(1S,2R,4R)-4-isopropyl-1-methyl-2-(o-tolylmethoxy)-7-oxabicyclo[2 .2.1]heptane | 87818-31-3

• 物质功能分类: 化学农药原药 - 除草剂 - 二苯醚类除草剂
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1S,2R,4R)-4-isopropyl-1-methyl-2-(o-tolylmethoxy)-7-oxabicyclo[2 .2.1]heptane
• 英文别名: (1S,2R,4R)-cinmethylin；Cinmethylin；(1S,2R,4R)-1-methyl-2-[(2-methylphenyl)methoxy]-4-propan-2-yl-7-oxabicyclo[2.2.1]heptane
• CAS: 87818-31-3
• 化学式: C₁₈H₂₆O₂
• 分子量: 274.403
• InChiKey: QMTNOLKHSWIQBE-FGTMMUONSA-N

物化性质

• 熔点：
  25°C
• 沸点：
  313°C
• 密度：
  d20 1015 kg/m3
• 闪点：
  147 °C
• 溶解度：
  2.30e-04 M
• 蒸汽压力：
  7.57e-05 mmHg

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

对氧磷酶（PON1）是有机磷代谢的关键酶。PON1可以通过水解使一些有机磷失活。PON1水解多种有机磷杀虫剂以及神经毒剂（如梭曼、沙林和VX）的活性代谢物。PON1的多态性导致不同个体之间酶水平和催化效率的差异，这反过来表明不同个体可能更容易受到有机磷暴露的毒性影响。

Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

丁氧基甲基氯乙基磷酰氯（Cinmethylin）是一种胆碱酯酶或乙酰胆碱酯酶（AChE）抑制剂。胆碱酯酶抑制剂（或“抗胆碱酯酶”）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，低剂量时会导致过度流涎和眼泪，随后是肌肉痉挛，最终导致死亡。神经气体和许多用于杀虫剂的物质已被证明通过结合乙酰胆碱酯酶活性位点的丝氨酸，完全抑制该酶。乙酰胆碱酯酶分解神经递质乙酰胆碱，该递质在神经和肌肉接头处释放，以使肌肉或器官得以放松。乙酰胆碱酯酶抑制的结果是乙酰胆碱积聚并继续发挥作用，使得任何神经冲动不断传递，肌肉收缩不会停止。最常见的乙酰胆碱酯酶抑制剂之一是基于磷的化合物，它们被设计成与酶的活性位点结合。结构要求是一个带有两个亲脂性基团的磷原子、一个离去基团（如卤素或硫氰酸盐）以及一个末端的氧。

Cinmethylin is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. 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. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

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

急性接触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，如果呼吸肌受到影响，可能会导致死亡。在运动神经积累的乙酰胆碱会导致神经肌肉接头处尼古丁受体的过度刺激。当这种情况发生时，可以看到肌肉无力、疲劳、肌肉痉挛、肌束震颤和麻痹的症状。当自主神经节积累乙酰胆碱时，这会导致交感系统中尼古丁受体的过度刺激。与此相关的症状包括高血压和低血糖。由于乙酰胆碱积累，中枢神经系统中尼古丁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。当由于副交感神经乙酰胆碱受体处乙酰胆碱过量而出现毒蕈碱样过度刺激时，可能会出现视力障碍、胸闷、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、肠蠕动和排尿等症状。与有机磷农药暴露特别相关的生育效应，包括男性和女性的生育能力、生长和发育。关于生育效应的研究大多是在农村地区使用杀虫剂和杀虫剂的农民中进行的。在女性中，月经周期紊乱、怀孕时间延长、自然流产、死产以及后代的一些发育效应与有机磷农药暴露有关。产前暴露与胎儿生长和发育受损有关。神经毒性效应也与有机磷农药中毒有关，导致人类出现四种神经毒性效应：胆碱能综合征、中间综合征、有机磷诱导的迟发性多发性神经病（OPIDP）和慢性有机磷诱导的神经精神障碍（COPIND）。这些综合征在急性接触和慢性接触有机磷农药后出现。

