Orientation of substituents in electrophilic substitution MCQs With Answer

Orientation of substituents in electrophilic substitution MCQs With Answer is an essential topic for B. Pharm students studying aromatic chemistry and pharmaceutical synthesis. This introduction covers key concepts such as electrophilic aromatic substitution (EAS), ortho/para/meta directors, activating and deactivating groups, resonance (+R/–R) and inductive (+I/–I) effects, Wheland intermediate stabilization, and practical implications for nitration, sulfonation and Friedel–Crafts reactions. Understanding how substituents control orientation helps predict regioselectivity in drug-like aromatic scaffolds and design synthetic routes. These MCQs emphasize mechanistic reasoning, examples of common functional groups, and problem-solving skills relevant to pharmaceutical chemistry. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which substituent is a strong activating ortho/para director in electrophilic aromatic substitution?

• -NH2
• -NO2
• -Cl
• -CF3

Correct Answer: -NH2

Q2. Which substituent directs incoming electrophiles predominantly to the meta position?

• -OH
• -OCH3
• -NO2
• -CH3

Correct Answer: -NO2

Q3. Which statement about halogen substituents (F, Cl, Br, I) on benzene is correct?

• They are activating and ortho/para directing
• They are deactivating and meta directing
• They are deactivating but ortho/para directing
• They have no effect on reactivity or orientation

Correct Answer: They are deactivating but ortho/para directing

Q4. What is the key resonance-stabilized intermediate formed during electrophilic aromatic substitution?

• Carbocationic sigma complex (Wheland intermediate)
• Free radical
• Benzyne intermediate
• Carbanion

Correct Answer: Carbocationic sigma complex (Wheland intermediate)

Q5. Which substituent is considered the strongest electron-withdrawing deactivator listed?

• -CF3
• -NO2
• -Cl
• -CH3

Correct Answer: -NO2

Q6. Why is nitrobenzene unreactive toward Friedel–Crafts acylation?

• Because nitro is a strong activator that overreacts
• Because nitro is a strong deactivator that destabilizes the arenium ion
• Because nitrobenzene forms chelates with AlCl3
• Because nitrobenzene is too basic

Correct Answer: Because nitro is a strong deactivator that destabilizes the arenium ion

Q7. Nitration of toluene predominantly gives which major product?

• Ortho-nitrotoluene and para-nitrotoluene with para major
• Meta-nitrotoluene only
• Para-nitrotoluene only
• Meta-nitrotoluene with meta major

Correct Answer: Ortho-nitrotoluene and para-nitrotoluene with para major

Q8. Chlorobenzene undergoes nitration to give which regioisomer distribution primarily?

• Only meta product
• Ortho and para products with para predominating
• Only para product
• Equimolar ortho, meta, para

Correct Answer: Ortho and para products with para predominating

Q9. Which electronic effect primarily causes -CF3 to be a meta director?

• +R (resonance donation)
• +I (inductive donation)
• -I (inductive withdrawal)
• -M (resonance withdrawal)

Correct Answer: -I (inductive withdrawal)

Q10. Which pair of substituents are both strong ortho/para directors due to resonance donation?

• -NO2 and -CN
• -OH and -OCH3
• -COOH and -SO3H
• -F and -Cl

Correct Answer: -OH and -OCH3

Q11. Why is aniline usually acetylated (to acetanilide) before nitration?

• To increase its basicity and reactivity
• To block the ortho positions permanently
• To reduce the strong activating effect of -NH2 and prevent oxidation/overreaction
• To convert it into a meta-director

Correct Answer: To reduce the strong activating effect of -NH2 and prevent oxidation/overreaction

Q12. Which of the following is a common electrophile in aromatic nitration?

• NO+
• NO2+
• N2+
• NH2+

Correct Answer: NO2+

Q13. Carbonyl-containing substituents such as -CHO, -COCH3, -COOH typically direct electrophiles to which position?

• Ortho/para
• Meta
• They do not direct (random)
• They direct to benzyne path

Correct Answer: Meta

Q14. Which substituent increases the rate of electrophilic aromatic substitution the most among the choices?

• -NH2
• -Cl
• -NO2
• -CF3

Correct Answer: -NH2

Q15. When a benzene ring has two substituents directing differently, which substituent typically controls the orientation of a new electrophile?

• The more sterically bulky substituent
• The substituent introduced first historically
• The stronger activating (or stronger directing) substituent
• The one closest to the electrophile

Correct Answer: The stronger activating (or stronger directing) substituent

Q16. Nitration of tert‑butylbenzene gives which major isomer due to steric hindrance?

