3-(三氟甲氧基)苯甲酸甲酯 | 148438-00-0

• 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: 3-(三氟甲氧基)苯甲酸甲酯
• 中文别名: 间三氟甲氧基苯甲酸甲酯
• 英文名称: methyl 3-(trifluoromethoxy)benzoate
• CAS: 148438-00-0
• 化学式: C₉H₇F₃O₃
• 分子量: 220.148
• InChiKey: YWSQRIKZJLRGPT-UHFFFAOYSA-N

物化性质

• 沸点：
  85-87 °C (10 mmHg)
• 密度：
  1.445
• 闪点：
  85-87°C/10mm
• 稳定性/保质期：
  避氧化物

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 危险品标志：
  Xn,Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/38
• 海关编码：
  2918990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  保存方法：在密闭、阴凉、通风干燥的地方存放。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Methyl 3-(trifluoromethoxy)benzoate
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
Methyl 3-(trifluoromethoxy)benzoate
Ingredient name:
CAS number: 148438-00-0

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.
Storage: Store in closed vessels.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C9H7F3O3
Molecular weight: 220.1

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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, hydrogen fluoride.

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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

反应信息

• 作为反应物：
  描述：

  3-(三氟甲氧基)苯甲酸甲酯 在 一水合肼 作用下， 以 甲醇 为溶剂， 以89%的产率得到3-(三氟甲氧基)苯甲酰肼
  参考文献：
  名称：

  SAR基于真菌酰基鞘脂的芳香族酰基hydr抑制剂作为下一代抗真菌剂的研究。

  摘要：

  最近，真菌鞘脂糖基神经酰胺（GlcCer）的合成已成为下一代抗真菌药的药物开发的高度有希望的新目标，我们基于HTP筛选发现了两种芳香族酰基hydr作为GlcCer合成的有效抑制剂。在目前的工作中，我们设计了新的芳香族酰基hydr的文库，评估了它们对新孢子虫的抗真菌活性（MIC80和时间杀灭谱），并进行了广泛的SAR研究，从而鉴定了五种有前途的先导化合物，极高的选择性指数，具有出色的杀真菌活性。此外，两种化合物对其他六种临床相关真菌菌株均具有广谱抗真菌活性。研究了这五种先导化合物与五种临床药物对七种真菌菌株的协同作用/协同作用，并获得了令人鼓舞的结果。例如，所有五个先导化合物与伏立康唑的组合对所有七个真菌菌株均表现出协同作用或加和作用。

  DOI：

  10.1021/acs.jmedchem.9b01004
• 作为产物：
  描述：

  O-3-(methoxycarbonyl)phenyl S-methyl dithiocarbonate 在 吡啶 、 1,3-二溴-5,5-二甲基海因 、 氢氟酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以76%的产率得到3-(三氟甲氧基)苯甲酸甲酯
  参考文献：
  名称：

  二硫代碳酸酯氧化脱硫氟化简便合成三氟甲基醚

  摘要：

  三氟甲基醚 R-OCF3 很容易从相应的二硫代碳酸酯 R-OCS2Me（R = 芳基或伯烷基）通过由 70% HF/吡啶和 N-卤代酰亚胺组成的试剂系统合成。当反应应用于 R-OCS2Me 时，其中 R = 仲烷基、叔烷基或苄基，实现了产生相应烷基氟化物 RF 的氟化，而 50% HF/吡啶和 N-溴代琥珀酰亚胺的组合提供相应的三氟甲基醚 R-OCF3（R = 次要）。

  DOI：

  10.1246/bcsj.73.471

文献信息

• Radical Trifluoromethoxylation of Arenes Triggered by a Visible‐Light‐Mediated N−O Bond Redox Fragmentation
  作者：Benson J. Jelier、Pascal F. Tripet、Ewa Pietrasiak、Ivan Franzoni、Gunnar Jeschke、Antonio Togni

  DOI：10.1002/anie.201806296

  日期：2018.10.15

  method enables non‐directed functionalization of C−H bonds on a range of substrates, providing access to aryl trifluoromethyl ethers. This light‐driven process is distinctly different from conventional procedures and occurs through an OCF3 radical mechanism mediated by a photoredox catalyst, which triggers an N−O bond fragmentation. The pyridinium‐based trifluoromethoxylation reagent is bench‐stable and

  一种简单的三氟甲氧基化方法可以在一系列底物上实现CH键的非定向功能化，从而可以使用芳基三氟甲基醚。这种光驱过程与传统方法有明显不同，它是通过光氧化还原催化剂介导的OCF 3自由基机理发生的，该机理引发了N-O键断裂。基于吡啶鎓的三氟甲氧基化试剂具有台式稳定性，可通过操作简单的方式获得铅化合物的合成多样性。
• [EN] DIFLUOROMETHOXYLATION AND TRIFLUOROMETHOXYLATION COMPOSITIONS AND METHODS FOR SYNTHESIZING SAME<br/>[FR] COMPOSITIONS DE DIFLUOROMÉTHOXYLATION ET DE TRIFLUOROMÉTHOXYLATION ET LEURS PROCÉDÉS DE SYNTHÈSE
  申请人：UNIV NEW YORK STATE RES FOUND

  公开号：WO2019168874A1

  公开（公告）日：2019-09-06

  The present invention provides a compound having the structure (I), a processing of making the compound; and a process of using the compound as a reagent for the difluoromethoxylation and trifluoromethoxylation of arenes or heteroarenes.

