methyl 2-methoxyimino-2-[2-[[1-[3-(trifluoromethyl)phenyl]ethylideneamino]oxymethyl]phenyl]acetate | 139485-98-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 2-methoxyimino-2-[2-[[1-[3-(trifluoromethyl)phenyl]ethylideneamino]oxymethyl]phenyl]acetate
• 英文别名: trtifloxystrobin；trifloxystrobin；(E,E)-2-[α-{[(α-methyl-3-trifluoromethylbenzyl)imino]-oxy}-o-tolyl]glyoxylic acid methyl ester O-methyloxime；methyl 2-{2-[4-(3-trifluoromethylphenyl)-3-aza-2-oxa-3-pentenyl]-phenyl}-2-methoxyimino-acetate；methyl{2-[(1-(3-trifluoromethyl-phenyl)ethylidene)-aminooxymethyl]-phenyl}-2-methoximinoacetate；Methyl 2-[(alpha-methyl-3-trifluoromethylbenzylidene)aminooxymethyl]-alpha-methoxyiminophenylacetate
• CAS: 139485-98-6
• 化学式: C₂₀H₁₉F₃N₂O₄
• 分子量: 408.377
• InChiKey: ONCZDRURRATYFI-UHFFFAOYSA-N

物化性质

• 沸点：
  470.3±55.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)
• 颜色/状态：
  White powder
• 气味：
  Odorless
• 熔点：
  72.9 °C
• 闪点：
  >70.00 °C (>158.00 °F)
• 溶解度：
  In water, 0.610 mg/L at 25 °C
• 蒸汽压力：
  2.55X10-8 mm Hg at 25 °C
• 稳定性/保质期：
  No change after 2 years storage at 20 °C in commercial packing. /Stratego 250 EC/ /from table/
• 分解：
  Decompn starting at 285 °C.
• 解离常数：
  Trifloxystrobin does not show any dissociation in the pH ranges 2 to 12.
• 保留指数：
  2339;2344;2336

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  69.5
• 氢给体数：
  0
• 氢受体数：
  9

ADMET

代谢

在大鼠中，吸收的化合物通过广泛的代谢被迅速清除，特别是通过酯基的水解。其他重要的代谢途径包括甲基氧基亚硝基团的O-脱甲基化和甲基侧链的氧化，生成相应的醇和羧酸。

In rats, the absorbed compound was rapidly cleared with extensive metabolism, particularly through hydrolysis of the ester group. Other significant metabolic routes were O-demethylation of the methoxyimino group and oxidation of the methyl side chain to the corresponding alcohol and carboxylic acid.

来源:Hazardous Substances Data Bank (HSDB)

代谢

雄性和雌性大鼠通过灌胃给予[Glyoxyl-Phenyl-(U)-14C]（放射性化学纯度范围：>97至>99%）或[Trifluormethyl-Phenyl-(U)-14C]-/三氟苯-(U)-14C]-/三氟苯氧基苯甲酸/（CGA-279202）（放射性化学纯度：>99%）。除了D2组外，所有组的动物都给予了[Glyoxyl-Phenyl-(U)-14C]-/三氟苯氧基苯甲酸/（CGA 279202）...从尿液、粪便和胆汁样本中分离并鉴定出35种代谢物。主要的代谢途径包括1）甲基酯水解为相应的酸，2）甲氧基亚氨基的O-去甲基化，以及3）甲基侧链氧化为初级醇，随后进一步氧化为羧酸。最后这个反应在雌性大鼠中是一个更突出的代谢途径，从而分离出主要的性别特异性尿代谢物。Glyoxyl-phenyl和trifluoromethyl-phenyl部分的裂解占总剂量的10%。对于三氟甲基苯基片段，羟基亚氨基的氧化导致硝基化合物的形成，甲基的氧化导致羧酸的形成。此外，亚氨基的水解形成了一个中间酮，随后的反应最终导致三氟甲基苯甲酸的形成。对于glyoxyl-phenyl部分，氧化导致苯甲酸的形成。甲氧基亚氨基的O-去甲基化导致羟基亚氨基化合物。亚氨基的水解产生α-酮酸，随后通过脱羧作用转化为邻苯二甲酸。胆汁中分离出与葡萄糖醛酸或硫酸结合的共轭物。低剂量和高剂量的4%至7%和31%至47%，分别以未代谢的测试材料形式在粪便中排出。吸收的剂量主要在胆汁中分离。进一步的加工将测试材料及其代谢物返回到肠道，并通过粪便排出或通过肝肠循环再吸收。

