Mechanism of Nucleophilic Addition Reaction
Nucleophilic addition is the most common reaction shown by aldehydes and ketones. Aldehydes react faster than ketones because they are less hindered and their carbonyl carbon is more positive.
The carbonyl group (C=O) is strongly polarized. Oxygen carries a partial negative charge, while carbon carries a partial positive charge. Because of this, the carbonyl carbon behaves as an electrophile and is easily attacked by nucleophiles.
Nucleophiles may be negatively charged (HO–, RO–, H–) or neutral (water, alcohol). Strong nucleophiles attack directly, forming a tetrahedral intermediate which later gets protonated.
Weak nucleophiles require acid catalysis. The acid protonates the carbonyl oxygen, making the carbonyl carbon more electrophilic and easier to attack.
Nucleophilic Addition–Elimination
In some reactions, after the nucleophile adds to the carbonyl compound, water is eliminated. This is called a nucleophilic addition–elimination process and is commonly seen in reactions of acid derivatives.
Ionisation of Carboxylic Acids & Acidity Constants
Carboxylic acids ionise in water to form a carboxylate ion and hydronium ion. The acidity constant Ka tells us how strongly an acid ionises. A high Ka means the acid is stronger.
Typical aliphatic and aromatic acids are weak acids (Ka ≈ 10-4 to 10-5), which means they ionise only slightly. Their conjugate bases (carboxylates) are moderately basic.
Why Carboxylic Acids Are More Acidic Than Alcohols
The acidity of carboxylic acids is mainly due to resonance stabilisation of the carboxylate ion. The carboxylate ion has two equivalent resonance structures, allowing the negative charge to be evenly spread over the two oxygen atoms.
Because this stabilisation is much greater than in the unionised acid, the equilibrium shifts toward ionisation, making the acid stronger.
Structure of Carboxylate Ions
Carboxylate ions are resonance hybrids. Both C–O bonds are equal in length (intermediate between single and double bond). X-ray studies support this.
The carbon uses sp² hybrid orbitals, and the remaining p orbital overlaps with oxygen p orbitals, creating a delocalised π system that stabilises the ion.
Effect of Substituents on Acidity
Substituents affect the stability of the acid and its conjugate base:
- Electron-withdrawing groups (Cl, NO₂) increase acidity.
- Electron-releasing groups (CH₃, OH, NH₂) decrease acidity.
Inductive effects decrease rapidly with distance. Halogen substitution near the carboxyl group greatly increases acidity, but the effect weakens when the substituent is farther away.
Nucleophilic Acyl Substitution Reaction
Carboxylic acids and their derivatives undergo nucleophilic acyl substitution. A nucleophile attacks the carbonyl carbon, forming a tetrahedral intermediate that expels a leaving group and reforms the carbonyl bond.
Negatively charged nucleophiles attack directly. Neutral nucleophiles require acid catalysis for the carbonyl group to become more electrophilic.
Conversions of Carboxylic Acids
1. Conversion to Acid Chlorides
Acid chlorides are usually prepared by reacting carboxylic acid with thionyl chloride (SOCl₂) or oxalyl chloride in the presence of pyridine.
2. Conversion to Esters (Fischer Esterification)
Carboxylic acids react with alcohols in the presence of acid catalyst to give esters. Removing water or using excess alcohol drives the reaction forward.
3. Conversion to Amides
Carboxylic acids react with ammonia or amines to form amides. Heating is required as the carboxylate intermediate must lose water to form the amide.
4. Conversion to Anhydrides
Anhydrides form by removing water between two carboxylic acids or by reacting acid chlorides with sodium salts of carboxylic acids.
Comparison: Alkyl vs. Acyl Nucleophilic Substitution
Nucleophilic substitution is much easier at an acyl carbon than at an alkyl carbon because:
- Acyl compounds have a planar carbonyl group, making attack easier.
- The π bond of the carbonyl breaks easily to form a tetrahedral intermediate.
- In alkyl substitution, the transition state is highly crowded (SN2) and less favourable.
Thus, acid chlorides are more reactive than alkyl chlorides, and amides/esters show characteristic reactivity due to the carbonyl group.
Detailed Notes:
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