The discovery of pyridalyl: a novel insecticidal agent for controlling lepidopterous pests

Synthesis of analogues of two compounds with known insecticidal activity, both of which contain a 3,3-dichloro-2-propenyloxy group, produced 2-(trifluoromethyl)-4-phenoxyphenyl 3,3-dichloro-2-propenyl ether, which had weak activity against lepidopterous larvae. Structural modifications around this lead compound led to the development of pyridalyl [Pleo, S-1812; 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether], which belongs to a new class of insecticides. Pyridalyl gives very good control of various lepidopterous and thysanopterous pests on cotton and vegetables, without phytotoxicity. It controls populations of Heliothis virescens F and Plutella xylostella (L) which are resistant to various currently used insecticides. It also produces unique insecticidal symptoms, so it may have a different mode of action from other existing insecticides. Pyridalyl is also less harmful than existing insecticides to various beneficial arthropods, so it should provide an important tool in IPM and insecticidal management programmes for the control of lepidopterous and thysanopterous pests. The first market introduction is expected in Japan and some Asian countries in the years between 2004 and 2005.     

新型含吡唑杂环邻氨基苯甲酰胺类化合物的合成与杀螨活性

以氯虫苯甲酰胺和氟虫腈的结构为基础,通过活性亚结构拼接的方法,设计合成了24个新型含吡唑杂环邻氨基苯甲酰胺类化合物,其结构经1H NM R、IR及APCI-M S表征。初步生物活性测试结果表明:化合物5-溴-N-[4-氯-2-甲基-6-(甲氨基甲酰基)苯基]-1-1-[2,6-二氯-4-(三氟甲基)苯基]-4-三氟甲基亚磺酰基-1H-吡唑-3-甲酰胺(5k)和5-溴-N-[4-溴-2-甲基-6-(甲氨基甲酰基)苯基]-1-[2,6-二氯-4-(三氟甲基)苯基]-4-三氟甲基亚磺酰基-1H-吡唑-3-甲酰胺(5l)在500 mg/L下对朱砂叶螨Tetranychus cinnabarinus的致死率为100%,但在100 mg/L下其致死率则分别降至30%和50%。所得结果可为邻氨基苯甲酰胺类化合物构效关系研究提供参考。     

Design, synthesis, insecticidal activity and structure-activity relationship of 3,3-dichloro-2-propenyloxy-containing phthalic acid diamide structures

BACKGROUND: Phthalic acid diamide derivatives are among the most important classes of synthetic insecticides. In this study, a 3,3‐dichloro‐2‐propenyloxy group, the essential active group of pyridalyl derivatives, was incorporated into phthalic acid diamide derivatives with the aim of combining the active groups to generate more potent insecticides. RESULTS: Thirty‐one new phthalic acid diamides were obtained, and these were characterised by ¹H and ¹³C NMR. The structure of N²‐[1,1‐dimethyl‐2‐(methoxy)ethyl]‐3‐iodo‐N¹‐[4‐(3,3‐dichloro‐2‐propenyloxy)‐3‐(trifluoromethyl)phenyl]‐1,2‐benzenedicarboxamide was determined by X‐ray diffraction crystallography. The insecticidal activities of the compounds against Plutella xylostella were evaluated. The title compounds exhibited excellent larvicidal activities against P. xylostella. Structure‐activity relationships revealed that varying the combination of aliphatic amide and aromatic amide moieties, or the nature and position of substituent Y on the aniline ring, could aid the design of structures with superior performance. CONCLUSION: A series of novel phthalic acid diamides containing a 3,3‐dichloro‐2‐propenyloxy group at the 4‐position of the aniline ring were designed and synthesised. Structure‐activity relationships with the parent structure provided information that could direct further investigation on structure modification. Copyright © 2012 Society of Chemical Industry     

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.     

1,2-Diphenylaziridines as pesticides: Studies on acute toxicity and delayed effects

The insecticidal activities of 15 different 1,2-diphenylaziridines were evaluated. These compounds are readily obtained by photolysis of 1,2,3-triazolines; the latter can be conveniently prepared by the addition of diazomethane to Schiff bases in dioxane in the presence of water. Compounds containing a chloro, bromo or trifluoromethyl group in the para position of the 1-phenyl and a chloro in the ortho position of the 2-phenyl caused acute toxicity in 5th-instar Manduca sexta larvae via both oral and topical routes of exposure. Lower concentrations resulted in delayed effects such as reduced growth rate, pupal and adult malformations and reduced fecundity. When either phenyl group was unsubstituted, the activity was reduced. Unsubstituted 1,2-diphenylaziridine was inactive. Topical applications of l-(4-fluorophenyl)-2-(2-chlorophenyl) aziridine were active against representative species in the insect orders Lepidoptera, Coleoptera and Orthoptera.     

