Reactions of cyclobutane MCQs With Answer

Reactions of cyclobutane MCQs With Answer is a focused review for B.Pharm students covering essential chemistry, mechanisms, and pharmaceutical relevance of cyclobutane derivatives. This introduction highlights ring strain, conformational features, thermal and photochemical reactions (including [2+2] cycloadditions and ring-opening), and common functional-group transformations such as halogenation, hydrogenation, ozonolysis, and nucleophilic ring cleavage. Emphasis is placed on reaction mechanisms, stereochemistry, and synthetic applications relevant to drug design and metabolic pathways. These MCQs reinforce conceptual understanding and problem-solving skills for exams and practical courses. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which factor primarily accounts for the increased reactivity of cyclobutane compared to linear alkanes?

• Resonance stabilization
• Greater hyperconjugation
• Significant ring strain due to bond angle compression
• Higher molecular weight

Correct Answer: Significant ring strain due to bond angle compression

Q2. What is the approximate ring strain energy of cyclobutane?

• ~3 kcal/mol
• ~7 kcal/mol
• ~26 kcal/mol
• ~40 kcal/mol

Correct Answer: ~26 kcal/mol

Q3. Cyclobutane typically adopts which conformation to reduce torsional strain?

• Planar square
• Puckered (butterfly) conformation
• Boat conformation
• Chair conformation

Correct Answer: Puckered (butterfly) conformation

Q4. Which photochemical process commonly forms cyclobutanes from alkenes?

• Norrish type I reaction
• [2+2] Photochemical cycloaddition
• Diels–Alder reaction
• Friedel–Crafts alkylation

Correct Answer: [2+2] Photochemical cycloaddition

Q5. Thermal [2+2] cycloadditions between alkenes are generally:

• Stereospecific and allowed by orbital symmetry
• Forbidden by orbital symmetry rules
• More common than photochemical [2+2]
• Catalyzed by Brønsted acids

Correct Answer: Forbidden by orbital symmetry rules

Q6. Vinylcyclobutane can rearrange thermally to give which product commonly seen in synthetic chemistry?

• Cyclopropane
• Cyclohexene via ring expansion
• Butane
• Benzene

Correct Answer: Cyclohexene via ring expansion

Q7. Ring opening of substituted cyclobutanes under radical conditions proceeds mainly through formation of:

• Carbocations exclusively
• Carbanions exclusively
• Diradical or radical intermediates with C–C bond cleavage
• Concerted pericyclic cleavage without intermediates

Correct Answer: Diradical or radical intermediates with C–C bond cleavage

Q8. Which reagent is commonly used to hydrogenate cyclobutane derivatives to give saturated products?

• H2 with Pd/C
• KMnO4
• Br2 in CCl4
• PCC

Correct Answer: H2 with Pd/C

Q9. Ozonolysis of cyclobutane derivatives containing double bonds typically yields:

• Alcohols only
• Carbonyl compounds (aldehydes/ketones)
• Alkanes
• Nitriles

Correct Answer: Carbonyl compounds (aldehydes/ketones)

Q10. Which statement about cyclobutanone is true?

• It is less reactive than acyclic ketones due to less ring strain
• It undergoes facile ring-opening reactions due to ring strain at the carbonyl
• It cannot participate in nucleophilic addition reactions
• It has no synthetic utility in medicinal chemistry

Correct Answer: It undergoes facile ring-opening reactions due to ring strain at the carbonyl

Q11. Nucleophilic attack on cyclobutanone often leads to which outcome?

• Formation of stable cyclobutane without bond cleavage
• Ring-opening to form acyclic or expanded products
• Immediate aromatization
• Elimination of CO2

Correct Answer: Ring-opening to form acyclic or expanded products

Q12. Which type of reaction explains photochemical cleavage of cyclobutane into two alkenes?

• Electrophilic aromatic substitution
• [2+2] Cycloreversion via diradical pathway
• SN2 substitution
• Hydrogen abstraction only

Correct Answer: [2+2] Cycloreversion via diradical pathway

Q13. In pharmaceutical molecules, cyclobutane rings are used primarily because they:

• Increase molecular flexibility dramatically
• Provide conformational constraint and metabolic stability
• Always enhance water solubility
• Act as strong ionic handles

Correct Answer: Provide conformational constraint and metabolic stability

Q14. Which mechanism is most relevant for halogenation of cyclobutane under radical conditions?

