EA-4056 is a deadly carbamate

nerve agent 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 ...

. It is lethal because it inhibits acetylcholinesterase. Inhibition causes an overly high accumulation of acetylcholine between the nerve and

muscle cells A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a mus ...

. This paralyzes the muscles by preventing their relaxation. The paralyzed muscles includes the muscles used for breathing. Patent assigned to

US Army The United States Army (USA) is the land service branch of the United States Armed Forces. It is one of the eight U.S. uniformed services, and is designated as the Army of the United States in the U.S. Constitution.Article II, section 2, cla ...

for EA-4056 among other similar nerve agents was filed in December 7, 1967.

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

molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...

s. Despite this, EA-4056 is claimed to be about three times more toxic than VX (another nerve agent). 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 In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', ''molar concentration'', '' number concentration'', ...

of the vapor per length of time exposed, is estimated to be 30–50 mg·min/m³. These values for EA-4056 can be estimated to be 3.3 mg and 10–16.7 mg·min/m³ by

division Division or divider may refer to: Mathematics *Division (mathematics), the inverse of multiplication *Division algorithm, a method for computing the result of mathematical division Military *Division (military), a formation typically consisting ...

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

Properties

EA-4056's CAS is 110913-96-7,

mass Mass is an intrinsic property of a body. It was traditionally believed to be related to the quantity of matter in a physical body, until the discovery of the atom and particle physics. It was found that different atoms and different eleme ...

732.6 g/mol, melting point 100–105 °C, and it is soluble in water and alcohols. It is a crystalline solid. 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 Humidity is the concentration of water vapor present in the air. Water vapor, the gaseous state of water, is generally invisible to the human eye. Humidity indicates the likelihood for precipitation, dew, or fog to be present. Humidity depe ...

) upon it are neglected. Various other

salts In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...

than just

bromine Bromine is a chemical element with the symbol Br and atomic number 35. It is the third-lightest element in group 17 of the periodic table ( halogens) and is a volatile red-brown liquid at room temperature that evaporates readily to form a simi ...

salts have been reported.

Synthesis

2-dimethylaminomethyl-3-dimethylcarbamoxypyridine precursor is prepared. It is made via

Mannich reaction In organic chemistry, the Mannich reaction is a three-component organic reaction that involves the amino alkylation of an acidic proton next to a carbonyl () functional group by formaldehyde () and a primary or secondary amine () or ammonia (). ...

by using 3-pyridol (CAS 109-00-2),

dimethylamine 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 aroun ...

and

formaldehyde Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...

. Resulting 2-((Dimethylamino)methyl)pyridin-3-ol (CAS 2168-13-0) is then carbamoylated with

dimethylcarbamoyl chloride Dimethylcarbamoyl chloride (DMCC) is a reagent for transferring a dimethylcarbamoyl group to alcoholic or phenolic hydroxyl groups forming dimethyl carbamates, usually having pharmacological or pesticidal activities. Because of its high toxicity ...

. For a different product other secondary

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen Hydrogen is the chemical element wi ...

s than dimethylamine can be used; such as those containing methyl, ethyl,

propyl In organic chemistry, propyl is a three-carbon alkyl substituent with chemical formula for the linear form. This substituent form is obtained by removing one hydrogen atom attached to the terminal carbon of propane. A propyl substituent is often ...

isopropyl In organic chemistry, propyl is a three-carbon alkyl substituent with chemical formula for the linear form. This substituent form is obtained by removing one hydrogen atom attached to the terminal carbon of propane. A propyl substituent is often ...

butyl In organic chemistry, butyl is a four- carbon alkyl radical or substituent group with general chemical formula , derived from either of the two isomers (''n''-butane and isobutane) of butane. The isomer ''n''-butane can connect in two ways, gi ...

and

benzyl In organic chemistry, benzyl is the substituent or molecular fragment possessing the structure . Benzyl features a benzene ring () attached to a methylene group () group. Nomenclature In IUPAC nomenclature, the prefix benzyl refers to a substi ...

groups. 2

moles Moles can refer to: * Moles de Xert, a mountain range in the Baix Maestrat comarca, Valencian Community, Spain * The Moles (Australian band) *The Moles, alter ego of Scottish band Simon Dupree and the Big Sound People *Abraham Moles, French engin ...

of 2-dimethylaminomethyl-3-dimethylcarbamoxypyridine and app. 1 mol α,ω-dihalo alkane (e.g. 1,9-dibromononane in this case) in acetonitrile is heated on a

steam bath A steam bath is a steam-filled room for the purpose of relaxation and cleansing. It has a long history, going back to Greek and Roman times. History The origins of the steam bath come from the Roman bath, which began during the height of the R ...

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 Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...

. If no solid separates,

ethyl acetate Ethyl acetate ( systematically ethyl ethanoate, commonly abbreviated EtOAc, ETAC or EA) is the organic compound with the formula , simplified to . This colorless liquid has a characteristic sweet smell (similar to pear drops) and is used in glues ...

is added to

precipitate In an aqueous solution, precipitation is the process of transforming a dissolved substance into an insoluble solid from a super-saturated solution. The solid formed is called the precipitate. In case of an inorganic chemical reaction leading ...

the crude product. The product is then dissolved in hot

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...

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%. Other stable salts of EA-4056 than

bromide A bromide ion is the negatively charged form (Br−) of the element bromine, a member of the halogens group on the periodic table. Most bromides are colorless. Bromides have many practical roles, being found in anticonvulsants, flame-retardant ...

can be made such as

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

, nitrate,

hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic ...

oxalate Oxalate (IUPAC: ethanedioate) is an anion with the formula C2O42−. This dianion is colorless. It occurs naturally, including in some foods. It forms a variety of salts, for example sodium oxalate (Na2C2O4), and several esters such as dimethyl ...

and

perchlorate A perchlorate is a chemical compound containing the perchlorate ion, . The majority of perchlorates are commercially produced salts. They are mainly used as oxidizers for pyrotechnic devices and to control static electricity in food packaging. Per ...

. Other α,ω-dihaloalkanes can be used to obtain similar molecules with different carbon chain lengths.

References

{{Neurotoxins Carbamate nerve agents Pyridines Quaternary ammonium compounds Bromides Acetylcholinesterase inhibitors Biscarbamates Bisquaternary anticholinesterases Aromatic carbamates

Lethality

Properties

Synthesis

See also

References