• Ortho-nitrotert‑butylbenzene
• Para-nitrotert‑butylbenzene
• Meta-nitrotert‑butylbenzene
• Equal ortho and para

Correct Answer: Para-nitrotert‑butylbenzene

Q17. Which notation denotes resonance electron donation commonly used in physical organic chemistry?

• +I
• -I
• +M (or +R)
• -S

Correct Answer: +M (or +R)

Q18. For anisole (methoxybenzene), nitration gives which major product distribution?

• Meta-nitroanisole only
• Ortho and para with para predominating
• Only para product due to steric blocking
• Only ortho due to resonance

Correct Answer: Ortho and para with para predominating

Q19. Which general description fits halogens as substituents in EAS?

• Activating and meta directing
• Deactivating and ortho/para directing
• Neutral and do not affect rate
• Strong activators and para only

Correct Answer: Deactivating and ortho/para directing

Q20. Which of the following benzene derivatives is nitrated fastest under identical conditions?

• Nitrobenzene
• Benzene
• Anisole
• Chlorobenzene

Correct Answer: Anisole

Q21. Stabilization of the Wheland intermediate is most effective when the positive charge can be delocalized onto which substituent?

• -NO2
• -OH
• -CF3
• -COOH

Correct Answer: -OH

Q22. For halogen substituents, which electronic effect is mainly responsible for their deactivating influence?

• +R resonance donation
• -I inductive withdrawal
• +I inductive donation
• -R resonance withdrawal

Correct Answer: -I inductive withdrawal

Q23. Which reagent combination generates the nitrating electrophile NO2+ in situ?

• HNO2 and HCl
• HNO3 and H2SO4
• NO2 and AlCl3
• NH3 and O2

Correct Answer: HNO3 and H2SO4

Q24. Which substituent both donates electrons by resonance and withdraws slightly by induction, often making it ortho/para directing but deactivating overall?

• -OH
• -Cl
• -NO2
• -CF3

Correct Answer: -Cl

Q25. Which is the correct order of activating strength (most to least) among these groups?

• -NO2 > -Cl > -OH > -NH2
• -NH2 > -OH > -OCH3 > -CH3
• -CH3 > -OCH3 > -OH > -NH2
• -Cl > -Br > -I > -F

Correct Answer: -NH2 > -OH > -OCH3 > -CH3

Q26. Which substituent will preferentially direct sulfonation to the meta-position?

• -NHCOCH3 (acetanilide)
• -OCH3
• -COCH3
• -CH3

Correct Answer: -COCH3

Q27. A benzene ring with a strong electron-donating group reacts faster because:

• It raises the energy of the aromatic π-system making it less stable
• It stabilizes the electrophile
• It stabilizes the arenium ion (Wheland intermediate) by resonance
• It converts the reaction into a radical pathway

Correct Answer: It stabilizes the arenium ion (Wheland intermediate) by resonance

Q28. Which substituent is both strongly electron-withdrawing and a meta director due to resonance and induction?

• -NH2
• -NO2
• -OCH3
• -CH3

Correct Answer: -NO2

Q29. In nitration of p-xylene (1,4-dimethylbenzene), which position(s) are available for substitution?

• Positions ortho to either methyl (2 and 6) giving a single set of products
• Only meta positions to methyl groups
• Only the position between the methyl groups (3)
• No reaction occurs

Correct Answer: Positions ortho to either methyl (2 and 6) giving a single set of products

Q30. Which group would you protect to prevent overreaction during electrophilic substitution of aniline?

• Protect -NH2 as an amide (acetylation)
• Protect -NH2 as a nitro
• Protect benzene ring by hydrogenation
• No protection necessary

Correct Answer: Protect -NH2 as an amide (acetylation)

Q31. Which substituent directs electrophiles to the para position most strongly due to minimal steric hindrance and resonance donation?

• -NO2
• -OCH3
• -CF3
• -SO3H

Correct Answer: -OCH3

Q32. Which functional group is a weakly activating ortho/para director purely due to hyperconjugation rather than resonance?

• -CH3
• -OH
• -NH2
• -NO2

Correct Answer: -CH3

Q33. Which substituent will direct electrophiles to positions that place the positive charge next to a resonance donor in the Wheland intermediate?

• -NO2
• -OH
• -CF3
• -SO3H

Correct Answer: -OH

Q34. Which is true about meta directors generally?

• They stabilize the sigma complex best at ortho/para positions
• They withdraw electron density from the ring, destabilizing ortho/para arenium ions
• They are always halogens
• They increase the rate of EAS

Correct Answer: They withdraw electron density from the ring, destabilizing ortho/para arenium ions

Q35. In electrophilic aromatic halogenation using Br2/FeBr3, the bromination of anisole occurs preferentially at which position?

