灭多威 | 16752-77-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机碳酸及其衍生物
• 中文名称: 灭多威
• 中文别名: 乙肟威；S-甲基-N[(甲基氨基甲酰)-氧]硫代乙酰胺；1-(甲硫基)亚乙基氮N-甲基氨基甲酸酯；灭虫快；灭索威；万灵；1-(甲硫基)亚乙基氨甲基氨基甲酸酯；灭多虫；灭多威原药
• 英文名称: Methomyl
• 英文别名: methyl N-(methylcarbamoyloxy)ethanimidothioate
• CAS: 16752-77-5
• 化学式: C₅H₁₀N₂O₂S
• 分子量: 162.213
• InChiKey: UHXUZOCRWCRNSJ-UHFFFAOYSA-N

物化性质

• 稳定性/保质期：
  Stable, but incompatible with strong bases and strong oxidizing agents.

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  76
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

(14)C-甲硫威在大鼠体内转化为(14)CO2（约25%）、乙腈（约50%）和未识别的尿液代谢物（约25%）。通过与对照组物质的比较研究，确认尿液中不存在母体肟和母体化合物的亚砜和砜。

(14)C-METHOMYL ... WAS BIOTRANSFORMED IN RATS INTO (14)CO2 (ABOUT 25%), ACETONITRILE (ABOUT 50%), & UNIDENTIFIED URINARY METABOLITES (ABOUT 25%). ABSENCE IN URINE OF PARENT OXIME & ... SULFOXIDE & SULFONE OF PARENT CMPD WAS CONFIRMED BY COMPARISON STUDIES WITH AUTHENTIC MATERIAL.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 甲霜灵的代谢主要是通过水解途径。在大鼠接受(14)C-标记甲霜灵处理后，尿液中发现的主要代谢物包括氧肟酸酯硫酸盐、游离氧肟酸酯和氧肟酸酯葡萄糖苷酸 ...。

... METABOLISM OF METHOMYL IS PRIMARILY BY HYDROLYTIC ROUTE. PRINCIPAL METABOLITES FOUND IN URINE FOLLOWING TREATMENT OF RATS WITH (14)C-LABELED METHOMYL WERE OXIME-O-SULFATE, FREE OXIME, OXIME GLUCURONIDE ... .

来源:Hazardous Substances Data Bank (HSDB)

代谢

Methomyl can exist in 2 geometric configurations. ... In rats, carbonyl- or oximino-labeled syn-methomyl was metabolized to carbon dioxide & acetonitrile at a 2:1 ratio. In contrast, the anti isomer was metabolized predominately to acetonitrile. It was concluded on the basis of this & other evidence that a Beckman rearrangement of the syn & anti oximes occurs prior to formation of carbon dioxide & acetonitrile.

Methomyl can exist in 2 geometric configurations. ... In rats, carbonyl- or oximino-labeled syn-methomyl was metabolized to carbon dioxide & acetonitrile at a 2:1 ratio. In contrast, the anti isomer was metabolized predominately to acetonitrile. It was concluded on the basis of this & other evidence that a Beckman rearrangement of the syn & anti oximes occurs prior to formation of carbon dioxide & acetonitrile.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠体内，甲硫基迅速转化为甲硫基甲基醇、肟、亚砜和亚砜肟；这些不稳定的中间体被转化为乙腈和二氧化碳，主要通过呼吸和尿液排出体外。

In rats, methomyl was rapidly converted to methomyl methylol, oxime, sulfoxide, & sulfoxide oxime; these unstable intermediates were converted to acetonitrile & carbon dioxide, which were eliminated primarily via respiration & in the urine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：E组 人类非致癌性证据

Cancer Classification: Group E Evidence of Non-carcinogenicity for Humans

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A4；不能归类为人类致癌物。

A4; Not classifiable as a human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 暴露途径

该物质可以通过吸入其气溶胶和通过摄入被身体吸收。

The substance can be absorbed into the body by inhalation of its aerosol and by ingestion.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 暴露途径

