Synthesis of pyridine MCQs With Answer

Synthesis of pyridine MCQs With Answer

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Synthesis of pyridine MCQs With Answer

The Synthesis of pyridine MCQs With Answer is a focused study resource tailored for B.Pharm students studying heterocyclic chemistry and pharmaceutical synthesis. This guide covers key concepts such as Hantzsch and Bohlmann-Rahtz routes, pyridine N-oxide strategies, regioselectivity, mechanism steps, common oxidants, and synthetic applications in drug design. Each question emphasizes practical reagents, reaction conditions, and mechanistic insight to build exam-ready understanding. Questions are designed to reinforce named reactions, substitution patterns, and spectral/functional group implications relevant to medicinal chemistry. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which set of reagents is classically used in the Hantzsch pyridine synthesis?

  • Two equivalents of β-ketoester, one aldehyde and ammonia
  • One ketone, one aldehyde and hydrazine
  • Three equivalents of acetyl chloride and ammonia
  • One nitrile, one aldehyde and base

Correct Answer: Two equivalents of β-ketoester, one aldehyde and ammonia

Q2. The immediate product formed in the Hantzsch synthesis before oxidation is:

  • Aromatic pyridine
  • Dihydropyridine (1,4-dihydropyridine)
  • Pyridinium salt
  • Pyridine N-oxide

Correct Answer: Dihydropyridine (1,4-dihydropyridine)

Q3. Which oxidizing agent is commonly used to oxidize dihydropyridines to pyridines in Hantzsch synthesis?

  • DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)
  • LiAlH4
  • HBr in acetic acid
  • POCl3

Correct Answer: DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)

Q4. In pyridine, the lone pair on nitrogen is located in which orbital and how does it participate in aromaticity?

  • In an sp2 orbital and not part of the aromatic π-system
  • In a p-orbital and part of the aromatic π-system
  • In an sp3 orbital and not part of the aromatic π-system
  • Delocalized across the ring and part of a 10 π-electron system

Correct Answer: In an sp2 orbital and not part of the aromatic π-system

Q5. Which position(s) on pyridine are most activated for nucleophilic aromatic substitution (SNAr)?

  • 2- and 4-positions (ortho and para to nitrogen)
  • 3-position only (meta to nitrogen)
  • All positions equally
  • Only the nitrogen atom

Correct Answer: 2- and 4-positions (ortho and para to nitrogen)

Q6. Which reaction is described by the Chichibabin reaction in pyridine chemistry?

  • Nucleophilic amination at C2 using sodium amide to give 2-aminopyridine
  • Oxidative formation of pyridine from dihydropyridine
  • Aldol condensation to form substituted pyridines
  • Metal-catalyzed cross-coupling to introduce aryl groups

Correct Answer: Nucleophilic amination at C2 using sodium amide to give 2-aminopyridine

Q7. Pyridine N-oxide is often prepared using which oxidant?

  • m-CPBA (meta-chloroperbenzoic acid)
  • LiAlH4
  • PCl5
  • Hydrogen iodide

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

Q8. Conversion of pyridine to pyridine N-oxide generally has what effect on electrophilic aromatic substitution (EAS)?

  • Activates the ring and directs electrophiles to 2- and 4-positions
  • Deactivates the ring toward EAS
  • No effect on EAS reactivity or regiochemistry
  • Makes EAS impossible

Correct Answer: Activates the ring and directs electrophiles to 2- and 4-positions

Q9. The Bohlmann–Rahtz pyridine synthesis is particularly useful for making which type of substituted pyridines?

  • 2,3,6-trisubstituted pyridines from propargyl alcohol derivatives and enamines
  • Unsubstituted pyridine only
  • N-alkylpyridinium salts exclusively
  • Only 3-substituted pyridines via nitration

Correct Answer: 2,3,6-trisubstituted pyridines from propargyl alcohol derivatives and enamines

Q10. The Kröhnke pyridine synthesis generally uses which type of intermediate to build substituted pyridines?

  • Pyridinium salts formed from pyridine precursors and α,β-unsaturated carbonyl compounds
  • Direct cyclization of three aldehydes
  • Radical polymerization followed by aromatization
  • Hydrogenation of pyridine N-oxides

Correct Answer: Pyridinium salts formed from pyridine precursors and α,β-unsaturated carbonyl compounds

Q11. Which property makes pyridine less reactive towards electrophilic aromatic substitution compared to benzene?

