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。     

3-苄基-5-(1-(2-氧代-1-氧杂螺[4,5]癸-3-烯-3-基) 亚乙基)-2-氨基咪唑啉-4-酮类化合物的合成及杀菌活性

为寻找高活性的杀菌化合物,在前期合成5-(1-(4-甲基-2-氧代-1-氧杂螺[4,5]癸-3-烯-3-基) 亚乙基)-2-氨基咪唑啉-4-酮类化合物的基础上进行结构修饰,在咪唑啉-4-酮的3-位引入苄基,设计并合成了一系列未见文献报道的化合物,其结构经过核磁共振氢谱 (1H NMR)、碳谱 (13C NMR) 及高分辨质谱 (HR-ESI-MS) 确证。经高效液相色谱 (HPLC) 分析显示,Z-构型中间体化合物 6 在酸性条件下会发生氮质子化开环再环化,转化为E-构型化合物 7 。离体杀菌活性测定结果表明,3-位苄基的引入改善了该类化合物的杀菌活性,其中化合物 (E)-3-苄基-5-(1-(4-甲基-2-氧代-1-氧杂螺[4,5]癸-3-烯-3-基) 亚乙基)-2-(4-甲氧基苯基) 氨基-咪唑啉-4-酮 ( 9c ) 和 (E)-3-苄基-5-(1-(4-甲基-2-氧代-1-氧杂螺[4,5]癸-3-烯-3-基) 亚乙基)-2-(4-氟苯基) 氨基-咪唑啉-4-酮 ( 9h ) 对油菜菌核病菌的EC₅₀ 值分别为14.3和21.1 mg/L。活体杀菌活性测试结果显示,在400 mg/L下化合物 9c 对于黄瓜霜霉病和小麦白粉病的防治效果分别为 80%和85%。     

Synthesis,structure and herbicidal activity of pyrazol-4-yl alkyl ketone derivatives

Novel 5-amino-1-phenylpyrazol-4-yl alkyl ketones were synthesised and their herbicidal properties evaluated. Active compounds in the series induced accumulation of protoporphyrin IX in etiolated cucumber cotyledons and caused light-dependent herbicidal effects in 21-day-old cucumber plants. Structural features of the pyrazoles that contributed to herbicidal potency were found to be a high degree of halogen substitution in the 1-phenyl ring, no substitution in the pyrazole 3-position, and an ethyl group as the alkyl component of the ketone. The structure of 1-[5-amino-1-(2,4,6-trichlorophenyl)pyrazol-4-yl]-2-methylpropan-1-one was determined by X-ray crystallography.     

Localizing the action of two thiadiazolyl herbicidal derivatives

Enzymatically isolated leaf cells from navy beans (Phaseolus vulgaris L., cv. “Tuscola”) were used to study the effect of buthidazole (3-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-4-hydroxy-1-methyl-2-imidazolidinone) and tebuthiuron (N-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]-N,N′-dimethylurea) on photosynthesis, protein, ribonucleic acid (RNA), and lipid synthesis. The incorporation of NaH¹⁴CO₃, [¹⁴C]leucine, [¹⁴C]uracil, and [¹⁴C]acetic acid as substrates for the respective metabolic process was measured. Time-course and concentration studies included incubation periods of 30, 60, and 120 min and concentrations of 0.1, 1, 10, and 100 μM of both herbicides. Photosynthesis was very sensitive to both buthidazole and tebuthiuron and was inhibited in 30 min by 0.1 μM concentrations. RNA and lipid syntheses were inhibited 50 and 87%, respectively, by buthidazole and 42 and 64%, respectively, by tebuthiuron after 120 min at 100 μM concentration. Protein synthesis was not affected by any herbicide at any concentration or any exposure time period. The inhibitory effects of buthidazole and tebuthiuron on RNA and lipid syntheses may be involved in the ultimate herbicidal action of these herbicidal chemicals.     

