Methyl fluoroacetate
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Preferred IUPAC name
Methyl fluoroacetate | |
Other names
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Identifiers | |
3D model (
JSmol ) |
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ChemSpider | |
ECHA InfoCard
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100.006.563 |
EC Number |
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PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
FCH2CO2CH3 | |
Molar mass | 92.069 g·mol−1 |
Appearance | Colorless liquid |
Odor | Odorless or faint fruity |
Melting point | −40 °C (−40 °F; 233 K) |
Boiling point | 104 °C (219 °F; 377 K) |
117 g/L at 25 °C | |
Hazards | |
Occupational safety and health (OHS/OSH): | |
Main hazards
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Extremely toxic |
GHS labelling: | |
Danger | |
H226, H300, H315, H319, H335, H400 | |
P210, P233, P240, P241, P242, P243, P261, P264, P270, P271, P273, P280, P301+P310, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P370+P378, P391, P403+P233, P403+P235, P405, P501 | |
Flash point | −32 °C (−26 °F; 241 K) |
Lethal dose or concentration (LD, LC): | |
LD50 (median dose)
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6 mg/kg (mice) |
Related compounds | |
Related compounds
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Methyl fluoroacetate (MFA) is an
The general population is not likely to be exposed to methyl fluoroacetate. People who use MFA for work, however, can breathe in or have direct skin contact with the substance.[2]
History
MFA was first synthesized in 1896 by the Belgian chemist Frédéric Swarts by reacting methyl iodoacetate with silver fluoride. It can also be synthesized by reacting methyl chloroacetate with potassium fluoride[1]
Because of its toxicity, MFA was studied for potential use as a chemical weapon during World War II. It was considered a good water poison since it is colorless and odorless and therefore it can toxify the water supply and kill a big part of the population. By the end of the war, several countries began to make methyl fluoroacetate to debilitate or kill the enemy.[2]
Synthesis
The synthesis of methyl fluoroacetate consists of a two-step process:[3]
- catalyst are added into the solvent within the reactor; this is then stirred and heated up. The catalyst mentioned in this step is a phase-transfer catalyst and can be the chemicals dodecyl(trimethyl)ammonium chloride [(CH3(CH2)11)(CH3)3N]+Cl−, tetrabutylammonium chloride [(CH3(CH2)3)4N]+Cl−, tetrabutylammonium bromide [(CH3(CH2)3)4N]+Br−, or tetramethylammonium chloride [(CH3)4N]+Cl−. The mass ratio of the potassium fluoride and the catalyst in this step is 0.5~1 : 0.02~0.03. With the solvent mentioned in this step being a mixture of dimethylformamide (HCON(CH3)2) and acetamide(CH3CONH2) with a mass ratio of 1.4~1.6: 1. The mass ratio of the solvent and potassium fluoride is 1.1~2.0 : 0.5~1.
- When the reaction temperature of 100~160 °C is reached, methyl chloroacetate ClCH2CO2CH3 is continuously added in the reactor at a speed of 5~10 kg/min with the mass ratio of methyl chloroacetate and potassium fluoride being 1:0.5~1. The reaction between these chemicals produces a gas mixture, with the gases within this mixture then being split between two condensers according to their condensation temperature. Methyl chloroacetate is condensed within the condenser set at 100~105 °C, it is then returned to the reactor to continue participating in the chemical reaction. Methyl fluoroacetate in the other condenser then enters a two-stage nitration condensation at a temperature of 20~25 °C which then ensures that the methyl fluoroacetate is condensed into a liquid with it being the product of this reaction.[3]
Structure and reactivity
Methyl fluoroacetate is a methyl ester of fluoroacetic acid.