  • Electron-withdrawing effect of the ring nitrogen reduces electron density
  • Lack of aromaticity
  • Higher ring strain in pyridine
  • Presence of an sp3-hybridized nitrogen

Correct Answer: Electron-withdrawing effect of the ring nitrogen reduces electron density

Q12. Minisci reactions are used to functionalize heteroaromatics. What is the general mechanism?

  • Radical addition to electron-deficient heteroaromatic rings (e.g., pyridine)
  • Electrophilic aromatic substitution under acidic conditions
  • Nucleophilic substitution at the nitrogen atom
  • Pericyclic cycloaddition to form dihydropyridines

Correct Answer: Radical addition to electron-deficient heteroaromatic rings (e.g., pyridine)

Q13. Which reagent is commonly used to selectively introduce a nitro group into pyridine under strongly activating conditions?

  • Nitration with HNO3/H2SO4 is difficult; strong conditions or pyridine N-oxide are used
  • Friedel–Crafts nitration with AlCl3 and HNO3
  • Nucleophilic nitration using NaNO2
  • Direct nitration with NBS

Correct Answer: Nitration with HNO3/H2SO4 is difficult; strong conditions or pyridine N-oxide are used

Q14. Which of the following best describes the aromaticity of pyridine?

  • Six π-electrons delocalized over a planar six-membered ring (aromatic)
  • Non-aromatic due to localized lone pair
  • Anti-aromatic with 8 π-electrons
  • Only partially aromatic with conjugation interrupted at nitrogen

Correct Answer: Six π-electrons delocalized over a planar six-membered ring (aromatic)

Q15. Which pathway is often used to synthesize nicotinic acid (pyridine-3-carboxylic acid) industrially?

  • Oxidation of nicotine or pyridine derivatives followed by functional group manipulation
  • Direct nitration of benzene followed by ring contraction
  • Hydrogenation of nicotinamide under mild conditions
  • Dehalogenation of 3-chloropyridine

Correct Answer: Oxidation of nicotine or pyridine derivatives followed by functional group manipulation

Q16. In the synthesis of substituted pyridines via cyclocondensation, the initial step commonly involves formation of which intermediate?

  • Conjugated enamine or α,β-unsaturated carbonyl intermediate
  • Stable carbocation attached to nitrogen
  • Free radical at the ring nitrogen
  • Azide intermediate attached to alkene

Correct Answer: Conjugated enamine or α,β-unsaturated carbonyl intermediate

Q17. Which of the following is a typical strategy to achieve regioselective functionalization at C4 of pyridine?

  • Use of a temporary N-oxide to direct electrophilic substitution and then deoxygenation
  • Direct Friedel–Crafts acylation at room temperature
  • Hydrogenation to piperidine then selective reoxidation
  • Base-promoted lithiation at C3 followed by electrophile

Correct Answer: Use of a temporary N-oxide to direct electrophilic substitution and then deoxygenation

Q18. Which cross-coupling method is commonly used to install aryl substituents on halopyridines?

  • Suzuki–Miyaura coupling using boronic acids and Pd catalyst
  • Friedel–Crafts alkylation with AlCl3
  • Nucleophilic substitution with sodium phenoxide directly
  • Oxidative coupling with KMnO4

Correct Answer: Suzuki–Miyaura coupling using boronic acids and Pd catalyst

Q19. Which substituent pattern is favored for electrophilic substitution on pyridine N-oxide compared to pyridine?

  • 2- and 4-substitution becomes easier on the N-oxide
  • Only 3-substitution is possible on N-oxide
  • N-oxide completely prevents substitution
  • Substitution occurs exclusively at nitrogen on N-oxide

Correct Answer: 2- and 4-substitution becomes easier on the N-oxide

Q20. For preparing 2-aminopyridines, which method provides direct access via nucleophilic aromatic substitution?

  • Chichibabin amination using sodium amide on halopyridines
  • Direct nitration followed by reduction at C3
  • Hydroboration–oxidation of pyridine
  • Oxidation of piperidine to 2-aminopyridine

Correct Answer: Chichibabin amination using sodium amide on halopyridines

Q21. Which factor predominantly controls regioselectivity in Hantzsch pyridine products?

