The Fine-Chemical Industry

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. 

Total sales of the fine chemical industry were estimated to amount to about 12 biUion in 1991, by an in-depth analysis of the product portfolio of representative fine chemicals manufacturers (11) and by performing top-down analyses of the fife science industry (12). However, some consulting firms gave higher (- 60 x 10 ) figures for the size of the fine chemicals business (13). 

In certain applications it has not always been easy to hnd suitable metallic container materials, particularly in the nuclear-energy industry, where, for certain applications, corrosion resistance of the same order as that required by the fine chemical industry has to be achieved in order to prevent contamination of the process stream. Such difflculties have stimulated the study of corrosion in fused salts and have led to a fairly high degree of understanding of corrosion reactions in these media. 

In the pharmaceutical industry, and to some extent the fine chemicals industry, an important advantage of a batch reactor is traceability. The product from a particular batch will have a uniform consistency, and can be uniquely labelled and readily traced. In contrast, the product from a continuous process may change gradually over time, and it is therefore more difficult to trace a particular impurity or fault in the material. Batch reactors are, however, rarely the most efficient in terms of throughput and energy use when the reaction kinetics are fast. Batch systems are also much more labour intensive than continuous processes. 

The fine chemical industry has been characterised for decades by batch processes in laboratories as well as in production plants. Owing to the requirement of high flexibility (capacity,... 

Acid-catalysed rearrangement of epoxides is another widely used reaction in the fine chemicals industry. Here again the use of solid acid catalysts such as zeolites is proving advantageous. Two examples are shown in Fig. 2.25 the isomerization of rsophorone oxide (Elings et al., 1997) and the conversion of a-pinene oxide to campholenic aldehyde (Holderich et al., 1997 Kunkeler etal., 1998). Both products are fragrance intermediates. 

These examples represent the proverbial tip of the iceberg. In the future, zeolites and related solid acids will be widely applied as catalysts in the fine chemicals industry. One final example, worthy of mention, is a widely used reaction of long standing aromatic nitration. 

PT catalysts are often difficult to separate from the product, while it is also desirable that the catalyst should be reusable or recyclable. Distillation and extraction are the most common separation processes. The main disadvantage of lipophilic quats is their tendency to remain in the organic phase and consequently contaminate the product. Therefore, extraction in water often is not satisfactory. Furthermore, products in the fine chemicals industry often have high boiling points and/or are heat sensitive, which makes separation of the catalyst by distillation impossible. Often the only means to remove the catalyst in these cases is to adsorb it using a high surface area sorbent such as silica, Florisil or active carbon (Sasson, 1997). After filtration, the catalyst can then be recovered by elution. 

Hydrogenations involving consecutive reactions are common in the organic process industry and even in the hydrogenation of fats. In the fine chemicals industry we have examples of acetylenic (triple) bonds to be selectively converted to olefinic (double) bonds. Lange et al. (1998) have shown, for the comversion of the model substance 2-hexyne into cis-2-hexene, how catalytically active microporous thin-film membranes can accomplish 100% selectivity. This unusual selectivity is attributed to avoidance of backmixing. 

Examples of separation of mixtures in the fine chemicals industry... 

In the fine chemical industry, reduction of carbonyl groups mainly relies on the use of complex metal hydrides sodium dihydrobis-(2-methoxyethoxy)-aluminate, commercialized as RedAl or Vitride is one of the most used (4). 

Considerable effort has gone into learning how to hydrogenate the C=0 bond and retain the C=C bond to produce a,p-unsaturated alcohols (allylic alcohols), which are useful in the fine chemicals industry. Early works toward selectively hydrogenating the C=0 bond have been reviewed and discussed.146 An excellent review was published in 1995.147... 

Nonetheless, a wide variety of potential methods are available to achieve the goal of nanoencapsulation for the purpose of facilitating the use of two or more incompatible catalysts in cascade reactions. The many multistep reactions that are of importance in the fine chemicals industry are prime targets for the application of the principles of nanoencapsulation and, therefore, of green chemistry. 

Although the mesoporous materials, such as Ti-MCM-41, have lower intrinsic epoxidation selectivity than TS-1 and Ti-beta, they must nevertheless be used as catalysts for reactions of large molecules typical in the fine chemicals industry. It is, therefore, interesting to elucidate how these ordered mesoporous materials compare with the earlier generation of amorphous titania-silica catalysts. Guidotti et al (189) recently compared Ti-MCM-41 with a series of amorphous titania-silica catalysts for the epoxidation of six terpene molecules of interest in the perfumery industry (Scheme 6). Anhydrous TBHP was used as the oxidant because the catalytic materials are unstable in water. The physical characteristics of these catalysts are compared in Table XII. 

Obviously, in a relatively small work such as this it is not possible to be comprehensive. Preparations of bulk, achiral materials (e.g. simple oxiranes such as ethylene oxide) involving key catalytic processes will not be featured. Only a handful of representative examples of preparations of optically inactive compounds will be given, since the emphasis in the main body of this book, i.e. the experimental section, is on the preparation of chiral compounds. The focus on the preparation of compounds in single enantiomer form reflects the much increased importance of these compounds in the fine chemical industry (e.g. for pharmaceuticals, agrichemicals, fragrances, flavours and the suppliers of intermediates for these products). 

The hydrolysis of racemic non-natural amides has led to useful products and intermediates for the fine chemical industry. Thus hydrolysis of the racemic amide (2) with an acylase in Rhodococcus erythrolpolis furnished the (S)-acid (the anti-inflammatory agent Naproxen) in 42 % yield and > 99 % enantiomeric excess1201. Obtaining the 7-lactam (—)-(3) has been the subject of much research and development effort, since the compound is a very versatile synthon for the production of carbocyclic nucleosides. An acylase from Comamonas acidovor-ans has been isolated, cloned and overexpressed. The acylase tolerates a 500 g/ litre input of racemic lactam, hydrolyses only the (+)-enantiomer leaving the desired intermediate essentially optically pure (E > 400)[211. 

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... 

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. 

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. 

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