SN1 versus SN2 reactions MCQs With Answer

Introduction: As a B. Pharm student, mastering SN1 versus SN2 reactions is essential for understanding drug metabolism, synthesis, and reaction prediction. This concise guide highlights key differences in mechanism, rate law, stereochemistry, leaving group ability, nucleophile strength, and solvent effects to help you confidently approach reaction problems. Emphasis on carbocation stability, backside attack, and solvent choice will improve problem-solving and synthetic strategy. These MCQs with answer focus on real B. Pharm applications — kinetics, rearrangements, and experimental probes — to deepen conceptual clarity and exam readiness. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which rate law correctly describes a typical SN2 reaction?

• rate = k[substrate]
• rate = k[nucleophile]
• rate = k[substrate][nucleophile]
• rate = k[substrate][leaving group]

Correct Answer: rate = k[substrate][nucleophile]

Q2. What is the stereochemical outcome of a pure SN2 reaction at a chiral carbon?

• Complete racemization
• Retention of configuration
• Inversion of configuration (Walden inversion)
• No change in stereochemistry

Correct Answer: Inversion of configuration (Walden inversion)

Q3. Which substrate is most likely to undergo an SN1 reaction?

• Methyl halide
• Primary alkyl halide
• Secondary alkyl halide with no resonance
• Tertiary alkyl halide

Correct Answer: Tertiary alkyl halide

Q4. Which factor most increases the rate of an SN1 reaction?

• Stronger nucleophile
• Better leaving group
• Higher concentration of nucleophile
• Less polar solvent

Correct Answer: Better leaving group

Q5. How does a polar aprotic solvent (e.g., DMSO) influence SN2 reactions?

• It stabilizes carbocations and favors SN1
• It solvates anions strongly and reduces nucleophilicity
• It increases nucleophile strength and favors SN2
• It prevents backside attack by steric hindrance

Correct Answer: It increases nucleophile strength and favors SN2

Q6. In SN1 reactions, what intermediate is formed after the rate-determining step?

• Carbanion
• Radical
• Carbocation
• Concerted transition state only

Correct Answer: Carbocation

Q7. Which leaving group is considered the best among the following for SN reactions?

• OH-
• Cl-
• Br-
• NH2-

Correct Answer: Br-

Q8. What experimental observation indicates a reaction follows SN1 kinetics?

• Rate depends on nucleophile concentration
• Rate is second order overall
• Rate is first order in substrate only
• Rate decreases with increasing solvent polarity

Correct Answer: Rate is first order in substrate only

Q9. Why do tertiary carbons favor SN1 over SN2?

• Tertiary carbons have less steric hindrance for nucleophiles
• Tertiary carbocations are highly stabilized by hyperconjugation
• Tertiary substrates form strong hydrogen bonds with nucleophiles
• Tertiary carbons cannot form carbocations

Correct Answer: Tertiary carbocations are highly stabilized by hyperconjugation

Q10. Which nucleophile property most strongly favors SN2 reactions?

• High nucleophilicity and low steric bulk
• High polarizability but bulky
• Weak base and poor nucleophile
• Large, resonance-stabilized anion

Correct Answer: High nucleophilicity and low steric bulk

Q11. What is the role of the solvent in stabilizing the transition state for SN1?

• Solvent destabilizes carbocations to slow SN1
• Polar protic solvents stabilize carbocations and leaving groups, lowering activation energy
• Nonpolar solvents favor ionization in SN1
• Solvent strength is irrelevant to SN1 rates

Correct Answer: Polar protic solvents stabilize carbocations and leaving groups, lowering activation energy

Q12. Which of the following is a hallmark of an SN2 transition state?

• Planar carbocation intermediate
• Simultaneous bond making and bond breaking at one step
• Two-step mechanism with discrete intermediate
• Formation of a radical pair

Correct Answer: Simultaneous bond making and bond breaking at one step

Q13. For a secondary alkyl bromide reacting with a strong nucleophile in DMSO, which mechanism is most likely?

• Always SN1
• Always E1
• Likely SN2, though competing E2 possible with strong base
• Radical substitution

Correct Answer: Likely SN2, though competing E2 possible with strong base

Q14. Which experimental technique can distinguish SN1 from SN2 by measuring dependence on nucleophile concentration?

