CHEM 212 - 7 Nucleophilicity and Substitution Reactions (1)

Nucleophilicity

  • Definition: The reactivity of a nucleophile in substitution reactions.

  • Relevance: Most relevant to SN2 rates since nucleophile (Nu) is involved in the rate-determining step (RDS).

  • In SN1 reactions, the nucleophile is involved after the RDS.

Factors Affecting Nucleophilicity

  1. Solvation:

    • The solvent shell must be shed for the reaction to occur.

  2. Electronegativity:

    • More electronegative nucleophiles are less reactive; however, this is solvent-dependent.

  3. Polarizability:

    • Refers to the ease of distortion of electrons towards the electrophile.

Nucleophile Examples

  • Trends for Nu-

    • left to right on periodic table = worse Nu- (Ex: F)

    • moving down = better Nu- (Ex: I, because larger atoms can better stabilize the negative charge)

    • moving down means its also solvent dependent

  • Poor Nucleophiles: F, Cl, O

  • Good Nucleophiles: N, I, Br

Polarizability

  • Definition: How easy it is to distort the electron cloud of a nucleophile towards an electrophile.

  • Characteristics of Nucleophiles:

    • Hard Nucleophiles (less polarizable): These do not have easily distortable electron clouds.

    • Soft Nucleophiles (more polarizable): These nucleophiles, with higher distortion capabilities, are typically better nucleophiles.

  • Examples:

    • Less polarizable: F-

    • More polarizable: I-, Cl-, R2N-, R-, O-.

    • Conclusion: Nucleophilicity increases with polarizability. more polarizable = better Nu-

Trends in Nucleophilicity

  1. **Charge:

    • Negatively charged nucleophiles are more reactive than their conjugate acids.**

  2. Comparison of Nucleophilic Reactivity:

    • When nucleophilic atom is the same, compare via pKa of Nu-H.

      • pKa 16 -> Nu− (best)

      • pKa 15.7 -> Nu− (better)

      • pKa 10 -> Nu− (worst)

      • pKa 4.6 -> Nu− (least basic, worst nucleophile)

      • lower pKa of CA = worst Nu- = least basic

  3. Basicity Correlation:

    • Nucleophilicity parallels basicity; higher charge equals better nucleophilicity.

  1. Periodic Table Consideration:

    • Along a row, nucleophilicity and basicity are correlated.

      • Example comparison of pKa values (higher pKa = better nucleophile =more basic).

Solvent Effects on Nucleophilicity – Polar Protic Solvents

  • Polar Protic Solvents:

    • nucleophilicity correlates with polarizability, not with basicity.

    • Strong solvation of small negatively charged nucleophiles via hydrogen bonding reduces their reactivity compared to larger, diffuse nucleophiles.

  • Examples of Nucleophiles:

    • Better Nu−: Larger, weaker solvation

    • Worse Nu−: Smaller, strong solvation

    • I- > Br- > Cl- > F- (from best Nu to worst Nu)

Solvent Effects on Nucleophilicity – Polar Aprotic Solvents

  • Polar Aprotic Solvents:

    • Negatively charged nucleophiles are not strongly solvated, leading to correlation with basicity.

    • Reverse trend in reactivity compared to polar protic solvents observed here.

      • Example: I- < Br- < Cl- < F- (from worst to best Nu)

Summary of Solvent Effects Along a Group

  • Trends in Polar Protic Solvents:

    • Nucleophillicity correlates with polarizability

    • Increasing size and polarity makes a better Nu

    • dominated by solvation degree

  • Trends in Polar Aprotic Solvents:

    • Nucleophilicity correlates with basicity

    • increasing basicity makes a better Nu

    • dominated by the strong bond with carbon

  • Examples:

    • I− is the better nucleophile in PP solvents

    • F− is the better nucleophile in PA solvents.

Mechanisms in SN1 and SN2 Reactions

  • 2° + Allylic Mechanisms = SN1 or SN2

    • Strong nucleophile favors SN2.

    • Polar aprotic solvent favors SN2

    • polar protic solvent favours SN1

  • Product Formation:

    • Single product formed with inverted stereocenter when SN2 favored.

    • when both SN1 and SN2 compete it creates a mixture of products (includes both the inverted stereocenter from the SN2 and the racemic mixture from the SN1)

Knowledge Check Questions

  1. In a polar aprotic solvent, rank the nucleophiles:

    • The correct order: I−, Br−, Cl−, F−

    • If polar protic, rank changes favoring different nucleophiles.

  2. Which nucleophile favors SN2 mechanism?

    • Only charged nucleophile indicates favorability.

  3. Will the reaction undergo SN1 or SN2?

    • Likely results as a mixture of both, difficulty in prediction based on conditions.