3-cyanopyridine hydration

Interestingly, the same authors [13b] have isolated the l,2-dihydro-l,2,4,5-tetra-zine intermediate 21 by condensation of 2-cyanopyridine 20 with hydrazine hydrate in presence of flower of sulfur (Scheme 8.9 b). The reaction time is reduced under the action of microwave irradiation (125 W) protic solvents also promote the transformation. 

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. 

Reisch et stated that 6-chloro-3-cyanopyridin-2(l//)-one and anthranilic acid in acetic acid or in dimethylformamide in the presence of potassium carbonate and copper powder gave the hydrate of pyrido[2,l-i ]quinazolinone (492). When compound 492 was treated with diazomethane, a ring-opened product (493) was obtained. 

The same whole cell catalyst can be used in the hydration of 3-cyanopyridine to nicotinamide (Scheme 12.1-17). This vitamin, broadly applied in animal feeding, is currently produced biocatalytically on an industrial scale (> 3000 t/a) by the Lonza AG. For this substrate Yamada and Kobayashi showed that the whole cell catalyst of Rhodococcus rhodocrous Jl, containing a nitrile hydratase induced with crotonamide, can even tolerate substrate concentrations up to 12 m 121 (see Fig. 12.1-3). 

R. rhodochrous J1 cells and 3-cyanopyridine as the substrate, the highest yield achieved was almost 1.5 kg of nicotinamide per liter of reaction mixture without formation of nicotinic acid (Fig. 2)5. Due to the high yields of this process, the use of this enzymatic hydration is promising for the industrial production of various aliphatic, aromatic and hetero cyclic amidese. 

Tyler and coworkers found that [Cp Moln-OHlj MoCpj] (Cp = ti -CH3C5H4) is a catalyst precursor for the hydration of nitriles in aqueous solution [83]. Several nitriles were hydrated by their catalyst, including acrylonitrile, acetonitrile, isobu-tyronitrile, 4-cyanopyridine and methyl cycanoacetate. Equation 3.28 shows hydration of acrylonitrile to produce acrylamide, which is used on a large scale industrially due to many uses for polyacrylamide. 

An attempt has been made to study the working mechanism of ionites during the catalytic hydration of 4-cyanopyridine on AB-17-8 ionite in OH form [28-31a]. TWo mechanisms have been proposed the catalysis by counterions and the catalysis by fixed ionite ions. According to the former mechanism, the reaction proceeds by the homogeneous acid-base route ... 

Nitrile hydratases (NHases) catalyze the hydration of organic nitriles to amides under very benign reaction conditions (neutral aqueous environment and room temperature) and therefore offer a chemoselective alternative to classical approaches, where functional group compatibility is often limited due to the harsh acidic or basic solutions used [1], Starting with their application in acrylamide production [2,3], this enzyme class is one of the most prominent in industrial processes with respect to production volume (>3 X 10 kg/a for acrylonitrile hydration) [4]. Hence, Lonza (Switzerland) uses a nitrile hydratase to convert 3-cyanopyridine into nicotinamide (6 X 10 tons/year). Very recently, a one-pot industrial protocol for the synthesis of a chiral intermediate for dlastatin was published that employed a nitrile hydratease/amidase approach [5],... 

Lonza Fine Chemicals manufactures nicotinamide by a process in which 2-methyl-l,5-diaminopentane (a by-produa of nylon-6,6 manufacture) is first converted to 3-cyanopyridine 121 by a series of three chemically-catalyzed reactions, then the nitrile is hydrated to nicotinamide 122 (Figure 11.37) using Rhodococcus rhodochrous Jl cells immobilized in polyacrylamide particles [227-229]. A continuous feed of 3-cyanopyridine at concentrations of between 10-20 Avt /o is added in the direction of process flow, with a counter-current feed of biocatalyst in a series of stirred-tank batch bioreactors. The process generates... 

Reusable heterogeneous catalysts have been shown to catalyse the hydration of nitriles to give primary amides. Simple metal oxides such as Ce02 in H2O or H20/Et0H mix gave moderate to high yields of heterocyclic primaiy amides (Scheme 17.29). A heteroatom in the 2-position to the nitrile was key for catalytic activity, with no activity seen when it was further away, severely limiting substrate scope. 2-Pyridinecarboxamide was formed in near quantitative yield from 2-cyanopyridine in 12 hours at only 30 °C. Cao published a... 

Nickel catalyzed O-H additions to imsaturated systems are limited to the hydration reactions of nitriles for the synthesis of amides. These reactions have been widely studied by Prof. J. J. Garcia and his research group and their results recently reviewed [60]. They reported the isolation and characterization of Ni(0) complexes of type [(dippe)Ni(ri -NCR], R = aryl, heteroaryl or alkyl, derived from the reductive interaction of [(dippe)NiH]2 with organic cyanides. The catalytic and synthetic utility of these complexes was demonstrated first in the catalytic hydration of benzonitrile and acetonitrile [61] and then extended to dicyanobenzenes [62], to mono- and dicyanoalkanes [63] and finally to cyanopyridines [64]. 

Crisdsteuno C, Crestani MG, Garcia JJ (2010) Catalytic hydration of cyanopyridines using Nickel(0). InOTg Chim Acta 363 1092—1096... 

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