Synthesis,spectral properties and insecticidal,acaricidal and ovicidal activities of some O-(1,5-disubstituted- 6-oxo-12H-pyridazin-4-yl) phosphorothioates

A synthesis of O,O-dialkyl, O-alkyl O-2-chloroethyl (or O-2-ethoxyethyl) O-(1,5-disubstituted-6-oxo-1H-pyridazin-4-yl) phosphorothioates is described. Infrared, Raman and ultraviolet spectra of the compounds prepared are interpreted. The wave-numbers of the v(C? C) bands were correlated with substituent constants. Good linear correlations of v(C? O) with σ, σ^F, σ_I and σ_R were observed for compounds containing various substituents in the neighbourhood of the keto group of the pyridazinone ring. The insecticidal, acaricidal and ovicidal activities of O-(ethyl or isopropyl), O-(alkyl, 2-chloroethyl, or 2-ethoxyethyl) O-(5-methoxy-1-methyl-6-oxo-1H- pyridazin-4-yl) phosphorothioates, O-ethyl O-isopropyl O-(5-methoxy-1-substituted-6-oxo-1H-pyridazin-4-yl) phosphorothioates and O-ethyl O-isopropyl O-(1-methyl-5-substitutedd-oxo-1H-pyridazin-4-yl) phosphorothioates are reported together with the toxicity of some of these compounds to rats.     

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.     

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.     

The optical isomers of α-cyano-3-phenoxybenzyl 3-(1,2-dibromo-2,2-dichloroethyl)-2,2-dimethylcyclo-propanecarboxylate and their insecticidal activities

Bromination of the dichlorovinyl group of cypermethrin yielded a new compound which is a highly potent insecticide. This dibromo adduct has four asymmetric centres and therefore can exist as a mixture of 16 stereoisomers. To establish the influence of the absolute configuration at the chiral centres on the biological activities of these isomers, each of the isomers was isolated; their insecticidal activities against larvae of Heliothis virescens, and adult Calliphora erythrocephala and Blattella germanica were then determined and compared with those of (S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (deltamethrin NRDC 161), of fenvalerate, and of the eight stereoisomers of cyper methrin.     

Synthesis and insecticidal activity of 3-(haloalkyl-1,3-dienyl)-2,2-dimethylcyclopropanecarboxylates

New 2,2-dimethylcyclopropanecarboxylic acids bearing halogenated 1,3-alkadienyl substituents at position 3 of the cyclopropane ring were synthesised and the insecticidial activities of their 3-phenoxybenzyl and α-cyano-3-phenoxybenzyl esters against housefly (Musca domestica), Colorado potato beetle (Leptinotarsa decemlineata) and Egyptian cotton leafworm (Spodoptera littoralis) were determined. The activity of these compounds varied according to the relative position of the halogen substituents on the diene chain. The observed changes of activity with the structure of the side chain are discussed in terms of the coplanarity of the conjugated double bonds.     

In-vitro metabolism of O,O-diethyl S-(N-methylcarbamoylmethyl) phosphorodithioate by mouse liver

The in-vitro metabolism of O,O-diethyl S-(N-methylcarbamoymethyl) phosphorodithioate in mouse liver was studied. The major route of metabolism was via the mixed-function oxidases present in the microsomal fraction, which formed the oxygen analogue, O,O-diethyl hydrogen phosphorothioate and diethyl hydrogen phosphate upon addition of nicotinamide-adenine dinucleotide phosphate (NADPH). In the absence of NADPH, the carboxylic acid analogue (S-carboxymethyl O,O-diethyl phosphorodithioate) was isolated only from the microsomal fraction. Addition of glutathione to the 100 000 g supernatant resulted in no metabolism of the parent compound. However, addition of glutathione to the 10 000 g supernatant resulted in the carboxylic acid formed by amidase activity being further metabolised to O,O-diethyl hydrogen phosphorodithioate by a glutathione-dependent reaction.     

