Synthetic Reagents: N-Bromosuccinimide uses MCQs With Answer

Synthetic Reagents: N-Bromosuccinimide (NBS) uses MCQs With Answer

N-Bromosuccinimide (NBS) is a versatile brominating reagent widely used in organic synthesis, especially valuable in medicinal chemistry and drug development. For M.Pharm students, understanding NBS is essential for designing selective transformations such as allylic and benzylic bromination, α-bromination of carbonyl compounds, and formation of bromohydrins. NBS offers controlled bromine delivery, minimizing over-bromination and enabling chemoselective reactions under radical or electrophilic conditions. This quiz focuses on mechanisms, reaction conditions, solvent effects, stereochemical outcomes, and practical applications of NBS in complex molecule synthesis to build problem-solving skills and deepen conceptual knowledge relevant to pharmaceutical research.

Q1. Which of the following is the most typical synthetic use of N-bromosuccinimide (NBS)?

• Allylic bromination of alkenes (Wohl–Ziegler reaction) under radical conditions
• Direct fluorination of alkanes
• Oxidative cleavage of vicinal diols
• Nitration of aromatic rings

Correct Answer: Allylic bromination of alkenes (Wohl–Ziegler reaction) under radical conditions

Q2. The mechanistic pathway of allylic bromination with NBS under light or AIBN typically proceeds via:

• Electrophilic addition to the double bond followed by rearrangement
• Radical chain mechanism involving bromine radicals generated from NBS
• Nucleophilic substitution at sp2 carbon
• Pericyclic concerted cycloaddition

Correct Answer: Radical chain mechanism involving bromine radicals generated from NBS

Q3. Which solvent is historically and commonly used for NBS-mediated allylic bromination to favor radical selectivity?

• Carbon tetrachloride (CCl4) or other nonpolar solvents
• Water
• Strongly acidic media like concentrated H2SO4
• Liquid ammonia

Correct Answer: Carbon tetrachloride (CCl4) or other nonpolar solvents

Q4. NBS can be used to form bromohydrins from alkenes when performed in the presence of:

• Anhydrous ether with no nucleophiles present
• Water (or aqueous nucleophile) which attacks the bromonium intermediate
• A radical inhibitor like BHT
• Strong reducing agents like LiAlH4

Correct Answer: Water (or aqueous nucleophile) which attacks the bromonium intermediate

Q5. Compared to using molecular bromine (Br2), NBS is often preferred because it:

• Releases high concentrations of free Br2 leading to multiple brominations
• Provides controlled, low effective Br2 concentration and greater allylic/benzylic selectivity
• Is a stronger oxidant that converts alcohols to carboxylic acids
• Acts as a base to deprotonate acidic protons selectively

Correct Answer: Provides controlled, low effective Br2 concentration and greater allylic/benzylic selectivity

Q6. Which additive or condition is commonly used to initiate NBS radical reactions?

• AIBN, heat, or light (hv) to generate radicals
• Strong Lewis acids like AlCl3
• High-pressure hydrogen gas
• Strong bases such as NaH or t-BuOK

Correct Answer: AIBN, heat, or light (hv) to generate radicals

Q7. NBS is particularly effective for bromination at which stabilized positions?

• Allylic and benzylic C–H positions
• Unactivated primary sp3 C–H positions remote from π-systems
• Terminal alkynic sp C–H exclusively
• Carboxylic acid hydroxyl groups

Correct Answer: Allylic and benzylic C–H positions

Q8. Under appropriate conditions, NBS can perform α-bromination of carbonyl compounds. Which intermediate is typically involved in such transformations?

• Free carbanion via strong base deprotonation only
• Enol or enolate/enamine that is electrophilically brominated
• Epoxide intermediate
• Carbene insertion into C–H bond

Correct Answer: Enol or enolate/enamine that is electrophilically brominated

Q9. In contrast to radical allylic bromination, NBS can also effect vicinal dibromination of alkenes when conditions favor:

• A radical chain with excess peroxide
• Electrophilic bromination (generation of Br+) leading to bromonium ion opening by Br−
• Strong nucleophilic substitution at sp3 carbon
• Photochemical formation of carbenes

Correct Answer: Electrophilic bromination (generation of Br+) leading to bromonium ion opening by Br−

Q10. What is the stoichiometric by-product formed when NBS donates a bromine atom in solution?

