DIMETHYL SULFATE

DIMETHYL SULFATE

Dimethyl sulfate 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 extremely toxic. Dimethyl sulfates use as a laboratory reagent has been superseded to some extent by methyl triflate, CF3SO3CH3, the methyl ester of trifluoromethanesulfonic acid.

CAS No. : 77-78-1
EC No. : 201-058-1

Synonyms:
Dimethyl sulphate; Sulfuric acid dimethyl ester; Me2SO4; DMSO4; Dimethyl ester of sulfuric acid; Methyl sulfate; dimetil sülfat; dymethyl sulfate; di-methyl sulfate; di methyl sulfate; di metil sülfat; di-metil-sülfat; dimetilsülfat; Dimethylsulphate; Dimethylsulfate; Me2SO4; DMS; DIMETHYL SULFATE; 77-78-1; Dimethyl sulphate; Sulfuric acid, dimethyl ester; dimethylsulfate; Dimethyl monosulfate; Dimethylsulfat; Sulfate dimethylique; Sulfuric acid dimethyl ester; Dimethylsulfaat; Dimetilsolfato; DMS (methyl sulfate); Dwumetylowy siarczan; Sulfato de dimetilo; Dimethoxysulfone; Methyle (sulfate de); DimethylSulphate; RCRA waste number U103; Sulfate de dimethyle; Dimethylester kyseliny sirove; Dimethylsulfat [Czech]; Methyl sulfate (VAN); Dimethylsulfaat [Dutch]; Dimetilsolfato [Italian]; Diethyl sulfate; UNII-JW5CW40Z50; NSC 56194; CCRIS 265; Dwumetylowy siarczan [Polish]; Sulfate dimethylique [French]; Sulfate de dimethyle [French]; Sulfato de dimetilo [Spanish]; HSDB 932; Methyle (sulfate de) [French]; EINECS 201-058-1; Methyl sulfate, Me2SO4; UN1595; Dimethylester kyseliny sirove [Czech]; RCRA waste no. U103; Dimethyl sulfate, 99+%, AcroSeal(R); Me2SO4; dimethlysulfate; dimethysulfate; dimetylsulphate; Dimethyl sulphate; Sulfuric acid dimethyl ester; Me2SO4; DMSO4; Dimethyl ester of sulfuric acid; Methyl sulfate; dimetil sülfat; dimethyl-sulfate; dirnethyl sulfate; Sulfate de methyle; dimethylsulfuric acid; dimethyl sulfuric acid; ACMC-20p1dz; DI-METHYL SULFATE; Dimethyl sulfate, 99+%; EC 201-058-1; SCHEMBL1249; WLN: 1OSWO1; Dimethyl sulfate, >=99%; Sulphuric acid dimethyl ester; CHEMBL162150; Dimethyl sulfate, >=99.8%; DTXSID5024055; (CH3)2SO4; NSC-56194; STL264200; ZINC43426977; AKOS000119929; Dimethyl sulfate [UN1595] [Poison]; LS-1714; MCULE-2861298645; UN 1595; Dimethyl sulfate [UN1595] [Poison]; Dimethyl sulfate, purum, >=95.0% (GC); Dimethyl sulfate, SAJ first grade, >=99.0%; Q413421; Dimethyl sulfate, puriss. p.a., >=99.0% (GC); Dimethyl sulfate, for GC derivatization, >=99.0% (GC)

Dimethyl Sulfate

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 Me2SO4, where CH3 or Me is methyl. Me2SO4 is mainly used as a methylating agent in organic synthesis.

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 extremely toxic. Its use as a laboratory reagent has been superseded to some extent by methyl triflate, CF3SO3CH3, the methyl ester of trifluoromethanesulfonic acid.

History of Dimethyl sulfate
Dimethyl sulfate was discovered in the early 19th century in an impure form. P. Claesson later extensively studied its preparation. It was used in chemical warfare in WWI.