含苯丙氨酸和1H-茚-1-酮类氯虫苯甲酰胺类似物的合成及杀虫活性

为了开发新的杀虫化合物，以氯虫苯甲酰胺为先导，2-甲基-3-氨基苯甲酸为起始原料，经过卤化生成5-氯-3-甲基-2-氨基苯甲酸；再与3-溴-1-(3-氯吡啶-2-吡啶基)-1H-吡唑-5-甲酸进行缩合反应，生成6-氯-2-(3-溴-1-(3-氯吡啶-2-吡啶基)-1H-吡唑-5-基)-8-甲基-4H-3,1-苯并噁嗪-4-酮；最后引入苯丙氨酸片段并经环化反应，分别合成了两个系列共计23 个新化合物( 4 和 5 )，其中化合物 4 为含苯丙氨酸的氯虫苯甲酰胺类似物，化合物 5 为由化合物4环化生成的含1H-茚-1-酮片段的氯虫苯甲酰胺类似物，所有化合物的结构均通过核磁共振氢谱(1H NMR)、碳谱(13C NMR)和高分辨质谱(HRMS)的表征及确证。初步室内杀虫活性测试结果表明，多数目标化合物对黏虫Mythinma separata具有较高的杀虫活性，其中14个化合物在100 mg/L下对黏虫Mythinma separata的致死率为100%，化合物 5k ( 1H-茚-1-酮片段中取代基为羟基 ) 在4和0.8 mg/L下的致死率分别为90%和70%，其LC₅₀值为0.55 mg/L。分子对接结果表明，化合物 5k 与氯虫苯甲酰胺一样，也是作用于鱼尼汀受体(RyR)，但与靶标结合的氨基酸残基不同，这种差异可能对黏虫的抗药性治理研究有益。     

A root bioassay procedure for the determination of chlorsulfuron, diclofop acid and sethoxydim residues in soils

Measurement of the root lengths of pre-ger-minated oat seedlings (Avena sativa L. var. Sioux) grown in the dark in treated soils was used to assay residues of diclofop acid (2-[4-(2,4-dichloro-phenoxy)phenoxy]propionate) and sethoxydim (2-[1-(ethoxyimino)-butyl]-5-[2-(ethylthio)-propy]-3-hydroxy-2-cyclohexene-1-one). Similar measurements involving maize seedlings (Zea Mays L. var. Sunny Vee) were also used to determine residues of the herbicide chlorsulfuron (2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbony]benzenesulfonamide) in soils. The procedure appeared to be reproducible with residues of chlorsulfuron, diclofop acid and sethoxydim being detectable at amounts of 0.001, 0.2 and 0.05 μg g^?1 respectively.     

Novel 1,3,5-triazine derivatives with herbicidal activity

New fluoroalkyl-substituted 1,3,5-triazine derivatives were synthesized and screened for herbicidal activity using a greenhouse pot test. Surprisingly, a series of 2-alkyl-4-fluoroalkyl-6-aralkylamino-1,3,5-triazines e.g. 6-(4-bromobenzylamino)-2-methyl-4-trifluoromethyl-1,3,5-triazine was found to possess strong pre- and post-emergence herbicidal activities, although the conventional herbicidal 1,3,5-triazines generally should have a 2-substituted-4,6-diamino-1,3,5-triazine structure for herbicidal activity. Our compounds show strong Photosynthetic Electron Transport inhibitory activity (PI₅₀ c 7). Although their herbicidal effect is considered to be caused by a process similar to that for the conventional 1,3,5-triazine herbicide atrazine, they can control atrazine-resistant Chenopodium album effectively, and will thus form promising trial compounds for new triazine herbicide design.     

