Step 1: Identify the atoms that can donate electrons
Begin by identifying which atoms in each molecule have lone pairs available to donate. These are your nucleophilic centers.
💡 Tip:
Lone pairs on heteroatoms like nitrogen, oxygen, and sulfur are often omitted in chemical structures. Be sure to recognize that these atoms almost always have lone pairs, and it’s important to know how many each one has in a given structure.
Step 2: Consider charge
Key rule:
Negatively charged species are stronger nucleophiles than their neutral counterparts.
Why?
Because they possess more electron density, making them more eager to donate electrons.
Step 3: Compare different nucleophilic atoms
Next, compare nucleophiles that involve different atoms — like NH2– vs. OH–, or F– vs. I–. Two key trends will help you here: electronegativity and atomic size.
Electronegativity (same row)
Key rule:
When the nucleophilic atoms are in the same period (row) of the periodic table, nucleophilicity decreases as electronegativity increases.
Why?
Because more electronegative atoms hold onto their electrons more tightly, making them less likely to donate.
Size (same column)
Key rule:
When nucleophilic atoms are in the same column (group), nucleophilicity generally increases as size increases.
For halides, this trend depends heavily on the solvent
In polar protic solvents (e.g., water, alcohols), nucleophilicity increases with size.
Why?
Because in these solvents, anions are strongly solvated (surrounded) by hydrogen bonds.
F– ions are small and highly stabilized by solvation and become less reactive.
I– ions are larger and less solvated, making them more available to react.
In polar aprotic solvents (e.g., DMSO, acetone), the trend reverses.
Polar aprotic solvents do not form strong hydrogen bonds with anions, so solvation is minimal.
This allows smaller, more basic nucleophiles like F– to remain highly reactive.
Step 4: Compare the same nucleophilic atoms
Now, compare nucleophiles that contain the same nucleophilic atom — like the oxygen in ethoxide vs. the oxygen in acetate.
The key difference lies in how stable the lone pair is.
Key rule:
A less stable lone pair is more reactive, which makes the nucleophile stronger.
Let’s break down the factors that influence lone pair stability:
Resonance
If a lone pair is delocalized through resonance (as in acetate), it’s less nucleophilic because the electron density is spread out and less reactive.
Inductive effects
Nearby electronegative atoms can pull electron density away through sigma bonds, stabilizing the lone pair and making the atom less nucleophilic.
Orbital hybridization
Electrons in orbitals with more s-character are held closer to the nucleus, making them more stable and less nucleophilic.
Each of these factors — resonance, induction, hybridization — ties back to basicity, since less stable bases are sometimes more reactive nucleophiles.
Step 5: Consider steric hinderance
Even a reactive nucleophile may struggle if it’s too bulky to access the electrophile.
These steric effects are especially important in SN2 reactions, where nucleophiles need a direct, backside approach.
Step 6: Rank the nucleophiles
Now that you’ve:
- Identified nucleophilic atoms
- Considered their charge
- Compared different atoms (electronegativity and size)
- Compared the same atoms (resonance, induction, orbitals)
- Factored in steric hindrance
You’re ready to combine all of these factors and rank nucleophiles by strength, depending on the specific conditions — especially the solvent!
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