07 Carboxylic Acid Derivatives and Acyl Substitution Free Online FlashCards

What is the general structure of a carboxylic acid derivative?

Carboxylic acid derivatives have the general structure R–C(=O)–Y, with Y attached directly to the acyl carbon.

What changes in nucleophilic acyl substitution?

In nucleophilic acyl substitution, a nucleophile replaces Y at the acyl carbon.

What is the general reactivity order of acyl derivatives?

Acid chlorides > acid anhydrides > thioesters > esters > amides. Carboxylate ions are especially unreactive.

How does leaving-group ability affect acyl derivative reactivity?

Weaker bases generally make better leaving groups. Chloride and carboxylate leave more readily than alkoxide, while an amide-derived nitrogen anion is especially unfavorable.

Why are amides relatively unreactive toward nucleophilic acyl substitution?

Resonance donation reduces the partial positive charge on the acyl carbon. Nitrogen donates strongly, which makes amides relatively unreactive.

Why are thioesters generally more reactive than esters?

Sulfur donates electron density to the carbonyl less effectively than ester oxygen, helping make thioesters more reactive than esters.

What happens in the addition step of acyl substitution?

A nucleophile attacks the electrophilic acyl carbon, and the carbonyl π electrons move onto oxygen, forming a tetrahedral intermediate.

How does the tetrahedral intermediate collapse?

The oxygen lone pair reforms the carbonyl, and a leaving group departs from the tetrahedral intermediate.

What enables acyl derivatives to undergo substitution unlike aldehydes and ketones?

It has a group that can leave when the tetrahedral intermediate collapses. Aldehydes and ketones lack this feature.

How can acidic conditions promote acyl substitution?

In acidic conditions, protonation can make the carbonyl more electrophilic and convert a poor leaving group into a better one.

What product forms from benzoyl chloride and 2-propanol?

Benzoyl chloride reacts with 2-propanol to form isopropyl benzoate; the alcohol-derived oxygen replaces chloride.

What amide forms when acetic anhydride reacts with ammonia?

Acetic anhydride and ammonia produce acetamide, along with acetate-derived products after proton transfer.