Pyrophosphate tetraethyl

Toy prepared this ester (as well as related esters) by the com trolled hydrolysis of 2 mol. of diethyl phosphorochloridate  

The hydrogen chloride is removed either by reduced pressure or by salt formation with pyridine or sodium bicarbonate the latter procedure gave high yields of the pure ester. Toy also measured the hydrolysis rates and compared the toxicities of a series of tetra-alkyl pyrophosphates. 

is a colourless, odourless, water-soluble toxic liquid, more toxic than parathion and rapidly absorbed through the skin. It is quickly hydrolysed, even in the absence of alkah, to the non-toxic diethyl hydrogen phosphate. It has found use as an aerosol to control pests on greenhouse vegetables and flowers, and is relatively free from residual toxicity hazards. 

Schrader, by the action of 3 mol. of triethyl phosphate on 1 mol. of phosphorus oxychloride, obtained what he considered to be hexaethyl tetraphosphate (H.E.T.P.)  

The product was undoubtedly a mixture and contained some T.E.P.P. It may be noted that we showed that one of the primary actions of triethyl phosphate on phosphorus oxychloride is to give Et0-P0Cl2 and (EtO)2POCl, hence a complex mixture is likely to result from the further sphtting out of ethyl chloride between the primary product and the original ethyl phosphate. 

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Phosphoric Acid and Phosphorothioic Acid Anhydrides. The aUphatic organophosphoms esters originally developed by Schrader (27) are extremely toxic to mammals and are largely of historic interest. Tetraethyl pyrophosphate [107-49-3] (40) (bp 104—110°C at 10.7 Pa, d 1.185, vp 6.1 mPa at 30°C) is miscible with water and hydrolyzes very rapidly with a half-life of 6.8 h at 25°C. The rat LD qS ate 1.1 (oral) and 2.4 (dermal) mg/kg. 

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. 

Tetraethyl lead Tetraethylene glycol Tetraethyl pyrophosphate Tetrahydrofuran Tetramethyl lead (as Pb)... 

G.l.c. studies of tributylphosphine, dialkyl phosphites, and dialkyl alkylphosphonates are reported. Tributyl phosphate in nitric acid can be estimated by g.l.c. if a glass column is used. Tetraethyl pyrophosphate has been directly determined on a nanogram scale by g.l.c., whereas it was found most convenient to first convert the tetra-aryl pyrophosphates by methanolysis to diarylmethyl phosphates. Phosphorochloridates were converted by t-butyl alcohol into t-butyl chloride before analysis. G.l.c. studies of pesticides have been reported and the isomeric thiophosphates (138a) and (138b) have quite different retention times. ... 

Chlorodiphenylphosphine 488 reacts with a-sulphinyl carbanions to give a-sulphinylphosphines 489 which undergo ready isomerization to a-sulphenylphosphine oxides 4W (equation 295). The report of Almog and Weissman that a-sulphinyl carbanions react with phosphorochloridates 491 to give a-phosphoryl sulphoxides 492 calls for correction (equation 296). Actually, the phosphorylation occurs at the oxygen atom of the ambident dimsyl anion, and is followed by the Pummerer-type reaction affording diethylphosphoric acid and tetraethyl pyrophosphate among other products . ... 

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. 

Tetraethyl pyrophosphate was first manufactured in Germany about 1940 as hexa-... 

Fly cage sprayed with tetraethyl pyrophosphate and weathered in laboratory. Flies introduced at stated intervals... 

Formulations of tetraethyl pyrophosphate as an emulsive concentrate proved to be relatively complex, considering the apparent ease of formulation. Because of the unstable nature of the chemical, dust formulations were considered impossible. It was found after extensive research work that a dust which would be stable for 10 days to 2 weeks could be made with a specially selected and processed filler. 

A sample of hops which had been treated with tetraethyl pyrophosphate showed a negative chemical analysis. The plant material was also extracted and the extract added to the drinking water of test animals and sensitive insects. The animals and insects that drank this treated water for several days showed no reaction. With the sensitive insects it would have been possible to detect even a few parts per million. In addition, there have been extensive commercial field applications of the chemical in dust and spray form to crops such as apples, pears, grapes, celery, broccoli, Brussels sprouts, and others up to within a few days of harvest there has been no detectable poison residue on any of the crops. The lack of poison residue with use of tetraethyl pyrophosphate is due to the fact that it hydrolyzes within a few hours of application, breaking down into transient nonresidual and nonpoisonous chemicals. Thus it is possible to use tetraethyl pyrophosphate well up to harvest time of food products without danger of residual poison on crops. The fact that the chemical is used in extremely small amounts is a definite advantage in respect to freedom from poison residue. 

In all cases the reaction products are mixtures of ethyl polyphosphates, and, on the basis of elementary analysis, they approximate the empirical formulas given in the above equations. In Equations 3 and 5 the product has been arbitrarily called hexaethyl tetraphosphate, which may contain 8 to 20% of the active tetraethyl pyrophosphate. In Equations 4 and 6 the products have been called technical tetraethyl pyrophosphate, which may contain up to 40% of pure tetraethyl pyrophosphate. Hexaethyl tetra-phosphate has also been made from phosphoric anhydride and diethyl ether by a process recently patented by Adler (1). 

The purified tetraethyl pyrophosphate is a colorless, odorless, water-soluble, hygroscopic liquid (24, 4 )- It possesses a very high acute toxicity (28), exceeding that of parathion, and is rapidly absorbed through the skin. There is no spray-residue problem, however, for tetraethyl pyrophosphate hydrolyzes even in the absence of alkali to nontoxic diethyl phosphoric acid. Hall and Jacobson (24) and Toy (47) have measured its rate of hydrolysis, which is a first-order reaction. Its half-life at 25° C. is 6.8 hours and at 38° C. is 3.3 hours. Coates (10) determined the over-all velocity constant at 25° C. k = 160 [OH-] + 1.6 X 10 3 min.-1 Toy (47) has described an elegant method for preparing this ester as well as other tetraalkyl pyrophosphates, based upon the controlled hydrolysis of 2 moles of dialkyl chlorophosphate ... 

Several chemical-assay methods (15,23,50) for tetraethyl pyrophosphate were recently developed and applied by seven collaborating laboratories to samples of representative commercial products and to a sample of purified tetraethyl pyrophosphate which served as a common standard. Concordant results, which correlated well with bioassay results,... 

Schrader (38) in a brief description characterized tetraethyl pyrophosphate as not completely water-stable, the mono thio analog as water-stable, and the dithio analog as lime-stable. ... 

As a solvent for this reaction, anhydrous methyl ethyl ketone was found satisfactory. Coates (10) determined the rate of hydrolysis of the monothio analog as approximately one fifth that of tetraethyl pyrophosphate under similar conditions. The dithio analog has been prepared (22) in 90% yield from diethyl chlorothiophosphate, water, and pyridine in a modification of the reaction Toy (47) used to make tetraethyl pyrophosphate ... 

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