Named Reactions: Doebner-Miller reaction MCQs With Answer

Named Reactions: Doebner-Miller reaction MCQs With Answer

This short quiz set is designed for M.Pharm students preparing for MPC 102T Advanced Organic Chemistry I. The Doebner–Miller reaction is an important method for constructing quinoline frameworks by condensing anilines with α,β‑unsaturated carbonyl compounds under acidic conditions followed by cyclization and oxidation. These MCQs focus on mechanism steps (Michael addition, cyclization, dehydrogenation), reagents, catalysts, scope, limitations and comparisons with other quinoline syntheses. Questions emphasize conceptual understanding, typical conditions and practical considerations relevant to medicinal chemistry and pharmaceutical synthesis. Use these items to test recall and deepen comprehension of how the Doebner–Miller reaction is applied in drug‑like heterocycle construction.

Q1. What is the classical definition of the Doebner–Miller reaction?

• Condensation of aniline derivatives with α,β‑unsaturated carbonyl compounds to form quinolines after cyclization and oxidation
• Oxidation of anilines to nitroarenes using peracids
• Cycloaddition between dienes and anilines to afford indoles
• Hydrogenation of quinolines to tetrahydroquinolines

Correct Answer: Condensation of aniline derivatives with α,β‑unsaturated carbonyl compounds to form quinolines after cyclization and oxidation

Q2. What is the initial elementary step in the Doebner–Miller mechanism?

• Electrophilic aromatic substitution of aniline by the enone
• 1,4‑Michael (conjugate) addition of aniline to the α,β‑unsaturated carbonyl compound
• Direct nucleophilic acyl substitution at the carbonyl carbon
• Radical addition of aniline to the double bond

Correct Answer: 1,4‑Michael (conjugate) addition of aniline to the α,β‑unsaturated carbonyl compound

Q3. Which intermediate is typically formed immediately after the Michael addition in the Doebner–Miller sequence?

• β‑Amino carbonyl compound (β‑amino ketone or β‑amino ester)
• Isocyanate intermediate
• Quinoline directly without any intermediate
• Azoxy compound

Correct Answer: β‑Amino carbonyl compound (β‑amino ketone or β‑amino ester)

Q4. The cyclization step that leads towards the dihydroquinoline skeleton in the Doebner–Miller reaction most closely resembles which type of reaction?

• Intramolecular electrophilic aromatic substitution / Friedel–Crafts‑type cyclization
• Pericyclic [4+2] cycloaddition
• Nucleophilic acyl substitution on the aromatic ring
• Radical cyclization mediated by tin hydride

Correct Answer: Intramolecular electrophilic aromatic substitution / Friedel–Crafts‑type cyclization

Q5. Which step is required to convert the dihydroquinoline intermediate into an aromatic quinoline product?

• Oxidation / dehydrogenation to aromatize the heterocycle
• Hydrogenation to saturate the ring
• Reduction of the carbonyl to an alcohol
• Carbene insertion into the C–H bond

Correct Answer: Oxidation / dehydrogenation to aromatize the heterocycle

Q6. Which class of reagents is commonly used as the oxidant in Doebner–Miller transformations to effect aromatization?

• Dehydrogenating oxidants such as MnO2, DDQ or molecular oxygen (air)
• Strong hydride donors such as NaBH4
• Organolithium reagents
• Phase transfer catalysts exclusively

Correct Answer: Dehydrogenating oxidants such as MnO2, DDQ or molecular oxygen (air)

Q7. What role does an acid catalyst play in the Doebner–Miller reaction?

• Protonates intermediates to facilitate cyclization and stabilize iminium‑type species
• Inhibits the reaction by deactivating aniline
• Serves solely as a radical initiator
• Removes water by forming a stable salt that stops the reaction

Correct Answer: Protonates intermediates to facilitate cyclization and stabilize iminium‑type species

Q8. Which of the following is a typical solvent/medium for doing a Doebner–Miller reaction?

• Acidic medium such as glacial acetic acid or refluxing acetic acid with acid catalyst
• Strongly basic aqueous sodium hydroxide at room temperature
• Cryogenic inert solvents like liquid nitrogen
• Pure hexane with no catalyst

Correct Answer: Acidic medium such as glacial acetic acid or refluxing acetic acid with acid catalyst

Q9. Which class of amines is required for a successful Doebner–Miller reaction?

• Primary aromatic amines (anilines)
• Secondary aliphatic amines only
• Tertiary amines lacking an N–H hydrogen
• Ammonia exclusively

Correct Answer: Primary aromatic amines (anilines)

Q10. How do electron‑donating substituents on the aniline ring affect the Doebner–Miller reaction?

• They generally accelerate Michael addition and cyclization, improving yields
• They always prevent cyclization entirely
• They render the aniline inert to Michael addition
• They cause exclusive formation of indoles instead of quinolines

Correct Answer: They generally accelerate Michael addition and cyclization, improving yields

Q11. Which of the following substrates is least likely to give a good yield in the Doebner–Miller reaction?

