EA-3990

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Contents

EA-3990
EA 3990.png
EA-3990 3D structure.png
Names
Preferred IUPAC name
N1,N8-Bis({3-[(dimethylcarbamoyl)oxy]pyridin-2-yl}methyl)-N1,N1,N8,N8-tetramethyloctane-1,8-bis(aminium) dibromide
Identifiers
3D model (JSmol)
  • InChI=1S/C30H50N6O4.2BrH/c1-33(2)29(37)39-27-17-15-19-31-25(27)23-35(5,6)21-13-11-9-10-12-14-22-36(7,8)24-26-28(18-16-20-32-26)40-30(38)34(3)4;;/h15-20H,9-14,21-24H2,1-8H3;2*1H/q+2;;/p-2
    Key: ABTAGUMOWVVEGK-UHFFFAOYSA-L
  • [Br-].[Br-].CN(C)C(=O)Oc1cccnc1C[N+](C)(C)CCCCCCCC[N+](C)(C)Cc2ncccc2OC(=O)N(C)C
Properties
C30H50N6O4 · Br2
Molar mass 718.7 g/mol
Appearancewhite, odorless crystalline solid.
Density 1.33 g/cm3
Melting point 190–191 °C
Solubility soluble in alcohols, acetic acid and chloroform
Vapor pressure negligible
Hazards
Lethal dose or concentration (LD, LC):
6.3 µg/kg for mice and 2.6 µg/kg for rabbits via IV
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

EA-3990 is a deadly carbamate nerve agent. It is lethal because it inhibits acetylcholinesterase. [1] Inhibition causes an overly high accumulation of acetylcholine between the nerve and muscle cells. This paralyzes the muscles by preventing their relaxation. The paralyzed muscles include the muscles used for breathing. [2]

Patent assigned to US army for EA-3990 among other similar nerve agents was filed in December 7, 1967. [3]

Lethality

EA-3990 lethality in humans is unknown but estimates have been made.

Carbamates like EA-3990 are well absorbed by the lungs, gastrointestinal tracts, and the skin. Signs and symptoms from exposure to such carbamates are similar to other nerve agents. In general their penetration through the blood-brain barrier is difficult due to quaternary nitrogens in these molecules. [4] Despite this, EA-3990 is claimed to be about three times more toxic than VX (another nerve agent). [1] For VX, the median lethal dose (LD50) for 70 kg men via exposure to the skin is estimated to be 10 mg, and the lethal concentration time (LCt50), measuring the concentration of the vapor per length of time exposed, is estimated to be 30–50 mg·min/m3. [5] These values for EA-3990 can be estimated to be 3.3 mg and 10–16.7 mg·min/m3 by division.

Intravenous LD50 for EA-3990 is 0.0063 mg/kg for mice and 0.0026 mg/kg for rabbits. [3]

Properties

EA-3990's CAS is 110913-95-6, mass 718.7 g/mol, [1] melting point 190–191 °C, [3] density 1.33 g/cm3, vapor pressure is negligible, and it is soluble in alcohols, acetic acid and chloroform. It is a white, odorless crystalline solid. EA-3990 evaporates slowly in to the air; thus it can be classified as being extremely persistent in the environment if any possible effects of external factors like sun light and water (air humidity) upon it are neglected. Various salts other than bromide have been reported. [1]

Synthesis

Two methods have been described for synthesizing EA-3990 along with similar nerve agents.

The 2-dimethylaminomethyl-3-dimethylcarbamoxypyridine precursor is prepared via a Mannich reaction using 3-pyridol (CAS 109-00-2), dimethylamine and formaldehyde. The resulting 2-((Dimethylamino)methyl)pyridin-3-ol (CAS 2168-13-0) is then carbamoylated with dimethylcarbamoyl chloride. Other secondary amines can be used, such as those containing methyl, ethyl, propyl, isopropyl, butyl and benzyl groups. [6]

In the first method 2 moles of 2-dimethylaminomethyl-3-dimethylcarbamoxypyridine and app. 1 mol α,ω-dihaloalkane (e.g. 1,8-dibromooctane in this case) in acetonitrile is heated on a steam bath for 6 hours. It is then allowed to stand overnight at room temperature. The crystalline product is collected by filtration. [3] [6]

