Effect of substituents on acidity of phenols MCQs With Answer

Effect of substituents on acidity of phenols MCQs With Answer is a focused study area for B.Pharm students exploring how electron-withdrawing and electron-donating groups alter phenol acidity through inductive, resonance, steric and hydrogen-bonding effects. This introduction covers concepts like pKa trends, ortho/para/meta positions, Hammett parameters, solvation and intramolecular hydrogen bonding to help you predict and rationalize acidity changes in substituted phenols. Understanding these effects is vital for drug design, predicting reactivity and interpreting spectra. The questions below reinforce mechanistic thinking and pKa comparisons with practical examples and explanations. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which substituent on the benzene ring increases the acidity of phenol the most among these options?

• –NO₂ (nitro)
• –CH₃ (methyl)
• –OCH₃ (methoxy)
• –NH₂ (amino)

Correct Answer: –NO₂ (nitro)

Q2. How does an electron-withdrawing group (EWG) attached to phenol generally affect acidity?

• Decreases acidity by destabilizing phenoxide
• Increases acidity by stabilizing phenoxide
• No effect on acidity
• Makes the molecule basic

Correct Answer: Increases acidity by stabilizing phenoxide

Q3. Which position of a nitro substituent typically gives the greatest resonance stabilization of the phenoxide ion?

• Meta position
• Ortho position
• Para position
• Both meta and para equally

Correct Answer: Para position

Q4. Why is o-nitrophenol often less acidic than p-nitrophenol despite ortho being close to the –OH?

• Ortho nitro withdraws less by induction
• Intramolecular hydrogen bonding stabilizes the undissociated phenol
• Ortho position enhances resonance stabilization of phenoxide
• Ortho nitro is electron-donating

Correct Answer: Intramolecular hydrogen bonding stabilizes the undissociated phenol

Q5. Which effect primarily stabilizes the phenoxide ion when a para nitro group is present?

• Inductive effect only
• Resonance (mesomeric) effect
• Steric hindrance
• Hyperconjugation from alkyl groups

Correct Answer: Resonance (mesomeric) effect

Q6. How does an electron-donating substituent (e.g., –OCH3) at the para position affect phenol acidity?

• Increases acidity by stabilizing phenoxide
• Decreases acidity by destabilizing phenoxide
• No effect on acidity
• Converts phenol into a strong base

Correct Answer: Decreases acidity by destabilizing phenoxide

Q7. Which substituted phenol is expected to be most acidic?

• p-Methoxyphenol
• p-Nitrophenol
• p-Methylphenol (p-cresol)
• Phenol (unsubstituted)

Correct Answer: p-Nitrophenol

Q8. What is the approximate pKa value of simple phenol (useful for trend comparison)?

• About 0
• About 4
• About 10
• About 16

Correct Answer: About 10

Q9. Which substituent type exerts a negative Hammett sigma (σ) value indicating electron donation?

• –NO₂
• –CN
• –OCH₃
• –CF₃

Correct Answer: –OCH₃

Q10. Which phenol is strongest: phenol, p-chlorophenol, p-nitrophenol, or p-methoxyphenol?

• Phenol
• p-Chlorophenol
• p-Nitrophenol
• p-Methoxyphenol

Correct Answer: p-Nitrophenol

Q11. Halogen substituents (e.g., –Cl, –Br) on phenol typically affect acidity by which net effect?

• Strongly donating by resonance
• Strongly donating by induction
• Weakly electron-withdrawing overall, slightly increasing acidity
• No electronic effect

Correct Answer: Weakly electron-withdrawing overall, slightly increasing acidity

Q12. Which factor most directly stabilizes the negative charge on phenoxide after deprotonation?

• Hydrogen bonding to the phenolic hydrogen
• Resonance delocalization into the aromatic ring and substituents
• Increased molecular weight
• Presence of nonpolar solvent only

Correct Answer: Resonance delocalization into the aromatic ring and substituents

Q13. Comparing m-nitrophenol and p-nitrophenol, which is more acidic and why?

• m-Nitrophenol, because meta enables better resonance
• p-Nitrophenol, because para offers resonance stabilization of phenoxide
• Both equal in acidity
• m-Nitrophenol, because meta has stronger inductive effect

Correct Answer: p-Nitrophenol, because para offers resonance stabilization of phenoxide

Q14. Which ortho substituent commonly leads to intramolecular hydrogen bonding with the phenolic –OH?

• –CH₃
• –NO₂
• –CF₃
• –F

Correct Answer: –NO₂

Q15. Intramolecular hydrogen bonding in o-substituted phenols typically does what to acidity?

• Increases acidity by stabilizing phenoxide
• Decreases acidity by stabilizing the undissociated phenol
• No change in acidity
• Always converts phenol to a stronger base

Correct Answer: Decreases acidity by stabilizing the undissociated phenol

Q16. Which substituent would most strongly decrease phenol acidity at para position?

