Effect of substituents on reactivity of monosubstituted benzene MCQs With Answer

Introduction: The effect of substituents on reactivity of monosubstituted benzene MCQs With Answer is essential for B.Pharm students studying aromatic chemistry and medicinal chemistry. Grasping how electron-donating and electron-withdrawing substituents alter electrophilic aromatic substitution rates, directing effects (ortho/para vs meta), resonance and inductive influences, and steric factors helps predict synthesis routes and metabolic behavior of drug molecules. This focused set explores activating vs deactivating groups, resonance vs inductive dominance, reaction-specific trends (nitration, halogenation, sulfonation, Friedel–Crafts), and regioselectivity principles with applied examples. Clear, exam-oriented practice boosts problem-solving and practical understanding in pharmaceutical contexts. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which substituent strongly activates benzene toward electrophilic aromatic substitution?

• –NO2 (nitro)
• –CH3 (methyl)
• –NH2 (amino)
• –COOH (carboxyl)

Correct Answer: –NH2 (amino)

Q2. A substituent that directs incoming electrophiles to the meta position is typically:

• Electron-donating by resonance
• Electron-withdrawing by resonance
• Electron-donating by induction only
• Nonpolar alkyl group

Correct Answer: Electron-withdrawing by resonance

Q3. Which of the following is a deactivating but ortho/para-directing substituent?

• –OCH3
• –F (fluoro)
• –NO2
• –NHCOCH3

Correct Answer: –F (fluoro)

Q4. In electrophilic aromatic substitution, the rate-determining step is:

• Loss of a proton from the sigma complex
• Formation of the arenium (sigma) ion
• Nucleophilic attack on benzene
• Formation of a radical intermediate

Correct Answer: Formation of the arenium (sigma) ion

Q5. Which substituent increases the rate of nitration of benzene the most?

• –NO2
• –CH3
• –CF3
• –COOH

Correct Answer: –CH3

Q6. Which pair lists strong deactivating, meta-directing groups?

• –NH2, –OCH3
• –NO2, –SO3H
• –CH3, –OCH3
• –F, –Cl

Correct Answer: –NO2, –SO3H

Q7. Why is –OH an activating ortho/para director?

• Because it withdraws electron density by induction
• Because it donates electron density by resonance into the ring
• Because it increases steric hindrance
• Because it forms stable carbocations

Correct Answer: Because it donates electron density by resonance into the ring

Q8. Which substituent makes Friedel–Crafts alkylation difficult or impossible?

• –OCH3
• –NH2
• –NO2
• –CH3

Correct Answer: –NO2

Q9. Halogen substituents on benzene are generally:

• Activating and ortho/para directing
• Deactivating and ortho/para directing
• Activating and meta directing
• Deactivating and meta directing

Correct Answer: Deactivating and ortho/para directing

Q10. Which concept explains why –F directs ortho/para despite being deactivating?

• Hyperconjugation
• Inductive donation
• Resonance donation (+R) competing with strong –I effect
• Steric hindrance

Correct Answer: Resonance donation (+R) competing with strong –I effect

Q11. Which substituent stabilizes the arenium ion most and thus activates the ring?

• –NO2
• –OMe
• –CF3
• –CN

Correct Answer: –OMe

Q12. For monosubstituted toluene undergoing nitration, the major product is at which position?

• Meta position
• Para position
• Only ortho positions equally
• Benzylic position

Correct Answer: Para position

Q13. Which substituent increases the acidity of benzoic acid when placed on the ring?

• –OCH3
• –NH2
• –NO2
• –CH3

Correct Answer: –NO2

Q14. In aromatic nitration, anisole reacts faster than benzene because:

• Methoxy group withdraws by induction
• Methoxy group donates by resonance, stabilizing the sigma complex
• Anisole is a stronger base
• Steric hindrance reduces activation energy

Correct Answer: Methoxy group donates by resonance, stabilizing the sigma complex

Q15. Which of the following substituents is an ortho/para director due to hyperconjugation?

• –NO2
• –CF3
• –CH3
• –CN

Correct Answer: –CH3

Q16. The presence of a strong electron-withdrawing group at the ortho or para position facilitates which aromatic substitution mechanism?

• Electrophilic aromatic substitution (EAS)
• Nucleophilic aromatic substitution (SNAr) via Meisenheimer complex
• Radical substitution on the ring
• Metal-catalyzed hydrogenation

Correct Answer: Nucleophilic aromatic substitution (SNAr) via Meisenheimer complex

Q17. Which substituent decreases the electron density of benzene primarily through the inductive effect?

