EA-4056

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Contents

EA-4056
EA 4056.png
EA-4056 3D structure.png
Names
IUPAC name
1,9-Bis[methyl-2(3-dimethylcarbamoxypyridyl)methylamino]nonane dimethobromide
Preferred IUPAC name
N1,N9-Bis({3-[(dimethylcarbamoyl)oxy]pyridin-2-yl}methyl)-N1,N1,N9,N9-tetramethylnonane-1,9-bis(aminium) dibromide
Identifiers
3D model (JSmol)
  • InChI=1S/C31H52N6O4.2BrH/c1-34(2)30(38)40-28-18-16-20-32-26(28)24-36(5,6)22-14-12-10-9-11-13-15-23-37(7,8)25-27-29(19-17-21-33-27)41-31(39)35(3)4;;/h16-21H,9-15,22-25H2,1-8H3;2*1H/q+2;;/p-2
    Key: AQIHLGWYYFRMKZ-UHFFFAOYSA-L
  • [Br-].[Br-].CN(C)C(=O)Oc1cccnc1C[N+](C)(C)CCCCCCCCC[N+](C)(C)Cc2ncccc2OC(=O)N(C)C
Properties
C31H52N6O4 · Br2
Molar mass 732.6 g/mol
Appearancecrystalline solid
Melting point 100–105 °C
Solubility soluble in water and alcohols
Hazards
Lethal dose or concentration (LD, LC):
11 µg/kg for mice and 2.7 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-4056 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 includes the muscles used for breathing. [2]

Patent assigned to US Army for EA-4056 among other similar nerve agents was filed in December 7, 1967. [3] It patents derivatives with 3 to 11 carbons in the connecting alkane chain.

Lethality

Carbamates like EA-4056 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-4056 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-4056 can be estimated to be 3.3 mg and 10–16.7 mg·min/m3 by division.

Intravenous LD50 for EA-4056 is 0.0011 mg/kg for mice and 0.0027 mg/kg for rabbits. [3]

Properties

EA-4056's CAS is 110913-96-7, mass 732.6 g/mol, melting point 100–105 °C, and it is soluble in water and alcohols. It is a crystalline solid. [1] EA-4056 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 other salts than just bromine salts have been reported. [1]

Synthesis

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

2 moles of 2-dimethylaminomethyl-3-dimethylcarbamoxypyridine and app. 1 mol α,ω-dihaloalkane (e.g. 1,9-dibromononane 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 and then 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-4056 product is then collected and dried. Yield is 95%. [3] [6]

Other stable salts of EA-4056 than bromide can be made such as sulfate, nitrate, hydrogen, oxalate and perchlorate. Other α,ω-dihaloalkanes can be used to obtain similar molecules with different carbon chain lengths. [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 irreversible acetylcholinesterase inhibitors used as poison.

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

Sarin is an extremely toxic organophosphorus compound. A colourless, odourless liquid, it is used as a chemical weapon due to its extreme potency as a nerve agent. Exposure can be lethal even at very low concentrations, where death can occur within one to ten minutes after direct inhalation of a lethal dose, due to suffocation from respiratory paralysis, unless antidotes are quickly administered. People who absorb a non-lethal dose and do not receive immediate medical treatment may suffer permanent neurological damage.

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

Tabun is an extremely toxic compound of the organophosphate family. It is not present in nature. At room temperature, the pure compound presents itself as a clear and viscous liquid. However, impurities imparted during its manufacture are almost always present in some amount, turning it into a yellow or brown liquid. Exposed to environs, it slowly volatizes into the atmosphere, with the vapor having a slight fruity or almond-like odor. As the compound has a much higher molecular mass compared to air, Tabun gas tends to accumulate in low-lying areas.

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

Soman is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiting the enzyme cholinesterase. It is an inhibitor of both acetylcholinesterase and butyrylcholinesterase. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations according to UN Resolution 687. Its production is strictly controlled, and stockpiling is outlawed by the Chemical Weapons Convention of 1993 where it is classified as a Schedule 1 substance. Soman was the third of the so-called G-series nerve agents to be discovered along with GA (tabun), GB (sarin), and GF (cyclosarin).

<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 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">Carbaryl</span> Chemical compound

Carbaryl is a chemical in the carbamate family used chiefly as an insecticide. It is a white crystalline solid previously sold under the brand name Sevin, which was a trademark of the Bayer Company. The Sevin trademark has since been acquired by GardenTech, which has eliminated carbaryl from most Sevin formulations. Union Carbide discovered carbaryl and introduced it commercially in 1958. Bayer purchased Aventis CropScience in 2002, a company that included Union Carbide pesticide operations. Carbaryl was the third-most-used insecticide in the United States for home gardens, commercial agriculture, and forestry and rangeland protection. As a veterinary drug, it is known as carbaril (INN).

<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">Tetraethylammonium</span> Polyatomic ion (N(C₂H₅)₄, charge +1)

Tetraethylammonium (TEA) is a quaternary ammonium cation with the chemical formula [Et4N]+, consisting of four ethyl groups attached to a central nitrogen atom. It is a counterion used in the research laboratory to prepare lipophilic salts of inorganic anions. It is used similarly to tetrabutylammonium, the difference being that its salts are less lipophilic, more easily crystallized and more toxic.

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

Ethion (C9H22O4P2S4) is an organophosphate insecticide. It is known to affect the neural enzyme acetylcholinesterase and disrupt its function.

<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. It was first reported in 1958 as a pesticide.

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

Dimethylamine is an organic compound with the formula (CH3)2NH. This secondary amine is a colorless, flammable gas with an ammonia-like odor. Dimethylamine is commonly encountered commercially as a solution in water at concentrations up to around 40%. An estimated 270,000 tons were produced in 2005.

<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">Edgewood Arsenal human experiments</span> US military chemical warfare research

From 1948 to 1975, the U.S. Army Chemical Corps conducted classified human subject research at the Edgewood Arsenal facility in Maryland. These experiments began after the conclusion of World War II, and continued until the public became aware of the experiments, resulting in significant outcry. The purpose was to evaluate the impact of low-dose chemical warfare agents on military personnel and to test protective clothing, pharmaceuticals, and vaccines. A small portion of these studies were directed at psychochemical warfare; grouped under the title "Medical Research Volunteer Program" (1956–1975), driven by intelligence requirements and the need for new and more effective interrogation techniques.

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

Methiocarb is a carbamate pesticide which is used as an insecticide, bird repellent, acaricide and molluscicide since the 1960s. Methiocarb has contact and stomach action on mites and neurotoxic effects on molluscs. Seeds treated with methiocarb also affect birds. Other names for methiocarb are mesurol and mercaptodimethur.

<span class="mw-page-title-main">EPN (insecticide)</span> Chemical compound

EPN is an insecticide of the phosphonothioate class. It is used against pests such as European corn borer, rice stem borer, bollworm, tobacco budworm, and boll weevil.

<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-3990</span> Chemical compound

EA-3990 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 include the muscles used for breathing.

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

Octamethylene-bis(5-dimethylcarbamoxyisoquinolinium bromide) (4-673-745-01) is an extremely potent carbamate nerve agent. It works by inhibiting acetylcholinesterase, causing acetylcholine to accumulate. Since the agent molecule is positively charged, it does not cross the blood brain barrier very well.

<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">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. pp. 116–117. 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 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