  • Nature of aldehyde and β-ketoester substituents influencing condensation and cyclization
  • Only temperature, independent of substrates
  • Presence of radical initiators exclusively
  • Choice of solvent only

Correct Answer: Nature of aldehyde and β-ketoester substituents influencing condensation and cyclization

Q22. Which method is useful to synthesize 4-substituted pyridines via C–H activation?

  • Pd-catalyzed direct C–H arylation under directing-group control
  • Simple radical bromination of pyridine
  • Direct nucleophilic alkylation at nitrogen
  • Electrochemical reduction followed by alkylation

Correct Answer: Pd-catalyzed direct C–H arylation under directing-group control

Q23. Which intermediate is characteristic in many pyridine syntheses where an enamine condenses with an electrophile?

  • Conjugated iminium or imine intermediate leading to cyclization
  • Carbene insertion intermediate
  • Free radical cation trapped by oxygen
  • Stable diazonium salt intermediate

Correct Answer: Conjugated iminium or imine intermediate leading to cyclization

Q24. Which reagent combination is typically avoided for Friedel–Crafts reactions on pyridine due to deactivation by nitrogen?

  • AlCl3 with alkyl halides for direct alkylation
  • Pd-catalyzed cross-coupling with boronic acids
  • Oxidation with DDQ
  • Formation of N-oxides for directed substitution

Correct Answer: AlCl3 with alkyl halides for direct alkylation

Q25. Which is a practical laboratory oxidant to convert Hantzsch dihydropyridines to pyridines with high yield?

  • MnO2 or DDQ under controlled conditions
  • NaBH4 in methanol
  • TFAA (trifluoroacetic anhydride) without oxidant
  • PCl3 in dry ether

Correct Answer: MnO2 or DDQ under controlled conditions

Q26. The presence of a pyridine ring in a drug molecule most commonly affects which property?

  • Basicity and ability to act as a hydrogen-bond acceptor influencing pharmacokinetics
  • Always makes the drug highly lipophilic
  • Removes all metabolic liability
  • Makes the compound inert to enzymes

Correct Answer: Basicity and ability to act as a hydrogen-bond acceptor influencing pharmacokinetics

Q27. Which approach can convert 3-substituted pyridine into 2-substituted derivative?

  • Directed metalation at C2 followed by electrophile introduction (e.g., lithiation with TMEDA and electrophile)
  • Direct acid-catalyzed rearrangement at room temperature
  • Hydrogenation to pyrrolidine then regioselective reoxidation
  • Photochemical isomerization of the ring atoms

Correct Answer: Directed metalation at C2 followed by electrophile introduction (e.g., lithiation with TMEDA and electrophile)

Q28. Which solvent system is often preferred for Hantzsch reactions to promote condensation steps?

  • Ethanol or acetic acid as protic solvents facilitating condensation
  • Neat liquid ammonia only
  • Hexane for nonpolar conditions
  • Anhydrous diethyl ether exclusively

Correct Answer: Ethanol or acetic acid as protic solvents facilitating condensation

Q29. Which technique provides selective functionalization of pyridine at C3 via radical pathways?

  • Minisci-type radical alkylation using carboxylic acids and oxidants
  • Electrophilic bromination with NBS under neutral conditions
  • Direct nucleophilic substitution using sodium methoxide
  • Pericyclic Diels–Alder reaction

Correct Answer: Minisci-type radical alkylation using carboxylic acids and oxidants

Q30. Which statement about pyridine acidity/basicity is correct?

  • Pyridine is a weak base (pKa of conjugate acid around 5.2), less basic than aliphatic amines
  • Pyridine is a strong base with pKa > 10
  • Pyridine is neutral and non-basic
  • Pyridine is an acid with pKa < 0

Correct Answer: Pyridine is a weak base (pKa of conjugate acid around 5.2), less basic than aliphatic amines

Q31. In medicinal chemistry, pyridine rings are often introduced to improve which property?

  • Water solubility and H-bonding interactions with biological targets
  • Convert drugs into permanent cations in blood
  • Make molecules completely lipophobic
  • Eliminate all stereocenters

Correct Answer: Water solubility and H-bonding interactions with biological targets

Q32. Which transformation can convert a pyridine N-oxide back to pyridine after functionalization?

