Tetraethyl pyrophosphate

Last updated
Tetraethyl pyrophosphate
Tetraethyl pyrophosphate Structural Formula V2.svg
Tetraethyl-pyrophosphate-3D-balls.png
Names
Preferred IUPAC name
Tetraethyl diphosphate
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.003.179 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 203-495-3
KEGG
PubChem CID
RTECS number
  • UX6825000
UNII
UN number 3018 2783
  • InChI=1S/C8H20O7P2/c1-5-11-16(9,12-6-2)15-17(10,13-7-3)14-8-4/h5-8H2,1-4H3 Yes check.svgY
    Key: IDCBOTIENDVCBQ-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C8H20O7P2/c1-5-11-16(9,12-6-2)15-17(10,13-7-3)14-8-4/h5-8H2,1-4H3
    Key: IDCBOTIENDVCBQ-UHFFFAOYAI
  • O=P(OP(=O)(OCC)OCC)(OCC)OCC
Properties
C8H20O7P2
Molar mass 290.189 g·mol−1
Appearancecolorless to amber liquid [1]
Odor faint, fruity [1]
Density 1.19 g/mL (20°C) [1]
Melting point 0 °C; 32 °F; 273 K [1]
Boiling point decomposes [1]
miscible [1]
Vapor pressure 0.0002 mmHg (20°C) [1]
Hazards
GHS labelling:
GHS-pictogram-skull.svg GHS-pictogram-silhouette.svg
Danger
H300, H310, H400
P262, P264, P270, P273, P280, P301+P310, P302+P350, P310, P321, P322, P330, P361, P363, P391, P405, P501
NFPA 704 (fire diamond)
NFPA 704.svgHealth 4: Very short exposure could cause death or major residual injury. E.g. VX gasFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 1: Normally stable, but can become unstable at elevated temperatures and pressures. E.g. calciumSpecial hazards (white): no code
4
1
1
Lethal dose or concentration (LD, LC):
0.5 mg/kg (rat, oral)
2.3 mg/kg (guinea pig, oral)
3 mg/kg (mouse, oral) [2]
NIOSH (US health exposure limits):
PEL (Permissible)
TWA 0.05 mg/m3 [skin] [1]
REL (Recommended)
TWA 0.05 mg/m3 [skin] [1]
IDLH (Immediate danger)
5 mg/m3 [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Tetraethyl pyrophosphate, abbreviated TEPP, is an organophosphate compound with the formula [(C2H5O)2P(O)]2O. It is the tetraethyl derivative of pyrophosphate (P2O74-). It is a colorless oil that solidifies near room temperature. It is used as an insecticide. The compound hydrolyzes rapidly. [3]

Contents

Applications

TEPP is an insecticide to aphids, mites, spiders, mealybugs, leafhoppers, lygus bugs, thrips, leafminers, and many other pests. [4] TEPP and other organophosphates are the most widely used pesticides in the U.S. due to their effectiveness and relative small impact on the environment because this organophosphate breaks down so easily.

TEPP has been used for treatment for myasthenia gravis, an autoimmune disease. The treatment would deliver an increase in strength. [5]

Synthesis

The synthesis by De Clermont and Moschnin was based on the earlier work by Alexander Williamson (who is well known for the Williamson-synthesis of ethers). [6] Their synthesis made use of ethyl iodide and silver salts to form esters in combination with pyrophosphate. [7]

Ag4P2O7 + 4EtI → [(EtO)2P(O)]2O + 4AgI

Commercial routes to TEPP often use methods developed by Schrader, Woodstock, and Toy. Triethyl phosphate reacts with phosphorus oxychloride (Schrader-method) or phosphorus pentoxide (Woodstock-method). [8] [9] Alternatively, controlled hydrolysis of diethyl phosphorochloridate delivers the compound: [10] [11]

2(EtO)2P(O)Cl + H2O → [(EtO)2P(O)]2O + 2HCl

The related tetrabenzylpyrophosphate is prepared by dehydration of dibenzylphosphoric acid: [12]

2(RO)2P(O)OH → [(EtO)2P(O)]2O + H2O

Hydrolysis

TEPP and most of the other organophosphates are susceptible to hydrolysis. [13] The product is diethyl phosphate. [13] [14]

Toxicity

TEPP is bioactive as an acetylcholinesterase inhibitor. It reacts with the serine hydroxyl group at the active site, preventing this enzyme from acting on its normal substrate, the neurotransmitter acetyl choline.

