Fine Chemical Production Process

The perspectives for an increasing use of biotechnology processes (biocatalysis, microbial fermentation) for LMW fine chemicals are promising. Substitution of traditional chemicals by biotechnology processes constitutes the most important means for reduction of manufacturing cost for existing fine chemicals. By 2010,30-60% of fine-chemical production processes are expected to comprise a biotechnology step ... 

Carbon monoxide chemistry has been extensively studied, leading to a wide range of methods used in small scale organic syntheses up to industrial processes.8 Despite the versatility of carbonylation reactions, carbon monoxide suffers from major drawbacks that restricts its utilisation. From an industrial point of view, the cumbersome handling of this toxic gas necessitates very expensive facilities which prevent its use for the majority of fine chemical production processes. An alternative process equivalent to a carbonylation reaction which avoids carbon monoxide introduction into the reactor and that can be used in standard polyvalent type units would be of great interest. Of course, catalyst cost, stability and productivity should also fulfil economic requirements. 

A frequent application of batch distillation in pharmaceutical and fine chemical production processes involves solvent exchange. The solvent employed in a particular reaction step needs to be replaced by another for the next reaction step. Alternatively, the replacement solvent is needed to carry out crystallization of the final product, which is, in general, nonvolatile. If the final or intermediate product is thermally labile, then distillation is carried out at a lower temperature under partial vacuum. The conventional procedure is as follows. First, the batch is boiled down to remove a lot of the original solvent. Then the replacement solvent is added, and the resulting batch is distilled to reduce further the amount of original solvent... 

In order to convert the raw oils into useful material, transesterification technology is used. The oil is reacted with a low molecular weight alcohol, commonly methanol, in the presence of a catalyst to form the fatty acid ester and glycerol (Scheme 6.1). The ester is subsequently separated from the glycerol and used as biodiesel, the glycerol being used as a raw material for fine chemicals production. Although the chemistry is simple, in order to make biodiesel commercially viable the process must be... 

The main driver was to develop a laboratory-scale micro-channel process and transfer it to the pilot-scale, aiming at industrial fine-chemical production [48, 108]. This included fast mixing, efficient heat transfer in context with a fast exothermic reaction, prevention offouling and scale-/numbering-up considerations. By this means, an industrial semi-batch process was transferred to continuous processing. 

Based on these positive results, a continuously operating Cytos Pilot Plant was constructed by CPC Systems GmbH and is used for fine chemical production. The results of the evaluation on production scale confirm those results obtained already during the process development stage, which have been discussed in detail elsewhere. ... 

This chapter focuses on heterogeneous catalysis, which is most important in fine chemicals production. Table 3.1 presents a number of examples of catalysis in fine chemistry. These examples are divided in heterogeneously catalysed processes and homogeneously catalysed processes. A detailed treatment of heterogeneously catalysed processes for the production of fine chemicals is also given in the book edited by Sheldon and van Bekkum (2001). 

When hydrogenation is carried out in a continuous process often so-called trickle-ttow reactors are used. Mass-tran.sfer limitations often occur. An elegant improvement is the application of extrudates with a noncircular cross section, which increa.ses the external surface without increasing the pressure drop. Trilohe and Quadrilohe shapes are generally used in oil-refinery processes and they might also be useful in fine chemicals production. 

At present, the major applications of zeolites in catalysis are in the oil refinery. They find increasing application in petrochemical processes. When considering the enormous success of the application of zeolites in bulk chemistry, it is to be expected that the same trend will be seen in fine chemicals production. For this sector, it is fortunate that in bulk chemistry so much development work is being done in catalysis and in particular in zeolite synthesis and application. 

In homogeneous catalysis soluble catalysts are applied, usually in the liquid phase, in contrast to heterogeneous catalysis, where solid catalysts are used. Homogeneous catalysis is applied in many processes in both bulk and fine chemicals production. 