• –NO₂
• –OCH₃
• –CF₃
• –CN

Correct Answer: –OCH₃

Q17. Which phenomenon explains why electron-withdrawing groups increase acidity via sigma bonds?

• Resonance donation
• Inductive effect (-I)
• Hyperconjugation
• Spin delocalization

Correct Answer: Inductive effect (-I)

Q18. Which substituted phenol is likely to have the lowest pKa (most acidic) among these?

• Phenol
• 4-Nitrophenol
• 2,4-Dinitrophenol
• p-Methoxyphenol

Correct Answer: 2,4-Dinitrophenol

Q19. Picric acid (2,4,6-trinitrophenol) is much stronger than phenol because:

• Multiple EWGs greatly stabilize the phenoxide ion
• Nitro groups donate electrons to phenoxide
• It forms intramolecular hydrogen bonding that stabilizes undissociated acid
• It is bulky and cannot solvate

Correct Answer: Multiple EWGs greatly stabilize the phenoxide ion

Q20. Which of the following best describes the net effect of a para –NH₂ substituent on phenol acidity?

• Strongly increases acidity
• Decreases acidity due to electron donation by resonance
• No effect because nitrogen is neutral
• Increases acidity via inductive withdrawal

Correct Answer: Decreases acidity due to electron donation by resonance

Q21. The Hammett rho (ρ) value for deprotonation of benzoic acids or phenols indicates:

• Magnitude of resonance only
• Sensitivity of reaction to substituent electronic effects
• Steric hindrance exclusively
• Molecular weight dependence

Correct Answer: Sensitivity of reaction to substituent electronic effects

Q22. Which substituent has the largest positive sigma (σ) value indicating strong electron-withdrawing character?

• –CH₃
• –OCH₃
• –NO₂
• –NH₂

Correct Answer: –NO₂

Q23. Why do electron-donating groups reduce the acidity of phenol?

• They destabilize the phenoxide ion by increasing negative charge density
• They increase resonance stabilization of phenoxide
• They enhance solvation of phenoxide
• They remove the ring entirely

Correct Answer: They destabilize the phenoxide ion by increasing negative charge density

Q24. Which solvent effect increases observed acidity of phenols in protic solvents?

• Reduced solvation of phenoxide
• Enhanced solvation and hydrogen bonding to phenoxide
• Solvent polarity has no effect
• Only gas phase matters

Correct Answer: Enhanced solvation and hydrogen bonding to phenoxide

Q25. Which description best explains why para electron-withdrawing substituents are effective?

• They donate electrons through resonance to the oxygen
• They withdraw electron density by resonance and inductive effects, stabilizing phenoxide
• They increase steric hindrance only
• They form covalent bonds with the phenoxide oxygen

Correct Answer: They withdraw electron density by resonance and inductive effects, stabilizing phenoxide

Q26. Which method is commonly used experimentally to determine pKa of substituted phenols?

• Mass spectrometry
• Infrared spectroscopy alone
• Potentiometric titration
• Elemental analysis

Correct Answer: Potentiometric titration

Q27. When two electron-withdrawing groups are present on phenol, acidity generally:

• Decreases compared to monosubstituted
• Increases further compared to monosubstituted
• Stays same as monosubstituted
• Becomes neutral

Correct Answer: Increases further compared to monosubstituted

Q28. For resonance-capable substituents, which positions on the ring allow resonance interaction with phenoxide?

• Only meta
• Only ortho and para
• All positions equally
• No positions allow resonance

Correct Answer: Only ortho and para

Q29. Which of the following will stabilize the negative charge in phenoxide most effectively?

• Electron-donating alkyl groups at para
• Electron-withdrawing groups at ortho or para
• Bulky groups at ortho blocking solvation
• Nonpolar substituents

Correct Answer: Electron-withdrawing groups at ortho or para

Q30. Which pair shows the correct acidity order (most to least acidic)?

• p-Nitrophenol > phenol > p-methoxyphenol
• p-Methoxyphenol > phenol > p-nitrophenol
• Phenol > p-nitrophenol > p-methoxyphenol
• p-Methoxyphenol > p-Nitrophenol > phenol

Correct Answer: p-Nitrophenol > phenol > p-methoxyphenol

Q31. Which substituent is an example of a strong inductive electron-withdrawing group?

• –CH₃
• –CF₃
• –OCH₃
• –NH₂

Correct Answer: –CF₃

Q32. How does steric hindrance at ortho positions generally influence acidity in phenols?

• Always increases acidity by stabilizing phenoxide
• Can decrease acidity by reducing solvation of phenoxide
• No effect because sterics are irrelevant
• Makes phenol unable to deprotonate

Correct Answer: Can decrease acidity by reducing solvation of phenoxide

Q33. In gas phase compared to aqueous solution, substituted phenols often show different acidity trends because:

• Resonance is different in gas phase
• Solvation effects are absent in gas phase
• Inductive effects vanish in gas phase
• Substituents change identity in gas phase

Correct Answer: Solvation effects are absent in gas phase

Q34. Which substituent combination will most greatly increase acidity: –NO₂ at para or –OCH₃ at para?

