The structure and properties of O-ethyl O-isopropyl O-(5-methoxy-1-methyl-6-oxo-1H-pyridazin-4-yl) phosphorothioate and by-products in the technical product

The structure and some chemical and physical properties of a new insecticide O-ethyl O-isopropyl O-(5-methoxy-1-methyl-6-oxo-1H-pyridazin-4-yl) phosphorothioate ( I ) and by-products present in the technical product are described. The structures of I and the by-products were proved by infrared, ultraviolet, ¹H-n.m.r., Raman and mass spectrometry.     

O-ethyl O-isopropyl O-(5-methoxy-1-methyl-6-oxo-1H-pyridazin-4-yl) phosphorothioate,a new experimental insecticide and acaricide

The insecticidal and acaricidal action, anti-cholinesterase activity and toxicity to rats of a new experimental pesticide, O-ethyl O-isopropyl O-(5-methoxy-1-methyl-6-oxo-1H-pyridazin-4-yl) phosphorothioate ( I ), and those of some by-products found in the technical material, are described. High insecticidal and acaricidal effectiveness of I was found in laboratory and field trials. The activity as a soil insecticide in field trials was equal to, or greater than, that of other chemicals used at present.     

Synthesis and insecticidal and acaricidal properties of some 5-methoxy-1-methyl-6-oxo-1H-pyridazin-4-yl phosphorus esters. III

A series of new 5-methoxy-1-methyl-6-oxo-1H-pyridazin-4-yl phosphorus esters, which was prepared by phosphoroylation of 5-methoxy-1-methyl-6-oxo-1H-pyri-dazin-4-ol, is described. Many of the compounds showed high insecticidal and acaricidal activity.     

Synthesis,insecticidal and acaricidal properties of some 5-alkoxy-, 5-alkylthio-6-oxo-1-phenyl-1H-pyridazin-4-yl and 6-oxo-5-phenoxy-1-phenyl-1H-pyridazinyl phosphorus esters. II

A series of novel 5-alkoxy-, 5-alkylthio-6-oxo-1-phenyl-1H-pyridazin-4-yl and 6-oxo-5-phenoxy-1-phenyl-1H-pyridazin-4-yl phosphorus esters was prepared from the corresponding alkali pyridazin-4-olates and their insecticidal and acaricidal activities studied. Many of the compounds, especially the diethyl and dimethyl phosphates and OO-diethyl and OO-dimethyl phosphorothioates, showed high insecticidal and acaricidal activity.     

The insecticidal and anticholinesterase activities of O,O-diethyl O-4-(2,2-disubstituted vinyl)phenyl phosphates and phosphorothioates

A series of O,O-diethyl O-4-(2,2-disubstituted-vinyl)phenyl phosphorothioates and phosphates was synthesised and examined for anticholinesterase activity to housefly and bovine erythrocyte ChE, and also for their toxicity to Musca domestica and Triatoma infestans. The synthesised phosphates were potent anticholinesterases and stronger inhibitors of housefly acetylcholinesterase than bovine erythrocyte acetyl-cholinesterase. Satisfactory correlation was obtained between the anticholinesterase activity and the Hammett σ^? constants against both enzymes, but it was not significantly improved by introducing a term for the Hansch π constant. The phosphorothioates showed poor and variable toxicity to M. domestica. On T. infestans, the only compound that showed some toxicity was the di(acetyl)-substituted product [O-4-(2-acetyl-3-oxobut-1-enyl)phenyl O,O-diethyl phosphorothioate]. For comparative studies, some commercial products were also assayed on T. infestans.     

A novel series of O,O-diethyl O-(1,3-disubstituted-1,2,4-triazol-5-yl) phosphorothioates. Part I. Synthesis and laboratory evaluation

A novel series of O,O-diethyl O-(1-R′-3-R″-1,2,4-triazol-5-yl) phosphorothioates, in in which R″ was an alkyl group and R″ was a radical characterised by the presence of a conjugated multiple bond, generally of a vinyl nature, has been synthesised and tested in the search for new insecticides. Several of the compounds showed a broad spectrum of activity, covering important species of Orthoptera, Hemiptera, Lepidoptera, Coleoptera, Diptera and mites. At the same time they were characterised by a relatively low oral toxicity to rats.     

