Protecting Groups: Carbonyl protection – acetals and ketals MCQs With Answer

Protecting Groups: Carbonyl protection – acetals and ketals MCQs With Answer

This short MCQ collection is designed for M.Pharm students studying MPC 102T Advanced Organic Chemistry I. It focuses on carbonyl protection using acetals and ketals — a fundamental tactic in multi-step synthesis to mask aldehydes and ketones selectively. The questions cover formation and hydrolysis mechanisms, choice of reagents, stability under acidic/basic and nucleophilic conditions, cyclic versus acyclic acetals, use of orthoesters and diols, and practical aspects such as water removal and selective deprotection. These targeted items will help reinforce theoretical understanding and improve problem-solving skills needed in medicinal chemistry and synthesis planning.

Q1. Which of the following best describes the general requirement for converting a carbonyl into a stable acetal?

• Base-catalyzed reaction with a primary amine
• Acid-catalyzed reaction with an alcohol or diol and removal of water
• Radical addition of tert-butyl hydroperoxide
• Oxidation with Jones reagent

Correct Answer: Acid-catalyzed reaction with an alcohol or diol and removal of water

Q2. Which reagent is commonly used to form cyclic acetals from aldehydes using ethylene glycol?

• Sodium borohydride (NaBH4)
• p-Toluenesulfonic acid (p-TsOH)
• Potassium tert-butoxide (KOtBu)
• Chromium trioxide (CrO3)

Correct Answer: p-Toluenesulfonic acid (p-TsOH)

Q3. Why are acetals and ketals considered good protecting groups for carbonyls in the presence of strong nucleophiles like Grignard reagents?

• They are strong electrophiles that react preferentially with Grignard reagents
• They convert the carbonyl into an sp3 center, which is not reactive toward nucleophilic addition
• They chelate magnesium and deactivate the Grignard reagent
• They oxidize the Grignard reagent to suppress its reactivity

Correct Answer: They convert the carbonyl into an sp3 center, which is not reactive toward nucleophilic addition

Q4. Which condition will efficiently hydrolyze an acetal back to the parent carbonyl?

• Strong base such as NaOH at high temperature
• Neutral water at room temperature
• Acidic aqueous conditions (e.g., dilute HCl) at mild temperature
• Dry methanol with molecular sieves

Correct Answer: Acidic aqueous conditions (e.g., dilute HCl) at mild temperature

Q5. Which of these reagents can be used to form an acetal without needing an external acid catalyst by using an orthoester?

• Trimethyl orthoformate (HC(OMe)3)
• Sodium cyanoborohydride (NaBH3CN)
• Diisobutylaluminium hydride (DIBAL-H)
• Benzoyl chloride (BzCl)

Correct Answer: Trimethyl orthoformate (HC(OMe)3)

Q6. Compared to acyclic acetals, cyclic acetals such as 1,3-dioxolanes are preferred because:

• They are less stable to acid than acyclic acetals
• They form irreversibly and cannot be hydrolyzed
• They often show greater thermodynamic stability and facilitate easy isolation
• They readily undergo oxidation to carboxylic acids

Correct Answer: They often show greater thermodynamic stability and facilitate easy isolation

Q7. Which statement is correct about the stability of acetals under basic conditions?

• Acetals are rapidly cleaved under mild basic conditions
• Acetals are generally stable to base but susceptible to acid-catalyzed hydrolysis
• Base converts acetals into epoxides
• Base reduces acetals to alcohols directly

Correct Answer: Acetals are generally stable to base but susceptible to acid-catalyzed hydrolysis

Q8. In a synthesis where an aldehyde must be protected while a nearby ester is reduced with DIBAL-H, which protecting group choice is most appropriate?

• Convert aldehyde to an acetal (ethylene glycol)
• Oxidize the aldehyde to a carboxylic acid
• Form an imine with aniline
• Convert aldehyde to its corresponding hydrate

Correct Answer: Convert aldehyde to an acetal (ethylene glycol)

Q9. Which of the following is a common driving technique to shift the equilibrium toward acetal formation?

• Add excess water to dilute reactants
• Perform reaction under high pressure of CO2
• Remove produced water by molecular sieves or Dean–Stark apparatus
• Use a strong base to neutralize the acid

Correct Answer: Remove produced water by molecular sieves or Dean–Stark apparatus

Q10. What is a “benzylidene acetal” commonly used for in carbohydrate chemistry?

• To oxidize sugar hydroxyls to carbonyls
• As a protecting group that masks two adjacent hydroxyl groups and can be selectively removed
• To permanently block all hydroxyl functionality against any reagent
• To isomerize sugars from pyranose to furanose forms

Correct Answer: As a protecting group that masks two adjacent hydroxyl groups and can be selectively removed

Q11. Which of the following reagents would most likely cleave a ketal under mild conditions?