TEPP is highly toxic for all warm-blooded animals, including humans. [15] There are three types of effects on these animals that have come forward during laboratory studies.

Death is mostly due to either respiratory failure and in some cases cardiac arrest. The route of absorption might be responsible for the range of effect on certain systems. [16]

For cold-blooded animals the effects are slightly different. In a study with frogs, acute exposure caused a depression in the amount of erythrocytes in the blood. There was also a reduction of white bloodcells, especially the neutrophil granulocytes and lymphocytes. There was no visible damage to the bloodvessels to explain the loss of blood cells. Further there were no signs like hypersalivation or tears like in warm-blooded animals, though there was hypotonia leading to paralysis. [17]

History

It was first synthesized by Wladimir Moschnin in 1854 while working with Adolphe Wurtz. A fellow student Philippe de Clermont is often incorrectly credited as the discoverer of TEPP despite his recognition of the Moschnin primacy in two publications. [18]

The ignorance about the potential toxicity of TEPP is evidenced by De Clermont himself, who described the taste of TEPP as having a burning taste and a peculiar odor. [6] Even though TEPP has repeatedly been synthesized by other chemists during the years that followed, not until the 1930s had any adverse effects been observed. Furthermore, Philippe de Clermont has never been reported ill by his family up to his passing at the age of 90. In the meantime, organophosphorus chemistry has really started developing with the help of A. W. von Hofmann, Carl Arnold August Michaelis and Aleksandr Arbuzov. [19]

It was not until 1932 before the first adverse effects of compounds similar to TEPP had been recognized. Willy Lange and Gerda von Krueger were the first to report such effects, about which the following statement was published in their article (in German): [20]

"Interestingly, we report the strong effect of monofluorophosphate phosphoric acid alkyl esters on the human organism. The vapor of these compounds have a pleasant odor and sharply aromatic. After only a few minutes of inhaling the vapor, there is a strong pressure on the larynx, associated with shortness of breath. Then comes decreased awareness, opacities, and dazzling phenomena causing painful sensitivity of the eye to light. Only after several hours is there relief from these phenomena. They are apparently not caused by acidic decomposition products of the ester, but they are probably due to the Dialkyl monofluorophosphates themselves. The effects are exerted by very small amounts."

Starting in 1935 the German government started gathering information about new toxic substances, of which some were to be classified as secret by the German Ministry of Defence. [19] Gerhard Schrader, who has become famous for his studies into organophosphorus insecticides and nerve gases, was one of the chemists who was also studying TEPP. In his studies, in particular his studies into the biological aspects, he noticed that this reagent could possibly be used as an insecticide. This would make the classification of the compound as secret disadvantageous for commercial firms. [19]

Around the beginning of the Second World War, TEPP was discovered to be an inhibitor of cholinesterases. [6] Schrader referred to the studies by Eberhard Gross, who was the first to recognize the mechanism of action for TEPP in 1939. More experiments were conducted including those of Hans Gremels, who confirmed Gross's work. [19] Gremels was also involved in the development of nerve gases at that time. His studies involved several species of animals and human volunteers. Around that same time, atropine was discovered as a possible antidote for the anticholinesterase activity of TEPP.

