What are the key differences between bases and nucleophiles? What factors influence whether something is a good base or good nucleophile or both?

A key point few students get is that basicity is thermodynamic (regarding energetic stability) and nucleophilicity is kinetic (regarding the speed or rate of the process).

In other words...

• a "better" base wants an #"H"^(+)# more (as a Bronsted-Lowry base), and more energetically favors donating a lone pair of electrons to get it (as a Lewis base).
• a "better" nucleophile can donate a lone pair of electrons more quickly.

Some factors that effect an increase in basicity are:

• More electron-donating groups (e.g. alkyl groups, #"CH"_3-"CH"_2 - cdots #) surrounding the central atom that has a lone pair of electrons, since the lone pair electron density becomes more concentrated.

For example, the second molecule here is the better base.

• Higher #bb("pKa")#. A stronger base has a higher #"pKa"#, or lower #"pKb"# (but #"pKa"# is used more often in organic chemistry).

For example, #"NH"_3# compared to #"H"_2"O"# is a better base, since its #"pKa"# is #~~ 36# compared to #15.7#, respectively (in organic chemistry).

Some factors that effect an increase in nucleophilicity are:

• Less steric hindrance.

For example, in the above image, although #("CH"_3)_3"C"-"O":^(-)# is a better base, it is a worse nucleophile than #"CH"_3"CH"_2-"O":^(-)# because it's bulkier, slower, and less capable of donating electron density into cramped spaces.

• A solvent that does not increase the basicity of the nucleophile, e.g. an aprotic solvent (such as dimethylsulfoxide [DMSO], dimethyl ether, etc). In this consideration, we note that a high thermodynamic tendency to be a base can interfere with the ability to act as a good nucleophile.

For example, the first scenario here more effectively allows the nucleophile to act as a nucleophile, because the solvent does not donate a proton to the nucleophile.