2,3-二氢-2,2-二甲基苯并呋喃-7-基N,N'-二甲基-N,N'-硫代二氨基甲酸丁酯 | 65907-30-4

• 物质功能分类: 化学农药原药 - 杀虫剂 - 氨基甲酸酯杀虫剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 中文名称: 2,3-二氢-2,2-二甲基苯并呋喃-7-基N,N'-二甲基-N,N'-硫代二氨基甲酸丁酯
• 中文别名: 2,4-二甲基-6-氧杂-5-氧代-3-硫杂-2,4-二氮杂癸酸2,3-二氢-2,2-二甲基-7-苯并呋喃酯；呋线威；保苗
• 英文名称: Furathiocarb
• 英文别名: (2,2-dimethyl-3H-1-benzofuran-7-yl) N-[butoxycarbonyl(methyl)amino]sulfanyl-N-methylcarbamate
• CAS: 65907-30-4
• 化学式: C₁₈H₂₆N₂O₅S
• mdl: MFCD00078698
• 分子量: 382.5
• InChiKey: HAWJXYBZNNRMNO-UHFFFAOYSA-N

物化性质

• 熔点：
  <25 °C
• 沸点：
  197°C (rough estimate)
• 密度：
  1.2125 (rough estimate)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）
• LogP：
  4.700
• 颜色/状态：
  Yellow, viscous liquid.
• 蒸汽压力：
  3.9X10-3 mPa (2.9X10-8 mm Hg) @ 25 °C
• 稳定性/保质期：
  Stable up to 400 °C.
• 分解：
  In water DT50 4 days (pH 9).
• 碰撞截面：
  190.73 Ų [M+H]+ [CCS Type: TW]
• 保留指数：
  2520.5;2495

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.555
• 拓扑面积：
  93.6
• 氢给体数：
  0
• 氢受体数：
  6

ADMET

代谢

在大鼠体内的代谢转化通过快速且完全的水解进行，随后是氧化和结合反应。主要通过肾脏排泄。

Metabolic transformation in rats proceeds via rapid and complete hydrolysis, followed by oxidation and conjugation. Excretion occurs mainly via kidney.

来源:Hazardous Substances Data Bank (HSDB)

代谢

甲酸酯类化合物的新陈代谢的第一步是水解成甲酸，然后甲酸分解成二氧化碳（CO2）和相应的胺。N-甲基和N, N-二甲基衍生物的水解机制不同。N-甲基甲酸酯通过异氰酸中间体，而在N, N-二甲基甲酸酯的水解中，会形成一个加成产物，即羟基离子，产生醇和N, N-二甲基取代的酸。酯酶催化的水解速率在哺乳动物中比植物和昆虫快。除了水解，还会发生氧化反应，包括：芳香环的羟基化，O-脱烷基化，N-甲基羟基化，N-脱烷基化，脂肪族侧链的氧化，以及亚砜化成相应的砜。氧化与混合功能氧化酶（MFO）酶相关。共轭作用在哺乳动物中形成O-和N-葡萄糖苷酸、硫酸盐和巯基尿酸衍生物。糖苷和磷酸盐是植物中更常见的共轭产物。/甲酸酯类杀虫剂/

The first step in the metabolism of carbamates is hydrolysis to carbamic acid, which decomposes to carbon dioxide (CO2) and the corresponding amine. The mechanism of hydrolysis is different for N -methyl and N-dimethyl derivatives. The N-methyl carbamates pass through an isocyanate intermediate, whereas in the hydrolysis of N-dimethylcarbamates, an addition product with a hydroxyl ion is formed yielding the alcohol and N-dimethyl substituted acid. The rate of hydrolysis by esterases is faster in mammals than in plants and insects. Apart from hydrolysis, oxidation also takes place including: hydroxylation of the aromatic ring, O-dealkylation, N -methyl hydroxylation, N-dealkylation, oxidation of aliphatic side chains, and sulfoxidation to the corresponding sulfone. Oxidation is associated with the mixed-function oxidase (MFO) enzymes. Conjugation leads to the formation of O- and N- glucuronides, sulfates, and mercapturic acid derivatives in mammals. Glycosides and phosphates are conjugation products more common in plants. /Carbamate Pesticides/

来源:Hazardous Substances Data Bank (HSDB)

