Making Alcohols Into Good Leaving Groups

by James

Alcohols have hydroxyl groups (OH) which are not good leaving groups. Why not? Because good leaving groups are weak bases, and the hydroxide ion (HO–)  is a strong base.

So how do we make OH a good leaving group, so we can use alcohols for subsequent substitution or elimination reactions? Turn it into something which will produce a weaker base!

There are three main ways to do this.

  1. Turn it into an alkyl halide through the use of PBr3 or SOCl2. This will convert the alcohol into an alkyl bromide or alkyl chloride, respectively, and halides (being weak bases) are great leaving groups. However, *watch the stereochemistry*; these reactions involve an SN2 reaction, and will proceed with inversion at carbon.
  2. Turn it into an alkyl sulfonate using tosyl chloride (TsCl) or mesyl chloride (MsCl). Sulfonates are also *great* leaving groups (similar to halides). Here, we’re not changing the stereochemistry on carbon – we’re just replacing the H with the Ts.
  3. Add acid. Acid will convert an alcohol to its oxonium ion (positively charged oxygen), which can then lose water (a weak base!). Since a carbocation will be formed at the same time, this can be particularly effective for tertiary alcohols (remember that tertiary carbocations = more stable). Just watch out – anytime you form carbocations, rearrangements can sometimes occur.

Thanks for reading! James

PS – Further reading: What makes a good leaving group?
Reagent Friday: SOCl2
Reagent Friday: TsCl