Online NIR Analysis and Prediction Model for Synthesis Process of Ethyl 2-Chloropropionate

Online NIR Analysis and Prediction Model for Synthesis Process of Ethyl 2-Chloropropionate Wei Zhang, Hang Song, Jing Lu, Wen Liu, Lirong Nie, and Shun Yao School of Chemical Engineering, Sichuan University, Chengdu 610065, China Received 13 May 2015; Accepted 15 July 2015 Academic Editor: Richard G. Brereton Copyright © 2015 Wei Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Online near-infrared spectroscopy was used as a process analysis technique in the synthesis of 2-chloropropionate for the first time. Then, the partial least squares regression (PLSR) quantitative model of the product solution concentration was established and optimized. Correlation coefficient () of partial least squares regression (PLSR) calibration model was 0.9944, and the root mean square error of correction (RMSEC) was 0.018105 mol/L. These values of PLSR and RMSEC could prove that the quantitative calibration model had good performance. Moreover, the root mean square error of prediction (RMSEP) of validation set was 0.036429 mol/L. The results were very similar to those of offline gas chromatographic analysis, which could prove the method was valid. 1. Introduction Ethyl 2-chloropropionate (CAS number 535-13-7) is a clear colorless liquid with a pungent odor. Its flash point is 100°F and it is denser than water and insoluble in water. In recent years, as an important chemical intermediate and industrial reagent, it has been popularly applied in the synthesis of herbicides (e.g., phenoxypropionates, 2-(4-hydroxyphenoxy)propionate, and amino (or aryloxy) sulfonyl phenoxy propanates), plant auxiliaries (e.g., 2-chloroethyl trimethyl ammonium chloride, dimethylaminosuccinic acid), nonsteroidal antipyretic and anti-inflammatory drugs (e.g., naproxen, indomethacin, and ibuprofen), and so forth. Though the synthetic process of ethyl 2-chloropropionate is relatively simple, the current offline quantitative method for its production monitoring and quality control can hardly meet the requirements of related researchers and producers. Previously, Food and Drug Administration (FDA) issued a guidance document to pharmaceutical industry regarding the implementation of process analytical technology (PAT) in 2004. Process analytical technology (PAT) has been defined as “a system for designing, analyzing, and controlling manufacturing through timely measurements of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality” [1]. Recently, the application of near-infrared (NIR) spectroscopy has grown rapidly as an efficient online monitoring technique [2], which has been used as an ideal tool for PAT. The growing concentration on NIR is probably a direct result for its advantages of outstanding sensitivity, high speed, low noise, nondestruction, and enabling the analysis of complex samples without the need for pure samples compared to others [3–5]. Near-infrared (NIR) spectroscopy was used as a process analytical technology to monitor the amino acids concentration profile during hydrolysis process of Cornu Bubali by Wu et al. [6]. And the use of near-infrared diffuse reflectance spectroscopy for qualification of Ginkgo biloba extract was described as raw material for use in pharmaceutical products by Rose and coworkers [7]. NIR spectroscopy has also been used as an analyzer to determine the effect of several operating conditions on recovery, selectivity, and productivity for production of methyl isobutyl ketone (MIBK). The use of this PAT approach enabled the researchers to perform the necessary experiments in a time-efficient fashion and resulted in 30% improved productivity of MIBK [8]. Based on the above research status, the aim of this study was to use UV-NIR spectroscopy for online and nondestructive analysis of synthesis process of 2-chloropropionate catalyzed by ion exchange resin for the first time. The method of model updating was utilized to make the models more accurate and obtained better prediction results. The concentration values were very close to those obtained by offline gas chromatographic analysis. The developed method was supposed to provide foundation for further process chemical analysis and useful reference for similar online analytical research of synthetic reaction. 2. Experimental2.1. Chemicals and Materials All reagents used were of analytical grade. Methanol, ethanol, 2-chloropropionic acid (purity: 0.9956%), and ethyl 2-chloropropionate (purity: 0.9913%) were obtained from Kelong Chemical Inc. (Chengdu, China). D001 strong acidic cation exchange resin was purchased from Shengquan Chemical Inc. (Langfang, China). NIR spectrometer (NIRQUEST512), DH-2000-BAL deuterium light source, and optical fiber (T300-UV-VIS) were obtained from Ocean Optics (...truncated)