Male and female rats were dosed by gavage with either [Glyoxyl-Phenyl-(U)-14C] (radiochemical purity range: >97 to >99%) or [Trifluormethyl-Phenyl-(U)-14C]-/trifloxystrobin/ (CGA- 279202) (radiochemical purity: >99%). For all of the groups except D2, the animals were dosed with [Glyoxyl-Phenyl-(U)-14C]-/trifloxystrobin/ (CGA 279202). ...Thirty five metabolites were isolated and identified from the urine, feces and bile samples. Major metabolic pathways included 1) hydrolysis of the methyl ester to the corresponding acid, 2) O-demethylation of the methoxyimino group, and 3) oxidation of the methyl side chain to a primary alcohol, followed by further oxidation to the carboxylic acid. This last reaction was a more prominent metabolic pathway in the female rats with the resultant isolation of major sex-specific urinary metabolites. Cleavage of the glyoxyl-phenyl and trifluoromethyl-phenyl moieties accounted for 10% of the dose. For the trifluoromethyl phenyl fragment, oxidation of the hydroxyimino group led to the formation of a nitro compound and oxidation of the methyl group resulted in the formation of the carboxylic acid. In addition, hydrolysis of the imino group formed an intermediate ketone with succeeding reactions ultimately leading to trifluoromethyl benzoic acid. For the glyoxyl-phenyl moiety, oxidation resulted in the formation of a benzoic acid. O-demethylation of the methoxyimino group resulted in the hydroxyimino compound. Hydrolysis of the imino group yielded the a-keto acid followed by decarboxylation to the phthalic acid. Conjugates with glucuronide or sulfate were isolated from the bile. Four to 7% and 31 to 47% of the low and high doses, respectively, were eliminated in feces as the unmetabolized test material. The absorbed dose was predominantly isolated in the bile. Further processing returned the test material and/or metabolites to the intestinal tract and elimination in the feces or reuptake via the enterohepatic pathway.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：三氟戊菌胺是一种白色粉末。它被用作农业杀菌剂。人类暴露和毒性：三氟戊菌胺如果通过皮肤吸收是有害的。长时间或频繁的皮肤接触可能会使某些人产生过敏反应。动物研究：在小鼠和大鼠口服、家兔经皮以及大鼠吸入途径中，三氟戊菌胺被认为是低急性毒性的。在大鼠急性灌胃或亚慢性饮食给药后，三氟戊菌胺没有显示出选择性的神经毒性。在大鼠中，处理对交配、生育或窝仔数没有影响。在S. typhimurium TA98、TA100、TA102、TA1535或TA1357菌株以及E. coli WP2 uvrA菌株（无论是否经过代谢激活）中，三氟戊菌胺没有表现出诱变性。生态毒性研究：三氟戊菌胺对非目标水生生物有毒。三氟戊菌胺可能会影响抗氧化酶的活动，干扰小球藻的光合作用，并损害细胞结构。三氟戊菌胺对鱼类胚胎高度有毒。对水蚤（Daphnia magna）非常有毒，即使在环境相关浓度下也可能对其造成伤害。三氟戊菌胺对羊头鱼（sheepshead minnows）极具毒性。

IDENTIFICATION AND USE: Trifloxystrobin is a white powder. It is used as agricultural fungicide. HUMAN EXPOSURE AND TOXICITY: Trifloxystrobin is harmful if absorbed through skin. Prolonged or frequently repeated skin contact may cause allergic reactions in some individuals. ANIMAL STUDIES: Trifloxystrobin was considered to be of low acute toxicity by the oral route in mice and rats, by the dermal route in rabbits, and by the inhalation route in rats. Trifloxystrobin was not selectively neurotoxic following acute gavage or subchronic dietary administration in rats. There were no treatment-related effects upon the mating, fertility, or litter size in rats. It was not mutagenic in S. typhimurium strains TA98, TA100, TA102, TA1535, or TA1357, or in E. coli strain WP2 uvrA with and without metabolic activation. ECOTOXICITY STUDIES: Trifloxystrobin is toxic to nontarget aquatic organisms. Trifloxystrobin could affect the activities of antioxidant enzymes, disrupt photosynthesis in Chlorella vulgaris, and damage cellular structure. Trifloxystrobin is highly toxic to fish embryos. It is very toxic to Daphnia magna and can cause harm to D. magna at environmentally relevant concentrations. Trifloxystrobin was very highly toxic to sheepshead minnows.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：不太可能对人类致癌

