地氟烷 | 57041-67-5

• 物质功能分类: 原料药 - 解热镇痛药 - 镇痛药
• 分子结构分类: 有机化合物 - 有机卤素化合物 - 有机氟化物
• 中文名称: 地氟烷
• 中文别名: 地氟醚；脱氟醚1-653；2-(氟甲氧基)-1,1,1,2-四氟乙烷；1,2,2,2-四氟乙基二氟甲醚；去氟烷；地氟醚；优宁；去氯氟烷；去氟醚
• 英文名称: desflurane
• 英文别名: 2-(difluoromethoxy)-1,1,1,2-tetrafluoroethane；1,2,2,2-tetrafluoroethyl difluoromethyl ether；2-Difluoromethoxy-1,1,2,2-tetrafluoroethane；2-(difluoromethoxy)-1,1,1,2-tetrafluoro-ethane；1-difluoromethoxy-1,2,2,2-tetrafluoroethane
• CAS: 57041-67-5
• 化学式: C₃H₂F₆O
• mdl: MFCD00236716
• 分子量: 168.039
• InChiKey: DPYMFVXJLLWWEU-UHFFFAOYSA-N

物化性质

• 沸点：
  23-24°C
• 密度：
  1,47 g/cm3
• 溶解度：
  几乎不溶于水，与无水乙醇混溶。
• 物理描述：
  Liquid
• 颜色/状态：
  Liquid
• 气味：
  Slight non-pungent odor
• 蒸汽密度：
  1.44
• 蒸汽压力：
  88.53 kPa at 20 °C; approximately 700 mm Hg at 22-23 °C
• 保留指数：
  425.8

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  7

ADMET

代谢

Desflurane是一种吸入性麻醉药，由CYP2E1酶最小程度地脱卤化，以至于血清中的氟化物水平不会超过基线水平。

Desflurane is minimally defluorinated by CYP2E1, to the extent that serum fluoride levels do not increase above baseline levels.

来源:DrugBank

代谢

氟化醚挥发性麻醉剂的肾毒性和肝毒性是由生物转化为有毒代谢物引起的。代谢也显著影响了一些挥发性麻醉剂的消除药代动力学。尽管有无数的研究探索了动物麻醉剂的代谢，但关于人类挥发性麻醉剂代谢的比较速率或负责去氟化的酶的身份的信息却很少。此次调查的第一个目的是比较人类肝微粒体中氟化醚麻醉剂的代谢。第二个目的是检验细胞色素P450 2E1是人类挥发性麻醉剂去氟化的特定P450同工酶的假设。从人肝中制备微粒体。通过氟化物产生量测量微粒体培养中的麻醉剂代谢。评估P450 2E1在麻醉剂去氟化中的作用涉及三种方法：对于12个人类肝脏的一系列，将微粒体去氟化速率与微粒体P450 2E1含量（通过西方印迹分析测量）相关联，将去氟化速率与使用标记底物（对硝基酚羟基化和氯唑松6-羟基化）的微粒体P450 2E1催化活性相关联，以及通过P450同工酶选择性抑制剂进行化学抑制。在饱和底物浓度下，通过氟化物产生量评估的麻醉剂代谢的顺序是甲氧氟烷 > 七氟烷 > 恩氟烷 > 异氟烷 > 地氟烷 > 0。七氟烷和甲氧氟烷去氟化与抗原性P450 2E1含量显著线性相关（分别为r = 0.98和r = 0.72），但与P450 1A2或P450 3A3/4无关。将麻醉剂去氟化与对硝基酚或氯唑松羟基化进行比较，七氟烷（r = 0.93，r = 0.95）和甲氧氟烷（r = 0.78，r = 0.66）显示出显著相关性。七氟烷去氟化也与已知的由人类P450 2E1代谢的恩氟烷的去氟化高度相关（r = 0.93）。二乙基二硫代氨基甲酸盐，一种选择性P450 2E1抑制剂，产生了浓度依赖性的七氟烷、甲氧氟烷和异氟烷去氟化的抑制。没有其他同工酶选择性抑制剂降低七氟烷的去氟化，而甲氧氟烷去氟化被选择性P450抑制剂呋拉非林（P450 1A2）、磺胺苯唑（P450 2C9/10）和奎尼丁（P450 2D6）抑制，但抑制程度远低于二乙基二硫代氨基甲酸盐。这些结果表明，细胞色素P450 2E1是人类肝微粒体中催化七氟烷去氟化的主要，如果不是唯一的酶。P450 2E1是甲氧氟烷代谢的主要，但非唯一酶，甲氧氟烷的代谢似乎也由P450s 1A2、2C9/10和2D6催化。数据还表明，P450 2E1负责异氟烷代谢的很大一部分。确定P450 2E1是人类主要麻醉剂代谢酶，为临床氟化醚麻醉剂代谢和毒性的机制理解提供了依据。

