Reactions of oxazole MCQs With Answer

Reactions of oxazole MCQs With Answer — This concise, Student-friendly post covers key reaction patterns of oxazole relevant to B. Pharm students. Oxazole is an aromatic 5-membered heterocycle whose chemistry includes electrophilic substitution (favored at C5), directed metalation/lithiation (commonly at C2), Vilsmeier–Haack formylation, Robinson–Gabriel and Van Leusen syntheses, N‑alkylation to oxazolium salts, and cross-coupling after halogenation. Understanding site selectivity, mechanisms, and common reagents (TosMIC, POCl3/DMF, LDA, n‑BuLi) is crucial for medicinal chemistry and drug design. This guide emphasizes reaction scope, limitations and practical reagents. ‘Now let’s test your knowledge with 50 MCQs on this topic.’

Q1. Which atoms occupy positions 1 and 3 in the oxazole ring according to standard numbering?

• Carbon and carbon
• Oxygen and nitrogen
• Nitrogen and oxygen
• Sulfur and nitrogen

Correct Answer: Oxygen and nitrogen

Q2. Oxazole is classified as which type of aromatic system?

• Non-aromatic
• Anti-aromatic
• Aromatic 6 π-electron heterocycle
• Radical aromatic

Correct Answer: Aromatic 6 π-electron heterocycle

Q3. Which heteroatom in oxazole primarily contributes a lone pair to the aromatic sextet?

• Oxygen lone pair
• Nitrogen lone pair
• Both oxygen and nitrogen equally
• Neither oxygen nor nitrogen

Correct Answer: Nitrogen lone pair

Q4. Which position on oxazole is most reactive toward electrophilic aromatic substitution (EAS)?

• C2 (alpha to oxygen)
• C3 (adjacent to nitrogen)
• C4 (beta to oxygen)
• C5 (alpha to oxygen and beta to nitrogen)

Correct Answer: C5 (alpha to oxygen and beta to nitrogen)

Q5. Which position in oxazole has the most acidic hydrogen and is most susceptible to deprotonation by strong bases?

• C5
• C4
• C3
• C2

Correct Answer: C2

Q6. Which named synthesis converts alpha‑acylamino ketones to oxazoles via cyclodehydration?

• Van Leusen reaction
• Robinson–Gabriel synthesis
• Paal–Knorr synthesis
• Fischer indole synthesis

Correct Answer: Robinson–Gabriel synthesis

Q7. The Van Leusen oxazole synthesis commonly employs which reagent as a key building block?

• Tosylmethyl isocyanide (TosMIC)
• Phosgene
• Sodium azide
• Diazomethane

Correct Answer: Tosylmethyl isocyanide (TosMIC)

Q8. Which reagent pair is typically used for Vilsmeier–Haack formylation of oxazoles at the activated position?

• POCl3 and DMF
• PCl5 and benzene
• H2SO4 and HNO3
• LiAlH4 and THF

Correct Answer: POCl3 and DMF

Q9. Protonation of oxazole under strong acidic conditions predominantly occurs at which site?

• Oxygen atom
• Nitrogen atom
• Carbon C5
• Carbon C2

Correct Answer: Nitrogen atom

Q10. Which statement best describes the basicity of oxazole compared to pyridine?

• Oxazole is significantly more basic than pyridine
• Oxazole and pyridine have identical basicity
• Oxazole is less basic than pyridine
• Oxazole is non-basic

Correct Answer: Oxazole is less basic than pyridine

Q11. Among the following heterocycles, which is generally more reactive toward electrophilic substitution than oxazole?

• Thiophene
• Pyridine
• Furan
• Oxazole

Correct Answer: Furan

Q12. N‑Alkylation of oxazole gives which type of species useful in some catalytic or synthetic contexts?

• Oxazolidinone
• Oxazolium salt
• Oxaziridine
• Oxime ether

Correct Answer: Oxazolium salt

Q13. Directed metalation (lithiation) of oxazole to install substituents typically targets which carbon?