代谢

呋线丹的药代动力学在Sprague-Dawley雄性大鼠体内进行了研究，通过皮肤给药。使用高效液相色谱（HPLC）和柱后衍生化方法来分析呋线丹及其代谢物（克百威、3-羟基克百威和3-酮克百威）。在大鼠的血浆和尿液中检测到了克百威和3-羟基克百威，而不是呋线丹本身。另一种潜在的代谢物3-酮克百威在任何样本中均未观察到。

The pharmacokinetics of furathiocarb were studied in vivo in male Sprague-Dawley rats following dermal treatment. HPLC and post-column derivatization were used for the analysis of furathiocarb and its metabolites (carbofuran, 3-hydroxycarbofuran and 3-ketocarbofuran). Carbofuran and 3-hydroxycarbofuran were detected in plasma and urine rather than furathiocarb. 3-Ketocarbofuran, another potential metabolite, was not observed in any sample. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

甲酰胺通过肝脏酶促水解；降解产物由肾脏和肝脏排出。

The carbamates are hydrolyzed enzymatically by the liver; degradation products are excreted by the kidneys and the liver. (L793)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

非草胺是胆碱酯酶或乙酰胆碱酯酶（AChE）的抑制剂。碳酰胺通过与酶的活性位点上的碳酰胺化形成不稳定的复合物来抑制胆碱酯酶。这种抑制作用是可逆的。胆碱酯酶抑制剂抑制乙酰胆碱酯酶的作用。由于其基本功能，干扰乙酰胆碱酯酶作用的化学物质是强效的神经毒素，即使在低剂量下也会导致过度流涎和流泪。在高剂量暴露下，头痛、流涎、恶心、呕吐、腹痛和腹泻通常是显著的症状。乙酰胆碱酯酶分解在神经和肌肉接头释放的神经递质乙酰胆碱，以使肌肉或器官放松。乙酰胆碱酯酶抑制的结果是乙酰胆碱积累并继续发挥作用，使得任何神经冲动不断传递，肌肉收缩不会停止。

Furathiocarb is a cholinesterase or acetylcholinesterase (AChE) inhibitor. Carbamates form unstable complexes with chlolinesterases by carbamoylation of the active sites of the enzymes. This inhibition is reversible. A cholinesterase inhibitor suppresses the action of acetylcholine esterase. Because of its essential function, chemicals that interfere with the action of acetylcholine esterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

急性暴露于胆碱酯酶抑制剂可能会导致胆碱能危象，表现为严重的恶心/呕吐、流涎、出汗、心动过缓、低血压、崩溃和抽搐。肌肉无力可能性增加，如果呼吸肌肉受累，可能导致死亡。在运动神经积累的乙酰胆碱会导致神经肌肉接头处烟碱表达的过度刺激。当这种情况发生时，可以看到肌肉无力、疲劳、肌肉痉挛、肌肉跳动和麻痹的症状。当自主神经节有乙酰胆碱积累时，这会导致交感系统中烟碱表达的过度刺激。与此相关的症状是高血压和低血糖。由于乙酰胆碱积累，中枢神经系统中烟碱乙酰胆碱受体的过度刺激会导致焦虑、头痛、抽搐、共济失调、呼吸和循环抑制、震颤、全身无力，甚至可能昏迷。当由于乙酰胆碱过多而在毒蕈碱乙酰胆碱受体上表现出毒蕈碱过度刺激时，可能会出现视力障碍、胸部紧绷、由于支气管收缩引起的喘息、支气管分泌物增加、唾液分泌增加、流泪、出汗、肠蠕动和排尿的症状。长期高（>10年）暴露会导致神经心理学后果，包括感知和视动处理方面的障碍（A15321）。

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Chronically high (>10 years) exposure leads to neuropsychological consequences including disturbances in perception and visuo-motor processing (A15321).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

吸入 (L793)；口服 (L793)；皮肤给药 (L793)

Inhalation (L793) ; oral (L793); dermal (L793)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

与有机磷化合物一样，症状和体征基于过度的胆碱能刺激。与有机磷中毒不同，氨基甲酸酯中毒的持续时间往往较短，因为神经组织乙酰胆碱酯酶的抑制作用是可逆的，且氨基甲酸酯的代谢速度更快。肌肉无力、眩晕、出汗和轻微的身体不适是常见的早期症状。头痛、流涎、恶心、呕吐、腹痛和腹泻在较高暴露水平时常常更为明显。瞳孔收缩伴视力模糊、不协调、肌肉抽搐和言语不清也有报道。(L795)

