Tetraethyl pyrophosphate, abbreviated TEPP, is an
organophosphate compound with the formula . It is the tetra
ethyl
Ethyl may refer to:
Arts and entertainment
* Cold Ethyl, a Swedish rock band
*Ethyl Sinclair, a character in the ''Dinosaurs'' television show
Science and technology
* Ethyl group, an organic chemistry moiety
* Ethyl alcohol (or ethanol)
* E ...
derivative of
pyrophosphate
In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a P–O–P linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate (Na2H2P2O7) and tetrasodium pyrophosphate (Na4P2O7), among other ...
(P
2O
74-). It is a colorless oil that solidifies near room temperature. It is used as an
insecticide
Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to b ...
. The compound hydrolyzes rapidly.
Applications
TEPP is an insecticide to aphids, mites, spiders, mealybugs, leafhoppers, lygus bugs, thrips, leafminers, and many other pests.
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
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
. The treatment would deliver an increase in strength.
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).
Their synthesis made use of
ethyl iodide
Ethyl iodide (also iodoethane) is a colorless flammable chemical compound. It has the chemical formula C2H5I and is prepared by heating ethanol with iodine and phosphorus.''Merck Index of Chemicals and Drugs'', 9th ed., monograph 3753 On contact ...
and silver salts to form esters in combination with pyrophosphate.
:
Commercial routes to TEPP often use methods developed by Schrader, Woodstock, and Toy.
Triethyl phosphate
Triethyl phosphate is an organic chemical compound with the formula (C2H5)3PO4 or OP(OEt)3. It is a colorless liquid. It is the triester of ethanol and phosphoric acid and can be called "phosphoric acid, triethyl ester".
Its primary uses are a ...
reacts with
phosphorus oxychloride
Phosphoryl chloride (commonly called phosphorus oxychloride) is a colourless liquid with the formula . It hydrolyses in moist air releasing phosphoric acid and fumes of hydrogen chloride. It is manufactured industrially on a large scale from phosp ...
(Schrader-method) or
phosphorus pentoxide
Phosphorus pentoxide is a chemical compound with molecular formula P4 O10 (with its common name derived from its empirical formula, P2O5). This white crystalline solid is the anhydride of phosphoric acid. It is a powerful desiccant and dehydra ...
(Woodstock-method).
Alternatively, controlled hydrolysis of
diethyl phosphorochloridate delivers the compound:
:
The related tetrabenzylpyrophosphate is prepared by dehydration of dibenzylphosphoric acid:
:
Hydrolysis
TEPP and most of the other organophosphates are susceptible to hydrolysis.
The product is diethyl phosphate.
Toxicity
TEPP is bioactive as an
acetylcholinesterase inhibitor
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 ...
. It reacts with the
serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...
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. There are three types of effects on these animals that have come forward during laboratory studies.
* DERMAL: LD
50 = 2.4 mg/kg (male rat)
* ORAL: LD
50 = 1.12 mg/kg (rat)
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.
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.
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.
[The history of cholinesterase inhibitors: who was Moschnin(e)?]
/ref>
The ignorance about the potential toxicity
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...
of TEPP is evidenced by De Clermont himself, who described the taste of TEPP as having a burning taste and a peculiar odor ("''un liquide visqueux d’une saveur brulante(et) d’une odeur particuliere''"). 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
Organophosphorus compounds 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 ins ...
has really started developing with the help of A. W. von Hofmann, Carl Arnold August Michaelis and Aleksandr Arbuzov
Aleksandr Erminingeldovich Arbuzov (russian: Алекса́ндр Ермининге́льдович Арбу́зов; 12 October 1877 – 22 January 1968) was a Russian and Soviet chemist who discovered the Michaelis–Arbuzov reaction.
A n ...
.
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):
"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
The Federal Ministry of Defence (german: Bundesministerium der Verteidigung, ), abbreviated BMVg, is a top-level Federal agency (Germany), federal agency, headed by the Federal Minister of Defence as a member of the Cabinet of Germany. The mini ...
. Gerhard Schrader
Gerhard Schrader (25 February 1903 – 10 April 1990) was a German chemist specializing in the discovery of new insecticides, hoping to make progress in the fight against hunger in the world. Schrader is best known for his accidental discovery of ...
, 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 .
Around the beginning of the Second World War
World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
, TEPP was discovered to be an inhibitor
Inhibitor or inhibition may refer to:
In biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...
of cholinesterases. 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. 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
Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...
was discovered as a possible antidote for the anticholinesterase
Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. This increases the amount of the acetylcholine or butyrylcholine in the sy ...
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.
References
{{Acetylcholine metabolism and transport modulators
Pyrophosphates
Ethyl esters
Acetylcholinesterase inhibitors