邻氯苯酚 | 95-57-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 邻氯苯酚
• 中文别名: 邻羟基氯苯；2-羟基氯苯；邻基(苯)酚；2-氯-1-羟基苯；2-氯苯；2-氯苯酚；奥尔多氯酚；邻氯酚；2-氯酚
• 英文名称: 2-Chlorophenol
• 英文别名: 2-monochlorophenol；o-Chlorophenol
• CAS: 95-57-8；25167-80-0
• 化学式: C₆H₅ClO
• mdl: MFCD00002159
• 分子量: 128.558
• InChiKey: ISPYQTSUDJAMAB-UHFFFAOYSA-N

物化性质

• 物理描述：
  2-chlorophenol appears as a colorless to amber liquid with an unpleasant, penetrating odor. Density 1.265 g / cm3. Sinks in water and slowly dissolves. Freezing point 7°C (46°F). Boiling point 175°C (347°F).
• 颜色/状态：
  Light amber liquid
• 气味：
  Unpleasant penetrating odor
• 味道：
  Strong medicinal taste and odor
• 沸点：
  174.9 °C
• 熔点：
  9.8 °C
• 闪点：
  64 °C (147 °F) CLOSED CUP
• 溶解度：
  2.85 PARTS SOL IN 100 PARTS WATER @ 20 °C
• 密度：
  1.2634 at 20 °C/4 °C
• 蒸汽密度：
  Relative vapor density (air = 1): 4.4
• 蒸汽压力：
  2.53 mm Hg at 25 °C
• 亨利常数：
  1.12e-05 atm-m3/mole
• 分解：
  When heated to decomposition it emits toxic fumes of /hydrogen chloride/.
• 粘度：
  3.579 cP at 25 °C
• 燃烧热：
  2790.0 kJ.mol at 77 °F (liquid) /25 °C/
• 汽化热：
  40.12 kJ/mole at 174.53 °C / 447.53 K/
• 表面张力：
  40.50 dynes/cm at 25 °C
• 气味阈值：
  2 ug/L in water at 25 °C /Table/
• 折光率：
  Index of refraction: 1.5524 @ 20 °C
• 解离常数：
  Ka = 3.2X10-9 at 25 °C
• 保留指数：
  960.5;967.3;973;975;975;979;987;991;1000;1000;987;991;993;987;992;985.9;947;948;952;992;973.3;965

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  8
• 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：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

O-氯苯酚在大鼠体内转化为O-氯茴香醚。在兔体内，O-氯苯酚转化为3-氯儿茶酚。产生O-氯苯基-β-D-葡萄糖醛酸苷和O-氯苯基硫酸盐。O-氯苯酚在大鼠体内可能转化为氯喹啉。

O-Chlorophenol yields o-chloroanisole in guinea pigs. /In rabbits/ o-chlorophenol yields 3-chlorocatechol. Yields o-chlorophenyl-beta-d-glucuronide & o-chlorophenyl sulfate. O-chlorophenol yields chloroquinol probably in rats.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在鱼缸水中浸泡48小时的亚致死浓度下，研究了12种淡水鱼对(14)C标记的邻氯酚的尿液和胆汁排泄。在所有鱼类的鱼缸水和胆汁中检测到了邻氯酚硫酸盐和邻氯酚葡萄糖苷酸。

The urinary and biliary excretion of (14)C-labeled o-chlorophenol were investigated in 12 species of freshwater fish when immersed in sublethal concentrations of the cmpd in the aquarium water for 48 hr. o-Chlorophenol sulfate and o-chlorophenol glucuronide were detected in both the aquarium water and the bile of all the fish species.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 各种氯酚作为中间代谢物，在微生物降解除草剂2,4-D和2,4,5-T以及杀虫剂Silvex、Ronnel、林丹和六氯化苯的过程中形成。/氯酚/

... Various chlorophenols are formed as intermediate metabolites during the microbiological degradation of the herbicides 2,4-D & 2,4,5-T and the pesticides Silvex, Ronnel, lindane, and benzene hexachloride. /Chlorophenols/

来源:Hazardous Substances Data Bank (HSDB)

代谢

哺乳动物对氯苯的新陈代谢产生2-氯酚作为主要产物之一。

Mammalian metabolism of chlorobenzene yields 2-chlorophenol as /one of/ the major products.