Renal and hepatic toxicity of the fluorinated ether volatile anesthetics is caused by biotransformation to toxic metabolites. Metabolism also contributes significantly to the elimination pharmacokinetics of some volatile agents. Although innumerable studies have explored anesthetic metabolism in animals, there is little information on human volatile anesthetic metabolism with respect to comparative rates or the identity of the enzymes responsible for defluorination. The first purpose of this investigation was to compare the metabolism of the fluorinated ether anesthetics by human liver microsomes. The second purpose was to test the hypothesis that cytochrome P450 2E1 is the specific P450 isoform responsible for volatile anesthetic defluorination in humans. Microsomes were prepared from human livers. Anesthetic metabolism in microsomal incubations was measured by fluoride production. The strategy for evaluating the role of P450 2E1 in anesthetic defluorination involved three approaches: for a series of 12 human livers, correlation of microsomal defluorination rate with microsomal P450 2E1 content (measured by Western blot analysis), correlation of defluorination rate with microsomal P450 2E1 catalytic activity using marker substrates (para-nitrophenol hydroxylation and chlorzoxazone 6-hydroxylation), and chemical inhibition by P450 isoform-selective inhibitors. The rank order of anesthetic metabolism, assessed by fluoride production at saturating substrate concentrations, was methoxyflurane > sevoflurane > enflurane > isoflurane > desflurane > 0. There was a significant linear correlation of sevoflurane and methoxyflurane defluorination with antigenic P450 2E1 content (r = 0.98 and r = 0.72, respectively), but not with either P450 1A2 or P450 3A3/4. Comparison of anesthetic defluorination with either para-nitrophenol or chlorzoxazone hydroxylation showed a significant correlation for sevoflurane (r = 0.93, r = 0.95) and methoxyflurane (r = 0.78, r = 0.66). Sevoflurane defluorination was also highly correlated with that of enflurane (r = 0.93), which is known to be metabolized by human P450 2E1. Diethyldithiocarbamate, a selective inhibitor of P450 2E1, produced a concentration-dependent inhibition of sevoflurane, methoxyflurane, and isoflurane defluorination. No other isoform-selective inhibitor diminished the defluorination of sevoflurane, whereas methoxyflurane defluorination was inhibited by the selective P450 inhibitors furafylline (P450 1A2), sulfaphenazole (P450 2C9/10), and quinidine (P450 2D6) but to a much lesser extent than by diethyldithiocarbamate. These results demonstrate that cytochrome P450 2E1 is the principal, if not sole human liver microsomal enzyme catalyzing the defluorination of sevoflurane. P450 2E1 is the principal, but not exclusive enzyme responsible for the metabolism of methoxyflurane, which also appears to be catalyzed by P450s 1A2, 2C9/10, and 2D6. The data also suggest that P450 2E1 is responsible for a significant fraction of isoflurane metabolism. Identification of P450 2E1 as the major anesthetic metabolizing enzyme in humans provides a mechanistic understanding of clinical fluorinated ether anesthetic metabolism and toxicity.