Comparison of symptomatic and neurophysiological activities of enantiomers of the insecticide 3-phenoxybenzyl 1-(4-ethoxyphenyl)-2,2-dichlorocyclopropane-1-carboxylate

The insecticidal activities of optical isomers of 3-phenoxybenzyl 1-(4-ethoxyphenyl)-2,2-dichlorocyclopropanecarboxylate and related compounds were measured with American cockroaches and their knockdown activities were evaluated with house flies. The activities of the S(?)-isomer of the dichlorocyclopropanecarboxylate were higher than those of the R(+)-isomer. The effects of the compounds on the inward membrane currents induced by a stepdepolarizing pulse in crayfish axonal membranes were examined under voltage clamp conditions by the sucrose gap method. The compounds induced a tail current upon step repolarization of the membrane. The tail current decayed to zero in each record, but developed with time after the start of application of the compound until a steady level was reached. The rate of decay of the tail current observed in axonal membranes treated with the S(?)-isomer was slower than with the R(+)-isomer. The rates of development of the tail current induced by the two isomers were not very different.     

7-(1-酰基哌嗪-4-基)甲基喜树碱衍生物的合成及杀虫活性

以(20S)-喜树碱(CPT)为原料,根据类同合成法和亚结构连接法原理,对CPT的7-C位进行修饰,得到了系列新型7-(1-酰基哌嗪-4-基)甲基喜树碱衍生物(4a~4m),所有衍生物的结构均通过核磁共振氢谱(1H NM R)和液-质联用(LC-M S)等方法确证;并初步测定了其对朱砂叶螨Tetranychus cinnabarinus和松材线虫Bursaphelenchu xylophilus的室内杀虫活性。结果表明:与喜树碱相比,各衍生物均表现出不同程度的杀虫活性,其中化合物7-[1-(4-甲氧基苯酰基)哌嗪-4-基]-甲基喜树碱(4g)和7-(1-环戊酰基哌嗪-4-基)-甲基喜树碱(4j)对朱砂叶螨24 h的半数致死浓度(LC50值)分别为8.10和9.05 mg/L,对松材线虫的LC50值分别为6.34和6.68 mg/L。研究结果可为喜树碱衍生物杀虫活性构效关系研究奠定基础。     

含4-正庚/正辛氧基苯基杂环化合物的设计、合成及生物活性

通过研究苯甲脒类抑制剂与酮醇酸还原异构酶(KARI)对接的结合模式,设计合成了一系列含正庚氧基及正辛氧基苯基的杂环化合物。用核磁共振氢谱、红外光谱、质谱及元素分析对26个目标产物(其中22个是新化合物)的结构进行了表征和确认。初步生物活性测试结果表明,目标化合物大多具有不同程度的水稻KARI酶抑制活性和除草活性,其中化合物 9a和9b 在200 μg/mL浓度下对KARI酶的抑制率分别为65.7%和71.1%,在100 μg/mL浓度下对双子叶植物油菜Brassica campestris的抑制率分别达78.6%和89.0%。     

Systemic fungicidal and insecticidal activities of 1- and 2-[bis (dimethylamido)phosphoryl]-3-alkyl-5-anilino-1,2,4-triazoles

The compounds referred to in the title have been investigated for fungicidal, insecticidal and acaricidal activities in laboratory and greenhouse tests. Several representatives of this class of compounds were active against powdery mildew on apple, cucumber, and barley, and against aphids and spider mites, both when applied to the leaves and when added to the nutrient solutions of test plants. Treatment of leaf halves resulted in protection of the entire leaves. A striking difference in pesticidal activity was observed between two series of isomers. Representatives of the series with the phosphoryl group in the 1-position showed much greater pesticidal activities than their corresponding isomers with the phosphoryl group in the 2-position. The optimum activity within the two homologous series (R-H, CH₃ ... C₆H₁₃) was determined: generally the lower homologues (R-H, CH₃, C₂H₅ and i-C₃H₇) showed the greatest pesticidal activity in the systemic tests. After leaf-application the influence of the length of R was less pronounced or even reversed.Samenvatting De in de titel genoemde stoffen zijn onderzocht op fungicide, insecticide en acaricide werking in laboratorium en kasproeven. Verscheidene vertegenwoordigers van dit type verbindingen waren werkzaam tegen echte meeldauw van appel, komkommer en gerst, en tegen bladluizen en spint, dit zowel na toepassing op de bladeren als na toevoeging aan de voedingsoplossingen van proefplanten. Behandeling van bladhelften resulteerde in bescherming van de gehele bladeren. Een opvallend verschil werd waargenomen tussen de werking van twee reeksen isomeren. Vertegenwoordigers van de reeks met de fosforylgroep op de 1-plaats waren veel werkzamer dan hun isomeren met de fosforylgroep op de 2-plaats. Het optimum binnen de twee homologe reeksen (R-H, CH₃ ... C₆H₁₃) werd bepaald: in het algemeen waren de lagere homologen (R-H, CH₃; C₂H₅ en i-C₃H₇) het werkzaamst in de systemische proeven. Na een preventieve bladbespuiting was de invloed van de lengte van R minder uitgesproken of zelfs omgekeerd.     

