Protecting Groups: Role and strategies for hydroxyl protection MCQs With Answer

Protecting Groups: Role and strategies for hydroxyl protection MCQs With Answer

This quiz collection targets M.Pharm students studying MPC 102T Advanced Organic Chemistry I and focuses on hydroxyl-protecting groups: their selection, installation, stability, orthogonality and deprotection strategies. Questions cover common silyl, benzyl, acyl and acetal protections, reagents and mechanistic considerations that influence multi-step syntheses. Emphasis is placed on practical decision-making—choosing groups compatible with acidic, basic, oxidative or reductive steps; achieving regio- and chemoselectivity; and planning orthogonal sequences. These MCQs are designed to deepen conceptual understanding and prepare students for problem-solving in synthetic route design involving alcohol protection and deprotection.

Q1. What is the primary purpose of using a protecting group on a hydroxyl function during multi-step organic synthesis?

• To temporarily mask hydroxyl groups to prevent undesired reactions during multi-step synthesis.
• To permanently convert hydroxyls to inert groups for final product stability.
• To increase the acidity of the alcohol to facilitate eliminations.
• To convert the alcohol into a better leaving group for SN1 reactions.

Correct Answer: To temporarily mask hydroxyl groups to prevent undesired reactions during multi-step synthesis.

Q2. Which set of criteria best describes an ideal protecting group for an alcohol?

• High cost, irreversible attachment, and introduction of chirality.
• Stability under target reaction conditions, easy and chemoselective removal, and orthogonality with other protecting groups.
• Maximum polarity, resistance to all reagents, and permanent incorporation.
• Only installed under extremely forcing conditions and removed by strong oxidants.

Correct Answer: Stability under target reaction conditions, easy and chemoselective removal, and orthogonality with other protecting groups.

Q3. Which protecting group for alcohols is most labile to acidic conditions among the following?

• TMS (trimethylsilyl) ether
• TBDMS (t-butyldimethylsilyl) ether
• Benzyl (Bn) ether
• Acetate (Ac) ester

Correct Answer: TMS (trimethylsilyl) ether

Q4. Which reagent combination is typically used to install a tert-butyldimethylsilyl (TBDMS) protecting group on an alcohol?

• TBDMSCl and imidazole
• TMSCl and pyridine
• BnBr and NaH
• Ac2O and pyridine

Correct Answer: TBDMSCl and imidazole

Q5. Which deprotection method is most commonly used to remove a benzyl (Bn) ether without affecting esters or silyl ethers under neutral conditions?

• Catalytic hydrogenation (H2, Pd-C)
• TBAF (tetrabutylammonium fluoride)
• NaOMe/MeOH (basic hydrolysis)
• BCl3 in dichloromethane

Correct Answer: Catalytic hydrogenation (H2, Pd-C)

Q6. Which protecting group for alcohols is particularly stable to strong bases but can be cleaved by fluoride sources?

• TBDMS (t-butyldimethylsilyl) ether
• Benzyl (Bn) ether
• Acetate (Ac) ester
• Methyl (Me) ether

Correct Answer: TBDMS (t-butyldimethylsilyl) ether

Q7. Which pair of protecting groups is considered orthogonal, allowing selective removal of one without affecting the other?

• TBDMS ether and benzyl (Bn) ether
• Acetate (Ac) ester and methyl (Me) ether
• TMS ether and TBDMS ether
• Methyl (Me) ether and benzyl (Bn) ether

Correct Answer: TBDMS ether and benzyl (Bn) ether

Q8. What is a principal advantage of using an acetate (Ac) protecting group for an alcohol?

• It is permanent and resists most hydrolysis conditions.
• It is bulky and provides steric protection for neighboring centers.
• It is easily installed and removed by mild basic hydrolysis or hydrazine.
• It requires strong oxidants for removal, which is useful for selective sequences.

Correct Answer: It is easily installed and removed by mild basic hydrolysis or hydrazine.

Q9. For selective protection of a primary alcohol in the presence of a secondary alcohol, which protecting group is often chosen due to its steric bulk and selectivity?