Production of Dimethyl sulfate
Dimethyl sulfate can be synthesized in the laboratory by many different methods, 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:
2 CH3HSO4 → H2SO4 + (CH3)2SO4

Methyl nitrite and methyl chlorosulfonate also result in dimethyl sulfate:
CH3ONO + (CH3)OSO2Cl → (CH3)2SO4 + NOCl

Dimethyl sulfate has been produced commercially since the 1920s. A common process is the continuous reaction of dimethyl ether with sulfur trioxide.
(CH3)2O + SO3 → (CH3)2SO4

Uses of Dimethyl sulfate
Dimethyl sulfate is best known as a reagent for the methylation of phenols, amines, and thiols. One methyl group is transferred more quickly than the second. Methyl transfer is 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 Dimethyl sulfate 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:

RO− Na+ + (CH3O)2SO2 → ROCH3 + Na(CH3)SO4
The methylation of sugars is called Haworth methylation.

Methylation at amine nitrogen
Dimethyl sulfate 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. Methylation to create a tertiary amine is illustrated as:

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 Dimethyl sulfate:
RS−Na+ + (CH3O)2SO2 → RSCH3 + Na(CH3)SO4

An example is:
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

Properties of Dimethyl sulfate
Chemical formula    C2H6O4S
Molar mass    126.13 g/mol
Appearance    Colorless, oily liquid
Odor    faint, onion-like
Density    1.33 g/ml, liquid
Melting point    −32 °C (−26 °F; 241 K)
Boiling point    188 °C (370 °F; 461 K) (decomposes)
Solubility in water    Reacts
Solubility    Methanol, dichloromethane, acetone
Vapor pressure    0.1 mmHg (20°C)
Magnetic susceptibility (χ)    -62.2·10−6 cm3/mol

Reactions with nucleic acids
Dimethyl sulfate (DMS) is used to determine the secondary structure of RNA. At neutral pH, DMS methylates unpaired adenine and cytosine residues at their canonical Watson-Crick faces, but it cannot methylate base-paired nucleotides. Using the method known as DMS-MaPseq, RNA is incubated with DMS to methylate unpaired bases. Then the RNA is reverse-transcribed; the reverse transcriptase frequently adds an incorrect DNA base when it encounters a methylated RNA base. These mutations can be detected via sequencing, and the RNA is inferred to be single-stranded at bases with above-background mutation rates.

Dimethyl sulfate can effect the base-specific cleavage of DNA by attacking the imidazole rings present in guanine. 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.

Alternatives of Dimethyl sulfate
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. Dimethyl carbonate, which is less reactive, has far lower toxicity compared to both dimethyl sulfate and methyl iodide. 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.

Safety of Dimethyl sulfate
Dimethyl sulfate is carcinogenic and mutagenic, highly poisonous, corrosive, and environmentally hazardous. Dimethyl sulfate is absorbed through the skin, mucous membranes, and gastrointestinal tract, and can cause a fatal delayed respiratory tract reaction. An ocular reaction is also common. There is no strong odor or immediate irritation to warn of lethal concentration in the air. The LD50 (acute, oral) is 205 mg/kg (rat) and 140 mg/kg (mouse), and LC50 (acute) is 45 ppm / 4 hours (rat). The vapor pressure of 65 Pa 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. 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, treatment with water cannot be assumed to decontaminate dimethyl sulfate.

Dimethyl sulfate is a colorless oily liquid, odorless to a faint onion-like odor. Dimethyl sulfate is very toxic by inhalation. It is a combustible liquid and has a flash point of 182°F. It is slightly soluble in water and decomposed by water to give sulfuric acid with evolution of heat. It is corrosive to metals and tissue. It is a potent methylating agent.

Dimethyl Sulfate is an odorless, corrosive, oily liquid with an onion-like odor that emits toxic fumes upon heating. Dimethyl sulfate is used in industry as a methylating agent in the manufacture of many organic chemicals. Inhalation exposure to its vapors is highly irritating to the eyes and lungs and may cause damage to the liver, kidney, heart and central nervous system, while dermal contact causes severe blistering. It is a possible mutagen and is reasonably anticipated to be a human carcinogen based on evidence of carcinogenicity in experimental animals.

Following a single iv injection of 75 mg/kg body weight in 0.5 ml of 0.1 M sodium citrate buffer (pH 7.4), there was a rapid fall in the concentration of dimethyl sulfate in the blood of the rat to 1/6 of the amount that would be expected if the compound had been evenly distributed ... No detectable dimethyl sulfate was found, 5 min after the injection.

