Chloromethyl methyl sulfide
[CAS 2373-51-5]

Identification

• Classification: Organic raw materials >> Ether compounds and their derivatives
• Name: Chloromethyl methyl sulfide
• Synonyms: Chloromethyl methyl sulphide
• Molecular Formula: C₂H₅ClS
• Molecular Weight: 96.58
• CAS Registry Number: 2373-51-5
• EC Number: 219-148-4
• SMILES: CSCCl

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*, 1.16 g/mL (Expl.)
• Boiling point: 105.0 °C 760 mmHg (Calc.)^*, 105 °C (Expl.)
• Flash point: 17.2 °C (Calc.)^*, 17 °C (Expl.)
• Index of refraction: 1.468 (Calc.)^*, 1.498 (Expl.)

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS02;GHS07 DangerGHS02
• Risk Statements: H225-H315-H319-H335
• Safety Statements: P210-P233-P240-P241-P242-P243-P261-P264-P264+P265-P271-P280-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	2	H225
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

• Transport Information: UN 1993

chemBlink Chemical Story

Chloromethyl methyl sulfide, CAS 2373-51-5, is a small organosulfur compound used as a specialized reagent in organic synthesis. It is also widely known as methylthiomethyl chloride, or MTMCl. Its molecular formula is C₂H₅ClS and its molecular weight is 96.58. Structurally, the molecule is remarkably simple: CH₃-S-CH₂-Cl. Yet the combination of a thioether sulfur and a reactive chloromethyl group gives this small molecule several useful roles in synthetic chemistry.

One of its best-known applications is the introduction of the methylthiomethyl, or MTM, protecting group. Protecting groups are temporary modifications used when a functional group must survive reactions intended for another part of a molecule. Chemists temporarily mask the reactive group, perform the required chemistry elsewhere, and later remove the protecting group to restore the original functionality.

Alcohols provide a classic example. A hydroxyl group can participate in acid-base reactions, oxidation, substitution, or other processes that may interfere with a multistep synthesis. Chloromethyl methyl sulfide can convert an alcohol into an MTM ether with the general structure R-O-CH₂-S-CH₃. The original O-H bond is temporarily replaced by a structure that behaves differently under many reaction conditions.

The development of MTM protection became particularly useful in complex organic synthesis. In 1975, E. J. Corey and M. G. Bock reported the protection of primary hydroxyl groups as methylthiomethyl ethers. Later work by Suzuki, Inanaga, and Yamaguchi described a mild and convenient method for preparing MTM ethers. The chemistry subsequently became part of the established toolbox summarized in standard references such as Greene's Protective Groups in Organic Synthesis.

Why introduce sulfur into a protecting group? Sulfur has electronic and coordination properties quite different from oxygen or carbon. These differences provide chemists with alternative ways to manipulate and remove an MTM group. A protecting group is most valuable not merely when it can be installed, but when it can later be removed selectively without damaging other sensitive parts of a complex molecule.

This idea is known as orthogonality. In a multistep synthesis, several functional groups may be protected simultaneously with different molecular masks. Ideally, one protecting group can be removed while the others remain intact. Choosing among MTM, methoxymethyl, benzyl, silyl, acyl, and many other protecting groups therefore becomes part of the overall synthetic strategy.

Chloromethyl methyl sulfide is not limited to alcohol chemistry. Carboxylic acids can also be converted into methylthiomethyl esters. In this case, the carboxylate oxygen attacks the chloromethyl carbon and installs the -CH₂-SCH₃ group. Such derivatives provide another temporary way to modify the chemical behavior of a carboxylic acid during a synthetic sequence.

The reagent has also been described as a methylthiomethylating reagent for carbonyl and aromatic compounds. Commercial literature records additional applications involving methylene-transfer chemistry and organometallic reagents. These uses arise from the same fundamental structural feature: the carbon attached to chlorine provides a reactive site through which the CH₃SCH₂- fragment can enter other molecular systems.

Its chemistry illustrates an important difference between a reagent and a conventional building block. A building block is often chosen because a recognizable part of it will remain in the final product. Chloromethyl methyl sulfide is frequently used for the opposite reason. The MTM fragment may be deliberately installed, allowed to protect a functional group through several transformations, and then deliberately removed.

The molecule is therefore a form of temporary molecular engineering. During a long synthesis, the chemist must control not only which bonds are formed, but also which bonds are prevented from reacting at the wrong time. Protecting groups make that control possible.

The physical properties of chloromethyl methyl sulfide also reflect its small molecular size. It is a liquid, and reference data report a boiling point around 105-107 °C. NIST identifies CAS 2373-51-5 with the formula C₂H₅ClS and lists methylthiomethyl chloride among its synonyms. Commercial safety information classifies the material as a hazardous laboratory reagent requiring appropriate ventilation and handling controls.

This last point is especially relevant because organosulfur compounds can have powerful odors, and chloromethyl methyl sulfide is no exception. Organic Syntheses specifically warns that the compound has a very unpleasant, penetrating odor and should be handled in a properly ventilated fume hood. Its usefulness in synthesis therefore comes with practical handling requirements that are quite disproportionate to its tiny molecular structure.

Chloromethyl methyl sulfide is a good example of a reagent whose importance is easy to miss by looking only at the final product of a synthesis. The atoms it introduces may not be present when the synthesis is finished. Their purpose is temporary: protect a hydroxyl or carboxyl group, allow difficult chemistry to occur somewhere else, and then step aside when their job is done.

In that sense, MTM chemistry resembles scaffolding used in construction. The scaffolding is not part of the finished building, but without it certain stages of construction would be difficult or impossible. Chloromethyl methyl sulfide supplies one such piece of molecular scaffolding, demonstrating that in organic synthesis, temporary bonds can sometimes be just as important as permanent ones.

References

1. NIST Chemistry WebBook. Chloromethylmethyl sulfide, CAS 2373-51-5. Molecular formula C₂H₅ClS; molecular weight 96.579.
https://webbook.nist.gov/cgi/cbook.cgi?ID=C2373515

2. Corey, E. J.; Bock, M. G. (1975). Protection of primary hydroxyl groups as methylthiomethyl ethers. Tetrahedron Letters, 16, 3269.

3. Suzuki, K.; Inanaga, J.; Yamaguchi, M. (1979). A mild and convenient method for the preparation of methylthiomethyl ethers: protection of hydroxyl groups. Chemistry Letters, 8, 1277.

4. Wuts, P. G. M. (2014). Greene's Protective Groups in Organic Synthesis, 5th ed. Wiley. Chapter 2: Protection for the Hydroxyl Group.

5. Organic Syntheses. Synthetic procedures employing chloromethyl methyl sulfide; handling information for the reagent.
https://www.orgsyn.org/demo.aspx?prep=CV9P0372