来源:Hazardous Substances Data Bank (HSDB)

代谢

2-氯苯酚在胃和小肠中被吸收。通过胃肠道的吸收是通过简单扩散，预计会非常迅速且几乎完全。2-氯苯酚的代谢主要是通过结合作用。主要排泄的代谢物是葡萄糖苷酸。其他代谢物包括醚硫酸盐等硫酸结合物。这些代谢物通过尿液排出。

Absorption of 2-chlorophenol is favored in the stomach and the intestine. Absorption through the gastrointestinal tract is by simple diffusion and is expected to be both rapid and virtually complete.The metabolism of the 2-chlorophenol is principally via conjugation. The principal metabolite excreted is the glucuronide. Other metabolites are sulfate conjugates such as the ethereal sulfate. The metabobites are excreted in urine (L159).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

2-氯苯酚作为氧化磷酸化解偶联的弱剂和细胞呼吸的抑制剂。随着氯化程度的增加，氯苯酚解偶联氧化磷酸化的能力增强。实际上，研究表明氯苯酚对磷酸化和细胞呼吸的影响与浓度有关，呈现三阶段效应。在低浓度下，解偶联会导致静息状态呼吸的刺激，这是由于在没有磷酸盐受体的情况下腺苷三磷酸酶（ATP酶）活性增加的结果。也观察到活动性呼吸的抑制。在中等浓度下，静息呼吸既不被刺激也不被抑制。在非常高的浓度下，会出现显著的呼吸抑制，伴随着电子传递过程的破坏和ATP酶活性的降低。解偶联活性归因于质子传递效应（氯苯酚在膜磷脂双层中的分布导致线粒体膜上的能量梯度破坏），而细胞呼吸的抑制归因于对细胞内蛋白的直接作用（L159）。

2-chlorophenol works as a weak uncoupler of oxidative phosphorylation and inhibitors of cellular respiration. The ability of chlorophenols to uncouple oxidative phosphorylation increases with increasing chlorination. In fact, studies indicate a concentration-dependent triphasic effect of chlorophenols on phosphorylation and cellular respiration. At low concentrations, uncoupling produces stimulation of the resting state respiration as a result of increased adenosine triphosphatase (ATPase) activity in the absence of a phosphate acceptor.Inhibition of active respiration is also observed. At moderate concentrations, resting respiration is neither stimulated nor inhibited. Significant inhibition of respiration, associated with a breakdown of the electron transport process and decreased ATPase activity, occurs at very high concentrations. Uncoupling activity has been attributed to a protonophoric effect (a disruption of the energy gradient across the mitochondrial membrane resulting from distribution of chlorophenols in the phospholipid bilayer of the membrane), whereas inhibition of cellular respiration has been attributed to a direct action on intracellular proteins (L159).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

无致癌性迹象（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity (not listed by IARC). (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

2-氯苯酚对上皮组织具有腐蚀性。当其应用于角膜时，可产生从轻微充血到严重腐蚀的各种效果。急性吸入暴露可能导致肺部出血和呼吸急促。口服暴露于2-氯苯酚可能产生多种神经系统效应，包括震颤、肌阵挛性抽搐、驼背姿势、呼吸困难、瘫痪和昏迷（L159）。

2-chlorophenol is corrosive to epithelial tissue. It produce effects ranging from slight hyperemia to severe corrosion when applied to the corneas. Acute inhalation exposure may lead to hemorrhage in the lungs and tachypnea. Oral exposure to 2-chlorophenol can produce a variety of neurological effects, including tremors, myoclonic convulsions, a hunched posture, dyspnea, collapse, and coma (L159).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

该物质可以通过吸入其蒸汽、通过皮肤接触以及摄入进入人体。

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

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

毒理性

• 暴露途径

吸入 (L723)； 口服 (L723)； 皮肤给药 (L723)

Inhalation (L723) ; oral (L723) ; dermal (L723)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

许多兔子的研究表明，单氯酚的代谢主要是通过结合作用进行的。在/一个/研究中，将6只兔子分成一组，通过灌胃方式一次性给予171.3 mg/kg的2-CP或4-CP，将其乳化在水中。对于两种异构体，24小时尿液分析表明，78.1%到88.3%的给药剂量以葡萄糖苷酸形式排出，12.8%到20.6%的给药剂量以醚硫酸盐形式排出。总的来说，分别有101.7%和101.1%的2-CP或4-CP给药剂量以尿液中的葡萄糖苷酸和硫酸盐结合物形式被计算在内。

A number of rabbit studies have shown that metabolism of the monochlorophenols is principally via conjugation. In /one/ study, groups of 6 rabbits were treated by gavage with 171.3 mg/kg of 2-CP or 4-CP emulsified in water as a single dose. For both isomers, the 24-hour urine analysis indicated that between 78.1 and 88.3% of the administered dose was excreted as the glucuronide, and between 12.8 and 20.6% of the administered dose was excreted as the ethereal sulfate. A total of 101.7 and 101.1% of the administered 2-CP or 4-CP doses, respectively, was accounted for as urinary glucuronide and sulfate conjugates.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

