Nucleophilic Substitution Of Pyridine

Due to the electron absorption of the nitrogen atom on the pyridine ring, the electron cloud density of the carbon atom on the ring decreases, especially the electron cloud density at the 2 and 4 sites is lower, so the nucleophilic substitution reaction on the ring is easy to occur, and the substitution reaction mainly occurs at the 2 and 4 sites.
The reaction of pyridine with sodium amino to form 2-aminopyridine is called the Chizhibabin reaction, and if the 2 sites are already occupied, the reaction occurs at 4 sites to obtain 4-aminopyridine, but the yield is low. If there is a good leaving group (such as halogen, nitro) in the α or γ position of the pyridine ring, it is easy to occur nucleophilic substitution reaction. For example, pyridine can have a nucleophilic substitution reaction with ammonia (or amine), alkoxide, water and other weak nucleophilic reagents.