Now what about leaving groups joined to the carbon atom by a C–O bond? There are many of these but the most important are OH itself, the carboxylic esters, and the sulfonate esters. First, we must make one thing clear: alcohols themselves do not react with nucleophiles. In other words, OH⁻ is never a leaving group. Why not? For a start hydroxide ion is very basic, and if the nucleophile were strong enough to displace hydroxide ion it would be more than strong enough to remove the proton from the alcohol.

But we do want to use alcohols in nucleophilic substitution reactions because they are easily made (by the reactions in Chapter 9, for example). The simplest solution is to protonate the OH group with strong acid. This will work only if the nucleophile is compatible with strong acid, but many are. The preparation of t-BuCl from t-BuOH simply by shaking it with concentrated HCl is a good example. This is obviously an SN1 reaction with the t-butyl cation as intermediate.

Similar methods can be used to make secondary alkyl bromides with HBr alone and primary alkyl bromides using a mixture of HBr and H₂SO₄.

The second of these two reactions must be SN2, with substitution of the protonated hydroxyl group by bromide.

Another way to approach the substitution of OH is to make it a better leaving group by com bination with an element that forms very strong bonds to oxygen. The most popular choices are phosphorus and sulfur. Making primary alkyl bromides with PBr3 usually works well. The phosphorus reagent is fi rst attacked by the OH group (an SN2 reaction at phosphorus) and the displacement of an oxyanion bonded to phosphorus is now a good reaction because of the anion stabilization by phosphorus.

مواضيع ذات صلة

A very bad nucleophile in a good SN1 reaction: the Ritter reaction

The nucleophile in SN1 reactions

Epoxides as electrophiles

Ethers as electrophiles

Substituting alcohols with the Mitsunobu reaction

A closer look at electronic effects

The effect of solvent

A closer look at steric effects

Adjacent C=C or C=O π systems increase the rate of SN2 reactions

An adjacent C=C π system stabilizes a carbocation: allylic and benzylic carbocations

Alkyl substituents stabilize a carbocation

Shape and stability of carbocations