Synthesis of imidazole MCQs With Answer

Synthesis of imidazole MCQs With Answer

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Imidazole synthesis is a core topic in medicinal and heterocyclic chemistry for B. Pharm students, covering methods to build the five-membered N,N-heterocycle found in many drugs. This introduction reviews key synthetic routes — Debus–Radziszewski cyclocondensation, Van Leusen TosMIC procedures, cyclization of 1,2-dicarbonyls with ammonia/amines, and modern microwave- and solvent-free approaches — plus mechanistic steps, regiochemical control, catalysts, and oxidation requirements. Understanding reagent selection, reaction intermediates, substitution patterns on C2/C4/C5, practical conditions and spectral identification helps students design and optimize imidazole derivatives in medicinal chemistry and drug discovery. These MCQs focus on mechanisms, reagents, spectral identification, laboratory techniques and exam-style problem solving. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which classic method uses a 1,2-dicarbonyl compound, an aldehyde and ammonia to synthesize substituted imidazoles?

  • Debus–Radziszewski synthesis
  • Fischer indole synthesis
  • Skraup synthesis
  • Pictet–Spengler reaction

Correct Answer: Debus–Radziszewski synthesis

Q2. In the Debus–Radziszewski mechanism, what is the key intermediate formed before cyclization?

  • Aziridine
  • Diimine (or diimine-like) intermediate
  • Nitrene
  • Oxazoline

Correct Answer: Diimine (or diimine-like) intermediate

Q3. Which reagent is commonly used as the amino source in many imidazole syntheses?

  • Ammonium acetate
  • Potassium permanganate
  • N-Bromosuccinimide
  • Sodium borohydride

Correct Answer: Ammonium acetate

Q4. The Van Leusen imidazole synthesis prominently employs which reagent?

  • TosMIC (p-toluenesulfonylmethyl isocyanide)
  • Methyl iodide
  • Phenylhydrazine
  • Phosphorus oxychloride

Correct Answer: TosMIC (p-toluenesulfonylmethyl isocyanide)

Q5. Which position on the imidazole ring is flanked by both nitrogen atoms (the carbon between N1 and N3)?

  • C2
  • C3
  • C4
  • C5

Correct Answer: C2

Q6. Which nitrogen in imidazole is primarily responsible for basicity (pyridine-like lone pair)?

  • The pyridine-like nitrogen (N3)
  • The pyrrole-like nitrogen (N1)
  • Both nitrogens equally
  • Neither nitrogen is basic

Correct Answer: The pyridine-like nitrogen (N3)

Q7. Which step often follows cyclization to give aromatic imidazole in Debus–Radziszewski reactions?

  • Oxidation to aromatize the ring
  • Hydrogenation to saturate the ring
  • Halogenation at C2
  • Reduction of carbonyls

Correct Answer: Oxidation to aromatize the ring

Q8. A common method to prepare 2,4,5-trisubstituted imidazoles involves which starting materials?

  • 1,2-dicarbonyl compound, aldehyde, and ammonia
  • Alkyne, azide, and copper catalyst
  • Arene, nitro compound and reducing agent
  • Epoxide and Grignard reagent

Correct Answer: 1,2-dicarbonyl compound, aldehyde, and ammonia

Q9. Which condition can accelerate imidazole formation in modern laboratory practice?

  • Microwave irradiation
  • Ultra-low temperature (-78 °C)
  • Photochemical UV at 254 nm only
  • Complete absence of solvent only

Correct Answer: Microwave irradiation

Q10. In Van Leusen chemistry, TosMIC reacts with imines to form imidazoles. What is TosMIC supplying to the ring?

  • An isocyanide-derived carbon and nitrogen unit
  • A nitrene fragment
  • An acyl radical
  • A diazonium group

Correct Answer: An isocyanide-derived carbon and nitrogen unit

Q11. Which reagent pair is typical for the formation of an imine intermediate in imidazole syntheses?

  • Aldehyde and ammonia (or primary amine)
  • Carboxylic acid and alcohol
  • Alkene and hydrogen peroxide
  • Ketone and Grignard reagent

Correct Answer: Aldehyde and ammonia (or primary amine)

Q12. For regioselectivity in substituted imidazoles, substitution at C2 is most influenced by which component?

