Reactivity

The reactivity map of a carboxylic acid is defined, in the first place, by the high acidity of its OH group and, in the second, by the electrophilicity of its carbonyl carbon.

The relative acidity of the hydrogens α to a carbonyl group is completely masked in carboxylic acids by the much higher acidity of the OH group.

Reactivity map of a carboxylic acid: strongly acidic OH hydrogen, electrophilic carbonyl carbon, basic oxygen centers and weakly acidic α-hydrogen

The high acidity of the carboxyl group strongly interferes with any reaction carried out in basic medium. The base is instantly neutralized by the carboxyl group and the reaction won't proceed. Therefore, the nucleophilic attack on the carbonyl carbon of a carboxylic acid can only be performed in acidic medium.

The mechanism of nucleophilic attack on a carboxylic acid or an acid derivative is known as addition-elimination because it consists of (at least) these two steps. Addition takes place first and elimination follows.

General addition-elimination mechanism

Protonation of the carboxylic acid at the carbonyl oxygen and its two resonance forms, with the positive charge on the carbon

The nucleophilic attack on a carboxylic acid is performed in mineral or Lewis acidic medium, in order to avoid interference from the acidity of the OH group and also to increase the electrophilicity of the carbonyl carbon. In fact, a carboxylic acid partially protonates in acidic medium thus decreasing the electron density at the C=O carbon.

The oxygen of the C=O group is a weak base that can react with the mineral or Lewis acid. The equilibrium is shifted to the left but the few molecules that react with the external acid are much more reactive towards a nucleophile because their electron deficiency is greatly increased. Look at the resonance forms!

Addition step: the protonated nucleophile (Nu–H) attacks the protonated carbonyl carbon, giving a tetrahedral intermediate with an emergent water molecule as a good leaving group

At this favorable stage of increased electrophilicity, the protonated nucleophile - we are in acidic medium! - adds to the C=O group.

Note that in the addition step the initially sp²-hybridized C=O carbon (trigonal planar) changes to sp³ hybridization (tetrahedral).

Elimination step: a water molecule leaves and, after loss of a proton, the acid derivative bearing the nucleophile instead of the OH is obtained

In the addition step an incipient water molecule is formed, which is an excellent leaving group, leading to the carboxylic acid derivative where its initial OH has been formally replaced by the nucleophile.

In the elimination step the reacting carbon returns to its initial sp² hybridization. The used proton or Lewis acid is recovered and thus the needed amount of acid for this reaction is just a catalytic one.

Reactions of carboxylic acids

Complete Fischer esterification: protonation of the acid, addition of the alcohol, elimination of water and loss of the proton to give the ester

Ester Formation

Formation of the acid chloride with thionyl chloride: attack of the acid on sulfur, addition of chloride to the carbonyl group and elimination of HCl and SO₂

Acid (Acyl) Halides
Formation

Hell-Volhard-Zelinsky reaction: PBr₃ converts the acid into the acid bromide, whose enol is brominated at the α position; hydrolysis gives the α-bromo acid

α-Halogenation

Scale of carbon oxidation states, from C⁴⁻ to C⁴⁺: alkanes, alkenes, alcohols, alkynes, aldehydes and ketones, acids and derivatives and, finally, CO, CO₂ and H₂CO₃