Phenobarbital

Phenobarbital (5-etbyl-5-phenylbarbituric acid) possesses specific usefulness in epilepsy. 

Phenobarbital, like other barbituric acid derivatives, is manufactured from phenylethylmalonic diethyl ester, which is condensed with urea to form the product. 

Phenol (hydroxybenzene freezing point 40.9°C, boiling point 181.8°C, density 1.0722 flash point 79°C) at room temperature is a white, crystalline mass. Phenol gradually turns pink if it contains impurities or is exposed to heat or light. It has a distinctive sweet, tarry odor, and burning taste. Phenol has limited solubility in water between 0 and 65°C. Above 65.3°C, phenol and water are miscible in all proportions. Phenol is very soluble in alcohol, benzene, chloroform, ether, and partially disassociated organics in general, but it is less soluble in paraffinic hydrocarbons. 

Phenol has been made, over the years, by a variety of processes. Historically, an important method was the sulfonation of benzene followed by desulfonation with caustic soda  

The principal process in use is the peroxidation of cumene (wo-propyl benzene) at 130°C in the presence of air and a catalyst followed by decomposition of the peroxide at 55 to 65°C in the presence of sulfuric acid. 

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Aryl halides react too slowly to undergo substitution by the Sn2 mechanism with the sodium salt of diethyl malonate and so the phenyl substituent of phenobarbital cannot be introduced in the way that alkyl substituents can... 

One synthesis of phenobarbital begins with ethyl phenylacetate and diethyl car bonate Using these starting materials and any necessary organic or inorganic reagents devise a synthesis of phenobarbital (Hint See the sample solution to Problem 21 3a )... 

Many pharmaceutical compounds are weak acids or bases that can be analyzed by an aqueous or nonaqueous acid-base titration examples include salicylic acid, phenobarbital, caffeine, and sulfanilamide. Amino acids and proteins can be analyzed in glacial acetic acid, using HCIO4 as the titrant. For example, a procedure for determining the amount of nutritionally available protein has been developed that is based on an acid-base titration of lysine residues. ... 

This experiment describes the quantitative analysis of the asthma medication Quadrinal for the active ingredients theophylline, salicylic acid, phenobarbital, ephedrine HGl, and potassium iodide. Separations are carried out using a Gi8 column with a mobile phase of 19% v/v acetonitrile, 80% v/v water, and 1% acetic acid. A small amount of triethylamine (0.03% v/v) is included to ensure the elution of ephedrine HGl. A UV detector set to 254 nm is used to record the chromatogram. 

In this experiment the enantiomers of cyclobarbital and thiopental, and phenobarbital are separated using MEKC with cyclodextran as a chiral selector. By adjusting the pH of the buffer solution and the concentration and type of cyclodextran, students are able to find conditions in which the enantiomers of cyclobarbital and thiopental are resolved. 

This experiment describes a quantitative analysis for caffeine, theobromine, and theophylline in tea, pain killers, and cocoa. Separations are accomplished by MEKC using a pH 8.25 borate-phosphate buffer with added SDS. A UV detector set to 214 nm is used to record the electropherogram. An internal standard of phenobarbital is included for quantitative work. 

Miscellaneous Pharmaceutical Processes. Solvent extraction is used for the preparation of many products that ate either isolated from naturally occurring materials or purified during synthesis. Among these are sulfa dmgs, methaqualone [72-44-6] phenobarbital [50-06-6] antihistamines, cortisone [53-06-5] estrogens and other hormones (qv), and reserpine [50-55-5] and alkaloids (qv). Common solvents for these appHcations are chloroform, isoamyl alcohol, diethyl ether, and methylene chloride. Distribution coefficient data for dmg species are important for the design of solvent extraction procedures. These can be determined with a laboratory continuous extraction system (AKUEVE) (244). 

Primidone [125-33-7] C22H24N2O2 (39) is an analogue of phenobarbital that is used for the treatment of generalized tonic-clonic seizures. It is metabolized in humans to phenobarbital (6) and phenylethyLmalondiamide [7206-76-0J, C22H24N2O2 (40) and these metaboUtes are probably responsible for its anticonvulsant actions. Primidone has many of the side effect HabiUties seen with phenobarbital. 

The potential for normal brain tissue injury is one of the limiting factors in the use of XRT for brain tumors. Pentobarbital is a cerebral radioprotectant in rodent and primate models after single doses, but is associated with significant risks. Of alternative barbiturates, thiopental given to tats receiving 70-Gy (7000-rad) whole-brain irradiation in a single fraction enhances the 30-day survival similarly to pentobarbital, whereas ethohexital and phenobarbital show no radioprotective activity (250). 

These have generally been replaced in veterinary medicine by inhalation anesthetics. Phenobarbital /T(9-(9G, phenytan [57-41-0], and primidone [125-33-7] are used as anticonvulsants. 

Phazyme-PB 15/100 charcoal/bismuth/barbetis /hydrastis amylase / protease /Hpase / simethicone / phenobarbital Reed and Carnrick... 

Panase 21/100 e/scopolamine/phenobarbital pancreatic enzymes QuaHtest... 

The anticonvulsant primidone (1035) resembles phenobarbital but lacks the 2-oxo substituent. It was introduced in 1952 and has remained a valuable drug for controlling grand mal and psychomotor epilepsy. As might be expected, primidone is metabolized to yield phenobarbital (1034 X = 0) and C-ethyl-C-phenylmalondiamide (1036), both of which have marked anticonvulsant properties however, primidone does have intrinsic activity and an appropriate mixture of its metabolites has only a fraction of its activity (73MI21303). Primidone may be made in several ways, of which desulfurization by Raney nickel of the 2-thiobarbiturate (1034 X = S) or treatment of the diamide (1036) with formic acid (at 190 °C) seem to be the most satisfactory (54JCS3263). 

FIGURE 5.41 <<]) Physiological model for phenobarbital. (b) Physiological model for the voJaule... 

Detection and result The chromatogram was freed from mobile phase (first dried for 5 min in a stream of cold air, then heated for 10 min at 110°C and allowed to cool), immersed for 5 s in the reagent solution and finally heated for 2 min at 110°C. Grey to grey-blue zones were formed on a light background. The following hRf values were obtained primidone QiR( 10-15) carbamazepine hRf 40 — 45) phenytoin hR( 50 — 55) phenobarbital hRf 60) ethosuximide hRf 75) hexobarbital hRf 90 — 95). 

Fig. 1 Reflectance scan of a blank (A) and of a mixture of antiepileptics with 500 ng substance per chromatogram zone (B). Start (1), primidone (2), carbamazepine (3), phenytoin (4), phenobarbital (5), ethosuximide (6), hexobarbital (7) and solvent front (8).

Phenmetrazine 260 Phenobarbital 1, 268 Phenol phthal ei n 1, 316 Phenomorphan 294 Phenoperidine 302... 

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