Protecting Group Strategy: Orthogonality and the Order of Removal · seed 1 · A4, ink-friendly. The answer key prints on its own page for grown-ups.

Scheduling protection across a long route

Science · Chemistry · ages 22-23
Name ______________________   Date ____________

  1. What does orthogonal mean for a pair of protecting groups?

    • Both remove in the same single wash
    • Each removes under conditions leaving the other untouched
    • Neither group can ever be removed

  2. Why do chemists mask carbonyls as acetals?

    • To make them react faster with every reagent
    • To protect them through harsh steps, then unmask with aqueous acid
    • To change their color for easier tracking

  3. A capped ether behaves exactly like a free hydroxyl toward strong reagents.

    Circle one:   True   False

  4. A deprotection uses strong base. What must you check first?

    • Which other groups in the molecule would not survive it
    • The alphabetical order of the reagents
    • The brand of the glassware

  5. Two hydroxyls must free at different points. Which pair do you pick?

    • Two identical acid labile masks
    • No masks at all, plus hope
    • One hydrogen stripped mask with one acid stripped mask

  6. When do esters serve well as masked acids?

    • When you want a mask that no condition can ever open
    • When the route contains no steps at all
    • When you need a mask steady through neutral and acidic steps, opened by base later

  7. A colleague proposes global deprotection to save three steps, sacrificing one ester you wanted. How do you decide?

    • Always refuse global steps on principle
    • Weigh the saved steps against the yield hit on the lost ester
    • Flip a coin and skip the analysis

  8. A route strips an acid labile ether while a needed acetal sits nearby. What is the risk?

    • The acetal may also fall, since acid unmasks it too
    • Acetals always survive any acid wash
    • Ethers can never be removed selectively
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Answer key

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

Scheduling protection across a long route W1-mt_-TvfTGZ-_Z-s1

  1. Each removes under conditions leaving the other untouched · Orthogonal sets free sites in any chosen order.
  2. To protect them through harsh steps, then unmask with aqueous acid · Acetals survive bases and hydrides, then open cleanly at the end.
  3. False · The capped ether sits quiet while the free hydroxyl attacks.
  4. Which other groups in the molecule would not survive it · Stability tables tell you what lives through each strip.
  5. One hydrogen stripped mask with one acid stripped mask · Different strip recipes let you unveil the sites one at a time.
  6. When you need a mask steady through neutral and acidic steps, opened by base later · Esters install easily, stand steady, then open when the acid is wanted.
  7. Weigh the saved steps against the yield hit on the lost ester · The endgame call balances speed against what the shared wash costs.
  8. The acetal may also fall, since acid unmasks it too · Shared weak spots mean one wash can fell masks you hoped to keep.
Worksheet · LightMySky