Synthesis of azepines MCQs With Answer

Mastering the synthesis of azepines is essential for B. Pharm students focusing on heterocyclic chemistry and medicinal chemistry. This concise guide, “Synthesis of azepines MCQs With Answer,” covers key concepts such as ring expansion, ring-closing metathesis (RCM), intramolecular cyclizations, Beckmann and Schmidt rearrangements, and transition-metal catalyzed C–N bond formation (e.g., Buchwald–Hartwig). Learn about common reagents, reaction mechanisms, regioselectivity, stereochemistry, and spectral characterization (NMR, IR) that influence seven-membered nitrogen heterocycle construction and biological scaffold design. These focused MCQs will deepen conceptual understanding and practical problem-solving for synthesis strategies and experimental planning. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is an azepine?

• A six-membered heterocycle with one nitrogen
• A five-membered nitrogen-containing ring
• A seven-membered heterocycle containing one nitrogen atom
• An eight-membered oxygen-containing ring

Correct Answer: A seven-membered heterocycle containing one nitrogen atom

Q2. What is a benzazepine?

• An azepine fused to a benzene ring
• An azepane with an extra methyl group
• A seven-membered ring containing oxygen
• A bicyclic system without heteroatoms

Correct Answer: An azepine fused to a benzene ring

Q3. Which catalyst is most commonly associated with ring-closing metathesis (RCM) for making azepines?

• Grubbs ruthenium catalyst
• Pd/C hydrogenation catalyst
• Lewis acid AlCl3
• KMnO4

Correct Answer: Grubbs ruthenium catalyst

Q4. Which rearrangement converts oximes into amides and is useful in ring-expansion strategies?

• Baeyer–Villiger rearrangement
• Beckmann rearrangement
• Wagner–Meerwein rearrangement
• Buchwald–Hartwig amination

Correct Answer: Beckmann rearrangement

Q5. Which rearrangement uses hydrazoic acid to convert ketones into amides and can produce ring-expanded lactams?

• Curtius rearrangement
• Schmidt rearrangement
• Claisen rearrangement
• Favorskii rearrangement

Correct Answer: Schmidt rearrangement

Q6. What is a common synthetic challenge when preparing seven-membered rings like azepines?

• Excessive aromatic stabilization
• High entropic cost and competing intermolecular reactions
• Lack of available building blocks
• Immediate spontaneous polymerization to benzene

Correct Answer: High entropic cost and competing intermolecular reactions

Q7. Which cross-coupling method is widely used to form C–N bonds in azepine synthesis?

• Heck reaction
• Buchwald–Hartwig amination
• Grignard coupling
• Ozonolysis

Correct Answer: Buchwald–Hartwig amination

Q8. Which precursor is commonly used for RCM-based azepine synthesis?

• Dialkenyl amine (a diene tethered to an amine)
• Simple alkane
• Terminal alkyne only
• Carboxylic acid without unsaturation

Correct Answer: Dialkenyl amine (a diene tethered to an amine)

Q9. How does the aromatic stabilization of azepine typically compare to pyridine?

• Azepine is more aromatic than pyridine
• Azepine and pyridine have equal aromaticity
• Azepine generally shows less aromatic stabilization than pyridine
• Azepine is antiaromatic while pyridine is non-aromatic

Correct Answer: Azepine generally shows less aromatic stabilization than pyridine

Q10. Which IR absorption band is indicative of an N–H stretch often seen in azepine derivatives?

• ~2100 cm−1
• ~3300 cm−1
• ~1700 cm−1
• ~1600 cm−1

Correct Answer: ~3300 cm−1

Q11. Which NMR experiment is most useful for establishing long-range (2–3 bond) C–H connectivity in azepine structure elucidation?

• 1D 1H NMR
• COSY
• HMBC
• DEPT-135

Correct Answer: HMBC

Q12. The Beckmann rearrangement transforms oximes into which product class often used to make azepinones?

• Ethers
• Amides (lactams when cyclic)
• Carboxylic acids
• Alkenes

Correct Answer: Amides (lactams when cyclic)

Q13. Which method is commonly used for ring expansion from a six- to a seven-membered ring in heterocycle synthesis?

• Beckmann rearrangement of cyclic oximes
• Wittig olefination of aldehydes
• Direct hydrogenation of benzene
• Friedel–Crafts acylation only

Correct Answer: Beckmann rearrangement of cyclic oximes

Q14. What is the central metal in most Grubbs-type RCM catalysts used for azepine construction?

• Palladium
• Ruthenium
• Iron
• Copper

Correct Answer: Ruthenium

Q15. Which dehydrating, strong acid is often employed to promote the Beckmann rearrangement in ring-forming sequences?

