五甲基-1,3-二乙氰基苯 | 120511-72-0

• 物质功能分类: 有机原料 - 腈类化合物
• 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: 五甲基-1,3-二乙氰基苯
• 中文别名: 5,Α,Α,Α',Α'-五甲基-1,3-苯二乙腈；A,A,A',A',5-五甲基-1,3-苯二乙腈(阿那曲唑ANASTROZOLE中间体)；3,5-二(2-氰基-2-基)甲苯；2,2'-(5-甲基-1,3-苯基)双(2-甲基丙腈)；a,a,a',a',5-五甲基-1,3-苯二乙腈；阿那曲唑中间体1；4-氯-4-羟基苯甲酮
• 英文名称: 3,5-bis(2-cyanoprop-2-yl)toluene
• 英文别名: 2-[3-(cyano-dimethyl-methyl)-5-methyl-phenyl]-2-methyl-propionitrile；3,5-bis(2-cyanoisopropyl)toluene；2,2'-(5-methyl-1,3-phenylene)bis(2-methylpropanenitrile)；2,2′-(5-methyl-1,3-phenylene)-bis(2-methylpropionitrile)；α,α,α',α'-5-pentamethyl-1,3-benzenediacetonitrile；α,α,α',α'-tetramethyl-5-methyl-1,3-benzene-diacetonitrile；α,α,α'α'-pentamethyl-1,3-benzene-diacetonitrile；2,2'-(5-methyl-1,3-phenylene)di(2-methyl-propiononitrile)；3,5-di(2,2'-dimethylcyanomethyl)toluene；3,5-bis(1-cyano-1-methylethyl)toluene；2,2'-(5-methyl-1,3-phenylene)-di-(2-methyl propionitrile)；2,2-(5-methyl-1,3-phenylene)-bis(2-methylpropionitrile)；2-[3-(2-cyanopropan-2-yl)-5-methylphenyl]-2-methylpropanenitrile
• CAS: 120511-72-0
• 化学式: C₁₅H₁₈N₂
• mdl: MFCD08062446
• 分子量: 226.321
• InChiKey: SJECEXNMZXMXNE-UHFFFAOYSA-N

物化性质

• 熔点：
  127-130°C
• 沸点：
  339.1±32.0 °C(Predicted)
• 密度：
  1.002±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.466
• 拓扑面积：
  47.6
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2926909090
• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  Refrigerator

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2,2’-(5-Methyl-1,3-phenylene)bis(2-methylpropanenitrile)
Synonyms: 2-[3-(1-cyano-1-methylethyl)-5-methylphenyl]-2-methylpropanenitrile

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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: 2,2’-(5-Methyl-1,3-phenylene)bis(2-methylpropanenitrile)
CAS number: 120511-72-0

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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.

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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: C15H18N2
Molecular weight: 226.3

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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.

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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

制备方法

阿那曲唑中间体。

用途简介

反应信息

• 作为反应物：
  描述：

  五甲基-1,3-二乙氰基苯 在 偶氮二异丁腈 盐酸 、 1,3-二溴-5,5-二甲基海因 、 sodium nitrite 作用下， 以 环己烷 、 水 、 异丙醇 为溶剂， 反应 21.0h， 生成 阿那曲唑
  参考文献：
  名称：

