Enflurane CAS 13838-16-9
Introduction：Basic information about Enflurane CAS 13838-16-9, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
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 |
| color | Colorless to light yellow |
| Merck | 14,3581 |
| BRN | 1737129 |
| Exposure limits | TLV-TWA 570 mg/m3 (75 ppm) (ACGIH). |
| InChI | 1S/C3H2ClF5O/c4-1(5)3(8,9)10-2(6)7/h1-2H |
| InChIKey | JPGQOUSTVILISH-UHFFFAOYSA-N |
| SMILES | FC(F)OC(F)(F)C(F)Cl |
| CAS DataBase Reference | 13838-16-9(CAS DataBase Reference) |
| EPA Substance Registry System | Enflurane (13838-16-9) |
Safety Information
| Hazard Codes | F,T,Xi |
| Risk Statements | 36 |
| Safety Statements | 23-26-36-39 |
| OEL | Ceiling: 2 ppm (15.1 mg/m3) [60-minute] [*Note: REL for exposure to waste anesthetic gas.] |
| RIDADR | UN 3334 |
| WGK Germany | WGK 3 |
| RTECS | KN6800000 |
| Hazard Note | Flammable/Toxic |
| HS Code | 2909191800 |
| Storage Class | 10 - Combustible liquids |
| Hazard Classifications | Eye Irrit. 2 |
| Hazardous Substances Data | 13838-16-9(Hazardous Substances Data) |
| Toxicity | LD50 oral in rat: 5450uL/kg |
| Description | Enflurane is a clear, colorless liquid with amild, sweet odor, which easily turns into a nonflammablegas. Molecular weight = 184.50; Specific gravity(H2O:1) = 1.52; Boiling point = 56.7 ℃; Vaporpressure 5 175 mmHg; Relative vapor density (air 5 1)=1.92. Hazard Identification (based on NFPA-704 M RatingSystem): Health 2, Flammability 1, Reactivity 0. Veryslightly soluble in water |
| Chemical Properties | The halogenated methyl ethyl ether enflurane is a geometric isomer ofisoflurane and boasts similar properties. It is no longer in use in modernclinical practice largely because of some unfavourable adverse effects.Enflurane has been associated with: tonic–clonic muscle activity;epileptiform EEG changes; sensitisation of the myocardium tocatecholamines causing dysrhythmias; and hepatotoxicity as a result of itssignificant liver metabolism. |
| 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 easilyturns into a nonflammable gas. Mild, sweet odor |
| 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, athermometer and a stirrer, was charged 1,180 grams (8 mols) ofCH3OCF2CHFCl.After flushing the system with nitrogen, chlorine gas wasadded via the inlet tube while the reaction was stirred and illuminated with a300 watt incandescent lamp. The chlorination was rapid and exothermic andthe reactor was cooled to hold the temperature between 30° and 35°C. Theeffluent gases were led from the top of the condenser to a water scrubberwhich was titrated at intervals with standard base. When a total of 1.45 molsof HCl per mol of ether was titrated the reaction was stopped. The crudeproduct obtained weighed 1,566 grams which corresponded to the addition of1.41 mols of chlorine per mol of the starting ether. The product was flashdistilled to yield 1,480 grams of product which had the following compositionas 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 to1.3875. The still bottoms were comprised mostly of CCl3OCF2CHFCl andCHCl2OCF2CFCl2. 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 anhydroushydrogen fluoride while the temperature was maintained at 0-5°C. Thereaction was carried out in a 3-necked stainless steel flask fitted with astainless steel stirrer, a thermocouple well and a copper Dry Ice condenser. The amount of hydrogen fluoride added was measured by titration of the HClgiven off. At the end of the reaction (total HCl evolved: 1.98 mols per mol ofstarting ether) the mixture was poured into water and the organic layer(1,803 grams, nD20 = 1.3080) recovered. The crude product was flash distilledin a 60 x 2 cm column packed with ?" Penn State packing giving 1,594 gramsof substantially pure CHF2OCF2CHFCl, BP 56° to 57°C. By further distillation1,450 grams of the pure ether were obtained, BP 56.5°C, nD20 = 1.3030 asdescribed in each of the patents cited as references. |
| Therapeutic Function | Anesthetic |
