tosylates

Tosylates are esters derived from p-toluenesulfonic acid, commonly formed when an alcohol is converted into a p-toluenesulfonate ester. The general product is R-OTs, where Ts stands for the p-toluenesulfonyl group. The tosylate moiety is a very good leaving group in nucleophilic substitution reactions, enabling transformations that convert alcohols into a wide range of products.

Preparation typically involves treating an alcohol with p-toluenesulfonyl chloride (TsCl) in the presence of a base such as pyridine or triethylamine, usually in an anhydrous organic solvent. Alternative reagents for installing the Ts group include p-toluenesulfonyl anhydride (Ts2O) or related sulfonyl chlorides.

Properties and reactivity: The tosylate group stabilizes the negative charge of the departing TsO– anion, making RO–OTs a highly effective leaving group. Tosylates are generally stable and can be manipulated under a variety of conditions. They undergo SN2 or, for certain substrates, SN1-type substitutions with nucleophiles such as azide, thiols, cyanide, fluoride, and alkoxides. The stereochemical outcome depends on the mechanism and substrate; secondary and primary tosylates commonly undergo SN2 with inversion when attacked by a chiral nucleophile.

Applications: Tosylates are widely used to activate alcohols for substitution reactions, enabling the introduction of many functionalities (e.g., azides, halides, ethers) that would be difficult to achieve directly from alcohols. They are also employed in multistep syntheses to assemble complex molecules where controlled leaving-group ability is required.

Note that the term “tosylate” can refer specifically to the ester, while the related tosyl group is also used as a protecting group for amines in other contexts. Safety data should be consulted for reagents like TsCl, which are moisture-sensitive and irritants.