• Maleimide
• Succinimide
• Nitrosobenzene
• Hydrogen bromide only

Correct Answer: Succinimide

Q11. Which of the following is NOT generally a limitation of NBS in synthetic practice?

• Overbromination is completely impossible with NBS under any conditions
• Low reactivity toward unactivated sp3 C–H bonds (non-allylic/benzylic)
• Potential formation of brominated side-products if conditions are not controlled
• Need for radical initiator or specific solvent for selectivity

Correct Answer: Overbromination is completely impossible with NBS under any conditions

Q12. For N-halosuccinimides, which order correctly ranks their typical electrophilic reactivity for halogenation reactions?

• NCS > NBS > NIS
• NIS > NBS > NCS
• NBS > NCS > NIS
• All have identical reactivity

Correct Answer: NIS > NBS > NCS

Q13. Direct electrophilic aromatic bromination using NBS without catalysts is generally:

• Highly efficient for deactivated aromatics at room temperature
• Not effective; requires Lewis acid catalysts or Br2 generation in situ
• The standard method for brominating electron-poor aromatics
• Commonly used to introduce bromine ortho to nitro groups

Correct Answer: Not effective; requires Lewis acid catalysts or Br2 generation in situ

Q14. When an enantiomerically pure allylic center is subjected to NBS-mediated radical bromination at that center, the stereochemical outcome is typically:

• Complete retention of configuration
• Complete inversion of configuration only
• Racemization or formation of a mixture due to planar radical intermediate
• Formation of a single diastereomer due to stereospecific concerted pathway

Correct Answer: Racemization or formation of a mixture due to planar radical intermediate

Q15. An allylic bromide produced by NBS is a useful intermediate because it can readily undergo which of the following transformations?

• Nucleophilic substitution (SN2/SN1), elimination, and transition-metal cross-coupling reactions
• Direct conversion to carboxylic acids without further reagents
• Selective hydrogenation to alkanes under acidic water only
• Spontaneous aromatization at room temperature

Correct Answer: Nucleophilic substitution (SN2/SN1), elimination, and transition-metal cross-coupling reactions

Q16. The presence of radical inhibitors (e.g., oxygen, BHT) in an NBS allylic bromination reaction will generally lead to:

• Acceleration of the allylic bromination
• Suppression of the radical pathway and reduced conversion
• Formation of more brominated products selectively
• Complete conversion to α-bromoketones

Correct Answer: Suppression of the radical pathway and reduced conversion

Q17. Safety and handling consideration specific to NBS reactions include:

• NBS solutions are completely inert and require no special ventilation
• NBS can liberate bromine vapors and should be handled in a fume hood with appropriate PPE
• NBS is a strong reducing agent and should be kept away from oxidizable organics
• NBS reactions always increase pressure and require explosion-proof vessels

Correct Answer: NBS can liberate bromine vapors and should be handled in a fume hood with appropriate PPE

Q18. In radical bromination selectivity by NBS, which C–H site is preferentially brominated when multiple allylic positions are present?

• The least substituted primary allylic site
• The most stabilized radical site (tertiary allylic > secondary allylic > primary allylic)
• All allylic sites are brominated equally
• The site closest to a carbonyl is always preferred regardless of stability

Correct Answer: The most stabilized radical site (tertiary allylic > secondary allylic > primary allylic)

Q19. Which statement about NBS reactivity toward saturated, unactivated alkanes (no adjacent π-systems) is correct?

• NBS efficiently brominates unactivated methylene C–H bonds at room temperature without initiator
• NBS shows low reactivity toward unactivated C–H bonds and is not the reagent of choice for such transformations
• NBS exclusively forms alcohols from alkanes under standard conditions
• NBS performs selective fluorination of unactivated alkanes

Correct Answer: NBS shows low reactivity toward unactivated C–H bonds and is not the reagent of choice for such transformations

Q20. Why is NBS often chosen for selective allylic bromination in complex molecule synthesis (e.g., API intermediate preparation)?

• Because it is the strongest brominating reagent available regardless of selectivity
• Due to its mildness, controlled bromine release, chemoselectivity, and compatibility with diverse functional groups
• Because it always gives a single stereoisomer without racemization
• Because it eliminates the need for purification of reaction mixtures

Correct Answer: Due to its mildness, controlled bromine release, chemoselectivity, and compatibility with diverse functional groups

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