Reactions of pyrazole MCQs With Answer

Reactions of pyrazole MCQs With Answer — This concise guide covers key reactions of pyrazole and their pharmaceutical relevance for B. Pharm students. You’ll review tautomerism, N- and C‑functionalization (N‑alkylation, N‑acylation, C‑electrophilic substitution), regioselective halogenation, Vilsmeier formylation, 1,3‑dipolar cycloadditions, metal‑catalyzed cross‑couplings, oxidation/reduction and reactivity of pyrazole N‑oxides. Emphasis is on mechanisms, regiochemistry and common reagents so you can apply concepts to drug synthesis and metabolic transformations. This keyword‑rich overview aids exam prep and practical understanding. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which tautomeric form predominates in unsubstituted pyrazole under normal conditions?

• 1H-pyrazole with proton on N1
• 2H-pyrazole with proton on N2
• Non-aromatic open-chain tautomer
• Equal mixture of 1H and 2H tautomers

Correct Answer: 1H-pyrazole with proton on N1

Q2. Which nitrogen in pyrazole contains the lone pair that participates in aromaticity?

• The pyrrole-type N (N1) whose lone pair is delocalized into the ring
• The pyridine-type N (N2) whose lone pair is delocalized into the ring
• Both nitrogens have non-delocalized lone pairs
• Neither nitrogen contributes to aromaticity

Correct Answer: The pyrrole-type N (N1) whose lone pair is delocalized into the ring

Q3. Pyrazole typically undergoes electrophilic substitution at which ring positions?

• C-3 and C-4
• C-4 and C-5
• C-2 and N-1
• N-1 and N-2

Correct Answer: C-4 and C-5

Q4. N‑alkylation of pyrazole preferentially occurs at which site in the presence of base?

• N1 (the pyrrole-type N)
• N2 (the pyridine-type N)
• C-4 carbon
• Both nitrogens equally

Correct Answer: N2 (the pyridine-type N)

Q5. Which reagent is commonly used for selective formylation of pyrazole at C-4?

• Vilsmeier–Haack reagent (POCl3/DMF)
• Nitrating mixture (HNO3/H2SO4)
• Boron tribromide (BBr3)
• Hydrazine hydrate

Correct Answer: Vilsmeier–Haack reagent (POCl3/DMF)

Q6. Which statement about pyrazole acidity/basicity is correct?

• Pyrazole is a stronger base than pyrrole
• Pyrazole is more acidic than typical aliphatic amines due to N‑H acidity
• Pyrazole has no acidic protons
• Pyrazole is as basic as pyridine

Correct Answer: Pyrazole is more acidic than typical aliphatic amines due to N‑H acidity

Q7. Which reagent is commonly used for bromination of pyrazole at the C‑4 position under mild conditions?

• N-bromosuccinimide (NBS)
• Hydrobromic acid (HBr)
• Phosphorus tribromide (PBr3)
• Sodium bromide in water

Correct Answer: N-bromosuccinimide (NBS)

Q8. In electrophilic aromatic substitution on N‑substituted pyrazoles, electron‑withdrawing N‑substituents cause what effect?

• Increase ring reactivity toward electrophiles
• Decrease ring reactivity and direct substitution to less activated positions
• No effect on reactivity
• Cause ring opening instead of substitution

Correct Answer: Decrease ring reactivity and direct substitution to less activated positions

Q9. Which method is most common for synthesizing pyrazoles from 1,3‑dicarbonyl compounds?

• Condensation with hydrazines (Knorr pyrazole synthesis)
• Diels–Alder cycloaddition
• Nitration then reduction cyclization
• Friedel–Crafts acylation

Correct Answer: Condensation with hydrazines (Knorr pyrazole synthesis)

Q10. Pyrazole N‑oxides are typically formed by oxidation with which oxidant?

• m-Chloroperbenzoic acid (m-CPBA)
• Sodium borohydride (NaBH4)
• Hydrogen gas with Pd/C
• Hydrochloric acid

Correct Answer: m-Chloroperbenzoic acid (m-CPBA)

Q11. Which position on the pyrazole ring is most nucleophilic in lithiation reactions using strong bases?

• C-4
• C-3
• N-1
• N-2

Correct Answer: C-4

Q12. Which cross‑coupling reaction is commonly used to install aryl groups on halogenated pyrazoles?

