Methanesulfonyl chloride (mesyl chloride) is an

organosulfur compound Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature abounds with organosulfur compounds—sulfu ...

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 is a colourless liquid that dissolves in polar organic solvents but is reactive toward water, alcohols, and many amines. The simplest organic

sulfonyl chloride In inorganic chemistry, sulfonyl halide groups occur when a sulfonyl () functional group is singly bonded to a halogen atom. They have the general formula , where X is a halogen. The stability of sulfonyl halides decreases in the order fluorides ...

, it is used to make methanesulfonates and to generate the elusive molecule

sulfene Sulfene is an extremely reactive chemical compound with the formula H2C=SO2. It is the simplest member of the sulfenes, the group of compounds which are ''S'',''S''-dioxides of thioaldehydes and thioketones, and have the general formula R2C=SO2. ...

(methylenedioxosulfur(VI)).Valerie Vaillancourt, Michele M. Cudahy, Matthew M. Kreilein and Danielle L. Jacobs "Methanesulfonyl Chloride" in E-EROS Encyclopedia for Reagents in Organic Synthesis.

Preparation

It is manufactured by the reaction of

methane Methane ( , ) is a chemical compound with the chemical formula (one carbon atom bonded to four hydrogen atoms). It is a group-14 hydride, the simplest alkane, and the main constituent of natural gas. The relative abundance of methane on Eart ...

and

sulfuryl chloride Sulfuryl chloride is an inorganic compound with the formula SO2Cl2. At room temperature, it is a colorless liquid with a pungent odor. Sulfuryl chloride is not found in nature, as can be inferred from its rapid hydrolysis. Sulfuryl chloride is ...

in a

radical reaction In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired electron, unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemical reaction, chemi ...

: : Another method of manufacture entails chlorination of

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

with

thionyl chloride Thionyl chloride is an inorganic compound with the chemical formula . It is a moderately volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a chlorinating reagent, with approximately per year bein ...

phosgene Phosgene is the organic chemical compound with the formula COCl2. It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. Phosgene is a valued and important industrial building block, espe ...

: : :

Reactions

Methanesulfonyl chloride is a precursor to many compounds because it is highly reactive. It is an electrophile, functioning as a source of the "CH₃SO₂⁺" group.

Methanesulfonates

Methanesulfonyl chloride is mainly used to give methanesulfonates by its reaction with

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. The term ''alcohol'' originally referred to the primary alcohol ethanol (ethyl alcohol), which is ...

in the presence of a non-nucleophilic base. In contrast to the formation of toluenesulfonates from alcohols and ''p''-toluenesulfonyl chloride in the presence of pyridine, the formation of methanesulfonates is believed to proceed via a mechanism wherein methanesulfonyl chloride first undergoes an

E1cb The E1cB elimination reaction is a type of elimination reaction which occurs under basic conditions, where the hydrogen to be removed is relatively acidic, while the leaving group (such as -OH or -OR) is a relatively poor one. Usually a moderate t ...

elimination to generate the highly reactive parent

(), followed by attack by the alcohol and rapid proton transfer to generate the observed product. This mechanistic proposal is supported by isotope labeling experiments and the trapping of the transient sulfene as cycloadducts. Sulfene-mechanism

Methanesulfonates are used as intermediates in

substitution reaction A substitution reaction (also known as single displacement reaction or single substitution reaction) is a chemical reaction during which one functional group in a chemical compound is replaced by another functional group. Substitution reactions ar ...

elimination reaction An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one- or two-step mechanism. The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 ...

reductions Reductions ( es, reducciones, also called ; , pl. ) were settlements created by Spanish rulers and Roman Catholic missionaries in Spanish America and the Spanish East Indies (the Philippines). In Portuguese-speaking Latin America, such redu ...

, and

rearrangement reaction In organic chemistry, a rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule. Often a substituent moves from one atom to another ...

s. When treated with a

Lewis acid A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any sp ...

oxime In organic chemistry, an oxime is a organic compound belonging to the imines, with the general formula , where R is an organic side-chain and R’ may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted ...

methanesulfonates undergo facile

Beckmann rearrangement The Beckmann rearrangement, named after the German chemist Ernst Otto Beckmann (1853–1923), is a rearrangement of an oxime functional group to substituted amides. The rearrangement has also been successfully performed on haloimines and nitrones ...

. Methanesulfonates are occasionally used as a

protecting group A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In many ...

for alcohols. They are stable to acidic conditions and is cleaved back to the alcohol using

sodium amalgam Sodium amalgam, commonly denoted Na(Hg), is an alloy of mercury and sodium. The term amalgam is used for alloys, intermetallic compounds, and solutions (both solid solutions and liquid solutions) involving mercury as a major component. Sodium amal ...

Methanesulfonamides

Methanesulfonyl chloride react with primary and secondary

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

s to give methanesulfonamides. Unlike methanesulfonates, methanesulfonamides are very resistant toward hydrolysis under both acidic and basic conditions. When used as a protecting group, they can be converted back to amines using

lithium aluminium hydride Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic ...

or a dissolving metal reduction.

Addition to alkynes

In the presence of

copper(II) chloride Copper(II) chloride is the chemical compound with the chemical formula CuCl2. The anhydrous form is yellowish brown but slowly absorbs moisture to form a blue-green dihydrate. Both the anhydrous and the dihydrate forms occur naturally as the ver ...

, methanesulfonyl chloride will add across alkynes to form β-chloro

sulfone In organic chemistry, a sulfone is a organosulfur compound containing a sulfonyl () functional group attached to two carbon atoms. The central hexavalent sulfur atom is double-bonded to each of two oxygen atoms and has a single bond to each of ...

Formation of heterocycles

Upon treatment with a base, such as

triethylamine Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine or tetraethylammonium, for which TEA ...

, methanesulfonyl chloride will undergo an elimination to form

. Sulfene can undergo

cycloaddition In organic chemistry, a cycloaddition is a chemical reaction in which "two or more Unsaturated hydrocarbon, unsaturated molecules (or parts of the same molecule) combine with the formation of a cyclic adduct in which there is a net reduction of th ...

s to form various heterocycles. α-Hydroxyketones react with sulfene to form five-membered

sultone In organosulfur chemistry, a sulfonate is a salt or ester of a sulfonic acid. It contains the functional group , where R is an organic group. Sulfonates are the conjugate bases of sulfonic acids. Sulfonates are generally stable in water, non-o ...

Miscellaneous

Forming acyliminium ions from α-hydroxy

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

s can be done using methanesulfonyl chloride and a base, typically

Safety

Methanesulfonyl chloride is highly toxic by inhalation,

corrosive A corrosive substance is one that will damage or destroy other substances with which it comes into contact by means of a chemical reaction. Etymology The word ''corrosive'' is derived from the Latin verb ''corrodere'', which means ''to gnaw'', ...

, and acts as a

lachrymator Tear gas, also known as a lachrymator agent or lachrymator (), sometimes colloquially known as "mace" after the early commercial aerosol, is a chemical weapon that stimulates the nerves of the lacrimal gland in the eye to produce tears. In ad ...

. It reacts with nucleophilic reagents (including water) in a strongly exothermic manner. When heated to decomposition point, it emits toxic vapors of sulfur oxides and

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

References

{{Reflist Reagents for organic chemistry Sulfonyl halides