses y-butyrolactone (GBL) and ethyl acetate (EtOAc) as raw materials, sodium as condensating agent and alkylbenzene as the solvent. The other method uses ethylene oxide and ethyl acetoacetate as raw materials. The former has more the advantages of low cost, high yield, unsafe hidden danger relatively small than the latter. The process is a commonly used method in domestic industrial production. However, the production process, using toluene as solvent, and mixtures of acetate and y-butyrolactone was added dropwise in the molten state of the sodium. In the inducing phase, a large amount of easily gasifiable acetate and the reaction generating byproduct of ethanol, hydrogen were produced. Red material, burning, even an explosion and other accidents were usually occured. In addition, due to a-acetyl-y-butyrolactone has larger solubility (about20%) in water. Water phase need organic solvent extract, post-processing operate relatively troublesome and serious pollution.This work systematically studied the entire production process, in order to make domestic synthetic a-acetyl-y-butyrolactone industrial production commonly method is more reasonable, safe, reduce pollution and streamline operations. An environmentally friendly, safe, simple and efficient new method was been established for the synthesis of ABL with the yield higher. Specific research contents and results are as follows.1. The mechanism of ABL synthesis was explored.The mechanism of ABL synthesis from GBL and EtOAc was explored by detecting the material changes involved with GC/MS and the enthalpies of formation of the synthons, products, and possible intermediates were calculated using the density functional theory. GBL forms a carbanion of y-butyrolactone by losing an a-H under strongly alkaline conditions. ABL is then obtained via two reaction mechanisms. One of the reaction mechanisms involves direct reaction of the carbanion of y-butyrolactone with EtOAc to produce ABL. The other involves the formation of a carbanion of a-(2-hydroxy-tetrahydrofuran-2-yl)-y-butyrolactone through the reaction of two molecules of GBL, and the subsequent combination of this anion with EtOAc to produce ABL2. Established the new process for synthetic ABL with raw material replacd toluene as solvent.The mechanism of ABL synthesis showed that it is unnecessary to take into account raw materials’local thickness, and their self-condensation under these conditions in the synthesis of ABL process. Considering the reasons above, this work applied raw material replaced alkylbenzene as the solvent, and avoided environmental pollution by alkylbenzene; also, accidents such as red material and fire were avoided by specific surface area of sodium metal control. Meanwhile, through to selecting the type and concentration of acid, neutralizing temperature and other conditions, Effective isolation of the organic and aqueous phases was performed using the salting out method.The operation of the aqueous phase using an organic solvent extraction was cancelled, and the post-processing was simplified. The production costs reduced more than3100yuan per ton, and the yield increased from76%to higher than90%. The industrialization production line with annual output of2,000t was established.3. Established a treatment method for phosphate wastewater combined production of a variety of phosphate.In the process of production ABL,1ton of ABL produces, meanwhile byproducts phosphate wastewater about2tons. Production conditions were systematically studied for Phosphate wastewater from the production ABL as raw material. A treatment method was established for phosphate wastewater combined production of a variety phosphate (sodium dihydrogen phosphate, disodium hydrogen phosphate, trisodium phosphate, sodium trimetaphosphate, sodium hexametaphosphate, and sodium tripolyphosphate). The indexes of phosphate products were analyzed and the results showed all of them met the requirements of corresponding in dustrial phosphate standards.4. A method for simultaneous determination of ABL, by-product and raw material was established by gas chromatography.In order to achieved effective control of industrial production.A method for simultaneous determination contents of ABL, GBL and α-(2-tetrahydro furanylidene)-y-butyrolactone (AGBL) by gas chromatography was established with ethyl hexanoate as an internal standard. The method has been applied to the process in which GBL and ethyl acetate were used as raw material to produce ABL.The results showed that the peak area ratio of the measured component to the internal standard has a good linear relationship with component concentration in the range of the0-30.13g/L for ABL,0-15.08g/L for GBL and0-9.06g/L for AGBL, the correlation coefficients are more than0.9991, recoveries were between96.5-102.9%; Relative standard deviations were between0.10-2.50%. And the method is applied in ABL production process control and product analysis, and satisfactory results were obtained, which provides the basis for the optimization of the best technological conditions and establishments of product standards of ABL.5. Revision of quality standard for industrial a-acetyl-y-butyrolactoneIn order to ensure the product quality, meet the requirements of production and quality of downstream products, the current status of the backward standards for product are changed present, a relatively scientific and reasonable product quality standards was established. A method for simultaneous determination contents of ABL, benzene and toluene by gas chromatography was established with correction area normalization method using ABL as an internal standard.