Butibufen CAS 55837-18-8
Introduction：Basic information about Butibufen CAS 55837-18-8, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Butibufen Basic information
| Product Name: | Butibufen |
| Synonyms: | Butibufen;Benzeneacetic acid, -alpha--ethyl-4-(2-methylpropyl)- (9CI);2-(4-Isobutylphenyl)butanoic acid;2-(p-Isobutylphenyl)butyric acid;Bitubufen;Butiropan;FF-106;Butilopan |
| CAS: | 55837-18-8 |
| MF: | C14H20O2 |
| MW: | 220.31 |
| EINECS: | 259-849-2 |
| Product Categories: | PHENYL;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals |
| Mol File: | 55837-18-8.mol |
Butibufen Chemical Properties
| Melting point | 51-53° |
| Boiling point | 335.1±11.0 °C(Predicted) |
| density | 1.015±0.06 g/cm3(Predicted) |
| storage temp. | 2-8°C |
| solubility | Chloroform (Slightly), Methanol (Slightly) |
| pka | 4.41±0.10(Predicted) |
| form | Solid |
| color | White to Off-White |
Safety Information
| Toxicity | LD50 orally in mice: 810 mg/kg (Carretero) |
| Description | Butibufen is a new phenylalkanoic antiinflammatory/analgesic useful in the treatmentof rheumatologic conditions. In a study of patients with osteoarthritis, the onset ofaction of butibufen was faster with less frequent and milder side effects thanindomethacin. |
| Chemical Properties | White to Off-White Solid |
| Originator | Juste (Spain) |
| Uses | Anti-inflammatory. |
| Definition | ChEBI: Butibufen is a monoterpenoid. |
| Manufacturing Process | 1st method: 4-Isobutylphenylbenzyl chloride was prepared by passing a stream ofhydrogen chloride into a suspension of p-bromoaldehyde and anhydrous zincchloride in isobutylbenzene. A mixture of 137 g (0.75 mol) of 4-isobutylbenzylchloride thus prepared, 44.1 g (0.90 mol) of sodium cyanide, 216 g of 99%ethanol, and 81.3 g of water was heated refluxed for 6 hours. The mixturebecame reddish-black in color. From this mixture, 215 ml of ethanol and water was then distilled and the residue was filtered. The solids that were separatedby filtration were washed with 100 ml of diethyl ether and the ether washingswere combined with the original filtrate, to which 800 ml of water was thenadded. The organic phase was then separated from the aqueous phase,washed with five 400 ml portions of water and dried over anhydrous sodiumsulfate. The ether was evaporated from the dried organic phase by vacuumdistillation and the residue which distilled between 130°C and 132°C at apressure of 7 mm of mercury was collected. The yields of 4-isobutylbenzenecyanide 100-113 g. To a solution of 6.7 g of sodium amide in 100 ml of anhydrous diethyl etherwas added dropwise 26 g of 4-isobutylbenzene cyanide while the mixture wasstirred and heated under gentle reflux. After all of the 4-isobutylbenzenecyanide had been added, the mixture was heated under gentle reflux for 15min, after which 23.4 g of ethyl iodide was slowly added dropwise theretofrom the dropping funnel. After completion of the addition of the ethyl iodide,the mixture was heated under gentle reflux for an initial period of 15 min,after which it was diluted with an equal volume of water and shaken. The twolayers that formed were separated and the aqueous layer was then extractedwith two 50 ml portions of diethyl ether. The ether extracts were combinedand then washed with two 80 ml portions of water and dried over anhydrousmagnesium sulfate. The dried ether extract was then distilled at asubatmospheric pressure. In this manner, 25 g of a clear transparentuncolored liquid having a boiling point of 118-122°C at a pressure of 1mm ofmercury, which consisted of 2-(4-isobutylphenyl)butyronitrile, was collected.This yield was equivalent to 83% of the theoretical. A mixture of 40 g (0.2 mol) of 2-(4-isobutylphenyl)butyronitrile and 78 ml ofa freshly prepared solution of sodium hydroxide that was prepared bydissolving 28 g of sodium hydroxide in 25 ml of distilled water and the volumeof which was brought to 100 ml by addition thereto of methanol, was heatedunder gentle reflux in a flask provided with a stirrer and reflux condenserwhile the mixture was stirred during a period of 9 hours. From the mixturethe methanol and a portion of the water were distilled and the mixture wasthen cooled, the crystals began to separate. The mixture