Named Reactions: Sandmeyer reaction and applications MCQs With Answer

This blog presents a focused question bank on the Sandmeyer reaction and its applications tailored for M.Pharm students studying MPC 102T Advanced Organic Chemistry I. You will find a concise introduction to the practical utility of converting aryl amines into aryl halides, nitriles, phenols and other derivatives via diazonium chemistry, followed by 20 carefully designed MCQs that probe mechanism, reagents, conditions, limitations and pharmaceutical relevance. These questions emphasize mechanistic insight (SET and aryl radicals), reagent selection (Cu(I) salts, CuCN, NaNO2/HCl), and practical considerations (temperature, side reactions, stability). Use this to test and deepen your understanding of diazonium-based transformations commonly used in drug synthesis.

Q1. What is the fundamental transformation effected by the Sandmeyer reaction?

• Conversion of an aromatic primary amine to an aromatic halide or nitrile via a diazonium intermediate using copper salts
• Oxidation of secondary alcohols to ketones using copper catalysts
• Reduction of nitroarenes to anilines using sodium dithionite
• Direct coupling of two arenes to form biaryls under palladium catalysis

Correct Answer: Conversion of an aromatic primary amine to an aromatic halide or nitrile via a diazonium intermediate using copper salts

Q2. Which reagents and temperature are typically used to generate an arenediazonium salt from a primary aromatic amine?

• NaNO2 and HCl at 0–5 °C
• NaBH4 and methanol at room temperature
• K2Cr2O7 and H2SO4 at 60–80 °C
• H2/Pd-C at ambient temperature

Correct Answer: NaNO2 and HCl at 0–5 °C

Q3. Which reagent is most commonly employed in the Sandmeyer protocol to introduce a cyano group (–CN) into an aryl ring?

• CuCN
• CuCl
• NaCN without copper
• H3PO2

Correct Answer: CuCN

Q4. What is the generally accepted mechanistic pathway for the Sandmeyer replacement of diazonium with halide or cyano?

• Single-electron transfer (SET) from Cu(I) to the diazonium to form an aryl radical which then gives the substituted arene
• Concerted nucleophilic aromatic substitution at the diazonium carbon
• Electrophilic aromatic substitution where the diazonium is the electrophile
• SN2 displacement at a sp2-hybridized carbon by halide ion

Correct Answer: Single-electron transfer (SET) from Cu(I) to the diazonium to form an aryl radical which then gives the substituted arene

Q5. Which copper salt is typically used in the Sandmeyer reaction to introduce a bromine atom on an aryl ring?

• CuBr
• CuSO4
• CuO
• Cu(acac)2

Correct Answer: CuBr

Q6. Which method is most reliable for preparing aryl fluorides from anilines (i.e., a common alternative to Sandmeyer for fluorination)?

• Balz–Schiemann reaction via arenediazonium tetrafluoroborate and thermal decomposition
• CuF-catalyzed Sandmeyer directly with NaNO2/HCl at 0 °C
• Direct nucleophilic aromatic substitution using KF on an aniline
• Electrophilic fluorination of the aniline with F2

Correct Answer: Balz–Schiemann reaction via arenediazonium tetrafluoroborate and thermal decomposition

Q7. In aqueous Sandmeyer-type conditions a common side product is an aryl alcohol (phenol). What process leads to this side product?

• Hydrolysis of the diazonium salt by water (nucleophilic attack leading to phenol formation)
• Oxidation of the aryl halide to phenol by copper(II)
• Direct nucleophilic aromatic substitution on the aniline prior to diazotization
• Radical dimerization of the diazonium salt to give diaryl ethers

Correct Answer: Hydrolysis of the diazonium salt by water (nucleophilic attack leading to phenol formation)

Q8. Why is diazotization normally carried out at 0–5 °C?

• To stabilize the arenediazonium salt and minimize its thermal decomposition and side reactions
• To keep the nitrite reagent solid for better mixing
• To prevent copper salts from oxidizing under warm conditions
• To ensure formation of azo dyes rather than diazonium salts

Correct Answer: To stabilize the arenediazonium salt and minimize its thermal decomposition and side reactions

Q9. Which para-substituted aniline would typically give the most stable diazonium salt?

• p-Nitroaniline (strong electron-withdrawing group)
• p-Methoxyaniline (strong electron-donating group)
• p-Alkyl aniline (weakly electron-donating)
• p-Aminoaniline (another electron-donating amino group)

Correct Answer: p-Nitroaniline (strong electron-withdrawing group)

Q10. To synthesize benzonitrile from aniline in a Sandmeyer sequence, which sequence of reagents is correct?