As with organophosphates, the signs and symptoms are based on excessive cholinergic stimulation. Unlike organophosphate poisoning, carbamate poisonings tend to be of shorter duration because the inhibition of nervous tissue acetylcholinesterase is reversible, and carbamates are more rapidly metabolized. Muscle weakness, dizziness, sweating and slight body discomfort are commonly reported early symptoms. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Contraction of the pupils with blurred vision, incoordination, muscle twitching and slurred speech have been reported. (L795)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

目前关于哺乳动物通过吸入或口服途径接触后，氨基甲酸盐在各器官和组织的分布情况的信息很少。报告有残留物的器官包括肝脏、肾脏、大脑、脂肪和肌肉。在大鼠中，半衰期约为3-8小时。人类通过尿液排出氨基甲酸盐的速度似乎也很快，而且人类的代谢途径与大鼠相同。/氨基甲酸酯类杀虫剂/

Little information is available on the distribution of carbamates in the various organs and tissues in mammals following exposure by inhalation or the oral route. The organs in which residues have been reported are the liver, kidneys, brain, fat, and muscle.The half-life in the rat is of the order of 3 - 8 hr. It seems that the excretion of carbamates via urine is also rapid in man, and that the metabolic pathways in man are the same as those in the rat. /Carbamate pesticides/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

甲氧基甲酯的药代动力学在Sprague-Dawley雄性大鼠体内进行了研究，这些大鼠在皮肤处理后。高效液相色谱和柱后衍生化技术用于分析甲氧基甲酯及其代谢物（克百威、3-羟基克百威和3-酮克百威）。在血浆和尿液中检测到克百威和3-羟基克百威，而不是甲氧基甲酯。另一种潜在的代谢物3-酮克百威在任何样本中均未观察到。血浆中克百威的浓度高于3-羟基克百威，但在尿液中情况则相反。1,500 mg/kg剂量下，克百威和3-羟基克百威的血浆浓度-时间曲线下面积、Tmax和Cmax值分别为2.4-8.0 mg等效/ml、12小时和0.1-0.4 mg等效/ml。仅对3-羟基克百威计算了半衰期（28小时）。两种代谢物以剂量依赖性方式排出，没有饱和。

The pharmacokinetics of furathiocarb were studied in vivo in male Sprague-Dawley rats following dermal treatment. HPLC and post-column derivatization were used for the analysis of furathiocarb and its metabolites (carbofuran, 3-hydroxycarbofuran and 3-ketocarbofuran). Carbofuran and 3-hydroxycarbofuran were detected in plasma and urine rather than furathiocarb. 3-Ketocarbofuran, another potential metabolite, was not observed in any sample. The concentration of carbofuran was higher than that of 3-hydroxycarbofuran in plasma, but the reverse was the case in urine. The corresponding area under the plasma concentration-time curve, Tmax, and Cmax values of carbofuran and 3-hydroxycarbofuran for 1,500 mg/kg doses were 2.4-8.0 mg equiv/ml, 12 hr and 0.1-0.4 mg equiv/ml, respectively. T1/2 was calculated only for 3-hydroxycarbofuran (28 hr). Two metabolites were excreted in a dose-dependent manner without saturation.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T+,N
• 安全说明：
  S28,S36/37,S38,S45,S60,S61
• 危险类别码：
  R43,R25,R26,R48/22,R36/38,R50/53
• 危险品运输编号：
  UN 2811
• RTECS号：
  DF6652100
• 包装等级：
  I
• 危险类别：
  6.1(a)
• WGK Germany：
  3

制备方法与用途

氨基甲酸酯类杀虫剂

呋线威

呋线威属于氨基甲酸酯类杀虫剂，是胆碱酯酶抑制剂。它主要用作杀线虫杀虫剂，并且对土壤栖息昆虫具有内吸作用。

这种杀虫剂的制备方法多样，可以通过取代苯氧基、萘氧基或肟基等烯醇与异氰酸甲酯反应生成，也可以在脱盐酸剂存在下与N-甲基氨基甲酰氯或氯甲酸苯酯等甲胺反应合成。早在1954年，Metcaf等人合成了许多中性取代苯基氨基甲酸酯，并发现它们有杀虫作用。美国Union Carbide公司于1956年成功研发了甲萘威。由于其高效、广谱的杀虫活性和对高等动物低毒的特点，以及合成简单且原料易得，该类杀虫剂迅速发展成为年产值万吨的产品。进入20世纪60年代后，氨基甲酸酯类杀虫剂的发展进入高速期，并形成了一个重要类别。

