Reactions of quinoline MCQs With Answer

Reactions of quinoline MCQs With Answer
Quinoline chemistry is essential for B.Pharm students studying heterocyclic reactions and drug scaffolds. This introduction covers key concepts like electrophilic substitution on the benzene ring (favored at C-5/C-8), nucleophilic addition/substitution at C-2 and C-4, N-oxidation (m-CPBA) and activation, catalytic hydrogenation to tetrahydroquinolines, radical (Minisci) alkylation, and reagent-specific mechanisms and regioselectivity. Understanding these reaction pathways, reagents, and intermediates helps predict products and design syntheses of pharmacologically important quinoline derivatives. Clear mechanistic insight improves problem-solving for medicinal chemistry and pharmaceutical analysis. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which positions on quinoline are most reactive toward classical electrophilic aromatic substitution?

• C-2 and C-4 (pyridine ring)
• C-5 and C-8 (benzene ring)
• N-1 and C-3
• All positions react equally

Correct Answer: C-5 and C-8 (benzene ring)

Q2. Which reagent is commonly used to oxidize quinoline to quinoline N-oxide?

• Sodium borohydride (NaBH4)
• m-CPBA (meta-chloroperbenzoic acid)
• Lithium aluminum hydride (LiAlH4)
• Pd/C and H2

Correct Answer: m-CPBA (meta-chloroperbenzoic acid)

Q3. Quinoline N-oxide typically increases electrophilic substitution at which position?

• C-2
• C-3
• C-7
• N-1

Correct Answer: C-2

Q4. Catalytic hydrogenation of quinoline (H2, Pd/C) most commonly gives which product?

• Quinoline N-oxide
• 1,2,3,4-Tetrahydroquinoline
• Decahydroquinoline
• 2-Aminoquinoline

Correct Answer: 1,2,3,4-Tetrahydroquinoline

Q5. Nucleophilic aromatic substitution on quinoline derivatives most readily occurs at which carbon when a good leaving group is present?

• C-5
• C-2
• C-7
• C-6

Correct Answer: C-2

Q6. The Chichibabin amination of pyridine-like rings introduces an amino group at which position? (Applicable conceptually to quinoline)

• C-4
• C-2
• C-6
• C-8

Correct Answer: C-2

Q7. In electrophilic nitration of quinoline under strong conditions, the major product is nitration at which position?

• C-2
• C-5
• C-3
• C-8

Correct Answer: C-5

Q8. Which statement best describes the basicity of quinoline compared to pyridine?

• Quinoline is much more basic than pyridine
• Quinoline is slightly less basic than pyridine
• Quinoline is non-basic
• Quinoline and pyridine have identical basicity

Correct Answer: Quinoline is slightly less basic than pyridine

Q9. Which reagent sequence is typically used to form 2-alkylated quinolines via a radical pathway?

• Friedel–Crafts alkylation
• Minisci reaction (peroxides/Ag, radical initiator with carboxylic acids)
• Vilsmeier–Haack formylation
• Grignard addition to quinoline

Correct Answer: Minisci reaction (peroxides/Ag, radical initiator with carboxylic acids)

Q10. Which transformation converts quinoline into 2-quinolone derivatives often used in drugs?

• Hydrogenation with H2/Pd
• Oxidation at C-2 followed by tautomerization (oxidative rearrangement)
• N-alkylation
• Friedel–Crafts acylation on the benzene ring

Correct Answer: Oxidation at C-2 followed by tautomerization (oxidative rearrangement)

Q11. Which reagent can introduce a formyl group into quinoline (formylation) under electrophilic conditions?

• Vilsmeier reagent (DMF + POCl3)
• NBS (N-bromosuccinimide)
• KMnO4
• H2, Pd/C

Correct Answer: Vilsmeier reagent (DMF + POCl3)

Q12. Quinoline reacts sluggishly in Friedel–Crafts alkylation on the pyridine ring because:

• The benzene ring is too activated
• The pyridine nitrogen deactivates the ring toward electrophiles
• Quinoline lacks π-electrons
• Friedel–Crafts works only on aliphatic systems

Correct Answer: The pyridine nitrogen deactivates the ring toward electrophiles

Q13. Which intermediate is commonly involved in nucleophilic addition to the 2-position of quinoline?

• σ-Complex on benzene ring
• 1,2-Dihydroquinoline (addition intermediate)
• Carbocation at N-1
• Benzyne intermediate

Correct Answer: 1,2-Dihydroquinoline (addition intermediate)

Q14. Bromination of quinoline under mild conditions typically occurs preferentially at which site?

