Amino acid synthesis
Strecker synthesis of an amino acid
How the Strecker synthesis of an amino acid 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: RCHO, NH₃ (or NH₄Cl), KCN; then H₃O⁺. Conditions: Aqueous / MeOH; then hot aqueous acid. Bonds formed: C=N; C–CN; C–COOH; bonds broken: C=O; C≡N (to acid). Stereochemistry: Racemic α-amino acid (new stereocentre). Rate and selectivity: Imine formation is fast and reversible; nitrile hydrolysis is slow.
At a glance
Step 1: Aldehyde + NH₃ gives an imine
Ammonia condenses with an aldehyde, losing water to form an electrophilic imine.
Step 2: Cyanide attacks the imine carbon
Cyanide's lone pair attacks the imine carbon exactly as it would a carbonyl, forming an α-aminonitrile.
Step 3: Nitrile hydrolysis gives the amino acid
Acidic hydrolysis converts the nitrile group to a carboxylic acid (via an amide intermediate), delivering a free α-amino acid.
Abbreviations and terms
- MeOH
- Methanol. Polar protic solvent (also a nucleophile in solvolysis).
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- Δ
- Heat. Reaction is run at elevated temperature.
How it compares with related reactions
| Strecker synthesis of an amino acid | Glutamate dehydrogenase | Strecker degradation | |
|---|---|---|---|
| Reagents | RCHO, NH₃ (or NH₄Cl), KCN; then H₃O⁺ | L-Glutamate, NAD⁺ or NADP⁺, H₂O | α-Amino acid + α-dicarbonyl (e.g. 2,3-butanedione, methylglyoxal) |
| Conditions | Aqueous / MeOH; then hot aqueous acid | Mitochondrial matrix, glutamate dehydrogenase; reversible | Heat, 100–180 °C (cooking) |
| Stereochemistry | Racemic α-amino acid (new stereocentre) | Hydride to one face of nicotinamide; planar iminium loses α-stereochemistry | Stereocenter of the amino acid is lost |
| Rate / selectivity | Imine formation is fast and reversible; nitrile hydrolysis is slow | Allosterically regulated: ADP/GDP activate, ATP/GTP inhibit | Decarboxylation of the imine is rate-limiting |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Strecker synthesis of an amino acid?
RCHO, NH₃ (or NH₄Cl), KCN; then H₃O⁺. Conditions: Aqueous / MeOH; then hot aqueous acid.
Which bonds are formed and which are broken?
Formed: C=N; C–CN; C–COOH. Broken: C=O; C≡N (to acid).
What is the stereochemical outcome?
Racemic α-amino acid (new stereocentre)
What controls the rate or the selectivity?
Imine formation is fast and reversible; nitrile hydrolysis is slow
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- Curved-arrow notation: rules and the mistakes students make