Nucleophilic Acyl Substitution and the Reactivity Ladder · seed 1 · A4, ink-friendly. The answer key prints on its own page for grown-ups.

One ladder, travelled downhill only

Science · Chemistry · ages 20-21
Name ______________________   Date ____________

  1. Which order ranks the acid derivatives from most to least reactive?

    • Amides, esters, anhydrides, acyl chlorides
    • Acyl chlorides, anhydrides, esters, amides
    • Esters, amides, acyl chlorides, anhydrides

  2. What happens first in nucleophilic acyl substitution?

    • The nucleophile attacks to give a tetrahedral intermediate
    • The leaving group departs on its own
    • The carbonyl oxygen leaves as water

  3. The tetrahedral intermediate collapses by reforming the carbonyl and ejecting the leaving group.

    Circle one:   True   False

  4. You need the ester that matches a given amide. What route works?

    • Hydrolyse to the acid first, then esterify
    • Stir the amide with alcohol and wait
    • Heat the amide until it rearranges

  5. Why do amides sit at the calm bottom of the ladder?

    • They carry no carbonyl group at all
    • Their leaving group departs most gladly
    • Resonance donation steadies them against attack

  6. How do acid and base hydrolysis of an ester differ?

    • Acid gives the salt, base gives the neutral acid
    • Acid gives the neutral acid, base leaves the carboxylate salt
    • Both give identical products by identical steps

  7. A student picks between two routes by comparing product stability only. What should they compare instead?

    • Whether each leaving group departs willingly
    • The colours of the starting materials
    • The number of atoms in each solvent

  8. Which interconversion runs on its own: ester to amide, or amide to ester?

    • Amide to ester, since amides are restless
    • Neither can ever run under any conditions
    • Ester to amide, since that step runs downhill
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Answer key

For grown-ups. Fold this page away before handing over the rest.

One ladder, travelled downhill only W1-mt_b60fq2aQ7r-s1

  1. Acyl chlorides, anhydrides, esters, amides · Leaving skill and resonance set this fixed ladder.
  2. The nucleophile attacks to give a tetrahedral intermediate · Addition always opens the two-act play.
  3. True · That collapse is the elimination act of the play.
  4. Hydrolyse to the acid first, then esterify · Both steps run downhill, unlike the direct climb.
  5. Resonance donation steadies them against attack · Donation from nitrogen calms the starting material.
  6. Acid gives the neutral acid, base leaves the carboxylate salt · The intermediate matches, but the product fate splits.
  7. Whether each leaving group departs willingly · Leaving skill decides whether a step can run.
  8. Ester to amide, since that step runs downhill · Downhill traffic flows from higher rungs to lower ones.
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