was then dilutedwith 150 ml of water and extracted with two 25 ml portions of diethyl ether.The remaining aqueous solution containing the sodium salt of 2-(4-isobutylphenyl)butyric acid was then saturated with sodium chloride until thesalt started to precipitate. The solution was then cooled to 5°C and theprecipitated salt was separated by filtration, recrystallized from isopropanol,and dried in a vacuum desiccator at a pressure of 1 mm of mercury until ithad attained a constant weight. In this manner, 32 g of sodium 2-(4-isobutylphenyl)butyrate having a melting point of 188-191°C, which isequivalent to a yield of 67% of the theoretical, was obtained. Dilute hydrochloric acid (19% by weight of hydrogen chloride) was slowlyadded to a cold solution of 25 g of the sodium 2-(4-isobutylphenyl)butyratethus prepared in 100 ml of water until the solution corresponded to pH of 1.0.The oil which precipitated was then allowed to solidify to a white solid bystanding in a refrigerator. The white solid was then separated by filtration,dried, and recrystallized from petroleum ether. It had a melting point of 50-52°C, and its elementary analysis corresponded to the 2-(4-isobutylphenyl)butyric acid. 2nd method: 5.0 g of small pellets of sodium metal were added slowly with stirring to 150ml of absolute ethanol, while a current of nitrogen gas was passed therethrough so as to blanket the solution from the atmosphere. After all of thesodium metal had been dissolved and while the solution was maintained at atemperature of 50°C, a solution of 52 g of ethyl 2-(4-isobutylphenyl)cyanoacetate in 50 ml of absolute ethanol was added dropwisewhile the mixture was stirred. Subsequently, 81 g of ethyl iodide wasgradually added to the mixture with stirring, after which the introduction ofnitrogen gas into the mixture was discontinued and the mixture was heatedfor a period of 2.5 hours under gentle reflux. Thereafter, the ethanol andexcess ethyl iodide were distilled from the mixture and the residue was thendiluted with three times its volume of water and shaken therewith. The 2-(4-isobutylphenyl)-2-(ethoxycarbonyl)butyronitrile was then extracted from themixture with three 50 ml portions of diethyl ether, the extracts werecombined, washed with a 20% aqueous solution of sodium bisulfate and driedover anhydrous magnesium sulfate. The ether was then expelled from theextract by distillation and the residue was distilled at a subatmosphericpressure, yielding 45 g of a fraction containing 2-(4-isobutylphenyl)-2-(ethoxycarbonyl)butyronitrile having a boiling point of 150-155°C/3 mm ofmercury (78% of the theoretical yield). In a 2-liter flask provided with a stirrer and reflux condenser a solution of 129g of 2-(4-isobutylphenyl)-2-(ethyoxycarbonyl)butyronitrile in 980 ml of a 20%solution of potassium hydroxide in methanol was heated with stirring at 40°Cfor a period of 1 hour. The mixture was then heated under gentle reflux withstirring for an additional period of 3 hours, during which a white solidprecipitated. This mixture was then poured into 1.5 liters of water andacidified with an aqueous solution of hydrochloric acid (concentratedhydrochloric acid diluted with an equal volume of water) to a hydrogen ionconcentration corresponding to a pH of 2.5, while carbon dioxide was evolvedtherefrom. The aqueous mixture was then extracted with diethyl ether. Theextracts were washed successively with a saturated solution of sodiumbicarbonate and water, dried over anhydrous magnesium sulfate, and distilledat a subatmospheric pressure, to yield 86.5 g of a fraction consisting of 2-(4-isobutylphenyl)butyronitrile having a boiling point of 124-128°C at a pressureof 1.5 mm of mercury, which is equivalent to approximately 0.43 mol and ayield of 91% of the theoretical based on the original 2-(4-isobutylphenyl)-2-(ethoxycarbonyl)butyronitrile. The 2-(4-isobutylphenyl)butyronitrile was converted to sodium 2-(4-isobutylphenyl)butyrate and subsequently to 2-(4-isobutylphenyl)butyric acidin the same manner as described in Method 1 hereinbefore. |
| Brand name | Butilopan |
| Therapeutic Function | Antiinflammatory, Analgesic |
Butibufen Preparation Products And Raw materials
| Raw materials | Benzeneacetonitrile-->Isobutylbenzene |
