光气 | 75-44-5

• 分子结构分类: 无机化合物 - 均质非金属化合物 - 卤代有机物
• 中文名称: 光气
• 中文别名: 氯代甲酰氯
• 英文名称: phosgene
• 英文别名: COCl2；carbonyl dichloride
• CAS: 75-44-5
• 化学式: CCl₂O
• 分子量: 98.9164
• InChiKey: YGYAWVDWMABLBF-UHFFFAOYSA-N

物化性质

• 稳定性/保质期：
  1. 稳定性^[18] - 稳定 2. 禁配物^[19] - 水、醇类、碱类 3. 避免接触的条件^[20] - 潮湿空气、受热 4. 聚合危害^[21] - 不聚合

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  4
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

ADMET

代谢

半胱氨酸在体外抑制了氯仿与肝微粒体蛋白的共价结合，并捕获了一种反应性代谢物，可能是光气，形成了2-氧噻唑烷-4-羧酸。这表明氯仿的碳-氢键被细胞色素P450单加氧酶氧化产生三氯甲醇，后者自发脱氯化氢生成光气。

Cysteine inhibited in vitro covalent binding of chloroform to liver microsomal protein and trapped a reactive metabolite, presumably phosgene, as 2-oxothiazolidine-4-carboxylic acid. This suggests that the carbon-hydrogen bond of chloroform is oxidized by a cytochrome P450 monooxygenase to produce trichloromethanol, which spontaneously dehydrochlorinates to yield phosgene.

来源:Hazardous Substances Data Bank (HSDB)

代谢

光气是在NADPH和氧气依赖的微粒体氧化四氯化碳过程中形成的。

Phosgene is formed during NADPH and oxygen dependent microsomal oxidation of /carbon tetrachloride/.

来源:Hazardous Substances Data Bank (HSDB)

代谢

光气与水反应迅速，但与组织大分子中某些化学基团，如游离胺和巯基反应更快。由于其高反应性，即使暴露于高浓度的光气中，也很少有未反应的光气进入血液循环。

Phosgene reacts rapidly with water, but more rapidly with certain chemical groups found in tissue macromolecules, such as free amines and sulfhydryls. Because of its high reactivity, it is doubtful that any unreacted phosgene will enter the general circulation even after exposure to high concentrations of the gas.

来源:Hazardous Substances Data Bank (HSDB)

代谢

对氯仿的敏感性 与肾脏代谢氯仿为有毒代谢物光气的能力有关。对氯仿敏感的雄性DBA/2J小鼠的肾脏匀浆比不太敏感的C57BL/6J小鼠更快地将氯仿代谢为光气。同样，对氯仿诱导的肾毒敏感性雄性小鼠的肾脏匀浆将氯仿代谢为光气的速度几乎比雌性小鼠快一个数量级。然而，用睾酮治疗雌性小鼠逆转了这一趋势。肾脏微粒体和线粒体组分中的细胞色素P450似乎催化了氯仿代谢为光气的过程。

... Sensitivity to chloroform correlates with the capacity of the kidney to metabolize chloroform to the toxic metabolite phosgene. ... Kidney homogenates of sensitive male DBA/2J mice metabolized chloroform to phosgene more rapidly than did the less sensitive C57BL/6J mice. Similarly, kidney homogenates from male mice, which are sensitive to chloroform induced nephrotoxicity, metabolized chloroform to phosgene at nearly an order of magnitude more rapidly than did those from female mice. Treatment of female mice with testosterone, however, reversed this trend. Cytochrome P450 in the microsomal and mitochondrial fraction of the kidney appeared to catalyze the metabolism of chloroform to phosgene.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

