Nitrile Hydrolysis in Basic Solution

THE OVERALL REACTION Nitriles are hydrolyzed in base to give ammonia and a carboxylate ion. An amide is an intermediate. 

Step 1 Hydroxide adds to the carbon-nitrogen triple bond. This step is analogous to nucleophilic addition to a carbonyl group. 

Step 2 The product of step 1 is the conjugate base of an imino acid to which it is converted by proton abstraction from water. 

Step 3 Proton abstraction from oxygen of the imino acid gives the conjugate base of an amide. 

Imino acid Hydroxide ion Conjugate base of amide Water 

Step 4 The conjugate base of the amide abstracts a proton from water. 

---

The hydrolysis of an organic nitrile, a compound containing a —C=N group, in basic solution, is proposed to proceed by the following mechanism. Write a complete balanced equation for the overall reaction, list any intermediates, and identify the catalyst in this reaction. 

A number of studies have also been made of the hydrolysis of nitriles in the coordination sphere of cobalt(III). Pinnell et al.3 4 found that benzonitrile and 3- and 4-cyanophenol coordinated to pentaamminecobalt(III) are hydrolyzed in basic solution to the corresponding N-bonded carboxamide (equation 22). The reaction is first order in hydroxide ion and first order in the complex with koH= 18.8M 1s 1 at 25.6 °C for the benzonitrile derivative. As fc0H for the base hydrolysis of benzonitrile is 8.2 x 10-6 M-1 s at 25.6 °C, the rate acceleration is ca. 2.3 x 106-fold. The product of hydrolysis is converted to [(NH3)5CoNH2COPh]3+ in acidic solution and the pJC of the protonated complex is 1.65 at 25 °C. Similar effects have been observed with aliphatic nitriles.315 Thus, base hydrolysis of acetonitrile to acetamide is promoted by a factor of 2 x 106 on coordination to [Co(NH3)5]3+. 

The first four steps of the mechanism for hydrolysis of nitriles in basic solution are given in Mechanism 19.8. These steps convert the nitrile to an amide, which then proceeds to the hydrolysis products according to the mechanism of amide hydrolysis in Mechanism 19.7 (page 846). 

Table 2 Kinetic parameters for the hydrolysis of co-ordinated nitriles in complexes [Co(NHs)5(NCR)] + in basic solution from ref 18)...

The difficulty of hydrolyzing amides in basic solution allows for some selectivity in the hydrolysis of nitriles (Figure 15.19). In neutral or weakly basic solutions, the amide is isolated, but under more forcing, and acidic, conditions, the carboxylic acid is obtained (Figure 15.20). Some examples of nitrile hydrolysis in synthesis are shown in Figure 15.21. In the first example, both the ester and the nitrile are hydrolyzed. In the second example, the reaction can be stopped at the amide stage. 

The increase in electrophilicity of coordinated ligands commonly leads to more favorable hydrolysis reactions. There are many reports on hydrolysis reactions of coordinated carboxamides, halogenated alkylamines, Schiff bases, thioamides, nitriles, etc. For example, thiourea and thioacetamide complexes of platinum metals decompose on heating in basic solution with formation of the corresponding metal sulfides, Eq. 1.26 and 1.27 ... 

Section 20.19 The hydrolysis of nitriles to carboxylic acids is ineversible in both acidic and basic solution. 

The hydrolysis of nitriles, which are organic molecules containing a cyano group, leads to carboxylic acid formation. These hydrolysis reactions can take place in either acidic or basic solutions. 

Other functional groups attached to the cyclopropane can also react when acidic and basic conditions are utilized to obtain cyclopropylamines from the corresponding amides and carbamates. In aqueous solution additional ester and nitrile functions undergo simultaneous hydrolysis thus, the product afforded will be an aminocyclopropanecarboxylic... 

On hydrolysis in either acidic or basic solution, nitriles are ultimately converted to the corresponding carboxylic acids (Eqs. 25.66 and 25.67). It is then possible to prepare a derivative of the acid using methods provided in Section 25.13. 

Basic Hydrolysis. In a small Erlenmeyer flask, mix 10 mL of 3 M sodium hydroxide solution and 1 g of the nitrile. Heat the mixture to boiling and note either the odor of ammonia or the color change that occurs when a piece of moist pHydrion paper is held over the flask. After the mixture is homogeneous, cool and then acidify it. If the acid solidifies, collect the crystals by vacuum filtration. If it is a liquid. extract the acidic solution with small portions of diethyl ether, dry and decant the ethereal solution, and then remove the solvent by one of the techniques described in Section 2.29. The residue is the acid. Prepare a suitable derivative of the acid (Sec. 25.13). 

We have seen (earlier in this section) that primary alcohols and aldehydes can be oxidized to carboxylic acids. Carboxylic acids can also be prepared by the hydrolysis of nitriles. The hydrolysis of a nitrile can be carried out in either acidic or basic solution, as suggested below ... 

Hydrolysis Conversion of Nitriles into Carboxylic Acids A nitrile is hydrolyzed in either basic or acidic aqueous solution to yield a carboxylic acid plus ammonia or an amine. 

Nitriles (RCN) get hydrolysed to carboxylic acids (RC02H) in acidic or basic aqueous solutions. The mechanism of the acid-catalysed hydrolysis (Following fig.) involves initial protonation of the nitrile s nitrogen atom. This activates the nitrile group towards nucleophilic attack by water at the electrophilic carbon. One of the nitrile n bonds breaks simultaneously and both the n electrons move onto the nitrogen yielding a hydroxyl imine. This rapidly isomerises to a primary amide which is hydrolysed under the reaction conditions to form the carboxylic acid and ammonia. 

Hydrolysis Conversion of Nitriles Into Carboxylic Acids (RCN —> RC02H) Nitriles are hydrolyzed in either acidic or basic aqueous solution to yield carboxylic acids plus ammonia or an amine ... 

---