来源:Hazardous Substances Data Bank (HSDB)

代谢

SUPRANE（地氟烷，美国药典）是一种挥发性液体吸入麻醉剂，在人类肝脏中仅轻微生物转化。

SUPRANE (desflurane, USP) is a volatile liquid inhalation anesthetic minimally biotransformed in the liver in humans.

来源:Hazardous Substances Data Bank (HSDB)

代谢

对异氟醚的生物转化和肝毒性在豚鼠肝切片培养系统中进行了评估。从600-650克的雄性哈特利豚鼠制备了250-300微米的肝切片。将这些切片在37摄氏度、95%氧气的条件下，在密封小瓶中的克雷布斯-亨塞勒缓冲液中孵化。异氟醚被蒸发以产生0.7-2.3 mM的介质浓度。孵化后（3-24小时），确定切片的存活率（K+含量；蛋白质合成分泌）以及异氟醚的生物转化（F-）。为了比较，研究中包括了2.3 mM的异氟烷。尽管异氟醚引起了一定程度的与浓度相关的切片K+含量降低（1.1-2.2 mM；对照组的20%-40%），但效果小于2.3 mM异氟烷产生的效果（对照组的50%）。高浓度的异氟醚在孵化前9小时降低了蛋白质合成，而异氟烷在整个孵化期间降低了蛋白质合成。两种麻醉剂对蛋白质分泌均无影响。异氟醚的生物转化是微乎其微的，产生的F-仅是异氟烷的三分之一。

Biotransformation and hepatotoxicity of desflurane were evaluated in the guinea pig liver slice culture system. Liver slices (250-300 microns) were prepared from 600-650-g male Hartley guinea pigs. The slices were incubated in sealed vials in a Krebs-Henseleit buffer at 37 degrees C under 95% O2. Desflurane was vaporized to produce media concentrations of 0.7-2.3 mM. After incubation (3-24 hr) viability of the slices was determined (K+ content; protein synthesis secretion) along with the biotransformation of desflurane (F-). Isoflurane (2.3 mM) was included in the studies for comparative purposes. Although desflurane caused a mild concentration-related reduction in slice K+ content (1.1-2.2 mM; 20%-40% of control), the effects were less than those produced by 2.3 mM isoflurane (50% of control). High concentrations of desflurane decreased protein synthesis at the first 9 hr of incubation, and isoflurane decreased protein synthesis throughout the incubation period. Neither anesthetic affected protein secretion. The biotransformation of desflurane was minimal with threefold less F- produced from desflurane than isoflurane.

来源:Hazardous Substances Data Bank (HSDB)

代谢

地氟烷的代谢已经在动物和人类中进行了评估，通过测量血液和尿液中氟代谢物（氟离子、非挥发性有机氟、三氟乙酸）的出现。给大鼠（无论是否用苯巴比妥或乙醇预处理）施用地氟烷3.2 MAC小时，给猪施用5.5 MAC小时后，血液中的氟离子水平与对照组动物测得的价值几乎无法区分。相比之下，在暴露于地氟烷后4小时内，猪血浆中氟离子浓度显著增加了17%。在人类研究中，给患者（3.1 MAC小时）和志愿者（7.35 MAC小时）施用地氟烷后，麻醉后的血清氟浓度与背景氟离子浓度没有差异。同样，志愿者麻醉后尿液中氟离子和有机氟的排泄率与麻醉前相当。在志愿者暴露于地氟烷后，血清和尿液中发现了小但统计学上显著水平的三氟乙酸。志愿者在地氟烷暴露后24小时，血清中三氟乙酸的峰值浓度平均为0.38 +/- 0.17 uM（平均值 +/- 标准差），尿液中排泄率的峰值平均为0.169 +/- 0.107 umol/hr。尽管这些在地氟烷暴露后三氟乙酸的增加在统计学上是显著的，但它们大约比异氟烷暴露后的水平低10倍。地氟烷强烈抵抗生物降解，在动物和人类中只有少量被代谢。