The pyrethrins and related compounds. XIX Geometrical and optical isomers of 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarboxylic acid and insecticidal esters with 5-benzyi-3-furylmethyi and 3-phenoxybenzyl alcohols

Esters of 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarboxylic acid with appropriate alcohols are more active insecticides than the corresponding 3-isobutenyl compounds (chrysanthemates). (±)-Cis and (±)-trans forms of the dichloro acid are obtained by fractional crystallisation of the mixed acids or by hydrolysis of the ethyl esters separated by fractional distillation. The (±)-cis and (±)-trans acids are resolved into their (+)- and (-)-forms with α-methyl-benzylamine and threo-l-p-nitrophenyl-2-N,N-dimethyiamino-propane-1,3-diol respectively. As for the corresponding chrysanthemates, the (+)-cis and (+)-trans acids give esters more active as insecticides than their enantiomers.     

Stereochemical and chiral aspects in the synthesis of 3-(2,2- dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids

The synthesis of (1RS)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid by dehydrohalogenation of 4,6,6,6-tetrahalohexanoates has been modified to produce stereo-selectively the cis-isomer. A new stereospecific synthesis of cis-3-(2,2-dihalovinyl)-2,2-dimethylcyclopropanecarboxylic acids using a bicyclic lactone and its extension to the preparation of the optically active (1R)-cis acid are described.     

The synthesis of 3-(2,2-Dichlorovinyl)-1- methylcyclopropane-1,2-dicarboxylic acid

3-(2,2-Dichlorovinyl)-1-methylcyclopropane-1,2-dicarboxylic acid, a metabolite of the pyrethroid insecticide permethrin, has been synthesised as a mixture of isomers, in four stages, in high overall yield.     

Synthesis and insecticidal activity of 4-perhaloalkoxy (or thioalkyl) benzophenonehydrazone derivatives

Benzophenonehydrazone derivatives containing a mesylate or triflate substituent are known to exhibit insecticidal activity. In the present study, such substituents have been replaced by perhaloalkoxy groups. High levels of activity against lepidopteran pests were observed in greenhouse trials. For optimum activity, the substituents should be relatively small. In semi-field trials, however, none of the compounds tested showed sufficient persistence to warrant further development.     

新型七氟异丙基取代2,2-二氟-1,3-苯并二氧-5-乙酰胺衍生物的合成与杀虫活性

为探索环境友好新型农药先导化合物,通过水相中酰胺缩合反应合成了16个未见文献报道的七氟异丙基苯基取代的2,2-二氟-1,3-苯并二氧-5-乙酰胺类目标化合物。其结构通过核磁共振氢谱、氟谱以及高分辨质谱确认。初步生物活性测定表明,部分目标化合物对蚕豆蚜虫和粘虫表现出良好的杀虫活性,初步构效关系显示苯环上取代基的种类和位置在化合物的杀虫活性中起关键作用。     

Stereoselectivity of acetylcholinesterase,arylester hydrolase,and chymotrypsin toward 4-nitrophenyl alkyl(phenyl)phosphinates

Acetylcholinesterases from electric eel and from bovine erythrocytes were inhibited stereoselectively by P(+) 4-nitrophenyl ethyl(phenyl)phosphinate (EPP) and P(+) 4-nitrophenyl isopropyl(phenyl)phosphinate (IPP). Bovine pancreatic α-chymotrypsin was inhibited stereoselectively also, but the P(−) enantiomers of both EPP and IPP were more active than P(+). Arylester hydrolase was nine times more active in the hydrolysis of P(−) EPP than P(+). Chiral-phase HPLC was employed to isolate the enantiomers from racemic mixture for experiments and to analyze reaction mixtures initiated with racemic EPP or IPP.     

