Lonza advantages

Batchwise operated multipurpose plants are per defmitionem the vehicle for the production of fine chemicals. There are, however, a few examples of fine chemicals produced ia dedicated, coatiauous plants. These can be advantageous if the raw materials or products are gaseous or Hquid rather than soHd, if the reaction is strongly exothermic or endothermic or otherwise hazardous, and if the requirement for the product warrants a continued capacity utilization. Some fine chemicals produced by continuous processes are methyl 4-chloroacetoacetate [32807-28-6] C H CIO [32807-28-6], and malononittile [109-77-3] C2H2N2, made by Lonza dimethyl acetonedicarboxylate [1830-54-2] made by Ube and L-2-chloropropionic acid [107-94-8] C2H C102, produced by Zeneca. 

Most of today s best-known hne-chemical companies, such as Cambrex, Clariant, Degussa, Dowpharma, DSM, and Rhodia (see Table 2.2), are subject to the abovementioned characteristics. Customers prefer to do business with midsize companies, because communications are easier (they typically deal directly with the decisionmaker)—and they can better leverage their purchasing power. Lonza s custom manufacturing business, apart from biotech, is still mainly concentrated on the original Visp, Switzerland site in terms of production and R D, and therefore has conserved a number of advantages that are typical of midsize companies. 

While these divestitures were taking place, traditional fine chemicals manufacturers were able to enjoy new contracts for the synthesis of active ingredients from companies involved in crop protection products and pharmaceuticals. Many European companies were the beneficiaries of the new trend. In Switzerland the leader was Lonza, which became independent in 1999 when its mother company, Alu Suisse, merged with the Canadian aluminum manufacturer Alcan. Other Swiss firms—such as Siegfried AG, EMS-Dottikon, Cilag, and Orgamol, Rohner, now part of Dynamit Nobel—took advantage of these developments. Clariant entered the field on a big scale in 2000 with its acquisition of BTP. 

Similarly, DuPont employs a nitrile hydratase (as whole cells of P. chlororaphis B23) to convert adiponitrile to 5-cyanovaleramide, a herbicide intermediate [122]. In the Lonza nitrotinamide (vitamin B6) process [123] the final step (Fig. 1.42) involves the nitrile hydratase (whole cells of Rh. rhodocrous) catalysed hydration of 3-cyanopyridine. Here again the very high product purity is a major advantage as conventional chemical hydrolysis affords a product contaminated with nicotinic acid, which requires expensive purification to meet the specifications of this vitamin. 

The alkaloid dextromethorphan is an antitussive drug manufactured by Lonza in enantiomerically pure form. While early synthesis involved the tedious resolution of an octahydroi-soquinoline intermediate with mandelic acid, a more recent process takes advantage of the catalytic reduction of a C-N double bond promoted by a chiral Ir/ferrocenylphosphine complex [70]. 

Production of acrylamide (Fig. 13) by hydration of acrylonitrile under the action of the intracelluar nitrile hydratase in Rhodococcus rhodochrous (Nitto Chemical Industry Co., Ltd., fed-batch process). The annual production amounts to >30000 tons (see also Table 6). Acrylamide is one of the most important commodity chemicals and is required in large quantities as the pre-polymer of polyacrylamide that is widely used in polymer and floccu-lent applications. The advantages of this hydratase approach in comparison with the classical chemical nitrile hydration are higher product end concentration, quantitative yields, no formation of acrylic acid, no need for copper catalyst, and only five chemical/technical operations instead of seven [73,112,113,171]. An analogous process for nicotinamide is being commercialized by Lonza (see also section 6). 

The process developed by Lonza/Alusuisse has the advantage of high selectivity and high molar yield a disadvantage is the loss of two carbon atoms for each molecule of ethylmethylpyridine. 

Based on the unequivocal advantages of microprocess technology, a lot of companies started to study microstructured devices as tools for process intensification [14]. BASF, Bayer, Clariant, Degussa, DSM, Lonza, and Merck are among them and have also published some studies they had performed to investigate the applicability of microstructured devices for chemical production [17-20]. Several pilot- and production-scale applications of microreactors have also been reported. There are about 20 plants published in the literature and 30-40 plants estimated to be installed worldwide [21]. 

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