• C5 using milder bases
• C3 exclusively
• C2 using strong bases like n‑BuLi or LDA
• C4 under neutral conditions

Correct Answer: C2 using strong bases like n‑BuLi or LDA

Q14. Halogenation of oxazole to prepare a substrate for Suzuki coupling is most commonly performed at which position?

• C1 (oxygen position)
• N position
• C5
• C3

Correct Answer: C5

Q15. Which cross‑coupling reaction is frequently used to install aryl groups onto halogenated oxazoles?

• Bucherer–Bergs reaction
• Suzuki–Miyaura coupling
• Aldol condensation
• Beckmann rearrangement

Correct Answer: Suzuki–Miyaura coupling

Q16. Nucleophilic attack on oxazole often occurs at which position under strongly nucleophilic conditions, potentially leading to ring opening?

• C5
• C2
• N atom
• O atom

Correct Answer: C2

Q17. Which reagent is typically used for selective bromination at the 5‑position of many heteroaromatics under mild conditions?

• N‑Bromosuccinimide (NBS)
• LiAlH4
• SOCl2
• KMnO4 in water

Correct Answer: N‑Bromosuccinimide (NBS)

Q18. Compared to furan, oxazole is generally:

• More electron-rich and more reactive toward EAS
• Less electron-rich and less reactive toward EAS
• Identical in reactivity toward EAS
• Non-aromatic while furan is aromatic

Correct Answer: Less electron-rich and less reactive toward EAS

Q19. Which type of intermediate is stabilized during electrophilic substitution at C5 of oxazole?

• Carbanion intermediate
• Wheland (sigma) complex stabilized by heteroatoms
• Free radical cation only
• Carbene intermediate

Correct Answer: Wheland (sigma) complex stabilized by heteroatoms

Q20. Which reagent is commonly used for lithiation at C2 of oxazole at low temperature?

• n‑Butyllithium (n‑BuLi)
• Sodium borohydride (NaBH4)
• Potassium permanganate (KMnO4)
• Boron trifluoride etherate (BF3·OEt2)

Correct Answer: n‑Butyllithium (n‑BuLi)

Q21. Which transformation converts a 5‑bromooxazole into a 5‑aryl oxazole using a palladium catalyst?

• Hydrogenation
• Suzuki coupling with aryl boronic acid
• Wittig reaction
• Friedel–Crafts acylation

Correct Answer: Suzuki coupling with aryl boronic acid

Q22. Which statement about nitration of oxazole is most accurate?

• Nitration is facile and gives high yields under standard HNO3/H2SO4
• Nitration is difficult and often leads to ring oxidation or low yields
• Nitration selectively occurs at N atom to give N‑nitrooxazole
• Oxazole cannot undergo nitration under any conditions

Correct Answer: Nitration is difficult and often leads to ring oxidation or low yields

Q23. Which reagent set is appropriate for converting an oxazole into its 5‑formyl derivative (formylation)?

• DMF + POCl3 (Vilsmeier reagent)
• HCl + Zn
• NaBH4 in methanol
• McMurry reagent (TiCl4/Zn)

Correct Answer: DMF + POCl3 (Vilsmeier reagent)

Q24. Which of the following best explains why the C5 position is favored for EAS on oxazole?

• C5 has the highest steric hindrance
• Resonance stabilization of the Wheland intermediate places positive charge away from heteroatoms
• C5 is the only sp3 carbon
• C5 has no neighboring heteroatoms

Correct Answer: Resonance stabilization of the Wheland intermediate places positive charge away from heteroatoms

Q25. Oxazole derivatives can be converted to oxazolium salts by reaction with:

• Alkyl halides (N‑alkylation)
• Strong bases only
• Catalytic hydrogenation
• Metal hydrides like LiAlH4

Correct Answer: Alkyl halides (N‑alkylation)

Q26. Which synthetic route is commonly used to introduce substituents at C5 after direct halogenation?

• Aldol condensation
• Cross-coupling reactions (e.g., Suzuki, Stille, Negishi)
• Mannich reaction
• Beckmann rearrangement

Correct Answer: Cross-coupling reactions (e.g., Suzuki, Stille, Negishi)

Q27. Which structural isomer differs from oxazole by swapping the positions of oxygen and nitrogen?