Cancer Classification: Not likely to be carcinogenic to humans

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒病例。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 毒性数据

LC50 (大鼠) > 4,646 毫克/立方米

LC50 (rat) > 4,646 mg/m3

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 解毒与急救

获得医疗援助。眼睛：立即用大量流动水冲洗。皮肤：用大量肥皂和水冲洗；移除受污染的衣物。吸入：将受害者移至新鲜空气处。如有必要，施行人工呼吸。

Get medical aid. Eyes: Immediately rinse with plenty of running water. Skin: Flush with plenty of soap and water; remove contaminated clothing. Inhalation: Remove victim to fresh air. Apply artificial respiration if necessary.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雄性和雌性大鼠通过灌胃给予[Glyoxyl-Phenyl-(U)-(14)C]（比活度范围：54.3至63.5 uCi/mg，放射化学纯度范围：>97至>99%）或[Trifluormethyl-Phenyl-(U)-14C]/三氟菌灵/（CGA-279202）（比活度：59.2 uCi/mg，放射化学纯度：>99%）。除了D2组外，所有组的大鼠都被给予[Glyoxyl-Phenyl-(U)-(14)C]-/三氟菌灵/（CGA 279202）。在B1和D1组中，从分别给予0.5或100 mg/kg测试物质的5只/性别的大鼠中收集尿液和粪便样本，持续7天。对于C1组，5只/性别的大鼠先用0.5 mg/kg未标记的/三氟菌灵/（CGA 279202）（纯度：99.7%）预处理14天，然后用0.5 mg/kg标记的测试物质。同样从这些动物中收集尿液和粪便样本，持续7天。在D2组中，5只/性别的大鼠给予100 mg/kg的[Trifluormethyl-Phenyl-(U)-(14)C]/三氟菌灵/（CGA-279202），并收集尿液和粪便样本，持续7天。在F1和5组以及F2和6组中，分别有12只/性别的大鼠给予0.5或100 mg/kg的测试物质。根据之前组别的药代动力学测定，在4个时间点测定组织残留。G组动物的胆管被插管。在G1和3组中，6只雄性和5只雌性大鼠用0.5 mg/kg的测试物质处理。在G2和4组中，分别有6只雄性和4只雌性大鼠用100 mg/kg的测试物质处理。在低剂量水平，56至65%的剂量被吸收，41至47%的剂量从胆汁中回收。在高剂量组，25至45%的剂量被吸收，19至35%的剂量从胆汁中回收。在低剂量处理中，雄性大鼠的18至19%和79%的剂量分别通过尿液和粪便排出。对于雌性大鼠，35至42%通过尿液排出，56至63%通过粪便排出。用未标记的测试物质预处理并未改变排泄模式。在高剂量组中，雄性大鼠分别有10至12%和82至84%通过尿液和粪便排出。雌性大鼠通过尿液排出27%，通过粪便排出64至66%。D2组动物呼出的气体中回收到的放射性标记物非常少。组织中的放射性标记物衰减的半衰期从13至42小时不等，除了高剂量雌性的脾脏和血液（分别为68和82小时）。血液中测试物质达到最大浓度的时间为给药后12至24小时。达到最大浓度的时间范围是给药后23至67小时。在7天后，尸体中的放射性标记物残留非常少，仅回收了给药剂量的0.3至0.5%。

