Reactivity of Carboxylic Acid Derivatives

Question 1

How do you make a carboxylic acid or derivative more reactive to nucleophillic acyl attack?

Answer 1

Add electronegative ions like halides, which draw electrons form the carbonyl carbon, making it more positive. Halides are also good leaving groups.

Increase conjugation, making the ionic intermediate more stabilized via resonance.

Question 2

Name the carboxylic acid derivatives from most to least reactive and why

Answer 2

Acyl halides (b/c good leaving group and e-withdrawing), Anhydrides (b/c resonance stabilized + and 3 e-withdrawing groups), acids/esters (2 e-withdrawing substituents), Amides (electron-donating amino group)

Question 3

How does steric hinderance affect reactivity?

Answer 3

larger leaving groups make the molecule less reactive because the carbonyl carbon is more difficult to access and attack.

Question 4

How does ring strain contribute to reactivity?

Answer 4

ring strain increases reactivity, making lactones and lactams more reactive than their non-cyclic counterparts. This is because the molecules become more stable when the ring is broken.