害扑威是日本最早的取代苯基氨基甲酸酯类杀虫剂之一，随后相继研发出速灭威、异丙威、仲丁威和灭杀威等多种此类杀虫剂。这些化合物主要在防治水稻飞虱和叶蝉类害虫方面表现优异，并对天敌蜘蛛影响较小。

美国在此期间还成功合成了肟基氨基甲酸酯类杀虫剂，如涕灭威和灭多威。这类杀虫剂通常具有内吸作用，适用于咀嚼式口器及刺吸式口器的害虫，但其毒性较高。70年代后，社会对高效且安全的农药需求增加，导致高毒品种被改造成低毒产品，例如由克百威开发出丁硫克百威和硫双灭多威。

与此同时，N,N-二甲基氨基甲酸酯类杀虫剂如抗蚜威和苯硫威也相继问世。前者主要用于防治蚜虫（包括对有机磷具有抗性的蚜虫），后者是有效的杀螨剂，能够有效对付卵、幼虫和若虫。此外，还开发了N-甲基氨基甲酸酯类杀虫剂双氧威以及肟基氨基甲酸酯类杀虫剂棉铃威和环线肟。

中国目前广泛使用的氨基甲酸酯杀虫剂包括：甲萘威、速灭威、异丙威、仲丁威、残杀威、涕灭威、灭多威、克百威、抗蚜威等。

理化性质

纯品为黄色液体，沸点160℃/1.33Pa，密度1.16g/cm³（20℃），蒸汽压0.084MPa（20℃）。溶解度（20℃）：水10mg/L，溶于丙酮、已烷、甲醇、正辛醇、异丙醇和甲苯。在400℃下稳定。

作用机理

呋线威是一种内吸性杀虫剂，并具有触杀和胃毒作用。

毒性

大鼠急性经口LD50大于2g ai/kg，对皮肤有轻微刺激，眼睛的刺激极为轻微。在4小时内的急性吸入LC50为0.214mg/L空气。

防治对象和使用方法

主要用于防治土壤寄生虫。建议播种时施用0.5～2.0kg ai/hm²以保护玉米、油菜、甜菜和蔬菜种子及幼苗不受损害，效果可持续42天。也可用于种子处理和茎叶喷雾，适用于棉花和其他作物田。

制备方法

采用甲基氨基甲酸正丁酯与二氯化硫反应生成CISN(CH₃)CO₂C₄H₉-n，再与2,3-二氢-2,2-二甲基-7-苯并呋喃基-N-甲基氨基甲酸酯（克百威）反应即可制得呋线威成品。

分析方法

产品分析和残留物测定均采用气相色谱法（GC）。

开发单位

该杀虫剂由F. Bachmann & J. Drabek首次报道。1982年，汽巴-嘉基公司（Ciba Geigy Co.）进行开发并投产。

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• [EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
  申请人：BASF SE

  公开号：WO2014206910A1

  公开（公告）日：2014-12-31

  The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及公式（I）中变量如索权和说明中所定义的自行车基取代异噻唑啉化合物。这些化合物对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫方面具有用途。该发明还涉及一种通过使用这些化合物来控制无脊椎动物害虫的方法，以及包含所述化合物的植物繁殖材料、农业和兽医组合物。
• [EN] AZOLINE COMPOUNDS<br/>[FR] COMPOSÉS AZOLINE
  申请人：BASF SE

  公开号：WO2015128358A1

  公开（公告）日：2015-09-03

  The present invention relates to azoline compounds of formula (I) wherein A, B1, B2, B3, G1, G2, X1, R1, R3a, R3b, Rg1 and Rg2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

  本发明涉及式（I）的噁唑啉化合物，其中A、B1、B2、B3、G1、G2、X1、R1、R3a、R3b、Rg1和Rg2如权利要求和描述中所定义。这些化合物对抗或控制无脊椎动物害虫，特别是节肢动物害虫和线虫方面具有用途。该发明还涉及一种利用这些化合物控制无脊椎动物害虫的方法，以及包括所述化合物的植物繁殖材料、农业和兽医组合物。
• [EN] MICROBIOCIDAL OXADIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXADIAZOLE MICROBIOCIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2017157962A1

  公开（公告）日：2017-09-21

  Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.

  式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
• Thieno-pyrimidine compounds having fungicidal activity
  申请人：Brewster Kirkland William

  公开号：US20070093498A1

  公开（公告）日：2007-04-26

  The present invention relates to thieno[2,3-d]-pyrimidine compounds having fungicidal activity.

  本发明涉及具有杀真菌活性的噻吩[2,3-d]-嘧啶化合物。