TMSCl

Trimethylsilyl chloride (TMSCl) is a chlorosilane with the formula (CH3)3SiCl. It is a colorless, volatile liquid widely used in organic synthesis as a silylating agent. Because it reacts readily with water and air, TMSCl is typically handled under strictly anhydrous conditions and stored under inert atmosphere.

In laboratory synthesis, TMSCl is most commonly employed to protect hydroxyl groups by converting alcohols and phenols into the corresponding trimethylsilyl ethers (TMS ethers). The reaction is usually carried out in an anhydrous solvent such as dichloromethane or tetrahydrofuran, in the presence of a base such as imidazole, DIPEA, or pyridine. TMSCl can also be used to form silyl enol ethers from carbonyl compounds when used with a suitable base; these enol ethers serve as versatile intermediates in various downstream transformations.

The trimethylsilyl group is relatively small compared to other silyl protecting groups, which makes TMS ethers easy to install but sometimes easier to remove. Deprotection or de-silylation is typically achieved with fluoride sources such as tetrabutylammonium fluoride or with aqueous HF, often under mild conditions.

Safety and handling: TMSCl reacts vigorously with water and oxygen, generating hydrochloric acid and silanols. It is corrosive and can cause skin and eye irritation. Proper handling requires dry glassware, inert gas as needed, and appropriate personal protective equipment. It should be stored in a dry, cool place away from moisture and incompatible materials.

See also: silyl protecting groups, silylation, trimethylsilyl ethers.