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. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

低剂量暴露的症状包括过度流涎和眼泪。急性剂量症状包括严重的恶心/呕吐、流涎、出汗、心动过缓、低血压、昏厥和抽搐。肌肉无力可能会逐渐加重，如果呼吸肌肉受影响，可能会导致死亡。还可能出现高血压、低血糖、焦虑、头痛、颤抖和共济失调。

Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include 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. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露处理

如果已经摄入该化合物，应使用5%碳酸氢钠进行快速洗胃。对于皮肤接触，应用肥皂和水清洗皮肤。如果化合物进入眼睛，应用大量等渗盐水或水清洗。在严重情况下，应给予阿托品和/或普瑞洛辛。抗胆碱能药物作用是抵消过量的乙酰胆碱的作用并重新激活乙酰胆碱酯酶。阿托品可以与普瑞洛辛或其他吡啶季铵盐（如三甲氧胺或欧比多辛）联合使用作为解毒剂，尽管至少有两项荟萃分析发现使用“-氧胺”没有益处，甚至可能有害。阿托品是一种毒蕈碱拮抗剂，因此可以阻断乙酰胆碱在外周的作用。

If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 危险品标志：
  Xn,N
• 安全说明：
  S22,S23,S61
• 危险类别码：
  R20
• WGK Germany：
  3
• 海关编码：
  29321900
• 危险品运输编号：
  UN3082 9/PG 3
• RTECS号：
  RN8762000

制备方法与用途

毒性 大鼠急性经口LD₅₀为4500毫克/公斤，兔急性经皮LD₅₀大于2000毫克/公斤。对兔眼睛有轻度刺激作用，对皮肤也有刺激性。在大鼠13周饲喂试验中，无作用剂量为300毫克/公斤；2年饲喂试验中，无作用剂量为小鼠30毫克/公斤、大鼠100毫克/公斤。该物质未见致癌或致突变作用。

虹鳟鱼LC₅₀为6.6毫克/升（96小时）、水蚤LC₅₀为7.2毫克/升（48小时）。鹌鹑经口LD₅₀大于2150毫克/公斤，野鸭则大于5620毫克/公斤。

化学性质 本品是一种深琥珀色液体。沸点313℃，相对密度1.014（20℃），蒸汽压为10.1×10^-3帕斯卡（20℃）。能溶于大多数有机溶剂，在水中溶解度约为63毫克/升，分配系数（正辛醇/水）为6850。在≤145℃条件下稳定，在pH值3～11时水解半衰期为30天（25℃）。

用途 这是一种选择性内吸传导型芽前土壤处理剂，属于桉树脑类除草剂，能被敏感植物根系吸收并经木质部传导至根及芽的生长点，抑制分生组织生长使其死亡。施用于水稻、棉花等作物后，会迅速代谢成羟基化合物并与植物体内的糖苷结合成共轭化合物失去毒性。该产品施药期长且用量少，在稻田防除稗草效果尤为显著。使用方法包括毒土或喷雾处理，移栽秧苗5～8天、稗草1.5叶期时，每平方米用10%乳油2～3毫升，保持水层3～5厘米，持续保水5～7天。在旱地如花生田中，则需要加大用量至每平方米82%乳油7.5～12.5毫升，在播后苗前进行土壤处理。

生产方法 以1-蒎烯为起始原料制备。

1. 萜品-4-醇的制备：将0.735摩尔1-蒎烯、0.714摩尔35%硫酸和催化剂0.2克混合均匀后，在20～30℃下搅拌反应20小时，随后加热至45℃保温8小时。弃去水层，在油层中加入50克25%氢氧化钠和50克异丙醇，回流并分馏出约48克1,4-桉树脑，纯度70%。
2. 将0.25摩尔1,4-桉树脑与10毫升甘油二甲醚混合，在10毫升甘醇二甲醚中加入0.8克无水醋酸钠，冷却后过滤浓缩，减压蒸馏得产物约28.4克。
3. 环庚草醚的合成：在氮气保护下，将150毫升干燥过的二甲基甲酰胺加热至60℃，滴加上一步产物与75毫升二甲基甲酰胺混合液，反应温度控制在60～70℃。降温后滴加36.6克2-甲基氯苄并继续搅拌反应6小时。将反应物倒入1000毫升水中，用浓盐酸酸化后用己烷萃取合并的萃取液，干燥、过滤脱溶于环庚草醚中。