• Tert-butyldiphenylsilyl (TBDPS) ether
• Trimethylsilyl (TMS) ether
• Methyl (Me) ether
• Acetate (Ac) ester

Correct Answer: Tert-butyldiphenylsilyl (TBDPS) ether

Q10. Which reagent is most frequently used to cleave silyl ethers such as TBDMS or TBS under mild conditions?

• TBAF (tetrabutylammonium fluoride)
• H2, Pd-C
• NaBH4
• HCl in ethanol

Correct Answer: TBAF (tetrabutylammonium fluoride)

Q11. Which statement best describes benzyl (Bn) ethers in terms of stability and deprotection?

• Benzyl ethers are stable to both mild acid and base and are cleaved by catalytic hydrogenolysis.
• Benzyl ethers are acid-labile and are removed by dilute HCl.
• Benzyl ethers are easily cleaved by fluoride sources.
• Benzyl ethers are removed by mild base without affecting other groups.

Correct Answer: Benzyl ethers are stable to both mild acid and base and are cleaved by catalytic hydrogenolysis.

Q12. Which protecting group is commonly used for phenolic OH when the group must survive strong basic conditions?

• Methyl ether (OMe)
• Benzyl ether (Bn)
• Acetate (Ac) ester
• TMS ether

Correct Answer: Methyl ether (OMe)

Q13. Which protecting group is typically cleaved readily by strong acids such as trifluoroacetic acid (TFA)?

• tert-Butyl (t-Bu) ether
• Benzyl (Bn) ether
• TBDMS (t-butyldimethylsilyl) ether
• Methyl (Me) ether

Correct Answer: tert-Butyl (t-Bu) ether

Q14. Which reagent is most appropriate for selective cleavage of an acetate ester protecting group on an alcohol?

• NaOMe in methanol (basic hydrolysis)
• H2, Pd-C (hydrogenolysis)
• TBAF in THF
• DDQ (2,3-dichloro-5,6-dicyano-p-benzoquinone)

Correct Answer: NaOMe in methanol (basic hydrolysis)

Q15. In protecting-group terminology, what does “orthogonality” mean?

• The ability to install two protecting groups in a single step.
• The ability to remove one protecting group selectively without affecting another protected function.
• The property of a protecting group to be inert to all reagents.
• The requirement that protecting groups be identical on all similar functionalities.

Correct Answer: The ability to remove one protecting group selectively without affecting another protected function.

Q16. Which protecting group tends to increase lipophilicity of a molecule and is therefore useful to improve chromatographic separation?

• Silyl ethers such as TBDMS
• Acetate (Ac) esters
• Methyl (Me) ethers
• Hydroxyl left unprotected

Correct Answer: Silyl ethers such as TBDMS

Q17. Which protecting group is commonly formed as an acetonide to protect vicinal diols (1,2- or 1,3-diols) in carbohydrate and polyol chemistry?

• Acetonide (isopropylidene) acetal
• Benzyl ether
• TBDMS ether
• Acetate (Ac) ester

Correct Answer: Acetonide (isopropylidene) acetal

Q18. Which reagent will selectively cleave a benzyl ether without substantially affecting a TBDMS ether under typical conditions?

• Hydrogenation with H2 and Pd-C
• TBAF (tetrabutylammonium fluoride)
• NaOMe in MeOH
• HCl in aqueous acetonitrile

Correct Answer: Hydrogenation with H2 and Pd-C

Q19. Which hydroxyl protecting group can be removed under neutral oxidative conditions, for example by DDQ, and is useful when acid or base-sensitive functionality is present?

• p-Methoxybenzyl (PMB) ether
• TBDMS ether
• Methyl (Me) ether
• Acetate (Ac) ester

Correct Answer: p-Methoxybenzyl (PMB) ether

Q20. During silylation of an alcohol with TBDMSCl, what is the role of imidazole in the reaction?

• It acts as both a base to deprotonate the alcohol and as a nucleophilic catalyst.
• It serves only as a solvent with no chemical role.
• It oxidizes the alcohol to a carbonyl prior to silylation.
• It acts as an oxidant to activate TBDMSCl.

Correct Answer: It acts as both a base to deprotonate the alcohol and as a nucleophilic catalyst.

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