What is Tosylate?

Tosylate is the shortened term for toluene sulfonate which is an ester functional group denoted by -$OTs$. It has a tolyl group and a sulfite group with a negative charge on one of the oxygen. Hence, the chemical formula is$H_{3}C{C}_6{H}_{4}S{O}_3{}^{-}$.

Structure and Naming of Tosylate Group 

The tosylate group has three components joined together, which are, a tolyl group ($H^{}{}_{3}C{C}^{}{}_6{H}^{}{}_4$), a sulfonyl group along with an extra oxygen singly bonded to sulfur with a negative charge on it. Thus the structure looks as follows:

Here, the IUPAC name is given as $4$-methylbenzene sulfonate. It can also be called as toluene-$4$-sulfonate.

Preparation of Tosylate           

Tosylates are usually prepared from alcohols using $S_{N}2$ mechanism. As $S_{N}2$ mechanism is used in the preparation, primary or secondary alcohols are preferred. When alcohol reacts with tosyl chloride, nucleophilic substitution takes place and tosylate is formed along with hydrochloric acid.

The lone pair in oxygen of the alcohol, first attacks the tosylate group as oxygen is electronegative and is a nucleophile. Tosyl group being slightly positively charged due to presence of electronegative chlorine, acts as an electrophile and gets attached to Oxygen. This creates a positive charge in oxygen, which is soon eliminated by losing of the hydrogen from oxygen, forming the tosylate. ($C{H}_{3}OTs$). The chlorine left behind by tosyl group and the hydrogen which is removed now will form hydrochloric acid. This reaction is advantageous as it does not need strong acidic conditions to occur.

How are Tosylates used for in Organic Synthesis?          

Tosylates are important functional groups in organic chemistry, mainly because of two important properties which they possess:

• Good leaving group
• Acts as a protecting group      

Why is Tosylate a Good Leaving Group?

Tosylates are considered as one of the best leaving groups, even better than halogens for that matter because of their resonance stabilization. Due to the presence of aromatic ring in the tosyl group and electronegative oxygen with a negative charge on it, the group is able to easily accommodate the negative charge due to its ability to delocalize the electrons around all the atoms in the aromatic ring. Delocalization of the developed negative charge in the oxygen during nucleophilic substitution will result in more resonant structures. The higher the resonance structures for a give species; greater is its stability. Therefore, the stability of tosylate ion is high and hence it can independently exist which makes an excellent leaving group when a nucleophilic attack happens.

Tosylate groups as a Protecting Group

As we know, alcohols are highly reactive due to the presence of lone pair on the oxygen of the alcohol group. There are certain reactions in which we would want to prevent alcohol from reacting in order to give a desirable product. This can be easily achieved by converting an alcohol group into a tosylate group by addition of tosyl chloride for nucleophilic substitution reaction as already discussed above. When tosylate is formed the lone pair of oxygen will now be getting into delocalization with the aromatic ring of tosyl group. As electron delocalization manages to stop lone pairs from attacking other electrophiles, it effectively reduces the reactivity and also become much more stable than alcohol.

Tosylate is a good leaving group. Hence, another advantage of using tosylate as protecting group for alcohols is that the alcohol can be reobtained.

Tosylate groups not only act as protecting agents for alcohols, they are also used to protect amines when tosyl chloride is added to pyridine in the presence of dichloromethane as the solvent. This can easily be removed by addition of concentrated acids like sulfuric acid and hydrogen bromide reflux.

Role of Tosylate groups in Stereochemistry

Tosylate groups in addition to being used in mainstream organic synthesis, also help to freeze the conformations of chiral compounds in stereochemistry. As Tosylate groups are heavy they tend to disable the free rotations about bond axis, which eventually leads to freezing the conformation of certain molecules to a specific one, desired for studying the molecule or to proceed further with a reaction. This is highly helpful sometimes in systems which has great tendency to get interconverted into each other and result in internal compensation. Tosylate groups help solve this by having the system conformationally frozen in one state.

Alternatives to Tosylate Groups         

Tosylate groups have some similarities in properties with some groups such as mesylates, nosylates and bromylates.

Common Mistakes    

Practice Problem   

Write the required reaction in order to prepare Tosylates and give the name of the starting materials.

Solution

Here a primary alcohol such as methanol is made to react with tosyl chloride. This reaction follows $S_{N}2$ mechanism of nucleophilic substitution and hence tosylates are formed along with side product hydrochloric acids.

Context and Applications

This topic is significant in the professional exams for both undergraduate and graduate courses, especially for

• Bachelors in Chemistry, Biochemistry.  and Chemical Engineering 
• Masters in Chemistry and Biochemistry.