  本发明提供了一种具有结构（I）的化合物，制备该化合物的方法；以及将该化合物用作芳烃或杂环芳烃的二氟甲氧基化和三氟甲氧基化试剂的方法。
• Redox‐Neutral TEMPO Catalysis: Direct Radical (Hetero)Aryl C−H Di‐ and Trifluoromethoxylation
  作者：Johnny W. Lee、Sanghyun Lim、Daniel N. Maienshein、Peng Liu、Ming‐Yu Ngai

  DOI：10.1002/anie.202009490

  日期：2020.11.23

  Applications of TEMPO. catalysis for the development of redox‐neutral transformations are rare. Reported here is the first TEMPO.‐catalyzed, redox‐neutral C−H di‐ and trifluoromethoxylation of (hetero)arenes. The reaction exhibits a broad substrate scope, has high functional‐group tolerance, and can be employed for the late‐stage functionalization of complex druglike molecules. Kinetic measurements

  TEMPO 的应用。氧化还原中性转化发展的催化作用很少见。这里报道的是第一个TEMPO 。（杂）芳烃的催化氧化还原中性 C−H 二氟甲氧基化和三氟甲氧基化。该反应表现出广泛的底物范围，具有较高的官能团耐受性，可用于复杂药物分子的后期功能化。动力学测量、催化中间体的分离和重新研究、UV/Vis 研究和 DFT 计算支持了所提出的氧化 TEMPO 。/TEMPO +氧化还原催化循环。机理研究还表明Li 2 CO 3在防止催化剂失活方面发挥着重要作用。这些发现将为通过氧化还原中性 TEMPO 设计和开发新型反应提供新的见解。催化。
• Catalytic C−H Trifluoromethoxylation of Arenes and Heteroarenes
  作者：Weijia Zheng、Cristian A. Morales‐Rivera、Johnny W. Lee、Peng Liu、Ming‐Yu Ngai

  DOI：10.1002/anie.201800598

  日期：2018.7.26

  The intermolecular C−H trifluoromethoxylation of arenes remains a long‐standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a novel trifluoromethoxylating reagent and redox‐active catalysts for the direct (hetero)aryl C−H trifluoromethoxylation. Our approach is operationally simple, proceeds at room temperature, uses easy‐to‐handle reagents, requires

  芳烃的分子间CH-C三氟甲氧基化仍然是有机合成中长期存在且未解决的问题。在此，我们报告了第一个采用新型三氟甲氧基化试剂和氧化还原活性催化剂进行直接（杂）芳基 C−H 三氟甲氧基化的催化方案。我们的方法操作简单，在室温下进行，使用易于处理的试剂，仅需要 0.03 mol% 的氧化还原活性催化剂，不需要专门的反应设备，并且可以耐受多种官能团和复杂结构，例如糖和天然产物衍生物。重要的是，基态和光激发氧化还原活性催化剂都是有效的。详细的计算和实验研究表明了一种独特的反应途径，其中三氟甲氧基化试剂的光激发释放被（杂）芳烃捕获的 OCF 3自由基。所得环己二烯基自由基被氧化还原活性催化剂氧化并去质子化，形成所需的三氟甲氧基化产物。
• Redox‐Active Reagents for Photocatalytic Generation of the OCF ₃ Radical and (Hetero)Aryl C−H Trifluoromethoxylation
  作者：Weijia Zheng、Johnny W. Lee、Cristian A. Morales‐Rivera、Peng Liu、Ming‐Yu Ngai

  DOI：10.1002/anie.201808495

  日期：2018.10.15

  importantly, the reagent allows catalytic, intermolecular C−H trifluoromethoxylation of a broad array of (hetero)arenes and biorelevant compounds. Experimental and computational studies suggest single electron transfer (SET) from excited photoredox catalysts to 1 resulting in exclusive liberation of the OCF3 radical. Addition of this radical to (hetero)arenes gives trifluoromethoxylated cyclohexadienyl radicals

  三氟甲氧基（OCF 3 ）自由基在有机化学中非常重要。然而，在室温和压力下催化和选择性产生这种自由基仍然是一个长期的挑战。在此，报道了一种氧化还原活性阳离子试剂（ 1 ）的设计和开发，该试剂能够在可见光光催化条件下以可控、选择性和催化的方式形成OCF 3自由基。更重要的是，该试剂可以对多种（杂）芳烃和生物相关化合物进行催化、分子间 CH 三氟甲氧基化。实验和计算研究表明，从激发的光氧化还原催化剂到1 的单电子转移 (SET) 导致 OCF 3自由基的排他性释放。该自由基与(杂)芳烃的加成得到三氟甲氧基化的环己二烯基自由基，其被氧化和去质子化以提供三氟甲氧基化的产物。

表征谱图