Amines as an example

Nitrogen bases

Nitrogen bases are the strongest neutral bases, ammonia is the simplest. Substituents that increase electron density on N, raise the energy of the lone pair, and therefore increases its availablity for protonation and so increases basicity of the amine. (larger pK_aH)

Substituents that withdraw electron density from N, lower energy of lone pair making it less available and hence the amine less basic (smaller pK_aH)

What increases electron density on nitrogen?

1. Electron donating substituents
2. lone pair in sp³ orbital

What decreases electron density on nitrogen

Lone pair is less available if

1. nitrogen atom attached to an electron withdrawing group
2. lone pair in sp or sp² hybridised orbital
3. lone pair is conjugated with an electron withdrawing group
4. lone pair involved in maintaining aromaticity

Effects of electron withdrawing groups

These groups have a greater effect on the base the closer they are to the lone pair donor atom. The effects fall off rapidly with distance.

Hybridisation

The more s character an orbital has the more tightly it will hold onto its electrons, and hence the more electron withdrawing it is. The effects are purely inductive electron withdrawal. So an amine substituted with an alkyne group will give the lowest basicity, an alkene will give the middle and an alkane the highest.

If the lone pair itself is in an sp² or sp orbital the electrons are held more tightly and hence are less available for protonation

Basicity of substituted amines

In NH₃ the nitrogen atom is partially negatively charged due to the inductive effects of the hydrogen atoms , but with a molecule such as NF₃ the reverse is true. Replacement of a hydrogen atom in NH₃ with an electron withdrawing group such as F or OH^- results in decreased basicity. This is because the electron withdrawing groups take electron density from the nitrogen atom reducing the availability of the lone pair of electrons.

Replacement of a H atom with an alkyl group usually results in incresed basicity as alkyl groups are usually more electron donating than hydrogen, hence this replacement results in increased basicity.