新化合物ZJ10361的除草活性研究

为明确对羟苯基丙酮酸双氧化酶（HPPD）抑制剂类新化合物ZJ10361[1,3-二甲基-4-（2-甲基-4-甲砜基-3-（2-对甲苯氧基）乙氧基）苯甲酰基-1H-吡唑-5-基碳酸乙酯]在玉米田的开发应用潜力,对该化合物的除草活性、安全性、选择性、杀草谱和田间药效进行了研究。室内生物测定结果表明,ZJ10361在有效剂量150 g/hm2下对玉米安全性好,而对其他5种供试作物均有不同程度药害;对不同玉米品种之间的安全性有一定差异,其中对糯玉米科糯986安全性最好,其次为杂交玉米掖单13,甜玉米华珍最为敏感。该化合物在目标作物玉米Zea mays与反枝苋Amaranthus retroflexus、鳢肠Eclipta prostrata之间的选择性系数为4.0~4.5,具有较好的选择性;对阔叶杂草的除草活性较高,杀草谱较广,但对禾本科和莎草科杂草除草活性一般。田间试验结果显示,ZJ10361在有效剂量225 g/hm2下对供试玉米安全性好,对玉米田杂草总草防效为86.9%,与对照药剂硝磺草酮有效剂量150 g/hm2处理相比无显著性差异。该化合物用于玉米田防除阔叶杂草具有一定的开发潜力。     

Herbicidal activity and selectivity of new 3-alkyl-4-amino-6-aryl-1,2,4-triazin-5-ones

3-Alkyl-4-amino-6-phenyl-1,2,4-triazin-5-ones are herbicidal compounds which act by inhibition of the electron transport in photosynthesis (Hill reaction). There is some correlation between phytotoxicity and photosynthesis inhibition data. An exception is found with sugar beets which are very tolerant towards triazinones with a methyl group in 3-position and an amino group in 4-position. The best compound from this series, 4-amino-4,5-dihydro-3-methyl-6-phenyl-1,2,4-triazin-5-one, metamitron, shows very promising properties as a selective herbicide in sugar beet crops.     

含大体积取代基的吡唑并三嗪酮类化合物的合成及除草活性

以1-(取代)苯基-5-氨基-1H-吡唑-4-甲酸乙酯或1-叔丁基-5-氨基-1H-吡唑-4-甲酰氯和2-甲基-4-炔丙基-6-氨基-7-氟-2H-苯并[b][1,4]-噁嗪-3(4H)-酮为初始原料，分别通过不同的合成路线，得到22个未见文献报道的含大体积取代基的吡唑并三嗪酮类化合物，所有化合物的结构均通过核磁共振氢谱(1H NMR)和高分辨质谱(HRMS)确证。初步生物活性测定结果表明:在375 g/hm2处理剂量下，大部分目标化合物表现出一定的除草活性，其中化合物 4h 、 4i 和 4j 对反枝苋Amaranthus retroflexus生长的抑制率接近100%。     

Environmental factors affecting the herbicidal activity of DPX-A7881

DPX-A7881, methyl 2-[(4-ethoxy-6-methyl-amino-1, 3, 5-triazin-2-yl)carbamoylsulphanoyl] benzoate, is a sulfonylurea herbicide being developed in Canada and Europe for post-emergence broadleaf weed control in spring and winter rapeseed. Growth room studies were conducted to determine the environmental factors affecting the herbicidal activity of DPX-A7881 applied post-emergence on winter rapeseed (Brassica napusu L. ‘Tandem’) and on a closely related weed species, Sinapis arvensis L. (wild mustard). Laboratory tests were carried out at tempera tures ranging from 2–26°C, at relative humidities from near 40% to >95%, with rain-free periods from 0.25–8 h after herbicide application, at soil moisture contents from 50–200% of field capacity, and with irradiances from 23–450 μEm^?2s^?1 Significant control of S. arvensis was demonstrated for all treatments except under poor growing conditions at the lowest temperatures and irradiances tested. After two weeks' exposure to each of the tem perature treatments, the herbicide maintained control of S. arvensis during a subsequent week of favourable growing conditions. Relative humidity, soil moisture or simulated rainfall did not significantly alter the herbicidal activity of DPX-A7881 on S. arvensis. DPX-A7881 showed a high degree of crop safety on B. napus. The herbicide did not significantly reduce the dry weights of B. napus grown under any of the environmental conditions tested.     

