medium · MCAT chem-phys

An organic chemist attempts to synthesize an ester via nucleophilic acyl substitution. He finds that reacting a carboxylic acid with an alcohol is slow, but reacting an acid chloride with the same alcohol is much faster.

What is the fundamental electronic reason for this difference?

  1. Chlorine is actually a larger atom than oxygen, so steric hindrance cannot explain this reactivity difference.
  2. The chlorine atom is a better leaving group and its electron-withdrawing effect makes the carbonyl carbon more electrophilic.
  3. Hydroxide is a poor leaving group compared to chloride, since the chloride ion is far more stable after leaving the molecule.
  4. The nucleophilicity of the alcohol itself is a fixed property that does not meaningfully change between the two reactions compared.

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