Friedel–Crafts acylation MCQs With Answer

Friedel–Crafts acylation MCQs With Answer is an essential review for B. Pharm students studying aromatic electrophilic substitution. This concise introduction covers mechanism, reagents (acid chlorides, anhydrides, AlCl3), formation of the acylium ion, regiochemical effects, limitations with deactivated rings, and practical workup issues. Emphasis on reaction scope, synthetic applications (ketone formation, subsequent reduction to avoid carbocation rearrangement), and troubleshooting will strengthen exam readiness and medicinal chemistry understanding. Targeted MCQs help reinforce key concepts, reagent selection, and real-case problems encountered in drug synthesis. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is the primary product of Friedel–Crafts acylation of benzene with an acid chloride?

• Aryl alkane
• Aromatic ketone
• Aromatic alcohol
• Carboxylic acid

Correct Answer: Aromatic ketone

Q2. Which Lewis acid is most commonly used to generate the electrophile in Friedel–Crafts acylation?

• H2SO4
• AlCl3
• NaOH
• Pd/C

Correct Answer: AlCl3

Q3. Which of the following is a typical acylating agent in Friedel–Crafts acylation?

• Alcohol
• Acyl chloride
• Alkene
• Amide

Correct Answer: Acyl chloride

Q4. What reactive electrophile is generated when an acid chloride reacts with AlCl3?

• Carbanion
• Acylium ion
• Nitronium ion
• Radical cation

Correct Answer: Acylium ion

Q5. How does an introduced acyl group direct further electrophilic substitution on benzene?

• Strongly ortho/para directing
• Strongly activating
• Deactivating and meta directing
• Non-directing

Correct Answer: Deactivating and meta directing

Q6. Why does Friedel–Crafts acylation avoid carbocation rearrangements common in alkylation?

• The acylium ion is resonance-stabilized and does not rearrange
• The reaction proceeds via a radical mechanism
• The aromatic ring forms an epoxide intermediate
• The catalyst prevents any ionic intermediates

Correct Answer: The acylium ion is resonance-stabilized and does not rearrange

Q7. Which solvent is generally preferred for Friedel–Crafts acylation?

• Water
• Protic solvents like ethanol
• Non-nucleophilic aprotic solvents (e.g., dichloromethane)
• Strongly basic solvents

Correct Answer: Non-nucleophilic aprotic solvents (e.g., dichloromethane)

Q8. Which aromatic substrate is least likely to undergo Friedel–Crafts acylation under normal conditions?

• Toluene
• Chlorobenzene
• Nitrobenzene
• Phenol (protected)

Correct Answer: Nitrobenzene

Q9. What role does hydrolysis (aqueous workup) play after Friedel–Crafts acylation?

• Converts alcohols to alkenes
• Liberates the ketone product and destroys AlCl3 complex
• Reduces the ketone to an alcohol
• Removes hydrogen from the aromatic ring

Correct Answer: Liberates the ketone product and destroys AlCl3 complex

Q10. Which alternative Lewis acid can sometimes be used in Friedel–Crafts acylation besides AlCl3?

• NaBH4
• FeCl3
• KMnO4
• H2

Correct Answer: FeCl3

Q11. What is the resonance form of the acylium ion commonly depicted as?

• R–C•–O
• R–C≡O+ and R–C+=O (resonance)
• R–COO–
• R–C–O–

Correct Answer: R–C≡O+ and R–C+=O (resonance)

Q12. Why is polyacylation less common in Friedel–Crafts acylation compared to polyalkylation?

• Acyl groups are activating and prevent further reaction
• Acyl groups deactivate the ring making additional substitution difficult
• The catalyst is consumed after first substitution
• Acylation always yields a sterically hindered product

Correct Answer: Acyl groups deactivate the ring making additional substitution difficult

Q13. How does a strongly electron-donating substituent on benzene affect the rate of Friedel–Crafts acylation?

• Decreases the rate dramatically
• Has no effect on the rate
• Increases the rate (activates the ring)
• Causes the reaction to produce carboxylic acids instead

Correct Answer: Increases the rate (activates the ring)

Q14. Which position on naphthalene is generally favored in Friedel–Crafts acylation?