• NMR spectroscopy at equilibrium only
• Rate law kinetic studies by varying concentrations
• IR spectroscopy of functional groups
• Melting point determination

Correct Answer: Rate law kinetic studies by varying concentrations

Q15. How do leaving group basicity and stability relate to SN reaction rates?

• Stronger bases are better leaving groups
• Better leaving groups are weak bases and more stable anions, increasing SN rates
• Leaving group ability is independent of basicity
• Only steric bulk determines leaving group ability

Correct Answer: Better leaving groups are weak bases and more stable anions, increasing SN rates

Q16. Which statement best summarizes nucleophilicity trends in polar protic solvents?

• Smaller, more basic anions are better nucleophiles due to less solvation
• Larger, more polarizable anions are better nucleophiles because small anions are strongly solvated
• Nucleophilicity equals basicity in all solvents
• Neutral molecules are always better nucleophiles than anions

Correct Answer: Larger, more polarizable anions are better nucleophiles because small anions are strongly solvated

Q17. Which reaction condition promotes SN1 but disfavors SN2?

• Strong, small nucleophile in polar aprotic solvent
• Weak nucleophile in polar protic solvent with a tertiary substrate
• Primary substrate with sterically hindered nucleophile
• High concentration of nucleophile in aprotic medium

Correct Answer: Weak nucleophile in polar protic solvent with a tertiary substrate

Q18. What stereochemical result is expected for an SN1 reaction at a chiral center?

• Complete retention only
• Complete inversion only
• Racemization, often with slight retention bias due to ion pair effects
• No reaction observed

Correct Answer: Racemization, often with slight retention bias due to ion pair effects

Q19. Which reagent pair and solvent is commonly used for Finkelstein reaction (halogen exchange via SN2)?

• NaI in acetone
• NaCl in water
• HBr in ethanol
• NaF in methanol

Correct Answer: NaI in acetone

Q20. How does resonance stabilization influence SN1 reactivity?

• Resonance stabilization of the carbocation decreases SN1 rate
• Resonance stabilization of the carbocation increases SN1 rate
• Resonance has no effect on SN1
• Resonance favors SN2 exclusively

Correct Answer: Resonance stabilization of the carbocation increases SN1 rate

Q21. Which isotopic experiment result supports an SN1 mechanism?

• No rate change upon using deuterated solvent
• Large primary kinetic isotope effect on the leaving-group bond cleavage
• Rate depends on nucleophile isotopic composition
• Rate is second order with respect to nucleophile

Correct Answer: Large primary kinetic isotope effect on the leaving-group bond cleavage

Q22. Neighboring group participation (anchimeric assistance) often results in:

• Slower substitution due to steric hindrance
• Formation of stabilized cyclic intermediates and altered stereochemistry
• No change to mechanism or rate
• Exclusive E2 elimination

Correct Answer: Formation of stabilized cyclic intermediates and altered stereochemistry

Q23. What does the Hammond postulate predict for the SN1 ionization transition state?

• Transition state resembles reactants for endothermic steps
• Transition state resembles products (carbocation) when ionization is endothermic
• Hammond postulate does not apply to SN1
• Transition state is always symmetrical

Correct Answer: Transition state resembles products (carbocation) when ionization is endothermic

Q24. In nucleophilic substitution, which leaving group makes the reaction fastest in protic solvent?

• F-
• Cl-
• Br-
• OH-

Correct Answer: Br-

Q25. A secondary alkyl tosylate is treated with sodium azide (NaN3) in DMF. The major mechanism is likely:

• SN1 due to tosylate leaving group
• SN2 due to good nucleophile and polar aprotic solvent
• E1 elimination primarily
• Radical substitution

Correct Answer: SN2 due to good nucleophile and polar aprotic solvent

Q26. Which observation indicates formation of a contact ion pair during SN1?

• Complete racemization with no retention
• Stereochemical retention predominates due to nucleophile approaching within solvent shell
• No carbocation formation
• Reaction is second order

Correct Answer: Stereochemical retention predominates due to nucleophile approaching within solvent shell

Q27. Which substrate would be most reactive toward SN2 by iodide ion?