After the Second World War, Schrader was among many German scientists who were interrogated by English scientists, among others. During the war, the English had been developing chemical weapons of their own to surprise their enemies. In these interrogations the existence of TEPP and other insecticides were disclosed. The existence of nerve gases, however also being disclosed by Schrader, was kept secret by the military. [10]

Related Research Articles

<span class="mw-page-title-main">Cholinesterase</span> Esterase that lyses choline-based esters

The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters:

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

Parathion, also called parathion-ethyl or diethyl parathion and locally known as "Folidol", is an organophosphate insecticide and acaricide. It was originally developed by IG Farben in the 1940s. It is highly toxic to non-target organisms, including humans, so its use has been banned or restricted in most countries. The basic structure is shared by parathion methyl.

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

Malathion is an organophosphate insecticide which acts as an acetylcholinesterase inhibitor. In the USSR, it was known as carbophos, in New Zealand and Australia as maldison and in South Africa as mercaptothion.

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

Chlorfenvinphos is an organophosphorus compound that was widely used as an insecticide and an acaricide. The molecule itself can be described as an enol ester derived from dichloroacetophenone and diethylphosphonic acid. Chlorfenvinphos has been included in many products since its first use in 1963. However, because of its toxic effect as a cholinesterase inhibitor it has been banned in several countries, including the United States and the European Union. Its use in the United States was cancelled in 1991.

<span class="mw-page-title-main">Organophosphate</span> Organic compounds with the structure O=P(OR)3

In organic chemistry, organophosphates are a class of organophosphorus compounds with the general structure O=P(OR)3, a central phosphate molecule with alkyl or aromatic substituents. They can be considered as esters of phosphoric acid.

Demeton-S-methyl is an organic compound with the molecular formula C6H15O3PS2. It was used as an organothiophosphate acaricide and organothiophosphate insecticide. It is flammable. With prolonged storage, Demeton-S-methyl becomes more toxic due to formation of a sulfonium derivative which has greater affinity to the human form of the acetylcholinesterase enzyme, and this may present a hazard in agricultural use.

<span class="mw-page-title-main">Pralidoxime</span> Chemical compound as an antidote

Pralidoxime or 2-PAM, usually as the chloride or iodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to treat organophosphate poisoning in conjunction with atropine and either diazepam or midazolam. It is a white solid.

Organophosphorus chemistry is the scientific study of the synthesis and properties of organophosphorus compounds, which are organic compounds containing phosphorus. They are used primarily in pest control as an alternative to chlorinated hydrocarbons that persist in the environment. Some organophosphorus compounds are highly effective insecticides, although some are extremely toxic to humans, including sarin and VX nerve agents.

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

Azinphos-methyl (Guthion) is a broad spectrum organophosphate insecticide manufactured by Bayer CropScience, Gowan Co., and Makhteshim Agan. Like other pesticides in this class, it owes its insecticidal properties to the fact that it is an acetylcholinesterase inhibitor. It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act, and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.

<span class="mw-page-title-main">Phosmet</span> Organophosphate non-systemic insecticide

Phosmet is a phthalimide-derived, non-systemic, organophosphate insecticide used on plants and animals. It is mainly used on apple trees for control of codling moth, though it is also used on a wide range of fruit crops, ornamentals, and vines for the control of aphids, suckers, mites, and fruit flies.

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

Chlorethoxyfos is an organophosphate acetylcholinesterase inhibitor used as an insecticide. It is registered for the control of corn rootworms, wireworms, cutworms, seed corn maggot, white grubs and symphylans on corn. The insecticide is sold under the trade name Fortress by E.I. du Pont de Nemours & Company.

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

Disulfoton is an organophosphate acetylcholinesterase inhibitor used as an insecticide. It is manufactured under the name Di-Syston by Bayer CropScience. Disulfoton in its pure form is a colorless oil but the technical product used in vegetable fields is dark and yellowish with a sulfur odor. Disulfoton is processed as a liquid into carrier granules, these granules are mixed with fertilizer and clay to be made into a spike, designed to be driven into the ground. The pesticide is absorbed over time by the roots and translocated to all parts of the plant. The pesticide acts as a cholinesterase inhibitor and gives long lasting control.