• –OCH3
• –NO2
• –NH2
• –CH3

Correct Answer: –NO2

Q18. Which best describes resonance versus inductive effects in substituent influence?

• Inductive acts through pi bonds, resonance through sigma bonds
• Resonance delocalizes electrons via pi system; inductive transmits electron withdrawal/donation through sigma bonds
• Only inductive effects determine directing power
• Resonance effects are negligible for aromatic reactivity

Correct Answer: Resonance delocalizes electrons via pi system; inductive transmits electron withdrawal/donation through sigma bonds

Q19. Which substituent would most strongly deactivate benzene toward electrophilic attack?

• –OCH3
• –NMe2
• –NO2
• –CH2OH

Correct Answer: –NO2

Q20. In chlorobenzene nitration, which position(s) are favored?

• Meta only
• Orth o and para
• Para only
• No substitution occurs

Correct Answer: Ortho and para

Q21. Which substituent’s +M (mesomeric) effect is strongest in stabilizing positive charge on the ring?

• –NH2
• –F
• –NO2
• –CF3

Correct Answer: –NH2

Q22. The nitration of nitrobenzene proceeds very slowly because nitro group:

• Is strongly activating
• Withdraws electron density and destabilizes the sigma complex
• Donates electrons by resonance
• Enhances electrophile formation

Correct Answer: Withdraws electron density and destabilizes the sigma complex

Q23. Which substituent favors para substitution predominantly due to steric and electronic factors?

• –H (hydrogen)
• Large bulky ortho-director like –tBu
• Small activating group like –CH3
• Moderately activating group like –OCH3

Correct Answer: Moderately activating group like –OCH3

Q24. Which substituent will most increase the rate of electrophilic bromination (with FeBr3) relative to benzene?

• –NO2
• –OCH3
• –CF3
• –SO3H

Correct Answer: –OCH3

Q25. Which functional group is meta-directing due to strong electron withdrawal by resonance?

• –CHO (formyl)
• –OR
• –NR2
• –R (alkyl)

Correct Answer: –CHO (formyl)

Q26. A para-directing substituent that is deactivating is:

• –NO2
• –Cl
• –NH2
• –OCH3

Correct Answer: –Cl

Q27. Which statement about hyperconjugation is correct?

• It is an inductive effect only
• It involves delocalization of sigma electrons into the aromatic pi system stabilizing carbocations
• It decreases electron density on the ring
• It only applies to halogens

Correct Answer: It involves delocalization of sigma electrons into the aromatic pi system stabilizing carbocations

Q28. Which substituent would facilitate nucleophilic aromatic substitution at a carbon bearing a leaving group?

• –NH2 para to the leaving group
• –CH3 para to the leaving group
• –NO2 ortho or para to the leaving group
• –OCH3 ortho to the leaving group

Correct Answer: –NO2 ortho or para to the leaving group

Q29. Which effect primarily causes –CF3 to strongly deactivate the aromatic ring?

• Strong +R resonance donation
• Strong electron-withdrawing inductive (–I) effect
• Hyperconjugation activating effect
• Steric activation

Correct Answer: Strong electron-withdrawing inductive (–I) effect

Q30. Which is true about sulfonation of activated rings (e.g., anisole)?

• Sulfonation is slower than nitration for activated rings
• Sulfonation favors ortho/para and is reversible under different conditions
• Sulfonation always gives only meta product
• Sulfonation does not depend on substituents

Correct Answer: Sulfonation favors ortho/para and is reversible under different conditions

Q31. In terms of directing effects, which list is exclusively ortho/para directors?

• –NO2, –CN, –COOH
• –OH, –NH2, –CH3
• –CF3, –SO3H, –COCl
• –CN, –SO2R, –CHO

Correct Answer: –OH, –NH2, –CH3

Q32. What is the primary reason anilines are more reactive than nitrobenzenes in EAS?

• Aniline withdraws electron density
• Aniline donates electron density via resonance stabilizing the sigma complex
• Nitrobenzene forms stable arenium ions
• Aniline is sterically hindered

Correct Answer: Aniline donates electron density via resonance stabilizing the sigma complex

Q33. Which substituent will direct electrophiles to the meta position and also reduce the ring’s reactivity?

• –NHCOCH3
• –NO2
• –OCH3
• –CH3

Correct Answer: –NO2

Q34. Which effect explains why alkyl groups activate the ring slightly?

• Inductive electron-withdrawal
• Hyperconjugation and weak +I effect
• Strong resonance donation
• Formation of hydrogen bonds

Correct Answer: Hyperconjugation and weak +I effect

Q35. For monosubstituted benzene with –CHO, which position will incoming electrophiles prefer?