• Electrophilic addition
• Free radical chain mechanism (hydrogen abstraction followed by halogenation)
• Nucleophilic aromatic substitution
• Pericyclic sigmatropic shift

Correct Answer: Free radical chain mechanism (hydrogen abstraction followed by halogenation)

Q15. The ring-opening of cyclobutanol under acid catalysis typically gives:

• Alkenes by dehydration only
• Carbocation-driven C–C bond cleavage to give carbonyl-containing products
• Stable cyclobutane with no reaction
• Aromatic compounds

Correct Answer: Carbocation-driven C–C bond cleavage to give carbonyl-containing products

Q16. Which spectroscopic change is most diagnostic of cyclobutane ring opening to yield conjugated diene?

• Loss of IR C=O stretch
• Appearance of UV–Vis absorption due to conjugation
• Disappearance of C–H stretches only
• No change in spectroscopic features

Correct Answer: Appearance of UV–Vis absorption due to conjugation

Q17. Which statement about the stereochemistry of photochemical [2+2] cycloaddition forming cyclobutanes is correct?

• Photochemical [2+2] reactions are stereospecific and preserve alkene stereochemistry through the reaction pathway
• They always give racemic mixtures regardless of starting stereochemistry
• They are completely non-stereospecific and random
• They proceed through ionic intermediates exclusively

Correct Answer: Photochemical [2+2] reactions are stereospecific and preserve alkene stereochemistry through the reaction pathway

Q18. Which catalyst can enable thermal [2+2] cycloaddition by altering orbital interactions?

• Lewis acids or transition-metal photocatalysts that enable stepwise pathways
• Strong Brønsted bases only
• PCC
• KMnO4

Correct Answer: Lewis acids or transition-metal photocatalysts that enable stepwise pathways

Q19. A cyclobutylcarbinyl radical tends to undergo which process rapidly?

• Beta-scission/ring opening to a more stable radical
• Direct substitution without cleavage
• Immediate protonation
• Aromatic substitution

Correct Answer: Beta-scission/ring opening to a more stable radical

Q20. Which reagent would convert a cyclobutanone to a ring-opened diol under reductive conditions?

• LiAlH4 followed by workup
• Ozone (O3) only
• H2O2 in base
• Br2 in water

Correct Answer: LiAlH4 followed by workup

Q21. Which reaction is a common method to synthesize substituted cyclobutanes medicinally?

• Wittig reaction on alkanes
• [2+2] Photochemical cycloaddition of alkenes
• Friedel–Crafts acylation of benzene only
• Ozonolysis of cyclohexanes

Correct Answer: [2+2] Photochemical cycloaddition of alkenes

Q22. In a retrosynthetic plan, cyclobutane can act as a masked form of which motif after ring opening?

• 1,4-dicarbonyl or 1,3-diene systems
• Aromatic ring
• Simple alkane chain only
• Nitrile group

Correct Answer: 1,4-dicarbonyl or 1,3-diene systems

Q23. Which of the following best describes the C–C bond lengths in cyclobutane compared to typical sp3 C–C bonds?

• Significantly longer due to strain relief
• Approximately similar, though slightly affected by angle strain
• Zero because bonds are ionic
• Much shorter to compensate for angle strain

Correct Answer: Approximately similar, though slightly affected by angle strain

Q24. The term “puckering” in cyclobutane refers to:

• Formation of a flat square geometry
• Out-of-plane bending of atoms to reduce torsional strain
• Conversion to cyclopropane
• Deprotonation of the ring

Correct Answer: Out-of-plane bending of atoms to reduce torsional strain

Q25. Which oxidation reagent will oxidize cyclobutane alkyl side chains to carboxylic acids under vigorous conditions?

• PCC at low temperature
• KMnO4 (hot, acidic or basic) strong oxidation
• NaBH4
• HCl in ethanol

Correct Answer: KMnO4 (hot, acidic or basic) strong oxidation

Q26. Which process can lead to cleavage of cyclobutane rings during metabolism of drug molecules?

