Concept Notes

Nucleophilicity

Base vs Nucleophile

• basicity is a subset of nucleophilicity. All nucleophiles are Lewis bases; they donate a lone pair of electrons. A “base” (or, “Bronsted base”) is just the name we give to a nucleophile when it’s forming a bond to a proton (H+).
• Basicity: nucleophile attacks hydrogen
• Nucleophilicity: nucleophile attacks any atom other than hydrogen. Because we’re talking about organic chemistry here, for our purposes, this is going to mean “carbon” most of the time.
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The three classes of nucleophiles

• 1) Lone Pairs

This is probably the easiest class of nucleophiles to understand, because of the parallels to basicity.

• The nucleophilicity increases as the charge of the atom it is attached to decreases. A simpler way to put this is, “the conjugate base is always a stronger nucleophile”.
• The nucleophilicity increases as you increase the basicity. So as you go across the periodic table from right to left, nucleophilicity also increases. [H3C-- > H2N– > HO– > F– ).
• Nucleophilicity increases as you go down the periodic table. So comparing halides, I– > Br– > Cl– > F–
• In polar protic solvents, nucleophilicity increases with polarizability, because hydrogen bonds form a shell around the less polarizable atoms and decrease their nucleophilicity. In polar aprotic solvents, this is not an issue, [ I– < Br– < Cl– < F– ] so basicity is the most important variable.

• 2) π bonds.

π bonds can also be thought of as nucleophiles: they donate a pair of electrons as well, but in this case the pair is shared between two atoms. This not only covers double bonds, but also triple bonds (alkynes) as well as aromatics and even enols and enolates

• 3) Sigma bonds

The pair of electrons in a sigma bond can, on occasion, also act as nucleophiles.

Four key factors contributing to nucleophilicity

• Charge
• Electronegativity
• Solvent
• Steric hindrance

The Role Of Charge: Nucleophilicity Increases As An Atom’s Electron Density Increases

Electronegativity: Across The Periodic Table, Nucleophilicity Increases With Decreasing Electronegativity

Assuming an atom has a pair of electrons to donate, the ability of a species to donate that pair should be inversely proportional to how “tightly held” it is.

The Choice Of Solvent (Polar Protic vs. Polar Aprotic) Can Drastically Affect Nucleophilicity Trends

A polar protic solvent can participate in hydrogen bonding with a nucleophile, creating a “shell” of solvent molecules around it.

Nucleophilicity Decreases With Increasing Steric Hindrance (“Bulkiness”)

The bulkier a given nucleophile is, the slower the rate of its reactions [and therefore the lower its nucleophilicity].

What makes a good leaving group?

A leaving group is a nucleophile acting in reverse; it accepts a lone pair as the bond between it and its neighbor (usually carbon for our purposes) is broken.

Good leaving groups are weak bases.

In other words pKa is a direct measurement of how “happy” and stable a lone pair of electrons is – the very definition of what we should be looking for when trying to quantify leaving group ability.

So it should be no surprise to find that very weak bases such as  halide ions (I-, Br-, Cl-) water (OH2), and sulfonates such as p-toluenesulfonate (OTs) and methanesulfonate (OMs) are excellent leaving groups.