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, with leaving groups deciding the traffic

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. On the unactivated addition route taught here, what happens first in nucleophilic acyl substitution?

    • The nucleophile attacks to give a tetrahedral intermediate
    • The leaving group departs on its own before anything attacks
    • 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 patiently
    • 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 of them all
    • 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 orders two routes by product stability alone and declares the most stable product the winner. Why is that ranking not enough?

    • A route works only if each step has a willing leaving group
    • The colours of the starting materials
    • The number of atoms in each solvent

  8. An ester meets an amine and amide forms directly. The reverse pairing needs hydrolysis first, then esterification under ordinary conditions. What does that show?

    • Amide to ester runs directly, since amides are restless
    • Neither pairing can run under any conditions
    • Ester to amide runs directly, while amide to ester needs the two-step detour under ordinary conditions
LightMySky · lightmysky.comW1-mt_b60fq2aQ7r-s1

Answer key

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

One ladder, with leaving groups deciding the traffic 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 · On the unactivated route, 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 with willing leaving groups under driving conditions, 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 · Both routes cross a tetrahedral motif. Acid returns the neutral acid directly, while base strands carboxylate until a separate acid workup.
  7. A route works only if each step has a willing leaving group · The ladder ranks how fast carbonyls suffer attack, set by resonance and leaving-group skill, not product stability alone.
  8. Ester to amide runs directly, while amide to ester needs the two-step detour under ordinary conditions · Resonance steadies the amide and its leaving group is poor, so only the ester-to-amide direction runs directly under ordinary conditions.
Worksheet · LightMySky