Process development in the fine chemical industry

As many other industries, the fine chemical industry is characterized by strong pressures to decrease the time-to-market. New methods for the early screening of chemical reaction kinetics are needed (Heinzle and Hungerbiihler, 1997). Based on the data elaborated, the digital simulation of the chemical reactors is possible. The design of optimal feeding profiles to maximize predefined profit functions and the related assessment of critical reactor behavior is thus possible, as seen in the simulation examples RUN and SELCONT. 

As many other industries, the fine chemical industry is characterized by strong pressures to decrease the time-to-market. New methods for the early screening of chemical reaction kinetics are needed (Heinzle and Hungerbiihler, 1997). 

---

The rest of this chapter is a discussion of selected examples of equipment used to study the kinetics of multiphase reactions. We begin with instrumentation suitable for industrial process development in the fine chemicals area and then move on to more sophisticated methods which can be used to extract true surface kinetics data even in the presence of sharp concentration gradients near the surface. 

Product innovation absorbs considerable resources in the fine chemicals industry, in part because of the shorter life cycles of fine chemicals as compared to commodities. Consequently, research and development (R D) plays an important role. The main task of R D in fine chemicals is scaling-up lab processes, as described, eg, in the ORAC data bank or as provided by the customers, so that the processes can be transferred to pilot plants (see Pilot PLANTS AND microplants) and subsequently to industrial-scale production. Thus the R D department of a fine chemicals manufacturer typically is divided into a laboratory or process research section and a development section, the latter absorbing the Hon s share of the R D budget, which typically accounts for 5 to 10% of sales. Support functions include the analytical services, engineering, maintenance, and Hbrary. 

Keller, A., E. Heinxle, and K. Hungerbuhler (1996). "Development and Assessment of Inherently Safe Processes in the Fine Chemical Industry. " International Conference and Workshop on Process Safety Management and Inherently Safer Processes, October 8-11, 1996, Orlando, FL, 213-223. New York American Institute of Chemical Engineers. 

In order to understand the challenges facing the application of catalysts in the fine chemicals industry, one has to understand not only the essential industrial requirements but also how process development is carried out, and which criteria determine the suitability of a catalyst. 

Surely, the concepts and paradigms of ionic liquids are new and still not fully accepted in the wider community many chemists consider with some skepticism the possibility of applying ILs as substitutes of common solvents in large-scale processes. Moreover, as has been recently evidenced,there are several prerequisites that determine the choices of development chemists working in the fine chemical industry ... 

Finally, in the fine chemical industry the time for the development of the production process for a new chemical entity is limited between a few months in the pharmaceutical industry to 1-2 years for agrochemicals. 

The electrochemical sensing of NADH is of great interest in the development of a dehydrogenase-based amperometric biosensor owing to the ubiquitous use of NADH as a cofactor for over 300 enzymes and in the fine chemicals industry using NAD -dependent biocatalysts [106]. The oxidation of NADH at bare and modified electrodes has been well studied and the oxidation process is dependent on the nature of the electrode used. The direct electrochemical oxidation of NADH at the bare electrode, irrespective of its nature, requires a high overpotential, despite the formal potential of the NAD /NADH redox couple at pH 7, which is reported to be... 

In the bulk chemicals business, where dedicated plants producing only one product are the norm, the optimisation of production through a combination of chemistry and plant design is much more straightforward than in the fine chemicals industry where multi-product plants are the norm. Volumes of individual products required by the market do not always permit the justification of dedicated plant. Consequently compromises have to be made in process operations to allow certain chemistries to be carried out on pre-established plant configurations. It is in this latter area where the talented process development chemist can make most impact on process optimisation and consequent waste minimisation. 

To select the best process for optimum manufacture is not a simple exercise. The process development chemist should be aware of all the possibilities but, on the other hand, is unlikely to be an expert in more than just a few techniques. As already discussed, the plant on which the process is to be operated is also an important factor. In the fine chemical industry, it has been recognised that a dedicated plant is difficult to justify, particularly at the early development stages. Processes must therefore be modified to fit the plant available at the time. The process development chemist has an armoury of approaches which can be regarded as a standard portfolio of variables to juggle. These include ... 

From the foregoing it will be clear that in fine chemicals process development the strategy differs profoundly from that in the bulk chemical industry. The major steps are (i) adaptation of procedures to constraints imposed by the existing facilities with some necessary equipment additions, or (ii) choice of appropriate equipment and determination of procedures for a newly built plant, in such a way that procedures in both cases guarantee the profitable, competitive, and safe operation of a plant. 

The reason for this is mostly rooted in the fact that historically the fine chemicals industry is a product (and not process) oriented industry, i.e. it focuses on the development of new products to maximize revenues in the... 

During the past decade, metal-catalyzed asymmetric reactions have become one of the indispensable synthetic methodologies in academic and industrial fields. The asymmetric isomerization of allylamine to an optically active enamine is a typical example of the successful application of basic research to an industrial process. We believe that Takasago s successful development of large-scale asymmetric catalysis will have a great impact on both synthetic chemistry and the fine chemical industries. The Rh-BINAP catalysts, though very expensive, have become one of the cheapest catalysts in the chemical industry through extensive process development. 

Quantitative failure frequency data are difficult to obtain for multipurpose batch plants in the way that they are often used in the fine chemicals and pharmaceutical industries. Moreover, a quantitative assessment requires detailed knowledge of the control instruments, which may not be available during process development Therefore, a semi-quantitative approach is proposed, providing the required reliability for future plant equipment. 

---