  • Deoxygenation using PCl3 or phosphines (e.g., PCl3 or PPh3)
  • Oxidation with KMnO4
  • Reduction with NaBH4 in water
  • Treatment with strong acid to protonate the ring permanently

Correct Answer: Deoxygenation using PCl3 or phosphines (e.g., PCl3 or PPh3)

Q33. The formation of pyridine rings via the Hantzsch method is valuable because it allows:

  • Modular introduction of three different substituents from simple precursors
  • Only synthesis of unsubstituted pyridine
  • Formation of five-membered rings exclusively
  • Direct installation of halogens without further steps

Correct Answer: Modular introduction of three different substituents from simple precursors

Q34. Which spectroscopy method is most diagnostic for confirming the formation of a pyridine ring?

  • 1H NMR showing characteristic aromatic proton pattern and 13C NMR for sp2 carbons
  • IR showing a strong OH stretch only
  • Mass spectrometry showing only molecular ion peak with no fragmentation
  • Polarimetry measurement of optical rotation

Correct Answer: 1H NMR showing characteristic aromatic proton pattern and 13C NMR for sp2 carbons

Q35. Which reagent is commonly used to introduce a halogen at the 3-position of activated pyridines under nucleophilic conditions?

  • Electrophilic halogenation is difficult; use halogenation of N-oxide followed by deoxygenation to access 3-halopyridines
  • Direct treatment with NaCl in water
  • Simple mixing with HBr at 25 °C
  • Photochemical halogenation without catalyst

Correct Answer: Electrophilic halogenation is difficult; use halogenation of N-oxide followed by deoxygenation to access 3-halopyridines

Q36. Which step is often rate-determining in multi-step condensations to form pyridine rings?

  • Cyclization step forming the new C–C and C–N bonds
  • Simple proton transfer in solvent
  • Final crystallization of the product
  • Evaporation of solvent under reduced pressure

Correct Answer: Cyclization step forming the new C–C and C–N bonds

Q37. Which functional group interconversion is frequently used after constructing substituted pyridines to access pharmacophores?

  • Selective oxidation of methyl to carboxylic acid or conversion of halide to amine via substitution
  • Hydrogenation of aromatic ring to cyclohexane directly
  • Cleavage of pyridine to form open-chain amines
  • Immediate chlorination at nitrogen only

Correct Answer: Selective oxidation of methyl to carboxylic acid or conversion of halide to amine via substitution

Q38. Which mechanistic pathway is common when pyridine acts as a nucleophile in acylation reactions?

  • Nucleophilic attack at the carbonyl forming an acylpyridinium intermediate at nitrogen
  • Direct electrophilic aromatic substitution on the ring
  • Pericyclic [4+2] cycloaddition forming adducts
  • Hydride transfer to reduce the carbonyl

Correct Answer: Nucleophilic attack at the carbonyl forming an acylpyridinium intermediate at nitrogen

Q39. Which transformation is often used to install an amino function at the 4-position of pyridine?

  • Nucleophilic replacement of a 4-halopyridine followed by reduction if needed
  • Direct electrophilic amination using NH3 under mild conditions
  • Oxidation of pyridine to open-chain amide
  • Photochemical insertion of N2 to yield an amine

Correct Answer: Nucleophilic replacement of a 4-halopyridine followed by reduction if needed

Q40. Which description fits the use of Vilsmeier–Haack formylation on pyridine derivatives?

  • Vilsmeier–Haack works poorly on pyridine directly but can be effective on activated derivatives or N-oxides to introduce formyl groups
  • It selectively reduces pyridine to piperidine
  • It is mainly used to halogenate pyridine at C2
  • It removes substituents by hydrolysis

Correct Answer: Vilsmeier–Haack works poorly on pyridine directly but can be effective on activated derivatives or N-oxides to introduce formyl groups

Q41. Which factor increases the rate of nucleophilic substitution on 2-halopyridines?

