4-二氟甲氧基-3-羟基苯甲醛 | 151103-08-1

• 物质功能分类: 化学试剂 - 有机试剂 - 芳香醛(含缩醛,半缩醛)
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-二氟甲氧基-3-羟基苯甲醛
• 中文别名: 4-二氟甲氧基-3-羟基苯甲醛(罗氟司特中间体5)；罗氟司特-imF；3-羟基-4-二氟甲氧基苯甲醛；3-羟基-4-(二氟甲氧基)苯甲醛；4-二氟甲氧基-3-羟基苯甲醚
• 英文名称: 4-difluoromethoxy-3-hydroxybenzaldehyde
• 英文别名: 3-hydroxy-4-difluoromethoxybenzaldehyde；4-(difluoromethoxy)-3-hydroxybenzaldehyde
• CAS: 151103-08-1
• 化学式: C₈H₆F₂O₃
• mdl: MFCD04406687
• 分子量: 188.131
• InChiKey: ZLIKNROJGXXNJG-UHFFFAOYSA-N

物化性质

• 熔点：
  85-90°C
• 沸点：
  280.6±35.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2913000090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存放于惰性气体中，避免与空气接触。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
4-Difluoromethoxy-3-hydroxybenzaldehyde
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H302: Harmful if swallowed
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
Toxic to aquatic life with long lasting effects
H411:
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P273: Avoid release to the environment
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

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Section 3. Composition/information on ingredients.
4-Difluoromethoxy-3-hydroxybenzaldehyde
Ingredient name:
CAS number: 151103-08-1

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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: C8H6F2O3
Molecular weight: 188.1

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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

制备方法与用途

用途：4-二氟甲氧基-3-羟基苯甲醛是一种苯基烷基酮衍生物，主要用于制备磷酸二酯酶-4 (PDE4) 抑制剂。此外，它也用作某些医药产品的中间体，如罗氟司特。

反应信息

• 作为反应物：
  描述：

  4-二氟甲氧基-3-羟基苯甲醛 在 sodium chlorite 、 氯化亚砜 、 氨基磺酸 、 potassium carbonate 、 N,N-二甲基甲酰胺 、 potassium iodide 、 sodium hydroxide 作用下， 以 水 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 29.0h， 生成 罗氟司特
  参考文献：
  名称：

  罗氟司特的简便合成方法

  摘要：

  已经开发了一种方便的合成方法，用于通过O-烷基化，氧化和N-酰化作用，由4-二氟甲氧基-3-羟基苯甲醛和溴甲基环丙烷合成罗氟司特。最后一步以氢氧化钠为碱，罗氟司特的总收率可达68.3％，目标产物的纯度达到99.2％。显然，氢氧化钠显示出比氢化钠或叔丁醇钾更大的经济优势。

  DOI：

  10.1007/s11164-012-0742-3
• 作为产物：
  描述：

  3-(benzyloxy)-4-(difluoromethoxy)benzaldehyde 在 5%-palladium/activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以43.7%的产率得到4-二氟甲氧基-3-羟基苯甲醛
  参考文献：
  名称：

  治疗肝病的药物化合物及其应用

  摘要：

  本发明公开了一类治疗肝病的药物化合物及其应用，其具体为通式(I)所示的化合物、光学异构体或其药学上可接受的盐。本发明所提供的化合物、光学异构体或其药学上可接受的盐对肝病，特别是脂肪肝具有疗效佳和毒性低的效果，实验显示，本发明化合物对斑马鱼非酒精性脂肪肝有明显的保护作用，因此其在应用于治疗或预防肝病，特别是脂肪肝、肝纤维化或肝硬化的药物方面，具有良好的应用前景。

  公开号：

  CN110294732B

文献信息

• [EN] NOVEL TRICYCLIC COMPOUNDS USEFUL FOR THE TREATMENT OF INFLAMMATORY AND ALLERGIC DISORDERS: PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] NOUVEAUX COMPOSES TRICYCLIQUES UTILES POUR TRAITER LES TROUBLES INFLAMMATOIRES ET ALLERGIQUES, PROCEDE DE PREPARATION DE CES COMPOSES ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：GLENMARK PHARMACEUTICALS LTD

  公开号：WO2004037805A1

  公开（公告）日：2004-05-06

  The present invention relates to novel tricyclic compounds useful for the treatment of inflammatory conditions, diseases of the central nervous and insulin resistant diabetes.

