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| | Enflurane Basic information |
| Product Name: | Enflurane | | Synonyms: | Alyrane;Anesthetic 347;Anesthetic Compound No. 347;anestheticcompoundno.347;C 347;Compound 347;compound347;Efrane | | CAS: | 13838-16-9 | | MF: | C3H2ClF5O | | MW: | 184.49 | | EINECS: | 237-553-4 | | Product Categories: | | | Mol File: | 13838-16-9.mol |  |
| | Enflurane Chemical Properties |
| Boiling point | 56 °C | | density | 1.517 | | refractive index | 1.303 | | Fp | 56-57°C | | storage temp. | 2-8°C | | solubility | Chloroform (Soluble), DMSO (Sparingly), Dichloromethane (Sparingly), Methanol (S | | form | Liquid | | Specific Gravity | 1.517 | | Merck | 14,3581 | | BRN | 1737129 | | Exposure limits | TLV-TWA 570 mg/m3 (75 ppm) (ACGIH). | | InChIKey | JPGQOUSTVILISH-UHFFFAOYSA-N | | CAS DataBase Reference | 13838-16-9(CAS DataBase Reference) | | EPA Substance Registry System | Enflurane (13838-16-9) |
| Provider | Language |
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ALFA
| English |
| | Enflurane Usage And Synthesis |
| Chemical Properties | Clear, colorless liquid; mild, sweet odor.
Soluble in organic solvents;
slightly soluble in water. | | Chemical Properties | Enflurane is a clear, colorless liquid that easily
turns into a nonflammable gas. Mild, sweet odor | | Chemical Properties | The halogenated methyl ethyl ether enflurane is a geometric isomer of
isoflurane and boasts similar properties. It is no longer in use in modern
clinical practice largely because of some unfavourable adverse effects.
Enflurane has been associated with: tonic–clonic muscle activity;
epileptiform EEG changes; sensitisation of the myocardium to
catecholamines causing dysrhythmias; and hepatotoxicity as a result of its
significant liver metabolism. | | Originator | Ethrane,Ohio Medical,US,1972 | | Uses | Anesthetic in clinical anesthesia | | Uses | Clinical anesthetic. | | Uses | Ethrane is widely used clinically as an anes thesia (by inhalation). Workers in operatingrooms are susceptible to inhaling this compound at low concentrations. | | Definition | ChEBI: An ether in which the oxygen atom is connected to 2-chloro-1,1,2-trifluoroethyl and difluoromethyl groups. | | Manufacturing Process | Preparation of the Intermediate CHCl2OCF2CHFCl: To a 3-necked roundbottomed flask fitted with a Dry Ice condenser, a fritted glass gas inlet tube, a
thermometer and a stirrer, was charged 1,180 grams (8 mols) of
CH3OCF2CHFCl.After flushing the system with nitrogen, chlorine gas was
added via the inlet tube while the reaction was stirred and illuminated with a
300 watt incandescent lamp. The chlorination was rapid and exothermic and
the reactor was cooled to hold the temperature between 30° and 35°C. The
effluent gases were led from the top of the condenser to a water scrubber
which was titrated at intervals with standard base. When a total of 1.45 mols
of HCl per mol of ether was titrated the reaction was stopped. The crude
product obtained weighed 1,566 grams which corresponded to the addition of
1.41 mols of chlorine per mol of the starting ether. The product was flash
distilled to yield 1,480 grams of product which had the following composition
as determined by vapor phase chromatography: 45.3% CH2ClOCF2CHFCl;
50.5% CHCl2OCF2CHFCl, plus a small amount of CH2ClOCF2CFCl2; 1.8%
CHCl2OCF2CFCl2 and 2.1% CCl3OCF2CHFCl.
Fractional distillation of this mixture using a 5 x 120 cm column packed with
?" Penn State packing yielded 670 grams of product containing 95%
CH2ClOCF2CHFCl and 5% CHCl2OCF2CHFCl; BP 55° to 60°C at 100 mm, nD20
= 1.3748 to 1.3795; and 670 grams of CHCl2OCF2CHFCl (95% pure,
containing 5% CH2ClOCF2CFCl2); BP 60°C at 100 mm, nD20 = 1.3870 to
1.3875. The still bottoms were comprised mostly of CCl3OCF2CHFCl and
CHCl2OCF2CFCl2.
