Nucleophilic Substitution Reactions1

Fifty question-and-answer flashcards covering definitions, mechanism details, kinetics, stereochemistry, solvent effects, periodic trends, and factors affecting SN1 and SN2 nucleophilic substitution reactions.

1. What is a nucleophilic substitution reaction?

A reaction in which an incoming nucleophile displaces a leaving group on a tetravalent carbon.

2. Why are alkyl halides common substrates for nucleophilic substitution?

Their C–X bond is polarized; the carbon carries a partial positive charge and halide is a good leaving group, making the carbon susceptible to nucleophilic attack.

3. Define a nucleophile in simple terms.

An electron-rich atom or ion that donates a lone pair to form a new covalent bond.

4. In nucleophilic substitution, what species is expelled from the substrate?

The leaving group, typically a halide ion.

5. What partial charge does carbon bear in an alkyl halide and why?

A partial positive (δ+) because the more electronegative halogen pulls electron density toward itself.

6. What happens if you keep the same alkyl halide but switch nucleophiles?

Different nucleophiles create different substitution products from the same substrate.

7. In SN1 and SN2, what does the abbreviation "SN" mean?

Substitution Nucleophilic.

8. What is the defining kinetic feature of an SN1 reaction?

The rate depends only on the substrate concentration; bond to the leaving group breaks before the nucleophile bonds.

9. What reactive intermediate is formed in most SN1 mechanisms?

A carbocation.

10. How many species appear in the rate-determining step of an SN1 reaction?

One; only the substrate (unimolecular).

11. What is the defining kinetic feature of an SN2 reaction?

Bond breaking and bond forming occur simultaneously in a single concerted step.

12. How many species participate in the rate-determining step of an SN2 reaction?

Two—the substrate and the nucleophile (bimolecular).

13. Do SN2 reactions generate a carbocation intermediate?

No; they proceed through a single transition state without intermediates.

14. Describe the timing of bond-breaking and bond-forming in an SN1 reaction.

They occur sequentially: the leaving group departs first, then the nucleophile attacks.

15. Describe the timing of bond-breaking and bond-forming in an SN2 reaction.

They occur simultaneously during one concerted transition state.

16. On which concentration(s) does the rate of an SN1 reaction depend?

Only on the substrate concentration (first-order).

17. On which concentrations does the rate of an SN2 reaction depend?

On both substrate and nucleophile concentrations (second-order overall).

18. Write the general rate equation for an SN2 reaction.

Rate = k [substrate][nucleophile].

19. What stereochemical outcome is characteristic of SN2 reactions?

Inversion of configuration (Walden inversion).

20. Why does backside attack produce inversion in SN2 reactions?

The nucleophile approaches opposite the leaving group, flipping the tetrahedral arrangement around the carbon.

21. In an SN2 energy profile, what is the highest-energy point called?

The transition state.

22. What does the activation energy (Ea) represent?

The energy barrier reactants must overcome to reach the transition state.

23. Are SN2 reactions typically exergonic or endergonic?

Exergonic; products are lower in energy than reactants (ΔE negative).

24. Define nucleophilicity.

A kinetic measure of how rapidly a species donates an electron pair to an electrophile.

25. Define basicity.

An equilibrium measure of how strongly a species accepts a proton (H⁺).

26. How are charge and nucleophilicity related?

Negatively charged species are generally more nucleophilic because they possess extra electron density to donate.

27. Across a period (left → right), does nucleophilicity increase or decrease?

It decreases due to higher electronegativity and lower polarizability.

28. Down a group (top → bottom), how does nucleophilicity change?

It increases because larger atoms are more polarizable and donate electrons more easily.

29. How does increasing atomic size within a group affect basicity?

Basicity decreases even though nucleophilicity rises.

30. Give an example of a strong, negatively charged nucleophile.

Hydroxide ion (OH⁻).

31. Why can bulky bases be poor nucleophiles?

Steric hindrance prevents them from approaching the electrophilic carbon even though they are strongly basic.

32. Name two good nucleophiles noted in the lecture.

Bromide (Br⁻) and hydrosulfide (HS⁻ or RS⁻).

33. Name two poor nucleophiles listed in the notes.

Water (H₂O) and alcohols (ROH).

34. In SN2 reactions, how does steric hindrance around the electrophilic carbon affect rate?

More hindrance slows the reaction because the nucleophile cannot easily approach.

35. Which alkyl halide class reacts fastest in SN2: methyl, primary, secondary, or tertiary?

Methyl halides react fastest (tertiary are slowest/negligible).

36. What is a protic solvent?

A solvent capable of donating hydrogen bonds; it contains H attached to O or N.

37. What is an aprotic solvent?

A solvent that cannot donate hydrogen bonds because it lacks H bonded to electronegative atoms.

38. Give one example of a polar protic solvent.

Ethanol (or water).

39. Give one example of a polar aprotic solvent.

Acetone (or DMSO).

40. What effect do polar protic solvents have on nucleophiles?

They hydrogen-bond to the nucleophile, forming a solvent cage that lowers its reactivity.

41. Why do polar aprotic solvents accelerate SN2 reactions?

They do not strongly solvate anions, leaving the nucleophile free and highly reactive.

42. What dielectric constant roughly separates polar from non-polar solvents?

A value around 15 ( >15 polar, <15 non-polar ).

43. For SN2 reactions, is a better leaving group weakly or strongly basic?

Weakly basic; good leaving groups stabilize the negative charge.

44. How does the nature of the leaving group influence SN2 rate?

Better leaving groups (weaker bases) increase the reaction rate.

45. Why is an SN2 reaction second order overall?

The rate-determining step involves a simultaneous collision of two reactant molecules (substrate and nucleophile).

46. What symbol represents the rate constant in rate equations?

k.

47. What is meant by a "bimolecular" elementary step?

A single mechanistic step whose rate depends on the concentrations of two reacting species.

48. In SN2 stereochemistry, the product is the __ of the starting stereocenter.

Enantiomer (configuration is inverted).

49. Why must the nucleophile attack opposite the leaving group in an SN2 reaction?

To minimize repulsion and align orbitals for the concerted bond-making/bond-breaking process.

50. In energy terms, what does a negative ΔE indicate about a reaction?

The reaction releases energy; products are lower in energy than reactants (exergonic).