Halothane is a clear colorless highly volatile liquid with a sweet chloroform-like odor . Density 1.875 g / cm3. Boiling point 122.4°F (50.2°C). Noncombustible.
颜色/状态：
Colorless, volatile liquid
气味：
Characteristic, sweetish, not unpleasant odor
蒸汽密度：
6.8 (calculated) (NTP, 1992) (Relative to Air)
蒸汽压力：
302 mm Hg at 25 °C (extrapolated)
水溶性：
-1.71
亨利常数：
0.02 atm-m3/mole
大气OH速率常数：
4.50e-14 cm3/molecule*sec
稳定性/保质期：
常温常压下稳定。禁配物：强氧化剂。
分解：
Halothane is decomposed by sunlight and should be stored in dark colored bottles.
折光率：
Index of refraction = 1.3697 at 0 °C/D
保留指数：
541;543;533;543;533
计算性质
辛醇/水分配系数(LogP)：
2.3
重原子数：
7
可旋转键数：
0
环数：
0.0
sp3杂化的碳原子比例：
1.0
拓扑面积：
0
氢给体数：
0
氢受体数：
3
ADMET
代谢
卤烷在肝脏中被代谢，主要是通过CYP2E1，其次是通过CYP3A4和CYP2A6。
Halothane is metabolized in the liver, primarily by CYP2E1, and to a lesser extent by CYP3A4 and CYP2A6.
Anywhere from 10 to 30 percent of inhaled halothane is metabolized, and metabolites may be detected in the urine for a period of several days after inhaling halothane. Various intermediate metabolites have been isolated; however, trifluoroacetic acid is the principal end-product isolated from the urine.
Halothane biotransformation by cytochrome p 450 produces reactive intermediates along both oxidative (acyl chloride) and reductive (free radical) pathways that ultimately generate the metabolites trifluoroacetic acid and flouride, respectively. Inhibiting oxidative metabolism with deuterated halothane reduces resultant injury in our guinea pig model of acute halothane hepatoxicity. To elucidate whether covalent binding of reactive intermediates to proteins (oxidative pathway) or lipids (reductive pathway) is a mechanism of necrosis, male outbred Hartley guinea pigs (600-725 g), N = 8, were exposed to either 1% (v/v) halothane or deuterated halothane at either 40% or 10% oxygen for 4 hr. One-half of the animals were killed immediately after exposure for binding studies; the remainder at 96 hr post exposure for evaluation of hepatotoxicity. Covalent binding of halothane intermediates to liver protein or lipid was determined by measuring the fluoride content of the bound moieties. The use of deuterated halothane and/or 10% oxygen during exposure led to 63-88% reductions (p< 0.01) in plasma trifluoroacetic acid concn (halothane-40% oxygen = 546; 73 mM, N = 8) which were accompanied by 33-60% decreases (p< 0.01) in binding to liver proteins (halothane-40% oxygen = 1.36; 0.26 nmoles bound fluoride/mg protein, N = 4), 78-84% decreases (p< 0.05) in 48 hr plasma ALT levels (halothane- 40% oxygen = 308; 219, control = 23 + 3, N = 4) and a total amelioration of centilobular necrosis.
Free radicals were detected from the in vitro metabolism of halothane (rat liver microsomes) by the PBN spin trapping method. The detected radical species include the 1-chloro-2,2,2-trifluoro-1-ethyl radical (I), as determined by mass spectral analysis, and lipid type radicals assigned by high resolution ESR spectroscopy with the use of d14-deuterated PBN. The lipid derived radicals are a carbon centered radical with the partially assigned structure CH2R and an oxygen centered radical of the OR' type. From the mass spectral analysis of the spin adduct mixture there is also evidence for a halocarbon double adduct of PBN of the type I-PBN-I.
An analogue of HCFC-123, the common inhalation anesthetic halothane (2-bromo-2-chloro-1,1,1-trifluoroethane), is metabolized by hepatic CYP2E1 to trifluoroacetyl chloride, causing trifluoroacetylation of liver proteins. These include cytochrome P450 itself and other enzymes, many of which have been identified as residing in the lumen of the endoplasmic reticulum and involved in the maturation of newly synthesized proteins. Both halothane and HCFC-123 induce peroxisome proliferation and increased beta-oxidation in rat liver cells. They are also highly effective in inducing excess uncoupled cytochrome P450 activity in rabbit liver microsomes, thus increasing hepatic oxygen consumption and facilitating the oxidation of other cytochrome P450 substrates.
Halothane causes general anaethesia due to its actions on multiple ion channels, which ultimately depresses nerve conduction, breathing, cardiac contractility. Its immobilizing effects have been attributed to its binding to potassium channels in cholinergic neurons. Halothane's effect are also likely due to binding to NMDA and calcium channels, causing hyperpolarization.