<span class="mw-page-title-main">Philippe de Clermont</span>

Philippe de Clermont (1831–1921) was a French organic chemist. He was known for the synthesis of the first organophosphate cholinesterase inhibitor. He worked in Adolphe Wurtz's laboratory in Paris.

<span class="mw-page-title-main">Acetylcholinesterase inhibitor</span> Drugs that inhibit acetylcholinesterase

Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and duration of action of acetylcholine in the central nervous system, autonomic ganglia and neuromuscular junctions, which are rich in acetylcholine receptors. Acetylcholinesterase inhibitors are one of two types of cholinesterase inhibitors; the other being butyryl-cholinesterase inhibitors. Acetylcholinesterase is the primary member of the cholinesterase enzyme family.

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

Sulfotep (also known as tetraethyldithiopyrophosphate and TEDP) is a pesticide commonly used in greenhouses as a fumigant. The substance is also known as Dithione, Dithiophos, and many other names. Sulfotep has the molecular formula C8H20O5P2S2 and belongs to the organophosphate class of chemicals. It has a cholinergic effect, involving depression of the cholinesterase activity of the peripheral and central nervous system of insects. The transduction of signals is disturbed at the synapses that make use of acetylcholine. Sulfotep is a mobile oil that is pale yellow-colored and smells like garlic. It is primarily used as an insecticide.

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

Diethyl chlorophosphate is an organophosphorus compound with the formula (C2H5O)2P(O)Cl. As a reagent in organic synthesis, it is used to convert alcohols to the corresponding diethylphosphate esters. It is a colorless liquid with a fruity odor. It is a corrosive, and as a cholinesterase inhibitor, highly toxic through dermal absorption. The molecule is tetrahedral.

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

Terbufos is a chemical compound used in insecticides and nematicides. It is part of the chemical family of organophosphates. It is a clear, colourless to pale yellow or reddish-brown liquid and sold commercially as granulate.

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

Triamiphos (chemical formula: C12H19N6OP) is an organophosphate used as a pesticide and fungicide. It is used to control powdery mildews on apples and ornamentals. It was discontinued by the US manufacturer in 1998.

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

Hexaethyl tetraphosphate (also known as HETP) is the organophosphorus compound with the chemical formula [(C2H5O)3P2O3]2O. The compound has not been isolated in pure form but appears to be a colorless liquid at room temperature. Commercial samples appear brown due to impurities. It is a constituent of the insecticide Bladan. In the 1940s, it was about as significant an insecticide as DDT and was referred to as "another of DDT's rivals for fame" in a 1948 book.

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

IPTBO is a bicyclic phosphate convulsant. It is an extremely potent GABA receptor antagonist that can cause violent convulsions in mice.

