Trimethylsilyldiazomethane
Encyclopedia
Trimethylsilyldiazomethane, (CH3)3SiCHN2, is a diazo compound widely used as a less-explosive replacement for diazomethane
.
used in organic chemistry
as a methylating agent. It is a less explosive alternative to diazomethane
for the methylidenation of carboxylic acid
s. It also reacts with alcohols to give methyl ethers, where diazomethane may not.
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.
The compound is a reagent in the Doyle-Kirmse reaction
with allyl sulfides and allyl amines.
Although less likely to explode than diazomethane, trimethylsilyldiazomethane may be just as toxic. Inhalation of diazomethane is known to cause pulmonary edema
; trimethylsilyldiazomethane is suspected to behave similarly.
When used as a reagent in organic synthesis to convert carboxylic acids to their methyl esters, trimethylsilyldiazomethane undergoes acid-catalysed methanolysis, forming diazomethane in situ. A similar hydrolysis reaction may take place when trimethylsilyldiazomethane comes into contact with water on the surface of a human lung.
Diazomethane
Diazomethane is the chemical compound CH2N2. It is the simplest of diazo compounds. In the pure form at room temperature, it is a extremely sensitive explosive yellow gas, thus it is almost universally used as a solution in diethyl ether...
.
Preparation
Trimethylsilyldiazomethane may be prepared from reacting (trimethylsilyl)methylmagnesium chloride with diphenyl phosphorazidate.Uses
Trimethylsilyldiazomethane is a commercially available reagentReagent
A reagent is a "substance or compound that is added to a system in order to bring about a chemical reaction, or added to see if a reaction occurs." Although the terms reactant and reagent are often used interchangeably, a reactant is less specifically a "substance that is consumed in the course of...
used in organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
as a methylating agent. It is a less explosive alternative to diazomethane
Diazomethane
Diazomethane is the chemical compound CH2N2. It is the simplest of diazo compounds. In the pure form at room temperature, it is a extremely sensitive explosive yellow gas, thus it is almost universally used as a solution in diethyl ether...
for the methylidenation of carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
s. It also reacts with alcohols to give methyl ethers, where diazomethane may not.
It has also been employed widely in tandem with GC-MS
Gas chromatography-mass spectrometry
Gas chromatography–mass spectrometry is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC-MS include drug detection, fire investigation, environmental analysis, explosives investigation,...
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
Methanol
Methanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with the formula CH3OH . It is the simplest alcohol, and is a light, volatile, colorless, flammable liquid with a distinctive odor very similar to, but slightly sweeter than, ethanol...
is present. Acid-catalysed methanolysis is necessary to achieve near-quantitative yields of the desired methyl esters, RCO2Me.
The compound is a reagent in the Doyle-Kirmse reaction
Doyle-Kirmse reaction
The Doyle-Kirmse reaction is an organic reaction in which in the original scope an allyl sulfide reacts with trimethylsilyldiazomethane to form the homoallyl sulfide compound. The reaction was first reported by W. Kirmse in 1968 and modified by M.P. Doyle in 1981.The Kirmse protocol required a...
with allyl sulfides and allyl amines.
Safety
Inhalation of trimethylsilyldiazomethane is potentially fatal and has been implicated in the death of at least two chemists, a pharmaceutical worker in Windsor, Nova Scotia, Canada and one in New Jersey.Although less likely to explode than diazomethane, trimethylsilyldiazomethane may be just as toxic. Inhalation of diazomethane is known to cause pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
; trimethylsilyldiazomethane is suspected to behave similarly.
When used as a reagent in organic synthesis to convert carboxylic acids to their methyl esters, trimethylsilyldiazomethane undergoes acid-catalysed methanolysis, forming diazomethane in situ. A similar hydrolysis reaction may take place when trimethylsilyldiazomethane comes into contact with water on the surface of a human lung.