Acrylamide from Acrylonitrile

Nitrile Hydratase Acrylamide from Acrylonitrile, Nicotinamide from 3-Cyanopyridine, and 5-Cyanovaleramide from Adiponitrile 

1 and Section 7.1.2). The substrate concentrations that can be employed are so extremely high that, in case of solid nitriles and amides, precipitation of amide 

The biocatalytic acrylamide process is run by the Nitto Chemical Corp., now part of the Mitsubishi Rayon Corp., in Tokyo Bay on a scale of 30 000 tpy, in fed-batch mode up to 25-40% acrylamide at 0-10°C to complete conversion and with product yields 99.9%, conditions under which a significant cost differential can be assumed with respect to the conventional chemical process. 

Acrylamide is the first bulk chemical manufactured using an industrial biotransformation. Acrylamide which is produced 200000 t/a is an important industrial chemical that is mainly processed into water-soluble polymers and copolymers, which find applications as flocculants, paper-making aids, thickening agents, surface coatings, and additives for enhanced oil recovery. The chemical manufacture of acrylamide has been established for a long time, it is based on Cu-catalysis. The production of acrylamide using immobilized whole cells of Rhodococcus rhodochrous is a remarkable example of a lyase-catalyzed commercial process. The enzyme responsible for water addition to the double bond of acrylonitrile is nitrile hydratase (Eq. 4-17)  

Both the conventional and bio-processes involve the same reaction. In Table 4-3 are given some details of each process for comparison  

Catalyst A copper salt the enzyme nitrile hydratase in whole cells of Rhodococcus rhodochrous, immobilized on polyfpropenamide) gel 

Separation and purification Copper ions need to be removed from product difficult to separate and purify the acrylamide large quantities of toxic waste no need to levover unreacted acrylonitrile because the yield is so high polyacrylamide of higher molecular weight 

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Hydrolases, which catalyze the hydrolysis of various bonds. The best-known subcategory of hydrolases are the lipases, which hydrolyze ester bonds. In the example of human pancreatic lipase, which is the main enzyme responsible for breaking down fats in the human digestive system, a lipase acts to convert triglyceride substrates found in oils from food to monoglycerides and free fatty acids. In the chemical industry, lipases are also used, for instance, to catalyze the —C N —CONH2 reaction, for the synthesis of acrylamide from acrylonitril, or nicotinic acid from 3-pyridylnitrile. 

In basic chemicals, nitrile hydratase and nitrilases have been most successful. Acrylamide from acrylonitrile is now a 30 000 tpy process. In a product tree starting from the addition of HCN to butadiene, nicotinamide (from 3-cyanopyridine, for animal feed), 5-cyanovaleramide (from adiponitrile, for herbicide precursor), and 4-cyanopentanoic acid (from 2-methylglutaronitrile, for l,5-dimethyl-2-piperidone solvent) have been developed. Both the enantioselective addition of HCN to aldehydes with oxynitrilase and the dihydroxylation of substituted benzenes with toluene (or naphthalene) dioxygenase, which are far superior to chemical routes, open up pathways to amino and hydroxy acids, amino alcohols, and diamines in the first case and alkaloids, prostaglandins, and carbohydrate derivatives in the second case. 

Acrylamide from Acrylonitrile with Nitrile Hydratase... 

Figure 1.15 The biocatalytic synthesis of acrylamide from acrylonitrile is performed in Japan on a scale of 10000 tons per year. The bacterial cells are immobilized in a poly(acrylamide) gel, and the process is run at pH 8.0-8.5 in semi-batch mode, keeping the substrate concentration below 3%.

The hydration of nitriles to form amides is promoted by metallic catalysts such as nickel and copper,9 and the copper catalyzed hydration has been utilized in an industrial process for the production of acrylamide from acrylonitrile.10 The hydration of... 

Rhodococcus sp. N-774 and Pseudomonas chlororaphis B23 resting cells have been used at industrial scale (as first- and second-generation biocatalysts) for the biological production of acrylamide from acrylonitrile since the 1980s [21]. Currently Rhodococcus rhodochrous J1 is being adopted as a third-generation biocatalyst (Mitsubishi Rayon Co.). The industrial production of nicotinamide from 3-cyanopyridine is also operated with this strain (Lonza AG). However, despite the enormous potentiality of nitrile-hydrolyzing biocatalysts for industrial applications, only a few commercial processes have been realized [22]. 

Mononuclear Active Sites). This reaction has important commercial applications, and nitrile hydratase has been nsed indnstrially for enzymatic production of acrylamide from acrylonitrile. The enzyme contains a mononuclear Fe(II) (or Co(II)) active site, the metal ion being bound in a highly unusual coordination involving two deprotonated peptide amides together with three cysteine side chains (Figure 4). 

