Trimethyl orthoformate (TMOF) is the
organic compound with the formula HC(OCH
3)
3. A colorless liquid, it is the simplest
orthoester. It is a
reagent
In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
used in
organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
for the formation of methyl ethers. The product of reaction of an aldehyde with trimethyl orthoformate is an
acetal. In general cases, these acetals can be deprotected back to the aldehyde by using
hydrochloric acid.
Synthesis
Trimethyl orthoformate is prepared on an industrial scale by the
methanolysis of
hydrogen cyanide
Hydrogen cyanide, sometimes called prussic acid, is a chemical compound with the formula HCN and structure . It is a colorless, extremely poisonous, and flammable liquid that boils slightly above room temperature, at . HCN is produced on an ...
:
[Ashford's Dictionary of Industrial Chemicals, Third edition, 2011, , page 9388]
:HCN + 3 HOCH
3 → HC(OCH
3)
3 + NH
3
Trimethyl orthoformate can also be prepared from the reaction between
chloroform
Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...
and
sodium methoxide, an example of the
Williamson ether synthesis.
Use
Trimethyl orthoformate is a useful building block for creating methoxymethylene groups and heterocyclic ring systems. It introduces a formyl group to a nucleophilic substrate, e.g. RNH
2 to form R-NH-CHO, which can undergo further reactions. It is used in the production of the fungicides,
azoxystrobin, and picoxystrobin, as well as for some members of the
floxacin family of antibacterial drugs.
A number of pharmaceutical intermediates are also made from trimethyl orthoformate.
Trimethyl orthoformate is also an effective reagent for converting compatible carboxylic acids to their corresponding methyl esters.
Alternatively, acid-catalyzed esterifications with methanol can be driven closer to completion by employing trimethyl orthoformate to convert water byproduct to methanol and methyl formate.
See also
*
Pinner reaction
The Pinner reaction refers to the acid catalysed reaction of a nitrile with an alcohol to form an imino ester salt (alkyl imidate salt); this is sometimes referred to as a Pinner salt.
The reaction is named after Adolf Pinner, who first described ...
References
{{DEFAULTSORT:Trimethyl Orthoformate
Reagents for organic chemistry
Orthoesters
Methyl esters