In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The molecule that contains the electrophile and the leaving functional group is called the substrate.

The most general form of the reaction may be given as the following:

${\displaystyle {\text{Nuc}}\mathbf {:} +{\ce {R-LG -> R-Nuc}}+{\text{LG}}\mathbf {:} }$

The electron pair (:) from the nucleophile (Nuc) attacks the substrate (R−LG) and bonds with it. Simultaneously, the leaving group (LG) departs with an electron pair. The principal product in this case is R−Nuc. The nucleophile may be electrically neutral or negatively charged, whereas the substrate is typically neutral or positively charged.

An example of nucleophilic substitution is the hydrolysis of an alkyl bromide, R-Br under basic conditions, where the attacking nucleophile is hydroxyl (OH⁻) and the leaving group is bromide (Br⁻).

${\displaystyle {\ce {R-Br + OH- -> R-OH + Br-}}}$

Nucleophilic substitution reactions are common in organic chemistry. Nucleophiles often attack a saturated aliphatic carbon. Less often, they may attack an aromatic or unsaturated carbon.