Synthesis and insecticidal and acaricidal activity of new N-(α-substituted phenoxybenzyl)-4-pyrimidinamines

A new class of insecticides and acaricides containing N-(α-substituted phenoxybenzyl)-4-pyrimidinamines as core structure were synthesized and their insecticidal and acaricidal potencies assessed. Among these, both the N-(3 or 4-phenoxybenzyl)-4-pyrimidinamine showed remarkable activity against diamondback moth, Plutella xylostella L., brown rice planthopper, Nilaparvata lugens (Stal) and two-spotted spider mite, Tetranychus urticae Koch. The potency of the new pyrimidinamines was particularly increased when a methyl, ethyl, iso-propyl, or cyclopropyl group was introduced at the α-position of benzyl moiety and it was evident that a single (+) optical isomer is more active than its antipode. Structure-activity relationships are discussed.     

Synthesis and herbicidal activities of novel 3-(substituted benzyloxy or phenoxy)-6-methyl-4-(3-trifluoromethylphenyl)pyridazine derivatives

BACKGROUND: 4‐(3‐Trifluoromethylphenyl)pyridazine represents a new series of compounds with bleaching and herbicidal activities. RESULTS: A total of 43 novel 3‐(substituted benzyloxy or phenoxy)‐6‐methyl‐4‐(3‐trifluoromethylphenyl)pyridazine derivatives were synthesised, and their bleaching and herbicidal activities were evaluated through Spirodela polyrrhiza and greenhouse tests. Some compounds exhibited excellent herbicidal activities, even at a dose of 7.5 g ha^?1. CONCLUSION: The results showed that a substituted phenoxy group at the 3‐position of the pyridazine ring and the electron‐withdrawing group at the para ‐position on the benzene ring were essential for high herbicidal activity. Copyright © 2011 Society of Chemical Industry     

Degradation of the insecticide SD 8280, 2-chloro-1-(2, 4-dichlorophenyl)vinyl dimethyl phosphate,in soils

The degradation of the insecticide SD 8280 [2-chloro-1-(2,4-dichlorophenyl)vinyl dimethyl phosphate] in soil has been examined under laboratory conditions using two soils from rice-growing areas in Japan and one UK soil. In all soils SD 8280 underwent degradation to 1-(2,4-dichlorophenyl)ethanol, 2,4-dichlorobenzoic acid, 2-chloro-1-(2,4-dichlorophenyl)vinyl methyl hydrogen phosphate and 2′,4′-dichloro-acetophenone. These degradation products were present in the soils as free (extractable) compounds and as bound forms and soil binding occurred most extensively with 2,4-dichlorobenzoic acid. Polar products were also formed and these appeared to be in part the result of complexing of degradation products with the soil organic matter. The effect on the degradation of the insecticide of varying the moisture content of one soil was also examined. In soil incubated at 11, 17, 30 and 62% moisture the recovery of SD 8280 after 60 days was 71.0, 12.3, 9.0 and 11.3%, respectively. Although the rate of degradation varied, the same degradation products were detected in all samples.     

Synthesis and plant growth regulating properties of derivatives of alkyl 3-benzoyl-3-(3-chloro-4-substituted phenyl)-2-methylcarbazates

Alkyl 3-benzoyl-3-(3-chloro-4-substituted-phenyl)-2-methylcarbazates (isoelectronic analogues of wild oat herbicides) have plant growth regulating properties for various weeds and crops. Some derivatives of carbazates, bearing halogen in the 4-position of the phenyl group, have been shown to have the highest activity of the prepared compounds.