Named Reactions: Brook rearrangement and synthetic use MCQs With Answer

Introduction: The Brook rearrangement is a fundamental named reaction in advanced organic chemistry where a silyl group migrates from carbon to oxygen in α-silyl alkoxides, generating a silanolate and a carbon-centered anion. For M.Pharm students, mastering this reaction is important because it exemplifies umpolung (polarity inversion), organosilicon reactivity, and strategic formation of reactive intermediates used in complex molecule synthesis. This quiz collection focuses on mechanistic details, factors affecting the rearrangement, stereochemical and electronic consequences, and practical synthetic applications such as carbon–carbon bond formation and functional group interconversion. Use these MCQs to test and deepen your conceptual and applied understanding.

Q1. Which description best defines the Brook rearrangement?

• 1,2-migration of a silyl group from oxygen to carbon in silyl ethers
• Radical cleavage of a C–Si bond to form silyl radicals
• 1,2-migration of a silyl group from carbon to oxygen in α-silyl alkoxides
• Nucleophilic substitution at silicon producing silanes

Correct Answer: 1,2-migration of a silyl group from carbon to oxygen in α-silyl alkoxides

Q2. The primary driving force for the Brook rearrangement is:

• Formation of a stronger Si–O bond and stabilization of the carbanion
• Formation of a stronger C–Si bond and release of H2
• Formation of a silicon-centered radical
• Formation of a stable carbocation intermediate

Correct Answer: Formation of a stronger Si–O bond and stabilization of the carbanion

Q3. What condition most commonly initiates the Brook rearrangement?

• Strong acid catalysis (e.g., HCl, H2SO4)
• Base-induced formation of an alkoxide or carbanion (e.g., organolithium, alkoxide)
• UV light causing homolysis of C–Si bond
• Heating neutral silyl ethers at 25–40 °C

Correct Answer: Base-induced formation of an alkoxide or carbanion (e.g., organolithium, alkoxide)

Q4. Which substrate is most likely to undergo a facile Brook rearrangement?

• Tertiary alkyl silyl ether without adjacent electron-withdrawing groups
• α-Silyl alkoxide where the carbon bearing silicon can stabilize negative charge (e.g., adjacent aryl or carbonyl)
• Simple trialkylsilyl-protected primary alcohols
• Alkyl chlorides bearing a remote silyl group

Correct Answer: α-Silyl alkoxide where the carbon bearing silicon can stabilize negative charge (e.g., adjacent aryl or carbonyl)

Q5. In the anionic Brook rearrangement mechanism, what intermediate is typically formed on the oxygen after migration?

• Silyl cation
• Silanolate (Si–O−)
• Silyl radical
• Neutral siloxane

Correct Answer: Silanolate (Si–O−)

Q6. Which solvent type generally favors the Brook rearrangement?

• Highly protic solvents such as water or methanol
• Polar aprotic solvents such as THF or DME that stabilize ions
• Nonpolar solvents like hexane exclusively
• Strongly coordinating solvents containing halides

Correct Answer: Polar aprotic solvents such as THF or DME that stabilize ions

Q7. The Brook rearrangement is an example of which broader synthetic concept?

• Retrosynthetic disconnection of ether bonds
• Umpolung (polarity inversion) of a carbon center
• Pericyclic electrocyclization
• Radical chain rearrangement

Correct Answer: Umpolung (polarity inversion) of a carbon center

Q8. Which statement about stereochemical outcome at silicon during Brook rearrangement is most accurate?

• Migration always leads to racemization at silicon
• Silyl migration typically proceeds through a pentacoordinate silicon transition state often giving retention of configuration at silicon
• Silyl migration necessarily inverts configuration at silicon via an SN2 at silicon
• Silicon stereochemistry is irrelevant because silicon cannot be stereogenic

Correct Answer: Silyl migration typically proceeds through a pentacoordinate silicon transition state often giving retention of configuration at silicon

Q9. Which synthetic application commonly uses the Brook rearrangement?

• Direct formation of amides from alcohols without activation
• Generation of α-carbanions for subsequent alkylation or acylation
• Oxidative cleavage of ethers to carbonyls
• Hydroboration–oxidation of alkenes

Correct Answer: Generation of α-carbanions for subsequent alkylation or acylation

Q10. Which reagent would most likely prevent the Brook rearrangement in an α-silyl alkoxide by trapping the oxygen?