Dimethyl sulfate is absorbed readily through mucous membranes, the intestinal tract, and the skin. It is rapidly metabolized in mammalian tissues and when injected intravenously into rats is undetectable in the plasma after 3 minutes. It is possible that the hydrolysis of dimethyl sulfate and the subsequent methylation of component molecules of the cells and tissues, including DNA, are responsible for its local effects, systemic toxic effects, and possible carcinogenicity. On the eye, dimethyl sulfate produces toxic effects similar to those of methanol and it is probable that its toxicity is in part a direct result of the dissolved methanol moiety of the molecule as well as being a result of alkylation reactions. The ultimate metabolites in the human body are sulfate and carbon dioxide, and these are excreted by the kidneys and released by the lungs, respectively.

Investigators found a maximum level of methanol of 18.7 mg/L in blood samples taken from 5 guinea pigs, at intervals, following an 18 min inhalation exposure to air containing dimethyl sulfate at a concentration of 393 mg/cu m (75 ppm). During the first 2 days following exposure, 0.064 to 0.156 mg methanol per day was excreted in the urine; if all the dimethyl sulfate inhaled had been absorbed and hydrolyzed, a maximum of 0.9 mg methanol would have been found.

Maximum concentration /of methanol/ found was 1.87 mg % in Guinea pig urine 18 min after inhalation of air containing 76 ppm of dimethyl sulfate.

7-Methylguanine and small quantities of 1-methyladenine and 3-methyladenine could be detected in the urine of mice exposed to dimethyl sulfate via inhalation. In two separate studies, 4 male NMRI mice were exposed to average H-dimethyl sulfate concentrations of 16.3 mg/cu m or 0.32 mg/cu m for 135 min and 60 min, respectively (maximum concentration approximately 4 times higher). The total amount of methyl purines found in the urine in 2 consecutive 24 hr periods was about 0.15-0.3% of the total dose, and, in each case, the major product isolated was 7-methylguanine.

Uses of Dimethyl sulfate
Dimethyl sulfate is used as a methylating agent in the manufacture of many organic chemicals. It is also used in the manufacture of dyes and perfumes, for the separation of mineral oils, and for the analysis of auto fluids. Formerly, dimethyl sulfate was used as a war gas.

Dimethyl sulfate (DMS) is used both as a methylating agent in industrial chemical synthesis and in medical laboratories for chemical cleavage of DNA.

The addition of sulfur trioxide to dimethyl ether is used industrially for the production of dimethyl sulfate.

Technical grade dimethyl sulfate contains small amounts of dimethyl ether.

Analytical techniques have been developed for the collection and determination of gas phase dimethyl sulfate and monomethyl sulfuric acid based on collection of the alkyl sulfate compounds with both denuder tubes and resin sorption beds and analysis of the collected material by ion chromatography.

Analyte: Dimethyl sulfate; Matrix: air; Procedure: Gas chromatography, electron capture detector; Desorption: 1 ml diethyl ether, 30 min; Range: 1 to 120 ug per sample; Est limit of detection: 0.25 ug/sample; Precision: 0.06 at 1.1 to 39 ug per sample.

Dimethyl sulfate is detected in air by gas chromatography with N-P detection of methyl cyanide produced in the reaction of dimethyl sulfate with KCN. Silica gel tubes are used for sampling dimethyl sulfate and triethylene glycol for desorption of the cmpd from the adsorbents. The charged silica gel tubes can be stored at -20 °For 3 days. The recovery is 65% for 1-50 ug dimethyl sulfate and is not dependent on air humidity. The relative deviation of single values is + or - 10% at 95% statistical accuracy. Dimethyl sulfate can be detected with certainty to 0.5 ug in 20 l air.

Exposure to dimethyl sulfate is primarily occupational. Acute (short-term) exposure of humans to the vapors of dimethyl sulfate may cause severe inflammation and necrosis of the eyes, mouth, and respiratory tract. Acute oral or inhalation exposure to dimethyl sulfate primarily damages the lungs but also injures the liver, kidneys, heart, and central nervous system (CNS), while dermal contact with dimethyl sulfate may produce severe blistering in humans. Human data on the carcinogenic effects of dimethyl sulfate are inadequate. Tumors have been observed in the nasal passages, lungs, and thorax of animals exposed to dimethyl sulfate by inhalation. EPA has classified dimethyl sulfate as a Group B2, probable human carcinogen.