普通人群和职业环境中的暴露主要是通过吸入。... 暴露的主要途径是通过吸入，气体渗透到呼吸道的组织中，因此只有极少量的一氧化碳在体内分布。在水溶液中非常短的半衰期（0.026秒）排除了在体内显著保留一氧化碳的可能性。... 一氧化碳的水解产物，即盐酸和二氧化碳，通过正常的生理过程排出体外。一氧化碳通过蛋白质的酰化以及产生盐酸来发挥其毒性。蛋白质中的氨基、羟基和巯基基团似乎是酰化的目标，导致与能量代谢相关的多种酶的显著抑制和气血屏障的破坏。在所有研究的物种中，肺是主要的靶器官。... 在所有物种中，典型的病理特征是肺水肿的临床表现延迟，这是剂量依赖性的。在低浓度时，终末细支气管和肺泡的病理变化是典型的肺部刺激物，而在更高暴露时，肺水肿发生，导致气体交换干扰和死亡。... 一氧化碳暴露可能导致眼睛和皮肤刺激。... 在人类和实验动物中，靶器官是肺。在暴露于一氧化碳水平在120至1200毫克/立方米-分钟之间后，已经报道了三个不同的临床病理阶段。初始阶段包括眼睛和喉咙疼痛以及胸部紧绷，常伴有呼吸急促、喘息和咳嗽；可能出现低血压、心动过缓和罕见的窦性心律失常。第二或潜伏期通常是无症状的，可以持续长达24小时，这取决于暴露的水平和持续时间。在第三阶段，可能会发展成肺水肿，导致某些情况下的死亡。在工业事故后暴露于一氧化碳的人群报告了包括头痛、恶心、咳嗽、呼吸困难、疲劳、咽痛、胸痛和紧绷、眼部剧痛和严重流泪在内的各种症状。... 由于缺乏暴露数据... 可以得出的关于一氧化碳慢性影响的结论是有限的。

Human exposure in both the general population and occupational setting is primarily by inhalation. ... The primary route of exposure is by inhalation, the gas penetrates into the tissues of the respiratory tract and so only minimal amounts of phosgene are distributed in the body. The very short half-life (0.026 seconds) in aqueous solutions precludes a significant retention of phosgene in the body. ... The hydrolytic products of phosgene, i.e., hydrochloric acid and carbon dioxide, are disposed of by the body through normal physiological processes. Phosgene exerts its toxicity through acylation of proteins, as well as through the production of hydrochloric acid. The amino, hydroxyl and sulfhydryl groups in the protein appear to be the target for acylation leading to marked inhibition of several enzymes related to energy metabolism and a breakdown of the blood:air barrier. In all species studied, the lung is the major target organ. ... In all species the characteristic pathological feature is the delayed clinical manifestation of pulmonary edema, which is dose-dependent. Pathological changes in the terminal bronchioles and alveoli at low concentrations are typical of a pulmonary irritant, whereas at higher exposures pulmonary edema occurs, leading to interference with gas exchange and death. ... Phosgene exposure can result in eye and skin irritation. ... The target organ in humans, as in experimental animals, is the lung. After exposure to phosgene levels between 120 and 1200 mg/cu m-min, three distinct clinical clinicopathological phases have been reported. The initial phase consists of pain in the eyes and throat and tightness in the chest, often with shortness of breath, wheezing, and coughing; hypotension, bradycardia and rarely sinus arrhythmias can occur. The second or latent phase, which is often asymptomatic, can last as long as 24 hr depending upon the level and duration of exposure. In the third phase, pulmonary edema may develop, leading to death in some cases. Populations exposed to phosgene after industrial accidents have reported a wide variety of symptoms, including headache, nausea, cough, dyspnea, fatigue, pharyngeal pain, chest tightness and pain, intense pain in the eye and severe lacrimation. ... In view of the lack of exposure data ... the conclusions regarding the chronic effects of phosgene that can be drawn are limited.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 暴露途径

该物质可以通过吸入被身体吸收。

The substance can be absorbed into the body by inhalation.

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

毒理性

• 暴露途径

吸入，皮肤和/或眼睛接触（液体）

inhalation, skin and/or eye contact (liquid)

来源:The National Institute for Occupational Safety and Health (NIOSH)

毒理性

• 症状

眼睛刺激；干咳喉咙；呕吐；咳嗽，泡沫痰，呼吸困难，胸痛，发绀；液体：冻伤

irritation eyes; dry burning throat; vomiting; cough, foamy sputum, dyspnea (breathing difficulty), chest pain, cyanosis; liquid: frostbite

来源:The National Institute for Occupational Safety and Health (NIOSH)

毒理性

• 吸入症状

咳嗽。喉咙痛。胸闷。呼吸急促。恶心。呕吐。症状可能出现延迟。

Cough. Sore throat. Chest tightness. Shortness of breath. Nausea. Vomiting. Symptoms may be delayed.

