Nicotinic Lonza process

Traditional Lonza Process for Preparation of Nicotinic Acid >15000 tons/year... 

Scheme 15.3 Traditional Lonza process for the preparation of nicotinic acid.

Nicotinic acid is an important intermediate for pharmaceuticals and serves as a provitamin in food additives for animal feeding. It is produced by the Lonza process (involving oxidation of 2-methyl-5-ethyl pyridine using nitric acid) or by the Degussa process.The latter process involved hydrolysis of P-cyanopyridine, which in turn was produced by amminoxidation of P-picoline. A third process involving selective vapour phase oxidation of P-picoline catalysed by vanadium titanium oxide catalyst has also been described. ... 

Another example of a biocatalytic transformation ousting a chemical one, in a rather simple reaction, is provided by the Lonza nitotinamide process (Fig. 2.34) (Heveling, 1996). In the final step a nitrile hydratase, produced by whole cells of Rh. rhodoccrous, catalyses the hydrolysis of 3-cyano-pyridine to give nitotinamide in very high purity. In contrast, the conventional chemical hydrolysis afforded a product contaminated with nicotinic acid. 

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. 

This chapter discusses the fulfillment of the requirements for a green process, together with the importance of the nicotinate vitamin B3. Lonza s contribution to green chemistry is then illustrated by its processes for producing nicotinates. The current niacinamide process running is China employs no fewer than six basic principles of green-sustainable chemistry. 

In contrast to the chemical alkaline hydrolysis of 3-cyanopyridine with 4% byproduct of nicotinic acid (96% yield) the biotransformation works with absolute selectivity and no acid or base is required. The biotransformation (a continuous process) is operated at low temperature and atmospheric pressure. In contrast to the old synthesis route of nicotinamide at Lonza, the new one is environmentally friendly and safe. There is only one organic solvent used throughout the whole process in four highly selective continuous and catalytic reactions. The process water, NH3 and H2 are recycled. 

Substituted nicotinic acid derivatives, such as 6-hydroxy nicotinic acid are important building blocks for the synthesis of pesticides and pharmaceuticals, acting as specific inhibitors of NAD/NADP-dependent enzymes. In a process developed by Lonza (Switzerland), 6-hydroxy nicotinic acid is produced by whole-cell microbial hydroxylation of nicotinic acid with Achromobacter xylosoxidans (yield > 100 g 1 ) (Fig. 16). A similar process for the production of 6-hydroxypicolinic acid (98 g l-1) and derivatives from picolinic acid (derivatives), based on Alcaligenes faecalis, has also been established [174,175]. 

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