Heterocyclic Chemistry: Imidazole, pyrazole, pyrimidine syntheses MCQs With Answer

Heterocyclic Chemistry: Imidazole, pyrazole, pyrimidine syntheses MCQs With Answer

This quiz set focuses on core synthetic routes, mechanisms and properties of imidazoles, pyrazoles and pyrimidines tailored for M.Pharm MPC 102T Advanced Organic Chemistry I students. Questions cover classical named reactions (Debus–Radziszewski, Van Leusen, Biginelli, Hantzsch), common reagents (TosMIC, hydrazine, guanidine), regioselectivity, tautomerism, aromaticity and key transformation steps such as cyclocondensation and oxidative aromatization. Each MCQ reinforces understanding of practical laboratory procedures, mechanistic reasoning and structure–reactivity relationships relevant to medicinal chemistry. Use these to test recall, apply mechanisms to syntheses and prepare for exams and problem-solving in heterocyclic drug design.

Q1. Which set of reagents is classically used in the Debus–Radziszewski synthesis of imidazoles?

• Glyoxal, formaldehyde and ammonia
• Tosylmethyl isocyanide and imines
• 1,3-diketone and hydrazine
• β-Dicarbonyl and amidine

Correct Answer: Glyoxal, formaldehyde and ammonia

Q2. Tosylmethyl isocyanide (TosMIC) used in the Van Leusen reaction is most commonly applied to synthesize which heterocycle?

• Imidazoles
• Pyrazoles
• Pyrimidines
• Indoles

Correct Answer: Imidazoles

Q3. How many π-electrons contribute to the aromaticity of imidazole?

• 6 π-electrons
• 4 π-electrons
• 8 π-electrons
• 10 π-electrons

Correct Answer: 6 π-electrons

Q4. Compared to pyrrole, the N–H proton of imidazole is:

• More acidic due to stabilization of the conjugate base by the adjacent pyridine-type nitrogen
• Less acidic because imidazole is more aromatic
• About the same acidity as pyrrole
• Not acidic at all under normal conditions

Correct Answer: More acidic due to stabilization of the conjugate base by the adjacent pyridine-type nitrogen

Q5. Under basic N-alkylation conditions, which nitrogen atom in imidazole is preferentially alkylated?

• N1 (the pyrrole-type nitrogen bearing the hydrogen)
• N3 (the pyridine-type nitrogen)
• Both nitrogens are alkylated equally
• The C2 carbon is preferentially alkylated

Correct Answer: N1 (the pyrrole-type nitrogen bearing the hydrogen)

Q6. Which pair of starting materials typically undergoes cyclocondensation to give pyrazoles?

• 1,3-diketone and hydrazine hydrate
• α-Diketone, aldehyde and ammonia
• Glyoxal, formaldehyde and ammonia
• Tosylmethyl isocyanide and imine

Correct Answer: 1,3-diketone and hydrazine hydrate

Q7. In the 1,3-dipolar cycloaddition of diazo compounds to alkynes to form pyrazoles, the observed regioselectivity is mainly controlled by:

• The electronic nature (electron-withdrawing or -donating) of the alkyne substituents
• The polarity of the solvent only
• The reaction temperature only
• The type of atmosphere (air vs inert) only

Correct Answer: The electronic nature (electron-withdrawing or -donating) of the alkyne substituents

Q8. How many π-electrons are present in the aromatic pyrazole ring?

• 6 π-electrons
• 4 π-electrons
• 8 π-electrons
• 10 π-electrons

Correct Answer: 6 π-electrons

Q9. The Biginelli multicomponent reaction primarily yields which class of compounds?

• Dihydropyrimidinones (DHPMs)
• Pyrimidines
• Imidazoles
• Pyrazoles

Correct Answer: Dihydropyrimidinones (DHPMs)

Q10. A common practical route to substituted pyrimidines involves condensation of β-dicarbonyl compounds with which type of nitrogen nucleophile?

• Amidines
• Hydrazines
• Primary amines (simple alkyl amines)
• Isocyanides

Correct Answer: Amidines

Q11. Condensation of β-diketones with guanidine typically yields which product class?

• 2-Aminopyrimidines
• Imidazoles
• Pyrazoles
• Pyrroles

Correct Answer: 2-Aminopyrimidines

Q12. In the Debus–Radziszewski synthesis mechanism, the initial interaction of glyoxal with ammonia leads to formation of:

• A diimine intermediate
• A diazo compound
• An enamine intermediate
• An aziridine intermediate

Correct Answer: A diimine intermediate

Q13. Conversion of non-aromatic pyrazoline intermediates into aromatic pyrazoles generally requires oxidation. Which oxidant is commonly used for this dehydrogenation?

• DDQ (2,3-dichloro-5,6-dicyano-p-benzoquinone)
• Sodium borohydride
• Tetramethylsilane
• Hydrochloric acid

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

Q14. Pyrazole exists in which tautomeric forms that are relevant to reactivity and N-substitution?

• 1H-pyrazole and 2H-pyrazole
• 1,3-pyrazole and 1,5-pyrazole
• Keto and enol pyrazole tautomers
• No tautomerism is possible for pyrazole

Correct Answer: 1H-pyrazole and 2H-pyrazole

Q15. The approximate aqueous pKa of the imidazolium ion (conjugate acid of imidazole) is:

• ~7.0
• ~3.0
• ~14.0
• ~25.0

Correct Answer: ~7.0

Q16. The Radziszewski modification of imidazole synthesis replaces glyoxal with which type of starting carbonyl compound to allow greater substitution patterns?

• α-Diketone (α-dicarbonyl)
• Tosylmethyl isocyanide
• Hydrazine hydrate
• Amidine

Correct Answer: α-Diketone (α-dicarbonyl)

Q17. Which named reaction is used to prepare dihydropyridines rather than dihydropyrimidines?

• Hantzsch reaction
• Biginelli reaction
• Debus–Radziszewski synthesis
• Van Leusen reaction

Correct Answer: Hantzsch reaction

Q18. Tosylmethyl isocyanide (TosMIC) contains which two functional fragments that make it a versatile one-carbon synthon?

• A tosyl (p-toluenesulfonyl) group and an isocyanide group
• An acyl chloride and a nitrile group
• A nitro group and an isocyanate
• A sulfone and an azide group

Correct Answer: A tosyl (p-toluenesulfonyl) group and an isocyanide group

Q19. Which heterocycle is more basic in aqueous medium: imidazole or pyridine?

• Imidazole is more basic than pyridine
• Pyridine is more basic than imidazole
• They have identical basicity
• Neither shows basicity in water

Correct Answer: Imidazole is more basic than pyridine

Q20. Which heterocyclic ring is found in the side chain of the amino acid histidine and is important in enzyme active sites?

• Imidazole
• Pyrazole
• Pyrimidine
• Pyrrole

Correct Answer: Imidazole

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