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

吸收、分配和排泄

老鼠暴露在0.1-1.0 ppm的14C-光气（0.4-4.1 mg/立方米）中0.5至4小时，研究了碳-14在组织中的分布。光气加合物的浓度（以每克干重纳米摩尔碳-14测量）在肺、气管、鼻咽和血液中最高，在鼻腔和支气管肺泡灌洗液的成分中也高度集中。肺组织的碳-14分布在脂质、大分子和水溶性部分中，与每个部分所贡献的重量成比例。

Rats were exposed to 0.1 - 1.0 ppm 14C-phosgene (0.4 - 4.1 mg/cu m) for 0.5 to 4 hr and tissue distribution of carbon-14 was investigated. Phosgene adduct concentrations (measured as nmol carbon-14/g dry weight) were highest in the lung, trachea, nasopharynx and blood, and were also highly concentrated in constituents of nasal and broncheolar lavage fluids. Lung tissue carbon-14 was distributed in lipid, macromolecule, and water-soluble fractions in a manner which was proportional to the weight contributed by each fraction.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

家兔、豚鼠、大鼠、仓鼠和老鼠同时暴露于1.6 ppm的14C-光气（6.6 mg/立方米）中3分钟，在一个封闭的有机玻璃室中进行。暴露后，这些动物肺部的碳-14平均浓度分别为3.15、2.50、5.33、5.05和11.13纳摩尔/克湿重。血液中的碳-14浓度从家兔的肺浓度的2.5%到老鼠的5.9%。鼻咽部的碳-14占呼吸道总碳-14的比例在家兔和豚鼠（0.46 - 0.50）中高于其他物种（0.22 - 0.36）。气管中的碳-14总是约占呼吸道总碳-14的3%。肝脏中的碳-14约为肺浓度的1%。光气与组织的结合通过组织的三氯乙酸沉淀物中大量的碳-14以及暴露后3天肺部仍然存在的碳-14（初始的20%）得到证实。

Rabbits, guinea pigs, rats, hamsters and mice were exposed simultaneously to 1.6 ppm 14C-phosgene (6.6 mg/cu m) for 3 min in a closed Plexiglas chamber. Mean lung concentrations of carbon-14 in these animals immediately following exposure were 3.15, 2.50, 5.33, 5.05 and 11.13 nmoles/g wet weight, respectively. Blood carbon-14 ranged from 2.5% of lung concentrations in rabbits to 5.9% in mice. The nasopharyngeal fraction of total respiratory tract carbon-14 was higher in rabbits and guinea pigs (0.46 - 0.50) than in the other species (0.22 - 0.36). Tracheal carbon-14 was always about 3% of total respiratory tract carbon-14. Liver carbon-14 was about 1% of lung concentrations. Tissue binding of phosgene was shown by a large percentage of carbon-14 in trichloroacetic acid precipitates of tissue and by the presence of carbon-14 in lungs (20% of initial) 3 days post exposure.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

气体渗透到呼吸道的组织中，并在一定程度上被肺部吸收。... 光气水解产生的盐酸和二氧化碳主要通过肾脏和肺部分别排出。

The gas penetrates into the tissues of respiratory tract and to some extent is absorbed by the lung. ... Hydrochloric acid and carbon dioxide produced by hydrolysis of phosgene are excreted largely by kidney and lung, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

老鼠、小鼠、仓鼠、豚鼠和兔子通过吸入方式暴露于1.6 ppm的14C-光气中3分钟。所有动物的血液和肝脏样本中均检测到极低水平的碳-14。

Rats, mice, hamsters, guinea pigs and rabbits were exposed by inhalation to 14C-phosgene at 1.6 ppm for 3 minutes. Carbon-14 was detected at very low levels in blood and liver samples of all animals.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

