Nucleophiles

A nucleophile is a chemical species that donates an electron pair to an electrophile to form a covalent bond. Under Lewis theory, nucleophiles are Lewis bases; electrophiles are Lewis acids. Nucleophiles can be negatively charged or neutral molecules bearing lone pairs or pi bonds.

Common nucleophiles include halide ions (Cl−, Br−, I−), hydroxide (OH−), alkoxides (RO−), cyanide (CN−), amines (R3N), thiolates (RS−), enolates, carbanions, and organometallic reagents such as Grignard reagents and organolithiums. Nucleophiles are classified as hard or soft per HSAB theory; hard nucleophiles tend to attack hard electrophiles and soft nucleophiles prefer soft electrophiles.

Nucleophilicity depends on electron density, charge, polarizability, and steric factors. In protic solvents, nucleophilicity often increases down a group due to solvation effects; in polar aprotic solvents, nucleophilicity tracks basicity, so smaller, strongly basic species can be very reactive (for example, fluoride in acetone).

Two main reaction types illustrate nucleophilic behavior: SN2, a concerted backside attack with inversion, favored by strong, small nucleophiles and less-substituted substrates; and SN1, where carbocation formation controls the rate and nucleophile strength mainly influences the product distribution. Nucleophiles also add to carbonyl groups and participate in substitution and polymerization reactions.

In synthesis, nucleophiles are essential for forming carbon–carbon and carbon–heteroatom bonds. Their selection depends on solvent, substrate, and the desired outcome, including stereochemistry and rate.