Reactions Involving Cleavage of C–OH Bond

In these reactions the entire $-OH$ of the carboxyl group is replaced by another group while the carbonyl carbon is retained — this is exactly analogous to reactions at the $C-OH$ bond of an alcohol.

1. Formation of Anhydride

Heating a carboxylic acid with a mineral acid such as concentrated $H_2SO_4$, or with phosphorus pentoxide ($P_2O_5$), brings about loss of a water molecule between two acid molecules, giving the corresponding acid anhydride:

(Ethanoic acid + Ethanoic acid $\rightarrow$ Ethanoic anhydride)

2. Esterification

Carboxylic acids react with alcohols (or phenols) in the presence of a mineral-acid catalyst — concentrated $H_2SO_4$ or dry $HCl$ gas — to form esters. The reaction is reversible:

Mechanism of esterification (Fischer esterification)

Esterification is a nucleophilic acyl substitution and proceeds as follows:

1. Protonation of the carbonyl oxygen of the carboxylic acid by $H^+$ activates the carbonyl carbon towards nucleophilic attack.
2. Nucleophilic addition of the alcohol. The oxygen of $R'OH$ attacks the activated (electrophilic) carbonyl carbon, generating a tetrahedral intermediate that carries both the original $-OH$ and the new $-\overset{+}{O}HR'$ (protonated alkoxy) group.
3. Proton transfer within the tetrahedral intermediate moves the positive charge from the newly added oxygen onto the original hydroxyl oxygen, converting that $-OH$ into a much better leaving group, $-\overset{+}{O}H_2$.
4. Loss of water. The protonated $-\overset{+}{O}H_2$ leaves as a neutral water molecule, giving the protonated ester.
5. Deprotonation. The protonated ester loses a proton to regenerate the acid catalyst and give the neutral ester.

Every step up to and including loss of water is reversible, which is why esterification itself is an equilibrium reaction (driven towards the ester by using excess alcohol or by removing water as it forms).

3. Reactions with PCl₅, PCl₃ and SOCl₂

The hydroxyl group of a carboxylic acid, like that of an alcohol, is readily replaced by chlorine on treatment with phosphorus pentachloride, phosphorus trichloride, or thionyl chloride, giving the acid chloride:

4. Reaction with Ammonia

Carboxylic acids react with ammonia to first give an ammonium salt; further heating of this salt at high temperature drives off water and gives an amide:

$CH_3COOH + NH_3 \;\rightleftharpoons\; \underset{\text{Ammonium acetate}}{CH_3COO^-NH_4^+} \;\xrightarrow[-H_2O]{\Delta}\; \underset{\text{Acetamide}}{CH_3CONH_2}$ …