Phenthoate

Phenthoate is a colorless crystalline substance. Solubility in water is 10 mg/L (25 C). It is readily soluble in most organic solvents. Log Kow = 3.69. It is relatively stable in neutral and acidic aqueous media but decomposed under alkaline conditions.

Phenthoate is an organothiophosphate insecticide used against lepidoptera and houseflies.

Phenthoate is used to control sucking insects and caterpillars in a very wide range of crops. It is also used to control larval and adult mosquitoes

ChEBI: An organic thiophosphate that is ethyl mandelate in which the hydroxy group has been replaced by a (dimethoxyphosphorothioyl)sulfanediyl group.

The industrial synthesis of phenthoate begins with the preparation of the key intermediate alpha-carbethoxybenzyl chloride, typically derived from ethyl mandelate or ethyl phenylacetate through chlorination. This intermediate is then reacted with O,O-dimethyl phosphorodithioic acid or its chloride derivative in the presence of a base such as triethylamine to form the phosphorodithioate ester. The reaction is carried out in organic solvents like toluene or xylene under controlled temperature and pH conditions to ensure high yield and minimise side reactions.

Non-systemic with contact and stomach action. Acetylcholinesterase (AChE) inhibitor.

Studies which have measured the degradation of phenthoate in buffered aqueous solution have shown that it can be hydrolysed at the carboethoxy group, by cleavage of the P-S and C-S bonds and by demethylation in addition to oxidative desulfuration to the oxon. Reports on the metabolism of phenthoate in plants, insects and mammals have shown that the metabolic products can be largely explained by cleavage of these reactive groups. P-S and C-S bond cleavage is demonstrated by the formation of both O,O-dimethyl phosphorothioate and O,O-dimethyl phosphorodithioate. Metabolism in plants, insects and mammals is similar with many of the possible metabolites being identified in most species. Phenthoate carboxylic acid is a major metabolite except in plants where hydrolysis of the phosphorodithioate moiety predominates. In mammals, little or none of the activated metabolite, phenthoate oxon, can be detected, suggesting that the predominant metabolic route is degradative, wkuch may in part explain the favourable mammalian toxicity of the compound.

Phenthoate is degraded by hydrolysis of the carboethoxy moiety. Demethylation and the cleavage of PSC linkages are also important degradation routes. Oxidative desulfuration to the oxon followed by hydrolysis occurs in animals and plants.The major metabolites excreted in the urine and feces are demethyl phenthoate, demethyl phenthoate acid, demethyl phenthoate oxon, and O,O-dimethyl hydrogen phosphorodithioate and phosphorothioate. It is rapidly degraded in soils; DT₅₀ was less than 1 d in both upland and submerged soil.

Phenthoate is stable in water under neutral and acid conditions but it degrades under alkaline conditions (PM). Takade et al. (1976b) examined the hydrolysis of [¹⁴C-phenyl]phenthoatein 0.01M phosphate buffer at pH 6, 7 and 8 and [³²P]phenthoatea t pH 8 (24.5 °C) and analysed the products by TLC in comparison with non-radiolabelled authenticated standards. The solutions were analysed for up to 28 days. Phenthoate was fairly stable and degraded fastest at pH 8 with a DT₅₀ of about 12 days. The major product of hydrolysis at all pH values was phenthoate carboxylic acid (2), indicating that the carboethoxy moiety was the most susceptible part of the molecule to hydrolysis. Significantly less phenthoate carboxylic acid (2) was produced at pH 6. Quantities of desmethylphenthoate oxon (3) were detected, particularly at pH 7 and 8, but no phenthoate oxon (4), indicating that 3 may have been formed by the oxidative desulfuration of desmethylphenthoate (5) which was a major product, particularly at pH 6. The preponderance of demethylation at lower pH values is found in most hydrolysis studies on organophosphorus esters. Other minor products found were mandelic acid (6), ethyl mandelate (7), bis-[a-(carboethoxy)benzyl] disulfide (8), a-(methylthio) phenylacetic acid (9), desmethylphenthoate carboxylic acid (10) and desmethylphenthoate oxon carboxylic acid (11) in addition to minor products which could not be identified. The ³²P study identified O,Odimethyl phosphorothioate (12) and O,O-dimethyl phosphorodithioate (13) as the hydrolytic products of the phosphorodithioate moiety. It was clear that although the major route of hydrolysis was due to cleavage of the carboethoxy group, phenthoate could also be hydrolysed by three additional mechanisms: (i) by cleavage of the P-O-Me linkage (demethylation) to yield desmethylphenthoate (5); (ii) by P-S bond cleavage to yield O,O-dimethyl phosphorothioate (12) and ethyl mercaptophenylacetate (14) which then dimerised to the disulfide (8); (iii) by C-S bond cleavage to O,O-dimethyl phosphorodithioate (13) and ethyl mandelate (7). The occurrence of α-(methy1thio)phenylacetic acid (9) is most likely explained by methylation of ethyl a-mercaptophenylacetate (14) by phenthoate followed by hydrolysis (see Scheme 1). Reactions involving each of these bonds give rise to a complex array of products, many of which are detected in studies which have investigated the degradation of phenthoate in biological systems.
Takade et al. (1976b) also investigated the photolysis of phenthoate films spread on glass slides which were exposed to natural sunlight for up to 42 hours. Much of the phenthoate was lost by volatilisation as well as photolysis with a DT₅₀ of about 15 hours and 90% disappeared after 42 hours. The principal photoproduct was phenthoate oxon (4) which gradually increased to 20-30% after 35 hours exposure. Minor photoproducts were desmethylphenthoate (5), mandelic acid (6), bis-[α-(carboethoxy )benzyl] disulfide (S), bis-[α-carboxybenzyl] disulfide (15) and O,O-dimethyl phosphorodithioate (13). The pathways for the hydrolytic and photolytic decomposition of phenthoate are shown in Scheme 1.

Acute oral LD₅₀ for rats is 410 mg/kg. Inhalation LC50 (4 h) for rats is 3.17 mg/L air. NOEL (104 w) for dogs is 0.29 mg/kg daily. ADI is 3 μg/kg b.w.

Insecticide; Acaricide