Studies on residues and the metabolic pathway of methidathion in tomato fruit

The residues and metabolism of methidathion [S-(2, 3-dihydro-5-methoxy-2-oxo-1, 3, 4-thiadiazol-3-ylmethyl) O, O-dimethyl phosphorodithioate] and its secondary metabolites: demethyl-methidathion [S-(2, 3-dihydro-5-methoxy-2-oxo-1, 3, 4-thiadiazol-3-ylmethyl) O-methyl O-hydrogen phosphorodithioate] ( IV ), the sulphide (2,3-dihydro-5-methoxy-3-methylthiomethyl-1,3,4-thiadiazol-2-one) ( I ), tsulphoxide(2,3-dihydro-5-methoxy-3- methylsulphinylmethyl-1,3,4-thiadiazol-2-one) ( II ) and the sulphone (2,3-dihydro-5-methoxy-3-methylsulphonylmethyl-1,3,4-thiadiazol-2-one ( III ) were studied in laboratory-treated tomato fruit. The metabolites and residues of methidathion were determined for the applied doses of 1, 7 and 14 mg of methidathion kg^?1 of fruit. Methidathion was metabolised extensively over a 14-day period. The amount of metabolites formed was a function of both the applied dose as well as the time after application. Major water-soluble metabolites were found to be IV and the cysteine conjugate S-(2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl)-L-cysteine ( VI ). The chloroform-soluble metabolites were identified as the oxygen analogue of methidathion [S-(2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl) O, O-dimethyl phosphorothioate] ( V ), the sulphoxide II , and the hydroxy compound 2,3-dihydro-3-hydroxymethyl-5-methoxy-1,3,4-thiadiazol-2-one. The oxygen analogue of methidathion ( V ) was found in small amounts, corresponding to <5% of the added methidathion. Demethyl-methidathion ( IV ) appeared to be a precursor in the formation of the cysteine conjugate VI . The sulphide I seemed to be more reactive in forming the cysteine conjugate than the sulphoxide II or the sulphone III .     

Quantitative bioassays for determining residues and availability to plants of sulphonylurea herbicides

A bioassay procedure for quantitative determination of sulphonylurea herbicides is described. Turnips (Brassica rapa) were found very suitable as test plants and gave results within 10 days. Six sulphonylurea compounds were investigated for their activity in three widely differing soils. The potential availability to plants was calculated from the dose-response curves of vermiculite (non-sorptive substrate) and the corresponding ED₅₀-values of the soils. The dose-response relationship (logistic curve) was described by a computer model by a position parameter, the slope of the curve and the minimum and maximum fresh weights of plants. The limit of quantitative detection in the range of ED₃₀ in vermiculite was 0·06 μg 1^?1 for sulfometuron and 1·03 μg 1^?1 for DPX-L5300, methy12-([4-methoxy-6-methyl-1,3,5-triazin-2-yl (methyl)carbamoyl]-sulphamoyl) benzoate. Results with turnips showed that sulfometuron was the most active compound in all substrates (ED₅₀ in vermiculite 0·12 μg 1^?1) followed by chlorsulfuron, metsulfuron-methyl, triasulfuron, DPX-M6316, methyl 3-([(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbamoyl]-aminosulphaphamoyl)-2-thiophenecarboxylate, and DPX-L5300 which had ED₅₀ or 1·98 μg 1^?1, The Horotiu sandy loam soil showed the highest ED₅₀-values and the lowest plant availability for all compounds compared to the other soils. Probit and logistic evaluation methods for deriving dose-response relationships are compared and their applicability is discussed.     

The absolute configuration of chiral organophosphorus anticholinesterases

Contrary to an earlier report in this journal by Wustner and Fukuto (1), bovine erythrocyte acetylcholinesterase is inhibited preferentially by the same (S)_P-isomers of the two closely related anticholinesterases O-2-butyl S-2-(dimethylammonium)-ethyl ethylphosphonothioate hydrogen oxalate(I) and O-isopropyl S-2-(trimethylammonio)ethyl methylphosphonothioate iodide(II).     

