Nucleophiles, Electrophiles, and Leaving Groups
High-Yield Summary
- A nucleophile donates electron density (lone pairs or π bonds) and acts as a Lewis base; forms include anions, π-bond molecules, and neutral lone-pair molecules.
- Nucleophilicity increases with negative charge, decreases with electronegativity and steric hindrance; protic solvents hydrogen-bond to and weaken nucleophiles.
- Polar protic solvents: nucleophilicity increases down the group, I⁻ > Br⁻ > Cl⁻ > F⁻. Polar aprotic solvents: trend reverses, F⁻ > Cl⁻ > Br⁻ > I⁻.
- An electrophile has a full/partial positive charge; electrophilicity is a kinetic property, distinct from (though correlated with) acidity. Strong electrophiles: carbocations, carbonyl carbons, good-leaving-group substrates.
- SN2: concerted, backside attack, primary/secondary only, rate = k[substrate][nucleophile], inverts stereochemistry. SN1: stepwise via carbocation, favors tertiary, rate = k[substrate], can rearrange.
SN2 vs. SN1
| SN2 | SN1 |
|---|---|
| Concerted, one step, one transition state | Stepwise, two steps, two transition states (via carbocation) |
| Backside attack — needs open access | Nucleophile attacks after leaving group departs |
| Best on primary; ok on secondary; ~none on tertiary | Best on tertiary; ok on secondary; ~none on primary |
| Rate = k[alkyl halide][nucleophile] — bimolecular | Rate = k[alkyl halide] — unimolecular |
| Inversion of configuration (R → S) | Racemization possible; carbocation may rearrange (hydride/alkyl shift) |
| Needs a strong nucleophile | Nucleophile strength doesn't affect rate |
Nucleophilicity Trend by Solvent
| Solvent type | Halide nucleophilicity order |
|---|---|
| Polar protic (H₂O, ROH, NH₃) | I⁻ > Br⁻ > Cl⁻ > F⁻ (larger anion = less solvated) |
| Polar aprotic (DMF, DMSO, acetone) | F⁻ > Cl⁻ > Br⁻ > I⁻ (no H-bonding to shield charge) |
Key Terms
- Nucleophile
- Electron-density donor (Lewis base) that forms a new bond with an electrophile; anions, π-bond molecules, or neutral lone-pair molecules.
- Electrophile
- Species with full/partial positive charge, reactive toward nucleophiles; carbocations, carbonyl carbons, or good-leaving-group substrates.
- Carbocation
- Positively charged carbon with an empty p orbital; the reactive intermediate in an SN1 mechanism.
- Hydride / alkyl shift
- Rearrangement where an H or alkyl group migrates with its bonding electrons to form a more stable carbocation before nucleophilic attack (SN1 only).
Common MCAT Trap
- Nucleophilicity ≠ basicity in polar protic solvents — I⁻ is the best nucleophile there despite being the weakest base of the halides, because solvation dominates.
- SN1 rate depends only on substrate concentration — adding more/stronger nucleophile does not speed up SN1, unlike SN2.
- Electrophilicity is kinetic, not thermodynamic — don't conflate 'good electrophile' with 'strong acid'; they correlate but aren't the same property.
Quick Recall
In a polar aprotic solvent, which halide is the strongest nucleophile, and why?
What stereochemical outcome does SN2 always produce?
Why does SN1 favor tertiary substrates?
Rank carboxylic acid derivatives by electrophilicity.
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