In the second method 2 mol and 1 mol of the previous reagents used in the first method are added together, but also a catalytic amount of sodium iodide in acetonitrile is added to the solution, which is then allowed to stand for 6 days. Crystalline material is usually formed during this period and it is then collected by filtration. [3]

In both methods, after filtration, the crystalline product is triturated with acetone. If no solid separates, ethyl acetate is added to precipitate the crude product. The product is then dissolved in hot ethanol and treated with decolorizing charcoal. Ethyl acetate is added to the filtered solution to precipitate the crystalline product. E-3990 is then collected and dried. Yield is 63%. [3] [6]

See also

Related Research Articles

Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (AChE), an enzyme that catalyzes the breakdown of acetylcholine, a neurotransmitter. Nerve agents are acetylcholinesterase inhibitors used as poison.

<span class="mw-page-title-main">Sarin</span> Chemical compound and chemical warfare nerve agent

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<span class="mw-page-title-main">VX (nerve agent)</span> Chemical compound and chemical warfare nerve agent

VX is an extremely toxic synthetic chemical compound in the organophosphorus class, specifically, a thiophosphonate. In the class of nerve agents, it was developed for military use in chemical warfare after translation of earlier discoveries of organophosphate toxicity in pesticide research. In recent years, VX was found to be the agent used in the assassination of Kim Jong-nam. In its pure form, VX is an oily, relatively non-volatile liquid that is amber-like in colour. Because of its low volatility, VX persists in environments where it is dispersed.

<span class="mw-page-title-main">Carbamate</span> Chemical group (>N–C(=O)–O–)

In organic chemistry, a carbamate is a category of organic compounds with the general formula R2NC(O)OR and structure >N−C(=O)−O−, which are formally derived from carbamic acid. The term includes organic compounds, formally obtained by replacing one or more of the hydrogen atoms by other organic functional groups; as well as salts with the carbamate anion H2NCOO−.

<span class="mw-page-title-main">VE (nerve agent)</span> Chemical compound

VE is a "V-series" nerve agent closely related to the better-known VX nerve agent.

<span class="mw-page-title-main">Ethyl acetate</span> Chemical compound

Ethyl acetate is the organic compound with the formula CH3CO2CH2CH3, simplified to C4H8O2. This colorless liquid has a characteristic sweet smell and is used in glues, nail polish removers, and in the decaffeination process of tea and coffee. Ethyl acetate is the ester of ethanol and acetic acid; it is manufactured on a large scale for use as a solvent.

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<span class="mw-page-title-main">Diisopropyl fluorophosphate</span> Chemical compound

Diisopropyl fluorophosphate (DFP) or Isoflurophate is an oily, colorless liquid with the chemical formula C6H14FO3P. It is used in medicine and as an organophosphorus insecticide. It is stable, but undergoes hydrolysis when subjected to moisture.

<span class="mw-page-title-main">VR (nerve agent)</span> Chemical compound

VR is a "V-series" unitary nerve agent closely related to the better-known VX nerve agent. It became a prototype for the series of Novichok agents. According to chemical weapons expert Jonathan Tucker, the first binary formulation developed under the Soviet Foliant program was used to make Substance 33, differing from VX only in the alkyl substituents on its nitrogen and oxygen atoms. "This weapon was given the code name Novichok."

<span class="mw-page-title-main">A-234 (nerve agent)</span> Chemical compound

A-234 is an organophosphate nerve agent. It was developed in the Soviet Union under the FOLIANT program and is one of the group of compounds referred to as Novichok agents that were revealed by Vil Mirzayanov. In March 2018 the Russian ambassador to the UK, Alexander Yakovenko, claimed to have been informed by British authorities that A-234 had been identified as the agent used in the poisoning of Sergei and Yulia Skripal. Vladimir Uglev, one of the inventors of the Novichok series of compounds, said he was "99 percent sure that it was A-234" in relation to the 2018 Amesbury poisonings, noting its unusually high persistence in the environment.

<span class="mw-page-title-main">EA-4056</span> Chemical compound

EA-4056 is a deadly carbamate nerve agent. It is lethal because it inhibits acetylcholinesterase. Inhibition causes an overly high accumulation of acetylcholine between the nerve and muscle cells. This paralyzes the muscles by preventing their relaxation. The paralyzed muscles includes the muscles used for breathing.