• NaNO2/HCl (0–5 °C) to form the diazonium, then CuCN
• HNO3/H2SO4 to nitrate, then NaCN
• SOCl2 to form acyl chloride, then NaCN
• Diazotization followed by addition of NaBH4

Correct Answer: NaNO2/HCl (0–5 °C) to form the diazonium, then CuCN

Q11. Which reagent is commonly used to reduce an arenediazonium salt to the parent arene (Ar–H)?

• Hypophosphorous acid (H3PO2)
• CuCl
• NaNO2
• HCl alone at 0 °C

Correct Answer: Hypophosphorous acid (H3PO2)

Q12. In the Sandmeyer reaction, what precise role does Cu(I) typically play?

• Acts as a single-electron transfer (SET) reagent/catalyst and can form transient aryl–Cu intermediates that deliver the substituent
• Serves only as a spectator ion with no redox involvement
• Protonates the diazonium to make it more electrophilic
• Directly supplies halide by nucleophilic substitution without redox changes

Correct Answer: Acts as a single-electron transfer (SET) reagent/catalyst and can form transient aryl–Cu intermediates that deliver the substituent

Q13. Which reagent or condition is commonly used to introduce an iodine atom into an aryl ring from its diazonium salt?

• KI (iodide ion) often in the presence or absence of Cu(I)
• CuF2
• HBF4 to form tetrafluoroborate then heat
• NaCl with stoichiometric copper(II)

Correct Answer: KI (iodide ion) often in the presence or absence of Cu(I)

Q14. Which statement best describes the fate of the diazonium group in the Sandmeyer mechanism?

• The diazonium unit is reduced or undergoes SET to eject N2, forming an aryl radical that is trapped to give the substituted arene
• The diazonium is directly substituted via SN1 displacement by halide to give the product
• The diazonium is converted into a stronger electrophile that undergoes Friedel–Crafts acylation
• The diazonium coordinates to copper and remains intact in the final product

Correct Answer: The diazonium unit is reduced or undergoes SET to eject N2, forming an aryl radical that is trapped to give the substituted arene

Q15. Which named reaction is most appropriate when the objective is conversion of an aniline into an aryl fluoride?

• Balz–Schiemann reaction (diazonium tetrafluoroborate decomposition)
• Standard Sandmeyer with CuF
• Buchwald–Hartwig amination
• Sandmeyer with CuCN

Correct Answer: Balz–Schiemann reaction (diazonium tetrafluoroborate decomposition)

Q16. What is the primary function of the strong acid (e.g., HCl) during the formation of diazonium salts from anilines?

• To generate nitrosonium ion (NO+) from nitrite which nitrosates the aniline
• To reduce the aniline to the corresponding hydrazine
• To protect the amine as its ammonium salt so it cannot react
• To precipitate copper salts from solution

Correct Answer: To generate nitrosonium ion (NO+) from nitrite which nitrosates the aniline

Q17. Which starting functional group is essential for initiating a Sandmeyer transformation?

• Aromatic primary amine (aniline)
• Aryl alcohol
• Aryl halide
• Nitrile

Correct Answer: Aromatic primary amine (aniline)

Q18. Which characteristic behavior is typical of arenediazonium salts upon thermal or photochemical decomposition?

• Loss of nitrogen gas (N2) to form highly reactive aryl radicals or cationic species
• Formation of stable azo compounds without gas evolution
• Reduction to primary alcohols with H2 evolution
• Polymerization to give insoluble resinous materials

Correct Answer: Loss of nitrogen gas (N2) to form highly reactive aryl radicals or cationic species

Q19. Which reagent/condition normally converts an arenediazonium salt into the corresponding phenol?

• Warm water (hydrolysis of the diazonium salt)
• CuBr under anhydrous conditions
• CuCN in DMF
• H3PO2 at 0 °C

Correct Answer: Warm water (hydrolysis of the diazonium salt)

Q20. What is a major advantage of employing Sandmeyer-type diazonium chemistry in medicinal chemistry syntheses?

• It allows selective conversion of an aromatic amino group into diverse functionalities (halide, CN, OH, H) under relatively mild conditions while retaining the aromatic framework
• It selectively hydrogenates aromatic rings to cyclohexanes without affecting other groups
• It introduces alkyl side chains via Friedel–Crafts alkylation on anilines
• It directly couples amino acids to aromatic rings under basic conditions

Correct Answer: It allows selective conversion of an aromatic amino group into diverse functionalities (halide, CN, OH, H) under relatively mild conditions while retaining the aromatic framework

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