3-氟-4-羟基苯腈 | 405-04-9

• 物质功能分类: 有机原料 - 有机氟化合物 - 氟苯腈系列
• 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-氟-4-羟基苯腈
• 中文别名: 3-氟-4-羟基腈苯；2-氟-4-腈基苯酚；3-氟-4-羟基苄腈
• 英文名称: 3-fluoro-4-hydroxybenzonitrile
• CAS: 405-04-9
• 化学式: C₇H₄FNO
• mdl: MFCD00215834
• 分子量: 137.113
• InChiKey: DPSSSDFTLVUJDH-UHFFFAOYSA-N

物化性质

• 熔点：
  133-135°C
• 沸点：
  253.9±25.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)
• 溶解度：
  溶于甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  6.1
• 危险品标志：
  Xi
• 安全说明：
  S26,S36/37/39,S37/39
• 危险类别码：
  R20/21/22
• 危险品运输编号：
  3439
• 海关编码：
  2926909090
• 危险类别：
  6.1
• 包装等级：
  III
• 危险性防范说明：
  P261,P301+P312,P302+P352,P304+P340,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Fluoro-4-hydroxybenzonitrile
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H331: Toxic if inhaled
H302: Harmful if swallowed
H312: Harmful in contact with skin
Causes skin irritation
H315:
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P280: Wear protective gloves/protective clothing/eye protection/face protection
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.
Ingredient name: 3-Fluoro-4-hydroxybenzonitrile
CAS number: 405-04-9

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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.
Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
Eye contact:
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.
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: C7H4FNO
Molecular weight: 137.1

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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, nitrogen oxides, 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
UN Number: UN3439 Class: 6.1 Packing group: III
Proper shipping name: NITRILES, TOXIC, SOLID, N.O.S. (3-Fluoro-4-hydroxybenzonitrile)

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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

3-氟-4-羟基苯腈是一种重要的有机中间体，主要用于医药和农药的生产。此外，在染料、工程塑料和感光材料的制造过程中也有广泛的应用。

制备

传统的合成方法包括氨氧化法、相转移催化合成法或苯甲酸氨化等。然而，这些方法存在反应路线长、污染大等问题，导致收率较低。3-氟-4-羟基苯甲酸经一步氨化反应可制得该化合物；3-氟-4-羟基苯可以通过氨氧化直接获得；而3-氟-4-羟基苯甲醛与盐酸羟胺的反应亦能生成所需物质，也可由4-羟基苯腈起始物，通过氟代反应制备。


反应信息

• 作为反应物：
  描述：

  3-氟-4-羟基苯腈 在 偶氮二甲酸二异丙酯 、 二异丁基氢化铝 、 三苯基膦 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 1.0h， 生成 4-[(3,4-dichlorobenzyl)oxy]-3-fluorobenzaldehyde
  参考文献：
  名称：

  Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P₅) Agonist for the Potential Treatment of Neurodegenerative Disorders

  摘要：

  S1P(5) is one of S receptors for sphingosine-1-phosphate and is highly expressed on endothelial cells within the blood brain barrier, where it maintains barrier integrity in in vitro models (j Neuroinflamm. 2012, 9, 133). Little more is known about the effects of S1P(5) modulation due to the absence of tool molecules with suitable selectivity and drug-like properties. We recently reported that molecule A-971432 (Harris et al., 2010) (29 in this paper) is highly efficacious in reversing lipid accumulation and age-related cognitive decline in rats (Van der Kam, et al., AAIC 2014). Herein we describe the development of a series of selective S1P(5) agonists that led to the identification of compound 29, which is highly selective for S1P(5) and has excellent plasma and CNS exposure after oral dosing in preclinical species. To further support its suitability for in vivo studies of S1P(5) biology, we extensively characterized 29, including confirmation of its selectivity in pharmacodynamic assays of S1P(1). and S1P(3) function in rats. In addition, we found that 29 improves blood brain barrier integrity in an in vitro model and reverses age-related cognitive decline in mice. These results suggest that S1P(5) agonism is an innovative approach with potential benefit in neurodegenerative disorders involving lipid imbalance and/or compromised blood brain barrier such as Alzheimer's disease or multiple sclerosis.