  • The 1,2-dicarbonyl component
  • The solvent identity only
  • The counterion of the base only
  • Atmospheric oxygen concentration

Correct Answer: The 1,2-dicarbonyl component

Q13. What is a green chemistry modification often used to synthesize imidazoles?

  • Solvent-free grinding or mechanochemistry
  • Using mercury as a catalyst
  • Heating with chlorinated solvents
  • Excess toxic heavy metals

Correct Answer: Solvent-free grinding or mechanochemistry

Q14. Which spectroscopic signal is characteristic for an imidazole NH (when present) in 1H NMR?

  • A downfield singlet around 10–14 ppm (exchangeable)
  • A sharp upfield singlet at 0–1 ppm
  • A multiplet at 2–3 ppm
  • No signal because NH is invisible

Correct Answer: A downfield singlet around 10–14 ppm (exchangeable)

Q15. Which oxidant can be used to aromatize non-aromatic cyclized intermediates to imidazole?

  • DDQ or air (molecular oxygen)
  • Sodium borohydride
  • Triphenylphosphine
  • Hydrazine

Correct Answer: DDQ or air (molecular oxygen)

Q16. The formation of imidazolium salts is commonly achieved by which transformation?

  • N-alkylation of imidazole with an alkyl halide
  • Reduction of imidazole with LiAlH4
  • Oxidative cleavage of the ring
  • Photochemical dimerization

Correct Answer: N-alkylation of imidazole with an alkyl halide

Q17. In designing imidazole-based drug candidates, which positions are often modified for tuning activity?

  • C2, C4 and C5 substituents
  • Only the N–H bond
  • Only ring fusion at C6
  • Only replacing nitrogen with oxygen

Correct Answer: C2, C4 and C5 substituents

Q18. Which solvent type is commonly avoided for Debus–Radziszewski reactions to prevent side reactions?

  • Strongly nucleophilic protic solvents that react with intermediates
  • Moderately polar aprotic solvents
  • Water when using ammonium acetate
  • Ethanol under controlled conditions

Correct Answer: Strongly nucleophilic protic solvents that react with intermediates

Q19. Which analytical technique confirms the formation of the imidazole ring by observing characteristic C–N and C=C stretches?

  • IR spectroscopy
  • Gas chromatography only
  • Polarimetry
  • Viscometry

Correct Answer: IR spectroscopy

Q20. A common laboratory protocol for imidazole synthesis uses heating with ammonium acetate. What role does ammonium acetate play?

  • Source of ammonia (NH2) for condensation
  • Oxidizing agent
  • Nucleophilic catalysis by acetate only
  • Provides heavy metal catalysis

Correct Answer: Source of ammonia (NH2) for condensation

Q21. Which of the following is an advantage of microwave-assisted imidazole synthesis?

  • Shorter reaction times and often higher yields
  • Complete elimination of the need for reagents
  • Guaranteed regioselectivity without design
  • No need for workup or purification

Correct Answer: Shorter reaction times and often higher yields

Q22. In Van Leusen imidazole synthesis, what is the typical immediate precursor that reacts with TosMIC?

  • An imine (from aldehyde and amine)
  • An epoxide
  • An alkene
  • A carboxylic acid

Correct Answer: An imine (from aldehyde and amine)

Q23. What is the typical outcome when using aromatic aldehydes in Debus–Radziszewski condensations?

  • Formation of aryl-substituted imidazoles at C4/C5 positions
  • Cleavage of the imidazole ring
  • Exclusive formation of pyrroles
  • No reaction occurs

Correct Answer: Formation of aryl-substituted imidazoles at C4/C5 positions

Q24. Which functional group on the 1,2-dicarbonyl component most directly determines substituent at C2?

  • The substituent on the carbonyl carbon adjacent to the condensation site
  • The ester group far from the reaction center
  • A remote alkyl chain length only
  • The presence of a terminal alkyne only

Correct Answer: The substituent on the carbonyl carbon adjacent to the condensation site

Q25. Which safety consideration is important when handling TosMIC in the Van Leusen reaction?

  • Work in a fume hood; TosMIC can be irritating and isocyanide-derived reagents can have odors
  • It is completely inert and requires no precautions
  • It is pyrophoric in air
  • It reacts violently with water to explode

Correct Answer: Work in a fume hood; TosMIC can be irritating and isocyanide-derived reagents can have odors

Q26. Which catalytic strategy can improve yields and selectivity in modern imidazole syntheses?

