Dimethyl sulfate
General
Other names	Sulfuric acid,  dimethyl ester
Molecular formula	(CH3)2SO4
Molar mass	126.13 g/mol
Appearance	Colorless liquid
CAS number	*
Properties
Density and phase	1.33 g/ml, liquid
Solubility in water	Reacts
Melting point	−32 °C
Boiling point	188 °C decomp.
Viscosity	? cP at ? °C
Hazards
MSDS	External MSDS
EU classification	Very toxic (T+) Carc. Cat. 2 Muta. Cat. 3
NFPA 704
R-phrases	, , , , ,
S-phrases	,
Flash point	83 °C
RTECS number	WS8225000
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Related compounds
Related compounds	Diethyl sulfate CH3OSO2CF3 CH3OSO2F
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Chemical infobox

Dimethyl sulfate is a chemical compound with formula (₃O)₂₂. As the dimethyl ester of sulfuric acid. its formula is often written as (CH₃)₂SO₄ or even Me₂SO₄ (where Me = CH₃) although such formulae do not convey the connectivity of the atoms. Me₂SO₄ is mainly used as a methylating agent in organic synthesis.

Under standard conditions, Me₂SO₄ is a colourless oily liquid with a slight onion-like odour. Like all strong alkylating agents, Me₂SO₄ is highly toxic. Its use as a laboratory reagent has been superseded to some extent by CF₃SO₃CH₃, the methyl ester of trifluoromethanesulfonic acid.

History

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Dimethyl sulfate was first discovered sometime in the early 1800's in an impure form. It was Claesson who later did extensive study on the preparation of dimethyl sulfate.²

Production

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Dimethyl sulfate can be synthesized in the laboratory with many different syntheses³:

2CH₃OH + H₂SO₄ → (CH₃)₂SO₄ + 2H₂O

Another possible synthesis involves distillation of methyl hydrogen sulfate²:

2CH₃HSO₄ → H₂SO₄ + (CH₃)₂SO₄

Methyl nitrite and methyl chlorosulfonate also result in dimethyl sulfate²:

CH₃ONO + (CH₃)OSO₂Cl → (CH₃)₂SO₄ + NOCl

In the United States Me₂SO₄ has been produced commercially since the 1920's. A common process is the continuous reaction of dimethyl ether with sulfur trioxide⁶.

(CH₃)₂O + SO₃ → (CH₃)₂SO₄

Uses

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Dimethyl sulfate is best known as a reagent for the methylation of phenols, amines, and thiols. Typically, one methyl group is removed more quickly than the other methyl group. The mechanism that typically occurs with dimethyl sulfate is a S_N2 reaction.

Methylation at oxygen

Most commonly, Me₂SO₄ is employed to methylate phenols. Some simple alcohols are also suitably methylated, as illustrated by the conversion of tert-butyl alcohol to t-butyl methyl ether:

2 (CH₃)₃COH + (CH₃O)₂SO₂ → 2 (CH₃)₃COCH₃ + H_2SO4

Alkoxide salts are rapidly methylated⁷:

RO ^- Na ⁺ + (CH₃O)₂SO₂ → ROCH₃ + Na(CH₃)SO₄

Methylation at amine nitrogen

Me₂SO₄ is used to prepare both quaternary ammonium salts or tertiary amines⁴:

C₆H₅CH=NC₄C₉ + (CH₃O)₂SO₂ → C₆H₅CH=N⁺(CH₃)C₄C₉ + CH_3OSO3^-

Quaternized fatty ammonium compounds are used as a surfactant or fabric softeners. The methylation of a tertiary amine is illustrated as⁷:

CH₃(C₆H₂)NH₂ + (CH₃O)₂SO₂ (in HNCO₂) → CH₃(C₆H₂)N(CH₃)₂ + Na(CH₃)SO₄

Methylation at sulfur

Similar to the methylation of alcohols, mercaptide salts are easily methylated by Me₂SO₄⁷:

RS^-Na⁺ + (CH₃O)₂SO₂ → RSCH₃ + Na(CH₃)SO₄

An example is ¹:

p-CH₃C₆H₄SO₂Na + (CH₃O)₂SO₂ → p-CH₃C₆H₄SO₂CH₃ + Na(CH₃)SO₄

This method has been used to prepare thioesters:

RC(O)SH + (CH₃O)₂SO₂ → RC(O)S(CH₃) + HOSO₃CH₃

Other Uses

Dimethyl sulfate can be used with DNA for the base-specific cleavage of guanine by rupturing the imidazole rings present in guanine⁹. This process can be used to determine base sequencing, cleavage on the DNA chain, and other applications.

Safety

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Dimethyl sulfate is likely carcinogenic, and is considered toxic. When administered to laboratory rats via inhalation or intravenously, cancer developed⁶. The toxicity of dimethyl sulfate is so extreme that some consider it a potential chemical weapon. Dimethyl sulfate is absorbed through the skin, mucous membranes, and gastrointestinal tract. Delayed toxicity allows potentially fatal exposures to occur prior to development of any warning symptoms⁸.

Since dimethyl sulfate is very toxic, other methylating reagents are often used. However, it is sometimes more appropriate to use dimethyl sulfate due to the effectiveness and affordability. Methyl iodide is a reagent used for O-methylation, like dimethyl sulfate, but is less hazardous and more expensive.¹ Dimethyl carbonate has a lower toxicity compared to both dimethyl sulfate and methyl iodide, and can be used to instead of dimethyl sulfate for N-methylation, depending on the reaction⁵.

References

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1. Fieser, L. F. and Fieser, M. Reagents for Organic Synthesis. John Wiley & Sons, Inc. 1967. p. 295
2. Suter, C. M. The Organic Chemistry of Sulfur Tetracovalent Sulfur Compounds. John Wiley & Sons, Inc. 1944. p 49-53
3. Shirley, D. A. Organic Chemistry. Holt, Rinehart and Winston. 1966. p. 253
4. Organic Synthesis
5. Shieh, W. Org. Lett., 3 (26), 4279-4281, 2001.
6. Dimethyl Sulfate
7. Dupont product information
8. Rippey, J. and Stallwood, M. Emergency Medicine Journal 2005;22:878-879
9. Streitwieser, A., Heathcock, C. H., and Kosower, E. M. Introduction to Organic Chemistry. Prentice-Hall Inc. 1992. p. 1169

External links

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• International Chemical Safety Card 0148
• IARC Monograph: "Dimethyl sulfate"

Organosulfates | Methylating agents | IARC Group 2A carcinogens

Dimethylsulfat | Диметилсульфат