Salts of barbiturates

Barbiturates are salts of barbituric acid. They can be used as hypnotics, sedatives, general anaesthetics, and... 

Morphine Sulfate Morphine sulfate precipitates in alkaline media and drugs that are incompatible with it, including aminophylline, sodium salts of barbiturates, and phenytoin. Precipitate was found after 2 horns when morphine sulfate was formulated with acyclovir sodium.70 Incompatibilities also are reported with chlorpromazine hydrochloride injections containing chlorocresol. Admixture of morphine sulfate (1 mg/mL), doxorubicin in doxorubicin hydrochloride... 

The thermal decomposition of tetramethylammonium salts of barbiturates is a procedure used extensively for their methylation [512-515]. Decomposition is performed at 240°C (temperature of the injection port) with analysis on SE-30, QF-1 and similar stationary phases. The use of trimethylanilinium hydroxide leads to better reproducibility of the preparation of the phenobarbital derivatives and to an improvement in the quantitative results [516,517]. The disadvantage of this procedure is the dependence of the course of the reaction on several parameters, e.g., geometry of the injection port, temperature. 

Stxlium salts of the barbiturates are readily prepared and are water soluble. Their aqueous. solutions generate an alkaline pH. A classic incompatibility is the addition of an agent with an acidic pH in solution, which rc.sults in formation and precipitation of the free water-insoluble disubsliluied barbituric acid. Sodium salts of barbiturates in aqueous solution decompose at varying rates by base-catalyzed hydrolysis, generating ring-opened sails of carboxylic acids. 

Jochym, K., Barton, H., and Bojarski, J., 1988, Photolysis of sodium salts of barbiturates in the solid state, Pharmazie 43, 623-624. 

For sodium or potassium salts of weak acids, the pH of the solution in a diffusion layer is greater than the pH of the diffusion layer for the corresponding weak acid. On the other hand, the pH of the solution in the diffusion layer for hydrochloride salts of weak bases is always smaller than the diffusion layer of the corresponding free base. Therefore, effective solubility and dissolution rate of soluble salts on drug absorption are available in the literature. The potassium salt of penicillin V yields a higher peak plasma concentration of antibiotic than the corresponding free acid (42). Sodium salts of barbiturates are reported by Anderson (43) to provide a rapid onset of sedation. Some salts have a lower solubility and dissolution rate than their parent compounds. Examples include aluminum salts of weak acids and pamoate salts of weak bases. In these particular examples, insoluble films of either weak acids or pamoic acid appear to form in the dissolving solids and further retard the dissolution rate. 

The term barbiturate is by long usage considered synonymous with hypnotic agents . However, the salts of barbituric acid, and of many of its derivatives, have no observable hypnotic properties in most systems. A consideration of the non-hypnotic barbiturates is one of the main objectives of this section. For comparison, a short review of the structural requirements... 

Both the relative potencies of the free-add and anionic forms of barbiturates and also the possible interference by barbiturates in the binding of calcium to phospholipids are subject to considerable controversy. In consequence, various derivatives and salts of barbituric add have been extensively investigated. The analysis of calcium 5,5-diethylbarbiturate trihydrate (41) reveals that the deprotonated nitrogen atoms are co-... 

Barbituric acids as their name implies are weakly acidic and are converted to then-sodium salts (sodium barbiturates) m aqueous sodium hydroxide Sometimes the drug is dispensed m its neutral form sometimes the sodium salt is used The salt is designated by appending the word sodium to the name of the barbituric acid—pentobarbital sodium for example... 

The ZwKKER reaction involving Co salts is frequently used for the detection of barbituric acid derivatives [31-35], but some purine, pyridine and piperidine derivatives and heterocyclic sulfonamides also yield colored derivatives. The Zwkker reaction is particularly sensitive when it is possible to form a tetrahedral complex [Co(Barb)2 Xj] (X = donor ligand, e.g. amine) [4]. 

In rabbits under light amytal anesthesia, chlordan has no direcr effect on the blood pressure, but produces a type of respiration having many characteristics in common with Cheyne-Stokes type. The generalized tremors, opisthotonus, tonic and clonic convulsions, produced by chlordan were decreased or abolished and respiration restored to normal by suitable injections of the sodium salts of amytal, phenobarbital, and pentothal. The LD60 of chlordan, which was about 20 mg. per kg. on intravenous administration to intact rabbits, was increased to about 60 mg. per kg. through the antidotal action of the barbiturates. An unidentified chlorine-containing degradation product with acidic properties was recovered from the urine of rabbits treated with chlordan. Approximately one third of its chlorine content was set free on hydrolysis at 100° C. with sodium hydroxide in either absolute alcohol or in water. 

