Methanesulfonyl chloride (CAS#124-63-0)
Methanesulfonyl chloride (MsCl), also known as mesyl chloride or methanesulfonic acid chloride, is a highly reactive organosulfur compound supplied as a colorless to pale-yellow liquid with a pungent, unpleasant odor.It has a molecular weight of 114.55 g/mol, a boiling point of 161 °C at 97.3 kPa (with a reduced-pressure boiling point of approximately 60 °C at 21 mmHg commonly used for purification), and a specific gravity of approximately 1.48–1.5 at ambient temperature.The compound is insoluble in water but reacts with it, hydrolyzing slowly rather than violently—a property that distinguishes it from thionyl chloride and sulfuryl chloride, which hydrolyze rapidly.
MsCl is characterized by a highly electrophilic sulfonyl center and an excellent chloride leaving group, making it a powerful sulfonylating agent. It reacts vigorously with water, alcohols, and many amines, and decomposes upon heating or burning to release toxic and corrosive fumes including hydrogen chloride and sulfur oxides.The compound is combustible, with a flash point above 110 °C, and reacts violently with bases including ammonia.It is a lachrymator and is classified as a corrosive, acutely toxic substance requiring strict handling controls.
Applications
Methanesulfonyl chloride is one of the most important sulfonylation reagents in organic synthesis and pharmaceutical manufacturing. Its primary function is the introduction of the methanesulfonyl (mesyl) group, a transformation central to medicinal chemistry and process development.
The single largest application is the conversion of alcohols to methanesulfonate esters (mesylates) . A hydroxyl group is a poor leaving group; mesylation with MsCl, typically in the presence of a non-nucleophilic base such as triethylamine or pyridine, converts it into an excellent leaving group that readily undergoes nucleophilic substitution, elimination, or reduction.This transformation is ubiquitous in the synthesis of complex drug molecules. Documented industrial applications include the preparation of montelukast sodium (where a diol intermediate is mesylated with MsCl in toluene or acetonitrile), and the synthesis of meropenem and pioglitazone hydrochloride, where high-purity MsCl (≥99%) is specified as a critical electrophilic reagent.
The second major application is the synthesis of sulfonamides from primary and secondary amines. Methanesulfonamides are highly stable structural motifs present in numerous pharmaceutical agents, and MsCl provides a direct and efficient route to this functionality.MsCl also serves as a protecting group for alcohols and amines, as a chlorinating agent, and as a carboxylic acid activating agent in synthetic sequences.
Beyond the pharmaceutical sector, MsCl is used in agrochemical synthesis and as a raw material for methanesulfonic acid production.Its derivatives, particularly methanesulfonamides, serve as intermediates for a broad range of fine chemicals.
Preparation Method
Several industrial routes have been developed for Methanesulfonyl chloride, reflecting its importance as a commodity sulfonylating agent.
A continuous process based on the simultaneous hydrolysis and chlorination of methyl mercaptan is described in patent literature. Gaseous methyl mercaptan and gaseous chlorine are contacted at elevated temperatures in a saturated aqueous hydrochloric acid reaction matrix, with the reaction mass maintained at approximately 40–75 °C, to produce MsCl directly.
An alternative route involves the reaction of dimethyl sulfoxide with chlorine in an aqueous medium.A related process uses monochlorodimethyl sulfide as the starting material, which is admixed with water and hydrochloric acid, refluxed, cooled to 0 °C, and treated with chlorine gas to effect the transformation.
A more recent solvent-free process produces MsCl from sodium methanesulfonate and thionyl chloride. A catalyst and thionyl chloride are added to dried sodium methanesulfonate, and the mixture is stirred while the temperature is gradually raised from −10 °C to 45 °C and then to 50–90 °C, driving the chlorination reaction to completion without a solvent.
Safety Information
Methanesulfonyl chloride is a highly hazardous, corrosive, and acutely toxic substance with a harmonized GHS classification that includes multiple severe hazard categories. The signal word is Danger.The core hazard statements are: H290 (May be corrosive to metals), H301 + H311 (Toxic if swallowed or in contact with skin), H330 (Fatal if inhaled), H314 (Causes severe skin burns and eye damage), and H317 (May cause an allergic skin reaction).Additional classifications include H335 (May cause respiratory irritation) and H402 (Harmful to aquatic life).The substance is a Skin Corrosion Sub-category 1B material and an Acute Toxicity Category 1 toxicant by inhalation, Category 3 by oral and dermal routes.It is also a lachrymator, producing intense tearing and eye irritation at low concentrations.
The primary target organ identified in single-exposure toxicity is the respiratory system.Symptoms of exposure include coughing, sore throat, burning sensation, labored breathing, and shortness of breath upon inhalation; redness, pain, and blistering upon skin contact; and severe burns upon eye contact.The compound reacts with water to generate hydrogen chloride, adding an inhalation hazard in the presence of moisture.
For safe handling, all manipulations must be performed in a well-ventilated fume hood with local exhaust ventilation.Personal protective equipment must include acid-resistant gloves, safety goggles and a face shield, protective clothing, and respiratory protection with type ABEK filters.In case of skin contact, remove contaminated clothing immediately and rinse with plenty of water; for eye contact, rinse cautiously with water for several minutes and seek immediate medical attention.If inhaled, move to fresh air and refer immediately for medical attention.Do not induce vomiting if swallowed; rinse the mouth and seek immediate medical care.For spills, evacuate the danger area, wear complete protective clothing including self-contained breathing apparatus, and absorb the liquid with sand or inert absorbent; do not wash into sewers.
Store MsCl in a dry, well-closed, well-ventilated area separated from food and feedstuffs and incompatible materials, in an area without drain or sewer access. Packaging must be airtight and unbreakable, with breakable containers placed inside closed unbreakable outer containers.The transportation classification is UN 3246, Hazard Class 6.1 (Toxic), Subsidiary Risk 8 (Corrosive), Packing Group I.
