On-line process control and reaction monitoring

Internal reflection spectroscopy is widely applied for on-line process control. In this type of application, the chemical reactor is equipped with an internal reflection probe or an IRE. The goal of this type of application is the quantification of reactant and/or product concentrations to provide real-time information about the conversion within the reactor. In comparison with other analytical methods such as gas chromatography, high-pressure liquid chromatography, mass spectrometry, and NMR spectroscopy, ATR spectroscopy is considerably faster and does not require withdrawal of sample, which can be detrimental for monitoring of labile compounds and for some other applications. 

For example, a high yield of an intermediate in a consecutive reaction depends sensitively on the instant in time when the reaction is quenched. For such applications, the fast response of the ATR method more than compensates for deficiencies related to sensitivity when the ATR technique is compared with other methods. The design of the equipment depends on the specific requirements of the application. 

Similar equipment for applications on the laboratory scale has been reported (and has recently been commercialized) (69-72). Most of the reported applications had the aim of investigating kinetics of chemical reactions as indicated by changes in liquid-phase concentrations. The equipment can typically be used at elevated temperatures and pressures. Applications to heterogeneous catalytic reactions include investigations of the enantioselective hydrogenation of exocyclic a,p-unsaturated ketones catalyzed by Pd/C in the presence of (A)-proline (73) and the esterification of hexanoic acid with octanol catalyzed by a solid acid (the resin Nafion on silica) (74). 

The combination of an ATR probe and a slurry reactor depicted in Fig. 10 yields IR spectra of the fluid containing dissolved reactants and products. However, if catalyst particles are found within the volume probed by the evanescent field, the catalyst itself and molecules adsorbed on it may be monitored as well. Indeed, 

Concentration profiles as measured with the equipment depicted in Fig. 10 (open symbols) and by GC analysis (closed symbols) for an esterification reaction between octanol and hexanoic acid. Conditions 200 ml, of reactant, 0.4mol/L of octanol, 0.4mol/L of hexanoic acid, l.Og Nafion resin/ silica, 447 K. The profiles were constructed from signals at 1720 and 1745 cm , and the spectra were corrected for solvent, octanol, and catalyst (74). 

This latter interpretation would mean that with the approach depicted in Fig. 10, the catalyst itself could be monitored. The authors reported that the silica-supported Nafion could not be observed in the beginning of their experiments and appeared in the spectra only after the catalyst interacted with octanol. This observation may indicate that the octyl groups promote the sticking of the catalyst particles onto the ATR probe, within the evanescent field. However, the example also shows that this approach may not be without problems, because it depends on the adsorption of the particles from the slurry reactor onto the ATR element. This process is accompanied by the adsorption of molecules on the catalyst surface and complicates the analysis. More important, as also indicated by the work of Mul et al. (74), this adsorption depends on the surface properties of the catalyst particles and the ATR element. These properties are prone to change as a function of conversion in a batch process and are therefore hardly predictable. 

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L. Zhu, R.G. Brereton, D.R. Thompson, P.L. Hopkins and R.E.A. Escott, On-line HPLC combined with mnltivariate statistical process control for the monitoring of reactions. Anal. Chim. Acta, 584, 370-378 (2007). 

Applications In contrast to El ionisation, ion-molecule reactions in IMR-MS usually avoid fragmentation [71]. This allows on-line multicomponent analysis of complex gas mixtures (exhaust gases, heterogeneous catalysis, indoor environmental monitoring, product development and quality control, process and emissions monitoring) [70], It should easily be possible to extend the application of the technique to the detection of volatiles in polymer/additive analysis. 

For all MicroSYNTH systems, reactions are monitored through an external control terminal utilizing the Easy WAVE software packages. The runs can be controlled by adjusting either the temperature, the pressure, or the microwave power output in a defined program of up to ten steps. The software enables on-line modification of any method parameter and the reaction process is monitored through an appropriate graphical interface. An included solvent library and electronic lab journal feature simplifies the experimental documentation. 

In some manufacturing process analysis applications the analyte requires sample preparation (dilution, derivatization, etc.) to afford a suitable analytical method. Derivatization, emission enhancement, and other extrinsic fluorescent approaches described previously are examples of such methods. On-line methods, in particular those requiring chemical reaction, are often reserved for unique cases where other PAT techniques (e.g., UV-vis, NIR, etc.) are insufficient (e.g., very low concentrations) and real-time process control is imperative. That is, there are several complexities to address with these types of on-line solutions to realize a robust process analysis method such as post reaction cleanup, filtering of reaction byproducts, etc. Nevertheless, real-time sample preparation is achieved via an on-line sample conditioning system. These systems can also address harsh process stream conditions (flow, pressure, temperature, etc.) that are either not appropriate for the desired measurement accuracy or precision or the mechanical limitations of the inline insertion probe or flow cell. This section summarizes some of the common LIF monitoring applications across various sectors. 

Process monitoring and control of API production, sans the regulatory environment, is analogous to that within the chemical industry. Since the early 1990s, numerous papers have been published noting on-line specnoscopic techniques as applied to API reaction monitoring. A representation of some of these on-line specnoscopic reaction monitoring techniques will be provided herein with additional information discussed in Chapter 15. 

Areas of application of reaction calorimetry include determination of calorimetric data for reactions and process design, for the kinetic characterization of chemical reactions and of physical changes, for on-line monitoring of heat release and other analytical parameters needed in subsequent process development as well as for the development and optimization of chemical processes with the objective, for instance, to increase yield or profitability, control the morphology or degree of polymerization and/or index of polydispersity, etc. 

Applications of the fibre optics transmittance or ATR probe are in quality control, reaction monitoring, skin analysis, goods-in checking, analysis at high and low temperature, radioactive or sterile conditions, and hazardous environments. Applications of the reflectance probe are for turbid liquids, powders, surface coatings, textiles, etc. By using an on-line remote spectrophotometer, real-time information is gathered about a chemical process stream (liquids, films, polymer melts, etc.), as often as necessary and without the need to collect samples. This determines more reliable process control. Remote spectroscopy costs less to maintain and operate than traditional techniques. Fernando et al. [48] have compared different types of optical fibre sensors to monitor the cure of an epoxy resin system. 

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