Male and female rats were dosed by gavage with either [Glyoxyl-Phenyl-(U)-(14)C] (spec. act. range: 54.3 to 63.5 uCi/mg, radiochemical purity range: >97 to >99%) or [Trifluormethyl-Phenyl-(U)-14C] /trifloxystrobin/ (CGA- 279202) (spec. act.: 59.2 uCi/mg, radiochemical purity: >99%). For all of the groups except D2, the animals were dosed with [Glyoxyl-Phenyl-(U)-(14)C]-/trifloxystrobin/ (CGA 279202). In Groups B1 and D1, urine and feces samples were collected up to 7 days from 5 animals/sex dosed with 0.5 or 100 mg/kg of the test material, respectively. For Group C1, 5 animals/sex were pretreated for 14 days with 0.5 mg/kg of unlabelled /trifloxystrobin/ (CGA 279202) (purity: 99.7%), followed by 0.5 mg/kg of the labelled test material. Urine and feces samples were likewise collected from these animals for up to 7 days. In Group D2, 5 animals/sex were dosed with 100 mg/kg of [Trifluormethyl-Phenyl-(U)-(14)C] /trifloxystrobin/ (CGA-279202) and urine and feces samples were collected up to 7 days. Twelve animals/sex were dosed with either 0.5 or 100 mg/kg of the test material in Groups F1 and 5 and Groups F2 and 6, respectively. Tissue residues were determined at 4 time points based upon pharmacokinetic determinations derived from the previous groups. The bile ducts of animals in Group G were cannulated. In Groups G1 and 3, 6 males and 5 females were treated with 0.5 mg/kg of the test material. Six males and 4 females were dosed with 100 mg/kg of the test material in Groups G2 and 4, respectively. At the low dose level, 56 to 65% of the dose was absorbed with 41 to 47% of the dose recovered from the bile. In the high dose group, 25 to 45% of the dose was absorbed with 19 to 35% of the dose recovered from the bile. In the low dose treatment, 18 to 19% and 79% of the dose was excreted in the urine and feces, respectively, of the males. For the females, 35 to 42% was excreted in the urine and 56 to 63% in the feces. Pretreatment with unlabelled test material did not alter the pattern of excretion. In the high dose groups, the males excreted 10 to 12% and 82 to 84% in the urine and feces, respectively. The females excreted 27% in the urine and 64 to 66% in the feces. Very minimal levels of radiolabel were recovered from the expired air of the animals in Group D2. The half lives for the depletion of radiolabel from the tissues ranged from 13 to 42 hours except for the spleen and blood of the high dose females (68 and 82 hours, respectively). The times to maximal concentration of the test material in the blood were either 12 to 24 hours after dosing. The times to maximal concentration ranged from 23 to 67 hours after dosing. Residual retention of the radiolabel in the carcass after 7 days was very minimal with 0.3 to 0.5% of the dose administered recovered.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

三氟苯醚菌胺通过胃肠道中等程度地被吸收并迅速分布。在低剂量组中，大约56%和65%的给药剂量（AD）分别在男性和女性中被吸收（基于尿液、粪便、胆汁和组织中的总回收量），其中胆汁中男性占41%，女性占47%。在高剂量组中，吸收程度分别为41%和27%，而胆汁含量分别为35%和19%，分别对应男性和女性。血液动力学显示，在两个性别中吸收率中等，有两个峰值（低剂量在0.5小时和12小时后，高剂量在12小时和24小时后）。在血液、肾脏、脾脏和肝脏中发现的残留物最高，并且两性之间相似。放射性物质的排泄是迅速的。大约85-96%的剂量在48小时内被排出。排泄途径受动物性别的影响，女性通过尿液排出的量是男性的两倍，分别占剂量的27-42%和12-19%。通过粪便排出的量在男性和女性中分别占剂量的79-82%和56-64%。在两性中，胆汁排泄是主要的排泄途径。消除过程中存在肠肝短路机制的参与。

Trifloxystrobin was moderately absorbed from the gastrointestinal tract and rapidly distributed. In the low-dose group, approximately 56% and 65% administered dose (AD) was absorbed in males and females respectively (based on the total recovery from urine, feces, bile and tissues), with 41 and 47% being in bile of males and females, respectively. In the high-dose, group, the degree of absorption was 41 and 27%, while the bile content was 35% and 19%, respectively for males and females. The blood kinetics revealed a moderate absorption rate in both sexes with two peaks (after 0.5 and 12 hours at the low dose and 12 and 24 hours at the high dose). The highest residues were found in blood, kidneys, spleen and liver and were comparable between sexes. Excretion of the radioactivity was rapid. Approximately 85-96% of the dose was excreted within 48 hours. The route of elimination was influenced by the sex of the animals, females eliminated twice the amount with the urine than males, accounting for 27-42% and 12-19% of the dose, respectively. The amounts excreted via feces were 79-82% and 56-64% of the dose in males and females, respectively. In both sexes biliary excretion was the major route of elimination. The involvement of an enterohepatic shunt mechanism in the elimination process is indicated.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  劳森试剂 、 methyl 2-methoxyimino-2-[2-[[1-[3-(trifluoromethyl)phenyl]ethylideneamino]oxymethyl]phenyl]acetate 以 5,5-dimethyl-1,3-cyclohexadiene 、 甲基叔丁基醚 、 Petroleum ether 为溶剂， 生成 methyl{2-[(1-(3-trifluoromethylphenyl)ethylidene)-aminooxymethyl]-phenyl}-2-methoximino-thioacetate
  参考文献：
  名称：

