7.2.3 Nucleophilic Addition

Aldehydes and Ketones partake in nucleophilic addition reactions, some examples of nucleophilic addition reactions include:

1. The reduction of aldehydes to primary alcohols, and ketones to secondary alcohols, using the reducing agent $NaBH_4$ in aqueous solution.
2. The reaction of the $-:CN$ ion with aldehydes and ketones to produce hydroxynitriles ($KCN$, followed by dilute acid)

Nucleophilic Addition Reactions of Carbonyl Compounds

Nucleophilic addition is an important mechanism in organic chemistry where a nucleophile (electron-rich species) adds to a carbonyl compound, such as an aldehyde or ketone.

• When carbonyl compounds react with potassium cyanide ($KCN$) followed by dilute acid, hydroxynitriles are formed. This reaction is significant in synthesis as it extends the carbon chain and introduces functional groups that can undergo further reactions.

Here's a comprehensive breakdown of the nucleophilic addition of carbonyls with $KCN$.

Nucleophilic Addition Mechanism

Carbonyl Group:

• Carbonyl compounds (aldehydes and ketones) contain a polar $C=O$ bond.

• The oxygen atom is more electronegative than carbon, creating a dipole with a partially positive carbon ($δ+$) and a partially negative oxygen ($δ−$). Nucleophile:

• In the presence of $KCN$ in aqueous solution, the cyanide ion ($CN⁻$) acts as a nucleophile, attracted to the $δ+$ carbon in the $C=O$ group.

Reaction Mechanism Steps

1. Attack by Cyanide Ion ($CN⁻$):

• The $CN⁻$ion attacks the carbonyl carbon, opening up the double bond and forming a tetrahedral intermediate. This step creates a negatively charged oxygen.

2. Protonation:

• The intermediate is protonated by $H⁺$ions from the dilute acid, forming a hydroxynitrile.
• Example of a product: If propanone ($CH₃COCH₃$) is the starting material, the product will be 2-hydroxy-2-methylpropanenitrile.

3. Overall Reaction:

$${R-CO-R'} + KCN + H⁺ → {R-CH(OH)-CN}$$

This reaction is particularly valuable in organic synthesis as it introduces both a hydroxyl ($-OH$) and a nitrile ($-CN$) group, enabling further functional group transformations.

Formation of Hydroxynitriles and Nomenclature

• The product of this reaction is known as a hydroxynitrile.
• Naming: The nitrile group takes priority, giving the suffix "-nitrile." The hydroxyl group is named with the prefix hydroxy-. For example:
  • If the starting material is ethanal ($CH₃CHO$), the product is 2-hydroxypropanenitrile.

Optical Isomerism and Formation of Enantiomers

• Chiral Centers: The addition of $CN⁻$to a carbonyl group in an unsymmetrical carbonyl compound (e.g., an aldehyde or asymmetric ketone) forms a new chiral centre at the carbon where the $CN⁻$is added.
• Enantiomers: Since the $CN⁻$ion can attack the planar carbonyl group from either above or below, this leads to the formation of two possible products, known as enantiomers.
• Racemic Mixture:
  • Both enantiomers are produced in equal amounts (50:50), resulting in a racemic mixture.
  • Racemic mixtures have no net optical rotation since the two enantiomers rotate plane-polarized light in equal but opposite directions. This feature can be tested using polarimetry.

Hazards of Using Potassium Cyanide ($KCN$)

Potassium cyanide is highly toxic and poses significant health risks. Here are the key points about handling $KCN$:

• Toxicity: KCN is extremely poisonous; it inhibits cellular respiration by binding to iron in cytochrome enzymes.
• Handling Precautions:
  • Always handle in a fume cupboard to avoid inhaling toxic vapors.
  • Use protective gloves and eyewear.
  • Dispose of any waste containing cyanide according to safety regulations.
• In Case of Exposure: Immediate first aid and emergency procedures are critical due to the high toxicity of cyanide compounds.

Reduction by Sodium Borohydride (NaBH4)

The $NaBH_4$ is a complex anion but behaves like a hydride ion ($H-$) So we draw it as a$H-$ in the mechanism; that's the species acting as the nucleophile.

Reduction of aldehydes

Reagent: Aqueous $NaBH_4$ followed by $H_2SO_4$ Conditions: Room temperature Mechanism: Nucleophilic $- H-$= nucleophile Reaction type: Addition/Reduction Product: Primary alcohol

Reduction of ketones

Reagent: Aqueous $NaBH_4$ followed by$H_2SO_4$ Conditions: Room temperature Mechanism: Nucleophilic $- H-$ = nucleophile Reaction type: Addition/Reduction Product: Secondary alcohol

Reaction with Hydrogen Cyanide (HCN)

Reagent: $HCN$ - formed by reaction with $KCN$ followed by dilute $H_2SO_4$

Conditions: Room temp.

Mechanism: Nucleophilic $SO$ $CN-$ is the nucleophile

Reaction type: Addition

Product: Hydroxynitrile

Overall equations:

For aldehydes:

$$RCHO + HCN → RCH(OH)CN$$

For ketones:

$$RCOR' + HCN → RC(OH)R'CN$$

Formation of racemic mixtures of hydroxynitriles

• Aldehydes and unsymmetrical ketones form mixtures of enantiomers when they react with $KCN$ followed by dilute acid. • This is because the products of the reactions contain chiral carbon atoms.
• Nucleophilic addition reactions of $KCN$, followed by dilute acid, can produce a racemic mixture of enantiomers which is optically inactive because:

4. The C atom in the planar carbonyl group can be attacked by a nucleophile from above or below.
5. There is an equal chance of attack from above or below. E.g. the products of the reaction propanal w/ potassium cyanide, under weakly acidic conditions are present as a racemic mixture.