The discovery of HNPC‐A3066: a novel strobilurin acaricide

BACKGROUND: Although more than ten strobilurin analogues have been commercialized since 1996 as fungicides, only one was available as an acaricide as of 2003. To search for novel strobilurin analogues with unique biological activities, a synthetic screening programme was carried out. RESULTS: Syntheses of compounds analogous to the commercialized fungicide metominostrobin and the acaricide fluacrypyrim led to the discovery of a lead compound, (E)‐2‐{2‐[[3,5‐bis(trifluoromethyl)phenoxy]methyl]phenyl}‐2‐(methoxyimino)‐N‐methylacetamide (3b), that showed moderate acaricidal activity against Tetranychus urticae Koch. Compound 3b has a 3,5‐(CF₃)₂‐phenoxymethyl group instead of the unsubstituted phenoxy substituent in metominostrobin. Optimization of compound 3b was achieved by introducing an oxime ether bridge along with an alkylthio(alkyl) branch in place of the oxymethylene chain between two aromatic moieties, as well as by replacing the methoxyiminoacetamide group with a methoxyacrylate structure, leading to (E)‐ methyl 2‐{2‐[[[(Z)[1‐(3,5‐bis(trifluoromethyl)phenyl)‐2‐methylthioethylidene]amino]oxy] methyl]phenyl}‐3‐methoxyacrylate (6c) and (E)‐ methyl 2‐{2‐[[[(Z)[1‐(3,5‐bis(trifluoromethyl)phenyl)‐1‐methylthiomethylidene]amino]oxy]methyl]phenyl}‐3‐methoxyacrylate (9a, HNPC‐A3066). CONCLUSION: The above two compounds (6c, 9a) were shown to exhibit potent acaricidal and fungicidal activity. Compound 9a (HNPC‐A3066) also exhibits larvicidal and ovicidal activities against various acarids. The acaricidal potency is comparable with those of commercial acaricides such as fluacrypyrim, tebufenpyrad and chlorfenapyr. Copyright © 2008 Society of Chemical Industry     

Synthesis and insecticidal activity of novel 1,3,4-oxadiazolin-5-one and pyrazolin-5-one derivatives

A series of novel 2-(2,4,6-trisubstituted phenyl)-1,3,4-oxadiazolin-5-one derivatives and 3-(2,4,6-trichlorophenyl)pyrazolin-5-one derivatives were synthesized and evaluated for insecticidal activity. It was found that a moderately bulky alkyl group, such as a tert-butyl group, on the heterocyclic ring, and a trifluoromethyl group on the benzene ring were optimal substituents on the molecule. The oxygen atom in the oxadiazoline ring was essential for insecticidal activity. Of the compounds assayed, 4-tert-butyl-2-(2,6-dichloro-4-trifluoromethylphenyl)-1,3,4-oxadiazolin-5-one gave the highest activity against Nephtotettix cincticeps, with an LC₅₀ value of 0.51 mg litre⁻¹. © 1999 Society of Chemical Industry     

The importance of trifluoromethyl pyridines in crop protection

The pyridine ring, substituted by a trifluoromethyl substituent has been successfully incorporated into molecules with useful biological properties. During the period 1990 to September 2017, 14 crop protection products bearing a trifluoromethyl pyridine have been commercialized or proposed for an ISO common name, covering fungicides, herbicides, insecticides and nematicides. Chemical processes have been developed to provide trifluoromethyl pyridine intermediates, from non‐fluorinated pyridine starting materials, at scale and with affordable costs of goods. These attractive starting materials were readily adopted by research chemists, and elaborated through simple chemical modifications into new active ingredients. In a second approach, substituted trifluoromethyl pyridine rings have been constructed from acyclic, trifluoromethyl starting materials, which again has served to identify new active ingredients. Molecular matched pair analysis reveals subtle, yet important differences in physicochemical and agronomic properties of trifluoromethyl pyridines compared with the phenyl analogues. This review focuses on the past 27 years, seeking to identify reasons behind the success of such research programmes, and inspire the search for new crop protection chemicals containing the trifluoromethyl pyridine ring. © 2017 Society of Chemical Industry     

