Phosphorothioate esters

Aliphatic Phosphorothioate Esters. Many of the eady developments of OP insecticides were simple esters of phosphorothioic acid, (H0)2P(0)SH, and phosphorodithioic acid, (HO)2P(S)SH. 

The reactivity of the individual O—P insecticides is determined by the magnitude of the electrophilic character of the phosphoms atom, the strength of the bond P—X, and the steric effects of the substituents. The electrophilic nature of the central P atom is determined by the relative positions of the shared electron pairs, between atoms bonded to phosphoms, and is a function of the relative electronegativities of the two atoms in each bond (P, 2.1 O, 3.5 S, 2.5 N, 3.0 and C, 2.5). Therefore, it is clear that in phosphate esters (P=0) the phosphoms is much more electrophilic and these are more reactive than phosphorothioate esters (P=S). The latter generally are so stable as to be relatively unreactive with AChE. They owe their biological activity to m vivo oxidation by a microsomal oxidase, a reaction that takes place in insect gut and fat body tissues and in the mammalian Hver. A typical example is the oxidation of parathion (61) to paraoxon [311-45-5] (110). 

Breau AP, Mitchell WM, Swinson J, et al. 1985. Mutagenic and cell transformation activities of representative phosphorothioate esters in vitro. J Toxicol Environ Health 16 403-413. 

The first step in the degradation of phosphate and phosphorothioate esters is hydrolysis, and substantial effort has been directed to all groups. Investigations have also been directed to the use of their degradation products as a source of phosphate for the growth of bacteria, and a wide range of phosphates, dialkylphosphates, and phosphorothioates has therefore been examined as sources of phosphorus (Cook et al. 1978). 

In the case of La3 + - and Zn2+-catalyzed methanolysis of the phosphorothioate esters the observed / ig values of —0.87 and —0.74 also signify an associative mechanism with some departure of the leaving group, but it is difficult to assign the extent of the bond cleavage since the /ieq value is not known for the phosphoryl transfer between thiol and oxygen nucleophiles. 

Honeycutt, R., Ballantine, H., LeBaron, H., Paulson, D., and Siem, V. Degradation ofhigh concentrations of a phosphorothioic ester by hydrolase in Treatment and Disposal of Pesticide Wastes, Krueger, R.F. and Seiber, J.N., Eds. (Washington, DC ACE, 1984). 

Degradation of High Concentrations of a Phosphorothioic Ester by Hydrolase... 

Goethite (surface are 50 m g" ) has been reported to catalyse the hydrolysis of carboxylate and phosphorothioate esters (Torrents and Stone, 1994). The authors suggest that the sulphur of the thioester binds to the surface Fe of the goethite and thereby reduces the electron density at the P atom which in turn facilitates the nucleophilic attack by OH and promotes hydrolysis. 

Torrents, A. Stone, A.T (1994) Oxide surface-catalysed hydrolysis of carboxylate esters and phosphorothioate esters. Soil Sd. Soc. Am. J. 58 738-745... 

A distinctive feature of the alkaline phosphatase-catalyzed hydrolysis is that the relative rates of hydrolysis of the many different phosphate and S-phosphorothioate esters are nearly the same (it is difficult to get precise rate values because of product inhibition by phosphate, the Km... 

Phosphorothioate Esters of Heterocyclic Enols, Chloropyrifos [2971-88-2], 0,0-diethyl 0-(3,5,6-trichloro-2-pyridinyl)... 

Reduction of aromatic nitro groups occurs in three steps, via nitroso and hydroxylamine intermediates, to the amine. The amine can go on to form polymeric residues by a mechanism analogous to that for oxidative coupling of phenols, as in Equation 2. Abiotic nitro reduction is well documented for pesticides that contain aromatic nitro groups, such as the phosphorothioate esters methyl and ethyl parathion (22, 30-33). 

The sulphenyl chloride (52) reacts with strongly activated aromatic rings to give 5 -aryl phosphorothioate esters the selenium analogue behaves similarly. ... 

As noted previously, the stereochemical course of the hydrolysis of a phosphate monoester can be studied only if an oxygen chiral phosphorothioate ester is used a substrate so that an enantiomer of 0-labeled chiral thiophos-... 

As noted previously, studies of the mechanisms of phosphate monoester solvolysis have been extended to the mechanisms of the analogous phosphorothioate ester solvolysis because the thiometaphosphate anion is believed to be more stable than the metaphosphate anion. Thus, a general method based upon P NMR spectroscopy for the configurational analysis of chiral thiophosphate monoesters (see Fig. 10) was described recently by Cullis and co-workers (38). 

Although the structure/reactivity studies conducted by Jencks and co-workers suggest that metaphosphate will not occur as an intermediate in aqueous reactions (54), and it is known that phosphorothioate esters undergo dissociative hydrolysis more rapidly than phosphate esters (40), Weiss and Cleland have recently utilized secondary 0 isotope effects to probe the mechanism of the hy-... 

Dialkyl phosphorochloridothioates are intermediate products in the preparation of most compounds of a phosphorothioate ester base. 

In the pure state it has only a slight cholinesterase-inhibiting effect, but is nevertheless toxic to warm-blooded animals its oral for male rats being 19 mg/kg. Following the metabolic pattern of most phosphorothioic esters, it is metabolised in animal tissues to its oxo analogue, which is a considerably more effective insecticide than the thio analogue. 

One of the cleanest and most general reactions undergone by trivalent phosphorus compounds occurs with sulfur (177). For example, tri-alkylphosphines react vigorously with sulfur to yield trialkylphosphine sulfides. The analogous reaction of phosphorus esters has received considerable attention as a synthetic method, due largely to the insecticidal potency of the phosphorothioate esters. 

Phosphorothioate esters. Mixtures of thiols and trialkyl phosphites react by a redox pathway in the presence of TeCl and lutidine (9 examples, 90-96%). 

The hydrolytic stability, as well as the biological activity, also can be affeeted by modifying other substituents at the phosphorus atom. For example, substitution of sulfur (P = S) for oxygen (P = O) in the ester moiety will reduce the electrophilicity of the phosphorus center because of the weaker electron withdrawing effect of sulfur. Accordingly, phosphorothioate esters (P = S) will exhibit greater stability toward... 

The triesters, which exist only in pyramidal form, can be made by recognised methods such as heating the appropriate phosphorothioate ester (9.461), or by trans esterification of such an ester (9.462). 

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