• Enzymatic radical-mediated C–C bond scission
• Complete resistance to metabolism
• Only hydrolysis at aromatic positions
• Direct aromatic substitution

Correct Answer: Enzymatic radical-mediated C–C bond scission

Q27. Which is true about substituted cyclobutanes in terms of conformational isomerism?

• They exhibit free rotation like open-chain alkanes
• Conformational interconversion is limited and stereochemistry can be locked
• They always exist as a single conformation
• They rapidly aromatize to benzene

Correct Answer: Conformational interconversion is limited and stereochemistry can be locked

Q28. Which reaction demonstrates ring expansion from cyclobutane to a six-membered ring?

• Vinylcyclobutane rearrangement to cyclohexene
• Simple hydrogenation
• Alkene metathesis only
• SN1 substitution at cyclobutane carbon

Correct Answer: Vinylcyclobutane rearrangement to cyclohexene

Q29. The reactivity of cyclobutane toward electrophiles is generally:

• Identical to benzene
• Enhanced due to ring strain and ability to form stabilized intermediates
• Zero because cyclobutane is inert
• Only dependent on solvent polarity

Correct Answer: Enhanced due to ring strain and ability to form stabilized intermediates

Q30. Which intermediate is commonly proposed in photochemical ring opening of cyclobutanes?

• Carbanion pair
• Diradical species
• Stable carbocation with no radicals
• Aromatic cation

Correct Answer: Diradical species

Q31. Which functional group on a cyclobutane makes it particularly susceptible to Baeyer–Villiger type oxidative rearrangement?

• Cyclobutane alkane without heteroatoms
• Cyclobutanone (carbonyl) functional group
• Tertiary amine far from ring
• Unsubstituted methyl groups only

Correct Answer: Cyclobutanone (carbonyl) functional group

Q32. Which protecting group strategy might be useful for a cyclobutanol to prevent acid-catalyzed ring opening during synthesis?

• Conversion to a silyl ether (e.g., TBS)
• Oxidation to a ketone directly
• Leaving it unprotected in strong acid
• Halogenation at remote position

Correct Answer: Conversion to a silyl ether (e.g., TBS)

Q33. Which of the following reactions can lead to formation of cyclobutane-containing natural product frameworks?

• [2+2] Cycloaddition between enones under photochemical conditions
• Fischer esterification only
• Free radical bromination exclusively
• Wurtz coupling of two alkanes

Correct Answer: [2+2] Cycloaddition between enones under photochemical conditions

Q34. In mass spectrometry, fragmentation of cyclobutane-containing molecules often shows peaks corresponding to:

• Loss of small neutral fragments after ring opening
• Only intact molecular ion with no fragments
• Exclusive formation of aromatic ions
• Fragments that are identical to benzene

Correct Answer: Loss of small neutral fragments after ring opening

Q35. Which reagent combination can promote ring-opening polymerization of cyclobutane derivatives selectively?

• Strong base only at low temperature
• Photochemical initiation with radical initiators
• Neutral salt in water
• Pure oxygen at room temperature

Correct Answer: Photochemical initiation with radical initiators

Q36. The frontier molecular orbital considerations for cyclobutane formation via [2+2] photochemical cycloaddition rely primarily on:

• HOMO-LUMO interactions in the excited state
• Only ground-state HOMO-HOMO interactions
• Acid-base complementarity
• Steric bulk of solvent molecules

Correct Answer: HOMO-LUMO interactions in the excited state

Q37. Which is a common synthetic transformation of cyclobutanones used to access gamma-lactones or esters?

• Baeyer–Villiger oxidation
• Hydrogenolysis only
• Wurtz coupling
• Direct nitration

Correct Answer: Baeyer–Villiger oxidation

Q38. Which reagent sequence would convert a substituted cyclobutane with an alkene to a diol across the double bond?

• OsO4 followed by NaHSO3 workup
• HBr addition
• PCl5 then hydrolysis
• Friedel–Crafts acylation

Correct Answer: OsO4 followed by NaHSO3 workup

Q39. Which of the following best explains why small-ring systems like cyclobutane can increase drug potency when used as bioisosteres?

