2-氯苯亚甲基丙二腈 | 2698-41-1

• 物质功能分类: 化学试剂 - 有机试剂 - 氰化物/腈
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氯苯亚甲基丙二腈
• 中文别名: 邻氯苄叉缩丙二腈；邻氯苄叉丙二腈
• 英文名称: o-chlorobenzylidene malononitrile
• 英文别名: 2-(2-chlorobenzylidene)malononitrile；2-Chlorobenzylidenemalononitrile；2-[(2-chlorophenyl)methylidene]propanedinitrile
• CAS: 2698-41-1
• 化学式: C₁₀H₅ClN₂
• mdl: MFCD00019784
• 分子量: 188.616
• InChiKey: JJNZXLAFIPKXIG-UHFFFAOYSA-N

物化性质

• 熔点：
  68-70 °C(lit.)
• 沸点：
  126 °C0.1 mm Hg(lit.)
• 密度：
  1.2906 (rough estimate)
• 溶解度：
  Soluble in acetone, benzene, 1,4-dioxane, ethyl acetate, and methylene chloride (Windholz et al., 1983)
• 暴露限值：
  NIOSH REL: ceiling 0.05 ppm (0.4 mg/m3), IDLH 2 mg/m3; OSHA PEL: TWA 0.05 ppm; ACGIH TLV: ceiling 0.05 ppm (adopted).
• 物理描述：
  O-chlorobenzylidene malononitrile appears as white crystalline solid or light beige powder. Odor of pepper. (NTP, 1992)
• 颜色/状态：
  White crystalline solid
• 气味：
  Pepper-like odor.
• 蒸汽密度：
  6.52 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  3.4X10-5 mm Hg at 20 °C
• 分解：
  When heated to decomposition it emits very toxic fumes of /hydrogen chloride, nitrogen oxides and cyanides./
• 保留指数：
  1516;1555;1516
• 稳定性/保质期：

  稳定存储，但不相容于强氧化剂。具有可燃性。

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  47.6
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

猫和老鼠血液中的代谢物，经鉴定为O-氯代苄基亚硝基甲烷。这种代谢物是在红细胞细胞质中发生苄基亚硝基双键还原时产生的，与CS（催泪瓦斯）的解毒过程有关。

... METABOLITE IN BLOOD OF CATS & RATS, TO WHICH CS, O-CHLOROBENZYLIDENE MALONONITRILE, HAD BEEN ADMINISTERED, HAS ... BEEN /IDENTIFIED/ ... AS O-CHLOROBENZYLMALONONITRILE. REDUCTION OF THE BENZYLIDENE DOUBLE BOND, WHICH OCCURS IN THE ERYTHROCYTE CYTOPLASM, IS ASSOCIATED WITH THE DETOXIFICATION OF CS.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在给予兔子的静脉注射剂量中，发生了两种反应：水解和还原。O-氯苯甲醛和丙二腈是水解的产物，而O-氯苯甲基丙二腈是还原的产物。生物转化主要发生在血液中，但与肾脏相比，肝脏在转化中也很重要。O-氯苯亚甲基丙二腈及其基本代谢物O-氯苯甲醛和O-氯苯甲基丙二腈在血液中的半衰期较短。

IN RABBITS ADMINISTERED IV DOSES 2 REACTIONS TAKE PLACE HYDROLYSIS & REDUCTION. O-CHLOROBENZALDEHYDE & MALONONITRILE ARE PRODUCTS OF HYDROLYSIS & O-CHLOROBENZYL MALONONITRILE IS PRODUCT OF REDUCTION. BIOTRANSFORMATION TAKES PLACE MAINLY IN THE BLOOD, BUT LIVER, IN CONTRAST TO KIDNEYS, IS ALSO IMPORTANT IN THE TRANSFORMATION. O-CHLOROBENZYLIDENE MALONONITRILE & ITS BASIC METABOLITES, O-CHLOROBENZALDEHYDE & O-CHLOROBENZYL MALONONITRILE HAVE SHORT HALF-LIVES IN THE BLOOD.

