A student is comparing the relative reactivities of different organic compounds. They are specifically interested in the susceptibility of a carbonyl carbon to nucleophilic attack. Which of the following compounds would have the most electrophilic carbonyl carbon, making it most reactive towards nucleophiles?
- ACarboxylic acid (RCOOH)
- BAcid chloride (RCOCl)
- CEster (RCOOR')
- DAmide (RCONR₂)
Show answer & explanationAnswer & explanation
Correct answer: B. Acid chloride (RCOCl)
The electrophilicity of a carbonyl carbon is enhanced by electron-withdrawing groups and diminished by electron-donating groups. The ability of the leaving group (or substituent on the carbonyl carbon) to donate electrons via resonance or induction affects this. Halides (like Cl) are highly electronegative and poor electron donors via resonance, making them strongly electron-withdrawing. Amides have a nitrogen atom that can strongly donate electrons via resonance, making the carbonyl carbon less electrophilic. Esters have an oxygen atom that can also donate electrons via resonance, but less effectively than nitrogen. Carboxylic acids fall in between, with the -OH group having some resonance donation. Acid chlorides, with the highly electronegative chlorine atom, have the least resonance stabilization of the carbonyl and the strongest inductive withdrawal, making their carbonyl carbon the most electrophilic and thus most reactive towards nucleophiles.
Why the other options are wrong
- A. Carboxylic acids are generally more reactive than amides and esters under acidic conditions but less reactive than acid chlorides due to the resonance contribution of the -OH group.
- C. Esters are more reactive than amides but less reactive than acid chlorides or carboxylic acids, as the oxygen atom's resonance donation is moderate.
- D. Amides are the least reactive towards nucleophiles due to the strong resonance donation from the nitrogen atom, which reduces the electrophilicity of the carbonyl carbon.
Carbonyl Electrophilicity
The electrophilicity of a carbonyl carbon refers to its ability to accept electrons from a nucleophile, which is enhanced by electron-withdrawing groups and reduced by electron-donating groups attached to the carbonyl.
- Electron-withdrawing groups increase electrophilicity.
- Electron-donating groups (especially via resonance) decrease electrophilicity.
- Reactivity order for carboxylic acid derivatives: Acid Chloride > Anhydride > Ester ≈ Carboxylic Acid > Amide.
Memory trick: Chlorine is Cruel, Nitrogen is Nice (to the carbonyl).