• C-2
• C-5
• C-1 (nitrogen)
• C-3

Correct Answer: C-5

Q15. Quinolines when treated with strong reducing agents like LiAlH4 typically:

• Reduce the pyridine ring to give tetrahydro derivatives
• Oxidize to quinoline N-oxide
• Undergo electrophilic substitution
• Form quaternary ammonium salts

Correct Answer: Reduce the pyridine ring to give tetrahydro derivatives

Q16. Which of the following is true about nucleophilic aromatic substitution (SNAr) on quinoline?

• SNAr never occurs on quinoline
• SNAr is facilitated by electron-withdrawing substituents and leaving groups at C-2 or C-4
• SNAr is fastest at benzene ring positions
• SNAr requires radical initiators

Correct Answer: SNAr is facilitated by electron-withdrawing substituents and leaving groups at C-2 or C-4

Q17. Which product results from N-alkylation of quinoline using methyl iodide?

• 2-Methylquinoline
• Quinoline N-oxide
• Quinolinium iodide (quaternary ammonium salt)
• Tetrahydroquinoline

Correct Answer: Quinolinium iodide (quaternary ammonium salt)

Q18. The Minisci reaction on quinoline requires which type of substrate to generate the alkyl radical?

• Alkyl halide with a palladium catalyst
• Carboxylic acid (with oxidant) to form radicals
• Organolithium reagent
• Alkene under photochemical conditions only

Correct Answer: Carboxylic acid (with oxidant) to form radicals

Q19. Which transformation is commonly used to activate quinoline for nucleophilic substitution at C-2?

• Formation of quinoline N-oxide
• Hydrogenation to tetrahydroquinoline
• Mild hydrolysis
• Photochemical irradiation

Correct Answer: Formation of quinoline N-oxide

Q20. Which reagent combination is suitable to introduce a nitroso group (–NO) onto a reactive aromatic ring — generally applicable concept for derivatives of quinoline under controlled conditions?

• NaNO2 / HCl at low temperature
• m-CPBA alone
• H2/Pd
• Grignard reagent

Correct Answer: NaNO2 / HCl at low temperature

Q21. Electrophilic sulfonation of quinoline most commonly occurs at which positions?

• C-2 and C-4
• C-5 and C-8
• N-1 and C-3
• C-6 only

Correct Answer: C-5 and C-8

Q22. Which of the following best explains why electrophiles avoid the pyridine ring of quinoline?

• Pyridine ring is strongly activated by nitrogen
• Nitrogen withdraws electron density, deactivating the ring toward electrophiles
• Pyridine ring has no π-electrons
• Pyridine ring is sterically hindered only

Correct Answer: Nitrogen withdraws electron density, deactivating the ring toward electrophiles

Q23. Addition of organolithium reagents to quinoline commonly gives which type of intermediate/product?

• Carbocation at C-5
• 1,2-Dihydroquinoline (after addition at C-2)
• Quinolinium salts
• Benzyne adducts

Correct Answer: 1,2-Dihydroquinoline (after addition at C-2)

Q24. Which reaction can convert quinoline into compounds useful as antimalarial or antibacterial cores by hydrogenating and then functionalizing?

• Sequential catalytic hydrogenation (to tetrahydroquinoline) followed by electrophilic substitution on the benzene ring
• Direct nitration only
• Chichibabin amination at C-8 exclusively
• Photolysis to give radical fragments

Correct Answer: Sequential catalytic hydrogenation (to tetrahydroquinoline) followed by electrophilic substitution on the benzene ring

Q25. Which technique is commonly used to introduce substituents selectively onto the benzene portion of quinoline while leaving the pyridine ring mostly intact?

• Electrophilic aromatic substitution under controlled conditions
• Nucleophilic aromatic substitution at C-2
• Chichibabin amination at N-1
• Hydrogenolysis

Correct Answer: Electrophilic aromatic substitution under controlled conditions

Q26. The use of strong bases such as NaNH2 with quinoline-related heterocycles can lead to:

• Chichibabin-type amination at C-2 (nucleophilic substitution)
• N-alkylation exclusively
• Electrophilic bromination
• Only oxidation reactions

Correct Answer: Chichibabin-type amination at C-2 (nucleophilic substitution)

Q27. Which spectral change often indicates formation of quinoline N-oxide?