• Beta (2-) position
• Alpha (1-) position
• Only at bridgehead carbons
• No reaction occurs with naphthalene

Correct Answer: Alpha (1-) position

Q15. What problem is commonly encountered when attempting Friedel–Crafts acylation of phenol without protection?

• Complete inactivity due to excess deactivation
• Preferential O-acylation (ester formation) instead of C-acylation
• Instant polymerization of phenol
• Formation of nitro derivatives

Correct Answer: Preferential O-acylation (ester formation) instead of C-acylation

Q16. Which mechanism step directly follows formation of the acylium ion in Friedel–Crafts acylation?

• Nucleophilic attack by a water molecule
• Electrophilic attack of the aromatic ring forming the sigma complex
• Beta-hydride elimination
• Free radical chain propagation

Correct Answer: Electrophilic attack of the aromatic ring forming the sigma complex

Q17. What is the typical effect of a halogen substituent (e.g., Cl) on Friedel–Crafts acylation reactivity and regiochemistry?

• Strongly activating and meta directing
• Deactivating but ortho/para directing
• Strongly deactivating and meta directing
• No effect at all

Correct Answer: Deactivating but ortho/para directing

Q18. For synthesizing an alkyl-substituted aromatic without rearrangement, which two-step route is often used?

• Friedel–Crafts alkylation followed by oxidation
• Friedel–Crafts acylation followed by reduction of the ketone
• Direct radical alkylation under UV
• Photochemical ring contraction

Correct Answer: Friedel–Crafts acylation followed by reduction of the ketone

Q19. Which reduction method is commonly used to convert the acyl group to an alkyl group after acylation?

• Wolff–Kishner or Clemmensen reduction
• Ozonolysis
• Mitsunobu reaction
• Hydroboration–oxidation

Correct Answer: Wolff–Kishner or Clemmensen reduction

Q20. Why are stoichiometric amounts of AlCl3 often required in acylation reactions?

• AlCl3 is too weak to be catalytic
• AlCl3 forms strong complexes with the ketone product and is consumed
• AlCl3 reacts irreversibly with benzene
• AlCl3 is volatile and evaporates during reaction

Correct Answer: AlCl3 forms strong complexes with the ketone product and is consumed

Q21. Which aromatic heterocycle is least compatible with Friedel–Crafts acylation without modification?

• Pyrrole (unprotected)
• Pyridine
• Furan

Correct Answer: Pyridine

Q22. Which statement about the Friedel–Crafts acylation intermediate (sigma complex) is correct?

• It is a free radical intermediate
• It is a carbocationic arenium ion stabilized by resonance
• It is a carbanion stabilized by the catalyst
• It is a pericyclic transition state

Correct Answer: It is a carbocationic arenium ion stabilized by resonance

Q23. What happens if water is present during the Friedel–Crafts acylation?

• Reaction proceeds faster
• Acyl chloride is hydrolyzed to carboxylic acid, stopping the reaction
• Water acts as a better Lewis acid
• Water converts product to an alcohol immediately

Correct Answer: Acyl chloride is hydrolyzed to carboxylic acid, stopping the reaction

Q24. Which reagent pair can generate an acylium ion from a carboxylic acid derivative besides acyl chloride + AlCl3?

• Acid anhydride + AlCl3
• Alcohol + H2
• Carboxylate + NaOH
• Amide + Pd/C

Correct Answer: Acid anhydride + AlCl3

Q25. What is a practical synthetic advantage of Friedel–Crafts acylation in medicinal chemistry?

• Introduces nitro groups selectively
• Provides a straightforward route to aromatic ketones useful as pharmacophores
• Always produces enantiomerically pure products
• Removes halogens from drug scaffolds

Correct Answer: Provides a straightforward route to aromatic ketones useful as pharmacophores

Q26. Which condition is most likely to favor ortho substitution during acylation of anisole?

