Tosylates and mesylates to make oxygen a good leaving group

As a student of organic chemistry, you will come across many reactions that are required to act in a certain way. Perhaps because your teacher asked you to show the mechanism, or perhaps because this reaction step is part of a larger sequence. However, molecules don’t always want to react as planned. In this article I will help you understand how to convert an OH group into a good leaving group by using a tosylate or mesylate.

A leaving group is an atom or group of atoms that will separate on their own from a larger molecule or be expelled by another group, such as what is seen in SN1 SN2 E1 E2 reactions.

While some atoms make really good leaving groups, like the larger halogens, other groups of atoms make poor and very slow leaving groups. An example of this is hydroxyl.

The OH group, when expelled from a molecule, results in a small, negatively charged hydroxide anion. Since the charge is small and concentrated, the hydroxide is very reactive and will find a way to come back and attack the molecule it started from.

In other words, the hydroxide is a very poor leaving group on its own due to the concentrated charge on the oxygen.

If your reaction requires the removal of this group, you can achieve this by making the oxygen more stable and less charged when it leaves.

2 molecules capable of helping in this reaction or the toxylate and mesylate

Toxylate: para-toluenesulfonyl chloride

Mesylate: methylsulfonyl chloride

The key common factor between these 2 groups is the presence of a sulfur atom with 2 double-bonded oxygen atoms and a chlorine

The reaction begins when oxygen attacks sulfur, eventually replacing the chlorine atom. This leaves you with a much larger leaving group containing oxygen attached to carbon, and also attached to sulfur which has 2 additional double bonded oxygen atoms

When all of this group leaves the carbon chain, you still end up with a negative oxygen atom. However, this oxygen is much less reactive and therefore much less likely to come back and attack the carbon chain.

This is due to the fact that charging is no longer based on individual oxygen alone. In fact, the negative charge will now be shared between the 3 oxygen atoms that are attached to the sulfur in the tosylate or mesylate as a result of resonance.