Why do amides require much harsher conditions for hydrolysis than esters?
I'm guessing amides are more stable for some reason, but I'm not completely sure. Is it conjugation?
Yes, you are indeed correct. Amides are more stable than esters, and this is primarily due to conjugation.
To understand why amides require harsher conditions for hydrolysis than esters, let's first look at their chemical structures. An amide consists of a carbonyl group (C=O) bonded to a nitrogen atom (N), while an ester consists of a carbonyl group (C=O) bonded to an oxygen atom (O).
The key difference between these two functional groups is the presence of the nitrogen atom in the amide compound. This nitrogen atom can participate in a process known as conjugation, where it can delocalize its lone pair of electrons into the adjacent carbonyl group.
Conjugation in amides increases their stability by distributing the negative charge resulting from the lone pair of electrons over a larger area, reducing the electrophilicity of the carbonyl carbon. Consequently, this makes it more difficult for a nucleophile to attack the carbonyl carbon and carry out hydrolysis.
On the other hand, esters do not possess a nitrogen atom and hence lack this conjugation effect. As a result, esters are less stable and more easily hydrolyzed compared to amides, even under milder conditions.
Therefore, when hydrolyzing amides, stronger conditions are required, such as heating them in the presence of concentrated acids or strong bases, in order to break the strong amide bond. Conversely, esters can be hydrolyzed under milder conditions like adding water or a weak acid or base.