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.
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]
^ abcdHank ED (2008). Handbook of chemical and biological warfare agents (2nd ed.). Boca Raton: CRC Press. p. 113. ISBN9780849314346. OCLC 82473582.
^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. PMC3648782. PMID 24179466.
^ abcdefUS patent 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
^Gupta RC (2015). "Carbamates". Handbook of toxicology of chemical warfare agents (2nd ed.). Amsterdam: Elsevier/Academic Press. pp. 338–339. ISBN9780128004944. OCLC 433545336.
^FAS Staff (2013). "Types of Chemical Weapons: Nerve Agents [Table. Toxicological Data]". Washington, DC: Federation of American Scientists [FAS]. from the original on November 26, 2016. Retrieved March 20, 2018.
^ abcUS patent 4677204A, Harold Z. Sommer, Havre de Grace, Omer O. Owens, "Chemical agents", issued 1987-06-30, assigned to US Secretary of Army
January 31, 2023
3990, deadly, carbamate, nerve, agent, lethal, because, inhibits, acetylcholinesterase, inhibition, causes, overly, high, accumulation, acetylcholine, between, nerve, muscle, cells, this, paralyzes, muscles, preventing, their, relaxation, paralyzed, muscles, i. 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 EA 3990 NamesPreferred IUPAC name N1 N8 Bis 3 dimethylcarbamoyl oxy pyridin 2 yl methyl N1 N1 N8 N8 tetramethyloctane 1 8 bis aminium dibromideIdentifiersCAS Number 110913 95 63D model JSmol Interactive imageInChI 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 2Key ABTAGUMOWVVEGK UHFFFAOYSA LSMILES Br Br CN C C O Oc1cccnc1C N C C CCCCCCCC N C C Cc2ncccc2OC O N C CPropertiesChemical formula C30H50N6O4 Br2Molar mass 718 7 g molAppearance white odorless crystalline solid Density 1 33 g cm3Melting point 190 191 CSolubility soluble in alcohols acetic acid and chloroformVapor pressure negligibleHazardsLethal dose or concentration LD LC LD50 median dose 6 3 µg kg for mice and 2 6 µg kg for rabbits via IVExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox references Patent assigned to US army for EA 3990 among other similar nerve agents was filed in December 7 1967 3 Contents 1 Lethality 2 Properties 3 Synthesis 4 See also 5 ReferencesLethality EditEA 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 EditEA 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 EditTwo 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 a w 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 Edit3152 CT EA 3887 EA 3966 EA 4056 T 1123References Edit a b c d Hank ED 2008 Handbook of chemical and biological warfare agents 2nd ed Boca Raton CRC Press p 113 ISBN 9780849314346 OCLC 82473582 Colovic MB Krstic DZ Lazarevic Pasti TD Bondzic AM Vasic VM May 2013 Acetylcholinesterase inhibitors pharmacology and toxicology Current Neuropharmacology 11 3 315 35 doi 10 2174 1570159X11311030006 PMC 3648782 PMID 24179466 a b c d e f US patent 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 Gupta RC 2015 Carbamates Handbook of toxicology of chemical warfare agents 2nd ed Amsterdam Elsevier Academic Press pp 338 339 ISBN 9780128004944 OCLC 433545336 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 a b c US patent 4677204A Harold Z Sommer Havre de Grace Omer O Owens Chemical agents issued 1987 06 30 assigned to US Secretary of Army Retrieved from https en wikipedia org w index php title EA 3990 amp oldid 1133583780, wikipedia, wiki, book, books, library,
