Carboxylic Acids & Derivatives

A carboxylic acid is a carbonyl group (C=O) with an OH attached to the same carbon: the –COOH group. At first glance, this looks like it should be just another alcohol. But the acidity is dramatically different. While a typical alcohol has a pKa around 16–18, acetic acid has a pKa of 4.75 — it is roughly a trillion times more acidic. The reason is resonance stabilisation of the conjugate base.

When a carboxylic acid loses its proton, the resulting carboxylate anion (RCOO⁻) has its negative charge delocalised equally across both oxygens through resonance. The two C–O bonds become equivalent (bond order ~1.5), and the negative charge is spread over two electronegative atoms instead of one. This makes the carboxylate far more stable than an alkoxide (RO⁻), which has a full negative charge concentrated on a single oxygen — and a more stable conjugate base means a stronger acid.

Carboxylic acids are named by replacing the terminal “-e” of the parent alkane with -oic acid. The carboxyl carbon is always C-1. A four-carbon chain is butanoic acid; five carbons = pentanoic acid. When the COOH is attached to a ring, use the suffix -carboxylic acid (e.g., cyclopentanecarboxylic acid). The acid derivatives (esters, amides, acyl halides, anhydrides) have their own suffixes based on the parent acid name.

Carboxylic acids have the highest boiling points among organic compounds of similar molecular weight — even higher than alcohols. This is because two carboxylic acid molecules form a hydrogen-bonded dimer: each molecule donates one H-bond and accepts one, creating a stable, doubly-linked pair. This dimerisation effectively doubles the molecular weight in the vapour phase, dramatically increasing the boiling point.

Small carboxylic acids (C1–C4) are fully miscible with water — the COOH group forms strong H-bonds with water. As the carbon chain grows, the hydrophobic tail overwhelms the hydrophilic head and water solubility falls. Fatty acids (C12+) are essentially insoluble. However, in base, fatty acids are converted to carboxylate salts (soaps), which ARE water-soluble — the basis of all soap chemistry.

An ester forms when a carboxylic acid reacts with an alcohol in the presence of a strong acid catalyst, with loss of water. This is the Fischer esterification, and it is reversible — you need to drive it forward by removing water or using excess of one reactant. The ester linkage (–COO–) is the same bond found in fats, oils, waxes, and aspirin.

The mechanism goes through a tetrahedral intermediate: the acid protonates the carbonyl oxygen (activating the carbonyl carbon), the alcohol attacks the carbonyl carbon, a molecule of water is lost, and the proton returns to give the ester. Because every step is reversible, esters can be hydrolysed back to acid + alcohol under aqueous acid conditions (reverse Fischer).

Saponification is the base-catalysed (or base-driven) hydrolysis of an ester to give a carboxylate salt and an alcohol. Unlike acid hydrolysis (which is reversible), saponification is irreversible: the base deprotonates the carboxylic acid product to give a stable carboxylate ion (RCOO⁻), which cannot reform the ester because it is no longer electrophilic enough. This is the chemistry of soap-making — treating fats (esters of glycerol) with NaOH gives glycerol and sodium carboxylate salts (soaps).

Amides form when a carboxylic acid (or more commonly, an acid chloride) reacts with an amine. Direct reaction of a carboxylic acid with an amine requires high temperatures because the initial product is an ammonium salt (RCOOH + RNH₂ → RCOO⁻ NH₃R⁺) that must be heated to eliminate water and form the amide. In the lab and in biochemistry, acid chlorides or anhydrides are used as more reactive acylating agents because they form amides readily at room temperature.

The amide bond (–CO–NH–) is one of the most stable and important bonds in biology. Proteins are built entirely from amide bonds (called peptide bonds in that context). The amide is stabilised by resonance: the nitrogen lone pair delocalises into the carbonyl, giving partial double-bond character to the C–N bond. This resonance explains why peptide bonds are planar, why they resist hydrolysis at physiological pH, and why proteins are stable.

All acid derivatives undergo the same fundamental reaction: nucleophilic acyl substitution. A nucleophile attacks the electrophilic carbonyl carbon, a tetrahedral intermediate forms, and then a leaving group departs to restore the C=O. The key variable is how good the leaving group is — and this determines how reactive each derivative is.

Acid chlorides are the most reactive because Cl⁻ is an excellent leaving group. Anhydrides are next. Esters are less reactive (RO⁻ is a weaker leaving group than Cl⁻). Amides are the least reactive among common derivatives because NH₂⁻ is a very poor leaving group and the resonance delocalisation of the nitrogen lone pair makes the amide carbonyl less electrophilic. Carboxylic acids themselves sit roughly between esters and anhydrides in reactivity.

Decarboxylation is the loss of CO₂ from a carboxylic acid. Simple carboxylic acids do not decarboxylate easily — you need very high temperatures. But β-keto acids (keto group at the β-carbon, two carbons from COOH) and malonic acid derivatives decarboxylate readily when heated. The mechanism goes through a six-membered cyclic transition state where the β-keto carbonyl accepts the electrons as CO₂ leaves, producing an enol which then tautomerises to the ketone.