Reactions of isoquinoline MCQs With Answer

Reactions of isoquinoline MCQs With Answer is an essential review for B. Pharm students studying heterocyclic chemistry and pharmaceutical synthesis. This introduction covers reactivity patterns of isoquinoline—electrophilic and nucleophilic substitution, reductions, oxidations, N-alkylation, and key named syntheses like Bischler–Napieralski and Pictet–Spengler. Knowing regioselectivity, common reagents, mechanisms, and spectral identification helps you predict products and design drug-like scaffolds. These concise, exam-focused MCQs reinforce understanding of mechanisms, synthetic routes, and biological relevance of isoquinoline derivatives. Keywords: isoquinoline reactions, isoquinoline MCQs, B. Pharm, heterocyclic chemistry, mechanism, reagents, synthetic applications. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which position in isoquinoline is most susceptible to nucleophilic addition under typical conditions?

• C-4
• C-1
• C-5
• C-8

Correct Answer: C-1

Q2. The Bischler–Napieralski reaction is primarily used to synthesize which intermediate class related to isoquinolines?

• Tetrahydroisoquinolines
• Dihydroisoquinolines
• Isoquinoline N-oxides
• Isoquinolinium salts

Correct Answer: Dihydroisoquinolines

Q3. In electrophilic aromatic substitution on isoquinoline, which ring is generally more reactive?

• The pyridine-type ring (containing N)
• The fused benzene ring
• Both rings react equally
• Neither ring undergoes electrophilic substitution

Correct Answer: The fused benzene ring

Q4. Which reagent is commonly used to convert an amide precursor into a dihydroisoquinoline in the Bischler–Napieralski reaction?

• Hydrogen gas with Pd/C
• Phosphorus oxychloride (POCl3)
• Sodium borohydride
• Chromic acid

Correct Answer: Phosphorus oxychloride (POCl3)

Q5. Pictet–Spengler reaction is important for forming which isoquinoline-related scaffold?

• Isoquinoline N-oxide
• Tetrahydroisoquinoline
• Isoquinolinium salt
• Dihydroisoquinoline N-oxide

Correct Answer: Tetrahydroisoquinoline

Q6. N-oxidation of isoquinoline typically has what effect on its ring reactivity?

• Deactivates the entire molecule to all substitutions
• Activates the formerly pyridine-type ring toward electrophilic substitution
• Converts it irreversibly into quinoline
• Makes nucleophilic addition impossible

Correct Answer: Activates the formerly pyridine-type ring toward electrophilic substitution

Q7. Which transformation reduces isoquinoline to tetrahydroisoquinoline selectively?

• Oxidation with KMnO4
• Catalytic hydrogenation (H2, Pd/C)
• Nitration with HNO3
• Alkylation with methyl iodide

Correct Answer: Catalytic hydrogenation (H2, Pd/C)

Q8. Quinoline and isoquinoline differ in reactivity because of:

• Different position of the nitrogen atom in the fused ring
• Different number of rings
• Quinoline lacks aromaticity
• Isoquinoline contains oxygen

Correct Answer: Different position of the nitrogen atom in the fused ring

Q9. Which product is expected from nucleophilic attack of a hydride at C-1 of isoquinoline?

• 1,2-Dihydroisoquinoline
• Fully aromatized isoquinoline
• Isoquinoline N-oxide
• Substituted benzene derivative

Correct Answer: 1,2-Dihydroisoquinoline

Q10. Friedel–Crafts acylation on isoquinoline derivatives typically occurs on which ring and why?

• On the pyridine ring due to strong activation by N
• On the benzene ring because the pyridine nitrogen deactivates the adjacent positions
• On both rings equally due to resonance
• No reaction occurs under Friedel–Crafts conditions

Correct Answer: On the benzene ring because the pyridine nitrogen deactivates the adjacent positions

Q11. Alkylation at the nitrogen of isoquinoline produces:

• Isoquinoline N-oxide
• Isoquinolinium salt
• Tetrahydroisoquinoline
• Dihydroisoquinoline

Correct Answer: Isoquinolinium salt

Q12. Which spectroscopic change indicates N-oxidation of isoquinoline?

• Disappearance of aromatic peaks in 1H NMR
• Appearance of a new signal for N–O group in IR around 1250–1350 cm-1
• Complete loss of UV absorption
• New peak at 2200 cm-1 in IR due to triple bond

Correct Answer: Appearance of a new signal for N–O group in IR around 1250–1350 cm-1

Q13. Which reagent is commonly used for N-oxidation of isoquinoline?