NIOSH considers dimethyl sulfate to be a potential occupational carcinogen.

Warning: Symptoms may be delayed up to 12 hours. Signs and Symptoms of Dimethyl Sulfate Exposure: Dimethyl sulfate is irritating to the eyes, skin, mucous membranes, and respiratory tract. Severe dermal burns may be seen. Headache and giddiness are early signs of acute exposure which may be followed by changes in vision, lacrimation (tearing), photophobia, cough, difficulty in breathing, nausea, and vomiting. In severe cases, seizures, paralysis, delirium, and coma may occur. Emergency Life-Support Procedures: Acute exposure to dimethyl sulfate may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination. Inhalation Exposure: 1. Move victims to fresh air. Emergency personnel should avoid self-exposure to dimethyl sulfate. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 4. Transport to a health care facility. Dermal/Eye Exposure: 1. Remove victims from exposure. Emergency personnel should avoid self-exposure to dimethyl sulfate.

Complete destruction of undiluted dimethyl sulfate in water miscible solvents (methanol, ethanol, dimethyl sulfoxide, acetone, and N,N-dimethylformamide), and dimethyl sulfate in immiscible or partially water miscible solvents (toluene, p-xylene, benzene, 1-pentanol, ethyl acetate, chloroform, carbon tetrachloride, and acetonitrile) was obtained using sodium hydroxide, sodium carbonate, and ammonium hydroxide solutions. Reaction times for degradation were 15 minutes (after homogeneity) for undiluted dimethyl sulfate; 15 minutes for solutions in methanol, ethanol, dimethyl sulfoxide, and N,N-dimethylformamide; 1 hour for acetone; 33 hours for acetonitrile; and 1 day for other solvents.

Absorption by diatomite is the best way to clean up spilled dimethyl sulfate; 1 kg of diatomite binds 5 - 6 kg of dimethyl sulfate to form a doughlike mass.

For the treatment and disposal of waste, the recommended methods are alkaline hydrolysis, incineration, and landfill. Do not use open burning (e.g., as a boiler fuel) or evaporation for waste disposal. For incineration, dimethyl sulfate should be dissolved in a combustible solvent and sprayed into a furnace with an afterburner and an alkali scrubber. Dimethyl sulfate may be decomposed by adding a dilute alkaline solution; the mixture should be stirred and then allowed to settle. The resulting solution is then neutralized by acid or alkali as appropriate and drained into a sewer. When rapid decomposition is needed the waste may be warmed. It may also be adsorbed on vermiculite, packed in drums, buried and covered immediately.

Showers and bubbler eye fountains must be available where dimethyl sulfate is used.

A violent reaction occurred which shattered the flask when liter quantities of dimethyl sulfate and conc aqueous ammonia were accidentally mixed. Use dilute ammonia in small quantities to destroy dimethyl sulfate.

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Dimethyl sulfate is included on this list.

Evaluation: There is inadequate evidence for the carcinogenicity in humans of dimethyl sulfate. There is sufficient evidence for the carcinogenicity in experimental animals of dimethyl sulfate. Overall evaluation: Dimethyl sulfate is probably carcinogenic to humans (Group 2A). In making the overall evaluation, the Working Group took into consideration that dimethyl sulfate is a potent genotoxic chemical which can directly alkylate DNA both in vitro and in vivo.

Dimethyl Sulfate: reasonably anticipated to be a human carcinogen.

Because of its delayed effects, early clinical monitoring and treatment during the first 24 to 72 hours are important. Patients exposed to dimethyl sulfate should be treated as a medical emergency. Induced emesis can be dangerous because of re-exposure of the esophagus to corrosive material and because of the danger of aspiration pneumonia and respiratory tract damage. Gastric lavage can be performed, preferably within 1 hour of ingestion with appropriate tracheal protection. Endoscopy determines the extent of esophageal and gastric injury. Oral exposure is managed as a corrosive acid ingestion. Eye exposure is treated with copious irrigation with water or normal saline for at least 20 to 30 minutes. For skin exposure, all contaminated clothing should be removed and exposed skin washed thoroughly with water or saline.