Halothane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Halothane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. Also appears to bind the D subunit of ATP synthase and NADH dehydogenase. Halothane also binds to the GABA receptor, the large conductance Ca<sup>2+</sup> activated potassium channel, the glutamate receptor and the glycine receptor.
Prospective, serial blood testing often demonstrates minor transient elevations in serum aminotransferase levels in the 1 to 2 weeks after major surgery and anesthesia with halothane and other halogenated anesthetics. Appearance of ALT levels above 10 times the upper limit of normal, however, is uncommon and points to significant hepatotoxicity. Clinically apparent, severe hepatic injury from halothane is rare, occurring in ~1/15,000 cases after initial exposure, but in ~1/1,000 cases after repeated exposures. The injury is marked by acute elevations in serum aminotransferase levels (5- to 50-fold) and appearance of jaundice within 2 to 14 days of surgery. There are usually minimal increases in alkaline phosphatase levels. Fever occurs before onset of jaundice in a high proportion of patients and eosinophilia in up to 30%. Rash and arthralgias can also accompany the onset of hepatic injury. The acute liver injury may be self-limited and resolve within 4 to 8 weeks, but can be severe and lead to 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. Other risk factors are hypotension, older age, obesity and concurrent use of CYP 2E1 inducers. The differential diagnosis of acute liver injury after surgery and anesthesia is sometimes difficult, and a clinical picture similar to halothane hepatitis can be caused by shock or ischemia, sepsis, other idiosyncratic forms of drug induced liver injury and acute viral or herpes hepatitis. Indeed, many cases of severe liver injury arising soon after surgery and attributed to halothane or other halogenated anesthetics in the literature probably represent liver injury from shock and ischemia. Factors favoring the diagnosis of ischemic hepatitis are rapid onset after surgery, extremely high values for ALT, AST and LDH, and subsequent rapid fall in serum enzymes.
来源:LiverTox
毒理性
致癌性证据
A4；不能归类为人类致癌物。
A4; Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类无致癌性（未列入国际癌症研究机构IARC清单）。
No indication of carcinogenicity to humans (not listed by IARC).
Most halothane is excreted by the lung unchanged. At least 12% of an absorbed dose is metabolized to chlorine, bromine, and trifluoroacetic acid, with toxic intermediates suspected of causing or contributing to hepatoxicity. Halothane is stored in fatty tissue and has been detected in the expired air of obese patients up to 2 weeks after exposure.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
在14名接受氟烷麻醉的患者中，有6名检测到了尿液中草酸钙结晶。
Urinary oxalate crystals were detected in 6 of 14 patients given halothane.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
目前尚不清楚卤烷是否分布进入乳汁中。
It is not known if halothane is distributed into breast milk.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
60到80%通过呼吸以原形排出。
60 to 80% Excreted unchanged by exhalation.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
吸入性麻醉剂可通过胎盘。
Inhalation anesthetics cross placenta.
来源:Hazardous Substances Data Bank (HSDB)
安全信息
职业暴露限值：
Ceiling: 2 ppm (16.2 mg/m3) [60-minute] [*Note: REL for exposure to waste anesthetic gas.]
An easy preparation of per- and poly-fluoroalkyl propenyl sulfones
摘要：
Sodium tridecafluorohexanesulfinate (1a) and sodium 1-chloro-2,2,2-trifluoroethanesulfinate (1b) were prepared by the treatment of 1-iodo-tridecafluorohexane and 1-bromo-1-chloro-2,2,2-trifluoroethane with sodium dithionite in a water-acetonitrile solution. Prolonged reaction of 1a with allyl bromide in DMF afforded tridecafluorohexane 1-propenyl sulfone 2 as the only product in good yield. A similar treatment of 1b gave exclusively 1-chloro-2,2,2-trifluoroethane 3-propenylsulfone 4. Bromination of 4 followed by dehydrobromination with Et3N resulted in a mixture of 1-chloro-2,2,2-trifluoroethane 3-bromo-1-propenyl sulfone 6 and 1-chloro-2,2,2-trifluoroethane 2-bromo-3-propenyl sulfone 7, while dehydrobromination with pyridine gave sulfone 6 practically as the only product. alpha,beta-Unsaturated sulfones 2 and 6 were shown to be active dienophiles. (C) 2005 Elsevier B.V All lights reserved.