• Very low temperature and bulky electrophile
• Sterically unhindered electrophile and lower temperature favor both ortho and para
• High temperature always gives ortho only
• No ortho substitution occurs with anisole

Correct Answer: Sterically unhindered electrophile and lower temperature favor both ortho and para

Q27. In the generation of the electrophile RCO+, which species is the counterion formed when AlCl3 reacts with RCOCl?

• Cl–
• AlCl4–
• H+
• OH–

Correct Answer: AlCl4–

Q28. Which substrate will likely give both O- and C-acylation products, requiring protection strategy?

• Chlorobenzene
• Phenol
• Benzene
• Nitrobenzene

Correct Answer: Phenol

Q29. How does the presence of a strong electron-withdrawing group (e.g., -NO2) on benzene affect acylation?

• Greatly increases reactivity
• Prevents acylation due to strong deactivation
• Changes product to an alcohol
• Makes the reaction radical instead of electrophilic

Correct Answer: Prevents acylation due to strong deactivation

Q30. Which of the following best describes the rate-determining step in Friedel–Crafts acylation?

• Hydrolysis of the Al complex
• Attack of the aromatic ring on the acylium ion forming the sigma complex
• Thermal decomposition of acyl chloride
• Re-aromatization by deprotonation

Correct Answer: Attack of the aromatic ring on the acylium ion forming the sigma complex

Q31. Why is Friedel–Crafts acylation often preferred over direct alkylation to introduce an alkyl group?

• Acylation is cheaper
• Acylation followed by reduction avoids carbocation rearrangement seen in alkylation
• Alkylation yields ketones directly
• Alkylation works only on heterocycles

Correct Answer: Acylation followed by reduction avoids carbocation rearrangement seen in alkylation

Q32. What happens to AlCl3 after reaction with the ketone product if not hydrolyzed?

• It remains as free AlCl3 unchanged
• It forms a complex with the ketone, reducing catalyst availability
• It is converted to Al metal
• It oxidizes the ketone to a carboxylic acid

Correct Answer: It forms a complex with the ketone, reducing catalyst availability

Q33. Which functional group on the aromatic ring will most readily promote Friedel–Crafts acylation?

• Nitro group
• Carbonyl group
• Electron-donating group like -OMe or -Me
• Trifluoromethyl group

Correct Answer: Electron-donating group like -OMe or -Me

Q34. Which of the following is a correct limitation of Friedel–Crafts acylation?

• It is effective on strongly deactivated aromatics
• It tolerates free amino groups without protection
• Lewis bases like pyridine coordinate to the catalyst and prevent reaction
• It always gives para substitution exclusively

Correct Answer: Lewis bases like pyridine coordinate to the catalyst and prevent reaction

Q35. Which reagent would you use to prepare benzophenone by Friedel–Crafts acylation of benzene?

• Benzoyl chloride and AlCl3
• Toluene and HCl
• Benzene and acetyl chloride
• Benzene and nitric acid

Correct Answer: Benzoyl chloride and AlCl3

Q36. What is a likely product when anisole undergoes Friedel–Crafts acylation?

• Predominantly ortho and para acylated anisole derivatives
• Predominantly meta acylated anisole derivatives
• Nitration products
• Complete ring cleavage

Correct Answer: Predominantly ortho and para acylated anisole derivatives

Q37. Which experimental precaution is important for a successful Friedel–Crafts acylation?

• Ensure moisture-free (anhydrous) conditions
• Keep a large excess of water present
• Use a strongly basic medium
• Heat the mixture to boiling water temperature

Correct Answer: Ensure moisture-free (anhydrous) conditions

Q38. When benzoyl chloride reacts with AlCl3, which species directly attacks the aromatic ring?

• AlCl3
• Chloride ion
• Acylium ion (RCO+)
• Carbanion

Correct Answer: Acylium ion (RCO+)

Q39. Which of the following is true about Friedel–Crafts acylation on chlorobenzene?

