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| Names | |
|---|---|
| Preferred IUPAC name Dimethyl sulfate | |
| Other names Dimethyl sulphate; Sulfuric acid dimethyl ester; Me2SO4; DMSO4; Dimethyl ester of sulfuric acid; Methyl sulfate, di- | |
| Identifiers | |
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3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| ECHA InfoCard | 100.000.963 |
| KEGG |
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| UNII | |
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| Properties | |
| C2H6O4S | |
| Molar mass | 126.13 g/mol |
| Appearance | Colorless, oily liquid |
| Odor | faint, onion-like[1] |
| Density | 1.33 g/ml, liquid |
| Melting point | −32 °C (−26 °F; 241 K) |
| Boiling point | 188 °C (370 °F; 461 K) (decomposes) |
| Reacts | |
| Solubility | Methanol,dichloromethane,acetone |
| Vapor pressure | 0.1 mmHg (20 °C)[1] |
| −62.2×10−6 cm3/mol | |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards | Extremely toxic, contact hazard, inhalation hazard, corrosive, environmental hazard, carcinogenic, mutagenic |
| GHS labelling: | |
   | |
| Danger | |
| H301,H314,H317,H330,H335,H341,H350 | |
| NFPA 704 (fire diamond) | |
| Flash point | 83 °C; 182 °F; 356 K[1] |
| Lethal dose or concentration (LD, LC): | |
LC50 (median concentration) | 8.6 ppm (rat, 4 hr) 75 ppm (guinea pig, 20 min) 53 ppm (mouse) 32 ppm (guinea pig, 1 hr)[2] |
LCLo (lowest published) | 97 ppm (human, 10 min)[2] |
| NIOSH (US health exposure limits): | |
PEL (Permissible) | TWA 1 ppm (5 mg/m3) [skin][1] |
REL (Recommended) | Ca TWA 0.1 ppm (0.5 mg/m3) [skin][1] |
IDLH (Immediate danger) | Ca [7 ppm][1] |
| Related compounds | |
Related compounds | Diethyl sulfate,methyl triflate,dimethyl carbonate |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Dimethyl sulfate (DMS) is achemical compound withformula (CH3O)2SO2. As thediester ofmethanol andsulfuric acid, its formula is often written as (CH3)2SO4 or Me2SO4, where CH3 or Me ismethyl. Me2SO4 is mainly used as a methylating agent inorganic synthesis. Me2SO4 is a colourless oilyliquid with a slight onion-like odour. Like all strongalkylating agents, Me2SO4 istoxic.[3] Its use as a laboratory reagent has been superseded to some extent bymethyl triflate, CF3SO3CH3, the methyl ester oftrifluoromethanesulfonic acid.
Impure dimethyl sulfate was prepared in the early 19th century.[4]J. P. Claesson later extensively studied its preparation.[5][6]
It was investigated for possible use in chemical warfare inWorld War I[7][8] in 75% to 25% mixture with methyl chlorosulfonate (CH3ClO3S) called "C-stoff" in Germany, or withchlorosulfonic acid called "Rationite" in France.[9]
The esterification ofsulfuric acid withmethanol was described in 1835:[10]
Dimethyl sulfate is produced commercially by the continuous reaction ofdimethyl ether withsulfur trioxide:[3]
Dimethyl sulfate can be synthesized in the laboratory by several methods.[11] The reaction ofmethyl nitrite andmethyl chlorosulfonate also results in dimethyl sulfate:[6]
Dimethyl sulfate is a reagent for themethylation ofphenols,amines, andthiols. One methyl group is transferred more quickly than the second. Methyl transfer is assumed to occur via anSN2 reaction. Compared to other methylating agents, dimethyl sulfate is preferred by the industry because of its low cost and high reactivity.
Commonly dimethyl sulfate is employed to methylatephenols.[12][13]
In some cases, simplealcohols are also methylated, as illustrated by the conversion oftert-butanol tot-butyl methyl ether:
The methylation ofsugars is calledHaworth methylation.[14] The methylation of ketones is called the Lavergne reaction.
Me2SO4 is used to prepare bothquaternary ammonium salts ortertiary amines:
Quaternized fatty ammonium compounds are used as a surfactant or fabric softener. Methylation to create a tertiary amine is illustrated as:[13]
Thiolate salts are easily methylated by Me2SO4 to give methylthioethers:[13]
In a related example:[15]
This method has been used to preparethioesters fromthiocarboxylic acids:
Dimethyl sulfate (DMS) is used to determine thesecondary structure ofRNA. 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 asDMS-MaPseq,[16] RNA is incubated with DMS to methylate unpaired bases. Then the RNA is reverse-transcribed; thereverse transcriptase frequently adds an incorrect DNA base when it encounters a methylated RNA base. These mutations can be detected viasequencing, and the RNA is inferred to be single-stranded at bases with above-background mutation rates.
Dimethyl sulfate can affect the base-specific cleavage of DNA by attacking theimidazole rings present in guanine.[17] Dimethyl sulfate also methylatesadenine in single-stranded portions of DNA (for example, those withproteins likeRNA 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 it is less hazardous and more expensive.[15]Dimethyl carbonate, which is far less reactive, has far lower toxicity compared to both dimethyl sulfate and methyl iodide.[18] 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.
Dimethyl sulfate iscarcinogenic[19] andmutagenic, highlypoisonous,corrosive, andenvironmentally hazardous.[20] It 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. TheLD50 (acute, oral) is 205 mg/kg (rat) and 140 mg/kg (mouse), and LC50 (acute) is 45 ppm per 4 hours (rat).[21] The vapor pressure of 65 Pa[22] 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.[20] Symptoms may be delayed 6–24 h. 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 it.
One hypothesis regarding the apparently mysterious 1994"toxic lady" incident is that the person at the centre of the incident had built updimethyl sulfone crystals in her blood, which were converted by an unknown mechanism to dimethyl sulfate vapour that poisoned attending medical staff.[23][24]
