Nitriles carboxylic acids, degradation

Trifluoroacetic acid sodium nitrite trifiuoroacetic anhydride Nitriles from carboxylic acids Degradation with loss of 1 C-atom... 

There are two pathways for the degradation of nitriles (a) direct formation of carboxylic acids by the activity of a nitrilase, for example, in Bacillus sp. strain OxB-1 and P. syringae B728a (b) hydration to amides followed by hydrolysis, for example, in P. chlororaphis (Oinuma et al. 2003). The monomer acrylonitrile occurs in wastewater from the production of polyacrylonitrile (PAN), and is hydrolyzed by bacteria to acrylate by the combined activity of a nitrilase (hydratase) and an amidase. Acrylate is then degraded by hydration to either lactate or P-hydroxypropionate. The nitrilase or amidase is also capable of hydrolyzing the nitrile group in a number of other nitriles (Robertson et al. 2004) including PAN (Tauber et al. 2000). 

Sandmeyer s synthesis of aromatic nitriles is far more elegant than the removal of water from the ammonium salts of carboxylic acids, which latter reaction is also applicable to benzene derivatives. In particular, the former synthesis permits of the preparation of carboxylic acids via the nitriles, and so provides a complete substitute for Kolbe s synthesis (alkyl halide and potassium cyanide), which is inapplicable to aromatic compounds. The simplest example is the conversion of aniline into benzoic add. The converse transformation is Hofmann s degradation (benzamide aniline, see p. 152). 

Notably, nitrile-degrading enzymes (e.g. nitrilase that converts the CN group to carboxylic acid, and nitrile hydratase that produces an amide function) have been described, and they co-exist with aldoxime-degrading enzymes in bacteria (Reference 111 and references cited therein). Smdies in this area led to the proposal that the aldoxime-nitrile pathway, which is implemented in synthesis of drugs and fine chemicals, occurs as a natural enzymic pathway. It is of interest that the enzyme responsible for bacterial conversion of Af-hydroxy-L-phenylalanine to phenacetylaldoxime, an oxidative decarboxylation reaction, lacks heme or flavin groups which are found in plant or human enzymes that catalyze the same reaction. Its dependency on pyridoxal phosphate raised the possibility that similar systems may also be present in plants . 

Figure 5.5 Degradation routes for nitriles. The first route is a two-step reaction involving a nitrile hydratase, which converts the nitrile to the amide, and an amidase, which converts the amide to the corresponding acid. The second pathway involves direct hydrolysis of the nitrile to the carboxylic acid and ammonia by a nitrilase.

Some relevant substituents are displayed in Table XV. Hydrolysis of esters or nitriles followed by thermal decarboxylation of 2-, 5-, 6-, and 7-carboxylic acids is often used for degradation reactions (61CPB883, 61JCS3046 64UP1). 5-Amino-l,2,4-triazole-3-carboxylic acid is decarbox-ylated in situ by condensation to TP (83S44) TP-5-amideoxime is cyclized to the 5-( 1,2,4-oxadiazol-3-yl) derivative (90EGP282009). 

The microbial degradation of nitriles can occur via two different enzymatic pathways [39], different from cyanogenesis [40] (i) nitrilase (EC 3.5.5.1) catalyzes the direct hydrolysis of nitriles to the corresponding carboxylic acids and ammonia (Eq. 1) [41] and (ii) nitriles are catabolized in two stages - they are first converted to the corresponding amides by nitrile hydratase (EC 4.2.1.84) (Eq. 2), and then to the acids and ammonia by amidase (Eq. 3). The microbial degradation of nitriles has also been reviewed elsewhere [42-45]. 

Some further monosubstituted furoxans which have been reported are either of very doubtful authenticity or have been discredited. The phenacyl derivatives of Harries and Tietz,462 formed by the nitrosation of /J-aryl-oc,/ -unsaturated oximes, have been shown to be pyrazolone di-JV-oxides 463 The degradation of Holleman s peroxide (29) by hydroxylamine and alkali was reported to form structure 218, or its 3-substituted isomer, by Boyer and Chang.29 It does, however, seem unlikely that a monosubstituted furoxan could withstand such reaction conditions. Decarboxylation of furoxandi-carboxylic acid has been suggested to provide the 4-monocarboxylic acid,464 but Ponzio and De Paolini465 have assigned a nitrile oxide structure to the product. 

When the reactivity of reactant (R-CH2-X) is relatively high, the condensation reactions take place more easily than the degradation reactions. As a result, the selectivity to the condensation products becomes high. This is the case of the reaction with aldehydes or ketones. The reaction with carboxylic acids and esters is more difficult and the reaction with nitriles is the most difficult especially in view of the selectivity based on HCHO. 

Oxidative decarboxylation a-Amino acids and a-hydroxy carboxylic acids are degraded, to give nitriles and carbonyl compounds, respectively. 

Table 7 lists further examples of one- or two-step degradation accomplished by hydrolysis, if necessary acidification, and decarboxylation. Azulenopyridine carboxylic ester 98b can be hydrolyzed by base to yield the stable carboxylic acid (63BCJ633). Imidazole 72 and triazole 73 could not be successfully degraded (73BCJ3161). Degradation of nitriles 31a (74BCJ1750) and 208 (97MI1) is depicted in Scheme 74. 

Unhindered aryl nitriles are rapidly hydrolyzed via the amide to the carboxylic acid, but the hindered aryl nitriles are only transformed slowly into amides that are even more stable. Whereas 8 (Hal = Br) and 9 (Hal = 1) form in soil, by hydrolysis and dehalogenation, less toxic substances such as 4-hydroxybenzoic acid [29], 10 undergoes degradation to the stable 2,6-dichlorobenzamide, which is slowly further hydrolyzed into the 2,6-dichlorobenzoic acid [30]. 

Microbial degradation of nitrile compounds was performed by different microorganisms, capable of growing on various aliphatic and aromatic nitriles [107-109], They are degraded through two pathways (Figure 7) one is the direct hydrolysis of nitriles to carboxylic acid and ammonia, catalyzed by nitrilases. Nitrilases, that utilize benzonitrile and related aromatic nitriles as substrates, have been purified from Pseudomonas sp. [110.111], Nocardia sp. strains NCIB 11215 [112] and NCIB 11216... 

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