Tetramethoxymethane Explained

Tetramethoxymethane is a chemical compound which is formally formed by complete methylation of the hypothetical orthocarbonic acid .

Preparation

The obvious synthetic route from the tetrahalomethanes does not yield the desired product, instead giving orthoformates and a halohydrin byproduct.^[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]}

Thallium methoxide reacts with carbon disulfide to give tetramethoxymethane and thallium sulfide; likewise dimethyl dibutylstannate gives tetramethoxymethane and dibutyltin sulfide.^[6] Further preparative methods are described in the literature.^[7]

Synthesis from chloropicrin only yields about 50% product. Syntheses from trichloromethanesulfenyl chloride or trichloroacetonitrile or the thallium-sulfide route yield about 70-80% product,^{[2] [7]} but the tin-sulfide synthesis has a 95% yield.^[6]

Properties

Tetramethoxymethane is water-clear, aromatic-smelling, low-viscosity liquid which is stable against peroxide formation.^[8]

Use

In addition to the use as a solvent, tetramethoxymethane is used as a fuel in polymer fuel cells,^[9] as an alkylating agent at elevated temperatures (180-200 °C)^[10] 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.^[11]

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. Reaction of dialkyltin dialkoxides with carbon disulfide at higher temperature. 1176–1180. Journal of Organic Chemistry. 36. 9. 1971. Sakai Shizuyoshi. Kobayashi Yoshihiro. Ishii Yoshio. 10.1021/jo00808a002 . 13 April 1970.
7. W. Kantlehner et al., Die präparative Chemie der O- und N-funktionellen Orthokohlensäure-Derivate, Synthesis; 1977(2): 73-90, .
8. 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 .
9. 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.
10. 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), .
11. 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), .