Trimethylsilyldiazomethane

Trimethylsilyldiazomethane is the organosilicon compound with the formula (CH3)3SiCHN2. It is classified as a diazo compound. Trimethylsilyldiazomethane, which is a commercially available, reagent used in organic chemistry as a methylating agent of carboxylic acids. Its behavior is akin to the reagent diazomethane, but the trimethylsilyl (TMS) analog is nonexplosive.

Preparation
Trimethylsilyldiazomethane can be prepared by treating (trimethylsilyl)methylmagnesium chloride with diphenyl phosphorazidate. An isotopically labelled variant, with 13C at the diazomethyl carbon, is also known.

Reactions
Trimethylsilyldiazomethane convert carboxylic acids to their methyl esters. It had been proposed that TMS reagent converts to diazomethane itself by a pathway involving the solvent and acidic substrate, giving the active methylating agent. More recent studies instead support that the TMS reagent itself is the active methylating agent. Regardless of the mechanistic details, the overall result is methylation of the substrate with Methoxytrimethylsilane (CH3OTMS) and nitrogen gas as byproducts:
 * RCO2H + TMSCHN2 + CH3OH -> RCO2CH3 + CH3OTMS + N2

It also reacts with alcohols to give methyl ethers, where diazomethane may not.

The compound is a reagent in the Doyle–Kirmse reaction with allyl sulfides and allyl amines.

Trimethylsilyldiazomethane is deprotonated by butyllithium:
 * (CH3)3SiCHN2 +  BuLi   →   (CH3)3SiCLiN2  +  BuH

The lithio compound is versatile. From it can be prepared other trimethylsilyldiazoalkanes:
 * (CH3)3SiCLiN2 +  RX   →   (CH3)3SiCRN2  +  LiX

(CH3)3SiCLiN2 reacts with ketones and aldehydes to give, depending on the substituents, acetylenes.

Applications
It has also been employed widely in tandem with GC-MS for the analysis of various carboxylic compounds which are ubiquitous in nature. The fact that the reaction is rapid and occurs readily makes it attractive. However, it can form artifacts which complicate spectral interpretation. Such artifacts are usually the trimethylsilylmethyl esters, RCO2CH2SiMe3, formed when insufficient methanol is present. Acid-catalysed methanolysis is necessary to achieve near-quantitative yields of the desired methyl esters, RCO2Me.

Safety
Trimethylsilyldiazomethane is highly toxic. It has been implicated in the death of at least two chemists, a pharmaceutical worker in Windsor, Nova Scotia and one in New Jersey. Inhalation of diazomethane is known to cause pulmonary edema; trimethylsilyldiazomethane is suspected to behave similarly.

It is possible that upon contact with water on the surface of the lung, trimethylsilyldiazomethane converts to diazomethane.

Trimethylsilyldiazomethane is nonexplosive.