The metabolism of desflurane has been assessed both in animals and humans by measuring the appearance of fluoride metabolites (fluoride ion, nonvolatile organic fluoride, trifluoroacetic acid) in blood and urine. Desflurane administered to rats (either pretreated or not pretreated with phenobarbital or ethanol) for 3.2 MAC-hours and to swine for 5.5 MAC-hours produced fluoride ion levels in blood that were almost indistinguishable from values measured in control animals. In contrast, a significant 17% increase in plasma fluoride ion concentration in swine was detected 4 hr after exposure to desflurane. In human studies, desflurane administered to patients (3.1 MAC-hours) and volunteers (7.35 MAC-hours) resulted in postanesthesia serum fluoride in concentrations that did not differ from background fluoride ion concentrations. Similarly, postanesthetic urinary excretion of fluoride ion and organic fluoride in volunteers was comparable to preanesthetic excretion rates. Small but statistically significant levels of trifluoroacetic acid were found in both serum and urine from volunteers after exposure to desflurane. Peak serum concentrations averaging 0.38 +/- 0.17 uM trifluoroacetic acid (mean +/- SD) and peak urinary excretion rates averaging 0.169 +/- 0.107 umol/hr were detected in volunteers 24 hr after desflurane exposure. Although these increases in trifluoroacetic acid after exposure to desflurane were statistically significant, they are approximately 10-fold less than levels seen after exposure to isoflurane. Desflurane strongly resists biodegradation, and only a small amount is metabolized in animals and humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

Desflurane诱导连接电导减少，通过减少间隙连接通道开启时间并增加间隙连接通道关闭时间。Desflurane还通过增加脂质膜的流动性激活肌浆网中的钙依赖性ATP酶。它似乎还能与ATP合酶的D亚单位和NADH脱氢酶结合。Desflurane还结合并激活GABA受体，大电导Ca²⁺激活的钾通道，甘氨酸受体，并拮抗谷氨酸受体。

Desflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Desflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Desflurane also binds to and agonizes the GABA receptor, the large conductance Ca²⁺ activated potassium channel, the glycine receptors, and antagonizes the glutamate receptors.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 肝毒性

预期的、连续的血液检测通常显示在大手术和使用卤化麻醉剂后的1到2周内，血清转氨酶水平有轻微的暂时性升高。然而，ALT水平超过正常上限10倍的情况非常不寻常，这表明有显著的肝毒性。临床上明显的、由地氟烷引起的严重肝损伤非常罕见，只有零星的病例报告发表，而且并非所有报告都非常有说服力。这种损伤表现为血清转氨酶水平的急性升高（5到50倍）以及在手术后的2到21天内出现黄疸。碱性磷酸酶和γ-谷氨酰转肽酶水平通常只有轻微升高。黄疸通常伴有1到2天的发热，并可能伴有皮疹和嗜酸性粒细胞增多。急性肝损伤可能是自限性的，在4到8周内解决，但可能会很严重，并伴有急性肝衰竭。一个强烈的风险因素是之前接触过任何卤化麻醉剂，特别是有卤烷肝炎病史或使用这些麻醉剂后出现不明原因的发热和皮疹。手术后和麻醉后急性肝损伤的鉴别诊断通常具有挑战性，与地氟烷诱导的肝炎相似的临床表现可能由休克或缺血、败血症、对乙酰氨基酚过量、急性病毒性或疱疹性肝炎以及其他特异质药物诱导的肝损伤引起。

Prospective, serial blood testing often demonstrates minor transient elevations in serum aminotransferase levels in the 1 to 2 weeks after major surgery and use of halogenated anesthetics. Appearance of ALT levels above 10 times the upper limit of normal, however, is distinctly unusual and points to significant hepatotoxicity. Clinically apparent, severe hepatic injury from desflurane is very rare, with only isolated case reports having been published and not all of which were very convincing. The injury is marked by acute elevations in serum aminotransferase levels (5- to 50-fold) and appearance of jaundice within 2 to 21 days of surgery. There are usually minimal increases in alkaline phosphatase and gammaglutamyl transpeptidase levels. Jaundice is usually preceded by a day or two of fever and may be accompanied by rash and eosinophilia. The acute liver injury may be self-limited and resolve within 4 to 8 weeks, but can be severe and associated with acute liver failure. A strong risk factor is previous exposure to any of the halogenated anesthetics and particularly a history of halothane hepatitis or unexplained fever and rash after anesthesia with one of these agents. The differential diagnosis of acute liver injury after surgery and anesthesia is often challenging, and a clinical picture similar to desflurane induced hepatitis can be caused by shock or ischemia, sepsis, acetaminophen overdose, acute viral or herpes hepatitis, as well as other idiosyncratic forms of drug induced liver injury.

