Methanesulfonic anhydride (Ms₂O) is the

acid anhydride An acid anhydride is a type of chemical compound derived by the removal of water molecules from an acid. In organic chemistry, organic acid anhydrides contain the functional group . Organic acid anhydrides often form when one equivalent of wa ...

methanesulfonic acid Methanesulfonic acid (MsOH, MSA) or methanesulphonic acid (in British English) is an organosulfuric, colorless liquid with the molecular formula and structure . It is the simplest of the alkylsulfonic acids (). Salts and esters of methanesul ...

. Like

methanesulfonyl chloride Methanesulfonyl chloride (mesyl chloride) is an organosulfur compound with the formula . Using the organic pseudoelement symbol Ms for the methanesulfonyl (or mesyl) group –, it is frequently abbreviated MsCl in reaction schemes or equations. It ...

(MsCl), it may be used to generate

mesylates In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (). In salts, the mesylate is present as the anion. When modifying the international nonproprietary name of a pharmaceutical substance containing the group o ...

(methanesulfonyl esters).

Preparation & purification

Ms₂O may be prepared by the dehydration of

with

phosphorus pentoxide Phosphorus pentoxide is a chemical compound with molecular formula Phosphorus, P4Oxygen, O10 (with its common name derived from its empirical formula, P2O5). This white crystalline solid is the anhydride of phosphoric acid. It is a powerful desic ...

. :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 Methyl ''tert''-butyl ether (MTBE), also known as ''tert''-butyl methyl ether, is an organic compound with a structural formula (CH3)3COCH3. MTBE is a volatile, flammable, and colorless liquid that is sparingly soluble in water. Primarily used a ...

toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon with the chemical formula , often abbreviated as , where Ph stands for the phenyl group. It is a colorless, water Water is an inorganic compound with the c ...

Reactions & Applications in synthesis

Passage of

hydrogen chloride The Chemical compound, compound hydrogen chloride has the chemical formula and as such is a hydrogen halide. At room temperature, it is a colorless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric water vapor. Hyd ...

through molten Ms₂O yields MsCl. Similar to MsCl, Ms₂O can perform

mesylation In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (). In salts, the mesylate is present as the anion. When modifying the international nonproprietary name of a pharmaceutical substance containing the group o ...

alcohols In chemistry, an alcohol (), is a type of organic compound that carries at least one hydroxyl () functional group bound to a Saturated and unsaturated compounds, saturated carbon atom. Alcohols range from the simple, like methanol and ethanol ...

to form

sulfonates In organosulfur chemistry, a sulfonate is a salt, anion or ester of a sulfonic acid. Its formula is , containing the functional group , where R is typically an organyl group, amino group or a halogen atom. Sulfonates are the conjugate bases of ...

. 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 Stearyl alcohol, or 1-octadecanol, is an organic compound classified as a saturated fatty alcohol with the formula CH3(CH2)16CH2OH. It takes the form of white granules or flakes, which are insoluble in water. It has a wide range of uses as an i ...

pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...

. * Secondary alcohol at the anomeric carbon of 2,3,4,5-O-

Benzyl In organic chemistry, benzyl is the substituent or molecular fragment possessing the structure . Benzyl features a benzene ring () attached to a methylene group (). Nomenclature In IUPAC nomenclature, the prefix benzyl refers to a substituent ...

-protected

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

reacted to form a glycosyl mesylate, which was found to be more stable than its

triflate In organic chemistry, triflate (Preferred IUPAC name, systematic name: trifluoromethanesulfonate), is a functional group with the Chemical formula, formula and Chemical structure, structure . The triflate group is often represented by , as opp ...

counterpart, in

2,4,6-collidine 2,4,6-Trimethylpyridine (2,4,6-collidine) is an organic compound which belongs to the Heterocyclic compound, heterocycles (more precisely, Heteroaromatic compound, heteroaromatics). It consists of a pyridine ring substituted with three methyl grou ...

. Ms₂O also converts

amines In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

sulfonamides In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the Chemical structure, structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this gro ...

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 Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

derivatives can form the corresponding sulfonatesin satisfactory yields with Ms₂O. Examples of aromatic sulfonation with Ms₂O: * Sulfonation of

chlorobenzene Chlorobenzene (abbreviated PhCl) is an aryl chloride and the simplest of the chlorobenzenes, consisting of a benzene ring substituted with one chlorine atom. Its chemical formula is C6H5Cl. This colorless, flammable liquid is a common solvent a ...

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 Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid (English in the Commonwealth of Nations, Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen, ...

, di-aryl sulfones were synthesized.

Esterification

Ms₂O catalyzes the esterification of alcohols by carboxylic acids. 2-Naphthyl acetate was prepared from

2-naphthol 2-Naphthol, or β-naphthol, is a fluorescent colorless (or occasionally yellow) crystalline solid with the formula C10H7OH. It is an isomer of 1-naphthol, differing by the location of the hydroxyl group on the naphthalene ring. The naphthols are ...

and glacial (anhydrous)

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main compone ...

in the presence of Ms₂O. Both

ethylene glycol Ethylene glycol ( IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes: as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an odo ...

successfully benzoylated with

benzoic acid Benzoic acid () is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. The benzoyl group is often abbreviated "Bz" (not to be confused with "Bn," which ...

and Ms₂O. However, for free alcohols on

monosaccharides Monosaccharides (from Greek ''monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built. Chemically, monosaccharides are polyhydr ...

, the

acetylation : In chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed ''acetate esters'' or simply ''acetates''. Deacetylation is the opposite react ...

was not completed.

Oxidation of alcohols

Pfitzner–Moffatt oxidation The Pfitzner–Moffatt oxidation, sometimes referred to as simply the Moffatt oxidation, is a chemical reaction for the redox, oxidation of primary and secondary alcohols to aldehydes and ketones, respectively. The oxidant is a combination of dime ...

and

Swern oxidation In organic chemistry, the Swern oxidation also known as Moffatt-Swern, named after Daniel Swern, is a chemical reaction whereby a primary or secondary Alcohol (chemistry), alcohol () is redox, oxidized to an aldehyde () or ketone () using oxalyl ...

, with

DMSO Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula . This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is ...

, Ms₂O can

oxidize Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

primary Primary or primaries may refer to: Arts, entertainment, and media Music Groups and labels * Primary (band), from Australia * Primary (musician), hip hop musician and record producer from South Korea * Primary Music, Israeli record label Work ...

and

secondary alcohols In chemistry, an alcohol (), is a type of organic compound that carries at least one hydroxyl () functional group bound to a saturated carbon atom. Alcohols range from the simple, like methanol and ethanol, to complex, like sugar alcohols an ...

aldehydes In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

and

ketones In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...

, respectively, in

HMPA Hexamethylphosphoramide, often abbreviated HMPA, is a phosphoramide (an amide of phosphoric acid) with the formula This colorless liquid is used as a solvent in organic synthesis. Structure and reactivity HMPA is the oxide of tris(dimethylamino ...

. This method applies to benzylic alcohol.

may be substituted by

dichloromethane Dichloromethane (DCM, methylene chloride, or methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odor is widely used as a solvent. Although it is not miscible with ...

but may result in more side-products.

References