  A process for the preparation of a benzylbromide intermediates

  摘要：

  本发明涉及一种改进的工艺，用于制备不含杂质如2,2-(5-甲基-1,3-苯基)-双(2-甲基丙腈)和3,5-双(1-氰基-1-甲基乙基)-苄溴化物的过程。

  公开号：

  EP2397472A1
• 作为产物：
  描述：

  5-甲基-1,3-二乙氰基苯 以79的产率得到五甲基-1,3-二乙氰基苯
  参考文献：
  名称：

  (Substituted aralkyl) heterocyclic compounds

  摘要：

  一种式子I的(A-取代-芳基)杂环化合物，其中R1是一个叠氮基，氨基甲酰基，氰基，甲酰基，羟基或硝基基团，1-6C 1-羟基烷基，烷氧基，烷基氨甲酰基，烷基硫醇基，烷基亚磺酰基或烷基磺酰基基团，2-氰基乙基基团，可选地带有1-4个1-6C烷基取代基，或2-6C脂肪酰基，卤代脂肪酰基，脂肪酰氧基，脂肪酰氨基，二烷基氨基甲酰基或烷氧羰基基团；R2和R3可以相同也可以不同，分别是氢原子，1-6C烷基，二氘烷基或卤代烷基基团，或苯基或苯基(1-6C烷基)基团，在其中苯基可以可选地带有一个或多个取代基；或R2和R3与它们附着的碳原子一起可以形成一个3-到6-成员的环；或R1 R2 R3 C-是一个1,1-二氰基乙基基团或三氟甲磺酰基基团；R4是氢或卤素原子，氰基或硝基基团或1-6C烷基或卤代烷基基团；R5具有上述定义的R1 R2 R3 C基团的任何值，但不一定与R1 R2 R3 C相同，或具有上述定义的R4的任何值，但不一定与R4相同，或是一个氨甲酰基，1-吡咯啉基甲酰基，哌啶基甲酰基，吗啉基甲酰基或硝基基团，1-6C烷氧基或卤代烷氧基基团或2-6C脂肪酰基或烷氧羰基基团；A是一个亚甲基或乙烯基基团，可选地带有一个或多个取代基，所选取代基包括氘和卤素原子，氨基甲酰基，氰基和羟基基团，1-6C烷基和烷氧基团，以及2-6C脂肪酰氧基基团，但当A通过其氮原子与R6连接时，它不得在与该氮原子相邻的碳原子上带有羟基，烷氧基或脂肪酰氧基取代基；R6是1H-1,2,4-三唑-1-基，4H-1,2,4-三唑-4-基，1H-咪唑-1-基，5-氰基-1H-咪唑-1-基，3-吡啶基或5-嘧啶基基团，或1H-咪唑-1-基，其在5-位置带有一个1-6C烷基取代基，该1-6C烷基本身可选地被一个或多个氨基甲酰基，氰基，羟基或2-6C烷氧羰基基团取代；并且当R2，R3，R4和R5为氢时，A是一个亚甲基基团，R6是3-吡啶基基团，R1不是氰基，羟基或羟甲基基团，当R1是羟基基团时，R3，R4和R5为氢，A是亚甲基基团，R6是3-吡啶基，R2不是甲基或2-氯-1-甲基乙基基团，当R1是甲氧羰基基团时，R2，R3，R4和R5为氢，A是亚甲基基团，R1不是1H-咪唑-1-基；以及其药学上可接受的酸盐。

  公开号：

  US04935437A1

文献信息

• Synthesis of α-Aryl Nitriles through Palladium-Catalyzed Decarboxylative Coupling of Cyanoacetate Salts with Aryl Halides and Triflates
  作者：Rui Shang、Dong-Sheng Ji、Ling Chu、Yao Fu、Lei Liu

  DOI：10.1002/anie.201006763

  日期：2011.5.2

  Worth its salt: The palladium‐catalyzed decarboxylative coupling of the cyanoacetate salt as well as its mono‐ and disubstituted derivatives with aryl chlorides, bromides, and triflates is described (see scheme). This reaction is potentially useful for the preparation of a diverse array of α‐aryl nitriles and has good functional group tolerance. S‐Phos=2‐(2,6‐dimethoxybiphenyl)dicyclohexylphosphine)

  值得其盐：描述了氰基乙酸盐及其与芳基氯化物，溴化物和三氟甲磺酸酯的钯催化的脱羧偶联反应（参见方案）。该反应对于制备各种α-芳基腈具有潜在的实用性，并具有良好的官能团耐受性。S-Phos = 2-（（2,6-二甲氧基联苯）二环己基膦），Xant-Phos = 4,5-双（二苯基膦基）-9,9-二甲基x吨。
• A facile and versatile electro-reductive system for hydrodefunctionalization under ambient conditions
  作者：Binbin Huang、Lin Guo、Wujiong Xia

  DOI：10.1039/d1gc00317h

  日期：——

  A facile electro-reductive hydrodefunctionalization system employing triethylamine as a sacrificial reductant is described, and the selectivity and capability of reduction can be conveniently switched by simple change of the reaction solvent.

  描述了一种使用三乙胺作为牺牲还原剂的简便电还原去功能化系统，通过简单地改变反应溶剂，可以方便地切换还原的选择性和能力。

• Process for the preparation of anastrozole and intermediates thereof
  申请人：Khile Shahaji Anil

  公开号：US20060189670A1

  公开（公告）日：2006-08-24

  A process for the preparation of anastrozole is provided, the process comprising: (a) reacting 3,5-bis(1-cyano-1-methylethyl)benzyl halide with a 4-Z-1,2,4-triazole compound of the formula wherein Z is a protecting group to produce 2,2′-[5-(4-Z-1,2,4-triazolium-1-ylmethyl)-1,3-phenylene]di(2-methylpropionitrile) halide; and (b) deprotecting the 2,2′-[5-(4-Z-1,2,4-triazolium-1-ylmethyl)-1,3-phenylene]di(2-methylpropionitrile)halide to produce anastrozole. Also provided is anastrozole substantially free of its isomers.