来源:LiverTox

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

当浓度超过10体积百分比时，它可能会导致心动过速和呼吸道刺激性。[维基百科]

It may cause tachycardia and airway irritability when administered at concentrations greater than 10 vol%. [Wikipedia]

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：目前没有关于地氟烷在哺乳期使用的已发表经验。由于地氟烷在母体中的血清半衰期短，且药物预期不会被婴儿吸收，因此不需要等待期或弃奶。只要母亲从全身麻醉中恢复到足以哺乳的程度，就可以恢复哺乳。当手术中使用多种麻醉剂组合时，请遵循手术期间使用的最具问题的药物的建议。在一项研究中，与哺乳期母亲哺乳被禁止或非哺乳妇女相比，全身麻醉诱导前哺乳可减少七氟烷和丙泊酚的需求。其他麻醉剂的需求可能也会受到类似影响。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关的已发表信息。 ◉ 对泌乳和母乳的影响：一项随机研究比较了使用全身麻醉、脊髓麻醉或硬脊膜外麻醉进行剖宫产与正常阴道分娩对血清催乳素和催产素的影响以及开始泌乳的时间。全身麻醉使用丙泊酚2 mg/kg和罗库溴铵0.6 mg/kg进行诱导，然后根据需要使用七氟烷和罗库溴铵0.15 mg/kg。分娩后，所有组别的患者接受了1 L生理盐水中含有30国际单位催产素的输注，如果她们没有高血压，则给予0.2 mg甲基麦角新碱。全身麻醉组在分娩后给予芬太尼1至1.5 mcg/kg。全身麻醉组（n = 21）的术后催乳素水平较高，开始泌乳的平均时间（25小时）比其他组（10.8至11.8小时）长。未用药阴道分娩组的产后催产素水平高于全身麻醉和脊髓麻醉组。 一项对土耳其一家医院接受择期剖宫产分娩的妇女进行的回顾性研究比较了接受布比卡因脊髓麻醉的妇女（n = 170）和接受丙泊酚诱导、七氟烷维持和分娩后给予芬太尼的全身麻醉的妇女（n = 78）。两组在产后1小时和24小时的哺乳率没有差异。然而，在产后6个月，全身麻醉组中仍有67%的妇女在哺乳，而脊髓麻醉组为81%，这是一个统计学上的显著差异。

◉ Summary of Use during Lactation:There is no published experience with desflurane during breastfeeding. Because the serum half-life of desflurane in the mother is short and the drug is not expected to be absorbed by the infant, no waiting period or discarding of milk is required. Breastfeeding can be resumed as soon as the mother has recovered sufficiently from general anesthesia to nurse. When a combination of anesthetic agents is used for a procedure, follow the recommendations for the most problematic medication used during the procedure. In one study, breastfeeding before general anesthesia induction reduced requirements of sevoflurane and propofol compared to those of nursing mothers whose breastfeeding was withheld or nonnursing women. It is possible that requirements for other anesthetic agents would be affected similarly. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:A randomized study compared the effects of cesarean section using general anesthesia, spinal anesthesia, or epidural anesthesia, to normal vaginal delivery on serum prolactin and oxytocin as well as time to initiation of lactation. General anesthesia was performed using propofol 2 mg/kg and rocuronium 0.6 mg/kg for induction, followed by sevoflurane and rocuronium 0.15 mg/kg as needed. After delivery, patients in all groups received an infusion of oxytocin 30 international units in 1 L of saline, and 0.2 mg of methylergonovine if they were not hypertensive. Fentanyl 1 to 1.5 mcg/kg was administered after delivery to the general anesthesia group. Patients in the general anesthesia group (n = 21) had higher post-procedure prolactin levels and a longer mean time to lactation initiation (25 hours) than in the other groups (10.8 to 11.8 hours). Postpartum oxytocin levels in the nonmedicated vaginal delivery group were higher than in the general and spinal anesthesia groups. A retrospective study of women in a Turkish hospital who underwent elective cesarean section deliveries compared women who received bupivacaine spinal anesthesia (n = 170) to women who received general anesthesia (n = 78) with propofol for induction, sevoflurane for maintenance and fentanyl after delivery. No differences in breastfeeding rates were seen between the groups at 1 hour and 24 hours postpartum. However, at 6 months postpartum, 67% of women in the general anesthesia group were still breastfeeding compared to 81% in the spinal anesthesia group, which was a statistically significant difference.