吸入，吞食，皮肤和/或眼睛接触

inhalation, ingestion, skin and/or eye contact

来源:The National Institute for Occupational Safety and Health (NIOSH)

毒理性

• 症状

眼睛刺激；视力模糊，瞳孔缩小；流涎；腹部绞痛，恶心，呕吐；呼吸困难；乏力（虚弱，疲惫），肌肉抽搐；肝脏，肾脏损害

irritation eyes; blurred vision, miosis; salivation; abdominal cramps, nausea, vomiting; dyspnea (breathing difficulty); lassitude (weakness, exhaustion), muscle twitching; liver, kidney damage

来源:The National Institute for Occupational Safety and Health (NIOSH)

吸收、分配和排泄

给大鼠施用标记甲硫眯后收集的呼出气中含标记的二氧化碳和丙酮。

EXPIRED AIR COLLECTED FOLLOWING ADMIN OF /LABELLED/ METHOMYL TO RATS CONTAINED LABELED CO2 & ACETONITRILE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

治疗过程和症状报告了一名患者摄入约2.25克甲硫威后企图自杀的情况。在摄入后6小时，血液中甲硫威的浓度为1.61 ppm，尿液中的浓度为10.91 ppm；在摄入后15小时，血液中的水平为0.04 ppm，尿液中的水平为0.25 ppm；在摄入后22小时，样本中未检测到甲硫威。

... The course of therapy & symptoms for a patient who had attempted suicide by ingesting about 2.25 g of methomyl /was reported/. At 6 hr postingestion, methomyl was present in the blood at 1.61 ppm & in the urine at 10.91 ppm; at 15 hr, levels were 0.04 ppm in the blood & 0.25 ppm in the urine; & at 22 hr, methomyl was not detectable in the samples.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

单次口服5毫克/公斤的14碳标记甲硫眯唑在雌性CD大鼠或雄性大鼠中几乎完全吸收（95-98%）。喂食了14碳标记甲硫眯唑的雄性大鼠在24小时内几乎排除了所有标记物质。处理一天后，在全身和器官中发现的原始放射性标签不到10%。尿液中（25%）、呼吸二氧化碳中（25%）和乙腈中（50%）的放射性活性占据了大部分恢复的放射性。尿液中没有出现母体甲硫眯唑。

Near complete (95-98%) absorption of a single 5 mg/kg oral dose of 14 carbon-labeled methomyl occurred in female CD or male rats. Male rats fed 14 carbon-labeled methomyl eliminated almost all of the labeled material in 24 hr. 10% or less of the original radiolabel was found in the whole body & organs one day after treatment. Urine (25%), respiratory carbon dioxide (25%), & acetonitrile (50%) accounted for most of the recovered radioactivity. No parent methomyl appeared in the urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一小时后，在将含有14C-甲硫基的药剂应用到小鼠皮肤上之后，剂量的2.9%出现在血液中，5%在肝脏中，56%在剩余的尸体中。8小时后，分布情况是血液中6.1%，肝脏中3.3%，消化道中3.8%，其他个别组织中含量较少（小于1%）。剩余的尸体中含有原始剂量的15%……。

One hour after the dermal applications of (14)C-methomyl to mice ..., 2.9% of the dose was present in blood, 5% in liver and 56% in the remaining carcass. After 8 h the distribution was 6.1% in blood, 3.3% in liver, 3.8% in the gastrointestinal tract and smaller amounts (< 1%) in other individual tissues. The remaining carcass contained 15% of the original dose ... .

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 储存条件：
  库房应保持通风、低温和干燥，并与食品原料分开储运。

制备方法与用途

制备方法

1. 将乙醛与硫酸羟胺在碱性溶液中反应，制成乙醛肟，并将其溶于γ-甲基吡咯烷酮中。
2. 经氯化处理制得氯代乙醛肟。随后，在氯代乙醛肟生成液中加入甲硫醇和水，于5℃下滴加50%氢氧化钠溶液至pH值为6～7，制成灭多威肟的γ-甲基吡咯烷酮溶液。
3. 最后，向该溶液中加入三乙胺和异氰酸甲酯进行反应，最终制得乙肟威。