Acute Exposure/ Adult male CrlCD:BR rats were exposed nose-only to several concentrations of dimethyl sulfate (DMS) vapors to determine the relationships between vapor uptake and DNA methylation. Following DMS exposure, nasal respiratory and olfactory mucosa and lung tissue were removed and DNA was isolated for the analysis of methylated purines. DMS vapor uptake was complex and related to exposure concentration; clearance appeared to increase with increasing DMS concentrations between 0.5 and 8 ppm. Plethysmorgraphic measurements correlated with the time-dependent disappearance of dimethyl sulfate from a closed exposure apparatus. Above an initial DMS concentration of 8 ppm, sensory irritancy apparently altered normal respiratory parameters, clearance, and regional DNA methylation. DMS-dependent N7-methylguanine formation in DNA isolated from nasal respiratory mucosa was detectable 30 min following a 20-min exposure to an initial DMS concentration of 1 ppm. DMS-dependent methylation of DNA, as evidenced by N7-methylguanine and N3-methyladenine formation, showed concentration-response relationships in all tissues examined and was correlated with vapor uptake. DNA adduct formation showed regional differences characteristic of the absorption of a water-soluble vapor; methylation was greatest in DNA isolated from respiratory mucosa, less in olfactory, and little in lung. Repair of N7-methylguanine did not appear to be significantly different between nasal respiratory and olfactory tissues

Dimethyl sulfate's production and use as a methylating agent, stabilizer and chemical intermediate may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.677 mm Hg at 25 °C indicates dimethyl sulfate will exist solely as a vapor in the atmosphere. Vapor-phase dimethyl sulfate will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 82 days. Vapor-phase dimethyl sulfate will be degraded in the atmosphere by reaction with water (estimated atmospheric lifetime of >2 days). Dimethyl sulfate does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, dimethyl sulfate is expected to hydrolyze in moist soils. Adsorption and volatilization from soil are not expected to be important fate processes because of hydrolysis. If released into water, dimethyl sulfate is expected to hydrolyze with a half-life of 1.15 hours; methanol and sulfuric acid have been identified as hydrolysis products. Volatilization, adsorption to suspended solids and sediments, biodegradation, and bioconcentration are not expected to be important fate processes in aquatic systems because of hydrolysis. Occupational exposure to dimethyl sulfate may occur through inhalation and dermal contact with this compound at workplaces where dimethyl sulfate is produced or used. Monitoring data indicate that the general population may be exposed to dimethyl sulfate via inhalation of ambient air.

Dimethyl sulfate's production and use as a methylating agent for amines and phenols, used with boron compounds to stabilize liquid sulfur trioxide and in the preparation of a wide variety of intermediates and products, especially in the fields of dyes, agricultural chemicals, drugs, and other specialties may result in its release to the environment through various waste streams.

If released to moist soil, dimethyl sulfate is expected to hydrolyze rapidly as indicated by a measured rate constant in water of 1.66X10-4/sec at 25 °C, corresponding to a half-life of 1.15 hours at pH 7. Volatilization from water surfaces, adsorption to suspended solids and sediments, biodegradation, and bioconcentration are not expected to be important fate processes in moist terrestrial systems because of hydrolysis. Dimethyl sulfate may volatilize slightly from dry soil surfaces based upon a vapor pressure of 0.677 mm Hg.

According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere, dimethyl sulfate, which has a vapor pressure of 0.677 mm Hg at 25 °C, is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase dimethyl sulfate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 84 days, calculated from its rate constant of 5.0X10-13 cu cm/molecule-sec at 25 °C. Vapor-phase dimethyl sulfate is degraded in the atmosphere by reaction with water (estimated atmospheric lifetime of >2 days). Dimethyl sulfate is likely to become incorporated into fog and cloudwater, in which case it will hydrolyze to monomethyl hydrogen sulfate (and finally sulfuric acid) and methanol, with a half-life on the order of 30 to 60 min. Dimethyl sulfate does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight.