Table 3.12 surveys current industrial applications of enantioselective homogeneous catalysis in fine chemicals production. Most chiral catalyst in Table 3.12 have chiral phosphine ligands (see Fig. 3.54). The DIP AMP ligand, which is used in the production of L-Dopa, one of the first chiral syntheses, possesses phosphorus chirality, (see also Section 4.5.8.1) A number of commercial processes use the BINAP ligand, which has axial chirality. The PNNP ligand, on the other hand, has its chirality centred on the a-phenethyl groups two atoms removed from the phosphorus atoms, which bind to the rhodium ion. Nevertheless, good enantio.selectivity is obtained with this catalyst in the synthesis of L-phenylalanine. 

While batch reactors remain the workhorse in fine chemical production, the need to switch to continuous processes will increase the use of meso- and micro-structured reactors both at the laboratory scale (for discovery, process data determination, demonstration, small-scale production) and at the production level. 

Process simulation, 20 710, 728-730 Process specific piping system, in fine chemical production, 11 429-430 Process-stream purification, 13 620 Process synthesis, 13 218 26 999... 

SCFs will find applications in high cost areas such as fine chemical production. Having said that, marketing can also be an issue. For example, whilst decaffeina-tion of coffee with dichloromethane is possible, the use of scCC>2 can be said to be natural Industrial applications of SCFs have been around for a long time. Decaffeination of coffee is perhaps the use that is best known [16], but of course the Born-Haber process for ammonia synthesis operates under supercritical conditions as does low density polyethylene (LDPE) synthesis which is carried out in supercritical ethene [17]. 

Several industrial processes use phase-transfer techniques with soluble catalysts, mostly for fine chemical productions (42,43). It is easy to believe that this technology will find a greater application in the near future, perhaps with the use of polymer-supported catalysts. 

Process technologies used primarily for the production of large-volume commodities, such as phosgenation or ammonoxidation, are further exploited for fine-chemical production. 

In addition to large-scale industrial applications, solid acids, such as amorphous silica-alumina, zeolites, heteropoly acids, and sulfated zirconia, are also versatile catalysts in various hydrocarbon transformations. Zeolites are useful catalysts in fine-chemical production (Friedel-Crafts reactions, heterosubstitution).165-168 Heteropoly compounds have already found industrial application in Japan, for example, in the manufacture of butanols through the hydration of butenes.169 These are water tolerant, versatile solid-phase catalysts and may be used in both acidic and oxidation processes, and operate as bifunctional catalysts in combination with noble metals.158,170-174 Sulfated zirconia and its modified versions are promising candidates for industrial processes if the problem of deactivation/reactivation is solved.175-178... 

In the pharmaceutical and fine chemical industries, process development and optimisation start when the target chemical structure and a possible synthetic path have been identified by chemical research. Chemical process development ends when the production has been successfully implemented in the final production facility. 

Furthermore, in the synthesis of fine chemicals typical process technology considerations, for example space-time-yield, are less important than for bulk chemicals. Because of the relatively small production outputs batch reactors are the most common apparatus in which to perform the synthesis. New chances in the field of fine chemistry may be offered by micro-reaction technology. Microstruc-tured systems can be used to improve heat transfer which may be critical for highly exothermic reactions and, furthermore, they may be also useful in reactions where fast mixing of components is recommended. 

To show how this complexity arises, let us consider the manufacture of a fictional, fine chemical product used in the pharmaceutical industry, called FCP1, by a multi-stage, batch process at a rate of 100 tonnes per year. 

The heterogeneous catalysts have a profound impact on the chemical industry in general for example 60% of all chemical processes, 75% of oil refining processes, nearly 100% of polymers and about one hundred petrochemicals depend on the action of catalysts, as well as a significant part of environmental technologies (VOCs, automotive emissions control, stationary sources, etc.) and fine chemical production. Actually, the worldwide catalysts market is worth about 10 billion USD, (i.e. 10 x 109 USD) a year and, according to some... 

---