• Polyphosphoric acid (PPA)
• Sodium bicarbonate
• Water
• Ammonia

Correct Answer: Polyphosphoric acid (PPA)

Q16. Why are benzazepine scaffolds important in medicinal chemistry?

• They are inert and non-interactive with biological targets
• They frequently serve as CNS-active pharmacophores
• They are exclusively used as preservatives
• They only act as solvents in reactions

Correct Answer: They frequently serve as CNS-active pharmacophores

Q17. Which cycloaddition is commonly exploited to build seven-membered rings such as azepine frameworks?

• [2+2] cycloaddition
• [3+2] cycloaddition
• [4+3] cycloaddition
• Diels–Alder [4+2] exclusively

Correct Answer: [4+3] cycloaddition

Q18. What primarily controls regioselectivity in intramolecular cyclizations toward azepines?

• Electronic effects and substituent patterns on reacting centers
• The color of the solvent
• The day of the week
• Only the concentration of oxygen

Correct Answer: Electronic effects and substituent patterns on reacting centers

Q19. Which protecting group is commonly used for amines during multi-step azepine synthesis?

• TBDPS (tert-butyldiphenylsilyl)
• Boc (tert-butyloxycarbonyl)
• MOM (methoxymethyl) for alcohols only
• Nitro group

Correct Answer: Boc (tert-butyloxycarbonyl)

Q20. How can microwave irradiation assist azepine synthesis?

• It reduces the molecular weight of reactants
• It accelerates reaction rates and can improve yields
• It always destroys catalysts
• It makes all products aromatic

Correct Answer: It accelerates reaction rates and can improve yields

Q21. The Curtius rearrangement converts an acyl azide into which intermediate?

• Isocyanate
• Nitrile
• Alcohol
• Alkene

Correct Answer: Isocyanate

Q22. Which solvent is commonly used for RCM reactions with Grubbs catalysts?

• Water
• Dichloromethane (DCM)
• Concentrated sulfuric acid
• Liquid ammonia

Correct Answer: Dichloromethane (DCM)

Q23. Which combination is typical for Buchwald–Hartwig amination?

• Pd catalyst with phosphine ligand
• Grubbs catalyst with a radical initiator
• KMnO4 without metals
• Photoredox catalyst only

Correct Answer: Pd catalyst with phosphine ligand

Q24. What is the key ionic intermediate in the Beckmann rearrangement mechanism?

• Carbanion
• Nitrilium ion
• Carbocation stabilized by resonance only in benzene
• Ozonide

Correct Answer: Nitrilium ion

Q25. Which side reaction commonly reduces yields when attempting azepine formation?

• Intermolecular polymerization or oligomerization
• Complete aromatization to benzene
• Instant crystallization of solvent
• Formation of elemental nitrogen

Correct Answer: Intermolecular polymerization or oligomerization

Q26. Which rearrangement is particularly effective to form azepinones (seven-membered lactams)?

• Schmidt rearrangement
• Wurtz coupling
• Ozonolysis
• Fischer esterification

Correct Answer: Schmidt rearrangement

Q27. Which analytical technique provides molecular weight and fragmentation patterns helpful for confirming azepine formation?

• Infrared spectroscopy only
• Mass spectrometry (MS)
• Thin-layer chromatography only
• Optical microscopy

Correct Answer: Mass spectrometry (MS)

Q28. Which Grubbs catalyst generation is noted for higher functional group tolerance in RCM?

• First-generation Grubbs
• Second-generation Grubbs
• Ziegler–Natta catalyst
• Raney nickel

Correct Answer: Second-generation Grubbs

Q29. What is the typical stereochemical outcome of the double bond formed by RCM in medium rings like azepines?

• Exclusively E isomer
• Exclusively Z isomer
• A mixture of E and Z isomers
• No double bond is formed

Correct Answer: A mixture of E and Z isomers

Q30. Which reducing agent is commonly used in reductive amination to form C–N bonds in ring closure?

• Sodium cyanoborohydride (NaBH3CN)
• KMnO4
• Ozone
• m-CPBA

Correct Answer: Sodium cyanoborohydride (NaBH3CN)

Q31. What major safety concern is associated with azide chemistry often used in nitrogen-insertion reactions?

• Azides are inert and safe
• Azides can be explosive and highly toxic
• Azides cause immediate polymerization to harmless products
• Azides always produce water as byproduct

Correct Answer: Azides can be explosive and highly toxic

Q32. Which experimental strategy improves intramolecular cyclization yields for medium-ring formation?

• High concentration to favor bimolecular reactions
• High-dilution conditions to suppress intermolecular reactions
• Cooling to −196 °C only
• Adding excess oxidant

Correct Answer: High-dilution conditions to suppress intermolecular reactions

Q33. Which reaction is commonly used to convert a carbonyl to an alkene as a precursor step for RCM?