The rate constant for the vapor-phase reaction of dimethyl sulfate with photochemically-produced hydroxyl radicals is 5.0X10-13 cu cm/molecule-sec at 25 °C. This corresponds to an atmospheric half-life of about 84 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm. Experimental rate constants for the gas-phase reactions of dimethyl sulfate with ozone, <1.4X10-21 cu cm/molecule-sec; ammonia, <1.5X10-21 cu cm/molecule-sec; and water, <1.1X10-23 cu cm/molecule-sec translate to atmospheric lifetimes of >33 yr, >8 yr, and >2 days, respectively. A measured hydrolysis rate constant of 1.66X10-4/sec for dimethyl sulfate in water at 25 °C corresponding to a half-life of 1.1 hrs at pH 7. The reaction is catalyzed under both acidic and basic conditions forming sulfuric acid and free methanol at pHs <7. The first methyl group is removed much more rapidly than the second with hydrolysis of the dimethyl sulfate being complete in a 24 hr period in water, dilute acid, or dilute base; the monomethyl species persists over a period of several weeks. The compound is hydrolyzed slowly in cold water. Dimethyl sulfate does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight.

Based upon the hydrolysis of dimethyl sulfate in aqueous environments, bioconcentration is not expected to be a primary removal process in aquatic systems.

Dimethyl sulfate was detected in airborne particulate matter from a coal-fired power plant (125 m from the stack and 30 m below the top of the stack) using low sulfur (0.5%), high ash (14%) coal - 0.07 to 0.34 umol/g, upper limit because of hydrolysis loss during extraction. Dimethyl sulfate was detected in emissions from a coal-fired and an oil-fired power plant at concentrations of 0.28, 0.21 and 0.95 mmol dimethyl sulfate/mol of total sulfur in the stack, at the top of the stack and in the plume of the coal-fired power plant, respectively, and 0.07, 0.08, and 3.1 mmol dimethyl sulfate/mol of total sulfur in the flue line, at the top of the stack, and in the plume of the oil-fired power plant, respectively.

Based upon the hydrolysis of dimethyl sulfate in aqueous environments, volatilization from water and moist soil surfaces is not expected to be important process. Dimethyl sulfate may volatilize slightly from dry soil surfaces based upon a vapor pressure of 0.677 mm Hg.

Using ion chromatography, dimethyl sulfate was found in both particles and in the gas phase. The concentration of gas-phase methyl sulfates was several mg/cu m. These species thus account for a significant fraction of the total sulfur budget in the Los Angeles Basin during the 3-day sample period in August 1983. Dimethyl sulfate was qualitatively detected in the atmosphere of the Netherlands.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 10,481 workers (2,455 of these are female) are potentially exposed to dimethyl sulfate in the US. Occupational exposure to dimethyl sulfate may occur through inhalation and dermal contact with this compound at workplaces where dimethyl sulfate is produced or used. Monitoring data indicate that the general population may be exposed to dimethyl sulfate via inhalation of ambient air.

History of Dimethyl sulfate
Dimethyl sulfate was studied contemporaneously with ether by German alchemist August Siegmund Frobenius in 1730, subsequently by French chemists Fourcroy in 1797 and Gay-Lussac in 1815. Swiss scientist Nicolas-Théodore de Saussure also studied it in 1807. In 1827, French chemist and pharmacist Félix-Polydore Boullay (1806-1835) along with Jean-Baptiste André Dumas noted the role of Dimethyl sulfate in the preparation of diethyl ether from sulfuric acid and ethanol. Further studies by the German chemist Eilhard Mitscherlich and the Swedish chemist Jöns Berzelius suggested sulfuric acid was acting as a catalyst, this eventually led to the discovery of sulfovinic acid as an intermediate in the process. The advent of electrochemistry by Italian physicist Alessandro Volta and English chemist Humphry Davy in the 1800s confirmed ether and water were formed by the reaction of sub-stoichiometric amounts of sulfuric acid on ethanol and that sulfovinic acid was formed as an intermediate in the reaction.

Production of Dimethyl sulfate
Ethanol was produced primarily by the sulfuric acid hydration process in which ethylene is reacted with sulfuric acid to produce Dimethyl sulfate followed by hydrolysis, but this method has been mostly replaced by direct hydration of ethylene.