• Suzuki–Miyaura coupling
• Aldol condensation
• Wurtz coupling
• Beckmann rearrangement

Correct Answer: Suzuki–Miyaura coupling

Q13. Aminopyrazoles can be diazotized and transformed via Sandmeyer reactions; diazonium formation requires which reagent?

• Sodium nitrite (NaNO2) with HCl
• Sodium borohydride (NaBH4)
• Potassium permanganate (KMnO4)
• Calcium carbonate

Correct Answer: Sodium nitrite (NaNO2) with HCl

Q14. Which transformation converts N‑unsubstituted pyrazole to N‑alkyl pyrazole selectively?

• Treat pyrazole with an alkyl halide under base (Williamson-type N‑alkylation)
• Hydrogenation over Pd/C
• Oxidation with KMnO4
• Treat with acyl chloride only

Correct Answer: Treat pyrazole with an alkyl halide under base (Williamson-type N‑alkylation)

Q15. Which reagent set is suitable to achieve selective N‑acylation of pyrazole?

• Acid chloride with pyridine
• Strong acid only
• Hydrogen peroxide
• Lithium aluminum hydride

Correct Answer: Acid chloride with pyridine

Q16. Why is direct nitration of pyrazole challenging compared to benzene?

• Pyrazole ring is more electron rich and undergoes polymerization under nitration conditions
• Pyrazole is less aromatic than benzene making nitration faster
• Nitration is identical in difficulty to benzene
• Nitric acid reduces pyrazole rather than nitrating it

Correct Answer: Pyrazole ring is more electron rich and undergoes polymerization under nitration conditions

Q17. In metal‑catalyzed C–H functionalization of pyrazoles, a directing group often used is:

• N-oxide functionality
• Methyl group at C-4
• Nitrile at a distant position
• Free N–H with no directing effect

Correct Answer: N-oxide functionality

Q18. Which mechanism best describes the formation of pyrazoles via 1,3‑dipolar cycloaddition?

• Huisgen 1,3‑dipolar cycloaddition between diazo compounds and alkynes
• Free radical polymerization
• Concerted Diels–Alder between diene and dienophile
• Electrophilic aromatic substitution

Correct Answer: Huisgen 1,3‑dipolar cycloaddition between diazo compounds and alkynes

Q19. Which spectral change indicates N‑alkylation of pyrazole in 1H NMR?

• Disappearance of the NH singlet
• Appearance of a new aldehyde proton
• Large downfield shift of all aromatic protons by 5 ppm
• Complete loss of all signals

Correct Answer: Disappearance of the NH singlet

Q20. Which reagent is typically used to convert a pyrazole into its corresponding pyrazoline by hydrogenation?

• Hydrogen gas with Pd/C
• Potassium permanganate
• N-bromosuccinimide
• Acetic anhydride

Correct Answer: Hydrogen gas with Pd/C

Q21. Electrophilic substitution at C‑5 of pyrazole is favored when which substituent is at C‑3?

• An electron‑donating substituent at C-3
• A strong electron‑withdrawing substituent at C-3
• No substituent effect
• A bulky tert‑butyl group at N1

Correct Answer: An electron‑donating substituent at C-3

Q22. Which reagent can selectively deprotonate pyrazole N–H to allow subsequent N‑functionalization?

• Sodium hydride (NaH)
• Sodium chloride (NaCl)
• Acetic acid
• Water

Correct Answer: Sodium hydride (NaH)

Q23. Conversion of a halogenated pyrazole to the corresponding hydroxypyrazole is most commonly achieved by:

• Nucleophilic aromatic substitution with hydroxide under heating
• Reduction with LiAlH4
• Direct hydration with water at room temperature
• Photochemical rearrangement

Correct Answer: Nucleophilic aromatic substitution with hydroxide under heating

Q24. Which reagent is used for chlorination at activated C‑positions of pyrazole?

• N-chlorosuccinimide (NCS)
• Sodium chloride solid
• Hydrogen chloride gas alone
• Ammonium persulfate

Correct Answer: N-chlorosuccinimide (NCS)

Q25. In a protected N‑alkyl pyrazole, directed ortho‑metalation for C‑functionalization typically uses which base?

• Butyllithium (n-BuLi) or LDA
• Sodium bicarbonate
• Pyridine only
• Hydrochloric acid

Correct Answer: Butyllithium (n-BuLi) or LDA

Q26. Which process commonly cleaves pyrazole rings under strong oxidative conditions?