Benzpyrimoxan: Design,synthesis, and biological activity of a novel insecticide

Benzpyrimoxan (5-(1,3-dioxan-2-yl)-4-{[4-(trifluoromethyl)phenyl]methoxy}pyrimidine, NNI-1501) was discovered as a novel insecticide structurally characterized by a pyrimidine derivative substituted with 1,3-dioxanyl and 4-trifluoromethylbenzyloxy groups. The compound showed remarkable activity against nymphs of rice planthoppers, including strains resistant to existing insecticides. Furthermore, benzpyrimoxan had low adverse effects on pollinators and beneficial arthropods. Because of these features, benzpyrimoxan is expected to be a suitable part of an integrated pest management strategy. In this report, the history of the discovery to reach benzpyrimoxan and details of the structure–activity relationships are described.     

Synthesis and insecticidal activity of lipophilic amides. Part 1: Introductory survey,and discovery of an active synthetic compound

A group of naturally occurring isobutylamides and related compounds exhibit a range of biological properties including activity against insects. Their potential as a starting point for developing new insecticides, needed to control pests resistant to other classes of insecticides, is discussed, following an extensive survey of known structures and activities. Few of the known compounds were sufficiently active and well characterised to point to sound structure-activity relationships, so synthetic analogues were examined. One of these [(2E,4E)-N-(2-methylpropyl)-6-phenylhexa-2,4-dienamide] was sufficiently active, and prompted the investigations reported here and in subsequent papers in the series. Analogues of this compound designed to establish areas where structural variation is possible are also described.     

Sulfoxaflor and the sulfoximine insecticides: Chemistry,mode of action and basis for efficacy on resistant insects

The sulfoximines, as exemplified by sulfoxaflor ([N-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl]ethyl]-λ⁴-sulfanylidene] cyanamide] represent a new class of insecticides. Sulfoxaflor exhibits a high degree of efficacy against a wide range of sap-feeding insects, including those resistant to neonicotinoids and other insecticides. Sulfoxaflor is an agonist at insect nicotinic acetylcholine receptors (nAChRs) and functions in a manner distinct from other insecticides acting at nAChRs. The sulfoximines also exhibit structure activity relationships (SAR) that are different from other nAChR agonists such as the neonicotinoids. This review summarizes the sulfoximine SAR, mode of action and the biochemistry underlying the observed efficacy on resistant insect pests, with a particular focus on sulfoxaflor.     

The activity of some pyrethroids against Periplaneta americana and Blattella germanica

The knockdown and contact killing actions of various pyrethroids were compared using Blattella germanica and Periplaneta americana. A wide range of knockdown activity was found; 5-benzyl-3-furylmethyl (1R)-cis-3-(dihydro-2-oxo-3-thienylidenemethyl)-2,2-dimethylcyclopropanecarboxylate (RU 15525) acted fastest, more rapidly than pyrethrins, against B. germanica as well as having a low LD₅₀ value. Topical application and direct spray tests showed that (S)-α-cyano-3-phenoxybenzyl (1R)-cir-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (NRDC 161) was more active as a killing agent, by an order of magnitude, than cismethrin, the next most active compound, and also had considerable knockdown activity. Piperonyl butoxide generally had little synergist effect. Female P. americana were over three times more tolerant than males to a range of insecticides applied topically. Residual knockdown action in the WHO resistance test was observed to provide baseline data. There was little overlap in speed of action between pyrethroids and other insecticides among the compounds tested.     

Quantitative structure-activity study of insecticidal 2-methoxy-5-(substituted-phenyl)-1, 3, 2-oxazaphospholidine 2-sulfides against Musca domestica L. by topical application

