Carboxylic Acids

While carboxylic acids are not the most reactive they are central in the reactivity of carboxylic acid derivatives.  They can be converted to any of the carboxylic acid derivatives.  Since the -OH of carboxylic acids is not the greatest leaving group a common theme is to convert it to a more reactive leaving group.  In general, the more reactive acid chlorides and anhydrides are easily converted to alcohols (alcoholysis) and amides (aminolysis).  

Conversion of Carboxylic Acids to Acid Chlorides.

Treating carboxylic acids with thionyl chloride (SOCl2) results in the formation of acid chlorides.


The carbonyl oxygen behaves like a nucleophile and undergoes an acyl substitution with the thionyl chloride (SOCl2).  This first step actually goes through a tetrahedral S intermediate and eventually a Cl anion leaves (I used the "Cheater Mechanism").  Deprotonation of this resonance stabilized intermediate results in an "activated" carboxylic acid, since the -OSOCl is an excellent leaving group.  

In the second part of the mechanism, the Cl ion undergoes acyl substitution with the activated carboxylic acid.

Conversion of Carboxylic Acids to Esters 

Fischer Esterification

Treating carboxylic acids with excess alcohol and acid while removing water results in the formation of esters.  This reaction is reversible and is often pulled or pushed to the right side to maximize product.  This is often done with drying agent (molecular sieves etc) or by using Dean-Stark apparatus to remove water as a toluene azeotrope - pulling the equilibrium to the right side (Le Chateliers Principle).  We often use an excess of alcohol as well to push the equilibrium to the right.

This proceeds by a typical acyl substitution mechanism under acidic catalysis.  A few drops of concentrated H2SO4 or PTSA are often used as the acid.

Substitution Reactions (SN2)

Converting a carboxylic acid to a carboxylate salt results in a rather good nucleophile for SN2 reactions with primary halides.  This can be employed to make esters of primary and secondary alkyl halides.

Carbodiimide Coupling Reagents

Amides and esters can be formed from carboxylic acids using carbodiimide coupling reagents.  There are a variety of carbodiimides available.  Dicyclohexylcarbodiimide (DCC) is one of the more prevalent ones used.

For example, the following amide could be easily prepared by this technique.

The carboxylic acid is activated by the carbodiimide as follows as follows.  

The activated carboxylic acid now easily undergoes acyl substitution with the amine nucleophile.