Dimethyl sulfate

Dimethyl sulfate
Dimethyl sulfate
CAS number 77-78-1 YesY
PubChem 6497
ChemSpider 6252 YesY
KEGG C19177 YesY
ChEBI CHEBI:59050 YesY
Jmol-3D images Image 1
Molecular formula C2H6O4S
Molar mass 126.13 g/mol
Appearance Colorless liquid
Density 1.33 g/ml, liquid
Melting point

-32 °C

Boiling point

188 °C decomposes

Solubility in water Reacts with water
Solubility Methanol, dichloromethane, acetone
R-phrases R45, R25, R26, R34,
R43, R68
S-phrases S53, S45
Main hazards Poison, contact hazard, inhalation hazard, corrosive, environmental hazard, carcinogenic, mutagenic
NFPA 704
NFPA 704.svg
Related compounds
Related compounds Diethyl sulfate, methyl triflate, dimethyl carbonate
 YesY sulfate (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Dimethyl sulfate is a chemical compound with formula (CH3O)2SO2. As the diester of methanol and sulfuric acid, its formula is often written as (CH3)2SO4 or even Me2SO4, where CH3 or Me is methyl. 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 (although smelling it would represent significant exposure). Like all strong alkylating agents, Me2SO4 is highly toxic. Its use as a laboratory reagent has been superseded to some extent by methyl triflate, CF3SO3CH3, the methyl ester of trifluoromethanesulfonic acid.



Dimethyl sulfate was first discovered in the early 19th century in an impure form. P. Claesson later extensively studied its preparation.[1] It may have been used in chemical warfare.[citation needed]


Dimethyl sulfate can be synthesized in the laboratory by many different syntheses,[2] the simplest being the esterification of sulfuric acid with methanol:

2 CH3OH + H2SO4 → (CH3)2SO4 + 2 H2O

Another possible synthesis involves distillation of methyl hydrogen sulfate:[1]

2 CH3HSO4 → H2SO4 + (CH3)2SO4

Methyl nitrite and methyl chlorosulfonate also result in dimethyl sulfate[1]:

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

In the United States, Me2SO4 has been produced commercially since the 1920s. A common process is the continuous reaction of dimethyl ether with sulfur trioxide.[3]

(CH3)2O + SO3 → (CH3)2SO4


Dimethyl sulfate is best known as a reagent for the methylation of phenols, amines, and thiols. Typically, one methyl group is transferred more quickly than the second. Methyl transfer is typically assumed to occur via an SN2 reaction. Compared to other methylating agents, dimethyl sulfate is preferred by the industry because of its low cost and high reactivity.

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-butanol to t-butyl methyl ether:

2 (CH3)3COH + (CH3O)2SO2 → 2 (CH3)3COCH3 + H2SO4

Alkoxide salts are rapidly methylated:[4]

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

The methylation of sugars is called Haworth methylation [5]

Methylation at amine nitrogen

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

C6H5CH=NC4H9 + (CH3O)2SO2 → C6H5CH=N+(CH3)C4H9 + CH3OSO3-

Quaternized fatty ammonium compounds are used as a surfactant or fabric softeners. The methylation of a tertiary amine is illustrated as[4]:

CH3(C6H4)NH2 + (CH3O)2SO2 (in NaHCO3 aq.) → CH3(C6H4)N(CH3)2 + Na(CH3)SO4

Methylation at sulfur

Similar to the methylation of alcohols, mercaptide salts are easily methylated by Me2SO4[4]:

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

An example is:[6]

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 effect the base-specific cleavage of guanine in DNA by rupturing the imidazole rings present in guanine.[7] This process can be used to determine base sequencing, cleavage on the DNA chain, and other applications.

Dimethyl sulfate also methylates adenine in single-stranded portions of DNA (e.g., those with proteins like RNA polymerase progressively melting and re-annealing the DNA). Upon re-annealing, these methyl groups interfere with adenine-guanine base-pairing. Nuclease S1 can then be used to cut the DNA in single-stranded regions (anywhere with a methylated adenine). This is an important technique for analyzing protein-DNA interactions.


