Trimethyl orthoformate

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Trimethyl orthoformate[1]
Structural formula
Ball-and-stick model
IUPAC name
Other names
2-Methoxyacetaldehyde dimethyl acetal; Methoxymethylal; Methyl orthoformate
3D model (JSmol)
ECHA InfoCard 100.005.224
EC Number 205-745-7
Molar mass 106.12 g·mol−1
Appearance Colorless liquid
Odor pungent
Density 0.9676 g/cm3
Melting point −53 °C (−63 °F; 220 K)
Boiling point 100.6 °C (213.1 °F; 373.8 K)
Solubility soluble in ethanol, ether
Vapor pressure 3.67
R-phrases (outdated) R11 R36
S-phrases (outdated) S9 S16 S26
Flash point 13 °C (55 °F; 286 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Trimethyl orthoformate is the simplest orthoester. It is a reagent used in organic synthesis for the introduction of a protecting group for aldehydes. 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.

The industrial synthesis of this chemical is from hydrogen cyanide and methanol.[2]

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. RNH2 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.[2]


Trimethyl orthoformate can also be prepared from the reaction between chloroform and excess methanol in the presence of sodium. Deprotonation of the methanol produces sodium methoxide, which acts as a nucleophile and substitutes the three chlorides on the methylylidine group via SN2, yielding trimethyl orthoformate and sodium chloride.

See also[edit]


  1. ^ Trimethyl orthoformate at Sigma-Aldrich
  2. ^ a b Ashford's Dictionary of Industrial Chemicals, Third edition, 2011, ISBN 978-0-9522674-3-0, page 9388