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:Trimethyl orthoformate

{{Chembox

|Reference =[http://www.sigmaaldrich.com/catalog/ProductDetail.do?lang=en&N4=305472|ALDRICH&N5=SEARCH_CONCAT_PNO|BRAND_KEY&F=SPEC Trimethyl orthoformate] at Sigma-Aldrich

|ImageFile = Trimethoxymethane.svg

|ImageSize = 180

|ImageAlt = Structural formula

|ImageFile1 = Trimethyl-orthoformate-3D-balls.png

|ImageSize1 = 180

|ImageAlt1 = Ball-and-stick model

|PIN = Trimethoxymethane

|OtherNames = 2-Methoxyacetaldehyde dimethyl acetal
Methoxymethylal
Methyl orthoformate

|Section1={{Chembox Identifiers

|CASNo = 149-73-5

|CASNo_Ref = {{cascite|correct|CAS}}

|UNII = XAM28819YJ

|UNII_Ref = {{fdacite|correct|FDA}}

|PubChem = 9005

|ChemSpiderID = 8655

|EINECS = 205-745-7

|SMILES = O(C)C(OC)OC

|InChI = 1S/C4H10O3/c1-5-4(6-2)7-3/h4H,1-3H3

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|Section2={{Chembox Properties

|C=4 | H=10 | O=3

|Appearance = Colorless liquid

|Odor = pungent

|Density = 0.9676 g/cm3

|MeltingPtC = -53

|BoilingPtC = 100.6

|SolubleOther = soluble in ethanol, diethyl ether

|VaporPressure = 1 kPa at 7 °CAlfa Aesar SDS

|RefractIndex = 1.3773

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|Section3={{Chembox Hazards

|FlashPtC = 13

|GHSPictograms = {{GHS02}}{{GHS07}}

|GHSSignalWord = Danger

|HPhrases = {{H-phrases|225|315|319|335}}

|PPhrases = {{P-phrases|210|233|240|241|242|243|261|264|271|280|302+352|303+361+353|304+340|305+351+338|312|321|332+313|337+313|362|370+378|403+233|403+235|405|501}}

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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.{{cite journal |doi=10.15227/orgsyn.076.0189|title=Dimethyl Squarate and ITS Conversion to 3-Ethenyl-4-Methoxycyclobutene-1,2-Dione and 2-Butyl-6-Ethenyl-5-Methoxy-1,4-Benzoquinone|journal=Organic Syntheses|year=1999|volume=76|page=189

|first1=Hui |last1=Liu|first2=Craig S. |last2=Tomooka|first3=Simon L.|last3=Xu|first4=Benjamin R.|last4=Yerxa|first5=Robert W.|last5=Sullivan|first6=Yifeng|last6=Xiong|first7=Harold W.|last7=Moore}} 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:Ashford's Dictionary of Industrial Chemicals, Third edition, 2011, {{ISBN|978-0-9522674-3-0}}, page 10744

: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 some fungicides (for example: 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.

Trimethyl orthoformate is also an effective reagent for converting compatible carboxylic acids to their corresponding methyl esters.{{cite journal |last1=Paine |first1=John B. |title=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 |journal=The Journal of Organic Chemistry |date=1 July 2008 |volume=73 |issue=13 |pages=4929–4938 |doi=10.1021/jo800543w|pmid=18522420 }} 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

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Category:Reagents for organic chemistry

Category:Orthoesters

Category:Methyl esters