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。     

Structural studies in azolylmethanes

The crystal structures of a number of fungicidal azolylmethanes are compared. In the benzyl compounds [1-aryl-4,4-dimethyl-2-(1,2,4-triazol-1-yl)pentan-3-ones, the corresponding pentan-3-ols, and 1-(4-chlorophenyl)-3-(2-fluorophenyl)-2-(1,2,4-triazol-1-yl)propan-1-one], the benzyl and tert-butyl groups (or 4-chlorophenyl group) are trans, whereas in the analogous phenoxy compounds [1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-one and the corresponding butan-2-ol], the tert-butyl groups are trans to the triazole and gauche to the phenoxy group. Coupling constants, determined by nuclear magnetic resonance (n.m.r.) spectroscopy, suggest that for some compounds there is one dominant solution conformation. Intramolecular hydrogen bonding, observed by infrared spectroscopy in two of the compounds, supports the findings by n.m.r. For some compounds, the crystal and solution conformations appear to be very similar, whereas in others they are quite different. Published data on the relative activity of the enantiomers of the benzyl- and phenoxy-compounds are discussed, but differences in the relative activity of enantiomers in the two series cannot be readily rationalised. It is concluded that different enantiomers may have different modes of binding at the active site.     

嘌呤氧基苯氧丙酸酯的合成及除草活性

以4,6-二氯-5-硝基嘧啶为起始原料,经过还原胺化、取代、醚化等一系列反应,得到11个未见文献报道的嘌呤氧基苯氧丙酸酯类化合物1a~1k,其结构经1H NM R和M S确认。初步生物活性测定表明:在200 mg/L下,所有目标化合物均表现出一定的除草活性,其中化合物1f((R)-2-(4-((9-(4-氯苯)-8-(三氟甲基-9H-嘌呤-6-基)氧)苯氧)丙酸丁酯)和1h((R)-2-(4-((9-(4-氯苯)-8-(三氟甲基-9H-嘌呤-6-基)氧)苯氧)丙酸乙酯)对靶标的抑制率几乎都达到100%。     

杀菌剂啶菌(噁)唑的高效液相色谱分析

建立了一种用反相高效液相色谱测定啶菌噁唑的定量分析方法。采用C18ODS色谱柱,以甲醇-水(75∶25,体积比)作为流动相,流速1.0mL/m in,检测波长220nm。啶菌噁唑色谱图显示两个吸收峰,分别为两个同分异构体Z体和E体。在400700μg/mL浓度范围内,标准溶液浓度和吸收峰面积之间有良好的线性关系,回归方程为Y=4.846 7x+232.85,相关系数r为0.999 2;对原药溶液及其制剂溶液测定的重复性SR分别为0.004 0和0.004 7。该方法准确、精密,适用于啶菌噁唑的定量分析。     

Synthesis and herbicidal activity of new oxazinone herbicides with a long-lasting herbicidal activity against Echinochloa oryzicola

Chemical modification of the herbicide 1-[2-(benzothiazol-2-yl)isopropyl]-4-methyl-3-phenyl-5H-pyrrolin-2-one (MI-2826) has revealed a new oxazinone herbicide, 3-[2-(7-chlorobenzothiazol-2-yl)isopropyl]-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazin-4-one (MI-3069), for use in paddy fields. In comparing the phyototoxicity of the two herbicides to transplanted rice, the latter was superior to the former and kept the same predominant characteristic to control Echinochloa oryzicola Vasin for a long period of time owing to its long-lasting residual effect.     

N-(pyrid-3-yl)thioureas and derivatives as acaricides. I. Synthesis and biological properties

In the course of optimization studies around diafenthiuron, the central aromatic nucleus linked directly to the thiourea unit was replaced by a pyridine moiety. A series of N-(pyrid-3-yl)thioureas, -isothioureas and -carbodiimides was synthesised and evaluated for acaricidal activity. The synthetic methodology used and the screening results against some spider mites (Tetranychus spp. and Panonychus ssp.) are discussed.     

