Question

Pyridine is used in the synthesis of tosyl chloride from tosic acid, and also in reactions that involve tosylate esters. What characteristic of pyridine makes it the base of choice for these reactions? What might happen if a base were used that did not have this particular characteristic?

Answer 1

1. pyridine is used to promote the acylation reaction, which is that it can act as a catalyst.Despite its basicity and the subsequent formation of its chlorhydrate salt after the tosylation reaction, pyridine is also an excellent nucleophile. Pyridine is, in fact, more nucleophilic than the alcohol, and it attacks the acyl chloride rapidly, forming a highly electrophilic (because of the positive charge) intermediate: N-tosyl pyridinium chloride. It is indeed this intermediate the actual acylating agent which reacts with the alcohol to give the ester. Because pyridine is acting as a nucleophile to speed up the reaction, yet is unchanged by the reaction, it is a "nucleophilic" catalyst.

Here I have drawn the mechanism.

The byproduct of the reaction is hydrochloric acid, and with pyridine forms the water soluble pyridinium chloride, which is readily removed in work-up. Other preparations might use triethyl amine instead of pyridine.

3. A base is needed to remove HCl. HCl produced in the reaction. A weakbase is needed because strong bases are usually strong nucleophiles as well and would react with tosil chloride themselves. A tertiary amine and not primary/secondary is used, because amines are in general stronger nucleophiles than alcohols, but tertiary amines would give quate electrophilic products themselves. Pyridine is used, because nitrogen in it is in sp2state, resulting in significantly lowered nucleophilicity.