Dimethoate hydrolysis

In addition to ester bonds with P (Section 10.2.1, Figures 10.1 and 10.2), some OPs have other ester bonds not involving P, which are readily broken by esteratic hydrolysis to bring about a loss of toxicity. Examples include the two carboxylester bonds of malathion, and the amido bond of dimethoate (Figure 10.2). The two carboxylester bonds of malathion can be cleaved by B-esterase attack, a conversion that provides the basis for the marked selectivity of this compound. Most insects lack an effective carboxylesterase, and for them malathion is highly toxic. Mammals and certain resistant insects, however, possess forms of carboxylesterase that rapidly hydrolyze these bonds, and are accordingly insensitive to malathion toxicity. 

Another example is dime thoate, the toxicity of which is related to its rate of hydrolysis. Those species, which are capable of metabolizing the insecticide, are less susceptible than those species, which are poor metabolizers. The metabolism of dimethoate is shown in Figure 5.13. Studies on the metabolism in vitro of dimethoate have shown that sheep liver produces only the first metabolite, whereas guinea pigs produce only the final product (Fig. 5.13). Rats and mice metabolize dimethoate to both products. The toxicity is in the descending order sheep>dog>rat>cattle>guinea pig>mouse. 

The hydrolysis of esters by esterases and of amides by amidases constitutes one of the most common enzymatic reactions of xenobiotics in humans and other animal species. Because both the number of enzymes involved in hydrolytic attack and the number of substrates for them is large, it is not surprising to observe interspecific differences in the disposition of xenobiotics due to variations in these enzymes. In mammals the presence of carboxylesterase that hydrolyzes malathion but is generally absent in insects explains the remarkable selectivity of this insecticide. As with esters, wide differences exist between species in the rates of hydrolysis of various amides in vivo. Fluoracetamide is less toxic to mice than to the American cockroach. This is explained by the faster release of the toxic fluoroacetate in insects as compared with mice. The insecticide dimethoate is susceptible to the attack of both esterases and amidases, yielding nontoxic products. In the rat and mouse, both reactions occur, whereas sheep liver contains only the amidases and that of guinea pig only the esterase. The relative rates of these degradative enzymes in insects are very low as compared with those of mammals, however, and this correlates well with the high selectivity of dimethoate. 

P.R.S. Chen, and W.C. Dauterman, Studies on the toxicity of dimethoate analogs and their hydrolysis by sheep liver amidase. Pestic. Biochem. Physiol. 1 340, 1971. 

Dimethoate has low persistence in soil with a half-life of 20 days. It evaporates from dry soil surfaces and is biodegradable. Since dimethoate is broken down rapidly by soil micro organisms, its breakdown is much faster in moist soils. In alkaline soils, it is degraded by hydrolysis. Since it is highly soluble in water and adsorbs very poorly to soil particles, it may leach into groundwater. 

The half-life of dimethoate in river water is 8 days. It does not bioaccumulate in aquatic organisms, nor does it adsorb to suspended particles in water. Dimethoate undergoes significant hydrolysis, especially under alkaline conditions. However, losses by photolysis and evaporation from open waters are not expected to be significant. Dimethoate is not toxic to plants. 

Many organophosphorus insecticides with aliphatic leaving groups have been developed. We shall describe trichlorfon, dichlorvos, dimethoate, and malathion. Trichlorfon has to be activated to dichlorvos by an intramolecular rearrangement combined with hydrolysis ... 

At room temperature, the solubility of dimethoate in water is 39 g/1, thus it belongs to the phosphorus ester insecticides of high water solubility. It is stable to hydrolysis in neutral and acidic media, but saponifies rapidly in alkaline media. 

The instability of aldehydo-acylsilane (46) required a different approach for its preparation (eq 22). Thus l-(methyldiphenylsilyl) propan-1-one (44) was converted into the corresponding NJSI-dimethylhydrazone that was alkylated with 3-bromo-1,1-dimetho-xypropane to give compound (45). Hydrolysis with Amber-lyst-15 as catalyst afforded the target aldehyde (46). 

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