啶菌噁唑对番茄灰霉病菌的抑菌作用研究

采用生物测定方法研究了啶菌噁唑对番茄灰霉病菌Botrytis cinerea不同发育阶段的影响。结果表明:其对菌落扩展、芽管伸长、分生孢子产生和菌核形成均具有显著的抑制活性,其中啶菌噁唑对P-9菌株菌丝生长和芽管伸长的EC50值分别为0.193和0.154 μ g/mL,0.5 μ g/mL的啶菌噁唑对菌丝生长和芽管伸长的抑制率大于77%,对分生孢子和菌核萌发的抑制率分别低于10％和40%,表明药剂对分生孢子萌发无明显抑制作用。紫外吸收分析显示,啶菌 NFDA1 唑可破坏细胞的膜结构,促使菌体核酸和蛋白外渗。离体叶片毒力测定结果表明,120 μ g/mL的啶菌 NFDA1 唑可有效抑制番茄灰霉病病斑扩展,抑制率达83.74%。     

异香豆素噁二唑类化合物的合成及除草活性

为了寻找具有较高除草活性的异香豆素类化合物,设计合成了16个新型异香豆素噁二唑类化合物4a～4p,其结构均经核磁共振氢谱、碳谱及高分辨质谱确证。初步除草活性测定结果表明,部分目标化合物在500 mg/L下对马唐Digitaria sanguinalis L.和反枝苋Amaranthusretroflexus L.具有一定的除草活性,其中化合物4j（4-[5-（4-氯-苯基）-[1,2,4]二唑-3-基]-3-己基-6,7-二甲氧基异香豆素）的活性最好,对马唐和反枝苋的致死率分别为64%和62%。     

Action of fungicidal triazoles of the diclobutrazol series on ustilago maydis

Diclobutrazol [(2RS, 3RS)-1-(2, 4-dichlorophenyl)-4, 4-dimethyl-2-(1,2, 4-triazol-1-yl)pentan-3-ol] decreased the rate of growth of Ustilago maydis during the log phase. Marked changes in sterol composition were observed with a decrease in ergosterol and an increase in methyl-sterols, indicating a block in the removal of the 14-methyl group. The inhibition was of rapid onset (<4 h). Changes in other lipid constituents were minor and there was no build up of unsaturated fatty acids. The fungicidal activity resides in the (2R, 3R)-isomer, which is known to be more potent in blocking a yeast 14-demethylase enzyme than the (2S, 3S)-isomer. This relationship held in the 4-chlorophenyl homologues, which as a group were less fungicidal and less potent inhibitors than the 2, 4-dichlorophenyl compounds. The evidence presented indicates that the primary lesion caused by the fungicide was a build up of membrane sterols containing extra methyl groups; this, in combination with a loss of ergosterol, is believed to prevent proper membrane ordering and thus to cause a loss of membrane function.     

Metabolic resistance mechanisms of the housefly (Musca domestica) resistant to pyraclofos

In vivo and in vitro metabolism of pyraclofos labeled with ¹⁴C on benzene ring was studied in the pyraclofos-resistant and -susceptible female houseflies. In vivo metabolism studies, the metabolic rate of pyraclofos was the same in both strains. Pyraclofos primarily undergoes metabolic detoxification by cleavage of P-S-alkyl bond, and cleavage of the P-O-aryl bond followed by CHP [1-(4-chlorophenyl)-4-hydroxypyrazole]]-glucose conjugation. Cleavage of P-O-aryl bond and CHP-glucose conjugation is more predominant in the resistant strain whereas the cleavage of P-S-propyl bond resulting in EHP-CHP [O-1-(4-chlorophenyl)pyrazol-4-yl ethyl hydrogen phosphate] is more preferred in the susceptible strain. CHP production by P-O-aryl bond cleavage was controlled by P450 monooxygenase and esterase. UDP-glucosyltransferase appeared to play an important role in the pyraclofos metabolism of the resistant strain. Production of CHP-glucose conjugate was largely reduced by piperonyl butoxide and S,S,S-tributylphosphorotrithioate in both strains. EHP-CHP production seemed to be controlled by P450 monooxygenase and stimulated by UDP-glucose.     

The laboratory evaluation of two promising new insecticides which interfere with cuticle deposition

1-(4-chlorophenyl)-3-(2,6-dichlorobenzoyl)-urea, PH 60-38 and 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)-urea, PH 60-40, are representatives of a new class of insecticides with an unprecedented mode of action. Susceptibility of insect species of different orders is demonstrated and the compounds are expected to be quite safe towards mammals. The compounds are stomach poisons and they are not plant systemic. Their insecticidal activity demonstrates itself mainly as a failure to moult or pupate, resulting in death. Histological examination revealed the cause of this failure to be a defect in the process of cuticle deposition.     