The quantitative relationship between the structure of 2-methoxy-5-(substituted-phenyl)-1, 3, 2-oxazaphospholidine 2-sulfides (5-PMOS) and their insecticidal activity against the house fly. Musca domestica L., was analyzed using reported physicochemical parameters and regression analysis. The electronic nature of the substituent on the phenyl group of 5-PMOS has the most significant effect on the activity, followed by hydrophobic and steric effects; the optimum value of Σρ is zero and the more hydrophobic the substituents on the phenyl group, the higher the insecticidal activity. The plots of observed pLD₅₀, values against calculated pLD₅₀ values for compounds having substituents in the ortho-position deviated downwards from those of compounds having substituents at the meta and/or para positions. This ortho-effect, which reduces the insecticidal activity of compounds having substituents at the ortho-position, was expressed by a dummy parameter D, which has the value 2 for di-ortho-substituted derivatives, 1 for mono-ortho-substituted derivatives and zero for others. Thus, the highest activity was obtained for 2-methoxy-5-phenyl-1, 3, 2-oxazaphospholidine 2-sulfide, and the activity was decreased by the introduction of any substituents on the phenyl group.     

11种杀虫剂对草皮中红火蚁的检疫除害效果

本文试验了11种杀虫剂对草皮中红火蚁的检疫灭除效果。结果表明,40%毒死蜱乳油30000倍液2、%阿维菌素乳油30000倍液、80%敌敌畏乳油6000倍液4、.5%高效氯氰菊酯乳油3000倍液浓度可完全杀死红火蚁,且对草皮生长没有影响,满足检疫处理要求;其余7种不能达到快速灭除草皮中红火蚁的要求。同时发现,草皮中的红火蚁数量与实际诱集到的数量之间关系符合模型Y=0.0032X-0.59(R2=0.9647,P=0.01)。     

取代双吡唑类化合物的合成及杀虫活性

以3-氯苯肼盐酸盐( 1 )和1,1,3,3-四甲氧基丙烷( 2 )为起始原料,经环化、Vilsmeier反应得1-(3-氯苯基)-1H-吡唑-4-甲醛( 4);(4 )与3-三氟甲基苯乙酮( 5 )经Claisen-Schmidt缩合反应得取代芳基烯酮类化合物( 6 ),再与水合肼发生环化反应得3-(3-三氟甲基苯基)-5-(3-氯苯基-1H-吡唑)-4,5-二氢吡唑( 7),其与取代异氰酸酯 作用,制得15个未见文献报道的结构新颖的取代双吡唑类化合物。利用核磁共振氢谱(1H NMR)和质谱(MS)对其结构进行了表征。初步生物活性测定结果表明,在 500 mg/L 质量浓度下,部分化合物对小菜蛾Plutella xylostella的致死率达100%,而对苜蓿蚜Aphis medicaginis、稻褐飞虱Nilaparvata lugens、朱砂叶螨Tetranychus cinnabarinus均无杀虫活性。     

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。     

Toxicity of botanical insecticides on Diaphania hyalinata,their selectivity for the predatory ant Paratrechina sp., and their potential phytotoxicity on pumpkin

The use of botanical insecticides could be an alternative efficient pest management in Cucurbitaceae against melonworm Diaphania hyalinata and less harmful to its predator. Few studies jointly assess the efficiency of botanical insecticides, their effects on pest, and their effect on the natural enemy and target crop. Here we examine (1) their impact against the melonworm D. hyalinata, a key pest of Cucurbitaceae, (2) their toxicity to the predatory ant Paratrechina sp., and (3) their phytotoxicity to pumpkin plants. The botanical insecticides citronella oil and eucalyptus oil were highly toxic to D. hyalinata and they exhibited to be less harmful for the predatory ant Paratrechina sp. Andiroba oil, eucalyptus oil, garlic extract, and citronella oil caused feeding inhibition of the D. hyalinata larvae. Eucalyptus oil, andiroba oil, garlic extract, and rotenone inhibited the oviposition of D. hyalinata. None of the insecticides was phytotoxic to pumpkin plants. Eucalyptus oil and citronella oil have induced high mortality and altered the behavior of target pests. In addition, they were selective for the predator Paratrechina sp. and not exhibited phytotoxicity on pumpkin plants. Eucalyptus oil and citronella oil seem the most promising compounds for incorporation into melonworm management programs, because they induced high mortality and altered the behavior of target pests and were selective for the predator Paratrechina sp.     

