Electrophilicity of Carboxylic Acids Derivatives.

As with aldehydes and ketones, the carbonyl group of carboxylic acid derivatives is electrophilic.  This is easily visualized by examining the resonance structures of a carboxylic acid derivative.

This resonance tells us the carbonyl carbon bears a partial positive charge and is therefore electrophilic.  

In general, the electrophilicity and hence the reactivity toward acyl substitution of the 4 main carboxylic acid derivatives following trend.  Acyl chlorides are the most reactive and amides the least.  This is the same reactivity order we saw when we considered the leaving groups.

Your instructor (some textbooks), especially those with a biochemical focus may include the acyl phosphate, thioester and carboxylic acid in this series as follows.

Acid Chlorides

Acid chlorides are the most electrophilic of the carboxylic acid derivatives.  Cl is an inductive withdrawing group that makes the already electrophilic carbonyl carbon even more electrophilic.  The Cl atom destabilizes the carbonyl making it more reactive. 

While the Cl atom has lone pairs that are in conjugation (resonance) with the carbonyl, the Cl atom it is a poor resonance donor because of its high electronegativity and the shape and size of a Cl p orbital is much different from that of a C p orbital.  They can't overlap very well to form a π bond.  Thus the last resonance structure does not contribute much to the overall structure and does not stabilize the carbonyl.


Anhydrides are not as electrophilic as acid chlorides but more so than esters and amides.  Oxygen is somewhat electronegative and a moderate electron donor by resonance. The competing pull of electrons to either carbonyl of the anhydride results in 1 out of 3 resonance structures show non-electrophilic character on the carbonyl carbon.  


With esters we have these two resonance structures.  One of these (the right one) shows electrons being pushed into the carbonyl.  In this case, half of the resonance structures show a non-electrophilic carbonyl carbon.


Amides are the least electrophilic and as a result the least reactive.  N atoms are not very electronegative in comparison to C atoms, N is next to C on the periodic table.  Nitrogen is a very good resonance donator its p orbitals are similar in shape and size to p orbitals on C.  Therefore it is a good resonance donator and the resonance structure on the right below is a significant contributor.