• Para –NO₂
• Para –OCH₃
• Both equal
• Neither affects acidity

Correct Answer: Para –NO₂

Q35. Which of the following statements about phenoxide resonance is true?

• Negative charge is localized only on oxygen
• Negative charge is delocalized into the ring and can be stabilized by EWGs at ortho/para
• Resonance does not affect acidity
• Only sigma bonds are involved in resonance

Correct Answer: Negative charge is delocalized into the ring and can be stabilized by EWGs at ortho/para

Q36. Which structural feature often makes an ortho-substituted phenol anomalous in acidity trends?

• Enhanced resonance at meta position
• Intramolecular hydrogen bonding and steric hindrance
• Complete loss of aromaticity
• Increased molecular symmetry

Correct Answer: Intramolecular hydrogen bonding and steric hindrance

Q37. Which of these substituents would best stabilize phenoxide via resonance donation (thereby decreasing acidity)?

• –NO₂
• –OCH₃
• –CF₃
• –CN

Correct Answer: –OCH₃

Q38. For drug molecules containing phenolic OH, why is understanding substituent effects important?

• It determines color only
• It affects acidity, metabolic stability and binding interactions
• It only affects solubility in organic solvents
• It is irrelevant for pharmacology

Correct Answer: It affects acidity, metabolic stability and binding interactions

Q39. Which experimental observation supports resonance stabilization of phenoxide by a para nitro group?

• Higher pKa compared to phenol
• Lower pKa compared to phenol
• No shift in UV spectrum
• Loss of aromaticity

Correct Answer: Lower pKa compared to phenol

Q40. Which of the following substituents is likely to make phenol a weaker acid than unsubstituted phenol?

• –CF₃
• –NO₂
• –OCH₃
• –CN

Correct Answer: –OCH₃

Q41. If two substituents are present, one donating and one withdrawing, the acidity will depend on:

• The net electronic balance (strength and positions of both groups)
• Only the donating group
• Only the withdrawing group
• Neither; acidity is fixed

Correct Answer: The net electronic balance (strength and positions of both groups)

Q42. Which technique can help quantify substituent electronic effects for correlation with acidity?

• Hammett equation and sigma constants
• Colorimetry only
• Simple mass measurement
• Thin layer chromatography alone

Correct Answer: Hammett equation and sigma constants

Q43. Which is true for the resonance effect of –OH substituent at para on phenol acidity?

• –OH at para withdraws electrons by resonance
• –OH at para donates electrons by resonance, reducing acidity
• –OH has no resonance interaction
• –OH converts phenol into a carboxylic acid

Correct Answer: –OH at para donates electrons by resonance, reducing acidity

Q44. Which of the following statements about methoxy (–OCH3) substituent is correct?

• It is purely electron-withdrawing by induction
• It donates electrons by resonance and slightly withdraws by induction
• It has no effect on acidity
• It always increases acidity drastically

Correct Answer: It donates electrons by resonance and slightly withdraws by induction

Q45. Which phenol is expected to be least acidic among these?

• p-Nitrophenol
• Phenol
• p-Methoxyphenol
• 2,4-Dinitrophenol

Correct Answer: p-Methoxyphenol

Q46. Why does a cyano group (–CN) at para increase phenol acidity?

• Because –CN donates electrons by resonance
• Because –CN withdraws electrons by both inductive and resonance effects stabilizing phenoxide
• Because –CN makes the molecule hydrophobic only
• Because –CN forms intramolecular hydrogen bonds with –OH

Correct Answer: Because –CN withdraws electrons by both inductive and resonance effects stabilizing phenoxide

Q47. In designing phenolic drug molecules, reducing phenol acidity may be desired to:

• Increase metabolic activation via conjugation
• Reduce levels of ionized species at physiological pH, affecting membrane permeability
• Make compound more water-soluble always
• Prevent any binding to targets

Correct Answer: Reduce levels of ionized species at physiological pH, affecting membrane permeability

Q48. Which substituent effect is most important when comparing acidity of ortho vs para substituted phenols of the same group?

• Only inductive effect
• Intramolecular hydrogen bonding and steric/solvation differences
• Mass differences of substituents
• Color differences

Correct Answer: Intramolecular hydrogen bonding and steric/solvation differences

Q49. For para substituents, which parameter correlates best with change in phenol pKa?

• Hammett sigma (σ) constants
• Boiling point of substituent
• Molecular weight of substituent
• Color of substituent

Correct Answer: Hammett sigma (σ) constants

Q50. When a substituent both donates by resonance and withdraws by induction (e.g., halogens), net effect on acidity is often:

• Simple to predict as strongly donating
• Opposing effects lead to a small net change, often slight increase in acidity
• Always decreases acidity strongly
• Converts phenol into an amino compound

Correct Answer: Opposing effects lead to a small net change, often slight increase in acidity

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