  • Use of Lewis acids or acid catalysts to activate carbonyls
  • Complete absence of catalyst always
  • Use of large excess of mercury salts
  • High concentration of elemental sulfur

Correct Answer: Use of Lewis acids or acid catalysts to activate carbonyls

Q27. Which reaction type best describes many imidazole syntheses like Debus–Radziszewski?

  • Cyclocondensation
  • Pericyclic [4+2] cycloaddition
  • Radical polymerization
  • SN2 nucleophilic substitution

Correct Answer: Cyclocondensation

Q28. For spectroscopic confirmation of imidazole, which NMR nucleus is especially informative about substitution pattern?

  • 13C NMR showing signals for C2, C4, and C5 carbons
  • Deuterium NMR only
  • 31P NMR
  • 19F NMR if no fluorine is present

Correct Answer: 13C NMR showing signals for C2, C4, and C5 carbons

Q29. Which transformation converts imidazole to an imidazolium salt?

  • Alkylation at the ring nitrogen (N-alkylation)
  • Hydrogenolysis of the ring
  • Oxidative deamination
  • Acid-catalyzed ring opening

Correct Answer: Alkylation at the ring nitrogen (N-alkylation)

Q30. Which substituent pattern is commonly obtained from using formaldehyde as the aldehyde component in Debus–Radziszewski reactions?

  • Simple hydrogen or unsubstituted position at C4/C5 depending on stoichiometry
  • Large aryl substituents at every position
  • Exclusive formation of fused bicyclic rings
  • Insertion of a nitro group at C2

Correct Answer: Simple hydrogen or unsubstituted position at C4/C5 depending on stoichiometry

Q31. Which one of these is a modern technique to perform imidazole synthesis with reduced solvent use?

  • Ball-milling mechanochemistry
  • Reflux in large volumes of chlorinated solvent
  • Using benzene under pressure
  • Extended cryogenic stirring

Correct Answer: Ball-milling mechanochemistry

Q32. The presence of electron-withdrawing groups on an aldehyde generally leads to what effect in condensation reactions forming imidazoles?

  • Increased electrophilicity and often faster condensation
  • Complete inhibition of any reaction
  • Guaranteed formation of isoxazoles instead
  • No change at all in reactivity

Correct Answer: Increased electrophilicity and often faster condensation

Q33. Which of the following is a limitation of the Debus–Radziszewski method?

  • Limited control over regioselectivity with unsymmetrical 1,2-dicarbonyls
  • It requires precious metal catalysts exclusively
  • It only makes six-membered rings
  • It cannot be used with aldehydes

Correct Answer: Limited control over regioselectivity with unsymmetrical 1,2-dicarbonyls

Q34. Which reagent can act both as a solvent and ammonia source in some imidazole syntheses?

  • Ammonium acetate
  • Hydrochloric acid
  • Sodium hydroxide
  • Dimethyl sulfoxide only

Correct Answer: Ammonium acetate

Q35. Which property of imidazole makes it useful as a ligand in coordination chemistry?

  • The pyridine-like nitrogen lone pair can coordinate to metals
  • Its extreme hydrophobicity
  • Its inability to donate electrons
  • Its permanently positively charged nature

Correct Answer: The pyridine-like nitrogen lone pair can coordinate to metals

Q36. What is an expected by-product if aldehydes are oxidized during imidazole synthesis in air?

  • Carboxylic acids
  • Alkanes
  • Alkenes
  • Epoxides

Correct Answer: Carboxylic acids

Q37. Which base is commonly used in Van Leusen reactions to deprotonate TosMIC?

  • Triethylamine or other tertiary amine bases
  • Hydrochloric acid
  • Silver nitrate
  • Mercury(II) chloride

Correct Answer: Triethylamine or other tertiary amine bases

Q38. To install a substituent specifically at C2 of imidazole, which approach is typically used?

  • Choose a 1,2-dicarbonyl with the desired substituent at the corresponding carbon
  • Only change the solvent polarity
  • Use N-oxidation to force substitution
  • Perform radical halogenation of the ring

Correct Answer: Choose a 1,2-dicarbonyl with the desired substituent at the corresponding carbon

Q39. What advantage does using ammonium salts (like ammonium acetate) offer over gaseous ammonia?