Although dimethyl sulfate is highly effective and affordable, its toxicity has encouraged the use of other methylating reagents. Methyl iodide is a reagent used for O-methylation, like dimethyl sulfate, but is less hazardous and more expensive.[6] Dimethyl carbonate, which is less reactive, has far lower toxicity compared to both dimethyl sulfate and methyl iodide and can be used to instead of dimethyl sulfate for N-methylation.[8] High pressure can be used to accelerate methylation by dimethyl carbonate. In general, the toxicity of methylating agents is correlated with their efficiency as methyl transfer reagents.[citation needed]


Dimethyl sulfate is likely carcinogenic[3] and mutagenic, poisonous, corrosive, environmentally hazardous and volatile (presenting an inhalation hazard). Some consider it a potential chemical weapon. Dimethyl sulfate is absorbed through the skin, mucous membranes, and gastrointestinal tract. There is no strong odor or immediate irritation to warn of lethal concentration in air. The LD50 (acute, oral) is 205 mg/kg (rat) and 140 mg/kg (mouse), and LC50 (acute) is 45 ppm / 4 hours (rat).[9] The vapor pressure of 65 Pa[10] is sufficiently large to produce a lethal concentration in air by evaporation at 20 °C. Delayed toxicity allows potentially fatal exposures to occur prior to development of any warning symptoms.[11] Symptoms may be delayed 6–24 hours. Concentrated solutions of bases (ammonia, alkalis) can be used to hydrolyze minor spills and residues on contaminated equipment, but the reaction may become violent with larger amounts of dimethyl sulfate (see ICSC). Although the compound hydrolyses in water, plain water cannot be assumed to hydrolyze dimethyl sulfate quickly enough for decontamination purposes. The hydrolysis products, monomethyl sulfate and methanol, are environmentally hazardous. In water, the compound is ultimately hydrolyzed to sulfuric acid and methanol.


  1. ^ a b c Suter, C. M. The Organic Chemistry of Sulfur Tetracovalent Sulfur Compounds John Wiley & Sons, Inc. 1944. p 49-53
  2. ^ Shirley, D. A. Organic Chemistry. Holt, Rinehart and Winston. 1966. p. 253
  3. ^ a b "Substance Profiles - Dimethyl Sulfate". 11th Report on Carcinogens. Department of Health and Human Services. http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s078dime.pdf. 
  4. ^ a b c Dupont product information
  5. ^ W. N. Haworth, J. Chem. Soc. 107, 13 (1915).
  6. ^ a b Fieser, L. F. and Fieser, M. Reagents for Organic Synthesis. John Wiley & Sons, Inc. 1967. p. 295
  7. ^ Streitwieser, A., Heathcock, C. H., and Kosower, E. M. Introduction to Organic Chemistry. Prentice-Hall Inc. 1992. p. 1169
  8. ^ W. C. Shieh, S. Dell and O. Repic (2001). "1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) and Microwave-Accelerated Green Chemistry in Methylation of Phenols, Indoles, and Benzimidazoles with Dimethyl Carbonate". Organic Letters 3 (26): 4279–4281. doi:10.1021/ol016949n. PMID 11784197. 
  9. ^ http://www.sciencelab.com/msds.php?msdsId=9927524
  10. ^ ICSC
  11. ^ Rippey, J. and Stallwood, M. Emergency Medicine Journal 2005;22:878-879

External links

Wikimedia Foundation. 2010.

Игры ⚽ Поможем решить контрольную работу

Look at other dictionaries:

  • dimethyl sulfate — An industrial chemical (sulfuric acid dimethyl ester (CH3)2SO4), used in synthesis as an alkylating agent; it causes nystagmus, convulsions, and death from pulmonary complications. * * * dimethyl sulfate …   Medical dictionary

  • dimethyl sulfate — noun Etymology: International Scientific Vocabulary dimethyl + sulfate : the methyl sulfate (CH3)2SO4 * * * Chem. a colorless or yellow, slightly water soluble, poisonous liquid, (CH3)2SO2, used chiefly in organic synthesis. Also, methyl …   Useful english dictionary

  • dimethyl sulfate — dimetilsulfatas statusas T sritis chemija formulė (CH₃O)₂SO₂ atitikmenys: angl. dimethyl sulfate rus. диметилсульфат …   Chemijos terminų aiškinamasis žodynas

  • dimethyl sulfate protection — dimethyl sulfate protection. См. защита от диметилсульфата. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • dimethyl sulfate — Chem. a colorless or yellow, slightly water soluble, poisonous liquid, (CH3)2SO2, used chiefly in organic synthesis. Also, methyl sulfate. * * * …   Universalium

  • dimethyl sulfate — noun The methyl ester of sulfuric acid, (CH)SO, used as a methylating agent in organic chemistry …   Wiktionary

  • Sulfate de diméthyle — Structure du sulfate de diméthyle …   Wikipédia en Français

  • Dimethyl sulfoxide — Dimethyl sulfoxide …   Wikipedia

  • Dimethyl sulfite — Dimethyl sulfite …   Wikipedia

  • Dimethyl ether — Systematic name …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”