Carboxylic acids nitrile hydrolysis

Section 19.12 Nitriles, which can be prepared from primary and secondary alkyl halides by nucleophilic substitution with cyanide ion, can be converted to carboxylic acids by 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. 

The Kolbe synthesis of nitriles is an important method for the elongation of an alkyl chain by one carbon center (see also the Arndt-Eistert synthesis). The nitrile 2 can for example easily be converted to the corresponding carboxylic acid by hydrolysis. 

You will recall that nitriles are easily converted into carboxylic acids by hydrolysis. This involves heating the nitrile with an aqueous acid. The hydrogen ions of the acid catalyse the reaction. 

Cyanohydrin formation is a useful synthetic reaction, in that it utilizes a simple reagent, cyanide, to create a new C-C bond. The cyano (nitrile) group may easily be modified to other functions, e.g. carboxylic acids via hydrolysis (see Box 7.9) or amines by reduction. 

Cyanoethylation of acrylonitrile with monohydric alcohols gives alkoxypropio-nitriles (Scheme 25). These nitriles can be converted into various types of carboxylic acids by hydrolysis, and they can be hydrogenated to give amines. Therefore, cyanoethylation of alcohols is an important reaction for the synthesis of drug intermediates and organic compounds of industrial interest. 

Primary or secondary alkyl halides can be converted into nitriles (alkyl cyanide) by nucleophilic substitution. The nitriles formed can in turn be converted to carboxylic acids by hydrolysis. 

Nitriles are synthetically versatile functional groups because they are readily converted to carboxylic acids by hydrolysis under addic or basic conditions, reduced with LiAlH4 to form primary amines, and reaction with Grignard reagents leads to the formation of ketones. These reactions are illustrated here ... 

Nifrilases catalyze the conversion of organonitriles directly to the corresponding carboxylic acids. Synthetic hydrolysis of nitriles into the corresponding amides and carboxylic acids requires severe reaction conditions. A typical synthetic approach would require the use of 70% H2SO4 and heat (13). Such a reaction condition is not compatible when selectivity and the conservation of other hydrolysable functional groups in a substrate are desired. Biotransformation of nitrites can be accomplished under mild conditions, in an aqueous environment (13). Additionally, enantioselectivity of the biocatalytic conversion of nitriles to chiral acids has been demonstrated (14-16). Therefore, nifrilases provide an alternative route for synthetic processes that require conversion of nitriles to corresponding acids. 

A soln. of 3-nitro-4-cyanodiphenyl in N NaOH and acetone treated with HgOg, gently warmed for 1.5 hrs., then refluxed 0.5 hr. 3-nitrodiphenyl-4-carbox-amide (Y 97%), 18.5 g. in H2S04-acetic acid-water stirred and treated portion-wise at 5-10° with Na-nitrite, stirring continued 1.5 hrs. at the same temp., then allowed to stand overnight 18.3 g. 3-nitrodipheny 1-4-carboxylic acid.—Direct hydrolysis of the nitrile failed. G. M. Atkinson and G. J. Sharpe, Soc. 1959, 2858. 

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

SYNTHESIS OF CARBOXYLIC ACIDS BY THE PREPARATION AND HYDROLYSIS OF NITRILES... 

Primary and secondary alkyl halides may be converted to the next higher carboxylic acid by a two step synthetic sequence involving the preparation and hydrolysis of nitriles Nitnles also known as alkyl cyanides are prepared by nucleophilic substitution... 

Nitrile groups m cyanohydrins are hydrolyzed under conditions similar to those of alkyl cyanides Cyanohydrin formation followed by hydrolysis provides a route to the preparation of a hydroxy carboxylic acids... 

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... 

Section 20 19 The hydrolysis of nitriles to carboxylic acids is irreversible m both acidic and basic solution... 

Among the methods for preparing carboxylic acids carboxylation of a Grignard reagent and preparation and hydrolysis of a nitrile convert RBr to RCO2H The malonic ester synthesis converts RBr to RCH2CO2H... 

Because cyano groups may be hydrolyzed to carboxylic acids (Section 20 19) the Sand meyer preparation of aryl nitriles is a key step m the conversion of arylammes to sub stituted benzoic acids In the example just cited the o methylbenzomtnle that was formed was subsequently subiected to acid catalyzed hydrolysis and gave o methylbenzoic acid in 80-89% yield... 

In fact, most pyrimidinecarboxylic acids are made by hydrolysis of the corresponding esters, nitriles or sometimes amides, many of which can be made more easily by primary synthesis than can the acids themselves. Thus, pyrimidine-5-carboxylic acid may be made by alkaline hydrolysis of its ethyl ester (62JOC2264) and pyrimidin-5-ylacetic acid (789 ... 

In the Strecker synthesis an aldehyde is converted to an a-amino acid with one more carbon atom by a two-stage procedure in which an a-fflnino nitrile is an intenne-diate. The a-fflnino nitrile is fonned by reaction of the aldehyde with ffliimonia or an fflTtmonium salt and a source of cyanide ion. Hydrolysis of the nitrile group to a carboxylic acid function completes the synthesis. 

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