• MCPBA (meta-chloroperbenzoic acid)
• Hydrazine
• LiAlH4
• H2 with Pd/C

Correct Answer: MCPBA (meta-chloroperbenzoic acid)

Q14. In nucleophilic aromatic substitution on isoquinoline, activation is highest when a leaving group is at which position?

• At C-1
• At a ring carbon adjacent to nitrogen (alpha to N)
• On the remote benzene ring far from nitrogen
• At C-7 only

Correct Answer: At a ring carbon adjacent to nitrogen (alpha to N)

Q15. The Bischler–Napieralski reaction mechanism involves which key step?

• Nucleophilic aromatic substitution
• Cyclodehydration to form an iminium or cyclic imine intermediate
• Direct oxidative cleavage of the ring
• Radical chain propagation

Correct Answer: Cyclodehydration to form an iminium or cyclic imine intermediate

Q16. Which of the following best describes the acidity/basicity of isoquinoline compared to pyridine?

• Isoquinoline is significantly more basic than pyridine
• Isoquinoline is generally slightly less basic than pyridine due to ring fusion effects
• Both have identical basicity
• Isoquinoline is a strong acid

Correct Answer: Isoquinoline is generally slightly less basic than pyridine due to ring fusion effects

Q17. Regioselective nitration of isoquinoline typically gives substitution on which region?

• Pyridine ring exclusively
• Benzene ring positions (e.g., C-5 or C-8)
• Only at the nitrogen atom
• No nitration occurs under normal conditions

Correct Answer: Benzene ring positions (e.g., C-5 or C-8)

Q18. Which of the following is a typical outcome of N-alkylation of isoquinoline followed by base treatment?

• Formation of an ylide
• Quaternization to give stable salts and possible dequaternization to substituted isoquinolines
• Complete fragmentation to benzene derivatives
• Oxidation to nitro compounds

Correct Answer: Quaternization to give stable salts and possible dequaternization to substituted isoquinolines

Q19. Which reaction commonly used in medicinal chemistry converts beta-phenylethylamine derivatives into tetrahydroisoquinolines?

• Buchwald–Hartwig amination
• Pictet–Spengler reaction
• Diels–Alder reaction
• Mannich reaction

Correct Answer: Pictet–Spengler reaction

Q20. Which reagent is suitable for selective reduction of a dihydroisoquinoline double bond to a tetrahydroisoquinoline?

• Sodium nitrite
• Sodium borohydride (NaBH4)
• Ozone (O3)
• Chlorine gas

Correct Answer: Sodium borohydride (NaBH4)

Q21. Which is a common synthetic precursor in isoquinoline synthesis via Bischler–Napieralski?

• Benzaldehyde directly
• β-Phenylethylamide
• Aniline
• Toluene

Correct Answer: β-Phenylethylamide

Q22. Oxidative aromatization of tetrahydroisoquinolines typically yields:

• Isoquinoline
• Benzene derivatives
• Aliphatic amines
• Nitroisoquinolines

Correct Answer: Isoquinoline

Q23. In the presence of strong electrophiles, isoquinoline behaves like which moiety?

• Electron-rich benzene ring only
• Pyridine-like base at nitrogen, attracting electrophiles to benzene ring
• Completely inert
• Alkane-like saturated hydrocarbon

Correct Answer: Pyridine-like base at nitrogen, attracting electrophiles to benzene ring

Q24. Which of the following increases the rate of nucleophilic addition to isoquinoline?

• Protonation at nitrogen
• Formation of an N-oxide
• Removal of a benzene substituent
• Cooling the reaction to 0°C

Correct Answer: Protonation at nitrogen

Q25. Which reagent set is appropriate to convert an isoquinoline to its corresponding isoquinoline N-oxide?

• NaBH4 in methanol
• MCPBA in dichloromethane
• Pd/C under hydrogen
• HCl and heat

Correct Answer: MCPBA in dichloromethane

Q26. Electrophilic substitution at C-1 of isoquinoline is uncommon because:

• C-1 is part of the benzene ring and highly activated
• C-1 is adjacent to nitrogen and deactivated toward electrophiles
• There is no C-1 in isoquinoline
• C-1 is sterically hindered by bulky substituents in all derivatives

Correct Answer: C-1 is adjacent to nitrogen and deactivated toward electrophiles

Q27. Which type of reaction would you use to install an aryl group onto the benzene ring of isoquinoline?