The antidotal action of the barbiturates was also investigated in intact rabbits by the intravenous administration of both chlordan and the barbiturate. Sixty milligrams per kg. of chlordan were injected as a 40% solution in Tween 20 at a uniform rate over a period of 3 minutes. The sodium salts of the barbiturates were injected slowly as a 2.5% solution in distilled water in two doses. The first dose was given 2 to 5 minutes preceding... 

Ohrui and Fox128 obtained the sodium salt of 5-(2,3-0-isopropylidene-5-0-trityl-/3-D-ribofuranosyl)barbituric acid (271) by treatment of the corresponding C-malonyl derivative (173) with urea... 

A plethora of weakly acidic pharmaceutical substances may be titrated effectively by making use of a suitable non-aqueous solvent with a sharp end-point. The wide spectrum of such organic compounds include anhydrides, acids, amino acids, acid halides, enols (viz., barbiturates), xanthines, sulphonamides, phenols, imides and lastly the organic salts of inorganic acids. 

The haloalkane (60 mmol for monoalkylation) is added with stirring to the heterocycle (50 mmol) and TBA-Br or TEBA-C1 (5 mmol) in PhH or CH2C12 (50 ml) and aqueous NaOH (50%, 20 ml). The mixture is stirred at 60 °C for ca. 4-5 h and then cooled to room temperature. The organic phase is separated, washed with H20 (2 x 25 ml), dried (MgS04), and evaporated to yield the /V-alkylated product. ( The preformed sodium salts of the barbiturates have been used in the absence of a solvent or aqueous NaOH.)... 

Another Methodfor 5 5-Diethyl Barbituric Acid. (This is a scaled down version.) 16 g of clean sodium is dissolved in 300 g of absolute ethanol. To this cooled solution is added 20 g of dry urea and 50 g of diethyl malonic ester (diethyl diethyl malonate). The mixture is heated in an autoclave (pressure cooker, very strong) for 4 to 5 hours at 100-110°. After removing from the autoclave, the mixture is cooled. Upon cooling, the sodium salt of diethyl barbituric acid separates, is filtered off, dissolved in water, and the free acid precipitated by the addition of hydrochloric acid. The acid is filtered and recrystallized from water, using decolorizing carbon, if necessary. Yield Depends on your ability to exclude H2O from the beginning of reaction. 

Tosylation of 1146 gave 1147, which was converted to the iodo derivative, whose reaction with the sodium salt of guanine, followed by acetylation to aid its purification and then deprotection, gave 1148 (86JMC1384). The hydroxymethyl groups on C-5 of barbituric acid were introduced starting with malonic ester and then reaction with urea (93MI12). 

Any substance which contains any quantity of a derivative of barbituric acid, or any salt of a derivative of barbituric acid. 

PREPARATION OF STANDARDS. Barbiturate Sodium salts in aqueous solution and glutethimide in 80% ethanol are used as stock standards. The sodium salt of Dilantin in NaOH (0.2 mol/ )is used as the stock standard. 

On the other hand, Mori64 could not obtain any precipitate of the 2-fural-dehyde-barbituric acid complex, characteristic of pentose, from 5 g. of the purified barium salt of the mucilage, whereas he obtained it from an unpurified specimen. From this he concluded that pentose should be recognized as an impurity in the mucilage. Johnston and Percival88 identified 2,3,4-trimethyl-D-xylose in the hydrolyzed products of car-rageenin but they have stated that it may have been derived from a contaminating xylan. These views find support in that pentose was not... 

The sodium salt of 5-ethyl-5-(l-methyl-81-butenyl)barbituric acid is prepared by dissolving 23 parts of sodium in 350 parts of absolute alcohol in a vessel... 

This reaction has been applied to a great number of carbonyl compounds, e.g., cyclopentanone,27 1,3-cyclohexanedione,36 5,5-dimethyl-l,3-cyclohexanedione,S5 1-acenaphthenone,24,25 1,3-indane-dione,35 1,3-phenalanedione,85 86 sodium salts of 3-aryl-3-oxo-propanals,39 2,3-dihydrobenzo[6]thiophen-3-one,40 sodium benzoyl-acetate,41 benzoylacetonitrile,29 30,88 ethyl cyanoacetate,30 35 cyano-acetanilide,30 barbituric acid,35 rhodanine,35 jV-phenylrhodanine,37 and iV-methylenebenzothiazoline.37... 

More recently, Iiu et al. reported that a variety of non-chiral amphiphilic diacetylenes, non-chiral barbituric acids or amphiphilic aryl-benzimidazoles self-assemble into chiral clusters at the air/water interface or on aqueous solutions containing Ag+ ions, as demonstrated by CD measurements [108-111]. The chiral macroscopic conformational morphology of the polymers generated from copper salts of non-chiral monomers was imaged after their transfer onto solid support [ 112,113]. 

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