来源:Drugs and Lactation Database (LactMed)

吸收、分配和排泄

• 吸收

关于地氟烷的Cmax（最大血药浓度）、Tmax（达到最大浓度的时间）和AUC（药时曲线下面积）的数据不容易获得。

Data regarding the Cmax, Tmax, and AUC of desflurane are not readily available.

来源:DrugBank

吸收、分配和排泄

• 消除途径

最初，地氟烷从肺部迅速消除。少量代谢物三氟乙酸通过尿液排出，只有吸入剂量的0.02%作为尿代谢物被回收。

Initially, desflurane is rapidly eliminated from the lungs. A small amount of the metabolite trifluoroacetic acid is eliminated in the urine and only 0.02% of an inhaled dose is recovered as urinary metabolites.

来源:DrugBank

吸收、分配和排泄

• 分布容积

Desflurane的分布容积中位数为612 mL/kg。

Desflurane has a median volume of distribution of 612 mL/kg.

来源:DrugBank

吸收、分配和排泄

• 清除

一个26克的desflurane剂量在大约33小时后有90%从大脑中消除。其代谢物三氟乙酸在尿液中的清除率为0.169 ± 0.107 µmol/L。

A 26 g dose of desflurane is 90% eliminated from the brain after 33 hours. The metabolite trifluoroacetic acid has a urinary clearance rate of 0.169 ± 0.107 µmol/L.

来源:DrugBank

吸收、分配和排泄

地氟烷在牛奶中的浓度可能在麻醉后24小时对临床没有重要性。

The concentrations of desflurane in milk are probably of no clinical importance 24 hours after anesthesia.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  GAS
• 危险品标志：
  Xi
• 安全说明：
  S23
• 海关编码：
  2909191800
• 危险类别码：
  R23
• WGK Germany：
  3

制备方法与用途

概述

地氟烷与异氟烷（CHF₂-O-CHCl-CF₃）相似，都是甲基乙烷的卤素化合物。不同之处在于，在α-乙基部分用氟替代了氯。由于氟具有较低的卤化作用，地氟烷在血液和组织中的溶解度降低，并且其沸点、蒸气压及稳定性发生了变化，增强了分子的稳定性和抗生物降解及抗碱性降解的能力。

化学性质

地氟烷是一种挥发性的液体，沸点为23.5℃，密度为D1.44。

用途

地氟烷是一种吸入性麻醉剂，诱导和苏醒速度较快，但其麻醉效力比其他卤化物略低。主要应用于临床麻醉中。

生产方法

通过将异氟烷与三氟化溴在室温下反应一整夜，可以得到地氟烷，收率为62%。

反应信息

• 作为反应物：
  描述：

  甲基锂 、 地氟烷 以 二乙氧基甲烷 为溶剂， 以18.4%的产率得到difluoromethyl 1,2,2-trifluoroethenyl ether
  参考文献：
  名称：