A novel series of O,O-diethyl O-(1,3-disubstituted-1,2,4-triazol-5-yl) phosphorothioates. Part II. Quantitative structure–activity relationships

The in-vivo toxicity data of 33 O,O-diethyl O-(1-alkyl-3-R″-1,2,4-triazol-5-yl) phosphorothioates, reported in Part I of this series, were subjected to multiregression analyses for the following organisms: Leptinotarsa decemlineata (larvae), Macrosiphum euphorbiae (aphids), Culex pipiens (adults), Spodoptera littoralis (larvae) and the rat. The activities were found to depend mainly on the steric parameters of R″, these being best expressed by the values L, B₁ and B₄ of the computer program STERIMOL. It was shown that there were different steric requirements for each species and these are discussed. The predictive values of the best equations were also estimated.     

Light-induced transformations of tribenuron-methyl in aqueous solution

Tribenuron-methyl a sulfonylurea herbicide, readily photodegraded in aqueous solution under sunlight and UV light. The photoproducts identified were N-methyl-4-methoxy-6-methyl-1,3,5-triazine-2-amine, methyl 2-(aminosulfonyl) benzoate, o-benzoic sulfimide, N-(4-methoxy-6-methyl1,3,5-triazin-2-yl)-N-methyl urea and N-(2-carbomethoxyphenyl)-N-(4-methoxy-6-methyl-1,3,5triazin-2-yl)-N′-methyl urea. The rate of photodegradation of tribenuron-methyl in different types of water followed first-order kinetics with significant correlation coefficient, increased with increase in pH and was also dependent upon the dissolved impurities. © 1999 Society of Chemical Industry     

嘧啶联吡唑甲酰胺类化合物的合成及除草活性

设计合成了一系列结构新颖的嘧啶联吡唑甲酰胺类化合物5a~5o,其结构均经过1H NM R和MS分析确证。初步生物活性测试结果表明:在有效成分150 g/hm2剂量下苗后茎叶喷雾处理时,化合物(R)-N-[1-(4-氯苯基)乙基]-3-二氟甲基-1-(4,6-二甲氧基嘧啶-2-基)-1H-吡唑-4-甲酰胺(5c)、N-[1-(4-氯苯基)乙基]-1-(4,6-二甲氧基嘧啶-2-基)-N-甲基-3-三氟甲基-1H-吡唑-4-甲酰胺(5i)和N-[1-(4-氯苯基)乙基]-1-(4,6-二甲氧基嘧啶-2-基)-3-三氟甲基-1H-吡唑-4-甲酰胺(5k)对繁缕Stellaria media的抑制率高达90%以上;而同样剂量下苗前土壤喷雾处理时,化合物N-[1-(4-氯苯基)乙基]-3-二氟甲基-1-(4,6-二甲氧基嘧啶-2-基)-1H-吡唑-4-甲酰胺(5b)和5c对繁缕的抑制率达100%。该类结构化合物有望作为除草先导化合物进行开发。     

Photolysis of organophosphorus insecticides on soil surfaces

Photolysis on soil surfaces of the organophosphorus insecticides diazinon, methidathion and profenofos was studied under artificial sunlight conditions. All three compounds were readily degraded under the conditions used. The rate of degradation decreased in the order diazinon, profenofos, methidathion and was always greater in moist than in dry soil. The same order of stability was also observed from photolysis studies in aqueous solution. The major photolysis products identified were 2-isopropyl-6-methylpyrimidin-4-ol from diazinon, 5-methoxy-3H-1,3,4-thiadiazol-2-one from methidathion and 4-bromo-2-chlorophenol and 4-bromo-2-chlorophenyl ethyl hydrogen phosphate from profenofos. The same compounds were formed in hydrolysis studies and also upon photodecomposition in aqueous solutions of diazinon and methidathion. Profenofos, however, showed a different photolytic reaction in aqueous systems, forming O-(2-chlorophenyl) O-ethyl S-propyl phosphorothioate. Soil photolysis studies together with hydrolysis experiments could be a useful quick method for obtaining early information on the chemical breakdown products which are to be expected in the soil environment.     