制备方法

1. 当需要少量光气时，可将四氯化碳与硫酸反应。将四氯化碳加热至55-60℃，滴加入发烟硫酸，即发生逸出光气，如需使用液态光气，则将发生的光气加以冷凝。
2. 工业上通常采用一氧化碳与氯气的反应得到光气。

工业制法以二氧化碳和氯气为原料，在活性炭催化下反应。控制温度在60～150℃之间生成的气体冷却至-25℃至-30℃，液化装入钢瓶中。实验室制法同样使用CCl4和发烟硫酸，在烧瓶中加入四氯化碳后加热至沸腾，滴加30%的发烟硫酸，此时生成光气COCl2，将之冷凝即可得到液体COCl2。

市售品中含有很多杂质，如CO2、CO、空气等，含量均在1%左右。可以采用以下方法提纯：

• 将气体导入烧瓶中，用冰盐水冷却液化。
• 在烧瓶上装上球形回流冷凝管通水冷凝，冷凝管和装满7～8℃的水的亨普尔气体量管连接，量管与冰盐水冷却的冷凝器相连，冷凝管和接收器相接。除去冷冻剂后，液体即会蒸发，冷却接收器便可得到COCl2。
• 将气体导入烧瓶中，用冰盐水使之冷凝后，再撤去冰盐水，在高真空下分馏残留物至所有馏分保持相同的蒸气压，纯COCl2的蒸气压为556.5mmHg。

合成制备方法

1. 当需要少量光气时，将四氯化碳与硫酸反应。具体操作同前。
2. 工业上通常采用一氧化碳与氯气的反应得到光气。

工业制法使用二氧化碳和氯气为原料，在活性炭催化下反应，温度控制在60～150℃之间生成气体，冷却至-25℃至-30℃液化装入钢瓶中。实验室制法则以CCl4和发烟硫酸为原料，操作步骤同前。

市售品含有CO2、CO、空气等杂质，含量均在1%左右。可以采用以下方法提纯：

• 将气体导入烧瓶中用冰盐水冷却液化。
• 在烧瓶上装上球形回流冷凝管通水冷凝，连接亨普尔气体量管和冷凝器，最后通过接收器收集COCl2。
• 也可以将气体导引入烧瓶后使用冰盐水使之冷凝，在高真空下分馏残留物至所有馏分保持相同的蒸气压。

用途简介

光气主要用于合成氨基甲酸酯类杀虫剂、聚氨酯硬泡、软泡、弹性体及人造革的重要原料。特殊品种还用于粘结剂，以及制备碳酸酯、氯甲酸酯、异氰酸酯、异腈、醛、氯代烷、酸酐，与腈生成杂环。

此外，光气广泛应用于有机合成领域，特别是制造异氰酸酯和聚氨酯等。它也被用作染料、橡胶、农药和塑料的原料。

用途

1. 合成氨基甲酸酯类杀虫剂，以及作为聚氨酯硬泡、软泡、弹性体及人造革的重要原料。
2. 用于制备碳酸酯、氯甲酸酯、异氰酸酯、异腈、醛、氯代烷、酸酐，并与腈生成杂环。
3. 有机合成中制造异氰酸酯和聚氨酯等，还应用于染料、橡胶、农药及塑料的生产。 [23]

反应信息

• 作为反应物：
  描述：

  光气 在 cadmium(II) sulphide 作用下， 生成 羰基硫
  参考文献：
  名称：

  Nuricsan, Chemische Berichte, 1891, vol. 24, p. 2970

  摘要：

  DOI：
• 作为产物：
  描述：

  calcium trichloroacetate 以 水 为溶剂， 生成 光气
  参考文献：
  名称：

  Henry, L., Berichte der Deutschen Chemischen Gesellschaft, 1879, vol. 12, p. 1844 - 1848

  摘要：

  DOI：
• 作为试剂：
  描述：

  环丙胺 、 2,6-dichloro-4-iodo-3-pyridinecarboxylic acid 在 光气 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  SALT-INDUCIBLE KINASES (SIK) INHIBITORS AND METHODS OF USES THEREOF

  摘要：

  The disclosure provides for compounds, compositions, and methods for modulating or inhibiting SIK.