  • Safer, easier handling and controlled release of ammonia in solution
  • It provides strong oxidizing power
  • It ensures complete dryness of the reaction
  • It reduces boiling point dramatically

Correct Answer: Safer, easier handling and controlled release of ammonia in solution

Q40. Which statement about the acidity/basicity of imidazole is correct?

  • Imidazole is amphoteric with a relatively acidic N–H and a basic nitrogen lone pair
  • Imidazole is a strong base like alkylamines
  • Imidazole has no acidic or basic character
  • Imidazole is a strong oxidizing agent

Correct Answer: Imidazole is amphoteric with a relatively acidic N–H and a basic nitrogen lone pair

Q41. Which synthetic modification can increase water solubility of imidazole derivatives for drug design?

  • Introduce polar or ionizable groups (e.g., carboxylate, amino)
  • Add long hydrophobic alkyl chains only
  • Convert imidazole to pure hydrocarbon
  • Remove all heteroatoms from the molecule

Correct Answer: Introduce polar or ionizable groups (e.g., carboxylate, amino)

Q42. In an exam question asking for a mechanism of Debus–Radziszewski synthesis, which step should students emphasize?

  • Formation of diimine followed by cyclization and oxidation to aromatize
  • Diels–Alder cycloaddition between two alkenes
  • SN1 substitution at an sp2 carbon
  • Radical chain polymerization

Correct Answer: Formation of diimine followed by cyclization and oxidation to aromatize

Q43. Which reagent combination is unlikely to produce imidazoles?

  • Tertiary alcohol, inert gas and silica gel
  • 1,2-dicarbonyl, aldehyde, and ammonia
  • Aldehyde, amine to form imine, then TosMIC
  • Alpha-haloketone and amidine derivatives under cyclization

Correct Answer: Tertiary alcohol, inert gas and silica gel

Q44. Which of the following is a useful protecting group strategy when N-functionality must be retained during synthesis?

  • N-acylation followed by later deprotection
  • Permanent removal of nitrogen atom
  • Nitration at the imidazole ring
  • Complete oxidation to imidazolium then discard

Correct Answer: N-acylation followed by later deprotection

Q45. Which method is suitable to synthesize fused imidazole-containing heterocycles?

  • Use of appropriately substituted precursors that undergo intramolecular cyclization
  • Simple mixing of imidazole with saltwater
  • Photolysis of benzene in absence of reagents
  • Heating pure elemental carbon

Correct Answer: Use of appropriately substituted precursors that undergo intramolecular cyclization

Q46. Which of the following is most helpful to confirm substitution pattern at C4 and C5 by NMR?

  • Analysis of proton coupling patterns and carbon chemical shifts in 1H and 13C NMR
  • Only melting point measurement
  • Thin-layer chromatography Rf alone
  • Color change on exposure to UV light only

Correct Answer: Analysis of proton coupling patterns and carbon chemical shifts in 1H and 13C NMR

Q47. In a lab, formation of a precipitate after reaction workup in imidazole synthesis most likely indicates:

  • Product or salt formation that may require filtration and purification
  • Complete failure of the reaction always
  • Immediate decomposition to gases
  • Formation of explosives

Correct Answer: Product or salt formation that may require filtration and purification

Q48. Which synthetic route is suitable for preparing 2-substituted imidazoles from alfa-haloketones?

  • Cyclization of alpha-haloketones with amidines or guanidine derivatives
  • Diels–Alder reaction of dienes exclusively
  • Fischer esterification of alcohols
  • Hydroboration–oxidation of alkenes

Correct Answer: Cyclization of alpha-haloketones with amidines or guanidine derivatives

Q49. Which parameter should be optimized when scaling up an imidazole synthesis for pilot production?

  • Reaction temperature, solvent choice, and reagent stoichiometry
  • Only the color of the reaction flask
  • Using ten times the catalyst without testing
  • Avoiding any workup or purification steps

Correct Answer: Reaction temperature, solvent choice, and reagent stoichiometry

Q50. For exam-style problems, which concept is important to predict the major imidazole product?

  • Understanding condensation partners, regiochemistry and mechanism (diimine formation and cyclization)
  • Assuming products are always symmetrical
  • Believing that substitution pattern is random
  • Ignoring the identity of starting carbonyl compounds

Correct Answer: Understanding condensation partners, regiochemistry and mechanism (diimine formation and cyclization)

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