• tert-Butyl chloride
• Isopropyl bromide
• n-Butyl chloride
• Benzyl chloride

Correct Answer: Benzyl chloride

Q28. What effect does increasing temperature typically have on SN1 vs SN2 competition?

• Favors SN1 exclusively
• Favors SN2 exclusively
• Often increases elimination (E1/E2) competition; effect depends on activation barriers
• No change in product distribution

Correct Answer: Often increases elimination (E1/E2) competition; effect depends on activation barriers

Q29. Which mechanism is likely when a poor nucleophile but weakly basic solvent (e.g., ethanol) is used with a secondary substrate?

• SN2 predominates
• SN1 or E1 may occur depending on conditions
• Radical halogenation
• Concerted pericyclic reaction

Correct Answer: SN1 or E1 may occur depending on conditions

Q30. In the presence of a very strong, bulky base, what pathway competes with SN2 for primary substrates?

• SN1
• E2 elimination
• Radical substitution
• Nucleophilic aromatic substitution

Correct Answer: E2 elimination

Q31. Which statement is true about solvolysis reactions (substitution by solvent)?

• They are typically concerted SN2 processes
• They commonly proceed via SN1 with solvent acting as nucleophile
• Solvolysis never gives racemic mixtures
• Solvolysis requires aprotic solvents only

Correct Answer: They commonly proceed via SN1 with solvent acting as nucleophile

Q32. What characterizes a borderline case where SN1 and SN2 compete?

• Extremely reactive methyl substrate
• Primary substrate in strongly protic solvent
• Secondary substrate with moderate nucleophile and solvent that neither strongly stabilizes carbocations nor nucleophiles
• Only radical pathways are possible

Correct Answer: Secondary substrate with moderate nucleophile and solvent that neither strongly stabilizes carbocations nor nucleophiles

Q33. In biological systems, which substituent commonly participates in SN2-like nucleophilic displacement?

• Hydrogen abstraction by radicals
• Phosphate backbone attack in phosphoryl transfer reactions
• Aromatic electrophile substitution
• Formation of carbocations in enzyme active sites only

Correct Answer: Phosphate backbone attack in phosphoryl transfer reactions

Q34. Why is fluoride a poor leaving group in protic solvents for SN reactions?

• Because F- is too large to leave
• Because F- is a very weak base
• Because F- is strongly solvated and is a relatively strong base, making it a poor leaving group
• Because fluoride forms stable carbocations

Correct Answer: Because F- is strongly solvated and is a relatively strong base, making it a poor leaving group

Q35. What product distribution is expected when tert-butyl chloride reacts with water?

• Major SN2 substitution product
• Major SN1 substitution product (tert-butyl alcohol) with possible elimination
• No reaction due to steric hindrance
• Exclusive formation of ethers via SN2

Correct Answer: Major SN1 substitution product (tert-butyl alcohol) with possible elimination

Q36. How does increasing the concentration of a nucleophile affect the rate of SN1 and SN2 reactions respectively?

• Increases SN1 rate, no effect on SN2
• No effect on SN1, increases SN2 rate
• Decreases both SN1 and SN2 rates
• Increases SN1 rate only at high temperature

Correct Answer: No effect on SN1, increases SN2 rate

Q37. Which experimental observation supports a backside attack in SN2?

• Retention of configuration at stereocenter
• Inversion of configuration at stereocenter
• No stereochemical information can be obtained
• Complete racemization

Correct Answer: Inversion of configuration at stereocenter

Q38. What is a common laboratory method to convert a poor leaving group (OH) into a better leaving group for substitution?

• Oxidize the alcohol to a ketone
• Convert OH to a tosylate (OTs) or mesylate (OMs)
• Replace OH with hydrogen
• Direct SN2 displacement of OH without activation

Correct Answer: Convert OH to a tosylate (OTs) or mesylate (OMs)

Q39. Which of the following best describes the energy profile of an SN2 reaction?

