C–X and C–C disconnections: alcohols and carbonyl compound strategies MCQs With Answer

C–X and C–C disconnections are central concepts in retrosynthetic analysis for the design of syntheses involving alcohols and carbonyl compounds. This quiz collection focuses on strategic disconnections, reagent choices, and functional group interconversions relevant to M.Pharm students studying MPC 102T Advanced Organic Chemistry I. Questions probe understanding of when to cleave C–X versus C–C bonds, how to plan homologation and carbonyl syntheses, the role of protecting groups, and the use of common carbon–carbon bond-forming reactions (Grignard, Wittig, aldol, etc.). Emphasis is placed on strategic reasoning, chemoselectivity, stereochemical outcomes, and practical disconnection patterns used in complex molecule preparation.

Q1. In retrosynthetic planning, which disconnection is preferred to form a secondary alcohol from a carbonyl precursor?

• Disconnection of C–C bond to give an alkene and a nucleophile
• Disconnection of C–X bond to give an alkyl halide and a carbonyl anion equivalent
• Disconnection of C–O bond to give an ether and a proton source
• Disconnection producing two radical fragments

Correct Answer: Disconnection of C–X bond to give an alkyl halide and a carbonyl anion equivalent

Q2. Which reagent pair is most suitable for converting an aldehyde into a primary alcohol under chemoselective conditions when ketones are present?

• Lindlar catalyst hydrogenation
• Sodium borohydride (NaBH4)
• Sodium cyanoborohydride (NaBH3CN)
• Lithium aluminum hydride (LiAlH4)

Correct Answer: Sodium borohydride (NaBH4)

Q3. For formation of a tertiary alcohol from a ketone, the common retrosynthetic disconnection involves adding which type of reagent?

• Organolithium or Grignard reagent (R–MgX/R–Li)
• Hydride donor (NaBH4)
• Wittig reagent (Ph3P=CR2)
• Acid chloride and base

Correct Answer: Organolithium or Grignard reagent (R–MgX/R–Li)

Q4. In planning a synthesis of a β-hydroxy carbonyl via retrosynthesis, which disconnection corresponds to the aldol condensation reverse step?

• Disconnection at the C–O bond to yield an alcohol and a leaving group
• Disconnection of the C–C bond between α-carbon and β-carbon to give two carbonyl fragments
• Disconnection to form an enolate and an electrophilic carbonyl partner
• Disconnection producing an acyl radical and an alkyl radical

Correct Answer: Disconnection to form an enolate and an electrophilic carbonyl partner

Q5. Which protecting group is most commonly used to protect primary and secondary alcohols during carbonyl chemistry and is easily removed under mild acidic conditions?

• Tert-butyldimethylsilyl (TBDMS) ether
• Benzyl (Bn) ether
• Tetrahydropyranyl (THP) ether
• Acetyl (Ac) ester

Correct Answer: Tetrahydropyranyl (THP) ether

Q6. Which retrosynthetic transformation is an example of umpolung (polarity inversion) useful for C–C bond formation at the carbonyl carbon?

• Use of organolithium addition to a carbonyl
• Use of cyanide to form a cyanohydrin followed by displacement
• Wittig olefination
• Aldol reaction between enolate and carbonyl

Correct Answer: Use of cyanide to form a cyanohydrin followed by displacement

Q7. Which reagent combination is typically used in a homologation of an aldehyde to give the next higher aldehyde (one-carbon elongation) via the Wittig-like strategy?

• Grignard reagent followed by oxidation
• Seyferth–Gilbert reagent (EBX) or Corey–Fuchs to give an alkyne then hydroboration–oxidation
• Sodium borohydride then Swern oxidation
• Ozonolysis of an alkene

Correct Answer: Seyferth–Gilbert reagent (EBX) or Corey–Fuchs to give an alkyne then hydroboration–oxidation

Q8. When retrosynthetically disconnecting a vicinal diol into two carbonyl fragments, which forward reaction is most directly implicated?

• Pinacol coupling
• Ozonolysis of an alkene
• Pinnick oxidation
• Oxidative cleavage (periodate cleavage) of a vicinal diol

Correct Answer: Oxidative cleavage (periodate cleavage) of a vicinal diol

Q9. For converting a tertiary alcohol into an alkene selectively, which mechanistic disconnection strategy is used retrosynthetically?

• Disconnection to a carbonyl and hydride donor
• Beta-elimination (E1) from a protonated alcohol to give C–C double bond
• SN2 displacement to substitute the OH
• Nucleophilic addition to the alcohol carbon

Correct Answer: Beta-elimination (E1) from a protonated alcohol to give C–C double bond

Q10. Which disconnection is most logical when designing a route to an α,β-unsaturated carbonyl from a saturated carbonyl precursor?

