What determines the nucleophile's strength?

1 Answer
Jun 2, 2015

The key factors that determine the nucleophile's strength are charge, electronegativity, steric hindrance, and nature of the solvent.


Nucleophilicity increases as the density of negative charge increases.

An anion is always a better nucleophile than a neutral molecule, so the conjugate base is always a better nucleophile.

Thus, #"HO"^(-) > "H"_2"O"#; #"H"_2"N"^(-) > "H"_3"N"#; #"HS"^(-) > "H"_2"S"#


A highly electronegative atom is a poor nucleophile because it is unwilling to share its electrons.

As electronegativity increases, nucleophilicity decreases.

The order of electronegativity is

#"C"# <# "N"# < #"O"# < #"F"#

So the order of nucleophilicity is

#"CH"_3^(-) > "NH"_2^(-) > "HO"^(-) > "F"^(-)#

Steric hindrance

The bulkier a nucleophile is, the more difficult it is to attack the substrate, and the weaker the nucleophile becomes.

So the order of nucleophilicity is

#("CH"_3)_3"CO"^(-) < ("CH"_3)_2"CHO"^(-) < "CH"_3"CH"_2"O"^(-) > "CH"_3"O"^(-)#

Effect of Solvent

A polar protic solvent such as water or methanol can hydrogen bond with a nucleophile.

This creates a shell of solvent molecules around the nucleophile that hinders its access to the substrate and decreases its nucleophilicity.

A polar aprotic solvent like acetone or dimethylformamide preferentially solvates cations, leaving an almost "bare" nucleophile. This increases its nucleophilicity .