Synthesis and Structure–Activity Relationships of Miticidal 4,5-Dihydropyrazole-5-thiones

A series of novel 4,5-dihydropyrazole-5-thiones (DHPs) was synthesised by treating the corresponding dihydropyrazolones with ‘Lawesson’s reagent and evaluated for miticidal activity against two-spotted spider mites (Tetranychus urticae Koch). Of these, 3-(4-chlorophenyl)-4,4-dimethyl-1-phenyl-4,5-dihydropyrazole-5-thione, 3-(4-chlorophenyl)-4-ethyl-4-methyl-1-phenyl-4,5-dihydropyrazole-5-thione, 3-(4-chlorophenyl)-1-phenyl-4,5-dihydropyrazole-5-thione-4-spirocyclopentane and 4,4-dimethyl-1-phenyl-3-(4-trifluoromethyl-phenyl)-4,5-dihydropyrazole-5-thione were highly active (pEC₅₀>4·0) and were more effective than the miticide dicofol (pEC₅₀=3·879), which has traditionally been used for the control of phytophagous mites. Structure–activity relationship (SAR) studies were performed on each position of the pyrazole ring of DHPs. The results indicated that the unsubstituted phenyl, 4-substituted phenyl and thioxo groups on the 1-, 3- and 5-positions of DHPs respectively were required for activity. Quantitative SAR studies using physicochemical parameters of substituents and the capacity factor k′ as a hydrophobicity index suggested that: (a) the activities of all types of DHPs examined were mainly dominated by hydrophobicity, (b) the bulkiness of 4-substituents of the 3-phenyl ring favoured the activity and (c) the log k′ optimum for all DHPs was 1·675, equivalent to a log P_ow value of c. 5·0.     

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。     

The cyclization transformation of the sulfonylurea herbicide flupyrsulfuron in the soil of winter wheat crops

The synthesis of 1-(4,6-dimethoxypyrimidine-2-yl)-7-trifluoromethyl-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidin-2,4-dione has been carried out in such a way that the dimethoxypyrimidine substituent was unambiguously in position 1 of the pyrido[2,3-d]pyrimidine ring. This regioisomer was obtained by cyclization with phosgene of 2-(4,6-dimethoxypyrimidin-2-ylamino)-6-trifluoromethylnicotinamide which had previously been ionized with sodium hydride. It was shown to be identical to the metabolite generated in the soil of winter wheat crops treated previously with the sulfonylurea herbicide flupyrsulfuronmethyl [(methyl 2-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-6-trifluoromethylnicotinate]. The position of the dimethoxypyrimidine substituent had not previously been assigned unambiguously to positions 1 or 3 of the pyrido[2,3-d]pyrimidine ring. The regioisomer was also identical to the cyclization compound generated chemically from flupyrsulfuron in a sterile water buffer at pH 9. The metabolism pathways of flupyrsulfuron in soil are discussed in the light these structure determinations and compared with the soil metabolism pathways frequently observed with other sulfonylurea herbicides.     

Metabolism of phenyl-3 H-indoles by cell suspension of Acer pseudoplatanus L. and their phytotoxicity

Phenyl-3H-indoles inhibited growth of Acer pseudoplatanus cells but were not toxic in vivo. Experiments were conducted to find out why the compounds gave a toxic response in cell suspension but not a phytotoxic response in whole plants. The behaviour of two phenyl-3H-indoles, (2-(4-chlorophenyl)-3,3-dimethyl-5-fluoro-3H-indole and 2-(4-chlorophenyl)-3,3-dimethyl-5-carboxy-3H-indole), was investigated in cell suspensions. Absorption and metabolism by cells were rapid. The major metabolite was identified as a polar conjugate of 2-(3-hydroxy-4-chlorophenyl)-3,3-dimethyl-5-fluoro-3H-indole. This metabolite did not inhibit cell growth. Different phenyl 3H-indole analogues with the hydroxylation site blocked were synthesised to determine if metabolism was involved in the disappearance of activity in vivo. The results indicated that this was not the case and thus the absence of phytotoxicity must be related to another factor.     

Synthesis and fungicidal activity against Pyricularia oryzae of 6-(1,2,4-triazol-4-yl) chromone and -1-thiochromone derivatives