| Biological Functions | Enflurane (Ethrane) depresses myocardial contractilityand lowers systemic vascular resistance. In contrast tohalothane, it does not block sympathetic reflexes, andtherefore, its administration results in tachycardia.However, the increased heart rate is not sufficient to opposeenflurane’s other cardiovascular actions, so cardiacoutput and blood pressure fall. In addition, enfluranesensitizes the myocardium to catecholamine-inducedarrhythmias, although to a lesser extent than withhalothane. Enflurane depresses respiration throughmechanisms similar to halothane’s and requires that thepatient’s ventilation be assisted. Neuromuscular transmission is depressed by enflurane,resulting in some skeletal muscle paralysis.Althoughmuscle relaxation is inadequate for many surgical procedures,the anesthetic enhances the action of neuromuscularblocking agents, thereby lowering the dose of the paralyticagent needed and minimizing side effects. Deep anesthesia with enflurane is associated withthe appearance of seizurelike electroencephalographic(EEG) changes. Occasionally frank tonic–clonic seizuresare observed. Consequently, other inhalationalagents are usually given to patients with preexistingseizure disorders. Another concern associated with the use of enfluraneis its biotransformation, which leads to increasedplasma fluoride. Following lengthy procedures inhealthy patients, fluoride may reach levels that result ina mild reduction in renal concentrating ability.Thus, enfluraneshould be used cautiously in patients with clinicallysignificant 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 systemimpairment. 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 aclosed bottle may occur at elevated temper atures. |
| Clinical Use | Enflurane was introduced into medical practice in the United States in 1973 and is aclear, colorless, nonflammable general liquid with a mild, sweet odor. Although relatively stablechemically, 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 itspharmacological properties are similar to those of halothane, although there may be slightly lessnausea, vomiting, arrhythmias, and postoperative shivering than observed with halothane. Highconcentrations of enflurane, however, are more likely to produce convulsions and circulatorydepression. Enflurane also relaxes the uterus and, thus, should not be used as an anestheticduring labor. Metabolism via CYP2E1 accounts for 2% of an inhaled dose and includestransformation to the fluoride ion and fluoromethoxydifluoroacetic acid. Duringrecovery, enflurane leaves the fatty tissues rapidly and, therefore, is not available for a prolongedperiod 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. |
| Synthesis | Enflurane is prepared by dichlorination ofthe methyl group of 1-chloro-1,2,2-trifluoro-2-methoxyethane and replacement of these twochlorine atoms by fluorine , : |
| Potential Exposure | FDA-proprietary drug, used as ananesthetic (gas). Axphyxiant |
| First aid | If this chemical gets into the eyes, remove any contact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin,remove contaminated clothing and wash immediately withsoap and water. Seek medical attention immediately. If thischemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR if heart actionhas stopped. Transfer promptly to a medical facility. Whenthis chemical has been swallowed, get medical attention.Give large quantities of water and induce vomiting. Do notmake an unconscious person vomit |
| storage | Prior to working with enflurane you should betrained on its proper handling and storage. Store in tightlyclosed containers in a cool, well-ventilated area. Check oxygen content before entering confined spaces. Where possible, automatically pump liquid from drums or other storagecontainers to process containers. Procedures for the handling, use, and storage of cylinders should be in compliancewith OSHA 1910.101 and 1910.169, as with the recommendations of the Compressed Gas Association. |
| Shipping | UN1851 Medicine, liquid, toxic, n.o.s., HazardClass: 6.1; Labels: 6.1-Poisonous materials. Cylinders mustbe transported in a secure upright position, in a wellventilated truck. Protect cylinder and labels from physicaldamage. The owner of the compressed gas cylinder is theonly entity allowed by federal law (49CFR) to transportand refill them. It is a violation of transportation regulations to refill compressed gas cylinders without the expresswritten permission of the owner. |
| Incompatibilities | Incompatible with oxidizers (chlorates,nitrates, peroxides, permanganates, perchlorates, chlorine,bromine, fluorine, etc.); contact may cause fires orexplosions. Keep away from alkaline materials, strongbases, strong acids, oxoacids, and epoxides. Decomposeson heating, forming toxic and corrosive fumes of hydrogenchloride, hydrogen fluoride, and phosgene. Decomposes instrong sunlight |
| Waste Disposal | Return refillable compressedgas cylinders to supplier |
Enflurane Preparation Products And Raw materials
| Raw materials | hydrogen fluoride-->Chlorine |