合成制备方法

1. 将乙醛与硫酸羟胺在碱性溶液中反应制成乙醛肟，并将其溶于γ-甲基吡咯烷酮中。
2. 经氯化处理制得氯代乙醛肟。随后，在氯代乙醛肟生成液中加入甲硫醇和水，于5℃下滴加50%氢氧化钠溶液至pH值为6～7，制成灭多威肟的γ-甲基吡咯烷酮溶液。
3. 最后，向该溶液中加入三乙胺和异氰酸甲酯进行反应，最终制得乙肟威。

反应信息

• 作为反应物：
  描述：

  灭多威 在 吡啶 、 二氯化硫 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 methyl N-(((((4-cyanophenyl)amino)thio)(methyl)carbamoyl)oxy)ethanimidothioate
  参考文献：
  名称：

  Insecticidal Benzoylphenylurea-S-Carbamate:  A New Propesticide with Two Effects of Both Benzoylphenylureas and Carbamates

  摘要：

  New propesticides with two effects of both benzoylphenylureas and carbamates were designed and synthesized by the key intermediate N-chlorosulfenyl-N-methylcarbamate, which was prepared for the first time. These benzoylphenylurea-S-carbamates were identified by H-1 NMR spectroscopy and elemental analyses. The bioactivities of the new compounds were evaluated. These benzoylphenylurea-S-carbamates exhibited excellent larvicidal activities against Oriental armyworm, some of which were good as compared to the parent benzoylphenylureas. Toxicity assays indicated that these benzoylphenylurea-S-carbamates had knockdown activities of carbamates at higher concentrations and insect growth regulator activities of benzoylphenylureas at lower concentrations. We found that the title compounds exhibited good systemic larvicidal activities against Oriental armyworm, which were especially advantageous when combating sucking pests. Some of these title compounds can kill aphids and mosquitoes as well.

  DOI：

  10.1021/jf063564g
• 作为产物：
  描述：

  硫代乙酰氧肟酸甲酯 、 异氰酸甲酯 在 四丁基硫酸氢铵 作用下， 以 水 为溶剂， 反应 0.5h， 以98.3%的产率得到灭多威
  参考文献：
  名称：

  一种灭多威的制备方法

  摘要：

  本发明公开了一种灭多威的制备方法，以甲硫基乙醛肟为原料，在相转移催化剂的作用下与甲基异氰酸酯在水中反应，反应结束后升温至50℃～60℃，物料全溶后冷却结晶，过滤，得到滤液和滤饼，滤液用有机溶剂萃取，然后脱溶，脱溶后的固体与滤饼合并干燥，得到灭多威产品。该制备方法具有收率高、成本低廉、操作简便等优点。

  公开号：

  CN111377843B

文献信息

• Genetic toxicity of <i>N</i>-methylcarbamate insecticides and their <i>N</i>-nitroso derivatives
  作者：T. C. Wang、C. M. Chiou、Y. L. Chang

  DOI：10.1093/mutage/13.4.405

  日期：——

  N-Methylcarbamate esters are an important group of insecticides. They have lower acute toxicity to vertebrates than organophosphates, although their genotoxicity has not been adequately studied. Here we investigate the cytotoxicity and genotoxicity of N-methylcarbamate insecticides and their N-nitroso derivatives in Chinese hamster V79 cells, using the hprt locus as a marker, and also assess inhibition