  METHODS FOR PREPARING FLUORINATED VINYL ETHERS

  摘要：

  一种制备氟化乙烯醚化合物的方法，包括将一种氟化醚底物与有机锂碱反应，所述氟化醚底物具有(i) 一个氢原子位于与乙醚氧原子相邻的碳原子的α位上，以及(ii) 一个氟原子位于与乙醚氧原子相邻的碳原子的β位上，以提供包含氟化乙烯醚化合物的反应产物。

  公开号：

  US20100267995A1
• 作为产物：
  描述：

  1,2,2,2-四氟乙基二氯甲基醚 在 potassium fluoride 、 18-冠醚-6 作用下， 以 环丁砜 为溶剂， 150.0 ℃ 、400.01 kPa 条件下， 反应 5.0h， 以70%的产率得到地氟烷
  参考文献：
  名称：

  １，２，２，２−テトラフルオロエチルジフルオロメチルエーテル（デスフルラン）の製造方法

  摘要：

  【问题】提供一种在工业规模下高效制造1,2,2,2-四氟乙基二氟甲基醚（Desflurane）的方法。 【解决方案】使用易于处理的氟化金属作为氟化试剂，对1,2,2,2-四氟乙基二氯甲基醚进行氟化反应，可以在抑制底物分解的同时高效地得到1,2,2,2-四氟乙基二氟甲基醚（Desflurane）。 【选择图】无。

  公开号：

  JP2019094292A

文献信息

• Synthesis of desflurane
  申请人：Anaquest, Inc.

  公开号：US05205914A1

  公开（公告）日：1993-04-27

  An improved preparation of desflurane, 1,2,2,2-tetrafluoroethyl difluoromethyl ether utilizing hexafluoropropene epoxide as a starting material. Hexafluoropropene epoxide is advantageous in that it is relatively inexpensive and is environmentally acceptable.

  一种改进的地氟烷制备方法，利用六氟丙烯环氧乙烷作为起始原料。六氟丙烯环氧乙烷具有价格相对较低且环保的优点。
• １，２，２，２−テトラフルオロエチルジクロロメチルエーテルの製造方法
  申请人：セントラル硝子株式会社

  公开号：JP2020002022A

  公开（公告）日：2020-01-09

  【課題】 １，２，２，２−テトラフルオロエチルジクロロメチルエーテルを効率的に製造する方法を提供する。【解決手段】 ラジカル開始剤もしくは光照射下、１，２，２，２−テトラフルオロエチルメチルエーテルを塩素化することにより、１，２，２，２−テトラフルオロエチルジクロロメチルエーテルと、高次塩素化物の１，２，２，２−テトラフルオロエチルトリクロロメチルエーテルとの混合物を得た後、得られた混合物に対し、水素を用いた加水素分解反応により、分離困難な副生物である１，２，２，２−テトラフルオロエチルトリクロロメチルエーテルを１，２，２，２−テトラフルオロエチルジクロロメチルエーテルへ効率的に変換できる。また、当該１，２，２，２−テトラフルオロエチルジクロロメチルエーテルを用いて、吸入麻酔薬として有用な１，２，２，２−テトラフルオロエチルジフルオロメチルエーテル（デスフルラン）を製造できる。【選択図】なし

  提供一种高效制备1,2,2,2-四氟乙基二氯甲基醚的方法。通过在自由基引发剂或光照射下，将1,2,2,2-四氟乙基甲基醚氯化，得到1,2,2,2-四氟乙基二氯甲基醚和高级氯化物1,2,2,2-四氟乙基三氯甲基醚的混合物，然后对得到的混合物进行加氢分解反应，可高效将难以分离的副产物1,2,2,2-四氟乙基三氯甲基醚转化为1,2,2,2-四氟乙基二氯甲基醚。此外，利用所述1,2,2,2-四氟乙基二氯甲基醚，可以制备用作吸入麻醉药的有用1,2,2,2-四氟乙基二氟甲基醚（地氟兰）。【选择图】无
• Compositions of a hydrofluoroether and a hydrofluorocarbon
  申请人：Klug Diana Lynn