MFA is a liquid, which is odorless or can have a faint, fruity smell. The boiling point of MFA is 104.5 °C and the melting point is −35.0 °C. It is soluble in water (117 g/L at 25 °C) and slightly soluble in petroleum ether.[2]
MFA is resistant to the displacement of
Mechanism of action and metabolism
Generally, fluoroacetates are toxic because they are converted to
The elimination
Toxicity
MFA is a convulsant poison. It causes severe convulsions in poisoned victims.[7] Death results from respiratory failure.[6]
For a variety of animals, the toxicity of methyl fluoroacetate has been determined orally and through subcutaneous injection. The dosage ranges from 0.1 mg/kg in dogs to 10–12 mg/kg in monkeys indicating considerable variation. An order of decreasing susceptibility has been determined within these animals which is: dog, guinea-pig, cat, rabbit, goat, and then likely horse, rat, mouse, and monkey. For the rat and mouse, the toxicity by inhalation has been investigated more fully than for other animals. The
Environmental exposure
Methyl fluoroacetate is produced and used as a chemical reagent and it can be released to the environment through several waste streams. When it was used as a rodenticide, it was released directly to the environment where it would be broken down in the air. If released to air, an estimated vapor pressure of 31
MFA does not contain
Effects on animals
The effects on animals occur very rapidly and strongly, all resulting in death. Exposure to a high concentration of MFA vapor does not show any symptoms in animals until 30–60 minutes.[6] Then violent reactions and death took place in a few hours, according to studies. From intravenous injection mice, rats, and guinea pigs show symptoms after 15 min to 2 hours. The animals become quiet and limp. Rabbits show a similar latent time period and muscle weakness.[6] Dogs show symptoms of hyperactivity. They are more sensitive because of higher rates of metabolism and, eventually, they also fail to respirate. Fish are more resistant because of slow metabolism[4] and therefore it is not expected that the substance will build up in fish. Also, Australian herbivores (e.g. possum and seed-eating birds) that live in a habitat consisting of plants with traces of fluoroacetate, have some tolerance. This can happen by detoxifying fluoroacetate or more resistivity of aconitase to fluorocitrate in the presence of GSH. Some insects can store the toxin in vacuoles and use it later.[4] The highly hazardous MFA cannot be used for poisoning animals without risking human life.
Antidotal therapy
There is no known antidote against MFA, but there are some suggestions regarding the treatment of MFA poisoning. Advised is to use an intravenous injection of fast-acting anesthetics directly after poisoning. The anesthetic should be pentothal sodium or evipan sodium followed by an intramuscular injection of long-acting cortical depressants like sodium phenobarbitone or rectal avertin. Afterward, careful supervision of oxygen supply is necessary together with a BLB mask[clarification needed] and the use of artificial respiration. Possibly, the use of hypertonic glucose intravenously is required as in status epilepticus. At last, careful use of tubocurarine chloride should be applied to control any convulsions.[6] If any vomiting occurs, lean the patient forward to maintain an open airway.
Alternatively, there is a therapy aimed at the prevention of fluorocitrate synthesis, the blocking of aconitase within the mitochondria, and to provide a citrate outflow from the mitochondria to keep the TCA cycle going. For now, ethanol has proven to be the most effective against FC formation. When ethanol is oxidized, it increases blood acetate levels which inhibits FC production. In humans, an oral dose of 40-60 mL 96% ethanol is advised followed by 1.0-1.5 g/kg of 5-10% ethanol intravenously during the first hour and 0.1 g/kg during the following 6–8 hours. This therapy is meant for fluoroacetate (FA) poisoning which is highly related MFA, so this therapy aimed at MFA may result in other outcomes.[8]
Treatment with
There is up until now, no proven treatment against MFA. However, the beforementioned treatments can provide starting points for therapy aimed at MFA since FA and MFA are closely related compounds.[8]
See also
References
- ^ PMID 4711243.
- ^ a b c d e f National Center for Biotechnology Information. PubChem Database. Methyl fluoroacetate, CID=9959, https://pubchem.ncbi.nlm.nih.gov/compound/Methyl-fluoroacetate (accessed on Mar. 20, 2020)
- ^ a b 侯红军杨华春司腾飞薛旭金杨明霞师玉萍邹英武贺志荣姚超 (2015). Patent identifier No. CN104292104B. Location: Google patents
- ^ a b c Leong, L., Khan, S., Davis, C. K., Denman, S. E., & McSweeney, C. S. (2017). Fluoroacetate in plants - a review of its distribution, toxicity to livestock and microbial detoxification. Journal of animal science and biotechnology, 8, 55.
- ^ a b Mead, R. J., Oliver, A. J., & King, D. R. (1979). Metabolism and defluorination of fluoroacetate in the brush-tailed possum (Trichosurus vulpecula). Australian journal of biological sciences, 32(1), 15-26.
- ^ PMID 18866990.
- PMID 18106001.
- ^ a b c Goncharov, N. V., Jenkins, R. O., & Radilov, A. S. (2006). Toxicology of fluoroacetate: a review, with possible directions for therapy research. Journal of Applied Toxicology: An International Journal, 26(2), 148-161.