Preparation of CHF2OCF2CHFCl: To a mixture of 2,172 grams (10 mols)
CHCl2OCF2CHFCl prepared as described above (containing approximately 5%
CH2ClOCF2CFCl2) and 40 grams (2% by weight) SbCl5 was added anhydrous
hydrogen fluoride while the temperature was maintained at 0-5°C. The
reaction was carried out in a 3-necked stainless steel flask fitted with a
stainless steel stirrer, a thermocouple well and a copper Dry Ice condenser.
The amount of hydrogen fluoride added was measured by titration of the HCl
given off. At the end of the reaction (total HCl evolved: 1.98 mols per mol of
starting ether) the mixture was poured into water and the organic layer
(1,803 grams, nD20 = 1.3080) recovered. The crude product was flash distilled
in a 60 x 2 cm column packed with ?" Penn State packing giving 1,594 grams
of substantially pure CHF2OCF2CHFCl, BP 56° to 57°C. By further distillation
1,450 grams of the pure ether were obtained, BP 56.5°C, nD20 = 1.3030 as
described in each of the patents cited as references. | | Therapeutic Function | Anesthetic | | Biological Functions | Enflurane (Ethrane) depresses myocardial contractility
and lowers systemic vascular resistance. In contrast to
halothane, it does not block sympathetic reflexes, and
therefore, its administration results in tachycardia.
However, the increased heart rate is not sufficient to oppose
enflurane’s other cardiovascular actions, so cardiac
output and blood pressure fall. In addition, enflurane
sensitizes the myocardium to catecholamine-induced
arrhythmias, although to a lesser extent than with
halothane. Enflurane depresses respiration through
mechanisms similar to halothane’s and requires that the
patient’s ventilation be assisted.
Neuromuscular transmission is depressed by enflurane,
resulting in some skeletal muscle paralysis.Although
muscle relaxation is inadequate for many surgical procedures,
the anesthetic enhances the action of neuromuscular
blocking agents, thereby lowering the dose of the paralytic
agent needed and minimizing side effects.
Deep anesthesia with enflurane is associated with
the appearance of seizurelike electroencephalographic
(EEG) changes. Occasionally frank tonic–clonic seizures
are observed. Consequently, other inhalational
agents are usually given to patients with preexisting
seizure disorders.
Another concern associated with the use of enflurane
is its biotransformation, which leads to increased
plasma fluoride. Following lengthy procedures in
healthy patients, fluoride may reach levels that result in
a mild reduction in renal concentrating ability.Thus, enflurane
should be used cautiously in patients with clinically
significant renal disease. | | General Description | 2-CHLORO-1,1,2-TRIFLUOROETHYL DIFLUOROMETHYL ETHER (Ethrane, 2-chloro-1,1,2-trifluoroethyldifluoromethyl ether) is a nonflammable halogenated hydrocarbon that exists as a clear, colorless, odorless to sweet, volatile liquid at ordinary temperature and pressure. Bp: 56.8°C. Density 1.50 g cm-3 at room temperature. Used as an anesthetic. | | General Description | Enflurane is a volatile liquid (bp＝56.5°C) with a blood:gas partition coefficient of 1.8 and an MAC of 1.68%.Approximately 2% to 8% of the drug is metabolized primarilyat the chlorofluoromethyl carbon. Little chlorofluoroaceticacid is produced suggesting minor metabolism at thedifluoromethyl carbon. Difluoromethoxydifluoroacetate andfluoride ion have been reported as metabolites. Enfluranemay increase heart rate, cause cardiac arrhythmias, increasecerebral blood flow, and increase intracranial pressure but allto a smaller degree than halothane. Enflurane also causeselectroencephalographic (EEG) patterns consistent withelectrical seizure activity. It has caused tonic–clonic convulsiveactivity in patients when used at high concentrations orduring profound hypocarbic periods. Enflurane is thereforenot recommended in patients with seizure disorders. | | Reactivity Profile | The material 2-CHLORO-1,1,2-TRIFLUOROETHYL DIFLUOROMETHYL ETHER is incompatible with the following oxidizing materials, peroxides, combustible materials. Although nonflammable, a fire may cause 2-CHLORO-1,1,2-TRIFLUOROETHYL DIFLUOROMETHYL ETHER to decompose to toxic compounds including phosgene, hydrogen chloride, and hydrogen fluoride. Decomposes slowly in the light. | | Hazard | Volatile with anesthetic properties, but nonflammable. Cardiac and central nervous system
impairment. Questionable carcinogen. | | Health Hazard | The acute toxicity of ethrane by inhalation,ingestion, or intraperitoneal or subcutaneousapplications in rodents was found tobe low to very low at concentrationsof <1000 ppm in air or dosages below1000 mg/kg. In humans it causes anesthesiaat 1.5–2% concentrations (by volume of air).Exposure to concentrations above this levelcan be dangerous. The target organs arethe central nervous system, cardiovascularsystem, kidney, and bladder. The symptomsare anesthesia, respiratory depression, andseizure. Hypotension can occur due toits action on the cardiovascular system.Exposure to a 1% concentration in air for6 hours caused anuria in humans
LC50 value, inhalation (mice): 8100 ppm/3 h
LD50 value, oral (mice): 5000 mg/kg
The pure liquid can cause mild to moder ate irritation of the eyes.