类别 农药

毒性分级 中毒

急性毒性 口服-大鼠 LD₅₀: 4500毫克/公斤

可燃性危险特性 10%乳油易燃

储运特性 库房通风低温干燥，与食品原料分开储存运输

灭火剂 干粉、泡沫、砂土

反应信息

• 作为产物：
  描述：

  (±)-2-exo-hydroxy-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1 ]heptane 生成 (1S,2R,4R)-4-isopropyl-1-methyl-2-(o-tolylmethoxy)-7-oxabicyclo[2 .2.1]heptane
  参考文献：
  名称：

  PAYNE, G. B.;SOLOWAY, S. B.;POWELL, J. E.;ROMAN, S. A.;KOLLMEYER, W. D.

  摘要：

  DOI：

文献信息

• [EN] A PROCESS FOR PREPARING AN OPTICALLY ACTIVE CINEOLE DERIVATIVE<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN DÉRIVÉ DE CINÉOLE OPTIQUEMENT ACTIF
  申请人：BASF AGRO BV

  公开号：WO2018210662A1

  公开（公告）日：2018-11-22

  The present invention relates to a process for preparing optically active 1,4-cineole derivatives by enzymatic resolution and enantiomerically pure optically active 1,4-cineole derivatives of purity greater than 99.9 % that have been prepared by this process. The present invention further relates to a process for preparing 7-oxabicyclo[2.2.1]heptane derivatives from the enantiomerically pure optically active 1,4-cineole derivatives.

  本发明涉及一种通过酶解和手性纯度大于99.9%的光学活性1,4-桉叶醇衍生物的制备过程。本发明还涉及一种从手性纯度高的光学活性1,4-桉叶醇衍生物制备7-氧杂双环[2.2.1]庚烷衍生物的过程。
• Herbicidal Activity of Cineole Derivatives
  作者：Allan F. M. Barton、Bernard Dell、Allan R. Knight

  DOI：10.1021/jf101827v

  日期：2010.9.22

  dose-dependent herbicidal activity against annual ryegrass and radish with many of the derivatives showing improved herbicidal activity relative to 1,8-cineole and high-cineole eucalyptus oil. Increased activity of cineole ester derivatives compared to their associated hydroxy-cineole and carboxylic acid was not observed. No relationship between lipophilicity of the carboxylic acid portion of cineole ester derivatives

  精油及其成分具有作为生态可接受的农药的潜力，也可能具有新颖的作用方式。在这项工作中，制备了大多数桉树油中主要成分天然单萜1,8-cineole 3和1,4-cineole 4的羟基和酯衍生物，并针对一年生黑麦草（黑麦草）进行了芽前除草活性。和萝卜（萝卜）变种 Long Scarlet（Long Scarlet）在基于实验室的生物测定法中进行了研究。1,8-桉树脑，桉树油和所有衍生物对一年生黑麦草和萝卜均表现出剂量依赖性的除草活性，其中许多衍生物相对于1,8-桉树脑和高桉树脑的桉树油具有更好的除草活性。与它们相关的羟基-桉树脑和羧酸相比，未观察到桉树脑酯衍生物的活性增加。没有观察到桉树脑酯衍生物的羧酸部分的亲脂性与除草活性之间的关系。结果表明这些桉树脑衍生物可能是环境可接受的除草剂。
• [EN] PROCESS FOR PREPARING 2-EXO-(2-METHYLBENZYLOXY)-1-METHYL-4-ISOPROPYL-7-OXABICYCLO[2.2.1]HEPTANE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 2-EXO-(2-MÉTHYLBENZYLOXY)-1-MÉTHYL-4-ISOPROPYL-7-OXABICYCLO[2.2.1]HEPTANE
  申请人：BASF AGRO BV

