SN2 - Second-order Nucleophilic Substitution
What are the characteristics of a good leaving group (nucleofuge), and what is the difference between a leaving group and a nucleophile? Frequently, the leaving group in a nucleophilic substitution is, like the nucleophile, negatively charged. So, why does the nucleophile enter the substrate, while the leaving group leaves it? The ability of the nucleofuge to leave the substrate is directly correlated to its ability in stabilizing the negative charge.
If the leaving group is a weak base, it is a good nucleofuge. This can be illustrated by the halide anions. The leaving ability decreases from that of iodide to that of fluoride. This tendency is equivalent to the acidity's tendency in the corresponding hydrohalic acids. Iodide is a good leaving group, while reactions of fluoroalkanes hardly occur, as the fluoride anion is a poor leaving group.
Aside from halide ions, some derivatives of sulfonic acid are also very good leaving groups. These sulfonic acid derivatives are particularly good leaving groups, because they possess substituents that considerably stabilize the negative charge by resonance stabilization.
Due to the extraordinary leaving ability of the triflate anion and other similar anions, such as mesylate and tosylate, these leaving groups are frequently applied to organic syntheses.
Hydroxide as leaving group
The hydroxide anion is a particularly poor leaving group, as its negative charge cannot be stabilized. However, a hydroxy group may be substituted if it has been previously chemically altered by one of the following methods:
- Esterification by one of the sulfonic acid derivatives mentioned above.
- Conversion to the more efficient leaving group water by protonation.