Methanesulfonic anhydride explained

Methanesulfonic anhydride (Ms₂O) is the acid anhydride of methanesulfonic acid. Like methanesulfonyl chloride (MsCl), it may be used to generate mesylates (methanesulfonyl esters).

Preparation & purification

Ms₂O may be prepared by the dehydration of methanesulfonic acid with phosphorus pentoxide.

P₂O₅ + 6 CH₃SO₃H → 3 (CH₃SO₂)₂O + 2 H₃PO₄

Ms₂O can be purified by distillation under vacuum (distillation of a solid) or by recrystallization from Methyl tert-butyl ether/toluene.

Reactions & Applications in synthesis

Passage of hydrogen chloride through molten Ms₂O yields MsCl.^[1]

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.^[2] Unlike MsCl, Ms₂O may not be suitable for mesylation of the unsaturated alcohols.^[3]

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.^[4]

Ms₂O also converts amines to sulfonamides.^[5]

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.^[6]

Examples of aromatic sulfonation with Ms₂O:

• Sulfonation of chlorobenzene resulted in addition of methylsulfonyl group at para and ortho positions (with respect to chloride), 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.^[7]

Esterification

Ms₂O catalyzes the esterification of alcohols by carboxylic acids. 2-Naphthyl acetate was prepared from 2-naphthol and glacial (anhydrous) 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.^[8] This method applies to benzylic alcohol. HMPA may be substituted by dichloromethane but may result in more side-products.

See also

• Methanesulfonyl chloride
• Disulfuric acid
• Sodium pyrosulfate
• Acetic anhydride
• Trifluoromethanesulfonic anhydride

Notes and References

1. Field . Lamar . Settlage . Paul H. . Reaction of Methanesulfonic Anhydride with Hydrogen Halides 1 . Journal of the American Chemical Society . January 1955 . 77 . 1 . 170–171 . 10.1021/ja01606a053 . en . 0002-7863.
2. Baumann . W. J. . Jones . L. L. . Barnum . B. E. . Mangold . H. K. . The formation of alkyl and alkenyl methanesulfonates and their reduction to hydrocarbons . Chemistry and Physics of Lipids . 1 November 1966 . 1 . 1 . 63–67 . 10.1016/0009-3084(66)90008-9 . en . 0009-3084.
3. Cegla . Gad . Mangold . Helmut K. . A new procedure for the preparation of alkyl methanesulfonates . Chemistry and Physics of Lipids . 1 May 1973 . 10 . 4 . 354–355 . 10.1016/0009-3084(73)90059-5 . en . 0009-3084.
4. Leroux . Jacques . Perlin . Arthur S. . Synthesis of glycosyl halides and glycosides via 1-O-sulfonyl derivatives . Carbohydrate Research . 1 November 1978 . 67 . 1 . 163–178 . 10.1016/S0008-6215(00)83739-8 . en . 0008-6215.
5. Lis . Randall . Morgan . Thomas K. . Marisca . Anthony J. . Gomez . Robert P. . Lind . Joan M. . Davey . David D. . Phillips . Gary B. . Sullivan . Mark E. . Synthesis of novel (aryloxy)propanolamines and related compounds possessing both class II and class III antiarrhythmic activity . Journal of Medicinal Chemistry . October 1990 . 33 . 10 . 2883–2891 . 10.1021/jm00172a033 . en . 0022-2623.
6. Vaillancourt . Valerie . Cudahy . Michele M. . Methanesulfonic Anhydride . Encyclopedia of Reagents for Organic Synthesis . 15 April 2001 . rm068 . 10.1002/047084289x.rm068 . John Wiley & Sons, Ltd . en.
7. Tyobeka . Themba E. . Hancock . Richard A. . Weigel . Helmut . Novel sulphonylating reagent: sulphuric acid–hexafluoroacetic anhydride . Journal of the Chemical Society, Chemical Communications . 1 January 1980 . 3 . 114–115 . 10.1039/C39800000114 . en . 0022-4936.
8. Albright . J. Donald . Sullfoxonium salts as reagents for oxidation of primary and secondary alcohols to carbonyl compounds . The Journal of Organic Chemistry . June 1974 . 39 . 13 . 1977–1979 . 10.1021/jo00927a054 . en . 0022-3263.