• Nucleophilic addition of hydride
• Cross-coupling reaction (e.g., Suzuki coupling) after halogenation
• Direct hydrogenation
• Oxidation with permanganate

Correct Answer: Cross-coupling reaction (e.g., Suzuki coupling) after halogenation

Q28. During catalytic hydrogenation of isoquinoline, which bonds are reduced first under mild conditions?

• Aromatic benzene ring bonds
• Pyridine-type ring double bonds to give partially saturated intermediates
• N–C bond to break the ring
• All bonds reduce simultaneously

Correct Answer: Pyridine-type ring double bonds to give partially saturated intermediates

Q29. Which reagent is often used to promote electrophilic substitution on the benzene ring of isoquinoline by increasing electrophile strength?

• Lewis acids such as AlCl3 or FeCl3
• Strong bases like NaOH
• Reducing agents like LiAlH4
• Peroxides

Correct Answer: Lewis acids such as AlCl3 or FeCl3

Q30. The term “1,2-dihydroisoquinoline” refers to:

• Isoquinoline with two hydrogens added at positions 1 and 2 resulting in partial saturation
• Isoquinoline oxidized at position 1 and 2
• Isoquinoline N-oxide
• Isoquinoline with methyl groups at positions 1 and 2

Correct Answer: Isoquinoline with two hydrogens added at positions 1 and 2 resulting in partial saturation

Q31. A common transformation of isoquinolinium salts in synthesis is:

• Deprotonation to give benzene
• Nucleophilic attack at the activated carbon positions leading to substitution
• Complete polymerization
• Spontaneous combustion

Correct Answer: Nucleophilic attack at the activated carbon positions leading to substitution

Q32. Which property of isoquinoline is most important when predicting sites of electrophilic attack?

• The basicity and electron-withdrawing effect of the nitrogen atom
• The weight of the molecule
• The melting point
• The taste of the compound

Correct Answer: The basicity and electron-withdrawing effect of the nitrogen atom

Q33. Which synthetic strategy is useful to introduce substituents at C-3 of isoquinoline derivatives?

• Electrophilic substitution at the pyridine ring
• Directed lithiation at adjacent positions followed by electrophile trapping
• Only photochemical methods work
• Hydrogenolysis

Correct Answer: Directed lithiation at adjacent positions followed by electrophile trapping

Q34. Which statement is true about acid-catalyzed reactions of isoquinoline?

• Protonation at nitrogen can activate adjacent carbons toward nucleophilic addition
• Acid catalysis always leads to ring cleavage
• Isoquinoline is completely unaffected by acids
• Acid causes immediate polymerization

Correct Answer: Protonation at nitrogen can activate adjacent carbons toward nucleophilic addition

Q35. An isoquinoline derivative shows a strong UV absorption band typical of conjugated heterocycles. UV spectroscopy is useful to:

• Assess conjugation and substitution pattern on the ring system
• Determine exact atomic connectivity like NMR
• Measure molecular weight accurately
• Identify stereochemistry at chiral centers

Correct Answer: Assess conjugation and substitution pattern on the ring system

Q36. Which oxidizing agent can convert tetrahydroisoquinolines back to isoquinolines?

• Potassium permanganate (KMnO4) under harsh conditions
• Concentrated HCl alone
• Hydrogen gas with Pd/C
• Triethylamine

Correct Answer: Potassium permanganate (KMnO4) under harsh conditions

Q37. For regioselective halogenation of isoquinoline at the benzene ring, which approach improves selectivity?

• Perform halogenation on the corresponding N-oxide then deoxygenate
• Use free radical halogenation at high temperature
• Halogenate without any catalyst or activation
• Use photochemical cleavage

Correct Answer: Perform halogenation on the corresponding N-oxide then deoxygenate

Q38. The presence of electron-donating groups on the benzene ring of isoquinoline will:

• Make the benzene ring less reactive to electrophiles
• Increase the rate of electrophilic aromatic substitution on the benzene ring
• Convert isoquinoline into a saturated amine
• Make nucleophilic additions at C-1 impossible

Correct Answer: Increase the rate of electrophilic aromatic substitution on the benzene ring

Q39. Which technique helps determine whether a substitution has occurred at C-1 versus C-3 in an isoquinoline?