Inhalation of ethrane vapors produced teratogenic effects in mice and rats. Theseeffects pertained to specific developmen tal abnormalities in the urogenital, mus culoskeletal, and central nervous systems.These reproductive effects, however, weremanifested at high exposure levels in therange of LC50 concentrations.
Under the conditions of its use, the con centrations of ethrane in air should be toolow to produce any adverse health effects onhumans. However, it should be borne in mindthat this compound is highly volatile [vaporpressure 175 torr at 20°C (68°F)] and its con centration in air can go up from a spill orimproper handling in confined space.
Inhalation of its vapors resulted in lungand liver tumors in mice. There is no evi dence of its carcinogenic actions in humans. | | Fire Hazard | Noncombustible liquid; flash point >94°C
(200°F); low reactivity. Pressure buildup in a
closed bottle may occur at elevated temper atures. | | Clinical Use | Enflurane was introduced into medical practice in the United States in 1973 and is a
clear, colorless, nonflammable general liquid with a mild, sweet odor. Although relatively stable
chemically, enflurane does not attack aluminum, copper, iron, or brass and is soluble in rubber
(partition coefficient = 74), which can prolong induction/recovery times, as seen with halothane.Enflurane has an intermediate solubility in blood and significant potency. Most of its
pharmacological properties are similar to those of halothane, although there may be slightly less
nausea, vomiting, arrhythmias, and postoperative shivering than observed with halothane. High
concentrations of enflurane, however, are more likely to produce convulsions and circulatory
depression. Enflurane also relaxes the uterus and, thus, should not be used as an anesthetic
during labor. Metabolism via CYP2E1 accounts for 2% of an inhaled dose and includes
transformation to the fluoride ion and fluoromethoxydifluoroacetic acid. During
recovery, enflurane leaves the fatty tissues rapidly and, therefore, is not available for a prolonged
period of time for significant metabolism to proceed. | | Safety Profile | Mildly toxic by
inhalation, ingestion, and subcutaneous
routes. Human systemic effects by
inhalation: decreased urine volume or
anuria. An experimental teratogen.
Experimental reproductive effects. Human
mutation data reported. An eye irritant.
Questionable carcinogen with experimental
carcinogenic data. An anesthetic. When
heated to decomposition it emits very toxic
fumes of Fand Cl-. See also ETHERS. | | Potential Exposure | FDA-proprietary drug, used as an
anesthetic (gas). Axphyxiant | | Shipping | UN1851 Medicine, liquid, toxic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials. Cylinders must
be transported in a secure upright position, in a wellventilated truck. Protect cylinder and labels from physical
damage. The owner of the compressed gas cylinder is the
only entity allowed by federal law (49CFR) to transport
and refill them. It is a violation of transportation regulations to refill compressed gas cylinders without the express
written permission of the owner. | | Incompatibilities | Incompatible with oxidizers (chlorates,
nitrates, peroxides, permanganates, perchlorates, chlorine,
bromine, fluorine, etc.); contact may cause fires or
explosions. Keep away from alkaline materials, strong
bases, strong acids, oxoacids, and epoxides. Decomposes
on heating, forming toxic and corrosive fumes of hydrogen
chloride, hydrogen fluoride, and phosgene. Decomposes in
strong sunlight | | Waste Disposal | Return refillable compressed
gas cylinders to supplier |
| | Enflurane Preparation Products And Raw materials |
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