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Tosyl chloride is used to make a hydroxyl group into a better leaving group. However, when the reaction of tosyl chloride and an alcohol occurs, a weak base such as pyridine should be used. Why?

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The function of pyridine is actually not so simple and not so easy to notice at first glance. There is a fundamental reason why 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-tosylpyridinium chloride. It is indeed this intermediate the actual tosylating 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.

Pyridine as a nucleophilic catalyst in tosylation

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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 triethylamine instead of pyridine.

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A base is needed to remove $\ce{HCl}$ produced in the reaction. A weak base 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 quite electrophilic products themselves. Pyridine is used, because nitrogen in it is in $\mathrm{sp^2}$ state, resulting in significantly lowered nucleophilicity.

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  • $\begingroup$ This answer is difficult to accept in the context of the pyridinium tosylate intermediate. $\endgroup$ – Lighthart Jan 30 '15 at 19:04
  • $\begingroup$ @Lighthart Elaborate, please. $\endgroup$ – permeakra Jan 30 '15 at 23:42
  • $\begingroup$ Pyridine reacts as a nucleophile with Tosyl Chloride and it is a stronger nucleophile than the alcohols in this reaction. You, yourself, pointed that out with tertiary amines. A base is needed for charge balance/acid neutralization, and said base must not irreversibly form an adduct with the tosyl chloride. Pyridine satisfies this requirement, so any mention of pyridine's lowered nucleophilicity is potentially misleading $\endgroup$ – Lighthart Jan 30 '15 at 23:55
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    $\begingroup$ @Lighthart Primary and secondary amines reacting with $\ce{TsCl}$ produce cation, that can throw away a proton, so the overall reaction would be $\ce{2R2NH2 + ClTs = {R2NH2}^{+} Cl^- + R2NTs} $, while in case of tertiary amines and pyridine the product would be $R_3NTs^+$ cation that cannot stabilise by throwing away a proton and is an electrophile itself, donating tosil fragment just as tosil chloride. So, unlike secondary and primary amines, tertiary amines can be used in this reaction. $\endgroup$ – permeakra Jan 31 '15 at 8:48
  • $\begingroup$ I'm not disputing your statements. What I'm saying is that comments about the nucleophilicity of pyridine make the issue somewhat more complex, and are not, strictly speaking, necessary for explaining the role of pyridine in the reaction (from the material balance perspective). The implied formation of a pyridindium tosylate may be interesting from the mechanistic perspective, but it is not clear that such a perspective is relevant to the OP. Also mixing the comments that tertiary amines are stringer nucleophiles than alcohols with 'pyridine [has lower nucleophilicity' may be confusing. $\endgroup$ – Lighthart Jan 31 '15 at 17:13

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