Mechanistic definition of trimethylstannylation of 1,3-dihaloadamantanes: delocalized radical anions as possible intermediates
摘要：
A series of 1,3-dihaloadamantanes (3, X = Y = halogens) have been synthesized, characterized, and treated with (trimethylstannyl) alkali reagents (Me3SnM, M = Li or Na) in the absence and presence of tert-butylamine (TBA) and dicyclohexylphosphine (DCPH). The product distributions of these reactions have been established by C-13 and Sn-119 NMR spectroscopy and vapor-phase chromatographic analyses. Tin substitution via an S(RN)1-type pathway is shown to be a significant reaction for several of the derivatives of 3 (X = F, Y Br or I; X = Cl, Y = Br or I; X = Y = Br) but not for the bromo iodide or diiodide (3, X = Br, Y = I and X = Y = I). For the latter two compounds, the formation of 1,3-dehydroadamantane or propellane 8 is the predominant reaction product while tin substitution is insignificant. Propellane 8 formation is also a significant reaction product for some of the other dihalo derivatives of 3 (X = Cl, Y = I and X = Y = Br) but not for others (3, X = F, Y = Br or I and X = Cl, Y = Br). The mechanism of formation of 8 is perplexing in light of the trapping experiments in the presence of TBA and DCPH. A possible pathway is proposed in which the key intermediate is a delocalized radical anion.
Zinc-Mediated Intermolecular Reductive Radical Fluoroalkylsulfination of Unsaturated Carbon-Carbon Bonds with Fluoroalkyl Bromides and Sulfur Dioxide
作者：Yongan Liu、Qiongzhen Lin、Zhiwei Xiao、Changge Zheng、Yong Guo、Qing-Yun Chen、Chao Liu
DOI：10.1002/chem.201805526
日期：2019.2.1
general zinc‐mediated intermolecular reductiveradical fluoroalkylsulfination of unsaturated C−C bonds has been developed using readily available fluoroalkyl bromides and 1,4‐diazabicyclo[2.2.2]octane‐bis(sulfur dioxide) adduct (DABSO) with wide substrate scope and excellent functional group tolerance. Sulfur dioxide anionradical generated in situ from the reduction of sulfur dioxide with zinc may be
PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
申请人：DOW AGROSCIENCES LLC
公开号：US20130288893A1
公开（公告）日：2013-10-31
This document discloses molecules having the following formula (“Formula One”):
and processes related thereto.
这份文件公开了具有以下公式（“公式一”）的分子以及与之相关的过程。
Visible Light Mediated, Redox Neutral Remote 1,6-Difunctionalizations of Alkenes
作者：Wei Shu、Estíbaliz Merino、Cristina Nevado
DOI：10.1021/acscatal.8b00707
日期：2018.7.6
A photoinduced cascade strategy is presented here for the remote functionalization of alkenes under redox neutral conditions. A broad portfolio of alkyl groups has been added to double bonds to produce, upon 1,5-HAT, remote C-centered radicals which can be harvested in the presence of O- or C-nucleophiles to efficiently form Csp3–O and Csp3–Csp2 bonds at room temperature.
CHXYZ, with bistrifluoromethyl nitroxide. The 1,2-bis(bistrifluoromethylamino-oxy)alkanes (CF3)2NOCH2CXYON(CF3)2 were obtained as by-products in the reactions involving the ethanes CH3CHXY (X = H, Y = F or Cl; X = Y = F); these products, like their analogues (CF3)2NOCHFCF2ON(CF3)2 and (CF3)2NOCH2CCl2ON(CF3)2, were also prepared via attack of bistrifluoromethyl nitroxide on the corresponding ethenes.
单（双三氟甲基氨基氧基）烷烃（CF 3）2 NOCXYZ（X = Y = F，Z = Cl; X = H，Y = F或Cl，Z = CH 3 ; X = Y = F，Z = CH 3； X ＝ H，Y ＝ Cl或Br，Z ＝ CF 3； X ＝ Cl，Y ＝ Br，Z ＝ CF 3）是通过用双三氟甲基硝基氧处理适当的卤代烷烃CHXYZ而合成的。在涉及乙烷CH 3 CHXY（X = H，Y = F或Cl）的反应中作为副产物获得1,2-双（双三氟甲基氨基-氧基）烷烃（CF 3）2 NOR 2 CXYON（CF 3）2。 ; X = Y = F）; 这些产品，如它们的类似物（CF 3）2 NOCHFCF 2 ON（CF 3）2和（CF 3）2 NOCH 2的CCl 2 ON（CF 3）2，也通过在对应的ethenes三氟甲基氮氧自由基的攻击制备。
Preparation of cyclopropane esters
申请人：Zeneca Limited
公开号：US05723649A1
公开（公告）日：1998-03-03
The invention provides an improved process for the preparation of a lower alkyl ester of 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylic acid in which the corresponding lower alkyl ester of a carboxylic acid selected from 6-bromo-6-chloro-3,3-dimethyl-7,7,7-trifluorohept-2-enoic acid and 6,6-dichloro-3,3-dimethyl-7,7,7-trifluorohept-2-enoic acid is treated with an alkali metal lower alkoxylate in the presence of an aromatic hydrocarbon solvent under conditions under which the lower alcohol of the alkoxylate is removed from the reaction mixture by distillation with the aromatic solvent. The products are useful as intermediates in the manufacture of pyrethroid insecticides.