... 从胃肠道和注射部位吸收。以硫酸和葡萄糖醛酸的结合物形式排出。尿液静置后变暗。/氯酚/

... Absorbed from ... gastrointestinal tract & ... parenteral sites of injection. ... Excreted as conjugates of sulfuric & glucuronic acid. ... Urine darkens after standing. /Chlorophenols/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一般来说，氯酚类物质很容易通过皮肤被吸收。使用无毛小鼠的皮肤进行实验，2-MCP、2,4-DCP和2,4,6-T3CP的水溶液可以轻易地渗透皮肤，前提是该化合物没有离子化。在体外研究中，从尸检中取得的人类皮肤表皮膜显示出2-MCP、4-MCP、2,4-DCP和2,4,6-T3CP的渗透。溶质的亲脂性特征和它们的氢键能力是决定这种渗透的两个主要特性。

In general, chlorophenols are readily absorbed through the skin. Using the skin of the hairless mouse, aqueous solutions of 2-MCP, 2,4-DCP, and 2,4,6- T3CP readily penetrated the skin, provided that the compound was not ionized. In vitro studies on epidermal membranes from human skin taken at autopsy showed penetration by 2-MCP, 4-MCP, 2,4-DCP, and 2,4,6-T3CP. The lipophilic character of the solutes and their hydrogen-bonding capacity are the 2 main features determining this penetration.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S16,S28,S28A,S36/37,S45,S61,S7
• 危险类别码：
  R51/53,R20/21/22
• WGK Germany：
  2
• 海关编码：
  2908199090
• 危险品运输编号：
  UN 2021 6.1/PG 3
• 危险类别：
  6.1
• RTECS号：
  SK2625000
• 包装等级：
  III

制备方法与用途

类别：有毒物质

可燃性危险特性：

• 可燃，燃烧时分解产生有毒氯化物气体

储运特性：

• 库房应保持低温、通风和干燥

灭火剂：

• 水、二氧化碳、干粉或砂土均可用于灭火

反应信息

• 作为反应物：
  描述：

  邻氯苯酚 在 苯膦酰二氯 、 五氯化磷 作用下， 反应 5.0h， 以76.3%的产率得到邻二氯苯
  参考文献：
  名称：

  PhPOCl2 作为苯酚与 PCl5 氯化反应的有效催化剂

  摘要：

  摘要 通过使用五氯化磷 (PCl5) 和催化量的苯基二氯化膦 (PhPOCl2)，苯酚很容易转化为相应的芳基氯，这是一种以良好收率合成芳基氯的有效新方法。图形概要

  DOI：

  10.1080/00397911.2016.1218897
• 作为产物：
  描述：

  邻二氯苯 在 sodium methylate 、 sodium thiomethoxide 作用下， 生成 邻氯苯酚
  参考文献：
  名称：

  HMPA中未活化的芳基卤化物与甲醇钠的反应：酚，茴香醚和甲氧基酚的合成

  摘要：

  由于S N Ar过程，甲醇钠与HMPA中的二氯苯反应生成氯茴香醚。然后过量的MeONa通过S N 2反应使醚脱甲基，得到氯酚。用三氯苯和四氯苯可以将最初形成的氯茴香醚脱烷基化为氯酚，或者可以进一步取代生成氯二甲氧基苯；它们与过量的MeONa反应，得到氯甲氧基苯酚。在取代基的电子效应的基础上，介绍并讨论了用二，三和四氯苯的各种异构体获得的结果。

  DOI：

  10.1016/s0040-4020(01)97647-1
• 作为试剂：
  描述：

  2',3'-O-异亚丙基胞苷 、 氯磷酸二乙酯 在 邻氯苯酚 、 甲胺,N-甲基-,盐铝 作用下， 生成 Diethyl 2',3'-O-isopropylidenecytidine 5'-phosphate
  参考文献：
  名称：

  Chemoselective phosphorylation of -unprotected nucleosides via aluminum alkoxides

  摘要：

  DOI：

  10.1016/s0040-4039(00)94162-5

文献信息

• Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20150231142A1

  公开（公告）日：2015-08-20

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及含有上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• [EN] 2,4-DIAMINOQUINAZOLINES FOR SPINAL MUSCULAR ATROPHY<br/>[FR] 2,4-DIAMINOQUINAZOLINES UTILES POUR LE TRAITEMENT D'UNE ATROPHIE MUSCULAIRE SPINALE
  申请人：DECODE CHEMISTRY INC

  公开号：WO2005123724A1

  公开（公告）日：2005-12-29

  2,4-Diaminoquinazolines of formulae I-IV and VI (I, II, III, IV and VI) are useful for treating spinal muscular atrophy (SMA).