  公开号：US06905630B2

  公开（公告）日：2005-06-14

  This invention relates to compositions that include at least one fluoroether and at least one hydrofluorocarbon. Included in this invention are compositions of a cyclic or acyclic hydrofluoroether of the formula C a F b H 2a+2−b O c wherein a=2 or 3 and 3≦b≦8 and c=1 or 2 and a hydrofluorocarbon of the formula C n F m H 2n+2−m wherein 1≦n≦4 and 1≦m≦8. Such compositions may be used as refrigerants, cleaning agents, expansion agents for polyolefins and polyurethanes, aerosol propellants, heat transfer media, gaseous dielectrics, fire extinguishing agents, power cycle working fluids, polymerization media, particulate removal fluids, carrier fluids, buffing abrasive agents, and displacement drying agents.

  这项发明涉及包括至少一种氟醚和至少一种氢氟烃的组合物。该发明包括具有下列式CaFbH2a+2−bOc的环状或非环状氢氟醚组合物，其中a=2或3，3≦b≦8，c=1或2，以及具有下列式CnFmH2n+2−m的氢氟烃组合物，其中1≦n≦4，1≦m≦8。这些组合物可用作制冷剂、清洁剂、聚烯烃和聚氨酯的膨胀剂、喷雾推进剂、传热介质、气体绝缘体、灭火剂、动力循环工作流体、聚合介质、颗粒去除流体、载体流体、抛光磨料剂和位移干燥剂。
• Monofluorination of fluorinated ethers with high-valency metal fluorides
  作者：Shigeru Kurosawa、Takashi Arimura、Akira Sekiya

  DOI：10.1016/s0022-1139(97)00075-4

  日期：1997.10

  Fluorinated ethers were fluorinated by high-valency metal fluorides such as MnF3, CoF3, and KCoF4. The monofluorinating reactivities of these reagents with 2,2,2-trifluoroethyl difluoromethyl ether, bis(2,2,2-trifluoroethyl) ether, and 2-chloro-1,1,2-trifluoroethyl methyl ether follow the order MnF3 > CoF3 > KCoF4. The order of monofluorination reactivity with fluorinated ethers did not agree with

  氟化醚被高价金属氟化物如MnF 3，CoF 3和KCoF 4氟化。这些试剂与2,2,2-三氟乙基二氟甲基醚，双（2,2,2-三氟乙基）醚和2-氯-1,1,2-三氟乙基甲基醚的单氟反应性遵循MnF 3 > CoF的顺序3 > KCoF 4。与氟化醚的单氟化反应性顺序与宝石-二氟氢氟烃的顺序不同（CoF 3 > MnF 3 > KCoF 4）。2,2,2-三氟乙氧基化合物与MnF 3的区域选择性单氟化 在与三氟甲基相邻的亚甲基位置上获得“α”。
• Production Method for 1,2,2,2-Tetrafluoroethyl Difluoromethyl Ether (Desflurane)
  申请人：Central Glass Company, Limited

  公开号：US20190345086A1

  公开（公告）日：2019-11-14

  Fluoral is obtained by gas-phase fluorination of chloral in the presence of a catalyst and then reacted with trimethyl orthoformate, thereby readily forming 1,2,2,2-tetrafluoroethyl methyl ether as an intermediate for production of desflurane. 1,2,2,2-Tetrafluoroethyl difluoromethyl ether (desflurane) is produced with high yield from the thus-formed 1,2,2,2-tetrafluoroethyl methyl ether by chlorination and fluorination. This method enables efficient industrial-scale production of desflurane useful as an inhalation anesthetic

  Fluoral是在催化剂存在下通过气相氟化氯醛获得，然后与三甲基正甲酸酯反应，从而轻松形成1,2,2,2-四氟乙基甲醚作为生产地氟醚的中间体。通过氯化和氟化反应，可以高产率地从形成的1,2,2,2-四氟乙基甲醚中生产1,2,2,2-四氟乙基二氟甲基醚（地氟醚）。该方法能够有效地工业规模生产地氟醚，作为吸入麻醉剂使用。