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%。     

Degradation of fluridone in submersed soils under controlled laboratory conditions

The experimental, aquatic herbicide fluridone (1-methyl-3-phenyl-5-[3-(trifluoromethyl)phenyl]-4(1H)-pyridinone) was degraded in two submersed soils and in the water above those soils to one acidic metabolite (identified as 1,4-dihydro-1-methyl-4-oxo-5-[3-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid by mass spectrometry). A sandy and a silt loam soil were treated with [¹⁴C]fluridone, immersed in water, and analyzed after 1, 3, 5, 7, 9, and 12 months. Seven to fifteen percent of the ¹⁴C applied to the soils was recovered in the water on each of the various collection dates. The acidic metabolite accounted for 86 to 93% of the radioactivity in the water fraction 7 months after treatment. The metabolite was absorbed strongly by both soils and comprised about 60% of the total ¹⁴C in each soil after 12 months. The remainder of the ¹⁴C in the soils after 12 months was either the parent compound (～30%) or an undefined insoluble residue (～10%).     

三氟羧草醚类似物的合成及除草活性

以2,5-二羟基苯甲酸甲酯和三氟羧草醚为起始原料,设计合成了3个系列20个新的三氟羧草醚类似物,通过核磁共振氢谱、碳谱对其结构进行了表征。分别采用小杯法和室内盆栽法测定了目标化合物的除草活性。结果表明,化合物 III-02 [5-(2-氯-4-三氟甲基苯氧基)-2-硝基苯甲酸-(6-甲基苯并噻唑-2-基)酯]对单子叶杂草的除草活性明显高于对照药剂三氟羧草醚,其对稗草Echinochloa crusgalli和马唐Digitaria sanguinalis根茎生长的EC₅₀值分别为2.03、0.93 μg/mL和1.49、0.52 μg/mL;在有效成分100 g/hm2的施药剂量下,化合物 III-02 对单子叶杂草稗草、马唐及狗尾草Setaria viridis的防治效果均在85%以上,明显高于三氟羧草醚,对阔叶杂草马齿苋Portulaca oleracea、反枝苋Amaranthus retroflexus及苘麻Abutilon theophrasti的防治效果可达100%。初步构效关系表明,2-硝基苯甲酰衍生物的除草活性明显优于其2-甲氧基衍生物,三氟羧草醚苯甲酸酯衍生物对单子叶杂草的除草活性明显高于其苯甲酰胺衍生物。     

Degradation of the sulfonylurea herbicide LGC-42153 in flooded soil

LGC-42153, 2-fluoro-1-[3-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)pyridin-2-yl] propyl methoxyacetate, is a new sulfonylurea herbicide for use in rice. Its breakdown and metabolism was studied in soil under flooded conditions using two radioactive tracer compounds labelled at either the propyl group or the pyrimidine ring. The half-life of LGC-42153 was approximately 3.0 days. The mass balance over 120 days ranged from 94.0 to 104.2% of applied radiocarbon, and no significant amount of volatiles or [14C]carbon dioxide were observed. Solvent non-extractable radiocarbon reached about 11-14% of applied radiocarbon at 120 days after treatment. The major metabolic reaction was the cleavage of the carboxyl ester bond to give 1-(4,6-dimethoxypyrimidin-2-yl)-3-[2-(1-hydroxy-2-fluoropropyl)pyridine-3-sulfonyl]urea, which underwent hydrolysis of the sulfonylurea bridge giving 2-(1-hydroxy-2-fluoro)propyl-3-pyridinesulfonamide and 4,6-dimethoxy-2-aminopyrimidine.     

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     

Conformational and intramolecular hydrogen bonding effects on post-emergence and pre-emergence selectivities of herbicidal pyrrole dicarboxylates

