(syn-Methyl)-Butanon-oxim | 10341-63-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (syn-Methyl)-Butanon-oxim
• 英文别名: Methyl ethyl ketoxime；(NE)-N-butan-2-ylidenehydroxylamine
• CAS: 10341-63-6
• 化学式: C₄H₉NO
• 分子量: 87.1216
• InChiKey: WHIVNJATOVLWBW-SNAWJCMRSA-N

物化性质

• 沸点：
  79.6 °C
• 密度：
  0.90±0.1 g/cm3(Predicted)
• 物理描述：
  Methyl ethyl ketoxime is a clear colorless liquid with a musty odor. (NTP, 1992)
• 颜色/状态：
  Liquid
• 熔点：
  -29.5 °C
• 闪点：
  138 °F (NTP, 1992)
• 溶解度：
  In water, 100,000 mg/L at 25 °C
• 蒸汽密度：
  3 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  1.06 mm Hg at 20 °C
• 分解：
  When heated to decomposition it emits toxic fumes of /oxides of nitrogen/.
• 折光率：
  Index of refraction = 1.4410 at 20 °C/D
• 解离常数：
  pKa = 12.45 at 25 °C

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  6
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  32.6
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

物质/2-丁酮肟/可以在动物体内代谢为2-丁酮和羟基胺。

The substance /2-butanone oxime/ can be metabolized in vivo in animals to 2-butanone and hydroxylamine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

甲基乙基酮肟在体内被广泛代谢，不会在组织中积累。给大鼠单次灌胃剂量为2.7、27或270 mg/kg时，主要转化为二氧化碳，大部分在给药后24小时内完成。静脉给药后，以百分比为基础排出的二氧化碳放射性比灌胃研究少，更多的给药剂量以尿液和挥发性物质形式排出。经皮给药后，排出的挥发性物质量显著大于灌胃或静脉给药。270 mg/kg的灌胃剂量可能导致代谢途径（s）饱和。有一些证据表明酮肟被代谢为酮，推测还有羟胺...

...Methyl ethyl ketoxime is extensively metabolized and does not accumulate in tissues. Single gavage doses of 2.7, 27, or 270 mg/kg administered to rats were primarily converted to carbon dioxide, mostly in the first 24 hours after dosing. After intravenous administration, less radioactivity on a percentage basis was excreted as carbon dioxide than in the gavage study, and more of the administered dose was excreted in urine and as volatiles. Following dermal administration, significantly greater amounts of volatiles were excreted than after gavage or intravenous administration. The 270 mg/kg gavage dose may result in saturation of a metabolic pathway(s). There is some evidence that the ketoxime is metabolized to the ketone and, presumably, hydroxylamine...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素 高铁血红蛋白血症 - 血液中增加的高铁血红蛋白的存在；这种化合物被归类为次要的毒性效应 溶血性贫血 - 血红蛋白或红细胞数量减少。 皮肤致敏剂 - 能诱导皮肤发生过敏反应的制剂。

Neurotoxin - Other CNS neurotoxin Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect Hemolytic anemia - Decreased hemoglobin or number of red blood cells. Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

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

毒理性

• 毒性数据

LC50 (大鼠) > 1350 ppm/4小时

LC50 (rat) > 1350 ppm/4hr

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

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β受体激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注5%葡萄糖水（D5W）/SRP: "保持开放"，最小流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。/毒物A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在妊娠第14天，给怀孕小鼠单次口服14(C)-2丁酮肟。此外，一只雄性小鼠也被给予单次口服(14)C-2-丁酮肟。看来该物质通过口服途径被迅速吸收，并完好地分布到全身。整个研究期间尿液和胆汁中含有显著的活动。肠道活动最小。这表明该物质主要通过肾脏排泄。

Pregnant mice were administered a single oral dose of 14(C)-2 butanone oxime on day 14 of gestation. In addition, a male mouse was administered a single oral dose of (14)C-2-butanone oxime. It appears that the substance is rapidly absorbed via the oral route, and distributed intact through the body. Urine and bile contained significant activity throughout the study. Intestinal activity was minimal. This suggests that the substance is primarily excreted via the kidneys.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

14(C)-甲基乙基酮肟（MEKO）在F344雄性大鼠体内的处置情况通过口服、静脉注射和皮肤给药后进行了确定。口服剂量为2.7、27和270 mg/kg的主要排泄方式为CO2（71-49%），随着剂量的增加，排泄百分比逐渐降低。尿液中（13-26%）和挥发性物质（5-18%）的排泄随着剂量的增加而增加。72小时后，大约5-6%的剂量仍留在主要组织中。静脉注射2.7 mg/kg的剂量也主要排泄为 （48.8%），尿液和呼出挥发性物质的排泄分别占21.4%和11.4%。大约7%的放射性物质在72小时后仍留在组织中。皮肤给药后，2.7和270 mg/kg剂量分别吸收了13%和26%。在放入代谢笼之前，从给药部位挥发的可能性解释了低吸收。MEKO被生物转化为至少五种极性代谢物，这些代谢物只能通过阴离子交换色谱部分分离。与葡萄糖苷酸酶孵育，但不与磺酸酯酶孵育，改变了尿液代谢谱。甲基乙基酮是挥发性物质中的主要成分。