  N-甲基氨基甲酸酯是重要的一组杀虫剂。尽管对它们的遗传毒性尚未进行充分研究，但它们对脊椎动物的急性毒性比有机磷酸盐低。在这里，我们使用hprt基因座作为标记，研究N-甲基氨基甲酸酯杀虫剂及其N-亚硝基衍生物在中国仓鼠V79细胞中的细胞毒性和遗传毒性，并评估对间隙连接细胞间通讯的抑制作用。将N-甲基氨基甲酸酯杀虫剂化学N-亚硝化以获得N-亚硝基衍生物。N-亚硝基化大大增加了中国仓鼠V79细胞hprt位点的N-甲基氨基甲酸酯的细胞毒性和致突变性。N-亚硝基-N-甲基氨基甲酸酯的诱变潜力远高于许多其他已知的诱变亚硝基化合物，以及一些非亚硝基诱变的烷基化剂。亲本N-甲基氨基甲酸酯本身没有致突变性，但是，它们抑制间隙连接的细胞间通讯的效率是经过充分研究的肿瘤启动子12-O-十四烷酰phorbol-13-乙酸酯的一半。研究结果表明，N-甲基氨基甲酸酯杀虫剂及其N-亚硝基衍生物具有在化学致癌作用的多个阶
• The delayed genotoxic effect of N-nitroso N-propoxur insecticide in mammalian cells
  作者：Chih-Min Lin、L.Y. Wei、Tsing-Cheng Wang

  DOI：10.1016/j.fct.2006.11.015

  日期：2007.6

  N-nitroso derivative of an extensively used insecticide, propoxur, consistently induced dose-responsive chromosome aberrations and sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO-W8) cells. Further investigations indicated that post-treatment incubation with a regular 1.5-cell-cycle period did not offer an unbiased estimation of the genotoxicity of N-nitroso carbamate insecticides. The scale

  广泛使用的杀虫剂丙氧磷的N-亚硝基衍生物在中国仓鼠卵巢（CHO-W8）细胞中持续诱导剂量反应性染色体畸变和姐妹染色单体交换（SCE）。进一步的研究表明，在规则的1.5个细胞周期内进行后处理孵育不会对N-亚硝基氨基甲酸酯类杀虫剂的遗传毒性提供公正的估计。染色体畸变诱导的规模随着治疗后潜伏期的延长而增加。在熟练O（6）-甲基鸟嘌呤-DNA-甲基转移酶的CHO-AGT细胞中未发现可比的现象。在CHO-W8细胞中，在第一个复制周期中对杀虫剂进行脉冲处理显示出比第二个周期中更高的SCE诱导率。在其他氨基甲酸酯类杀虫剂（包括涕灭威，呋喃丹和灭多威）的N-亚硝基衍生物诱导的SCE中也发现了类似现象。处理的细胞直到去除处理后12小时才显示出明显的扰动的细胞周期进程。基于上述观察结果，O（6）-甲基鸟嘌呤-DNA加合物被认为是由N-甲基氨基甲酸酯杀虫剂的延迟遗传毒性作用引起的主要病变，如本报告所述。
• 一种先导化合物硫代灭多威及其合成方法
  申请人：河南理工大学

  公开号：CN105348159B

  公开（公告）日：2017-03-29

  本发明公开了一种先导化合物硫代灭多威及其合成方法，属于农药杀虫剂或新药开发技术领域。本发明的技术方案要点为：硫代灭多威具有如下结构式，其中R为烷基、烯基或芳香基。本发明还公开了该硫代灭多威的合成方法。本发明制备过程中使用的磺酰氯是液体，相比于氯气易于操作且方便控制，对操作人员的危害大大降低，并且对于生产设备也没有特别的要求，适合工业化生产。
• Insecticidal carbamates
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US04198427A1

  公开（公告）日：1980-04-15

  A composition useful as an insecticide containing a reation product of formaldehyde and a compound such as methomyl.

  一种作为杀虫剂有用的组合物，包含甲醛和甲胺威等化合物的反应产物。
• Process for the preparation of carbamates of N-hydroxythioimidates
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US04096166A1

  公开（公告）日：1978-06-20

  An improved process for converting N-hydroxythioimidates to N-(methylcarbamoyloxy)-thioimidates by reaction with methylcarbamoyl chloride at pH above 10 in a two-phase reaction medium: water and a water-immiscible organic solvent.

  一种改进的方法，通过在pH值高于10的两相反应介质中，将N-羟基硫代亚胺酯与甲基氨甲酰氯反应，转化为N-(甲基氨甲酰氧基)-硫代亚胺酯。这两相反应介质包括水和一种与水不相溶的有机溶剂。

表征谱图