  公开号：WO2018177907A1

  公开（公告）日：2018-10-04

  This invention relates to a process for preparing (±)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane of the formula (I) (I), any of its individual enantiomers or any non-racemic mixture thereof, comprising the step of reacting (±)-2-exo-hydroxy-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptane of the formula (II) (II), any of its individual enantiomers or any non-racemic mixture thereof with a 2-Methylbenzyl compound of the formula (III) (III), wherein X is a leaving group, in the presence of at least one base, at least one catalyst selected from rubidium salts, cesium salts and any combination thereof and at least one inert organic solvent S1.

  该发明涉及一种制备(±)-2-外消旋-(2-甲基苄氧基)-1-甲基-4-异丙基-7-氧杂双环[2.2.1]庚烷的过程，其化学式为(I)，任何其个别对映体或其非外消旋混合物，包括以下步骤：将(±)-2-外消旋-羟基-1-甲基-4-异丙基-7-氧杂双环[2.2.1]庚烷的化学式为(II)，任何其个别对映体或其非外消旋混合物与化学式(III)的2-甲基苄基化合物反应，其中X是一个脱离基，在至少一种碱、至少一种选择自铷盐、铯盐和二者任意组合的催化剂和至少一种惰性有机溶剂S1的存在下。
• [EN] PROCESS FOR PREPARING 2-EXO-(2-METHYLBENZYLOXY)-1-METHYL-4-ISOPROPYL-7-OXABICYCLO[2.2.1]HEPTANE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 2-EXO- (2-MÉTHYLBENZYLOXY)-1-MÉTHYL-4-ISOPROPYL-7-OXABICYCLO [2.2.1] HEPTANE
  申请人：BASF AGRO BV

  公开号：WO2018050518A1

  公开（公告）日：2018-03-22

  This invention relates to a process for preparing (±)-2-exo-(2-Methylbenzyloxy)-1-methyl-4-iso- propyl-7-oxabicyclo[2.2.1]heptane of the formula (I), any of its individual enantiomers or any non-racemic mixture thereof, comprising the steps of (a) reacting (±)-2-exo-hydroxy-1-methyl-4-isopropyl-7-oxabicyclo[2.2.1]heptaneof the formula (II), any of its individual enantiomers or any non-racemic mixture thereof with a 2-Methylbenzyl compound of the formula (III) wherein X is a leaving group in the presence of at least one base capable of forming water or a C1 -C 4 alkyl alcohol under the reaction conditions, and at least one inert organic sol- vent, and (b) simultaneously removing water, the C1-C4 alkyl alcoholor any mixture thereof from the reaction mixture.

  这项发明涉及制备(±)-2-外消旋-(2-甲基苄氧基)-1-甲基-4-异丙基-7-氧代-2-环丙基[2.2.1]庚烷的方法，其化学式为(I)，包括以下步骤：(a)将(±)-2-外消旋-羟基-1-甲基-4-异丙基-7-氧代-2-环丙基[2.2.1]庚烷的化学式(II)，其任一手性体或非旋光混合物与化学式(III)中X为脱离基的2-甲基苄化合物在至少一种能够在反应条件下生成水或C1-C4烷基醇的碱存在下反应，并在至少一种惰性有机溶剂中进行；(b)同时从反应混合物中移除水、C1-C4烷基醇或二者的混合物。
• [EN] PROCESS FOR PREPARING TERPINENE-4-OL<br/>[FR] PROCÉDÉ DE PRÉPARATION DE TERPINÈNE-4-OL
  申请人：BASF AGRO BV

  公开号：WO2017144336A1

  公开（公告）日：2017-08-31

  The present invention relates to a process for preparing terpinene-4-ol from limonene-4-ol via a hydrogenation reaction in the presence of a nickel catalyst.

  本发明涉及一种通过在镍催化剂存在下进行氢化反应从柠檬烯-4-醇制备萜品-4-醇的方法。