The degradation of nitriles by nitrilases (EC 3.5.5.1) has been the subject of intense study, especially as it relates to the preparation of the commodity chemical acrylamide. Nitrilases catalyze the hydrolysis of nitriles to the corresponding acid plus ammonia (Figure 1 reaction 5), whereas nitrile hydratases (EC 4.2.1.84) add water to form the amide. Strains such as Rhodococcus rhodo-chrous Jl, Brevibacterium sp., and Pseudomonas chlororaphis have been used to prepare acrylamide from acrylonitrile, which contain the hydratase and not nitrilase activity [12]. A comparison of these strains has been discussed elsewhere [98]. Other uses of nitrilases, however, have primarily been directed at resolution processes to stereoselectively hydrolyze one enantiomer over another or regiose-lectively hydrolyze dinitriles [99-101]. 

Amides can be made by the enzymatic hydrolysis of nitriles. Nitto Chemical Industry of Japan uses Rhodococcus rhodocrous to prepare acrylamide from acrylonitrile... 

Production of acrylamide from acrylonitrile by nitrile hydratase (nitrile hydrolyase) is now, together with HFS production with glucose isomerase, the largest scale enzymatic process. Enzymatic production of acrylamide in Japan exceeded... 

Most industrial enzymatic processes refer to reactions conducted by hydrolases in aqueous medium for the degradation of complex molecules (often polymers) into simpler molecules in conventional processes with limited added value (Neidelman 1991). Reasons underlying are clear since hydrolases are robust, usually extracellular and have no coenzyme requirements, which makes them ideal process biocatalysts. Enzyme immobilization widened the scope of application allowing less stable, intracellular and non-hydrolytic enzymes to be developed as process biocatalysts (Poulsen 1984 D Souza 1999), as illustrated by the paradigmatic case of glucose isomerase for the production of HFS (Carasik and Carroll 1983) and the production of acrylamide from acrylonitrile by nitrile hydratase (Yamada and Kobayashi 1996). 

Biocatalytic processes and technologies are penetrating increasingly in all branches of the chemical process industries. In basic chemicals, nitrile hydratase and nitri-lases have been most successful. For example, acrylamide from acrylonitrile is now a 30,000 t/a process. In fine chemicals, enantiomerically pure amino acids are produces by several different companies. 

Acrylamide (from acrylonitrile) Propylene glycol (from propylene) Nitrilase Chloroperoxidase Carynebacterium sp. 

The production of amides from nitriles has been studied by several workers, and most of them focused on the accumulation of acetamide from acetonitrile [126,133-136]. The enz3nnatic production of acrylamide from acrylonitrile by nitrile hydratase of P. chlororaphis B23, Rhodococcus sp. N-774, and Klebsiella pneumoniae, respectively has been reported [137-142]. These microorganisms exhibited a high nitrile hydratase activity and a low amidase activity, allowing the accumulation of the corresponding amide. Nagasawa et al. optimized the reaction conditions for the production of nicotinamide by a nitrile hydratase, found in Rhodococcus rhodochrous Jl. The enzyme contains cobalt, and shows high activity towards 3-cyanopyridine [143,144]. 

Mitsubishi Rayon produces acrylamide from acrylonitrile with the help of an immobilized bacterial enzyme, nitrile hydratase (see Fig. 9.20). This acrylamide is then polymerized to the conventional plastic polyacrylamide. This process was one of the first large-scale applications of enzymes in the bulk chemical industry and replaced the conventional process that used sulfuric acid and inorganic catalysts. The enzymatic process has several advantages over the chemical process. The efficiency of the enzymatic process is 100%, while that of the previous chemical process was only 30-45%. The energy consumption is only 0.4MJ/kg product, compared to 1.9MJ/kg product for the chemical route. The process generates less waste. The CO2 production is only 0.3 kg/kg monomer, while the previous process produced 1.5 kg/kg. The reaction is carried out at 15°C, which is milder than the original chemical route. About 100,000 tons of acrylamide are produced yearly now via this approach in Japan and other countries. 

The first, and a very important, example of the enzymatic manufacture of a bulk synthetic chemical is the biosynthesis of acrylamide from acrylonitrile (Reaction 16.11). The chemical pathway that has been used for this transformation is definitely not a green process in that it involves the... 

Various nitrile hydratases are continued to be developed and compared to the existing wdld-type whole-cell catalysts (R. rhodochrous Jl) presently used in the commercial production of acrylamide from acrylonitrile. Mitsubishi Rayon has produced mutant enzymes of R. rhodochrous Jl with significantly improved thermal stabilities and ca ytic activities at 50-70°C [233,234]. Saint-Etierme France has licensed and commercialized the mamrfacture of acrylamide using Mitsubishi Rayon s immobilized R. rhodochrous ]l [235] and has independently developed a Rhodococcus pyridinovorans whole cell catalyst for this process [236]. 

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