A series of novel 6-(1,2,4-triazol-4-yl) chromone and -1-thiochromone (benzo[b]thiazin-4-one) derivatives was obtained by cyclisation via thiosemicarbazides which were prepared by reaction of hydrazines and the corresponding isothiocyanates. Their fungicidal activity was evaluated against the rice blast fungus Pyricularia oryzae. Of this series, 2,5,8-trimethyl-6-(1-propyl-5-thioxo-3-trifluoromethyl-1,2,4-triazol-4-yl) chromone, 6-(1-butyl-5-thioxo-3-trifluoromethyl-1,2,4-triazol-4-yl)-2,5,8-trimethylchromone, 6-(1-hexyl-3-methyl-5-thioxo-1,2,4-triazol-4-yl)-2,5,8-trimethylchromone and 6-(1-allyl-5-thioxo-3-trifluoromethyl-1,2,4-triazol-4-yl)-2,5,8-trimethylchromone were highly active (pEC₅₀>6·0). Structure–activity relationship studies using the capacity factor k′ as a hydrophobicity index suggested that the log k′ optimum for 2,5,8-trimethyl-chromone and -1-thiochromone derivatives was around 1·0, equivalent to a log P_ow value of c. 4·4. © 1998 SCI     

Residues of carbofuran and 2,3-dihydro-3-hydroxy- 2,2-dimethylbenzofuran-7-yl methylcarbamate in the mushroom,agaricus bisporus,cultivated in casing soils treated with the insecticide

Residues of carbofuran ( 1 ) and 2,3-dihydro-3-hydroxy-2,2-dimethylbenzofuran-7-yl methylcarbamate ( 2 ) in and on mushrooms, cultivated on casing soils containing added carbofuran granular insecticide, were determined. The quantitative estimations in cleaned mushroom extracts were done on thin-layer plates using a cholinesterase inhibition method. Samples were analysed, which had been harvested at different times from cultures, to which different amounts of carbofuran were added. Residues in washed and unwashed mushroom samples were compared. Residues did not exceed 0.5 mg (carbofuran) kg^?1 and 0.25 mg (compound 2 ) kg^?1 for fresh unwashed mushrooms grown on casing soil treated with carbofuran granules 1 g (a.i.) m^?2.     

Synthesis and fungicidal activity of 1,4-dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles

A series of eleven 1,4-dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles was prepared by reaction of 2,3-dichloroquinoxalines with disodium (2)-2,3-dimercapto-2-butenedinitrile in N,N-dimethylformamide. These products were tested for in-vitro fungicidal activity by a Minimum Inhibitory Concentration (MIC) method. Several of these compounds showed broad-spectrum fungicidal activity. The activity exhibited by these compounds was greatly dependent upon the substituents of the quinoxaline ring, with the nitro-substituted derivatives showing the highest levels of antifungal activity. None of the compounds prepared, however, showed fungicidal activity comparable to that of the commercial fungicides screened.     

Photolytic demethylation of monuron and demethylmonuron in aqueous solution

Photochemical demethylation of monuron [3-(4-chlorophenyl)-1, 1-dimethylurea] and of demethylmonuron [ 1-(4-chlorophenyl)-3-methylurea] in aqueous solution was investigated. The photoproducts identified in this study were formaldehyde, formic acid and carbon dioxide. These products indicate that demethylation occurs either by oxidation of a methyl group to hydroxymethyl which is readily cleaved to yield formaldehyde, or by further oxidation to an N-formyl group, which is slowly hydrolysed under weakly acidic conditions to yield formic acid. Samples equilibrated either with air or oxygen (> 99 % purity) gave essentially the same yield of oxidation products. Experimental evidence indicated that extensive photodegradation of formaldehyde was occurring during photolysis, causing low recoveries of formaldehyde. Consequently, with [²H₃-methyl]demethylmonuron and deuterated water, only steady state concentrations of formaldehyde could be measured in an isotopic study.     

Photolysis,metabolism and other factors influencing the performance of triadimefon as a powdery mildew fungicide

Triadimefon, 1-(4-chlorophenoxy)-3,3-dimethyl-1-( 1,2,4-triazol-1-yl)butanone, applied at low dosage rates to leaves of marrow, apple or barley plants gave effective control of the appropriate powdery mildew fungi. The compound appeared to be systemic and to have considerable vapour-phase activity. In marrow plants, up to 56% of triadimefon was metabolised to a mixture of two corresponding diastereoisomeric secondary alcohols. The mixture was identical with that obtained by chemical reduction of triadimefon. This mixture was also a very effective systemic fungicide and active in the vapour-phase. Triadimefon was also reduced when incubated with Aspergillus niger but this was important only in shake culture. In replacement culture experiments, mycelial mats of this fungus converted the compound into a different metabolite, its isopropyl analogue. This may have resulted from participation of triadimefon in the C-4 demethylation processes involved in fungal biosynthesis of ergosterol. Photolysis caused cleavage of the C-1 to triazole bond liberating 1,2,4-triazole, 4-chlorophenol and 4-chlorophenyl methyl carbonate, all of which were non-fungitoxic. The importance of this photolysis in the in-vivo situation is discussed.