Synthesis Process Optimization And Process Analysis Of Benorilate

As an anti-inflammatory and analgesic drug,benorilate has good medicinal value by overcoming the stimulation of the gastrointestinal tract under the premise of maintaining the efficacy.At present,the methods for preparing benorilate are divided into two major categories:direct synthesis and aspirinyl chloride two-step method.However,these two methods have problems such as low reaction temperature,long reaction time or easy hydrolysis in the reaction process,resulting in low yield.In this paper,aspirin and acetaminophen were used as raw materials to synthesize and dehydrate the benorilate under 4-pyrrolidinopyridine/dicyclohexylcarbodiimide.A synthetic method of benyl ester with suitable synthesis temperature,short synthesis time,small solvent dosage,easy process control and easy separation of product was obtained.For the analysis of the synthesis process of benorilate,high-performance liquid phase,gas chromatography,thin-layer chromatography and other analytical methods are currently used,but these traditional methods are not easy to operate and require long time,high cost,etc.While infrared spectroscopy,Raman spectroscopy has been widely used in rapid detection and online analysis.Based on the angle measurement method and spectral technique,an analytical model for predicting the content of benorilate was established,and the synthesis process of benorilate was realized online.The details are as follows:?1?Synthesis process optimization and qualitative analysis of benorilate:Aspirin and acetaminophen were used as raw materials,acetone was used as solvent,and benorilate was synthesized and dehydrated under 4-pyy/DCC conditions.The effects of different catalysts,material ratio,synthesis temperature,synthesis time and solvent dosage on the synthesis of benorilate were systematically studied.The synthesized products were qualitatively analyzed by infrared spectroscopy?IR?,gas chromatography?GC?and Raman spectroscopy?Raman?.The optimal process parameters for the optimization of benorilate synthesis process are:n_aspirin:n4-pyy</sub>=27.4,n?aspirin?:n?DCC?=1.08,V?acetone?=40mL,T=50°C,t=2 h.?2?Rapid analysis of the synthesis of benorilate using infrared spectroscopy:By collecting the original infrared spectrum data of the benorilate synthesis process sample and the benorilate reference substance,and the benorilate content of the process sample was determined by high performance liquid chromatography to be the true value,and the infrared spectrum data of the sample was converted into an angle to establish a synthesis process.A quantitative analysis predictive model of benorilate.The correlation coefficient between the model prediction result and the real value reaches 0.9953,and the predicted root mean square error is 0.0426.The established analytical prediction model can be used for the analysis of the reaction process of benorilate.?3?On-line analysis of benorilate synthesis process based on angle metric and Raman spectroscopy:Use Raman spectrometer collect on-line Raman spectrum data under different time points in the process,as a predictive model of the independent variable;meantime,the true content of benorilate at the corresponding time points is determined by HPLC and used as the dependent variable.A PLS prediction model for online analysis of benorilate synthesis process based on angle measurement was established.Compared with the true concentration value,the prediction result has a linear correlation coefficient of0.9909,and the obtained root mean square error is 0.0326,The established analytical prediction model can be used for the analysis of the reaction process of benorilate,and provide a new and effective method for the online monitoring of benoate content.</sub>