Insecticide tetraethyl pyrophosphate

In the normal process ( ), step (J) occurs very rapidly and step (/) is the rate-determining step, whereas in the inhibition process (B), step (3) occurs very slowly, generally over a matter of days, so that it is rate determining. Thus it has been demonstrated with AChE that insecticides, eg, tetraethyl pyrophosphate and mevinphos, engage in first-order reactions with the enzyme the inhibited enzyme is a relatively stable phosphorylated compound containing one mole of phosphoms per mole of enzyme and as a result of the reaction, an equimolar quantity of alcohoHc or acidic product HX is hberated. 

The importance of methods of analysis for new insecticides is evidenced by the fact that during the past two years industry and government have cooperated in developing methods for two of them—tetraethyl pyrophosphate and benzene hexachloride (1,2,3,4,5,6-hexachlorocyclohexane) (37, 45). 

Of the three organic phosphorus insecticides—hexaethyl tetraphosphate, tetraethyl pyrophosphate, and parathion—the first two have been shown to be mixtures (36) that contain tetraethyl pyrophosphate as the principal active ingredient. Several methods have been proposed for the determination of this compound in the commercial products (25, 35). All are based on the separation of the tetraethyl pyrophosphate from the related ethyl phosphates, followed by its hydrolysis to diethyl orthophosphoric acid and titration with standard alkali. Both hexaethyl tetraphosphate and tetraethyl pyrophosphate are soluble in water and are rapidly hydrolyzed to monoethyl and diethyl orthophosphoric acid. This rapid hydrolysis to nontoxic products greatly limits the duration of the in- secticidal effectiveness of tetraethyl pyrophosphate, but it also eliminates the danger of toxic residues on the crops treated. 

The purpose of this work was to determine the toxicity to mosquito larvae of insecticide spray residues. That certain insecticides are translocated in plants (4, 5) adds impetus to this study. Fresh orchard fruit sprayed or dusted with preparations containing parathion (0,0-diethyl O-p-nitrophenyl thiophosphate), tetraethyl pyrophosphate (TEPP, HEPP), DDD [2,2-bis(p-chlorophenyl)-l,l-dichloroethane], DDT [2,2-bis(p-chlorophenyl)-l,l,l-trichloroethane], chlorinated camphene, and basic lead arsenate were shipped from California to Yonkers, N. Y., by air express for bioassay. 

In addition to the tests made on peaches and apricots, samples of prunes from trees that had been sprayed with parathion, DDT, DDD, basic lead arsenate, and toxaphene at the rate of from 1 to 2 pounds of these insecticides per 100 gallons of water were tested on larvae of Aedes aegypti. The trees had been sprayed on April 20 and June 16, 1948. The fruit was harvested on or about September 10. Prunes from trees that had been treated with 1 quart of tetraethyl pyrophosphate and 12 pounds of sulfur dust per acre on June 15, and harvested about July 6, were tested on larvae of the above named species. None of the prune samples tested in this study exhibited any significant toxicity to mosquito larvae as compared with the unsprayed check. 

Tetraisopropyl Pyrophosphate. This ester, a water-white liquid, has been prepared by Toy (47) in 94% yield from diisopropyl chlorophosphate and water in the presence of pyridine. The ester is insecticidal and is about one tenth as toxic to white mice as tetraethyl pyrophosphate. An insecticidal dust of much greater stability than tetraethyl pyrophosphate dust can be formulated from tetraisopropyl pyrophosphate, inasmuch as the tetraisopropyl ester hydrolyzes at approximately V50th the rate at which the tetraethyl ester breaks down in the presence of moisture. 

Since selenium and all its compounds are toxic in some degree they are of no use as systemic insecticides because condition (4) is not realized. Parathion,3 however, has a low water-solubility and tetraethyl pyrophosphate (T.E.P.P.)4 is very readily hydrolysed by water. Therefore, although they have powerful insecticidal action, they are not considered by some workers as successful systemic insecticides. 

In the 1970s organophosphorus compounds became the leading type of insecticide and they still are, mainly because they are less persistent. Over 50 such compounds are registered in the U.S. today as insecticides. Gerhard Schrader synthesized the first organophosphorus insecticide in Germany in 1938, commonly called tetraethyl pyrophosphate (TEPP). 

In the 1970s, organophosphorus compounds became the leading type of insecticide. Over 40 such compounds have been registered in the United States as insecticides. The first organophosphorus insecticide was synthesized in 1938 and is known as tetraethyl pyrophosphate (TEPP). Another phosphate insecticide, Malathion is synthesized by condensing diethyl maleate with the o,o-dimethyl phosphorodithioic acid. 

It was at this time, which was very soon after the end of World War II, when we learned that Gerhardt Schraeder of Germany had found that tetraethyl pyrophosphate was a good insecticide. Schraeder had prepared the compound in a crude form by heating one mol of phosphorus oxychloride with three mols of triethyl phosphate (equation 24). 

Even though Schraeder reported that he obtained hexaethyl tetraphosphate, subsequent studies showed that actually various reorganization reactions occurred. The reaction mixture contained about 20 - 25% tetraethyl pyrophosphate. Tetraethyl pyrophosphate was the active insecticide ingredient. One of my laboratory colleagues discovered another... 

As you will recall, the initial goal of this research was to prepare a pure sample of diethyl phosphoric acid and we ended up with the discovery of a commercial insecticide. Such is the nature of industrial research. Incidentally, we eventually made the pure diethyl phosphoric acid. We did it by the controlled hydrolysis of tetraethyl pyrophosphate. 

Tetraethyl pyrophosphate. Very toxic anticholinesterase originally synthesized as a potential insecticide. Lethal dose oral 1.1 mg/kg, dermal 2.4 mg/kg. 

One of the first known examples of phosphorus ester insecticides was tetraethyl pyrophosphate (TEPP, 7). 

---