来源:Hazardous Substances Data Bank (HSDB)

代谢

MICE RECEIVED O-CHLOROBENZYLIDENE MALONONITRILE BY IP INJECTION (0.5 LD50) OR BY AEROSOL EXPOSURE (20000 MG/MIN/CU M). INCREASED EXCRETION OF THIOCYANATE IN THE URINE WAS OBSERVED, INDICATING A TRANSFORMATION OF CS TO CYANIDE IN VIVO. 小鼠通过腹腔注射(0.5 LD50)或气溶胶暴露(20000毫克/分钟/立方米)接收O-氯苯亚甲基丙二腈。观察到尿液中硫氰酸盐的排泄增加，表明CS在体内转化为氰化物。

MICE RECEIVED O-CHLOROBENZYLIDENE MALONONITRILE BY IP INJECTION (0.5 LD50) OR BY AEROSOL EXPOSURE (20000 MG/MIN/CU M). INCREASED EXCRETION OF THIOCYANATE IN THE URINE WAS OBSERVED, INDICATING A TRANSFORMATION OF CS TO CYANIDE IN VIVO.

来源:Hazardous Substances Data Bank (HSDB)

代谢

(3)H-环标记、(14C-氰化物标记和(14C=C)侧链标记的CS在波特恩大鼠体内的命运进行了研究，这些大鼠通过腹膜内或灌胃的方式给药，剂量范围从0.08到159微摩尔/千克。在大多数情况下，剂量的最大比例（44%-100%）通过尿液排出。确定的主要尿液代谢物包括2-氯苯甲酸、1-O-(2-氯苄基)葡萄糖醛酸、2-氯苄基半胱氨酸和2-氯苯甲酸。确定的其他次要代谢物包括2-氯苄醇和2-氯苯基-2-氰丙酸酯。

The fate of (3)H-ring labeled, (14(C-cyanide labeled, and (14C=C) side chain-labeled CS was studied in Porton rats given intraperitoneal or gavage doses ranging from 0.08 to 159 umol/kg. In most cases, the largest proportion (44%-100%) of the dose was eliminated in the urine. The major urinary metabolites identified were 2-chlorohippuric acid, 1-O-(2-chlorobenzyl)glucuronic acid, 2-chlorobenzyl cysteine, and 2-chlorobenzoic acid. Minor metabolites identified included 2-chlorobenzyl alcohol and 2-chlorophenyl-2-cyanopropionate.

来源:Hazardous Substances Data Bank (HSDB)

代谢

六名男性志愿者暴露于浓度为0.5-1.5毫克/立方米的CS中，持续90分钟。这些人的血液中未检测到CS或2-氯苯甲醛，只有一人的血液中检测到微量的2-氯苄基丙二腈。

... Six male volunteers /were exposed/ to CS at concn of 0.5-1.5 mg/cu m for 90 min. Neither CS nor 2-chlorobenzaldehyde was detected in the blood of those persons, and only in one was a trace of 2-chlorobenzyl malononitrile detected.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

有机腈在体内和体外均可分解成氰化物离子。因此，有机腈的主要毒性机制是它们产生有毒的氰化物离子或氢氰酸。氰化物是电子传递链第四个复合体（存在于真核细胞线粒体膜中）中的细胞色素c氧化酶的抑制剂。它与这种酶中的三价铁原子形成复合物。氰化物与这种细胞色素的结合阻止了电子从细胞色素c氧化酶传递到氧气。结果，电子传递链被中断，细胞无法再通过有氧呼吸产生ATP能量。主要依赖有氧呼吸的组织，如中枢神经系统和心脏，受到特别影响。氰化物也通过与过氧化氢酶、谷胱甘肽过氧化物酶、变性血红蛋白、羟钴胺素、磷酸酶、酪氨酸酶、抗坏血酸氧化酶、黄嘌呤氧化酶、琥珀酸脱氢酶以及Cu/Zn超氧化物歧化酶结合，产生一些毒性效应。氰化物与变性血红蛋白中的三价铁离子结合，形成无活性的氰化变性血红蛋白。

Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

A4：不能分类为人类致癌物。

A4: Not classifiable as a human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

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

2-氯苄基亚硝基甲烷会导致严重的肺损伤以及心脏和肝脏的损害。

2-Chlorobenzylidene malononitrile can cause severe pulmonary damage and damage of the heart and liver.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

这种物质可以通过吸入、皮肤接触和摄入被身体吸收。

The substance can be absorbed into the body by inhalation, through the skin and by ingestion.

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

吸收、分配和排泄

暴露于浓度为14-245毫克/立方米的光气雾剂5分钟的大鼠吸收了可测量的化合物量。在血液中检测到了CS和一种还原产物，2-氯苄基丙二腈。

... Rats exposed to CS aerosols at concn of 14-245 mg/cu m for 5 min absorbed measurable quantities of the compound. Both CS and a reduction product, 2-chlorobenzyl malononitrile, were detected in the blood.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 职业暴露限值：
  Ceiling: 0.05 ppm (0.4 mg/m3) [skin]
• 危险等级：
  6.1(a)
• 立即威胁生命和健康浓度：
  2 mg/m3
• 危险品标志：
  T
• 安全说明：
  S26,S27,S36/37/39,S37/39,S45
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 危险品运输编号：
  UN 2647
• RTECS号：
  OO3675000
• 海关编码：
  2926909090
• 包装等级：
  I
• 危险类别：
  6.1(a)
• 储存条件：
  库房应保持低温、通风和干燥，并将物品与食品原料及氧化剂分开存放，实行专人管理。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: [(2-Chlorophenyl)methylene]malononitrile
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: [(2-Chlorophenyl)methylene]malononitrile
CAS number: 2698-41-1

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

---

Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C10H5ClN2
Molecular weight: 188.6

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

邻氯苄叉缩丙二腈（CS） 简介

邻氯苄叉缩丙二腈，也称为 CS，是一种美国军队目前使用的防暴剂（RCA）。它于 1928 年合成，并以创造者 Corson 和 Stoughton 的名字命名为“CS”。由于其较高的安全性，CS 在 1959 年取代了氯苯乙酮（CN），成为主要的 RAC。相比 CN，CS 更有效、更安全。它可以通过烟火方式传播，也可以以粉末配方（如 CS1 和 CS2）形式传播。

理化性质

邻氯苄叉缩丙二腈是一种可燃的白色结晶固体，具有类似胡椒的气味。它是催泪瓦斯（CS 瓦斯）的主要成分。

用途

邻氯苄叉缩丙二腈广泛应用于探索刺激物对人体的影响，作为催泪瓦斯和防暴剂。

危害

邻氯苄叉缩丙二腈 (CS) 气雾剂是一种有效的催泪剂，对上呼吸道有刺激作用。CS 暴露的特征效应包括瞬时结膜炎、眼睑痉挛、灼烧感和疼痛。长时间暴露在高浓度下可能会导致肺水肿和严重支气管痉挛。

类别

有毒物质

毒性分级

高毒

急性毒性

• 口服-大鼠 LD50: 178 毫克/公斤
• 口服-小鼠 LD50: 282 毫克/公斤

刺激数据

• 皮肤-兔：12%/6小时 轻度刺激
• 眼睛-兔：1 毫克 轻度刺激

可燃性危险特性

可燃；热分解时排出有毒氮氧化物和氯化物烟雾

储运特性

库房低温通风干燥，与食品原料、氧化剂分开存放，专人管理

灭火剂

雾水、二氧化碳、泡沫、干粉

职业标准

• TWA 0.4 毫克/立方米
• CL 0.4 毫克/立方米（皮肤）

反应信息

• 作为反应物：
  描述：

  2-氯苯亚甲基丙二腈 在 吗啉 作用下， 以 甲醇 为溶剂， 生成 6-amino-4-(2-chlorophenyl)-3-methyl-1-phenyl-1,4-dihydro-pyrano[2,3-c]pyrazole-5-carbonitrile
  参考文献：
  名称：