• Wittig reaction
• Hydrogenation
• Hydrolysis
• Claisen condensation only

Correct Answer: Wittig reaction

Q34. What is the oxygen analog of azepine called?

• Azepane
• Oxepine
• Pyridine
• Furan

Correct Answer: Oxepine

Q35. Which computational method is routinely used to model reaction pathways in azepine synthesis?

• Classical mechanics only
• Density functional theory (DFT)
• Astrology charts
• Empirical boiling point tables

Correct Answer: Density functional theory (DFT)

Q36. Which reagent is commonly used to remove a Boc protecting group from amines during final deprotection?

• Trifluoroacetic acid (TFA)
• Sodium hydroxide (cold)
• Sodium bicarbonate
• Hydrogen gas without catalyst

Correct Answer: Trifluoroacetic acid (TFA)

Q37. What 1H NMR chemical shift range typically indicates aromatic protons relevant to benzazepine rings?

• 0–1 ppm
• 2–3 ppm
• 7–8 ppm
• 10–12 ppm only

Correct Answer: 7–8 ppm

Q38. Which catalytic approach is often used for C–H activation strategies in constructing azepine frameworks?

• Palladium-catalyzed C–H activation
• Simple thermal rearrangement without catalyst
• Photolysis in absence of catalysts only
• Saponification

Correct Answer: Palladium-catalyzed C–H activation

Q39. Which factor increases the effective rate of intramolecular ring closure?

• Decreasing effective molarity
• Increasing proximity (effective molarity) of reacting centers
• Complete dilution with water
• Adding excess radical initiator

Correct Answer: Increasing proximity (effective molarity) of reacting centers

Q40. Which solvent class generally favors intramolecular SN2-like cyclizations toward azepines?

• Polar protic solvents only
• Polar aprotic solvents (e.g., DMF, DMSO)
• Non-polar solvents always
• Supercritical CO2 exclusively

Correct Answer: Polar aprotic solvents (e.g., DMF, DMSO)

Q41. Which catalyst type often promotes [4+3] cycloadditions used to build seven-membered rings?

• Radical initiators only
• Lewis acid catalysts
• Base catalysts exclusively
• Enzymes only

Correct Answer: Lewis acid catalysts

Q42. What practical storage precaution is recommended for many azepine derivatives?

• Store exposed to sunlight and air
• Protect from light and oxygen; store under inert atmosphere if sensitive
• Keep at very high temperature (>150 °C)
• Store in strong acids only

Correct Answer: Protect from light and oxygen; store under inert atmosphere if sensitive

Q43. Beckmann rearrangement of a cyclic ketoxime typically yields which ring-contracted or ring-expanded product?

• Ring-contracted ether
• Ring-expanded lactam
• Simple alkane
• Carboxylic acid with loss of nitrogen

Correct Answer: Ring-expanded lactam

Q44. What strategy often gives high regioselectivity during ring-closing steps?

• Use of directing groups and temporary tethers
• Never use protecting groups
• Completely random substrate design
• Avoiding all catalysts

Correct Answer: Use of directing groups and temporary tethers

Q45. Which routine lab technique is used to monitor progress of azepine-forming reactions?

• Thin-layer chromatography (TLC)
• Sound-level meter
• pH paper only for solid reactions
• Visual color matching with a paint chart

Correct Answer: Thin-layer chromatography (TLC)

Q46. Incorporation of an azepine core into drug leads often affects which ADME property?

• Guaranteed renal clearance only
• May enhance CNS penetration and receptor interactions
• Converts all compounds into gases
• Always eliminates metabolic liability

Correct Answer: May enhance CNS penetration and receptor interactions

Q47. What is the name for the fully saturated seven-membered nitrogen heterocycle?

• Azepine
• Azepane
• Pyrrole
• Imidazole

Correct Answer: Azepane

Q48. Which solvent is commonly used in Pd-catalyzed Buchwald–Hartwig amination for forming C–N bonds?

• Toluene or dioxane
• Neat concentrated HCl only
• Liquid sulfur dioxide
• Glycerol exclusively

Correct Answer: Toluene or dioxane

Q49. Which advanced NMR technique can directly provide information about the nitrogen atom in an azepine ring?

• 31P NMR
• 15N NMR
• Deuterium NMR only
• Fluorine NMR

Correct Answer: 15N NMR

Q50. What is an environmental or safety concern commonly associated with many azepine synthetic routes?

• Use of only water as solvent
• Generation of azide waste and use of toxic metal catalysts
• Complete biodegradability without precautions
• Universal absence of hazardous reagents

Correct Answer: Generation of azide waste and use of toxic metal catalysts

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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