Tetramethoxymethane Explained

Tetramethoxymethane is a chemical compound which is formally formed by complete methylation of the hypothetical orthocarbonic acid C(OH)₄ (orthocarboxylic acid violates the Erlenmeyer rule and is unstable in free state).

Preparation

The obvious synthetic route from tetrachloromethane does not yield the desired product.^[1] The original preparation of the tetramethoxymethane was therefore based on chloropicrin:

Because of the unpleasant properties of the chloropicrin, other tetrasubstituted reactive methane derivatives were investigated as starting material for tetramethoxymethane. For example, trichloromethanesulfenyl chloride (also used as a chemical warfare agent and easily accessible from carbon bisulfide and chlorine) was used:^{[2] [3]}

A less problematic synthesis is based on trichloroacetonitrile,^{[4] [5]} with yields of about 70% be achieved:

Further preparative methods are described in the literature.^[6]

Properties

Tetramethoxymethane is water-clear, aromatic-smelling, low-viscosity liquid which is stable against peroxide formation.^[7]

Use

In addition to the use as a solvent, tetramethoxymethane is used as a fuel in polymer fuel cells,^[8] as an alkylating agent at elevated temperatures (180-200 °C)^[9] as a transesterification reagent (but showing less reactivity than trimethoxymethane^[1]) and as a reagent for the synthesis of 2-aminobenzoxazoles, which are used as molecular building blocks in pharmaceutical active ingredients used in neuroleptics, sedatives, antiemetics, muscle relaxants, fungicides and others.^[10]

Depending on the substituents, the one pot reaction proceeds in "modest to excellent" yields.

References

1. R. H. De Wolfe, Carboxylic ortho acid derivatives: preparation and synthetic applications, Organic Chemistry, Vol. 14, Academic Press, Inc. New York – London, 1970, .
2. H. Tieckelmann, H. W. Post, The preparation of methyl, ethyl, propyl, and butyl orthocarbonates, J. Org. Chem., 13 (2), 265-267 (1948), .
3. US-Patent US 4,059,656, Processes for neutralizing 2,3-dibromopropanol phosphoric acid esters contained in tris(2,3-dibromo-1-propyl) phosphate, Erfinder: M. Demarcq, Anmelder: Produits Chimiques Ugine Kuhlmann, erteilt am 22. November 1974.
4. US-Patent US 3,876,708, Orthocarbonic acid esters, Erfinder: R. Speh, W. Kantlehner, Anmelder: Akzo B.V., erteilt am 8. April 1975.
5. US-Patent US 6,825,385 B2, Process for the preparation of orthocarbonates, Erfinder: G. Fries, J. Kirchhoff, Anmelder: Degussa AG, erteilt am 30. November 2004.
6. W. Kantlehner et al., Die präparative Chemie der O- und N-funktionellen Orthokohlensäure-Derivate, Synthesis; 1977(2): 73-90, .
7. Canadian Journal of Chemistry. K. R. Kopecky. J. Molina . Bis(dimethoxymethyl) peroxide and bis(1,1-dimethoxyethyl) peroxide . 1987 . 65 . 10 . 2350 . 10.1139/v87-392 .
8. US-Patent US 6,864,001, Tetramethyl orthocarbonate fuel cells and systems and methods related thereto, Erfinder: J. Zhang, K. Colbow, Anmelder: Ballard Power Systems Inc., erteilt am 8. März 2005.
9. M. Selva et al., Esters and Orthoesters as Alkylating Agents at High Temperature. Applications to Continuous-flow Processes, J. Chem. Soc., Perkin Trans. 2, 519 (1992), .
10. C. L. Cioffi et al., Synthesis of 2-Aminobenzoxazoles Using Tetramethyl Orthocarbonate or 1,1-Dichloro-diphenoxymethane, J. Org. Chem., 75 (2), 7942-7945 (2010), .