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Study On Synthetic Technology Of Phenylglycine And P-Chlorophenylglycine

Posted on:2006-06-01Degree:MasterType:Thesis
Country:ChinaCandidate:Y R XuFull Text:PDF
GTID:2121360155464660Subject:Chemical Engineering
Abstract/Summary:PDF Full Text Request
D-phenylglycine, one of enantiomers of DL-phenylglycine, is an important medicinal intermediate material used to synthesize β-Lactam antibiotics such as ampicillin, cephallexin, cephradine. DL-chlorophenylglycine is also the raw material for many agriculture pesticides. For example, Chlorfenapyr is importmant medicinal intermediate products. Bucherer-bergs Method produced the two products in industry currently. In industrial process, benzhexol was generated by phenylaldehyde or P-chloro-phenylaldehyde reacted with sodium cyanide, then the goal product was produced by the alkaline hydrolysis of benzhexol. There are two drawbacks in the classical processes. Firstly, toxic substance sodium cyanide was used in reaction process, which needed more labour protection and longer synthesis step and brought serious environmental pollution. Secondly, hydrolysis reaction needed ro carry out at pressure condition and caused inconvenience for production. As people's environment protection conscious enhanced and much more attention have been paid to environment protection and hope to seek an environmental amity method.Analysis methods of DL-phenylglycine and DL-p-chlorophenylglycine are established.IRwas used to indentify DL-phenylglycine and DL-p-chlorophenylglycine. HPLC is selected to analyze their contents and trace the whole process of experiment. The optimal analytic conditions are selected by investigating the effects of wave length and the ingredient of mobile phase and flow rate on detection and isolation.On the base of reading the relevant documents, the features of various synthesis methods of phenylglycine were compared and an environmental friendly method was studied, in which Phenylglycine was synthesized by benzaldehyde, chloroform, sodium hydroxide and ammonia water in the presence of phase transfer catalyst. The reaction process is easy to proceed without the poisonous material, such as cyanide. Raw material is easily available and its price is lower. Reaction conditions are mildness. It is benefical to low production cost and lessen production management. Mono-factor experiments were carried out in order to investigate the effects ofreaction conditions on yield of p-chloro-phenylglycine. Synthesis reaction processes were traced by HPLC method and the changing rules of yield with different factors have been getten. Subsequently, Orthogonal experiments were tested and the optimal technological conditions were obtained by orthogonal experiment. At the same time, as required by industry and environment, the filter liquor of reaction (mother liquid) are recycled in order to reduce the waste water discharged and to recover raw material and intermedium and realized clean production.The products produced in reaction process needed to be purified and the purity of sample obtained by purification process was analysed by HPLC and its purity was as high as 99.5%, which can meet commercial standard.As D-phenylglycine is an important medical intermediate, the resolution of DL-phenylglycine was discussed preliminary. During the experiment D-camphorsulfonic acid was used as resolution agent. The yield of mono-pass resolution reached 44.15%. Recovered from the process with supplementing the consumption of fresh D-Camphorsulfornic can be used to the next reaction. Four experiment results of resolution of phenylglycine conform to standard sample. At the same time, the other enantiomer was racemized by various tests. All kinds of effect fators were studied. Optimal condition of resolution of phenylglycine was confirmed. According to resolution test and racemization test, the resolution rate of phenylglycine can reach to 78%.
Keywords/Search Tags:Phenylglycine, P-chloro-phenylglycine, Synthesis, HPLC, Resolution
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