A new fire ant (Hymenoptera: Formicidae) bait base carrier for moist conditions

BACKGROUND: A new water‐resistant fire ant bait (T‐bait; cypermethrin 0.128%) consisting of dried distillers grains with solubles (DDGS) as a carrier was developed and evaluated against a standard commercial bait (Advion^®; indoxacarb 0.045%) under both laboratory and field conditions. RESULTS: When applying the normal T‐bait or Advion^® in the laboratory, 100% of Solenopsis invicta Buren worker ants were killed within 4 days. However, when the T‐bait and Advion^® were wetted, 70.6 and 39.7% of the ants were killed respectively. Under field conditions, dry T‐bait and dry Advion^® had almost the same efficacy against ant colonies. However, when T‐bait and Advion^® came in contact with water, the former's ability to kill S. invicta colonies in the field was only marginally reduced, while Advion^® lost virtually all of its activity. In addition, DDGS was also shown to be compatible with a number of other insecticides, such as d‐allethrin, permethrin and pyrethrin. CONCLUSION: Based on its properties of remaining attractive to the fire ants when wetted, combined with its ant‐killing abilities both in the laboratory and in the field, T‐bait is an efficient fire ant bait, especially under moist conditions. Copyright © 2010 Society of Chemical Industry     

Inhibition of pheromone action in Sesamia nonagrioides by Haloacetate analogues

The electrophysiological activity of some halogenated analogues of the major component of the sex pheromone of the corn stalk borer Sesamia nonagrioides Lef. (1) is presented. The analogues comprise a series of fluoro-, chloro- and bromoacetate analogues 4 – 10 as well as trifluoromethyl ketone 11. The fluoro derivatives 4 – 6 displayed remarkable electro-antennogram (EAG) intrinsic activities in comparison with the parent acetate 1, while the remaining analogues elicited significantly lower response. The compounds have also been tested as inhibitors of the sex pheromone perception in EAG and in the field. In the laboratory. fluoro analogues 4 – 6 were better inhibitors than chloro derivatives 7 – 9 , which in turn behaved similarly to the bromoacetate 10 . Trifluoromethyl ketone 11, however, was a poor inhibitor of the pheromone action. In the field, baits of mixtures of compounds 5 – 11 with the corn stalk borer pheromone in 10 :1 ratio inhibited the concomitant attraction of the clover cutworm moth Scotogramma irifolii Rott., while the difluoro analogue 5, trichloroacetate 9 and trifluoromethyl ketone 11 also diminished the number of catches of the armyworm Mythimna unipuncta Haw. The monofluoroacetate 4. trifluoro analogue 6 and bromo derivative 10 significantly disrupted the pheromone action of the corn borer, whereas trifluoromethyl ketone 11 synergistically increased the number of males attracted to the pheromone trap alone. Addition of 11 to baits containing the corn borer pheromone caught S. nonagrioides selectively with regard to the other habitat-sharing species M. unipuncta and S. trifolii.     

Synthesis and structure–activity relationships of carbohydrazides and 1,3,4‐oxadiazole derivatives bearing an imidazolidine moiety against the yellow fever and dengue vector,Aedes aegypti

BACKGROUND

1,3,4‐Oxadiazole and imidazolidine rings are important heterocyclic compounds exhibiting a variety of biological activities. In this study, novel compounds with oxadiazole and imidazolidine rings were synthesized from 3‐(methylsulfonyl)‐2‐oxoimidazolidine‐1‐carbonyl chloride and screened for insecticidal activities. The proposed structures of the 17 synthesized compounds were confirmed using elemental analysis, infrared (IR), proton nuclear magnetic resonance (¹H‐NMR), and mass spectroscopy.

RESULTS

None of the compounds showed larvicidal activity at the tested concentrations against first‐instar Aedes aegypti larvae. However, nine compounds exhibited promising adulticidal activity, with mortality rates of ≥80% at 5 µg per mosquito. Further dose–response bioassays were undertaken to determine median lethal dose (LD₅₀) values. Compounds 1 , 2b , 2c , 2d , 2 g , 3b , 3c , 3 g, and 3 h were effective, with typical LD₅₀ values of about 5 ? 10 µg per mosquito against female Ae. aegypti. Compounds 2c (bearing a nitro group on the aromatic ring; LD₅₀ = 2.80 ± 0.54 µg per mosquito) and 3 h ( double halogen groups at 2,4 position on the phenyl ring; LD₅₀ = 2.80 ± 0.54 µg per mosquito) were the most promising compounds.

CONCLUSION

Preliminary mode of action studies failed to show consistent evidence of either neurotoxic or mitochondria‐directed effects. Further chemical synthesis within this series may lead to the development of new effective insecticides. © 2017 Society of Chemical Industry