The disposition of 14(C)-methyl ethyl ketoxime (MEKO) was determined in the male F344 rat following oral, iv and dermal administration. Oral doses of 2.7, 27 and 270 mg/kg were primarily excreted as CO2 (71-49%) in decreasing percentage as the dose increased. Excretion in urine (13-26%) and as volatiles (5-18%) increased as the dose increased. Five to 6% of the dose remained in the major tissues after 72 hr. An iv dose of 2.7 mg/kg was also principally excreted as CO2 (48.8%) with excretion in urine and as expired volatiles accounting for 21.4 and 11.4%, respectively. About 7% of the administered radioactivity remained in the tissues after 72 hr. Following dermal administration, 13 and 26% of a 2.7 and 270 mg/kg dose, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

甲基乙基酮肟在体内被广泛代谢，不会在组织中积累。给大鼠单次灌胃剂量的2.7、27或270毫克/千克后，主要转化为二氧化碳，大部分在给药后24小时内完成。静脉给药后，以百分比计算，排泄为二氧化碳的放射性活性比灌胃研究要少，更多的给药剂量以尿液和挥发性物质形式排出。经皮给药后，排出的挥发性物质量显著大于灌胃或静脉给药。270毫克/千克的灌胃剂量可能会导致某个（些）代谢途径饱和。有一些证据表明，酮肟被代谢为酮，可能还会转化为羟基胺...

...Methyl ethyl ketoxime is extensively metabolized and does not accumulate in tissues. Single gavage doses of 2.7, 27, or 270 mg/kg administered to rats were primarily converted to carbon dioxide, mostly in the first 24 hours after dosing. After intravenous administration, less radioactivity on a percentage basis was excreted as carbon dioxide than in the gavage study, and more of the administered dose was excreted in urine and as volatiles. Following dermal administration, significantly greater amounts of volatiles were excreted than after gavage or intravenous administration. The 270 mg/kg gavage dose may result in saturation of a metabolic pathway(s). There is some evidence that the ketoxime is metabolized to the ketone and, presumably, hydroxylamine...

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  (syn-Methyl)-Butanon-oxim 在 cerium(III) chloride 、 silica gel 、 sodium iodide 作用下， 反应 0.1h， 以72%的产率得到N-乙基乙酰胺
  参考文献：
  名称：

  Li, Zheng; Lu, Zhong; Ding, Runbo, Journal of Chemical Research, 2006, # 10, p. 668 - 670

  摘要：

  DOI：
• 作为产物：
  描述：

  丁酮 在 羟胺 作用下， 以 甲醇 为溶剂， 生成 (syn-Methyl)-Butanon-oxim
  参考文献：
  名称：

  三苯基膦催化肟在活化烯烃上的迈克尔加成

  摘要：

  使用催化量的三苯膦发现了一种新的反应条件，用于将肟迈克尔加成到活化的烯烃上。这是经典碱（氢氧化物、醇盐）催化的迈克尔加成肟的第一个也是更温和的替代方案。各种醛肟 la-h 和酮肟 2a-c (图 1) 与不同的迈克尔受体如丙烯酸乙酯、丙烯腈、苯基乙烯基砜、甲基乙烯基酮和 1-nitrocyclohex-1-ene 反应以获得相应的迈克尔加合物。尝试了大约 35 个不同的示例（表 1 和方案 1）；除了在六个反应没有产生所需产物的情况下，产率从良好到极好不等。没有三苯膦的反应没有进行。提出了本反应中催化作用的合理机制（图 2）。

  DOI：

  10.1055/s-2003-39162

文献信息

• Facile One-Pot Syntheses of Amidines and Enamines from Oximes via Beckmann Rearrangement Using Trifluoromethanesulfonic Anhydride
  作者：Tomofumi Takuwa、Tomofumi Minowa、Jim Yoshitaka Onishi、Teruaki Mukaiyama

  DOI：10.1246/bcsj.77.1717

  日期：2004.9

  Iminocarbocation intermediates were in situ-generated by treating various oximes with trifluoromethanesulfonic anhydride (Tf2O) in the presence of triethylamine in toluene and nucleophilic trapping with amines or sodium enolates under mild conditions afforded the corresponding amidines and enamines. Some of the thus-obtained enamines were converted to 2-substituted 4-oxo-3-quinolinecarboxylic acid derivatives by subsequent intramolecular Friedel–Crafts acylation.