• Two transition states with an intermediate valley
• Single concerted transition state with one activation barrier
• Formation of a stable carbocation intermediate
• No activation energy required

Correct Answer: Single concerted transition state with one activation barrier

Q40. In a competition experiment, a tertiary substrate reacts faster in methanol than in acetone. This suggests what mechanism?

• SN2 favored in methanol
• SN1 favored in methanol due to polar protic stabilization
• SN2 favored in acetone only
• No substitution occurs in methanol

Correct Answer: SN1 favored in methanol due to polar protic stabilization

Q41. Which mechanistic pathway best explains rearrangements (hydride or alkyl shifts) during nucleophilic substitution?

• Concerted SN2 mechanisms cause rearrangements
• SN1 via carbocation intermediates allows rearrangement to more stable carbocations
• Radical mechanisms only
• Pericyclic rearrangements unrelated to substitution

Correct Answer: SN1 via carbocation intermediates allows rearrangement to more stable carbocations

Q42. What effect does a bulky nucleophile have on SN2 reactions?

• It accelerates SN2 due to steric bulk
• It slows or prevents SN2 due to steric hindrance
• No effect; nucleophile size is irrelevant
• It converts mechanism to radical substitution

Correct Answer: It slows or prevents SN2 due to steric hindrance

Q43. Which statement is true about benzylic and allylic substrates in nucleophilic substitution?

• They are unreactive in SN1 due to instability of carbocations
• They often undergo SN1 or SN2 readily due to resonance-stabilized transition states or carbocations
• They only undergo radical substitution
• They cannot undergo nucleophilic substitution

Correct Answer: They often undergo SN1 or SN2 readily due to resonance-stabilized transition states or carbocations

Q44. Which factor explains why iodide is a better nucleophile than fluoride in protic solvents?

• Iodide is less polarizable than fluoride
• Fluoride is larger and less basic
• Iodide is less strongly solvated and more polarizable, making it a stronger nucleophile in protic solvents
• Fluoride is always a better nucleophile in protic solvents

Correct Answer: Iodide is less strongly solvated and more polarizable, making it a stronger nucleophile in protic solvents

Q45. During SN2, what is the geometry of the transition state at the reacting carbon?

• Tetrahedral-like but with partial bonds (trigonal bipyramidal analogy for backside approach)
• Perfect planar sp2 geometry
• Linear geometry
• Square planar geometry

Correct Answer: Tetrahedral-like but with partial bonds (trigonal bipyramidal analogy for backside approach)

Q46. Which reagent set illustrates an SN2-driven substitution via nucleophilic attack on a primary alkyl halide?

• KOH in water
• NaI in acetone
• H2SO4 at high temperature
• AgNO3 in ethanol with tertiary halide

Correct Answer: NaI in acetone

Q47. Which observation is consistent with a solvent-separated ion pair in SN1 reactions?

• Fast nucleophile capture with complete retention
• Free carbocation behavior leading to nearly complete racemization
• No intermediate formed
• Exclusive SN2 pathway

Correct Answer: Free carbocation behavior leading to nearly complete racemization

Q48. Which of the following increases SN2 reaction rate most effectively?

• Using a bulky, weak nucleophile
• Switching from protic to polar aprotic solvent and using a strong nucleophile
• Using a tertiary substrate
• Decreasing nucleophile concentration

Correct Answer: Switching from protic to polar aprotic solvent and using a strong nucleophile

Q49. In a substitution reaction on a chiral center, partial retention of stereochemistry suggests which mechanistic nuance?

• Pure SN2 with no intermediate
• SN1 with intimate ion pair or neighboring group participation causing stereochemical bias
• No substitution occurred
• Exclusive radical mechanism

Correct Answer: SN1 with intimate ion pair or neighboring group participation causing stereochemical bias

Q50. For designing a synthetic displacement to introduce an –N3 group into an organic drug intermediate, which strategy is generally preferred?

• Use a tertiary alkyl halide and weak nucleophile
• Use a primary or benzylic leaving group with NaN3 in polar aprotic solvent to favor SN2
• Always perform reaction in water to favor SN1
• Convert substrate to an epoxide first

Correct Answer: Use a primary or benzylic leaving group with NaN3 in polar aprotic solvent to favor SN2

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