Trimethyl orthoformate

From Wikipedia, the free encyclopedia
Trimethyl orthoformate[1]
Structural formula
Ball-and-stick model
Names
Preferred IUPAC name
Trimethoxymethane
Other names
2-Methoxyacetaldehyde dimethyl acetal; Methoxymethylal; Methyl orthoformate
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.005.224 Edit this at Wikidata
EC Number
  • 205-745-7
UNII
  • InChI=1S/C4H10O3/c1-5-4(6-2)7-3/h4H,1-3H3
  • O(C)C(OC)OC
Properties
C4H10O3
Molar mass 106.121 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 1 kPa at 7 °C[2]
1.3773
Hazards
GHS labelling:
GHS02: FlammableGHS07: Exclamation mark
Signal word
 Danger
H225, H315, H319, H335
P210, P233, P240, P241, P242, P243, P261, P264, P271, P280, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P370+P378, P403+P233, P403+P235, P405, P501
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 (TMOF) is the organic compound with the formula HC(OCH3)3. A colorless liquid, it is the simplest orthoester. It is a reagent used in organic synthesis for the formation of methyl ethers.[3] 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:[4]

HCN + 3 HOCH3 → HC(OCH3)3 + NH3

Trimethyl orthoformate can also be prepared from the reaction between chloroform 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. 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.[4]

Trimethyl orthoformate is also an effective reagent for converting compatible carboxylic acids to their corresponding methyl esters.[5] 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[]

References[]

  1. ^ Trimethyl orthoformate at Sigma-Aldrich
  2. ^ Alfa Aesar SDS
  3. ^ Liu, Hui; Tomooka, Craig S.; Xu, Simon L.; Yerxa, Benjamin R.; Sullivan, Robert W.; Xiong, Yifeng; Moore, Harold W. (1999). "Dimethyl Squarate and ITS Conversion to 3-Ethenyl-4-Methoxycyclobutene-1,2-Dione and 2-Butyl-6-Ethenyl-5-Methoxy-1,4-Benzoquinone". Organic Syntheses. 76: 189. doi:10.15227/orgsyn.076.0189.
  4. ^ a b Ashford's Dictionary of Industrial Chemicals, Third edition, 2011, ISBN 978-0-9522674-3-0, page 9388
  5. ^ Paine, John B. (1 July 2008). "Esters of Pyromellitic Acid. Part I. Esters of Achiral Alcohols: Regioselective Synthesis of Partial and Mixed Pyromellitate Esters, Mechanism of Transesterification in the Quantitative Esterification of the Pyromellitate System Using Orthoformate Esters, and a Facile Synthesis of the Ortho Pyromellitate Diester Substitution Pattern". The Journal of Organic Chemistry. 73 (13): 4929–4938. doi:10.1021/jo800543w.
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