Leaving group

A leaving group is an atom or group of atoms that detaches from a chemical substance. The remaining molecule or fragment remaining is known as the residual or main part. The term leaving group is dependent on the context of the statement.^[1]

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The ability for a functional group to leave is called lability. Leaving groups affect the intrinsic reactivity, not the nucleophilic discrimination factors.

The lower the pK_a of the conjugate acid, the better the leaving group. This is because the lower the pKa of the conjugate acid of the leaving group, the more it stays in its anion (leaving groups may be neutral), leaving group, form. This anion stability means that the leaving group is less likely to react with the cation formed by the leaving group's absence (this is the case with bad leaving groups). Without stabilization, a leaving group will become a nucleophile due to its negative charge, and if this happens, the reaction goes in circles. This is why a strong base is a poor leaving group. S_N1 reactions prefer halides, pseudohalides, and non-coordinating ions as leaving groups. Halide salts are particularly useful leaving groups because they can be abstracted by silver ions, to form insoluble silver halides.

In room temperature water, the sequence of lability is:

• Less lability
• amine NH₂⁻
• methoxy CH₃O⁻
• hydroxyl HO⁻
• carboxylate CH₃COO⁻
• F⁻
• water
• Cl⁻
• Br⁻
• I⁻
• azide N₃⁻
• thiocyanate SCN⁻
• nitro NO₂
• Greater Lability

  NO₃⁻ is also weaker than F⁻.

A direct application of the difference in leaving group stability is in the carboxylic acid derivatives. The worse the leaving group, the more stable the chemical, which makes these form a hierarchy that can be separated in the lab. Amines, which are the worst leaving group, are the most stable compound, and attacking any carboxylic acid derivative with an amine produces an amide. Esters are the second most stable followed by anhydrides and finally halides.

During the S_N2 nucleophilic attack, a partial negative charge forms on the leaving group. During S_N1 reactions, the leaving group anionizes and leaves. In general, amine, methoxy and hydroxyl groups never act as leaving groups in a substitution reaction.

In the non-mechanistic transformations, leaving group is the actual substituent group present in the substrate and product.

The structure of the leaving group affects the rates of both Sn1 and Sn2 reactions. In general, the more stable the leaving group is as a free species--that is after it has left--the faster it will leave. This stability also reflects the basicity of the species: the more stable it is, the weaker base it is.

See also

• Nucleofuge
• Electrofuge

References

1. ^ International Union of Pure and Applied Chemistry. "leaving group". Compendium of Chemical Terminology Internet edition.