Carboxylic Acid Derivatives

[thedolphin]

Kaplan Ch. 4 says carboxylic acids follow a hierarchy for reactivity toward nucleophilic attack: anhydride > carboxylic acid and ester > amide. Higher reactivity derivatives can form lower reactivity derivatives, but not vice versa.

However, I thought anhydrides are formed via carboxylic acid condensation, which involves nucleophilic attack? Would anyone be able to clarify please? Thank you!

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[JimKimSlim]

I think Kaplan is saying lower reactivity derivatives cannot form higher ones spontaneously. Yes, it is possible to form anhydrides with carboxylic acids but it would involve acid-base catalysis. It’s also possible to form anhydrides from amides, but you need to couple the reaction with another reaction that is highly thermodynamically favorable. The main takeaway of that section is the order of reactivity of carboxylic acid derivatives. Don’t delve too much in the chemistry because anything is possible in the world of synthesis, but MCAT doesn’t go that far.

 

[thedolphin]

I think Kaplan is saying lower reactivity derivatives cannot form higher ones spontaneously. Yes, it is possible to form anhydrides with carboxylic acids but it would involve acid-base catalysis. It’s also possible to form anhydrides from amides, but you need to couple the reaction with another reaction that is highly thermodynamically favorable. The main takeaway of that section is the order of reactivity of carboxylic acid derivatives. Don’t delve too much in the chemistry because anything is possible in the world of synthesis, but MCAT doesn’t go that far.

Ahh, gotcha. Thank you for the explanation!