• Excess strong base such as n-BuLi
• Electrophile such as trimethylsilyl chloride that reprotects oxygen as a silyl ether
• Polar aprotic solvent like THF
• Lewis base like pyridine

Correct Answer: Electrophile such as trimethylsilyl chloride that reprotects oxygen as a silyl ether

Q11. The retro-Brook rearrangement refers to:

• 1,2-migration of silicon from oxygen back to carbon under appropriate conditions
• Permanent cleavage of Si–O bonds to give siloxanes
• Spontaneous thermal fragmentation of silanolate to radicals
• Hydrolysis of silyl ethers to alcohols

Correct Answer: 1,2-migration of silicon from oxygen back to carbon under appropriate conditions

Q12. Which substituent on silicon increases the tendency for Brook rearrangement by stabilizing the pentacoordinate transition state?

• Bulky, strongly electron-donating alkyl groups only
• Electron-withdrawing substituents on silicon that increase Lewis acidity (e.g., phenyl)
• Substituents that make silicon nonpolar and sterically hindered always prevent migration
• Any substituent has no effect on the transition state stability

Correct Answer: Electron-withdrawing substituents on silicon that increase Lewis acidity (e.g., phenyl)

Q13. How does the presence of an adjacent carbonyl group influence Brook rearrangement?

• It disfavors the rearrangement by destabilizing the carbanion
• It accelerates the rearrangement by stabilizing the resulting carbanion through resonance
• It causes immediate protonation and stops any rearrangement
• It converts the pathway into a radical process

Correct Answer: It accelerates the rearrangement by stabilizing the resulting carbanion through resonance

Q14. Which of the following best describes a synthetic sequence where Brook rearrangement is deliberately used?

• Convert an alcohol to a protected ether followed by oxidative cleavage
• Generate α-silyl alcohol → deprotonate to cause Brook rearrangement → trap carbanion with electrophile to form new C–C bond
• Protect alcohols as acetates and then hydrolyze to obtain diols
• Use Brook rearrangement to directly form nitriles from alcohols

Correct Answer: Generate α-silyl alcohol → deprotonate to cause Brook rearrangement → trap carbanion with electrophile to form new C–C bond

Q15. Which experimental observation supports a concerted, intramolecular Brook rearrangement rather than an intermolecular silyl transfer?

• The reaction rate increases dramatically with added free silane
• Isotopic labeling shows migration of the silyl group from the same molecule’s carbon to its oxygen without crossover
• Formation of polymeric siloxanes is observed as the major product
• The reaction requires radical initiators to proceed

Correct Answer: Isotopic labeling shows migration of the silyl group from the same molecule’s carbon to its oxygen without crossover

Q16. In a typical mechanism, the carbanion formed after Brook rearrangement is best described as:

• A highly stabilized carbanion localized only on silicon
• An oxygen-centered radical
• An α-carbanion that can be trapped by electrophiles or protonated to give substituted products
• An unreactive species that cannot undergo further transformations

Correct Answer: An α-carbanion that can be trapped by electrophiles or protonated to give substituted products

Q17. Which analytical evidence would most directly confirm formation of a silanolate intermediate during a Brook rearrangement?

• Observation of a new strong Si–O stretching band in IR and presence of a negatively charged oxygen species in NMR (e.g., shifted 29Si NMR)
• Detection of molecular hydrogen evolution
• Color change only with no spectroscopic evidence
• Formation of gaseous silicon species detected by GC

Correct Answer: Observation of a new strong Si–O stretching band in IR and presence of a negatively charged oxygen species in NMR (e.g., shifted 29Si NMR)

Q18. Which limitation is commonly associated with applying Brook rearrangement in complex molecule synthesis?

• It cannot generate nucleophilic carbon centers
• Competing deprotection or elimination pathways and sensitivity to protic impurities can limit yields
• It only operates under aqueous conditions
• It always produces racemic mixtures of all products

Correct Answer: Competing deprotection or elimination pathways and sensitivity to protic impurities can limit yields

Q19. Which of the following transformations can be efficiently accomplished by harnessing the Brook rearrangement?

• Direct conversion of primary alcohols to primary amines without activation
• α-Alkylation of carbonyl compounds by generating nucleophilic carbanions adjacent to oxygen after silyl migration
• Formation of ethers by SN1 substitution at tertiary carbons
• Hydrogenation of alkenes under mild conditions

Correct Answer: α-Alkylation of carbonyl compounds by generating nucleophilic carbanions adjacent to oxygen after silyl migration

Q20. Which modification or related reaction is often combined with Brook rearrangement to access complex scaffolds?

• Combining Brook rearrangement with electrophilic trapping (e.g., alkylation, acylation) or subsequent oxidation to functionalize the carbon center
• Using it solely for peptide bond formation
• Applying Brook rearrangement as a terminal step to remove all protecting groups
• Employing it to directly form aromatic rings from alkanes

Correct Answer: Combining Brook rearrangement with electrophilic trapping (e.g., alkylation, acylation) or subsequent oxidation to functionalize the carbon center

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