Methanesulfonic anhydride

Methanesulfonic anhydride is the acid anhydride of methanesulfonic acid. Like methanesulfonyl chloride, it may be used to generate mesylates.

Preparation & purification

Ms₂O may be prepared by the dehydration of methanesulfonic acid with phosphorus pentoxide.
Ms₂O can be purified by distillation under vacuum or by recrystallization from Methyl tert-butyl ether/toluene.

Reactions & Applications in synthesis

Passage of hydrogen chloride through molten Ms₂O yields MsCl.
Similar to MsCl, Ms₂O can perform mesylation of alcohols to form sulfonates. Use of Ms₂O avoids the alkyl chloride, which often appears as a side-product when MsCl is used. Unlike MsCl, Ms₂O may not be suitable for mesylation of the unsaturated alcohols.
Examples of mesylation of alcohols with Ms₂O:

Octadecyl methanesulfonate was prepared from octadecanol in pyridine.
Secondary alcohol at the anomeric carbon of 2,3,4,5-O-Benzyl-protected glucose reacted to form a glycosyl mesylate, which was found to be more stable than its triflate counterpart, in 2,4,6-collidine.

Ms₂O also converts amines to sulfonamides.

Aromatic sulfonation

Assisted by Lewis acid catalyst, Friedel-Crafts methylsulfonation of aryl ring can be achieved by Ms₂O. In contrast to MsCl, either activated or deactivated benzene derivatives can form the corresponding sulfonatesin satisfactory yields with Ms₂O.
Examples of aromatic sulfonation with Ms₂O:

Sulfonation of chlorobenzene resulted in addition of methylsulfonyl group at para and ortho positions, with a ratio of 2 to 1, respectively; while reaction with Meta-dichlorobenzene gave monosulfonylated product at C4 position.
With sulfuric acid, di-aryl sulfones were synthesized.

Esterification

Ms₂O catalyzes the esterification of alcohols by carboxylic acids. 2-Naphthyl acetate was prepared from 2-naphthol and glacial acetic acid in the presence of Ms₂O. Both alcohols on ethylene glycol successfully benzoylated with benzoic acid and Ms₂O. However, for free alcohols on monosaccharides, the acetylation was not completed.

Oxidation of alcohols

Like Pfitzner–Moffatt oxidation and Swern oxidation, with DMSO, Ms₂O can oxidize primary and secondary alcohols to aldehydes and ketones, respectively, in HMPA. This method applies to benzylic alcohol. HMPA may be substituted by dichloromethane but may result in more side-products.