• Sodium methoxide in methanol
• Aqueous acetic acid (pH ~3)
• Triethylamine
• Tert-butanol under anhydrous conditions

Correct Answer: Aqueous acetic acid (pH ~3)

Q12. When protecting a sterically hindered ketone, which diol tends to give the most stable cyclic ketal?

• Glycolic acid
• Ethylene glycol (1,2-ethanediol)
• Propane-1,2-diol (1,2-propanediol)
• 1,3-Propanediol

Correct Answer: Ethylene glycol (1,2-ethanediol)

Q13. Which mechanism step is characteristic of acetal formation from a carbonyl and an alcohol under acid catalysis?

• Nucleophilic attack of alcohol on a protonated carbonyl forming a hemiacetal intermediate
• Concerted [2+2] cycloaddition between carbonyl and alcohol
• Free radical abstraction at the α-carbon
• Direct nucleophilic substitution at the oxygen atom of the carbonyl

Correct Answer: Nucleophilic attack of alcohol on a protonated carbonyl forming a hemiacetal intermediate

Q14. Which protecting group is more acid-sensitive and therefore easier to remove under mild conditions?

• Tetrahydropyranyl (THP) ether protecting an alcohol
• Acetal derived from ethylene glycol protecting an aldehyde
• Silyl ether (TBDMS) protecting an alcohol
• Benzyl ether protecting an alcohol

Correct Answer: Acetal derived from ethylene glycol protecting an aldehyde

Q15. What is the role of catalytic acid in ketal formation besides protonating the carbonyl?

• It neutralizes the alcohol nucleophile to slow the reaction
• It protonates the leaving group and helps eliminate water to form the oxonium ion
• It converts the diol into a more nucleophilic radical
• It coordinates to the carbonyl oxygen to form a stable metal complex

Correct Answer: It protonates the leaving group and helps eliminate water to form the oxonium ion

Q16. In selective protection, how can one protect an aldehyde in presence of a ketone when only the aldehyde must be masked?

• Use a very bulky diol that reacts faster with ketones
• Exploit the higher reactivity of aldehydes by using mild acid and short reaction times to form acetals selectively
• Oxidize the ketone to a carboxylic acid first
• Use a strong base to selectively deprotonate the aldehyde

Correct Answer: Exploit the higher reactivity of aldehydes by using mild acid and short reaction times to form acetals selectively

Q17. Which observation indicates that acetal formation has reached equilibrium under given conditions?

• Complete disappearance of starting carbonyl irrespective of reagent amounts
• Steady concentrations of carbonyl, hemiacetal, and acetal over time
• Immediate precipitation of product upon mixing reagents
• Evolution of hydrogen gas

Correct Answer: Steady concentrations of carbonyl, hemiacetal, and acetal over time

Q18. Which one of the following statements about orthoesters (e.g., HC(OR)3) in acetal chemistry is true?

• Orthoesters are strong acids that protonate carbonyls
• Orthoesters can be used as alkoxy group donors and drive acetal formation with elimination of an alcohol
• Orthoesters reduce carbonyls to alcohols under neutral conditions
• Orthoesters are stable to aqueous acid and do not participate in acetalizations

Correct Answer: Orthoesters can be used as alkoxy group donors and drive acetal formation with elimination of an alcohol

Q19. Which spectral change in proton NMR would indicate formation of a cyclic acetal from an aldehyde?

• Disappearance of aldehydic proton signal (~9–10 ppm) and appearance of new acetal methine/methylene signals (~3.5–5 ppm)
• Appearance of a strong signal at 200 ppm
• Shift of aldehydic proton further downfield to ~12 ppm
• Complete loss of all proton resonances

Correct Answer: Disappearance of aldehydic proton signal (~9–10 ppm) and appearance of new acetal methine/methylene signals (~3.5–5 ppm)

Q20. Which protective strategy would you choose if you need a carbonyl protected group that is stable to mild acid but removable under strongly acidic aqueous conditions?

• Use a dimethyl acetal (from methanol) which is generally less stable and cleaved under mild acid
• Form a cyclic ketal (e.g., 1,3-dioxolane) which resists mild acid but can be hydrolyzed under stronger acid
• Convert the carbonyl to an oxime which is acid-labile
• Form a thioacetal which is stable to all acidic conditions

Correct Answer: Form a cyclic ketal (e.g., 1,3-dioxolane) which resists mild acid but can be hydrolyzed under stronger acid

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