• Oxidative ring opening with strong oxidants like KMnO4
• Neutral hydrolysis with water
• Thermal isomerization only
• Photochemical dimerization

Correct Answer: Oxidative ring opening with strong oxidants like KMnO4

Q27. Which substituent pattern enhances the acidity of the pyrazole N‑H?

• Electron‑withdrawing groups on the ring (e.g., nitro)
• Electron‑donating groups (e.g., methoxy)
• Bulky alkyl groups at N
• No substituents

Correct Answer: Electron‑withdrawing groups on the ring (e.g., nitro)

Q28. Which reagent would you choose to reduce a pyrazole N‑oxide back to pyrazole?

• Phosphorus trichloride (PCl3) or PPh3
• m-CPBA
• Potassium permanganate
• Nitric acid

Correct Answer: Phosphorus trichloride (PCl3) or PPh3

Q29. Which reaction is commonly used to introduce alkynyl substituents onto a halopyrazole?

• Sonogashira coupling
• Aldol condensation
• Beckmann rearrangement
• Hydride reduction

Correct Answer: Sonogashira coupling

Q30. Which factor most strongly influences regioselectivity in electrophilic substitution of substituted pyrazoles?

• Electronic effects of existing substituents and N‑substitution
• Color of the reagent
• Presence of water only
• Ambient humidity

Correct Answer: Electronic effects of existing substituents and N‑substitution

Q31. What is the expected product when 3,5-dimethylpyrazole is treated with excess bromine under radical conditions?

• Bromination at methyl groups (benzylic-type bromination)
• Bromination at N1 exclusively
• Complete ring cleavage only
• No reaction occurs

Correct Answer: Bromination at methyl groups (benzylic-type bromination)

Q32. Formation of 1,3‑disubstituted pyrazoles via cyclocondensation typically requires which starting pair?

• Hydrazine derivative and a 1,3‑dicarbonyl compound
• Aniline and benzaldehyde
• Tertiary amine and alkyl halide
• Carboxylic acid and alcohol

Correct Answer: Hydrazine derivative and a 1,3‑dicarbonyl compound

Q33. Which pathway explains why pyrazole N‑protonation occurs at one nitrogen preferentially?

• Protonation occurs at the pyridine‑like N because its lone pair is not part of aromatic sextet
• Protonation is impossible on pyrazole
• Protonation always occurs at the pyrrole‑type N
• Both nitrogens are equally protonated simultaneously

Correct Answer: Protonation occurs at the pyridine‑like N because its lone pair is not part of aromatic sextet

Q34. How does N‑protection (e.g., N‑benzylation) influence C‑electrophilic substitutions on pyrazole?

• N‑protection often deactivates the ring toward electrophiles and alters regioselectivity
• N‑protection makes the ring infinitely more reactive without changing regioselectivity
• No effect on reactivity or regioselectivity
• Causes immediate ring opening

Correct Answer: N‑protection often deactivates the ring toward electrophiles and alters regioselectivity

Q35. Which reagent set is ideal for converting a pyrazole C–H into C–CN (cyanation) under cross‑coupling strategies?

• Halogenation to C–Br followed by Pd‑catalyzed cyanation (CuCN or K4[Fe(CN)6])
• Direct treatment with sodium cyanide without activation
• Oxidation with KMnO4 then addition of cyanide
• Hydrogenation with H2/Pd

Correct Answer: Halogenation to C–Br followed by Pd‑catalyzed cyanation (CuCN or K4[Fe(CN)6])

Q36. In medicinal chemistry, pyrazole functionalization to improve metabolic stability typically avoids modifications that:

• Increase electron density making sites prone to oxidation
• Reduce lipophilicity modestly
• Introduce polar groups to reduce clearance
• Block metabolically labile positions

Correct Answer: Increase electron density making sites prone to oxidation

Q37. Which reaction would convert a 3‑aminopyrazole to a 3‑hydroxy derivative via a diazonium intermediate?

• Diazotization followed by hydrolysis (thermal or aqueous workup)
• Direct oxidation with PCC
• Friedel–Crafts acylation
• Wittig reaction

Correct Answer: Diazotization followed by hydrolysis (thermal or aqueous workup)

Q38. Which reagent is suitable for selective C‑alkylation of a metallated pyrazole anion at C‑4?

• An alkyl halide (e.g., methyl iodide) reacting with the lithiated intermediate
• An acid chloride only
• Water
• Pyridine only

Correct Answer: An alkyl halide (e.g., methyl iodide) reacting with the lithiated intermediate

Q39. Which functional group on pyrazole is most prone to Phase I metabolic oxidation in vivo?