  6-Amino-5-cyano-1H,4H-pyrazolo[3,4-b]pyrans

  摘要：

  DOI：

  10.1007/bf00506154
• 作为产物：
  描述：

  邻氯苄醇 在 碘苯二乙酸 作用下， 以 乙腈 为溶剂， 反应 4.17h， 生成 2-氯苯亚甲基丙二腈
  参考文献：
  名称：

  一锅顺序反应在中孔碳中金属有机笼的约束自组装

  摘要：

  在超分子催化领域中已经广泛探索了定义明确的离散金属有机笼。但是，这些金属有机笼子很少被用作一锅反应的多相催化剂。在这里，我们介绍了氨基官能化介孔碳内含（2,2,6,6-四甲基哌啶-1-基）氧基（TEMPO）的金属有机笼的首次成功的封闭自组装，以实现一个新的双官能团非均相催化剂（Cage @ FDU-ED）进行一锅反应。所获得的双功能催化剂中分离的催化活性位点的正交特征导致增强的催化活性，选择性和可回收性，总转化率可达到96％。这些结果表明，通过精心设计分离的金属有机笼和中孔基质中的催化位点，可以实现连续高效的化学转化。这项研究为金属有机笼子铺平了道路，将其作为异质顺序反应的有前途的平台。

  DOI：

  10.1016/j.chempr.2020.06.038
• 作为试剂：
  描述：

  5-二苯并环庚烯酮 在 2-氯苯亚甲基丙二腈 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Franco, M. Luisa T. M. B.; Lazana, M. Celina R. L. R.; Herold, Bernardo J., Journal of the Chemical Society. Perkin transactions II, 1990, # 4, p. 513 - 520

  摘要：

  DOI：

文献信息

• Selective synthesis of E-isomers of aldoximes via a domino aza-Michael/retro-Michael reaction
  作者：Wei Chen、Wei-Guo Yu、Hai-Bo Shi、Xiao-Yan Lu

  DOI：10.2478/s11696-012-0137-3

  日期：2012.1.1

  A highly stereoselective synthesis of E-isomer of aldoximes was developed through a base-catalysed domino aza-Michael/retro-Michael reaction of hydroxylamine and 2-(R-benzylidene)malononitrile. This reaction generates (E)-aldoxime diastereomer in high yields (eight examples, isolated yields of 82-93 %), excellent diastereomeric purity (diastereomeric ratio higher than 95: 5 by 1H NMR), and proceeds under mild reaction conditions (aqueous NaOH, pH 12, room temperature, 4 h).

  一个高度立体选择性的合成E-异构体的aldoximes已经通过氢氧胺和2-(R-苄亚甲基)丙二腈的碱催化多米诺aza-Michael/retro-Michael反应开发出来。这个反应以高产率生成(E)-aldoxime对映异构体（八个例子，分离产率为82-93%），具有优秀的对映纯度（通过1H NMR，对映比高于95:5），并在温和的反应条件下进行（水性NaOH，pH 12，室温，4小时）。
• Molybdenum carbide as an efficient and durable catalyst for aqueous Knoevenagel condensation
  作者：Mina Tavakolian、Mohammad Mahdi Najafpour

  DOI：10.1039/c9nj04647j

  日期：——

  and benign catalysts were used for the Knoevenagel condensation reaction. Among the compounds (Mo2C, MoS2, MoB, MoSi2), molybdenum carbide showed efficient performance for the Knoevenagel condensation in aqueous media at room temperature, affording the corresponding products in high yields within a short reaction time. Notably, using this commercially available heterogeneous catalyst, the deaceta

