Hydrolysis of nitriles: Amide vs Carboxylic acid

Question

I was recently studying the preparation of amides,and one of the methods listed was acid hydrolysis of a nitrile. Up until now I thought acid hydrolysis of nitriles yielded carboxylic acids. How are the methods to get amides and acids different?

I can view the amide as sort of an intermediary stage while getting to the acid,but how do you stop the reaction at amide? Do you use stoichiometric quantities of the acid? This is puzzling me.

Answer 1

Hydrolysis of nitrile is pH dependent. It will lead to formation of different products based on pH.

Theoretically, nitrile hydrolyze to form amide and then ammonium salt.

$$\ce{RCN ->[H2O] RCONH2 ->[H2O] RCOONH4}$$

But in practice, the reaction between nitriles and water is so slow that it is considered negligible. The nitrile is instead heated with either a dilute acid such as dilute hydrochloric acid, or with an alkali such as sodium hydroxide solution to accelerate the hydrolysis reaction. But this pH dependent reaction yields different products.

1. Acid hydrolysis: yields carboxylic acid

$$\ce{RCN + 2H2O + HCl -> RCOOH + NH4Cl}$$

2. Alkaline hydrolysis: yields sodium carboxylate salt

$$\ce{RCN + H2O + NaOH-> RCOONa + NH3}$$

To obtain amide, hydrolysis is done selectively and in controlled manner. It can be done in both acidic and alkaline medium. In acidic medium, nitriles are converted into amide in a single step process using TFA-$\ce{H2SO4}$ mixture as reagent.

In alkaline medium, it can done using alkaline solution of hydrogen peroxide (see @Light Yagami's answer).

Reference

1. Chemguide
2. Facile and Highly Selective Conversion of Nitriles to Amides via Indirect Acid-Catalyzed Hydration Using TFA or AcOH−H2SO4, Jarugu Narasimha Moorthy and Nidhi Singhal, The Journal of Organic Chemistry 2005 70 (5), 1926-1929 DOI: 10.1021/jo048240a

Answer 2

Yes, you are correct. For converting a nitrile to amide, we do controlled hydrolysis.

So, first amide is obtained and then ammonium salt of the carboxylic acid is obtained.

So, the reaction would be $$\ce{RCN}+2 \ce{H_2O_2}+\ce{OH^{-1}} \ce{->} \ce{RCONH_2} +\ce{O_2}+\ce{H_2O}$$

Which is done at $\mathrm{pH}$ range of 7-8.

If you increase or decrease the $\mathrm{pH}$ more than this, you will get the acid.

Additional Reading:

1. Mcisaac, J. E.; Ball, R. E.; Behrman, E. J. Mechanism of the base-catalyzed conversion of nitriles to amides by hydrogen peroxide. J. Org. Chem. 1971, 36 (20), 3048–3050. DOI: 10.1021/jo00819a034.

2. The Hydrolysis of Nitriles: Chem Libretexts