• Meta
• Ortho and para with para major
• Only para if bulky conditions used
• No reaction

Correct Answer: Ortho and para with para major

Q36. What effect does a nitroso (-NO) or carbonyl substituent generally exert on orientation?

• Ortho/para directing via +R
• Meta directing via -M and -I
• Strong activating via hyperconjugation
• No effect on orientation

Correct Answer: Meta directing via -M and -I

Q37. When both ortho and para positions are electronically favored, what factor often determines the major product?

• Resonance only
• Steric hindrance and temperature (para often favored at low steric demand)
• Solvent polarity only
• Electrophile size has no effect

Correct Answer: Steric hindrance and temperature (para often favored at low steric demand)

Q38. Which substituent would most strongly deactivate benzene toward electrophilic substitution among these?

• -NHCOCH3
• -NO2
• -CH3
• -OCH3

Correct Answer: -NO2

Q39. Acylation (Friedel–Crafts) of anisole is often slower than anisole nitration because:

• The methoxy group strongly deactivates the ring
• The Lewis acid catalyst can complex with the methoxy oxygen reducing activation
• Acylation does not proceed on activated rings
• Acylation requires radical conditions

Correct Answer: The Lewis acid catalyst can complex with the methoxy oxygen reducing activation

Q40. Which directing behavior is expected for a -CN substituent?

• Strongly activating ortho/para director
• Moderately activating ortho/para director
• Strongly deactivating meta director
• No directing effect

Correct Answer: Strongly deactivating meta director

Q41. Which of the following reagents would favor para substitution over ortho when steric control is applied?

• Low temperature with bulky electrophile
• High temperature with small electrophile
• Using a strong nucleophile
• Electrochemical conditions

Correct Answer: Low temperature with bulky electrophile

Q42. In a ring with -OH and -NO2 substituents, where will a new electrophile most likely add?

• Positions activated by -OH (ortho/para to -OH) despite -NO2
• Positions activated by -NO2
• Equally to both directives
• Only meta to both

Correct Answer: Positions activated by -OH (ortho/para to -OH) despite -NO2

Q43. Which substituent converts an aniline into a less activating, safer-to-nitrate derivative when introduced as an amide?

• -NH2 retained and unprotected
• -NHCOCH3 (acetanilide)
• -NO2 substitution on the ring
• -OCH3 formation

Correct Answer: -NHCOCH3 (acetanilide)

Q44. Which of the following is a common reason halogens direct ortho/para despite being deactivating?

• They donate electron density by resonance while withdrawing by induction
• They are strong electron donors by induction
• They increase aromaticity of the ring
• They form radicals easily

Correct Answer: They donate electron density by resonance while withdrawing by induction

Q45. For meta-directing groups, which resonance argument explains their preference?

• They stabilize positive charge at ortho/para positions
• They destabilize positive charge at ortho/para positions, making meta relatively more favorable
• They make the ring more nucleophilic
• They always block ortho positions sterically

Correct Answer: They destabilize positive charge at ortho/para positions, making meta relatively more favorable

Q46. Which substituent is both strongly deactivating and makes electrophilic substitution difficult, often necessitating harsh conditions?

• -OCH3
• -NO2
• -NH2
• -CH3

Correct Answer: -NO2

Q47. In predicting substitution, why is the concept of resonance contributors important?

• Because only inductive effects matter
• Because resonance contributors show where positive charge is delocalized in the Wheland intermediate, indicating favored positions
• Because resonance only affects physical properties, not reactivity
• Because resonance eliminates all directing effects

Correct Answer: Because resonance contributors show where positive charge is delocalized in the Wheland intermediate, indicating favored positions

Q48. Which substituent combination on benzene will most likely direct a new electrophile to a position that is ortho to one group and meta to the other?

• Two strong meta directors
• One strong ortho/para director and one meta director
• Two identical ortho/para directors always force para only
• No substituents give mixed directing

Correct Answer: One strong ortho/para director and one meta director

Q49. Which positional numbering corresponds to ortho, meta, and para with respect to position 1 on benzene?

• Ortho = 1, Meta = 2, Para = 3
• Ortho = 2, Meta = 3, Para = 4
• Ortho = 3, Meta = 4, Para = 5
• Ortho = 4, Meta = 5, Para = 6

Correct Answer: Ortho = 2, Meta = 3, Para = 4

Q50. When designing a synthesis for a para-substituted pharmaceutical intermediate, which strategy often helps increase para-selectivity?

• Use a strong meta-director as starting substituent
• Use bulky ortho-directing groups or conduct reaction at low temperature to favor para
• Carry out reactions at very high temperature to scramble positions
• Always avoid protecting groups

Correct Answer: Use bulky ortho-directing groups or conduct reaction at low temperature to favor para

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

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