  2,4-二氨基喹唑啉的化学式I-IV和VI（I，II，III，IV和VI）可用于治疗脊髓性肌萎缩症（SMA）。
• ACYL-HYDRAZONE AND OXADIAZOLE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AND USES THEREOF
  申请人：Universidade Federal de Santa Catarina

  公开号：US20150191445A1

  公开（公告）日：2015-07-09

  The present invention relates to acyl-hydrazone compounds, in particular 3,4,5-trimethoxyphenyl-hydrazide derivatives, as well as the oxadiazole analogs thereof and other similar compounds, and to the pharmaceutical use of the same for the treatment of various diseases associated with cell proliferation, such as leukemias, including acute lymphoblastic leukemia (ALL), tumours and inflammation. Acyl-hydrazones have been obtained having activity similar to that of the compound used as a standard in experiments (colchicine). The greater selectivity of the compounds according to the invention is an important feature, associated with fewer side effects than the pharmaceuticals used at present in clinical treatments. The synthetised acyl-hydrazones, more particularly the compounds 02 and 07, exhibited important antileukemic activity, which suggests 02 and 07 as candidates to pharmaceutical prototypes, or to pharmaceuticals for the treatment of leukemias, in particular acute lymphoblastic leukemia (ALL), tumours and other proliferative diseases, such as inflammation. The action mechanism of the most active compounds was determined by using DNA microarrays and subsequent tests indicated by the chip, besides selectivity studies in healthy human lymphocytes.

  本发明涉及酰基腙化合物，特别是3,4,5-三甲氧基苯基腙衍生物，以及其噁二唑类似物和其他类似化合物，以及它们在治疗与细胞增殖相关的各种疾病，如白血病（包括急性淋巴细胞白血病（ALL））、肿瘤和炎症方面的药用。已获得具有与实验中使用的化合物（秋水仙碱）相似活性的酰基腙。根据本发明的化合物具有更大的选择性，与目前在临床治疗中使用的药物相比，副作用更少是一个重要特征。合成的酰基腙，尤其是化合物02和07，表现出重要的抗白血病活性，这表明02和07可能成为药物原型的候选，或用于治疗白血病，特别是急性淋巴细胞白血病（ALL）、肿瘤和其他增殖性疾病，如炎症的药物。最活性化合物的作用机制是通过使用DNA微阵列确定的，并且通过芯片指示的后续测试，以及对健康人类淋巴细胞的选择性研究。
• 1,1,2,2-Tetrahydroperoxy-1,2-Diphenylethane: An efficient and high oxygen content oxidant in various oxidative reactions
  作者：Kaveh Khosravi、Shirin Naserifar

  DOI：10.1016/j.tet.2018.09.041

  日期：2018.11

  Several oxidative approaches namely thiocyanation of aromatic compounds, epoxidation of alkenes, amidation of aromatic aldehydes, epoxidation of α, β-unsaturated ketones, oxidation of sulfides to sulfoxides and sulfones, bayer-villeger reaction, bromination and iodation of aniline and phenol derivatives oxidative esterification, oxidation of pyridines and oxidation of secondary, allylic and benzyllic

  几种氧化方法分别是芳族化合物的硫氰化，烯烃的环氧化，芳族醛的酰胺化，α，β-不饱和酮的环氧化，硫化物氧化为亚砜和砜，拜耳-维格反应，苯胺和苯酚衍生物的溴化和碘化氧化酯化，吡啶氧化和仲，烯丙基和苄基醇的氧化反应均使用1,1,2,2-四氢过氧-1,2-二苯乙烷作为潜在的固体氧化剂进行，可储存数月而不会损失其活性。所有步骤均通过温和的反应条件完成，并以高收率和较短的反应时间提供了产物。
• Carboxylation of Phenols with CO₂at Atmospheric Pressure
  作者：Junfei Luo、Sara Preciado、Pan Xie、Igor Larrosa

  DOI：10.1002/chem.201601114

  日期：2016.5.10

  A convenient and efficient method for the ortho‐carboxylation of phenols under atmospheric CO2 pressure has been developed. This method provides an alternative to the previously reported Kolbe–Schmitt method, which requires very high pressures of CO2. The addition of a trisubstituted phenol has proved essential for the successful carboxylation of phenols with CO2 at standard atmospheric pressure, allowing

  已经开发了一种在大气CO 2压力下使酚进行邻羧基羧化的便捷有效方法。该方法提供了以前报道的Kolbe-Schmitt方法的替代方法，后者需要非常高的CO 2压力。已证明添加三取代的苯酚对于在标准大气压下成功地将苯酚与CO 2羧化至关重要，从而可以有效制备各种水杨酸。

表征谱图