• Appearance of a strong IR band for N–O stretching and changes in 1H NMR chemical shifts
• Loss of all aromatic signals in NMR
• Increase in mass by 16 with no other changes
• No detectable spectroscopic change

Correct Answer: Appearance of a strong IR band for N–O stretching and changes in 1H NMR chemical shifts

Q28. Photochemical reactions of quinoline can lead to which outcome under UV irradiation in the presence of suitable substrates?

• Exclusive formation of quinoline N-oxide
• Generation of radicals and subsequent addition or cleavage reactions
• Only hydrogenation
• Complete inertness

Correct Answer: Generation of radicals and subsequent addition or cleavage reactions

Q29. Which reagent is commonly used to introduce a halogen (bromine) into the benzene portion of quinoline selectively?

• NBS (N-bromosuccinimide) under radical conditions or bromination with Br2/FeBr3 under controlled conditions
• NaBH4
• m-CPBA
• H2O2

Correct Answer: NBS (N-bromosuccinimide) under radical conditions or bromination with Br2/FeBr3 under controlled conditions

Q30. Which statement about reduction of quinoline N-oxide is correct?

• It cannot be reduced back to quinoline
• It can be reduced to quinoline using PCl5
• It can be reduced to quinoline using phosphorus reagents like PCl3 or TiCl3 or catalytic hydrogenation
• It spontaneously reverts to quinoline in air

Correct Answer: It can be reduced to quinoline using phosphorus reagents like PCl3 or TiCl3 or catalytic hydrogenation

Q31. Which type of mechanism explains nucleophilic addition to the C-2 position of quinoline followed by elimination of a leaving group?

• Electrophilic aromatic substitution (SEAr)
• Addition–elimination (S_NAr via addition intermediate)
• Radical chain mechanism only
• Pericyclic cycloaddition

Correct Answer: Addition–elimination (S_NAr via addition intermediate)

Q32. Which reagent is suitable to oxidize the benzylic positions on quinoline derivatives to carboxyl or carbonyl groups?

• KMnO4
• NaBH4
• H2, Pd/C
• N2 atmosphere only

Correct Answer: KMnO4

Q33. In medicinal chemistry, modification of quinoline at C-2 often affects which property the most?

• Melting point only
• Electronic, binding and biological activity (pharmacophore interactions)
• Only UV-visible absorption
• Only solubility, not activity

Correct Answer: Electronic, binding and biological activity (pharmacophore interactions)

Q34. The formation of quinolinium salts (N-alkylation) is reversible by which type of reaction to give back free quinoline?

• Hydrolysis under neutral conditions
• Strong nucleophilic attack at nitrogen to remove alkyl group (Hoffmann-like or nucleophilic displacement) or reductive conditions
• Simple heating only
• Photolysis always

Correct Answer: Strong nucleophilic attack at nitrogen to remove alkyl group (Hoffmann-like or nucleophilic displacement) or reductive conditions

Q35. Which step is crucial when performing directed lithiation on quinoline derivatives for selective functionalization?

• Use of bulky electrophiles only
• Choice of directing group and low temperature with strong base (e.g., LDA, n-BuLi)
• Aerobic conditions are essential
• Photochemical activation is required

Correct Answer: Choice of directing group and low temperature with strong base (e.g., LDA, n-BuLi)

Q36. Which transformation converts 2-chloroquinoline to 2-aminquinoline under nucleophilic conditions?

• Treatment with ammonia or amine nucleophiles under SNAr conditions
• Hydrogenation over Pd/C
• Oxidation with m-CPBA
• Photochemical halogenation

Correct Answer: Treatment with ammonia or amine nucleophiles under SNAr conditions

Q37. Which reagent is typically used to reduce the quinoline ring selectively to dihydro- or tetrahydroquinoline under controlled chemoselective conditions?

• NaOMe
• H2 with Pd/C or Pt catalysts under controlled pressure
• m-CPBA
• Conc. H2SO4

Correct Answer: H2 with Pd/C or Pt catalysts under controlled pressure

Q38. The regioselectivity of electrophilic substitution on quinoline is most influenced by:

• The solvent only
• The electronic effects of the nitrogen and substituents, and steric factors
• The molecular weight exclusively
• Only the temperature

Correct Answer: The electronic effects of the nitrogen and substituents, and steric factors

Q39. Which method is commonly used to prepare 2-substituted quinolines via building the heterocycle rather than direct substitution?