• Thin-layer chromatography only
• 1H and 13C NMR spectroscopy to analyze chemical shift and coupling patterns
• Weighing the sample before and after reaction
• Measuring boiling point only

Correct Answer: 1H and 13C NMR spectroscopy to analyze chemical shift and coupling patterns

Q40. Which reaction condition favors formation of isoquinolinium salts by N-alkylation?

• Heating with excess strong base
• Treatment with alkyl halides under nucleophilic substitution conditions
• Oxidative conditions with peroxides
• Photochemical radical conditions

Correct Answer: Treatment with alkyl halides under nucleophilic substitution conditions

Q41. In medicinal chemistry, isoquinoline scaffolds are valued because:

• They are inert and never metabolized
• They provide planar heteroaromatic frameworks enabling pi-stacking and H-bond interactions with biological targets
• They lack heteroatoms, increasing lipophilicity only
• They always act as prodrugs without activity

Correct Answer: They provide planar heteroaromatic frameworks enabling pi-stacking and H-bond interactions with biological targets

Q42. Which intermediate is characteristic in Pictet–Spengler cyclization en route to tetrahydroisoquinolines?

• Carbanion stabilized by resonance
• Iminium ion formed from aldehyde and amine
• Free radical centered on nitrogen
• Peroxide adduct

Correct Answer: Iminium ion formed from aldehyde and amine

Q43. Which transformation would be least appropriate for modifying an isoquinoline core in late-stage medicinal chemistry?

• Selective C–H functionalization on the benzene ring
• Oxidation to N-oxide followed by directed substitution
• Harsh oxidative cleavage of the heterocycle to open the ring
• N-alkylation to modulate basicity and solubility

Correct Answer: Harsh oxidative cleavage of the heterocycle to open the ring

Q44. When comparing nucleophilic addition rates, isoquinoline is generally:

• Less reactive than benzene
• More reactive toward nucleophilic addition at C-1 than quinoline
• Completely resistant to nucleophiles
• Only reactive toward radicals

Correct Answer: More reactive toward nucleophilic addition at C-1 than quinoline

Q45. Which protective strategy is used to allow electrophilic substitution on the pyridine-like ring of isoquinoline?

• Convert to the corresponding N-oxide to temporarily change electronics
• Reduce the benzene ring first
• Convert to an alkane
• Heat without reagents

Correct Answer: Convert to the corresponding N-oxide to temporarily change electronics

Q46. Halogen–metal exchange on a halogenated isoquinoline followed by electrophile capture is an example of:

• Electrophilic aromatic substitution
• Nucleophilic aromatic substitution
• Organometallic functionalization for C–C bond formation
• Photochemical rearrangement

Correct Answer: Organometallic functionalization for C–C bond formation

Q47. A common method to improve water solubility of isoquinoline drugs is:

• Introduction of lipophilic alkyl groups only
• Protonation as salts (e.g., form isoquinolinium salts or use hydrochloride salts)
• Complete aromatic ring saturation
• Attachment of long hydrophobic chains

Correct Answer: Protonation as salts (e.g., form isoquinolinium salts or use hydrochloride salts)

Q48. Which analytical technique best distinguishes between isoquinoline and its dihydro analogues?

• Mass spectrometry only, because masses differ dramatically
• 1H NMR spectroscopy due to the appearance/disappearance of characteristic alkyl and aromatic proton signals
• Simple melting point measurement always suffices
• Visual color inspection

Correct Answer: 1H NMR spectroscopy due to the appearance/disappearance of characteristic alkyl and aromatic proton signals

Q49. Which transformation can convert an isoquinoline into a useful electrophile at C-1 for further substitution?

• Protonation at nitrogen followed by nucleophilic trapping
• Direct hydrogen abstraction using light only
• Oxidation to benzaldehyde
• Base-catalyzed decarboxylation

Correct Answer: Protonation at nitrogen followed by nucleophilic trapping

Q50. For sustainable synthesis of isoquinoline derivatives, which principle is most relevant?

• Use of stoichiometric heavy metals whenever possible
• Designing atom-economical cyclizations and catalytic hydrogenations to minimize waste
• Avoiding catalysis and using excess reagents
• Maximizing solvent volume irrespective of toxicity

Correct Answer: Designing atom-economical cyclizations and catalytic hydrogenations to minimize waste

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