  遵循绿色化学原理，各种经济高效的钼化合物，可商购的非均相和良性催化剂被用于Knoevenagel缩合反应。在化合物（Mo 2 C，MoS 2，MoB，MoSi 2），碳化钼在室温下在水性介质中对Knoevenagel缩合反应表现出有效的性能，可在较短的反应时间内以高收率提供相应的产物。值得注意的是，使用这种可商购的非均相催化剂，苯甲醛二甲基乙缩醛和丙二腈在室温下的脱缩醛-Knoevenagel缩合可以成功地以优异的产率进行。通过操作简单的程序，碳化钼可以回收五次而不会失去活性。
• Silver Hexafluoroantimonate-Catalyzed Three-Component [2+2+1] Cycloadditions of Allenoates, Dual Activated Olefins, and Isocyanides
  作者：Jian Li、Yuejin Liu、Chunju Li、Xueshun Jia

  DOI：10.1002/adsc.201000795

  日期：2011.4.18

  The intermolecular [2+2+1] multicomponent cycloadditions from readily available allenoates, dual activated olefins and isocyanides catalyzed by silver hexafluoroantimonate were studied. This protocol allowed the syntheses of highly functionalized five‐membered carbocycles with exclusive regioselectivity and stereoselectivity in an efficient and atom‐economical manner.

  研究了由六氟锑酸银催化的易得的烯丙酸酯，双活化烯烃和异氰酸酯的分子间[2 + 2 + 1]多组分环加成反应。该协议允许以高效且原子经济的方式合成具有高度区域选择性和立体选择性的高度功能化的五元碳环化合物。
• Structure−Activity Relationship Study of Prion Inhibition by 2-Aminopyridine-3,5-dicarbonitrile-Based Compounds:  Parallel Synthesis, Bioactivity, and in Vitro Pharmacokinetics
  作者：Barnaby C. H. May、Julie A. Zorn、Juanita Witkop、John Sherrill、Andrew C. Wallace、Giuseppe Legname、Stanley B. Prusiner、Fred E. Cohen

  DOI：10.1021/jm061045z

  日期：2007.1.1

  2-Aminopyridine-3,5-dicarbonitrile compounds were previously identified as mimetics of dominant-negative prion protein mutants and inhibit prion replication in cultured cells. Here, we report findings from a comprehensive structure-activity relationship study of the 6-aminopyridine-3,5-dicarbonitrile scaffold. We identify compounds with significantly improved bioactivity (approximately 40-fold) against

  2-氨基吡啶-3,5-二甲腈化合物以前被鉴定为显性负病毒蛋白突变体的模拟物，并抑制病毒在培养细胞中的复制。在这里，我们报告从6-氨基吡啶-3,5-二甲腈支架的全面的结构-活性关系研究中发现的结果。我们确定了具有明显改善的生物活性（约40倍）的抗感染性ion病毒同工型（PrPSc）复制和合适的药代动力学特征的化合物，以保证在病毒疾病的动物模型中进行评估。
• Synthesis and characterization of the immobilized Ni–Zn–Fe layered double hydroxide (LDH) on silica-coated magnetite as a mesoporous and magnetically reusable catalyst for the preparation of benzylidenemalononitriles and bisdimedones (tetraketones) under green conditions
  作者：Masumeh Gilanizadeh、Behzad Zeynizadeh

  DOI：10.1039/c8nj00788h

  日期：——

  Magnetic Fe₃O₄@SiO₂@Ni–Zn–Fe LDH was prepared as an efficient nanocatalyst for the Knoevenagel and tandem Knoevenagel–Michael reactions to afford the products in water.

  磁性Fe3O4@SiO2@Ni-Zn-Fe LDH被制备为Knoevenagel和串联Knoevenagel-Michael反应的高效纳米催化剂，以在水中得到产物。

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