Nucleophilic substitution reaction

In chemistry, nucleophilic subsitution is a type of chemical reaction in which one nucleophile (electron donor) replaces another as a covalent substituent of some atom. In the examples given here, this is a carbon atom, but this is far from the only possibility.

An example of nucleophilic substitution is the hydrolysis of an alkyl bromide, R-Br, under alkaline conditions, where the "attacking" nucleophile is hydroxide ion, OH^-:

R-Br + OH^- --> R-OH + Br^-

The bromide ion, Br^-, is said to be the leaving group.

The two main mechanisms of nucleophilic substitution are called SN1 and SN2. S stands for chemical substitution, N stands for nucleophilic, and the number represents the kinetic order of the reaction.

SN1

The SN1 reaction takes place in two steps, for example

(CH₃)₃C-Br --> (CH₃)₃C⁺ + Br^-
(CH₃)₃C⁺ + OH^- --> (CH₃)₃C-OH

This gives the overall reaction

(CH₃)₃C-Br + OH^- --> (CH₃)₃C-OH + Br^-

SN1 tends to be important when the central carbon atom is surrounded by bulky groups, both because such groups interfere sterically with the SN2 reaction (discussed below) and because substituents on the central carbon increase the rate of carbocation formation (the first reaction in the scheme above).

The rate of the overall reaction is essentially equal to that of carbocation formation, which does not involve the attacking nucleophile. Thus the overall rate depends on the concentration of the substrate but not on that of the nucleophile, and the kinetic order of the reaction is one:

rate = k[RX]

Because the intermediate carbocation, R⁺, is planar, the central carbon is not a stereocenter, even if it was a stereocenter in the original reactant, so the original configuration at that atom is lost. Nucleophilic attack can occur from either side of the plane, so the product may consist of a mixture of two stereoisomers. In fact, if the central carbon is the only stereocenter in the reaction, the product will be a racemic mixture.

SN2

In the SN2 reaction, the addition of OH^- and the elimination of Br^- take place simultaneously.

SN2 occurs where the central carbon atom is easily accessible to the nucleophile. The rate is second order, depending on the nucleophile concentration as well as the substrate.

rate = k[RX][OH^-]

The nucleophile enters on the opposite side of the carbon to the leaving group, so a stereocenter is inverted by an SN2 reaction.