Nitrile to carboxylic acid
Acid-catalyzed hydrolysis of a nitrile
How the Acid-catalyzed hydrolysis of a nitrile works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Nitrile R–C≡N, H₃O⁺ (conc. HCl or H₂SO₄), H₂O. Conditions: Reflux, several hours. Bonds formed: C–O (acid C=O, C–OH); N–H (NH₄⁺); bonds broken: C≡N (π bonds); C–N (amide). Stereochemistry: No new stereocentre; α-stereocentres retained. Rate and selectivity: Water attack on the protonated nitrile is rate-limiting; amide hydrolysis is the slower, forcing stage.
At a glance
Step 1: N-Protonation activates the nitrile
Acid protonates the nitrile nitrogen, activating the carbon toward nucleophilic attack — the same electrophilic activation strategy used throughout carbonyl and nitrile chemistry.
Step 2: Water adds; tautomerisation to the amide
Water attacks that activated carbon, and tautomerization gives an amide — this intermediate is exactly the substrate for the amide hydrolysis mechanism covered earlier in this library.
Step 3: Amide hydrolysis gives the acid and NH₄⁺
Further acid-catalyzed hydrolysis of that amide (identical mechanism to the standalone amide hydrolysis entry) delivers the carboxylic acid and ammonium ion — nitrile hydrolysis is mechanistically just two hydrolysis reactions already in this library, chained together.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- H2SO4
- Sulfuric acid. Strong acid and dehydrating agent.
- HCl
- Hydrochloric acid / hydrogen chloride. Strong acid; chloride is the nucleophile in additions/substitutions.
How it compares with related reactions
| Acid-catalyzed hydrolysis of a nitrile | Hell-Volhard-Zelinsky reaction | LiAlH₄ reduction of a nitrile to a primary amine | |
|---|---|---|---|
| Reagents | Nitrile R–C≡N, H₃O⁺ (conc. HCl or H₂SO₄), H₂O | 1) PBr₃ (or cat. P), Br₂ 2) H₂O | LiAlH₄ (excess), then H₂O workup |
| Conditions | Reflux, several hours | Neat or CCl₄, 80–100 °C; then aqueous workup | Dry Et₂O or THF, 0 °C → reflux; then H₃O⁺ or Fieser workup |
| Stereochemistry | No new stereocentre; α-stereocentres retained | Racemic at a new α stereocentre | None (achiral CH₂NH₂) |
| Rate / selectivity | Water attack on the protonated nitrile is rate-limiting; amide hydrolysis is the slower, forcing stage | Enolization of acyl bromide is rate-limiting | Second hydride addition fast relative to the first |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Acid-catalyzed hydrolysis of a nitrile?
Nitrile R–C≡N, H₃O⁺ (conc. HCl or H₂SO₄), H₂O. Conditions: Reflux, several hours.
Which bonds are formed and which are broken?
Formed: C–O (acid C=O, C–OH); N–H (NH₄⁺). Broken: C≡N (π bonds); C–N (amide).
What is the stereochemical outcome?
No new stereocentre; α-stereocentres retained
What controls the rate or the selectivity?
Water attack on the protonated nitrile is rate-limiting; amide hydrolysis is the slower, forcing stage
Study guides that help with this reaction
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go