• Isoxazole
• Thiazole
• Pyrrole
• Furan

Correct Answer: Isoxazole

Q28. Which reagent is most appropriate to reduce the oxazole ring to a dihydrooxazole selectively?

• Pd/C hydrogenation under controlled pressure
• Strong base at room temperature
• Ozone (O3) in methanol
• Concentrated nitric acid

Correct Answer: Pd/C hydrogenation under controlled pressure

Q29. Which functional group interconversion is commonly used to prepare oxazoles from amino alcohols and carboxylic acid derivatives?

• Cyclodehydration (dehydrative cyclization)
• Hydroboration–oxidation
• Baeyer–Villiger oxidation
• Hydrolysis to form diols

Correct Answer: Cyclodehydration (dehydrative cyclization)

Q30. Which heterocycle is most similar to oxazole in terms of ring size and heteroatom count?

• Pyridine
• Imidazole
• Thiazole
• Benzoic acid

Correct Answer: Thiazole

Q31. Which reagent would you choose to convert a 5‑bromooxazole to 5‑methyloxazole using cross‑coupling methodology?

• Methylboronic acid with Pd catalyst (Suzuki)
• NaBH4 directly
• SOCl2 and MeOH
• Conc. H2SO4

Correct Answer: Methylboronic acid with Pd catalyst (Suzuki)

Q32. Which property explains why oxazole is less reactive than furan toward electrophiles?

• Oxygen in oxazole increases electron density more than in furan
• Nitrogen in oxazole withdraws electron density, reducing reactivity
• Oxazole is non-planar and cannot delocalize electrons
• Oxazole lacks π-electrons

Correct Answer: Nitrogen in oxazole withdraws electron density, reducing reactivity

Q33. Which step is most likely involved in the mechanism of electrophilic substitution on oxazole?

• Formation of a carbocation at oxygen followed by elimination
• Addition of electrophile to give a sigma complex followed by deprotonation
• Radical chain propagation only
• Nucleophilic attack followed by rearrangement

Correct Answer: Addition of electrophile to give a sigma complex followed by deprotonation

Q34. Which of the following is a common problem when attempting harsh electrophilic functionalization of oxazole?

• Complete inertness with no reaction
• Ring oxidation or ring opening under strong conditions
• Exclusive formation of N‑alkylated products
• Immediate polymerization to long chains

Correct Answer: Ring oxidation or ring opening under strong conditions

Q35. Electrophilic formylation at C5 of oxazole using Vilsmeier conditions yields what functional group at the 5‑position?

• Methyl group
• Formyl (aldehyde) group
• Carboxylic acid
• Nitro group

Correct Answer: Formyl (aldehyde) group

Q36. Which reagent is commonly used to prepare TosMIC reagents for Van Leusen oxazole synthesis?

• Tosyl chloride + chloromethyl isocyanide
• Tosylmethyl isocyanide is typically purchased or prepared from tosylmethyl derivatives
• Nitrobenzene + sodium azide
• Grignard reagent formation from bromobenzene

Correct Answer: Tosylmethyl isocyanide is typically purchased or prepared from tosylmethyl derivatives

Q37. Which transformation is a strategic advantage of converting oxazoles to halogenated derivatives?

• To make the ring non-aromatic
• To enable subsequent cross‑coupling for diversification
• To increase acidity of all ring hydrogens
• To convert oxazole into a carbohydrate

Correct Answer: To enable subsequent cross‑coupling for diversification

Q38. Which statement about ring opening of oxazoles under nucleophilic attack is correct?

• Oxazoles are completely resistant to nucleophiles
• Nucleophilic attack at C2 can trigger ring opening under forcing conditions
• Attack at C5 leads to immediate polymerization
• Ring opening produces only simple alkanes

Correct Answer: Nucleophilic attack at C2 can trigger ring opening under forcing conditions

Q39. Which catalyst type is most commonly used for cross‑coupling reactions on halogenated oxazoles?