• An aniline bearing strong electron‑withdrawing groups (e.g., nitro) at positions that deactivate the ring
• Aniline with para‑methoxy substituent
• An α,β‑unsaturated ketone with conjugated aromatic substituents
• An aniline with a moderate electron‑donating methyl substituent

Correct Answer: An aniline bearing strong electron‑withdrawing groups (e.g., nitro) at positions that deactivate the ring

Q12. Which related quinoline synthesis uses 2‑aminobenzaldehyde (or ortho‑aminoaryl carbonyl compounds) rather than aniline and enone and is therefore distinguished from Doebner–Miller?

• Friedländer synthesis
• Skraup synthesis
• Beckmann rearrangement
• Pictet–Spengler reaction

Correct Answer: Friedländer synthesis

Q13. In a Doebner–Miller reaction using an unsymmetrical enone, what is a principal regioselectivity consideration?

• The site of initial conjugate addition (β‑carbon) and subsequent orientation determines substitution pattern at positions 2 and 3 of quinoline
• Only the carbonyl carbon ever participates in bond formation
• Regioselectivity is irrelevant because the product is always symmetrical
• The reaction always yields a mixture of indole isomers instead

Correct Answer: The site of initial conjugate addition (β‑carbon) and subsequent orientation determines substitution pattern at positions 2 and 3 of quinoline

Q14. Why are secondary aromatic amines (N‑alkyl anilines) generally poor substrates for the Doebner–Miller reaction?

• They lack the free N–H required to form iminium‑type intermediates and facilitate cyclization
• They are too nucleophilic and give complex polymers exclusively
• They react too rapidly to control the product distribution
• They form stable salts that precipitate and stop the reaction

Correct Answer: They lack the free N–H required to form iminium‑type intermediates and facilitate cyclization

Q15. Which oxidant from the list below is commonly reported in modern Doebner–Miller oxidations to convert dihydroquinoline to quinoline?

• DDQ (2,3‑Dichloro‑5,6‑dicyano‑1,4‑benzoquinone)
• Sodium borohydride
• Hydrazine hydrate
• Lithium aluminium hydride

Correct Answer: DDQ (2,3‑Dichloro‑5,6‑dicyano‑1,4‑benzoquinone)

Q16. Compared with the Skraup quinoline synthesis, a practical advantage of the Doebner–Miller method is:

• It tolerates a wider variety of substituents on the enone and can be milder in oxidizing conditions
• It exclusively uses nitrobenzene as solvent and oxidant
• It produces quinolines without any need for acid catalysis
• It always gives higher yields regardless of substrate electronics

Correct Answer: It tolerates a wider variety of substituents on the enone and can be milder in oxidizing conditions

Q17. What practical precaution is often necessary when running Doebner–Miller reactions at scale in the lab?

• Control of exotherm and careful choice of oxidant to avoid over‑oxidation or runaway reactions
• Complete exclusion of air to prevent any oxidation
• Using large excess of strong base to neutralize acid byproducts
• Performing the reaction at cryogenic temperatures to slow the reaction

Correct Answer: Control of exotherm and careful choice of oxidant to avoid over‑oxidation or runaway reactions

Q18. Which pharmacologically relevant statement is true about quinolines synthesized via Doebner–Miller routes?

• Quinoline scaffolds prepared this way are core motifs in many therapeutic agents (e.g., antimalarial and antimicrobial leads)
• Quinolines have no known pharmaceutical applications and are only used as dyes
• Products are always too unstable for medicinal chemistry use
• Doebner–Miller quinolines are exclusively used as polymer additives

Correct Answer: Quinoline scaffolds prepared this way are core motifs in many therapeutic agents (e.g., antimalarial and antimicrobial leads)

Q19. During the mechanistic sequence, tautomerization of the β‑amino carbonyl intermediate can produce which useful intermediate that aids cyclization?

• An enamine (or iminium/enamine equilibrium) that can undergo intramolecular electrophilic attack
• A diazonium salt required for Sandmeyer chemistry
• A stable epoxide that prevents cyclization
• A carbanion that undergoes nucleophilic substitution at nitrogen

Correct Answer: An enamine (or iminium/enamine equilibrium) that can undergo intramolecular electrophilic attack

Q20. Which of the following is a common limitation of the Doebner–Miller reaction encountered in practice?

• Steric hindrance at ortho positions on the aniline or bulky substituents on the enone can significantly reduce cyclization efficiency
• It proceeds cleanly with all tertiary amines without exception
• It forms quinolines without any need for workup or purification steps
• There are no electronic effects on reactivity or selectivity in this reaction

Correct Answer: Steric hindrance at ortho positions on the aniline or bulky substituents on the enone can significantly reduce cyclization efficiency

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