Acid catalysis nitrile hydrolysis

Nitriles are hydrolysed to 1° amides, and then to carboxylic acids either by acid catalysis or base catalysis. It is possible to stop the acid hydrolysis at the amide stage by using H2SO4 as an acid catalyst and one mole of water per mole of nitrile. Mild basic conditions (NaOH, H2O, 50 °C) only take the hydrolysis to the amide stage, and more vigorous basic condition (NaOH, H2O, 200 °C) is required to convert the amide to a carboxylic acid. 

Initially, the 80 20 transxis mixture of pyrrolidine nitrile 50 was converted to a mixture of -butyl esters under snlfnric acid catalysis, followed by epimerization with n-BuONa, and then hydrolysis to the acid (Scheme 5.27). The best trans. cis ratio of n-bntyl esters achieved was 95 5. Hydrolysis of esters with HCl afforded the HCl salt of 3 in 89% overall yield, which led to a minor upgrade in the transxis ratio (97 3). On the other hand, hydrolysis of the n-bntyl ester by NaOH and snbseqnent pH adjnstment to 6.5 afforded pyrrolidine acid 3 in 86% yield and >99.9 chemical and optical parities. 

Even ia 1960 a catalytic route was considered the answer to the pollution problem and the by-product sulfate, but nearly ten years elapsed before a process was developed that could be used commercially. Some of the eadier attempts iacluded hydrolysis of acrylonitrile on a sulfonic acid ion-exchange resia (69). Manganese dioxide showed some catalytic activity (70), and copper ions present ia two different valence states were described as catalyticaHy active (71), but copper metal by itself was not active. A variety of catalysts, such as Umshibara or I Jllmann copper and nickel, were used for the hydrolysis of aromatic nitriles, but aUphatic nitriles did not react usiag these catalysts (72). Beginning ia 1971 a series of patents were issued to The Dow Chemical Company (73) describiag the use of copper metal catalysis. Full-scale production was achieved the same year. A solution of acrylonitrile ia water was passed over a fixed bed of copper catalyst at 85°C, which produced a solution of acrylamide ia water with very high conversions and selectivities to acrylamide. 

Nitrilases catalyze the synthetically important hydrolysis of nitriles with formation of the corresponding carboxylic acids [4]. Scientists at Diversa expanded the collection of nitrilases by metagenome panning [56]. Nevertheless, in numerous cases the usual limitations of enzyme catalysis become visible, including poor or only moderate enantioselectivity, limited activity (substrate acceptance), and/or product inhibition. Diversa also reported the first example of the directed evolution of an enantioselective nitrilase [20]. An additional limitation had to be overcome, which is sometimes ignored, when enzymes are used as catalysts in synthetic organic chemistry product inhibition and/or decreased enantioselectivity at high substrate concentrations [20]. 

Generally, enzymatic hydrolysis of nitriles to the corresponding acids can either proceed stepwise, which is the case for catalysis by the nitrile hydratase/amidase enzyme system, or in one step in the case of nitrilases. Both systems have been investigated for surface hydrolysis of PAN [10], Complete hydrolysis with either system was monitored by quantification of ammonia and/or polyacrylic acid formed as a consequence of hydrolysis of nitrile groups [70-72], As a result, considerable increases in colour levels (e.g. 156% for commercial nitrilase) were found upon dyeing [72],... 

Thus, many metal ions catalyze the hydrolysis of esters [7,8], amides [9], and nitriles [10] via electrophilic activation of the C=0 or C=N group. This type of catalysis is characteristic of coordination complexes and is very common in metalloenzyme-mediated processes. Zinc(II), for example, is a key structural component of more than 300 enzymes, in which its primary function is to act as a Lewis acid (see Chapter 4). The mechanism of action of zinc proteases, e.g., thermolysin, involves electrophilic activation of an amide carbonyl group by coordination to zinc(II) in the active site (Figure 4). 

Imines are readily hydrolysed to the carbonyl compound and amine by aqueous acid—in fact, except for the particularly stable special cases we discuss below, most can be hydrolysed by water without acid or base catalysis. You have, in fact, already met an imine hydrolysis at the end of Chapter 10 we talked about the addition of Grignard reagents to nitriles. The product is an imine that hydrolyses in acid solution to ketone plus ammonia. 

B. Izzo, C. L. Harrel, and M. T. Klein [AIChE J., 43, 2048-2058 (1997)] stndied the hydrolysis of nitriles in high-temperature pressurized aqueous solution. They report that the reaction is autocatalytic because of catalysis by the acid formed as a result of hydrolysis of the amide formed in the initial reaction. For benzonittile, the reaction network can be represented as... 

Analytical and Tast Methods. Numerous instrumental and chemical techniques are available for the determination of acrylonitrile. The method of choice is directed by the concentration and the medium involved. For direct assay of acrylonitrile, titrimetric procedures are frequently used. Dodecyl mercaptan reacts with acrylonitrile under base catalysis excess mercaptan is then hacktitrated with an acid bromate-iodide solution (63), or alternatively, for colored solutions, with silver nitrate (64). Hydrolysis of the nitrile with strong base generates ammonia, which can then be determined by Nessler s reagent (65). 

Carboxylic acids can also be obtained by the hydrolysis of nitriles, esters, or amides, generally with acid- or base-catalysis. 

Studies of chemical attack on nitrile rubber by fluids encountered in sealing applications in the oil industry are reported. The results showed that excessive hardening of nitrile rubber in the downhole oilfield environment occurs at the acrylonitrile sites, and that it could be due to either hydrolysis or reduction of the cyano group. Hydrolysis is driven by Bronsted acids (proton donors) and reduction by Lewis acids (electron donors). Catalysis by metal ions could possibly cause these reactions to occur at a greatly reduced activation energy. Oxidative attack at the butadiene sites is the primary cause of hardening in aboveground applications of nitrile rubber. 12 refs. 

S. Ofiwald, A. Yanenko, Hydrolysis of Nitriles to Carboxylic Acids, in K. Drauz, H. Groger, O. May (Eds.), Enzyme Catalysis in Organic Synthesis, Wiley-VCH, Weinheim, 2012, pp. 545-559. 

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