Amides nitrile hydrolysis

Nitriles are classified as carboxylic acid derivatives because they are converted to carboxylic acids on hydrolysis. The conditions required are similar- to those for the hydrolysis of amides, namely, heating in aqueous acid or base for several hours. Like the hydrolysis of amides, nitrile hydrolysis is ineversible in the presence of acids or bases. Acid hydrolysis yields fflnmonium ion and a carboxylic acid. 

Hydrolysis of Acetonitrile. Nitriles, like acid amides, undergo hydrolysis to give the corresponding carboxylic acid and ammonia. Consequently... 

Nitriles are classified as carboxylic acid derivafives because fhey are convened fo car boxylic acids on hydrolysis The condifions required are similar fo fhose for fhe hydrol ysis of amides namely healing m aqueous acid or base for several hours Like fhe hydrolysis of amides nilrile hydrolysis is irreversible m fhe presence of acids or bases Acid hydrolysis yields ammonium ion and a carboxylic acid... 

Nitrile Group. Hydrolysis of the nitrile group proceeds through the amide to the corresponding carboxyUc acid. Because cyanohydrins are unstable at high pH, this hydrolysis must be cataly2ed by acids. In cases where amide hydrolysis is slower than nitrile hydrolysis, the amide may be isolated. 

We aheady discussed both the acidic and basic hydrolysis of fflnides (see Section 20.17). All that remains to complete the mechanistic picture of nitrile hydrolysis is to examine the conversion of the nitrile to the conesponding amide. 

Base catalyzed nitrile hydrolysis involves nucleophilic addition of hydroxide ion to the polar C N bond to give an imine anion in a process similar to nucleophilic addition to a polar C=0 bond to give an alkoxide anion. Protonation then gives a hydroxy imine, which tautomerizes (Section 8.4) to an amide in a step similar to the tautomerization of an enol to a ketone. The mechanism is shown in Figure 20.4. 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

The cyano group is at the carboxylic acid oxidation level, so nitriles are potential precursors of primary amides. Partial hydrolysis is sometimes possible.146... 

Nitriles are well known to undergo acid and alkaline hydrolysis (Figure 13.5), but there is only one recent report of neutral hydrolysis. Thus, methacrylonitrile, even though it is conjugated with an alkenyl substituent, should undergo both acid-catalyzed and base-mediated hydrolysis via a pathway similar to that for alkyl and aryl nitriles. The amide is a likely intermediate product for nitrile hydrolysis, but it is reactive as well and can undergo acid- and base-mediated hydrolysis to the carboxylic acid and ammonia. The... 

Substitutionally inert Co(m) or Ir(m) complexes have been used to measure directly the effect of Lewis acid activation on the hydrolysis of an amide [35-37], a nitrile [38] and a phosphate triester [39] (Figure 6.4). The p/C, of the cobalt-bound water molecule in 5 is 6.6 [40], Thus the upper limit for the rate-acceleration due to Lewis acid activation with this metal in the hydrolysis of esters, amides, nitriles and phosphates should be close to 109-fold. Although the observed rate accelerations for the hydrolysis reac-... 

They can be hydrolysed just like amides too. Addition of water to the protonated nitrile gives a primary amide, and hydrolysis of this amide gives carboxylic acid plus ammonia. 

Kielbasirisky et al. (2008) have recently demonstrated the first case of enzymatic recognition of a nitrile with a P chiral snlfnr atom. Nine different commercial nitri-lases were screened using cyanomethyl p-tolyl sulfoxide as substrate all reactions occurred in a mixture of buffer phosphate and a co-solvent was used to dissolve the substrate. Very interestingly, they obtained both the acid and the amide as hydrolysis products with different ee and absolnte confignrations depending on the enzyme used (Table 17.17). 

Kobayashi, M., Goda, M., and Shimizu, S. 1998. Nitrilase catalyzes amide hydrolysis as well as nitrile hydrolysis. Biochemical and Biophysical Research Communications, 253 662-6. 

The mechanism of nitrile hydrolysis in both acid and base consists of three parts [1] nucleophilic addition of H2O or OH to form the imidic acid tautomer [2] tautomerization to form the amide, and [3] hydrolysis of the amide to form RCOOH or RCOO. The mechanism is shown for the basic hydrolysis of RCN to RCOO (Mechanism 22.11). 

Acid-catalyzed nitrile hydrolysis is similar to amide hydrolysis and occurs by initial protonation of the nitrogen atom, followed by nucleophilic addition of water. Write all the steps involved in the acidic hydrolysis of a nitrile to yield a carboxylic acid, using curved arrows to represent electron flow in each step. 

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