<span class="mw-page-title-main">Octamethylene-bis(5-dimethylcarbamoxyisoquinolinium bromide)</span> Chemical compound

Octamethylene-bis(5-dimethylcarbamoxyisoquinolinium bromide) is an extremely potent carbamate nerve agent. It works by inhibiting the acetylcholinesterase, causing acetylcholine to accumulate. Since the agent molecule is positively charged, it does not cross the blood brain barrier very well.

1,8-Dibromooctane is a chemical compound used in the synthesis of the carbamate nerve agents EA-3990 and octamethylene-bis(5-dimethylcarbamoxyisoquinolinium bromide).

<span class="mw-page-title-main">EA-2192</span> Chemical compound

EA-2192 is an extremely toxic degradation product of the VX nerve agent. It is a white solid that is very soluble and stable in water.

<span class="mw-page-title-main">EA-3966</span> Chemical compound

EA-3966 is a carbamate nerve agent. It is synthesized by reacting 2-dimethylaminomethyl-3-dimethylcarbamoxypyridine with 10-bromodecyltrimethylammonium bromide.

<span class="mw-page-title-main">A-230</span> Chemical compound

A-230 is an organophosphate nerve agent. It was developed in the Soviet Union under the FOLIANT program and is one of the group of compounds referred to as Novichok agents that were revealed by Vil Mirzayanov. A-230 is possibly the most potent nerve agent for which specific toxicity figures have been published, with a human lethal dose estimated to be less than 0.1 mg. However it was felt to be less suitable for weaponisation than other agents such as A-232 and A-234, due to issues with the liquid agent exhibiting low volatility and solidifying at low temperatures, as well as poor stability in the presence of water.

<span class="mw-page-title-main">EA-1763</span> Chemical compound

EA-1763, O-PPVX, V1 or propyl S-2-diisopropylaminoethylmethylphosphonothiolate, is a military-grade neurotoxic organophosphonate nerve agent related to VX. It is part of the V-series. The substitution of a proton for methyl makes its properties more similar to those of VX.

<span class="mw-page-title-main">4-686-293-01</span> Chemical compound

4-686-293-01, also known as Agent 1-10, is a highly potent experimental carbamate nerve agent, patented in May 1967. Due to its high molecular weight and thermal stability, it can remain embedded within various surfaces and clothes for prolonged periods of time. The agent can be decontaminated using bleach or hot caustic soda. The main effector pathway is through the inhibition and antagonization of acetylcholinesterase, achieved by the presence of quaternary ammonium groups in the structure. Perceived as one of the most potent agents in chemical warfare - it can be disseminated through aerosols, explosives or smoke generating munitions.

References

  1. 1 2 3 4 Hank ED (2008). Handbook of chemical and biological warfare agents (2nd ed.). Boca Raton: CRC Press. p. 113. ISBN   9780849314346. OCLC   82473582.
  2. ↑ Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM (May 2013). "Acetylcholinesterase inhibitors: pharmacology and toxicology". Current Neuropharmacology. 11 (3): 315–35. doi:10.2174/1570159X11311030006. PMC   3648782 . PMID   24179466.
  3. 1 2 3 4 5 6 USpatent 04512246,Harold Z. Sommer, Havre De Grace, John Krenzer, Oak Park, Omer O. Owens, Jacob I. Miller,"Chemical agents",issued 1987-06-30, assigned to US Secretary of Army
  4. ↑ Gupta RC (2015). "Carbamates". Handbook of toxicology of chemical warfare agents (2nd ed.). Amsterdam: Elsevier/Academic Press. pp. 338–339. ISBN   9780128004944. OCLC   433545336.
  5. ↑ FAS Staff (2013). "Types of Chemical Weapons: Nerve Agents [Table. Toxicological Data]". Washington, DC: Federation of American Scientists [FAS]. Archived from the original on November 26, 2016. Retrieved March 20, 2018.
  6. 1 2 3 USpatent 4677204A,Harold Z. Sommer, Havre de Grace, Omer O. Owens,"Chemical agents",issued 1987-06-30, assigned to US Secretary of Army
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