  本发明涉及用于治疗炎症性疾病、中枢神经系统疾病和胰岛素抵抗性糖尿病的新型三环化合物。
• Tri-aryl-substituted-ethane PDE4 inhibitors
  申请人：Merck Frosst Canada & Co.

  公开号：US06639077B2

  公开（公告）日：2003-10-28

  Novel ethanes substituted with i) a phenyl, ii) a thiazole, and iii) a pyridyl moiety are PDE4 inhibitors.

  含有i)苯基、ii)噻唑和iii)吡啶基团的新型乙烷衍生物是PDE4抑制剂。
• Phosphodiesterase 4 inhibitors
  申请人：Dunn F. Robert

  公开号：US20070254913A1

  公开（公告）日：2007-11-01

  Selective PDE4 inhibition is achieved by aryl and heteroaryl pyrazole compounds. The compounds exhibit improved PDE4 inhibition as compared to compounds such as rolipram and show selectivity with regard to inhibition of other classes of PDEs.

  选择性PDE4抑制是通过芳基和杂环基吡唑化合物实现的。与罗利普兰（rolipram）等化合物相比，这些化合物表现出更好的PDE4抑制作用，并且在抑制其他类PDE时表现出选择性。
• Identification of a PDE4-Specific Pocket for the Design of Selective Inhibitors
  作者：Xiaoqing Feng、Huanchen Wang、Mengchun Ye、Xue-Tao Xu、Ying Xu、Wenzhe Yang、Han-Ting Zhang、Guoqiang Song、Hengming Ke

  DOI：10.1021/acs.biochem.8b00336

  日期：2018.7.31

  Inhibitors of phosphodiesterases (PDEs) have been widely studied as therapeutics for the treatment of human diseases, but improvement of inhibitor selectivity is still desirable for the enhancement of inhibitor potency. Here, we report identification of a water-containing subpocket as a PDE4-specific pocket for inhibitor binding. We designed against the pocket and synthesized two enantiomers of PDE4

  磷酸二酯酶（PDE）抑制剂作为治疗人类疾病的疗法已被广泛研究，但为了增强抑制剂效力，仍需要提高抑制剂选择性。在这里，我们报告了一个含水子口袋的鉴定，作为抑制剂结合的 PDE4 特异性口袋。我们针对口袋进行设计，合成了PDE4抑制剂Zl-n-91的两种对映体。 ( S )-Zl-n-91 对映体对 PDE4D2 和 PDE4B2B 催化结构域的 IC 50值分别为 12 和 20 nM，选择性比其他 PDE 家族高数千倍，并且具有有效的神经保护活性。与每个 Zl-n-91 对映体复合的 PDE4D2 催化结构域的晶体结构表明 ( S )-Zl-n-91 而不是 ( R )-Zl-n-91 与口袋中的结合水形成氢键，从而解释了其更高的亲和力。 PDE家族之间的结构叠加表明，这种含水子口袋是PDE4所独有的，因此对于PDE4选择性抑制剂的设计很有价值。
• Catalytic radical difluoromethoxylation of arenes and heteroarenes
  作者：Johnny W. Lee、Weijia Zheng、Cristian A. Morales-Rivera、Peng Liu、Ming-Yu Ngai

  DOI：10.1039/c8sc05390a

  日期：——

  Intermolecular C–H difluoromethoxylation of (hetero)arenes remains a long-standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a redox-active difluoromethoxylating reagent 1a and photoredox catalysts for the direct C–H difluoromethoxylation of (hetero)arenes. Our approach is operationally simple, proceeds at room temperature, and uses bench-stable

  （杂）芳烃的分子间CH-H二氟甲氧基化在有机合成中仍然是一个长期存在且尚未解决的问题。在这里，我们报道了第一个使用氧化还原活性二氟甲氧基化试剂1a和光氧化还原催化剂对（杂）芳烃进行直接CHH二氟甲氧基化的催化方案。我们的方法操作简便，可在室温下进行，并使用稳定的试剂。其温和的反应条件可耐受多种官能团和生物相关分子，从而突出了其合成用途。实验和计算研究表明，单电子转移（SET）从激发的光氧化还原催化剂到1a，形成释放OCF 2的中性自由基中间体仅氢自由基。将该自由基加到（杂）芳烃上，得到二氟甲氧基化的环己二烯基，其被氧化和去质子化，得到二氟甲氧基化的产物。