  通过将各种肟在甲苯中与三氟甲磺酸酐（Tf2O）和三乙胺反应，原位生成亚胺碳正中间体，并在温和条件下用胺或烯醇钠捕捉，得到相应的脒和烯胺。部分获得的烯胺随后通过分子内 Friedel-Crafts 酰基化反应转化为 2-取代的 4-氧代-3-喹啉羧酸衍生物。
• Direct Synthesis of Nitrones via Transition-Metal-Free Ring-Opening of N-Tosylaziridines with the Nitrogen Atom of Various (E)-Aldoximes and (E)-Ketoximes
  作者：Xing Li、Wenjing Yan、Rui Zhang、Honghong Chang、Wenchao Gao、Xiuping Tian、Wenlong Wei

  DOI：10.1055/s-0039-1690186

  日期：2019.11

  The KOH-, K2CO3-, or Et3N-catalyzed ring-opening reaction of N-tosylaziridines using the nitrogen atom of a series of (E)-aldoximes and (E)-ketoximes as a nucleophilic atom instead of an oxygen atom was developed to construct various nitrones under mild reaction conditions. Diverse (E)-aldoximes and (E)-ketoximes were demonstrated to be compatible with this reaction and the products of O-ring-opening reactions were not detected for most examples.

  KOH-、K2CO3-或Et3N催化的N-对甲苯磺酰基环氧丙烷的开环反应，使用(E)-醛肟和(E)-酮肟系列化合物的氮原子作为亲核原子，而不是氧原子，以在温和的反应条件下构建各种亚硝酮。多种(E)-醛肟和(E)-酮肟已证明与该反应兼容，并且大多数示例中未检测到O-环开启反应的产物。
• Synthesis of Highly Substituted Pyrroles via Nucleophilic Catalysis
  作者：Simbarashe Ngwerume、Jason E. Camp

  DOI：10.1021/jo1011448

  日期：2010.9.17

  tri-, and tetrasubstituted pyrroles is described. This regioselective one-pot method relies on nucleophilic catalysis of the intermolecular addition of oximes to activated alkynes and thermal rearrangement of the in situ generated O-vinyl oximes to form pyrroles that contain a functional group handle at the C3/C4 position.

  描述了提供二，三和四取代吡咯的简明合成的亲核催化方法。这种区域选择性的一锅法依赖于在分子间加成肟到活化的炔烃上的亲核催化和原位生成的O-乙烯基肟的热重排形成吡咯，这些吡咯在C3 / C4位置上含有一个官能团。
• REGIOSELECTIVE SYNTHESIS OF<i>E</i>-OXIMES CATALYZED BY FERRIC CHLORIDE UNDER SOLVENT-FREE CONDITIONS
  作者：Hossein Eshghi、Asadollah Hassankhani

  DOI：10.1080/00304940509354989

  日期：2005.12

  Oximes are useful for the isolation, purification and characterization of carbonyl compounds.'q2 They undergo a number of transformations such as the Beckmann and the Neber rearrangement, halogenation, nitration, deoxygenation, or reaction with organometallic reagent^.^ The Beckmann rearrangement of cyclohexanone oxime to E-caprolactam has been used as a powerful method for its manufacture ind~strially

  肟可用于羰基化合物的分离、纯化和表征。'q2 它们经历了许多转化，例如贝克曼和内伯重排、卤化、硝化、脱氧或与有机金属试剂反应^。环己酮的贝克曼重排肟到ε-己内酰胺已被用作工业生产的一种强有力的方法。~肟通常是通过羰基化合物与盐酸羟胺和碱如吡啶的反应制备的。~除了对称的情况酮，生成两种异构肟，Z 和 E，它们具有不同的物理和生物活性。6 合成肟的化学方法通常会产生两种几何异构体的混合物，必须通过色谱法或重结晶进行分离。然而，用于酮肟化或贝克曼重排的试剂也可以催化这些几何异构体的相互转化^。2 和 E 异构体混合物的平衡速率和平衡位置取决于温度；7a因此，温度控制至关重要。虽然羰基化合物与盐酸羟胺的反应在相转移催化剂、微波辐照或无溶剂条件下加速，但选择性不受影响。有几种方法可以合成醛肟的 Z 和 E 异构体。'dq 在许多情况下，E 异构体是通过盐酸盐法 13 或柱色谱法从这两种形式中获得的。
• Simple, Efficient and One-Pot Method for Synthesis of Aminomethylene<i>gem</i>-Diphosphonic Acid Derivatives from Ketones via Beckmann Rearrangement
  作者：Ruyu Chen、You Huang、Mingshu Wu

  DOI：10.1055/s-2004-831233

  日期：——

  A simple, expeditious and convenient synthesis of aminomethylene gem-diphosphonic acid derivatives in one-pot reaction using ketones, hydroxylamine hydrochloride, phosphorus trichloride and water as starting materials in the presence of pyridine via Beckmann rearrangement is described in the modest yields.

  描述了在吡啶存在下，通过 Beckmann 重排，使用酮、盐酸羟胺、三氯化磷和水作为起始原料，在一锅法反应中简单、快速和方便地合成氨基亚甲基偕二膦酸衍生物，收率适中。

表征谱图