• Aliphatic N‑alkyl substituents
• Aromatic carbonyl directly on the ring
• Ring nitrogen atoms themselves are generally inert to oxidation
• Carboxylate formed on N

Correct Answer: Aliphatic N‑alkyl substituents

Q40. Which reagent pair can effect Vilsmeier formylation to introduce an aldehyde at C‑4 of pyrazole derivatives?

• DMF and POCl3
• H2O2 and AcOH
• LiAlH4 and THF
• Br2 and acetic acid

Correct Answer: DMF and POCl3

Q41. Which mechanism explains nucleophilic aromatic substitution (SNAr) on electron‑deficient halopyrazoles?

• Addition–elimination via a Meisenheimer‑type intermediate
• Pericyclic 6‑π electrocyclization
• Free radical chain propagation only
• Concerted [2+2] cycloaddition

Correct Answer: Addition–elimination via a Meisenheimer‑type intermediate

Q42. Which reagent is preferred for selective oxidation of a pyrazole‑bound methyl group to a carboxylic acid?

• Potassium permanganate (KMnO4) under strong oxidative conditions
• Sodium borohydride (NaBH4)
• Trimethylsilyl chloride (TMSCl)
• Diisobutylaluminium hydride (DIBAL‑H)

Correct Answer: Potassium permanganate (KMnO4) under strong oxidative conditions

Q43. During synthesis, protecting the pyrazole N–H as a benzyl (Bn) group is typically removed by which method?

• Hydrogenolysis (H2, Pd/C)
• Treatment with strong base only
• Treatment with NBS
• Oxidation with m-CPBA

Correct Answer: Hydrogenolysis (H2, Pd/C)

Q44. Which transformation converts a 4-bromopyrazole into a 4-arylpyrazole most efficiently?

• Palladium-catalyzed Suzuki coupling with an aryl boronic acid
• Direct electrophilic aromatic substitution with benzene
• Nucleophilic substitution with phenoxide under neutral conditions
• Photochemical radical dimerization

Correct Answer: Palladium-catalyzed Suzuki coupling with an aryl boronic acid

Q45. For regioselective C‑3 functionalization of pyrazole, which strategy is commonly used?

• Install a directing group or prefunctionalize neighboring positions then use metalation
• Use only HCl to catalyze direct substitution
• Heat with excess ethanol
• There is no way to selectively functionalize C-3

Correct Answer: Install a directing group or prefunctionalize neighboring positions then use metalation

Q46. Which reagent is effective for deprotecting an N‑tert‑butoxycarbonyl (Boc) protected pyrazole?

• TFA (trifluoroacetic acid)
• Sodium hydroxide at low temperature
• Sodium borohydride
• DMF alone

Correct Answer: TFA (trifluoroacetic acid)

Q47. Which transformation can convert a pyrazole into a fused bicyclic system used in many drug scaffolds?

• Intramolecular cyclization via functional group tethering (e.g., annulation)
• Simple dilution in water
• Exposure to sunlight only
• Neutral extraction with hexane

Correct Answer: Intramolecular cyclization via functional group tethering (e.g., annulation)

Q48. Which reaction is used to prepare 1,5‑disubstituted pyrazoles selectively?

• Condensation of hydrazones with alkynes via cycloaddition or metal‑catalyzed routes
• Direct nitration of unsubstituted pyrazole
• Oxidation with ozone only
• Hydrolysis with aqueous acid

Correct Answer: Condensation of hydrazones with alkynes via cycloaddition or metal‑catalyzed routes

Q49. Which factor is most important when choosing conditions for functionalizing a pyrazole in a drug molecule?

• Chemoselectivity to avoid modifying other sensitive functional groups
• Color of the solvent
• Room humidity exclusively
• Whether the flask is round‑bottomed

Correct Answer: Chemoselectivity to avoid modifying other sensitive functional groups

Q50. Which common medicinal chemistry modification on pyrazoles often improves metabolic stability and oral bioavailability?

• Introduction of small polar substituents to block metabolically labile positions and modulate lipophilicity
• Adding multiple long alkyl chains indiscriminately
• Removing all heteroatoms from the molecule
• Rapid heating without changing structure

Correct Answer: Introduction of small polar substituents to block metabolically labile positions and modulate lipophilicity

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