• Acidic acid catalysts
• Palladium catalysts
• Photoredox catalysts only
• Enzymatic catalysts

Correct Answer: Palladium catalysts

Q40. Which functional group on an aldehyde is directly useful in Van Leusen oxazole synthesis with TosMIC?

• Carboxylic acid
• Aldehyde carbonyl (aldehyde)
• Alkene
• Epoxide

Correct Answer: Aldehyde carbonyl (aldehyde)

Q41. Which condition should be applied for directed lithiation at C2 to avoid overreaction?

• High temperature (>100 °C)
• Room temperature for extended time
• Low temperature (e.g., −78 °C) with stoichiometric base
• Strong acid conditions

Correct Answer: Low temperature (e.g., −78 °C) with stoichiometric base

Q42. Which property is important when selecting a solvent for lithiation of oxazole derivatives?

• Protic solvents stabilize organolithium reagents
• Aprotic, non‑coordinating solvents like hexane only
• Aprotic, coordinating ethers like THF at low temp are commonly used
• Strongly acidic solvents increase lithiation selectivity

Correct Answer: Aprotic, coordinating ethers like THF at low temp are commonly used

Q43. Which transformation is least likely to occur directly on an intact oxazole ring under mild conditions?

• N‑alkylation to form oxazolium salts
• Electrophilic substitution at C5
• Complete ring hydrogenolysis to an open chain under mild conditions
• Metal-catalyzed cross‑coupling after halogenation

Correct Answer: Complete ring hydrogenolysis to an open chain under mild conditions

Q44. In medicinal chemistry, why are oxazole rings often found in drug scaffolds?

• They are highly reactive and unstable in biological systems
• They provide planar, heteroatom‑rich aromatic motifs that affect binding and metabolic stability
• They are identical to benzene in properties
• They always increase water solubility dramatically

Correct Answer: They provide planar, heteroatom‑rich aromatic motifs that affect binding and metabolic stability

Q45. Which reagent combination would you avoid when trying to preserve an oxazole ring in a synthesis?

• Mild base and low temperature
• Nucleophiles under forcing conditions or strong oxidizers like concentrated HNO3
• Pd/C hydrogenation under controlled pressure
• POCl3/DMF for selective formylation

Correct Answer: Nucleophiles under forcing conditions or strong oxidizers like concentrated HNO3

Q46. Which type of spectroscopy is most diagnostic for confirming aromaticity and substitution pattern in oxazoles?

• 1H NMR and 13C NMR spectroscopy
• Simple melting point only
• Paper chromatography only
• Refractometry

Correct Answer: 1H NMR and 13C NMR spectroscopy

Q47. Which catalyst would you choose for a Stille coupling on a 5‑stannyl oxazole to install an aryl group?

• Pd(0) catalyst (e.g., Pd(PPh3)4)
• Acidic sulfonic resin
• Base metal like sodium in water
• LiAlH4

Correct Answer: Pd(0) catalyst (e.g., Pd(PPh3)4)

Q48. Which modification increases the electrophilic reactivity at C5 of oxazole for further functionalization?

• Introducing electron‑withdrawing groups at C2 or C4
• Introducing electron‑donating groups at positions that increase electron density at C5
• Hydrogenating the ring fully
• Converting oxazole to a saturated tetrahydro derivative

Correct Answer: Introducing electron‑donating groups at positions that increase electron density at C5

Q49. Which of the following best summarizes a safe laboratory strategy to functionalize oxazole selectively at C5?

• Use harsh oxidizers and strong acids to drive substitution
• Install a halogen at C5 under controlled electrophilic conditions, then use palladium‑catalyzed cross‑coupling
• Randomly heat to high temperatures hoping for selectivity
• Always avoid metal catalysts

Correct Answer: Install a halogen at C5 under controlled electrophilic conditions, then use palladium‑catalyzed cross‑coupling

Q50. Which experimental precaution is most important when performing lithiation on oxazole derivatives?

• Perform at high temperature to speed reaction
• Exclude moisture and oxygen and maintain low temperature to control regioselectivity
• Use protic solvents to stabilize the organolithium
• Always add water to quench during lithiation

Correct Answer: Exclude moisture and oxygen and maintain low temperature to control regioselectivity

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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