  DOI：

  10.1021/acs.jmedchem.5b00928
• 作为产物：
  描述：

  间氟苯甲醚 在 三氯化铝 、 溴 、 sodium chloride 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.75h， 生成 3-氟-4-羟基苯腈
  参考文献：
  名称：

  2-氟-4-羟基苯甲酸酯和3-氟-4-羟基苯甲腈的苯甲酸酯衍生物的合成和转变温度

  摘要：

  描述了六十个4-氰基-2-氟苯基和4-氰基-3-氟门烷4-取代的苯甲酸酯的合成和液晶温度。大多数这些新型酯的向列各向同性液体转变温度仅略低于相应的含有H原子代替F取代基的酯的向列各向同性液体转变温度。在一些情况下，F-取代的苯基酯的透明点高于非取代的苯基酯的透明点。几种新酯的向列范围明显大于类似的非F-取代苯基酯的向列范围。

  DOI：

  10.1002/hlca.19840670623
• 作为试剂：
  描述：

  3-氟-4-羟基苯腈 、 Dicaesio carbonate 、 2-溴甲基苯甲酸甲酯 在 3-氟-4-羟基苯腈 、 2-溴甲基苯甲酸甲酯 、 silica gel 、 ethyl acetate n-hexane 作用下， 以 丙酮 为溶剂， 反应 12.0h， 以to give the desired product as a yellow sticky solid (90%)的产率得到2-(4-cyano-2-fluoro-phenoxymethyl)-benzoic acid methyl ester
  参考文献：
  名称：

  Benzimidazole derivatives

  摘要：

  本发明涉及式(I)化合物，以及其药学上可接受的盐，可以以制药组合物的形式使用，其中A、B、R1、R2、R3、R4、R5、n、m和p具有在此定义的意义。

  公开号：

  US08309581B2

文献信息

• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2017012647A1

  公开（公告）日：2017-01-26

  The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.

  本发明公开了根据式（I）的化合物，其中R1、R3、R4、R5、L1和Cy如本文所定义。本发明还提供了该发明的化合物、制备该化合物的方法、包括相同化合物的药物组合物以及它们在过敏或炎症症状、自身免疫疾病、增殖性疾病、移植排斥、涉及软骨周转障碍的疾病、先天软骨畸形和/或与IL6和/或干扰素过度分泌相关的疾病中的使用。本发明还提供了通过给予该发明的化合物来预防和/或治疗上述疾病的方法。
• Air‐Stable Pd ^I Dimer Enabled Remote Functionalization: Access to Fluorinated 1,1‐Diaryl Alkanes with Unprecedented Speed
  作者：Gourab Kundu、Filip Opincal、Theresa Sperger、Franziska Schoenebeck

  DOI：10.1002/anie.202113667

  日期：2022.1.3

  We report a remote arylation in less than 10 min reaction time at room temperature over a distance of up to 11 carbons. The unprecedented speed is enabled by the air-stable PdI dimer [Pd(μ-I)(PCy2tBu)]2.

  我们报告了在室温下在不到 10 分钟的反应时间内在长达 11 个碳的距离上进行的远程芳基化。空气稳定的 Pd 二聚体 [Pd(μ-I)(PCy 2 t Bu)] 2实现了前所未有的速度。
• [EN] SPHINGOSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA SPHINGOSINE KINASE
  申请人：LYNCH KEVIN

  公开号：WO2016054261A1

  公开（公告）日：2016-04-07

  Sphingosine kinases are enzymes that catalyze the biosynthesis of sphingosine-1-phosphate. The invention provides compounds that are effective for inhibition of sphingosine kinase type 1, sphingosine kinase type 2, or both. Certain compounds are selective for sphingosine kinase type 2 relative to sphingosine kinase type 1. Compounds of the invention can be used in treatment of a range of diseases wherein increasing the level of sphingosine-1-phosphate in blood is medically indicated. Diseases that can be treated by administration of an effective dose of a compound of the invention include a neoplastic disease that involves excess vascular growth; macular degeneration or diabetic retinopathy; an allergic disease such as asthma, an inflammatory disease of the eye such as uveitis, scleritis, or vitritis; an inflammatory disease of the kidney; a fibrotic disease; atherosclerosis; or pulmonary arterial hypertension. A compound of the invention can be used to improve the integrity of a vascular barrier in a disease where the vascular barrier is disrupted, such as cancer or Alzheimer's disease.