• Reaction is impossible due to deactivation
• Reaction proceeds, favoring ortho and para positions despite deactivation
• Only meta substitution occurs
• Chlorobenzene is fully reduced during reaction

Correct Answer: Reaction proceeds, favoring ortho and para positions despite deactivation

Q40. Which statement correctly compares AlCl3 and FeCl3 as Lewis acids in acylation?

• FeCl3 is stronger and more commonly used than AlCl3
• AlCl3 is generally a stronger Lewis acid than FeCl3 and often more effective
• Neither can generate acylium ions
• Both are poor choices; NaCl is preferred

Correct Answer: AlCl3 is generally a stronger Lewis acid than FeCl3 and often more effective

Q41. Which aromatic derivative is commonly resistant to Friedel–Crafts acylation due to strong coordination to AlCl3?

• Unsubstituted benzene
• Aromatic amine (aniline) without protection
• Toluene
• Ethylbenzene

Correct Answer: Aromatic amine (aniline) without protection

Q42. How can acylation be carried out when the substrate contains a strongly coordinating heteroatom?

• Run the reaction in water
• Protect the heteroatom or use milder Lewis acids/alternative methods
• Use excess AlCl3 without protection
• Heat to 200 °C to force reaction

Correct Answer: Protect the heteroatom or use milder Lewis acids/alternative methods

Q43. Which product results from Friedel–Crafts acylation of toluene with acetyl chloride?

• Para- and ortho-methyl acetophenone isomers (acetylated toluene)
• Toluene oxide
• Benzoic acid
• Benzyl chloride

Correct Answer: Para- and ortho-methyl acetophenone isomers (acetylated toluene)

Q44. Why might Friedel–Crafts acylation give lower yields with electron-poor aromatics?

• Electron-poor rings are less nucleophilic and attack the electrophile slowly or not at all
• The catalyst oxidizes electron-poor rings rapidly
• Electron-poor rings form stable adducts that cannot be hydrolyzed
• Yields are actually higher with electron-poor rings

Correct Answer: Electron-poor rings are less nucleophilic and attack the electrophile slowly or not at all

Q45. Which is a common troubleshooting strategy if Friedel–Crafts acylation stalls?

• Add water to speed up the reaction
• Increase the acidity by adding more Lewis acid or change solvent/temperature
• Neutralize the mixture with base immediately
• Replace aromatic substrate with an aliphatic one

Correct Answer: Increase the acidity by adding more Lewis acid or change solvent/temperature

Q46. Which structural feature of the acylium ion accounts for its stability?

• Delocalization of positive charge between carbon and oxygen (resonance)
• Presence of an unpaired electron
• Full negative charge on oxygen
• Coordination to water molecules

Correct Answer: Delocalization of positive charge between carbon and oxygen (resonance)

Q47. Which compound is least suitable as an acylating agent for Friedel–Crafts acylation?

• Acyl chloride
• Acid anhydride
• Carboxylic acid
• Acyl triflate

Correct Answer: Carboxylic acid

Q48. In drug synthesis, why is selectivity in Friedel–Crafts acylation important?

• Selectivity avoids formation of regioisomeric impurities that complicate purification and bioactivity
• Selectivity is not important in medicinal chemistry
• It ensures formation of radical byproducts
• It always leads to polymer formation otherwise

Correct Answer: Selectivity avoids formation of regioisomeric impurities that complicate purification and bioactivity

Q49. Which experimental outcome indicates the formation of an AlCl3–ketone complex during workup?

• Immediate precipitation of inorganic salt after quench
• Formation of a deep-colored complex and difficulty in isolating free ketone until hydrolyzed
• Evolution of hydrogen gas
• Formation of crystalline benzene

Correct Answer: Formation of a deep-colored complex and difficulty in isolating free ketone until hydrolyzed

Q50. Which effect does a meta-directing group on the aromatic ring have on Friedel–Crafts acylation product distribution?

• Promotes ortho/para acylation exclusively
• Favours substitution at positions meta to that group or prevents reaction if strongly deactivating
• Always increases reaction rate
• Causes ring cleavage

Correct Answer: Favours substitution at positions meta to that group or prevents reaction if strongly deactivating

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