• They always increase solubility and decrease lipophilicity
• They can rigidify conformations, improving receptor binding geometries
• They convert molecules into ionic salts
• They automatically introduce hydrogen-bond donors

Correct Answer: They can rigidify conformations, improving receptor binding geometries

Q40. What is a likely product when cyclobutane bearing an allylic substituent undergoes thermal rearrangement?

• Retention of starting material only
• Ring-opened conjugated diene or rearranged cyclohexene derivatives
• Immediate combustion to CO2 and H2O
• Formation of benzaldehyde

Correct Answer: Ring-opened conjugated diene or rearranged cyclohexene derivatives

Q41. Which catalytic system is known to allow [2+2] cycloadditions under visible light by single-electron transfer pathways?

• Photoredox catalysts such as Ir or Ru complexes
• Strong acids like HCl alone
• Classical bases like NaOH only
• KMnO4 in water

Correct Answer: Photoredox catalysts such as Ir or Ru complexes

Q42. In a medicinal chemistry context, replacing a gem-dimethyl group with a cyclobutane ring often aims to:

• Increase rotatable bond count
• Reduce metabolism and lock conformation
• Introduce an ionizable center
• Convert the molecule into a carbohydrate mimic

Correct Answer: Reduce metabolism and lock conformation

Q43. Which bond cleavage is favored in substituted cyclobutanes under heterolytic conditions?

• C–H bond cleavage at remote positions only
• C–C bond cleavage adjacent to electron-withdrawing substituents forming stabilized carbocations
• Aromatic C–C bond cleavage
• Only homolytic cleavage irrespective of substituents

Correct Answer: C–C bond cleavage adjacent to electron-withdrawing substituents forming stabilized carbocations

Q44. Which transformation can convert a cyclobutane diol into a diketone via oxidative cleavage?

• Periodic acid (HIO4) cleavage of vicinal diols
• Hydrogenation with H2/Pd
• Conversion to tosylates only
• SN2 substitution with cyanide

Correct Answer: Periodic acid (HIO4) cleavage of vicinal diols

Q45. Which method is commonly used to study the conformational preferences of substituted cyclobutanes experimentally?

• NMR spectroscopy (NOE, coupling constants)
• Only thin-layer chromatography (TLC)
• Colorimetric assays
• Infrared spectroscopy exclusively

Correct Answer: NMR spectroscopy (NOE, coupling constants)

Q46. For a drug molecule containing cyclobutane, which metabolic pathway could lead to ring opening and loss of activity?

• Phase II glucuronidation exclusively
• Oxidative C–C bond cleavage catalyzed by P450 enzymes
• Only renal excretion without metabolism
• Spontaneous polymerization in blood

Correct Answer: Oxidative C–C bond cleavage catalyzed by P450 enzymes

Q47. Which experimental condition favors selective formation of trans-substituted cyclobutanes in [2+2] cycloaddition?

• Using geometrically defined trans-alkenes or templates that control approach
• High temperature thermal conditions only
• Presence of strong acids to protonate alkenes
• Use of radical initiators that randomize stereochemistry

Correct Answer: Using geometrically defined trans-alkenes or templates that control approach

Q48. Which reagent can convert a cyclobutanone into its corresponding enolate for further C–C bond formation?

• LDA (lithium diisopropylamide)
• PCC in dichloromethane
• PBr3
• Silver nitrate in water

Correct Answer: LDA (lithium diisopropylamide)

Q49. Which photochemical behavior is characteristic of substituted cyclobutanes containing chromophoric groups?

• They can sensitively undergo cleavage or rearrangement upon UV/visible irradiation via excited-state pathways
• They are inert to all light wavelengths
• They only fluoresce without chemical change
• They always polymerize into insoluble solids

Correct Answer: They can sensitively undergo cleavage or rearrangement upon UV/visible irradiation via excited-state pathways

Q50. When designing cyclobutane-containing drug candidates, which consideration is most important?

• Only color of the compound matters
• Assessment of ring strain effects on stability, metabolic liability, and conformational impact on target binding
• Ensuring the ring is planar to increase reactivity
• Avoiding any polar functionality

Correct Answer: Assessment of ring strain effects on stability, metabolic liability, and conformational impact on target binding

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

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