  公开号：

  WO2024104441A1

文献信息

• 5-Norbornene-2,3-dicarboximido Carbonochloridate. A New Stable Reagent for the Introduction of Amino-Protecting Groups
  作者：Peter Henklein、Hans-Ulrich Heyne、Wolf-Rainer Halatsch、Hartmut Niedrich

  DOI：10.1055/s-1987-27873

  日期：——

  The synthesis of activated carbonates, based on a new carbonochloridate derived from N-hydroxy-5-norbornene-2,3-dicarboximide, is reported. These activated carbonic esters are excellent reagents for the introduction of all currently used urethane protecting groups.

  报道了一种基于N-羟基-5-降冰片烯-2,3-二羧亚胺衍生的新碳酰氯化物的活化碳酸盐的合成。这些活化碳酸酯是引入目前所有使用的氨基甲酸酯保护基团的优秀试剂。
• Alkyl 1-Chloroalkyl Carbonates: Reagents for the Synthesis of Carbamates and Protection of Amino Groups
  作者：Gérard Barcelo、Jean-Pierre Senet、Gérard Sennyey、Jean Bensoam、Albert Loffet

  DOI：10.1055/s-1986-31724

  日期：——

  The synthesis of 1-chloroalkyl carbonates and their reaction with various type of amines are described. This reaction is useful for the synthesis of carbamate pesticides and for the protection of various amino groups, including amino acids.

  描述了1-氯代烷基碳酸酯的合成及其与各种类型胺的反应。这一反应对于合成氨基甲酸酯类农药和保护包括氨基酸在内的各种氨基团具有重要作用。
• (2R,4S)-2-Aminomethyl-5,5-dimethyl-1,3-thiazolidine-4-carboxylic Acid Dihydrochloride: Synthesis, Epimerization, and Derivatives
  作者：Peter Imming

  DOI：10.1002/ardp.19953280115

  日期：——

  The preparation of the title compound 6a from penicillamine 5 or from penicillins 7, the spectroscopic data and stereochemical assignments are given. 6a quickly epimerizes at C‐2 in dilute aqueous solution. Details are given along with the preparation of the new thiazolidines 10–13 from 6.

  由青霉胺5或由青霉素7制备标题化合物6a，给出了光谱数据和立体化学归属。6a 在稀水溶液中在 C-2 处快速差向异构化。详细信息与新的噻唑烷 10-13 从 6 的制备一起给出。
• [EN] IMIDAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS IMIDAZOLE UTILES COMME INHIBITEURS DE LA FAAH
  申请人：MERCK & CO INC

  公开号：WO2009152025A1

  公开（公告）日：2009-12-17

  The present invention is directed to certain imidazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzeimer Disease, and Parkinson's Disease.

  本发明涉及某些咪唑衍生物，其可用作脂肪酰胺水解酶（FAAH）的抑制剂。该发明还涉及包含这些化合物作为活性成分的药物配方，以及这些化合物及其配方在治疗某些疾病中的使用，包括骨关节炎、类风湿性关节炎、糖尿病性神经病、带状疱疹后神经痛、骨骼肌肉疼痛和纤维肌痛，以及急性疼痛、偏头痛、睡眠障碍、阿尔茨海默病和帕金森病。
• [EN] PYRAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS DE PYRAZOLE UTILES COMME INHIBITEURS DE FAAH
  申请人：MERCK & CO INC

  公开号：WO2009151991A1

  公开（公告）日：2009-12-17

  The present invention is directed to certain imidazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer disease, and Parkinson's disease

  本发明涉及某些咪唑衍生物，其可用作脂肪酰胺水解酶（FAAH）的抑制剂。该发明还涉及包含这些化合物作为活性成分的药物配方，以及这些化合物及其配方在治疗某些疾病中的使用，包括骨关节炎、类风湿性关节炎、糖尿病神经病变、带状疱疹后神经痛、骨骼肌肉疼痛和纤维肌痛，以及急性疼痛、偏头痛、睡眠障碍、阿尔茨海默病和帕金森病。

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