You saw that acid anhydrides react with alcohols to give esters: they will also react with amines to give amides. But would you expect esters to react with amines to give amides, or amides to react with alcohols to give esters? Both appear reasonable.

In fact, only the top reaction works: amides can be formed from esters but esters cannot be formed from amides. The key question is: which group will leave from the common tetrahedral intermediate? The answer is MeO⁻ and not NH₂ ⁻. You should have worked this out from the stability of the anions. Alkoxides are reasonably strong bases (pKa of ROH about 15) so they are not good leaving groups. But NH₂ − is a very unstable anion (pKa of NH3 about 25) and is a very bad leaving group.

So MeO⁻ leaves and the amide is formed. The base used to deprotonate the fi rst formed inter mediate may be either the MeO⁻ produced in the reaction or, to start with, another molecule of NH₃.

Here is a slightly unusual example in that there is a ketone present in the molecule as well. Later in the book we shall consider how to work out whether another functional group might interfere with the reaction we want to do.

مواضيع ذات صلة

Strength of nucleophile and leaving group ability are related and pKa is a guide to both

Factors other than leaving group ability can be important

Amines react with acyl chlorides to give amides

pKa is a useful guide to leaving group ability

?How do we know that the tetrahedral intermediate exists

?Why are the tetrahedral intermediates unstable

Acid chlorides and acid anhydrides react with alcohols to make esters

The product of nucleophilic addition to a carbonyl group is not always a stable compound

Oxidation of alcohols

?Secondary and tertiary alcohols: which organometallic, which aldehyde, which ketone

Making primary alcohols from organometallics and formaldehyde

Making carboxylic acids from organometallics and carbon dioxide