Dimethyl 2-methyl-5-(chloropyridin-2-yl)pyrrole-3,4-dicarboxylates in which the chlorine atom is substituted at different positions of the pyridine ring have widely varying biological properties. The 3-chloro analog (I) is a post-emergence and pre-emergence herbicide, the 4- and 5-chloro analogs (II, III) are post-emergence herbicides but not pre-emergence, and the 6-chloro analog (IV) is inactive. Computer graphic and molecular mechanics analyses of their molecular conformations showed that the 4- and 5-chloro analogs adopt a coplanar, intramolecularly hydrogen bonded conformation whereas the 3-chloro analog does not. High-level quantum mechanical calculations of the conformational preferences of related model systems were in agreement with these results. Based on this, II and III were predicted to have higher octanol/water partition coefficients relative to I, leading to higher soil binding and weaker xylem transport, hence their observed weaker pre-emergence activities. Experimental measurements of octanol/water partition coefficients, soil binding, and infrared hydrogen bonding studies verified these predictions. Molecular modeling techniques are usually used for designing compounds to fit enzyme active sites and designing putative receptor models. This study demonstrates the usefulness of these techniques for dealing with transport problems.     

Degradation of the sulfonylurea herbicide LGC-42153 in flooded soil

LGC-42153, 2-fluoro-1-[3-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)pyridin-2-yl]propyl methoxyacetate, is a new sulfonylurea herbicide for use in rice. Its breakdown and metabolism were studied in soil under flooded condition using radioactive tracers labelled at either the propyl group or the pyrimidine ring. The half-life of LGC-42153 was approximately 3.0 days. The mass balance over 120 days ranged from 94.0 to 104.2% of applied radiocarbon, and no significant amount of volatiles or [14C]carbon dioxide were observed. Solvent non-extractable radiocarbon reached 11 approximately 14% of applied radiocarbon at 120 days after treatment. The major metabolic reaction was the cleavage of the carboxyl ester bond to give 1-(4,6-dimethoxypyrimidin-2-yl)-3-[2-(1-hydroxy-2-fluoropropyl)pyridine-3-sulfonyl]urea, which underwent hydrolysis of the sulfonylurea bridge giving 2-(1-hydroxy-2-fluoro)propyl-3-pyridinesulfonamide and 4,6-dimethoxy-2-aminopyrimidine.     

Metabolism of chlorsulfuron by plants: Biological basis for selectivity of a new herbicide for cereals

A major factor responsible for the selectivity of chlorsulfuron [2-chloro-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]benzenesulfonamide] (formerly DPX-4189), as a postemergence herbicide for small grains is the ability of the crop plants to metabolize the herbicide. Chlorsulfuron is the active ingredient in Du Pont “Glean” weed killer. Tolerant plants such as wheat, oats, and barley rapidly metabolize chlorsulfuron to a polar, inactive product. This metabolite has been characterized as the O-glycoside of chlorsulfuron in which the phenyl ring has undergone hydroxylation followed by conjugation with a carbohydrate moiety. Sensitive broadleaf plants show little or no metabolism of chlorsulfuron.     

放射性同位素碳-14标记氯虫苯甲酰胺的合成与分析

以[14C]碳酸钡为放射性同位素原料,通过格氏反应、亲核取代、胺化和缩合等8步放化反应制备了2种放射性同位素碳-14标记的氯虫苯甲酰胺粗品,经反相高效液相色谱(RPHPLC)纯化获得标记物纯品14C-氯虫苯甲酰胺[3-溴-N-[4-氯-2-甲基-6-(甲氨基[羰基-14C]甲酰基)苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酰胺(2,55.6 mCi)和3-溴-N-[4-氯-2-甲基-6-(甲氨基甲酰基)苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-[羰基-14C]甲酰胺(3,58.6 mCi)]。以[14C]碳酸钡计,两种标记物的总放化收率分别为32%和52%。其结构经核磁共振氢谱、质谱和在线放射性高效液相色谱(HPLC-FSA)分析确认。放射性薄层成像分析(TLC-IIA)、离线放射性高效液相色谱分析(HPLC-LSC)、在线放射性高效液相色谱-二极管阵列检测器/质谱联用(HPLCFSA/PDA/MS)和LSC分析表明,两种14C-氯虫苯甲酰胺的放化纯度分别为99.8%和99.6%,化学纯度分别为99.1%和98.4%,比活度分别为52.45 mCi/mmol和52.30 mCi/mmol。这2种标记物可作为放射性示踪剂,可满足氯虫苯甲酰胺在中国的登记代谢试验研究的需要。