  提供一种制备阿那曲唑的方法，该方法包括：(a)将3,5-双(1-氰基-1-甲基乙基)苄卤化物与具有以下结构的4-Z-1,2,4-三唑化合物发生反应，其中Z是保护基，以产生2,2′-[5-(4-Z-1,2,4-三唑-1-基甲基)-1,3-苯基]二(2-甲基丙腈)卤化物；和(b)去保护2,2′-[5-(4-Z-1,2,4-三唑-1-基甲基)-1,3-苯基]二(2-甲基丙腈)卤化物以产生阿那曲唑。还提供了基本不含异构体的阿那曲唑。
• Dual aromatase–sulfatase inhibitors based on the anastrozole template: synthesis, in vitro SAR, molecular modelling and in vivo activity
  作者：Toby Jackson、L. W. Lawrence Woo、Melanie N. Trusselle、Surinder K. Chander、Atul Purohit、Michael J. Reed、Barry V. L. Potter

  DOI：10.1039/b707768h

  日期：——

  crucial for enzyme inhibition, was modified to include a phenol sulfamate ester motif, the pharmacophore for potent irreversible steroid sulfatase inhibition. Adaption of a synthetic route to Anastrozole was accomplished via selective radical bromination and substitution reactions to furnish a series of inhibitory aromatase pharmacophores. Linking these fragments to the phenol sulfamate ester moiety employed

  描述了一系列新型双重芳香酶-硫酸酯酶抑制剂（DASIs）的合成和生物学评估。假定双重抑制芳香酶和类固醇硫酸酯酶，两者都负责雌激素的生物合成，在治疗激素依赖性乳腺癌中将是有益的。这些化合物基于阿那曲唑芳香化酶抑制剂模板，该模板在维持血红素连接三唑部分对酶抑制至关重要的同时，经过修饰，使其包括苯酚氨基磺酸酯基序，即有效抑制不可逆类固醇硫酸酯酶的药效基团。通过选择性自由基溴化和取代反应以提供一系列抑制性芳香化酶药效基团，可以使合成路线适应阿那曲唑。将这些片段连接至氨基磺酸氨基酚酯部分，使用S（N）2，Heck和Mitsunobu反应与酚类前体进行反应，从中通过氨磺酰化反应完成DASI。在体外，先导化合物11对芳香化酶（IC（50）3.5 nM）具有很高的效力，与阿那曲唑（IC（50）1.5 nM）相当，而对甾族硫酸酯酶的活性却中等。然而，在体内，11出人意料地表现出有效的双重抑制作用。将化合物1
• Process for the Preparation of 2,2'-[5-(1H-1,2,4-Triazole-1-Ylmethyl) -1,3-Phenylene] Di (2-Methylpropionitrile)
  申请人：Radhakrishnan Tarur Venkatasubramanian

  公开号：US20080207915A1

  公开（公告）日：2008-08-28

  The present invention discloses a process for the preparation of Anastrozole of the formula I in high purity and in high yield. 3,5-bis(halomethyl)toluene is prepared by reacting mesitylene with N-halosuccinimide in the presence of light or dibenzoyl peroxide or azobis isobutyronitrile as a catalyst and in a chlorinated solvent. 3,5-bis(halomethyl)toluene is cyanated with metal cyanide in the presence of a catalyst and in water, organic solvent or mixture thereof at temperature of 40 to 60° C. to obtain 2,2′-(5-methyl-1,3 phenylene)diacetonitrile which is further methylated with iodomethane in the presence of base and an organic solvent at temperature of 0 to 15° C. to obtain 2,2′-(5-methyl-1,3-phenylene)di(2-methyl-propiononitrile). The product obtained is treated with N-halosuccinimide in the presence of a catalyst and in a chlorinated solvent at temperature of 60 to 100° C. to obtain 2,2′-(5-halomethyl-1,3-phenylene)di(2-methyl propionitrile) which was further treated with potassium or sodium salt 1,2,4-triazole at temperature of 20 to 50° C. in dimethyl formamide to obtain crude 2,2′-[5-( 1 H-1,2,4-triazole-1-ylmethyl)-1,3-phenylene]di(2-methyl-propionitrile). The crude product is purified by column chromatography using a stationary phase and a mobile phase followed by recrystallization with a solvent or mixture of solvents to obtain highly pure Anastrozole.

  本发明揭示了一种制备高纯度和高产率的化学式I的阿那曲唑的方法。首先，通过将间二甲苯与N-卤代琥珀酰亚胺在光照或二苯甲酰过氧化物或异丁腈偶氮叔丁酰胺存在下在氯化溶剂中反应制备3,5-双(卤甲基)甲苯。然后，在催化剂的存在下，将3,5-双(卤甲基)甲苯与金属氰化物在水、有机溶剂或二者混合物中在40至60°C的温度下反应，得到2,2′-(5-甲基-1,3-苯基)双乙腈。接着，在碱和有机溶剂存在下，在0至15°C的温度下，将2,2′-(5-甲基-1,3-苯基)双乙腈与碘甲烷反应甲基化，得到2,2′-(5-甲基-1,3-苯基)双(2-甲基-丙酰亚胺)。随后，将所得产物在催化剂的存在下，在60至100°C的温度下，与N-卤代琥珀酰亚胺在氯化溶剂中反应，得到2,2′-(5-卤甲基-1,3-苯基)双(2-甲基丙腈)。最后，将该产物与钾盐或钠盐1,2,4-三唑在20至50°C的温度下在二甲基甲酰胺中反应，得到粗的2,2′-[5-(1H-1,2,4-三唑-1-基甲基)-1,3-苯基]双(2-甲基丙腈)。通过柱层析和再结晶，使用固定相和流动相纯化粗产品，最终获得高纯度的阿那曲唑。