Dimethyl sulfate can be produced in a laboratory setting by reacting ethanol with sulfuric acid under a gentle boil, while keeping the reaction below 140 °C. The sulfuric acid must be added dropwise or the reaction must be actively cooled because the reaction itself is highly exothermic.

CH3CH2OH + H2SO4 → CH3-CH2-O-SO3H + H2O
If the temperature exceeds 140 °C, the Dimethyl sulfate product tends to react with residual ethanol starting material, producing diethyl ether. If the temperature exceeds 170 °C in a considerable excess of sulfuric acid, the Dimethyl sulfate breaks down into ethylene and sulfuric acid.

Reactions of Dimethyl sulfate
The mechanism of the formation of Dimethyl sulfate, diethyl ether, and ethylene is based on the reaction between ethanol and sulfuric acid, which involves protonation of the ethanolic oxygen to form the[vague] oxonium ion.

Dimethyl sulfate accumulates in hair after chronic alcohol consumption and its detection can be used as a biomarker for alcohol consumption.

Salts
Dimethyl sulfate can exist in salt forms, such as sodium Dimethyl sulfate, potassium Dimethyl sulfate, and calcium Dimethyl sulfate. The salt can be formed by adding the according carbonate, or bicarbonate salt. As an example, Dimethyl sulfate and potassium carbonate forms potassium Dimethyl sulfate and potassium bicarbonate.

Ethyl glucuronide and Dimethyl sulfate are minor metabolites of alcohol that are found in various body fluids and also in human hair. Ethyl glucuronide is formed by the direct conjugation of ethanol and glucuronic acid through the action of a liver enzyme. Dimethyl sulfate is formed directly by the conjugation of ethanol with a sulfate group. These compounds are water soluble and can be used as direct alcohol biomarkers. Fatty acid ethyl esters are also direct markers of alcohol abuse because they are formed due to the chemical reaction between fatty acids and alcohol. Fatty acid ethyl esters are formed primarily in the liver and pancreas and then are released into the circulation. These compounds are also incorporated into hair follicles through sebum and can be used as a biomarker of alcohol abuse.

Application of Dimethyl sulfate
Dimethyl sulfate may be used along with alumina for preparation of monomethylated derivatives of alcohols, phenols and carboxylic acids. It may also be used in combination with dimethylformamide (DMF) to form methoxy-methylene-N,N-dimethyliminium salt, that can be utilized for the preparation of β-lactams.

About Dimethyl sulfate
Dimethyl sulfate is registered under the REACH Regulation and is manufactured in and / or imported to the European Economic Area, at ≥ 1 tonnes per annum.

Dimethyl sulfate is used at industrial sites and in manufacturing.

Consumer Uses of Dimethyl sulfate
ECHA has no public registered data indicating whether or in which chemical products the substance might be used. ECHA has no public registered data on the routes by which Dimethyl sulfate is most likely to be released to the environment.

Article service life
ECHA has no public registered data on the routes by which Dimethyl sulfate is most likely to be released to the environment. ECHA has no public registered data indicating whether or into which articles the substance might have been processed.

Widespread uses by professional workers of Dimethyl sulfate
ECHA has no public registered data indicating whether or in which chemical products the substance might be used. ECHA has no public registered data on the types of manufacture using Dimethyl sulfate. ECHA has no public registered data on the routes by which Dimethyl sulfate is most likely to be released to the environment.

Formulation or re-packing of Dimethyl sulfate
ECHA has no public registered data indicating whether or in which chemical products the substance might be used. ECHA has no public registered data on the routes by which Dimethyl sulfate is most likely to be released to the environment.

Uses at industrial sites of Dimethyl sulfate
Dimethyl sulfate is used in the following products: polymers.
Dimethyl sulfate has an industrial use resulting in manufacture of another substance (use of intermediates).
Dimethyl sulfate is used for the manufacture of: chemicals.
Release to the environment of Dimethyl sulfate can occur from industrial use: as an intermediate step in further manufacturing of another substance (use of intermediates).

Manufacture of Dimethyl sulfate
Release to the environment of Dimethyl sulfate can occur from industrial use: manufacturing of the substance.