• Skraup or Friedländer synthesis (heterocycle construction with suitable precursors)
• Direct chlorination at C-2
• Simple heating of quinoline with alcohols
• Photochemical ring opening

Correct Answer: Skraup or Friedländer synthesis (heterocycle construction with suitable precursors)

Q40. Which reagent is commonly used to introduce a carbonyl group adjacent to the nitrogen in quinoline derivatives (e.g., converting methyl substituent to aldehyde/carboxyl)?

• Ozonolysis without workup
• SeO2 for allylic/benzylic oxidation or KMnO4 for stronger oxidation
• NaBH4 for oxidation
• NBS only for reduction

Correct Answer: SeO2 for allylic/benzylic oxidation or KMnO4 for stronger oxidation

Q41. Quinoline derivatives undergo palladium-catalyzed cross-coupling most effectively when which functional group is present?

• A hydride
• Aryl halide (e.g., 2-bromoquinoline or 2-chloroquinoline)
• An alcohol only
• No leaving group is needed

Correct Answer: Aryl halide (e.g., 2-bromoquinoline or 2-chloroquinoline)

Q42. Which reaction is typically used to convert quinoline to hydroxyquinoline derivatives at the benzene ring?

• Nucleophilic aromatic substitution on an unactivated position
• Direct electrophilic hydroxylation using strong oxidants or via nitration followed by reduction and diazotization/hydrolysis
• Hydrogenolysis
• Simple mixing with water

Correct Answer: Direct electrophilic hydroxylation using strong oxidants or via nitration followed by reduction and diazotization/hydrolysis

Q43. Which factor makes the 2-position of quinoline relatively susceptible to nucleophilic attack compared to other positions?

• Resonance stabilization of the addition intermediate (1,2-dihydro form) and proximity to the electron-deficient pyridine nitrogen
• Higher steric hindrance
• Greater proton affinity at C-2
• Absence of π-electron density at C-2

Correct Answer: Resonance stabilization of the addition intermediate (1,2-dihydro form) and proximity to the electron-deficient pyridine nitrogen

Q44. Which reagent pair is typically used to transform a primary alcohol attached to a quinoline side chain into the corresponding aldehyde?

• PCC (pyridinium chlorochromate) or Dess–Martin periodinane (DMP)
• LiAlH4
• H2, Pd/C
• NaOH aqueous only

Correct Answer: PCC (pyridinium chlorochromate) or Dess–Martin periodinane (DMP)

Q45. Which of the following best describes the aromaticity of quinoline?

• Quinoline is non-aromatic
• Quinoline is aromatic, with a fused benzene and pyridine ring system sharing π-electrons
• Only the benzene ring is aromatic; the pyridine ring is not
• Quinoline is antiaromatic

Correct Answer: Quinoline is aromatic, with a fused benzene and pyridine ring system sharing π-electrons

Q46. Which functional group transformation on quinoline is least likely under mild acidic conditions?

• Electrophilic substitution on benzene ring
• Hydrolysis of aryl halide at C-2 without activation
• N-oxidation with peracid
• N-alkylation in presence of strong alkylating agent

Correct Answer: Hydrolysis of aryl halide at C-2 without activation

Q47. Which approach is commonly used to introduce substituents at C-4 of quinoline selectively?

• Direct electrophilic substitution at C-4 without activation
• Use of directed metalation or cross-coupling from 4-halogenated derivatives
• Simple heating with base
• Oxidation with mild oxidants only

Correct Answer: Use of directed metalation or cross-coupling from 4-halogenated derivatives

Q48. The benzannulated structure of quinoline affects its reactivity by:

• Making all positions equally reactive
• Altering electron distribution so benzene ring is more reactive to electrophiles while pyridine ring is electron-deficient
• Preventing any substitution reactions
• Removing aromatic stabilization entirely

Correct Answer: Altering electron distribution so benzene ring is more reactive to electrophiles while pyridine ring is electron-deficient

Q49. Which catalyst system is commonly used for C–H activation functionalization on quinoline scaffolds in modern organic synthesis?

• Pd(II) or Ru(II) catalysts for directed C–H activation
• NaCl only
• Strong protic acids without metal
• Only photochemical catalysts

Correct Answer: Pd(II) or Ru(II) catalysts for directed C–H activation

Q50. In designing a synthetic route to a substituted quinoline-based drug candidate, which considerations are most critical?

• Regioselectivity, choice of protecting/activating groups, tolerance of functional groups, and scalable reagents/conditions
• Only the color of intermediates
• Using the most expensive reagents possible
• Avoiding any use of catalysts

Correct Answer: Regioselectivity, choice of protecting/activating groups, tolerance of functional groups, and scalable reagents/conditions

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