References

  1. 1 2 3 4 5 6 7 8 9 10 NIOSH Pocket Guide to Chemical Hazards. "#0590". National Institute for Occupational Safety and Health (NIOSH).
  2. ↑ "TEPP". Immediately Dangerous to Life or Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
  3. ↑ Robert L. Metcalf. "Insect Control". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a14_263. ISBN   978-3527306732.
  4. 1 2 Henderson, Chas. F.; Tilton, Elvin. W. (1955). "Tests with Acaricides against the Brown Wheat Mite12". Journal of Economic Entomology. 48 (2): 157–161. doi:10.1093/jee/48.2.157.
  5. ↑ Marr, W.G.; Grob, David (1950-06-20). "Some Ocular Effects of a new Anticholinesterase Agent*". American Journal of Ophthalmology. 33 (6): 904–908. doi:10.1016/0002-9394(50)91606-0. ISSN   0002-9394.
  6. 1 2 3 Petroianu, G. A. (2009-04-01). "The synthesis of phosphor ethers: who was Franz Anton Voegeli?". Die Pharmazie. 64 (4): 269–271. doi:10.1691/ph.2009.8244. ISSN   0031-7144. PMID   19435147.
  7. ↑ Petroianu, Georg (2015). "History of organophosphorus cholinesterase inhibitors & reactivators". Military Medical Science Letters. 84 (4): 182–185. doi: 10.31482/mmsl.2015.023 .
  8. ↑ Sherma, Joseph; Zweig, Gunter (1973). Thin-Layer and Liquid Chromatography and Pesticides of International Importance: Analytical Methods for Pesticides and Plant Growth Regulators. Vol. 7. Academic Press. pp. 471–477. ISBN   978-1-4832-2084-0.
  9. ↑ National Research Council (U S. ) Pesticide Residues Committee (1965). Report on "no Residue" and "zero Tolerance". National Academies. pp. 3–4.
  10. 1 2 Toy, A. D. F. (1948). "The Preparation of Tetraethyl Pyrophosphate and Other Tetraalkyl Pyrophosphates". Journal of the American Chemical Society . 70 (11): 3882–3886. doi:10.1021/ja01191a104. PMID   18102975.
  11. ↑ Steinberg, Geo. M. (1950). "Reactions of Dialkyl Phosphites. Synthesis of Dialkyl Chlorophosphates, Tetraalkyl Pyrophosphates, and Mixed Orthophosphate Esters". Journal of Organic Chemistry. 15 (3): 637–47. doi:10.1021/jo01149a031.
  12. ↑ Todd D. Nelson; Jonathan D. Rosen; M. Bhupathy; James McNamara; Michael J. Sowa; Chad Rush; Louis S. Crocker (2003). "Tetrabenzyl Pyrophosphate". Organic Syntheses. 80: 219. doi:10.15227/orgsyn.080.0219.
  13. 1 2 Sogorb, Miguel A; Vilanova, Eugenio (2002-03-10). "Enzymes involved in the detoxification of organophosphorus, carbamate and pyrethroid insecticides through hydrolysis". Toxicology Letters. 128 (1–3): 215–228. doi:10.1016/S0378-4274(01)00543-4. PMID   11869832.
  14. ↑ Jokanović, Milan (2001-09-25). "Biotransformation of organophosphorus compounds". Toxicology. 166 (3): 139–160. doi:10.1016/S0300-483X(01)00463-2. PMID   11543910.
  15. ↑ "Benfluralin - National Library of Medicine HSDB Database". toxnet.nlm.nih.gov. Retrieved 2016-03-08.
  16. ↑ Clarke, Myra L.; Harvey, Douglas Graham; Humphreys, David John (1988). Veterinary Toxicology (2 ed.). London, England: Bailliere Tindal. p. 157.
  17. ↑ Kaplan, Harold M.; Glaczenski, Sheila S. (1965-06-01). "Hematological effects of organophosphate insecticides in the frog (Rana pipiens)". Life Sciences. 4 (12): 1213–1219. doi:10.1016/0024-3205(65)90335-8. PMID   4284682.
  18. ↑ Fest, Christa; Schmidt, Karl-Julius (1982). The Chemistry of Organophosphorus Pesticides. Springer. doi:10.1007/978-3-642-68441-8. ISBN   978-3-642-68443-2. S2CID   33095322. The history of cholinesterase inhibitors: who was Moschnin(e)?
  19. 1 2 3 4 "9: "Structure-Activity Relationships of the Organophosphorus Anticholinesterase Agents, Historical development of organophosphorus cholinesterase inhibitors"". Cholinesterases and Anticholinesterase Agents. Handbook of Experimental Pharmacology. Vol. 15. Springer Science & Business Media. 1963. pp. 434–437. ISBN   978-3-642-99875-1.
  20. ↑ Petroianu, G. A. (2010-10-01). "Toxicity of phosphor esters: Willy Lange (1900-1976) and Gerda von Krueger (1907-after 1970)". Die Pharmazie. 65 (10): 776–780. ISSN   0031-7144. PMID   21105582.
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