Tetramethoxymethane

Tetramethoxymethane
Names
	Preferred IUPAC name Tetramethoxymethane
	Other names Tetramethyl orthocarbonate
Identifiers
CAS Number	1850-14-2;
3D model (JSmol)	Interactive image;
ChemSpider	67188;
ECHA InfoCard	100.015.853
EC Number	217-438-5;
PubChem CID	74613;
UNII	FHC4GZ2SYJ ;
UN number	3272
CompTox Dashboard (EPA)	DTXSID70171695 ;
	InChI InChI=1S/C5H12O4/c1-6-5(7-2,8-3)9-4/h1-4H3 Key: AHJWSRRHTXRLAQ-UHFFFAOYSA-N;
	SMILES COC(OC)(OC)OC;
Properties
Chemical formula	C5H12O4
Molar mass	136.15 g·mol−1
Appearance	colourless liquid
Density	1.023 g/cm3 (25 °C)
Melting point	−5.5 °C
Boiling point	114 °C
Hazards
	GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H225, H315, H319, H335
Precautionary statements	P210, P261, P305+P351+P338
Related compounds
Other cations	Tetramethoxysilane
Related compounds	Tetraethoxymethane
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Tetramethoxymethane is a chemical compound which is formally formed by complete methylation of the hypothetical orthocarbonic acid C(OH)₄.

Preparation

The obvious synthetic route from the tetrahalomethanes does not yield the desired product, instead giving orthoformates and a halohydrin byproduct.^[2]^: 13 The original preparation of the tetramethoxymethane was therefore based on chloropicrin:^[1]

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:^[3]^[4]

A less problematic synthesis is based on trichloroacetonitrile:^[5]^[6]

Thallium methoxide reacts with carbon disulfide to give tetramethoxymethane and thallium sulfide;^[7] likewise dimethyl dibutylstannate gives tetramethoxymethane and dibutyltin sulfide.^[8] 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,^[3]^[7] but the tin-sulfide synthesis has a 95% yield.^[8]

Properties

Tetramethoxymethane is water-clear, aromatic-smelling, low-viscosity liquid which is stable against peroxide formation.^[9]

Use

In addition to the use as a solvent, tetramethoxymethane is used as a fuel in polymer fuel cells,^[10] as an alkylating agent at elevated temperatures (180-200 °C)^[11] as a transesterification reagent (but showing less reactivity than trimethoxymethane^[2]) 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.^[12]

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

References

^ ^a ^b ^c ^d H. v. Hartel, Über Existenz und Darstellung des Orthokohlensäure-tetramethylesters, Ber.dtsch.chem.Ges., 60(8), 1841 (1927), doi:10.1002/cber.19270600821.
^ ^a ^b R. H. De Wolfe, Carboxylic ortho acid derivatives: preparation and synthetic applications, Organic Chemistry, Vol. 14, Academic Press, Inc. New York – London, 1970, ISBN 978-0-12-214550-6.
^ ^a ^b H. Tieckelmann, H. W. Post, The preparation of methyl, ethyl, propyl, and butyl orthocarbonates, J. Org. Chem., 13 (2), 265-267 (1948), doi:10.1021/jo01160a014.
^ 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.
^ US-Patent US 3,876,708, Orthocarbonic acid esters, Erfinder: R. Speh, W. Kantlehner, Anmelder: Akzo B.V., erteilt am 8. April 1975.
^ 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.
^ ^a ^b ^c W. Kantlehner et al., Die präparative Chemie der O- und N-funktionellen Orthokohlensäure-Derivate, Synthesis; 1977(2): 73-90, doi:10.1055/s-1977-24283.
^ ^a ^b Sakai Shizuyoshi; Kobayashi Yoshihiro; Ishii Yoshio (1971) [13 April 1970]. "Reaction of dialkyltin dialkoxides with carbon disulfide at higher temperature" (PDF). Journal of Organic Chemistry. 36 (9): 1176–1180. doi:10.1021/jo00808a002.
^ K. R. Kopecky; J. Molina (1987). "Bis(dimethoxymethyl) peroxide and bis(1,1-dimethoxyethyl) peroxide". Canadian Journal of Chemistry. 65 (10): 2350. doi:10.1139/v87-392.
^ 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.
^ 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), doi:10.1039/P29920000519.
^ 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), doi:10.1021/jo1017052.

[von_Hartel-1] H. v. Hartel, Über Existenz und Darstellung des Orthokohlensäure-tetramethylesters, Ber.dtsch.chem.Ges., 60(8), 1841 (1927), doi:10.1002/cber.19270600821.

[De_Wolfe-2] R. H. De Wolfe, Carboxylic ortho acid derivatives: preparation and synthetic applications, Organic Chemistry, Vol. 14, Academic Press, Inc. New York – London, 1970, ISBN 978-0-12-214550-6.

[TP-3] H. Tieckelmann, H. W. Post, The preparation of methyl, ethyl, propyl, and butyl orthocarbonates, J. Org. Chem., 13 (2), 265-267 (1948), doi:10.1021/jo01160a014.

[4] 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.

[5] US-Patent US 3,876,708, Orthocarbonic acid esters, Erfinder: R. Speh, W. Kantlehner, Anmelder: Akzo B.V., erteilt am 8. April 1975.

[6] 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.

[Rev-7] W. Kantlehner et al., Die präparative Chemie der O- und N-funktionellen Orthokohlensäure-Derivate, Synthesis; 1977(2): 73-90, doi:10.1055/s-1977-24283.

[Tin-8] Sakai Shizuyoshi; Kobayashi Yoshihiro; Ishii Yoshio (1971) [13 April 1970]. "Reaction of dialkyltin dialkoxides with carbon disulfide at higher temperature" (PDF). Journal of Organic Chemistry. 36 (9): 1176–1180. doi:10.1021/jo00808a002.

[9] K. R. Kopecky; J. Molina (1987). "Bis(dimethoxymethyl) peroxide and bis(1,1-dimethoxyethyl) peroxide". Canadian Journal of Chemistry. 65 (10): 2350. doi:10.1139/v87-392.

[10] 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.

[11] 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), doi:10.1039/P29920000519.

[12] 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), doi:10.1021/jo1017052.

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