Root absorption and translocation of 5-substituted analogs of the imidazolinone herbicide,imazapyr

In preparation for assessing quantitative structure-activity relationships (QSAR) for root absorption and translocation of imidazolinones herbicides, 13 radiolabeled analogs of imazapyr (2-(4-isopropyl–4-methy1–5-oxo-2-imidazolin-2-yl) nicotinic acid) substituted in the 5-position of the pyridine ring were evaluated in corn (Zea mays L.) and sunflower (Helianthus annuus L.). The compounds (10 μm) were supplied to the roots through a hydroponic solution for 8 h and, following harvest, plant tissues were either combusted to measure total uptake of radiolabeled material or were extracted for determination of the extent of degradation of the parent compound. Root absorption in both species varied by two orders of magnitude among analogs while translocation, expressed as a percentage of absorption, varied by only three- or four-fold. Few differences were observed for translocation of radioactivity from sunflower stems to leaves. Although six of the analogs were partially metabolized in corn, little metabolism of the imidazolinone analogs occurred in sunflower. These data indicate that meaningful models of root absorption and subsequent translocation to shoots may be developed for 5-substituted analogs of imazapyr, particularly when applied to sunflower.     

Pyrazole phenyl ether herbicides inhibit protoporphyrinogen oxidase

Two isomeric pairs of pyrazole phenyl ether herbicides [AH 2.429, 4-chloro-1-methyl-5-(4-nitrophenoxy)-3-(trifluoromethyl)-1H-pyrazole; AH 2.430, 4-chloro-1-methyl-3-(4-nitrophenoxy)-5-(trifluoromethyl)-1H-pyrazole; AH 2.431, 5-((4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)oxy)-2-nitrobenzoic acid; and AH 2.432, 5-((4-chloro-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)oxy)-2-nitrobenzoic acid were evaluated for herbicidal activity in both intact plants and in tissue sections. Their capacity to induce accumulation of porphyrins in tissue sections and to inhibit protoporphyrinogen oxidase (Protox) in vitro were determined. In whole plant tests, the order of herbicidal activity was AH 2.430 AH 2.431 > AH 2.429 > AH 2.432. AH 2.430 consistently caused light-dependent membrane leakage in both green and far-red light grown cucumber cotyledon and barley primary leaf tissue sections after incubation for 20 hr in darkness in 0.1 mM solutions. The same treatment caused marked increases in protoporphyrin IX (PPIX) content during the 20-hr dark incubation. AH 2.429 and 2.431 were less effective and not effective in all tissues in causing herbicidal damage and PPIX accumulation. AH 2.432 was ineffective in tissue section assays. Mg-PPIX levels were not significantly affected by any of the compounds. Protochlorophyllide levels were decreased by AH 2.430 and 2.431 in barley and increased by AH 2.429, 2.431, and 2.432 in cucumber. A positive relationship was found between herbicidal activity and the amount of PPIX that was caused to accumulate by each compound. All of the compounds inhibited Protox activity. Positive correlations were found between herbicidal activity in planta over a 300-fold range and in vitro Protox inhibition and the amount of PPIX caused to accumulate in vivo. These data support the view that the pyrazole phenyl ethers exert their herbicidal activity entirely through inhibition of Protox.     

Joint action of root-absorbed mixtures of DPX-4189* and linuron in Sinapis alba L. and barley

The joint action of DPX-4189* (2 chloro-N-[(4-methoxy-6-methyl-1, 3, 5-triazin-2-yl)-aminocarbonyl] benzenesulfonamide) and linuron (N-[3, 4-dichlorophenyl]-N-methoxy-N-methylurea) mixtures, applied in fixed ratios of 1:15 and 1:30, was assessed using water culture experiments in growth chambers. The dose-response curves of DPX-4189 were fiat compared with these of linuron. At Gr₅₀-level (the dose required to reduce dry matter by 50% relative to the untreated control), DPX-4189 was 12-fold more potent in Sinapis alba than was linuron, whereas the potencies of the two compounds were almost similar in barley. The selectivity indices (Gr₈₀[barley]/Gr₂₀[S. alba]) of DPX-4189 and linuron were 3.1 and 1.8. In both species the mixtures were less active than expected from an additive dose model, and the detracted efficacy of the mixtures was of almost similar magnitude. The results indicated that if S. alba is regarded a weed, the loss of bioactivity of the mixtures may be compensated by some increase in dose rate without injuring the barley crop.     