  Oxime derivatives and their use as pesticides

  摘要：

  这项发明涉及新的肟衍生物，以及多种制备它们的方法，以及它们作为杀虫剂的用途。

  公开号：

  US06177463B1
• 作为产物：
  描述：

  在 sodium methylate 作用下， 以 甲醇 为溶剂， 以95.3 %的产率得到methyl 2-methoxyimino-2-[2-[[1-[3-(trifluoromethyl)phenyl]ethylideneamino]oxymethyl]phenyl]acetate
  参考文献：
  名称：

  CN116199598

  摘要：

  公开号：

文献信息

• 一种肟菌酯的制备方法
  申请人：江苏七洲绿色科技研究院有限公司

  公开号：CN113683527B

  公开（公告）日：2022-03-01

  本发明提供一种肟菌酯的制备方法，其包括如下步骤，（1）使原料A与碱在第一温度下进行反应；（2）使步骤（1）中反应得到的物质与原料B在第二温度下进行反应以生成肟菌酯；其中，所述第一温度大于所述第二温度，所述原料A为间三氟甲基苯乙酮肟，所述原料B为(E)‑2‑(2‑溴甲基苯基)‑2‑甲氧亚胺基乙酸甲酯。本申请通过使原料A先与强碱进行反应生成中间体，再使中间体与原料B反应生成肟菌酯，避免了原料B以及肟菌酯的分解，提高了肟菌酯的收率；另外，通过将反应体系中生成的水去除再加入原料B进行反应，避免了肟菌酯水解，进一步提高了肟菌酯的收率；本申请中工艺简单、溶剂易回收、制备过程绿色环保，适用于工业化生产。
• Oxime derivative and bactericide containing the same as active ingredient
  申请人：Shionogi & Co., Ltd.

  公开号：US06048885A1

  公开（公告）日：2000-04-11

  A compound represented by general formula (I) or a salt thereof, a process for producing the same, an intermediate for the production thereof, and a bactericide (fungicide) containing the same as the active ingredient wherein R.sup.1 represent optionally substituted aryl, optionally substituted heterocycle, mono- or di-substituted methyleneamino, optionally substituted (substituted imino)methyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, substituted carbonyl or substituted sulfonyl; R.sup.2 represents alkyl, alkenyl, alkynyl or cycloalkyl; R.sup.3 represents optionally substituted heterocycle; R.sup.4 represents hydrogen, alkyl, alkoxy, halogen, nitro, cyano or haloalkyl; M represents oxygen, S(O)i (i being 0, 1 or 2), NR.sup.16 (R.sup.16 being hydrogen, alkyl or acyl) or a single bond; n represents 0 or 1, provided n represent 1 when R3 represents imidazol-1-yl or 1H-1, 2, 4-triazol-1-yl; and the symbol .about. represents the E form, Z form or a mixture thereof: ##STR1##

  化合物的普通式(I)或其盐，制备方法，其制备的中间体以及含有其作为活性成分的杀菌剂（杀真菌剂），其中R.sup.1代表可选取代的芳基，可选取代的杂环，单取代或双取代的亚甲基氨基，可选取代的（取代亚胺）甲基，可选取代的烷基，可选取代的烯基，可选取代的炔基，取代的羰基或取代的磺酰基; R.sup.2代表烷基，烯基，炔基或环烷基; R.sup.3代表可选取代的杂环; R.sup.4代表氢，烷基，烷氧基，卤素，硝基，氰基或卤代烷基; M代表氧，S（O）i（i为0、1或2），NR.sup.16（R.sup.16为氢，烷基或酰基）或单键; n代表0或1，当R3代表咪唑-1-基或1H-1，2，4-三唑-1-基时，n代表1; 符号.表示E型，Z型或其混合物： ## STR1 ##
• Oxime derivatives and their use as pesticides
  申请人：Bayer Aktiengesellschaft

  公开号：US06177463B1

  公开（公告）日：2001-01-23

  The invention relates to new oxime derivatives, to a plurality of processes for their preparation, and to their use as pesticides.

  这项发明涉及新的肟衍生物，以及多种制备它们的方法，以及它们作为杀虫剂的用途。
• CN116199598
  申请人：——

  公开号：——

  公开（公告）日：——