• Disconnection of the C–C bond between α and β to give two radicals
• Retrosynthetic removal of H2 to reveal an enone precursor (dehydrogenation strategy)
• Disconnection to yield an acetal and a base
• Direct nucleophilic substitution at α-carbon

Correct Answer: Retrosynthetic removal of H2 to reveal an enone precursor (dehydrogenation strategy)

Q11. Which reagent is typically chosen for converting an alcohol to a good leaving group (alkyl halide) without rearrangement in retrosynthetic planning?

• Concentrated sulfuric acid
• PBr3 or SOCl2 with pyridine
• PCC (pyridinium chlorochromate)
• KMnO4 under acidic conditions

Correct Answer: PBr3 or SOCl2 with pyridine

Q12. In a retrosynthesis for a secondary alcohol formed by nucleophilic addition to a ketone, which approach helps control stereochemistry most directly?

• Using a chiral auxiliary or chiral reagent (e.g., chiral borane or CBS reduction)
• Using excess hydride source
• Protection as an ether before addition
• Oxidation to an ester followed by reduction

Correct Answer: Using a chiral auxiliary or chiral reagent (e.g., chiral borane or CBS reduction)

Q13. Which retrosynthetic disconnection would you use to break a C–C bond α to a carbonyl to form an enolate equivalent?

• Disconnection to give a carbocation and a nucleophile
• Disconnection to an enolate (or silyl enol ether) and an electrophile
• Radical disconnection to two alkyl radicals
• Disconnection into an acetal and a nucleophile

Correct Answer: Disconnection to an enolate (or silyl enol ether) and an electrophile

Q14. Which forward transformation corresponds to the retrosynthetic disconnection of an α-halo ketone into a ketone and halide?

• Halogenation at the α-position of a ketone via enolization
• Direct reduction of the halide followed by oxidation
• Ozonolysis of the ketone
• Formation of an acetal and substitution

Correct Answer: Halogenation at the α-position of a ketone via enolization

Q15. When planning a synthesis of an alcohol from an alkyl halide via C–X disconnection, which mechanism leads to inversion of configuration at a stereocenter?

• SN1 substitution
• SN2 substitution
• E2 elimination
• Radical halogenation

Correct Answer: SN2 substitution

Q16. Which reagent is preferred for converting a carbonyl compound into its corresponding oxime as a disconnection tactic for later formation of an amine (Beckmann-type strategies)?

• Hydroxylamine (NH2OH) under mildly acidic conditions
• Sodium borohydride
• PBr3
• DDQ (2,3-dichloro-5,6-dicyano-p-benzoquinone)

Correct Answer: Hydroxylamine (NH2OH) under mildly acidic conditions

Q17. In retrosynthesis, breaking a C–C bond next to an oxygen atom (α to ether) often suggests which forward transformation?

• Acid-catalyzed cleavage of the ether to give alcohol and carbocation-derived fragment
• Direct hydrogenation of the ether
• Oxidative cleavage of ether to carboxylic acids
• Base-catalyzed SN2 at the oxygen

Correct Answer: Acid-catalyzed cleavage of the ether to give alcohol and carbocation-derived fragment

Q18. For a retrosynthetic plan to synthesize an α-hydroxy ketone selectively, which forward reaction is commonly used?

• Boulevard oxidation
• Dakin oxidation
• Friedel–Crafts acylation
• α-Hydroxylation of enolates using Davis oxaziridine or oxygen insertion methods

Correct Answer: α-Hydroxylation of enolates using Davis oxaziridine or oxygen insertion methods

Q19. Which disconnection is most appropriate if your target alcohol is adjacent to an existing carbonyl and you plan to form it via intramolecular nucleophilic addition?

• Disconnection to form a tethered nucleophile and electrophile (intramolecular closure)
• Disconnection to two separate radicals
• Disconnection to an alkene and water
• Disconnection to form a diazonium salt

Correct Answer: Disconnection to form a tethered nucleophile and electrophile (intramolecular closure)

Q20. When retrosynthetically converting a carboxylic acid to a primary alcohol, which two-step sequence is most commonly planned?

• Direct reduction with NaBH4
• Conversion to acid chloride then reduction with LiAlH4
• Decarboxylation then hydration
• Oxidative cleavage then Grignard addition

Correct Answer: Conversion to acid chloride then reduction with LiAlH4

Download