  • Electron-withdrawing substituents on the ring stabilizing the Meisenheimer-type intermediate
  • Strong electron-donating groups on the ring
  • Lower polarity solvents always
  • Deprotonation of the nitrogen lone pair

Correct Answer: Electron-withdrawing substituents on the ring stabilizing the Meisenheimer-type intermediate

Q42. The Kröhnke pyridine synthesis advantage is:

  • Ability to assemble highly substituted pyridines under mild conditions using pyridinium salt intermediates
  • Requires high-pressure hydrogenation for aromatization
  • Produces only unsubstituted pyridine in high yield
  • Only suitable for making N-oxides

Correct Answer: Ability to assemble highly substituted pyridines under mild conditions using pyridinium salt intermediates

Q43. Which approach is commonly used to access 2,6-disubstituted pyridines selectively?

  • Directed ortho-metalation at C2 followed by introduction of substituents at C6 via sequential functionalization
  • Random halogenation followed by separation
  • Hydrogenation to piperidine then selective dehydrogenation
  • Only biosynthetic fermentation can achieve this pattern

Correct Answer: Directed ortho-metalation at C2 followed by introduction of substituents at C6 via sequential functionalization

Q44. Which reagent is appropriate for converting a pyridine methyl group to a carboxylic acid (side-chain oxidation)?

  • KMnO4 oxidation under controlled conditions
  • NaBH4 reduction in methanol
  • Hydrogenation with Pd/C only
  • Grignard reagent formation with RMgBr

Correct Answer: KMnO4 oxidation under controlled conditions

Q45. Which tactic helps improve regioselectivity when synthesizing polysubstituted pyridines?

  • Use of protecting or directing groups (e.g., N-oxides, removable auxiliaries) during key steps
  • A single excess of reagent without planning
  • Avoiding any use of catalysts or directing groups
  • Only performing reactions at low temperatures without reagents

Correct Answer: Use of protecting or directing groups (e.g., N-oxides, removable auxiliaries) during key steps

Q46. Which catalytic method can enable direct C–H functionalization on pyridines for late-stage diversification?

  • Transition-metal-catalyzed C–H activation using directing groups
  • Acid-catalyzed cleavage of the ring
  • Simple thermal decomposition at >300 °C
  • Photolysis without catalyst under ambient conditions

Correct Answer: Transition-metal-catalyzed C–H activation using directing groups

Q47. In designing MCQs for pyridine synthesis, why is understanding mechanism important for B.Pharm students?

  • Mechanistic insight predicts regiochemistry, reagent selection and downstream functional group interconversions in drug design
  • Mechanism is irrelevant; only memorizing reagents is needed
  • Mechanisms are only theoretical and not used in labs
  • Only spectral data matters for synthesis

Correct Answer: Mechanistic insight predicts regiochemistry, reagent selection and downstream functional group interconversions in drug design

Q48. Which of the following best describes a practical route to prepare 3-aminopyridine derivatives?

  • Nitration or halogenation at C3 followed by reduction or nucleophilic substitution to introduce amino groups
  • Direct amination at nitrogen to give 3-aminopyridine
  • Hydrogenation of pyridine to 3-aminopiperidine
  • Oxidative cleavage of the ring then reconstruction

Correct Answer: Nitration or halogenation at C3 followed by reduction or nucleophilic substitution to introduce amino groups

Q49. Which consideration is most important when selecting an oxidant to aromatize dihydropyridine intermediates in scale-up?

  • Oxidant selectivity, safety, cost and scalability (e.g., DDQ vs. nitric acid vs. air with catalysts)
  • Only the color of the oxidant
  • Oxidant must be a gaseous reagent only
  • Oxidant should be the most expensive option

Correct Answer: Oxidant selectivity, safety, cost and scalability (e.g., DDQ vs. nitric acid vs. air with catalysts)

Q50. Which concept is key for B.Pharm students to master regarding synthesis of pyridines for medicinal applications?

  • Integration of regiocontrol, functional group compatibility, named reactions (Hantzsch, Bohlmann–Rahtz, Kröhnke) and downstream modifications
  • Only memorizing reaction names without conditions
  • Ignoring substitution patterns and focusing on color changes
  • Believing that pyridine chemistry has no relevance to drug molecules

Correct Answer: Integration of regiocontrol, functional group compatibility, named reactions (Hantzsch, Bohlmann–Rahtz, Kröhnke) and downstream modifications

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