  鞘氨醇激酶是催化鞘氨醇-1-磷酸酯生物合成的酶。该发明提供了对鞘氨醇激酶1型、鞘氨醇激酶2型或两者均具有效抑制作用的化合物。某些化合物相对于鞘氨醇激酶1型具有选择性作用于鞘氨醇激酶2型。该发明的化合物可用于治疗一系列疾病，其中增加血液中鞘氨醇-1-磷酸酯水平在医学上是指示的。通过给予该发明的化合物有效剂量可以治疗的疾病包括涉及过度血管生长的肿瘤性疾病；黄斑变性或糖尿病视网膜病变；哮喘等过敏性疾病，眼部炎症性疾病如葡萄膜炎、巩膜炎或玻璃体炎；肾脏炎症性疾病；纤维化疾病；动脉粥样硬化；或肺动脉高压。该发明的化合物可用于改善血管屏障的完整性，在血管屏障受损的疾病中，如癌症或阿尔茨海默病。
• [EN] SUBSTITUTED CONDENSED THIOPHENES AS MODULATORS OF STING<br/>[FR] THIOPHÈNES CONDENSÉS SUBSTITUÉS UTILISÉS EN TANT QUE MODULATEURS DE STING
  申请人：CTXT PTY LTD

  公开号：WO2019219820A1

  公开（公告）日：2019-11-21

  A compound of formula (I), wherein: R1 is selected from (i) H, (ii) C3-6cycloalkyl, (iii) C3-7heterocyclyl optionally substituted with a group selected from: methyl and ester, and (iv) linear or branched C1-4alkyl optionally substituted with a group selected from: alkoxy, amino, amido, acylamido, acyloxy, alkyl carboxyl ester, alkyl carbamoyl, alkyl carbamoyl ester, phenyl, phosphonate ester, C3-7heterocyclyl optionally substituted with a group selected from methyl and oxo, and a naturally occurring amino acid, optionally N-substituted with a group selected from methyl, acetyl and boc; A1 is CRA or N; A2 is CRB or N; A3 is CRC or N; A4 is CRD or N; where no more than two of A1, A2, A3, and A4 may be N; one or two of RA, RB, RC, and RD, (if present) are selected from H, F, Cl, Br, Me, CF3, cyclopropyl, cyano, OMe, OEt, CH2OH, CH2OMe and CH2NMe2; the remainder of RA, RB, RC, and RD, (if present) are H; Y is O, NH or CH2; RY is selected from: (RYA) and (RYB).

  化合物的化学式（I），其中：R1选自（i）H，（ii）C3-6环烷基，（iii）C3-7杂环烷基，可选择地取代为：甲基和酯，以及（iv）线性或支链C1-4烷基，可选择地取代为：烷氧基，氨基，酰胺基，酰氧基，烷基羧酯，烷基氨基，烷基氨基酯，苯基，磷酸酯，C3-7杂环烷基，可选择地取代为甲基和氧代基，以及一种天然氨基酸，可选择地N-取代为：甲基，乙酰基和boc；A1为CRA或N；A2为CRB或N；A3为CRC或N；A4为CRD或N；其中A1，A2，A3和A4中最多有两个可以是N；RA，RB，RC和RD中的一个或两个（如果存在）选自H，F，Cl，Br，Me，CF3，环丙基，氰基，OMe，OEt，CH2OH，CH2OMe和CH2NMe2；RA，RB，RC和RD的其余部分（如果存在）为H；Y为O，NH或CH2；RY选自：（RYA）和（RYB）。
• [EN] DIRECTED CONJUGATION TECHNOLOGIES<br/>[FR] TECHNOLOGIES DE CONJUGAISON DIRIGÉE
  申请人：KLEO PHARMACEUTICALS INC

  公开号：WO2021102052A1

  公开（公告）日：2021-05-27

  Among other things, the present disclosure provides technologies for site-directed conjugation of various moieties of interest to target agents. In some embodiments, the present disclosure utilizes target binding moieties to provide high conjugation efficiency and selectivity. In some embodiments, provided technologies are useful for preparing antibody conjugates.

  本公开提供了用于将各种感兴趣的分子与目标剂进行定点偶联的技术。在某些实施方式中，本公开利用目标结合分子以提供高偶联效率和选择性。在某些实施方式中，所提供的技术可用于制备抗体偶联物。