Addition of Hydrogen Cyanide (HCN) to Carbonyls
Aldehydes and Ketones undergo Nucleophilic Addition with Hydrogen Cyanide ($HCN$) to yield Cyanohydrins. This reaction is synthetically very important because it introduces a new carbon-carbon bond and a functional group that can be easily converted into carboxylic acids, amines, or amides.
1. General Reaction
The carbonyl carbon reacts with the cyanide ion to form an addition product.
Note: Pure HCN is a very weak acid and dissociates poorly to give $CN^-$ ions. Therefore, the reaction is very slow with pure HCN. It is catalyzed by a Base.
2. Detailed Mechanism
The reaction follows a Nucleophilic Addition Mechanism.
Step 1: Generation of Nucleophile
A base ($OH^-$) removes a proton from HCN to generate the strong nucleophile, the Cyanide ion ($CN^-$).
Step 2: Nucleophilic Attack (Rate Determining Step)
The cyanide ion attacks the electrophilic carbonyl carbon. The $\pi$-electrons shift to the oxygen atom, forming a tetrahedral alkoxide intermediate.
Step 3: Protonation
The alkoxide ion abstracts a proton from the solvent (water or HCN) to form the neutral Cyanohydrin.
3. Reactivity and Equilibrium
The equilibrium favors the product (Cyanohydrin) for most Aldehydes and simple Ketones.
Reactivity Order
$$ \text{Formaldehyde} > \text{Aldehydes} > \text{Ketones} $$
Steric Reason: Ketones have two alkyl groups which hinder the attack of $CN^-$.
Electronic Reason: Alkyl groups (+I effect) reduce the positive charge on the carbonyl carbon, making it less electrophilic.
Note: Bulky aromatic ketones (e.g., Benzophenone) react very poorly.
4. Synthetic Applications
Cyanohydrins are versatile intermediates.
A. Synthesis of $\alpha$-Hydroxy Acids (Lactic Acid)
Acidic hydrolysis of the nitrile group converts it into a carboxylic acid.
$$ CH_3-CH(OH)-CN \xrightarrow{H_3O^+, \Delta} \underbrace{CH_3-CH(OH)-COOH}_{\text{Lactic Acid}} $$B. Synthesis of $\alpha,\beta$-Unsaturated Acids
Dehydration of the $\alpha$-hydroxy acid yields unsaturated acids (e.g., Acrylic acid from Acetaldehyde cyanohydrin).
$$ CH_2(OH)-CH_2-COOH \xrightarrow{\text{Conc. } H_2SO_4, \Delta} CH_2=CH-COOH $$C. Synthesis of $\beta$-Amino Alcohols
Reduction of the nitrile group ($LiAlH_4$) yields amines.
$$ >C(OH)-CN \xrightarrow{LiAlH_4} >C(OH)-CH_2NH_2 $$5. Stereochemistry
Since the carbonyl carbon is planar ($sp^2$), the nucleophile ($CN^-$) can attack from either face (top or bottom) with equal probability. If the starting molecule is achiral and $R \neq R'$, the product will be a Racemic Mixture ($\pm$ pair of enantiomers).
HCN Reaction Quiz
Test your concepts on Cyanohydrin formation. 10 MCQs with explanations.
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