• Ortho and para
• Meta
• Only para
• Unsubstituted positions only

Correct Answer: Meta

Q36. Which substituent would most increase the rate of electrophilic aromatic substitution compared to benzene?

• –NO2
• –COOH
• –OH
• –F

Correct Answer: –OH

Q37. The presence of electron-withdrawing groups on aromatic rings generally makes the ring:

• More nucleophilic
• Less susceptible to electrophilic attack
• More likely to undergo Friedel–Crafts alkylation
• More likely to donate electrons to electrophiles

Correct Answer: Less susceptible to electrophilic attack

Q38. Which substituent causes strong deactivation and is commonly used to block electrophilic substitution in drug scaffolds?

• –CH3
• –NO2
• –OCH3
• –NH2

Correct Answer: –NO2

Q39. Which of these substituents would make the benzene ring more susceptible to oxidation at benzylic positions?

• Electron-donating substituents increase benzylic stabilization and reactivity toward oxidation
• Electron-withdrawing substituents increase benzylic oxidation
• Substituents do not affect benzylic oxidation
• Only steric factors affect benzylic oxidation

Correct Answer: Electron-donating substituents increase benzylic stabilization and reactivity toward oxidation

Q40. Which is a correct order of activating power (strongest to weakest) among these substituents?

• –NO2 > –CHO > –Cl
• –NH2 > –OH > –CH3
• –CF3 > –CN > –COOH
• –Cl > –Br > –I

Correct Answer: –NH2 > –OH > –CH3

Q41. Why are resonance donors generally ortho/para directors?

• They destabilize the sigma complex at ortho/para
• They can stabilize positive charge at the ortho and para positions via resonance structures
• They withdraw electrons from the ortho/para positions only
• They block substitution through steric hindrance

Correct Answer: They can stabilize positive charge at the ortho and para positions via resonance structures

Q42. Which substituent is least likely to stabilize a positive charge developed during EAS?

• –OMe
• –NH2
• –NO2
• –CH3

Correct Answer: –NO2

Q43. In drug design, introducing electron-withdrawing groups on an aromatic ring often:

• Increases electron density and basicity
• Reduces metabolic activation by making the ring less reactive to electrophiles
• Always increases lipophilicity
• Makes the molecule more prone to electrophilic aromatic substitution

Correct Answer: Reduces metabolic activation by making the ring less reactive to electrophiles

Q44. Which substituent is expected to accelerate bromination of benzene the most?

• –NO2
• –NH2
• –COOH
• –CF3

Correct Answer: –NH2

Q45. If you need para-selective nitration on a monosubstituted benzene with an activating group, which practical issue must you consider?

• Only meta substitution occurs
• Ortho products may form due to lower steric hindrance unless blocked or controlled
• Friedel–Crafts will dominate
• Substitution will only occur at benzylic positions

Correct Answer: Ortho products may form due to lower steric hindrance unless blocked or controlled

Q46. Which substituent would most increase the ring’s susceptibility to electrophilic substitution: –CH3, –Cl, –NO2, or –CN?

• –CN
• –NO2
• –Cl
• –CH3

Correct Answer: –CH3

Q47. In comparing inductive and resonance effects, which substituent shows strong –I but also +R?

• –NO2
• –NH2
• –F
• –CF3

Correct Answer: –F

Q48. Which of the following is true about sulfonation of benzene rings bearing electron-withdrawing groups?

• Electron-withdrawing groups speed up sulfonation
• Sulfonation becomes slower and may require harsher conditions
• Sulfonation gives only ortho products with EWG
• Sulfonation replaces the substituent directly

Correct Answer: Sulfonation becomes slower and may require harsher conditions

Q49. Which substituent would favor formation of a Meisenheimer complex in SNAr reactions?

• Electron-donating groups ortho to leaving group
• Electron-withdrawing groups ortho/para to leaving group
• Bulky alkyl groups para to leaving group
• Nonpolar substituents far from leaving group

Correct Answer: Electron-withdrawing groups ortho/para to leaving group

Q50. Which of the following best summarizes why substituent effects matter in pharmaceutical aromatic chemistry?

• They only affect melting points
• They determine ring reactivity, regioselectivity, metabolic stability and synthetic accessibility of drug scaffolds
• They are irrelevant for drug metabolism
• They only influence color and odor

Correct Answer: They determine ring reactivity, regioselectivity, metabolic stability and synthetic accessibility of drug scaffolds

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