吡啶联三唑类衍生物的合成及杀虫活性

以3-氨基-2-氯吡啶(1)为起始原料,经重氮化、叠氮化、环合和酰氯化反应,生成1-(2-氯吡啶-3-基)-5-甲基-1H-1,2,3-三唑-4-甲酰氯(5),(5)与取代苯胺反应,制得13个未见文献报道的吡啶联三唑类化合物,其结构通过 1H NMR和LC-MS表征。初步生物活性测定结果表明:在500 mg/L质量浓度下,所有目标化合物对粘虫 Mythimna separate 均有一定的杀虫活性,部分化合物致死率达100%;但在100 mg/L下,除化合物ZJ-7的致死率仍达100%外,其余化合物的活性明显降低,甚至无活性。     

Quantification of GST and esterase activities in pyrethrin-resistant mosquitoes using pyrethroid-like fluorescent substrates

Botanical pyrethrins and synthetic pyrethroids are highly potent and environmentally safe insecticides that are used to control a wide range of disease vector and pest arthropods. Unfortunately, resistance to these insecticides has been demonstrated in numerous medically important mosquito species. In this study, adult Culex pipiens sensu lato were captured in agricultural and urban locations in Fresno County, California, and subsequently exposed to a commercial formulation of pyrethrin insecticide by ultra-low-volume spraying. Following insecticide exposure, two pyrethroid-like, fluorescent substrates (4-methyl-2-oxo-2H-chromen-6-yl, cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (cis-DCVC) and 4-methyl-2-oxo-2H-chromen-6-yl, cis-3-((Z)-2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate (cis-TFMCVC)) and 1-chloro-2,4-dinitrobenzene (CDNB) were used to measure esterase and glutathione S-transferase (GST) activities in surviving mosquitoes. Elevated esterase activity (2.5-fold) was found in surviving urban mosquitoes at 12-h post-pyrethrin exposure (in comparison to non-insecticide-exposed control mosquitoes) when cis-TFMCVC was used as a substrate. Additionally, when CDNB was used as a substrate, 2.8-fold higher GST activity was found. A simple assay was established using our pyrethroid-like, fluorescent substrates that was able to detect low-level esterase activities in homogenates made from individual mosquitoes. The cis-TFMCVC-based assay suggested that esterase activity plays a role in pyrethrin resistance in urban mosquitoes in California.     

Preparation of some novel phosphonamidates,their phytotoxicity and herbicidal properties

Fourteen new O-phenyl/4-chlorophenyl-N-alkyl/aryl-2-chloroethyl phosphonamidates have been prepared and screened for their phytotoxicity towards monocotyledonous (wheat) and dicotyledonous (mustard) plants and herbicidal activity against wild oat. O-Phenyl-N-propyl-2-chloroethyl phosphonamidate was found to be the most phytotoxic (pre-emergence) and also possessed herbicidal properties. Wheat showed maximum resistance to most of the compounds (post-emergence). N-propyl-4-chlorophenyl-2-chloroethyl phosphonamidate was the least active molecule. © 1998 SCI.     

Differential Metal Binding Interactions of the Imidazolinones Revealed by NMR and UV Spectroscopy

NMR and UV spectroscopy and molecular modeling methods were applied to probe the interaction of the two imidazolinones, imazethapyr (5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid) and its structural isomer CL 303,135 (5-ethyl-3-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)picolinic acid), with metal ions. Both the imidazolinones inhibit the enzyme acetohydroxyacid synthase (AHAS) in vitro. However, while imazethapyr is a herbicide that is used widely in agriculture, CL303,135 does not exhibit herbicidal activity. Imazethapyr and CL303,135 exhibited considerable differences in their interactions with metals. In the metal complex of imazethapyr, the carboxyl moiety binds strongly and the pyridine nitrogen binds weakly with metals. In the case of CL303,135, both the pyridine nitrogen and the carboxyl group that are positioned ortho to each other participated strongly in the binding and were found to act together as a strong bidentate ligand to a metal ion. Both of the imidazolinones form predominantly 2:1 complexes with multivalent metal ions. However, imazethapyr binds two orders-of-magnitude more weakly (1·0×10⁹ M ^-2) with metal ions compared to CL303,135 (1·7×10¹¹ M ^-2). The interactions of the model compounds, nicotinic acid and picolinic acid, with metals were examined similarly. It was concluded that the strong affinity of CL303,135 for metals compared to imazethapyr may affect its absorption from soil into plants, or its translocation in plants, thereby explaining the differences in herbicidal activity of imazethapyr and CL303,135. © 1997 SCI.