Barbiturates, separation

One part by weight of propyl-methyl-carbinyl allyl barbituric acid is added to enough alcohol to facilitate handling, in this case conveniently about six times its weight. To this is added a solution of sodium hydroxide, preferably carbonate-free or substantially so, containing °%38 parts by weight of sodium hydroxide, which is the amount of sodium hydroxide necessary to combine in equal molecular proportions with the propyl-methyl-carbinyl allyl barbituric acid. This solution is filtered clear, and is then evaporated under vacuum until the sodium propyl-methyl-carbinyl allyl barbiturate (alternatively named sodium allyl 1-methyl-butyl barbiturate) separates out in solid form. The salt as thus obtained in solid form contains a varying amount of moisture. 

Fig. 5-32. Separation of various barbiturates. — Separator column IonPac NS1 (10 pm) eluent 0.005 mol/L sodium octanesulfonate + 0.05 mol/L KH2P04 (pH 4.0) / acetonitrile (64 36 v/v) flow rate 1 mL/min detection UV (220 nm) injection volume 50 pL solute concentrations 10 ppm barbital, phenobarbital, and hexobarbital.

Conradi, S. Vogt, C. Rohde, E. Separation of Enatiomeric Barbiturates by Capillary Electrophoresis Using a Cyclodextrin-Containing Run Buffer, /. Chem. Educ. 1997, 74, 1122-1125. 

The Diacel columns can be used for the separation of a wide variety of compounds, including aromatic hydrocarbons having hydroxyl groups, carbonyls and sulfoxides, barbiturates, and P-blockers (35,36). There are presendy nine different cellulose derivative-based columns produced by Diacel Chemical Industries. The different columns each demonstrate unique selectivities so that a choice of stationary phases is available to accomplish a separation. 

The thus-washed crude product is dissolved in a mixture of 12 parts of ethanol and 20 parts of benzene, with mild warming if necessary. 1 Part of sodium chloride and 1.5 parts of saturated aqueous sodium chloride solution are added to the obtained solution in ethanol-benzene, and whole thoroughly admixed. When the brine layer has settled. It is separated and the afore-described washing repeated. The clear solution is concentrated under reduced pressure until incipient formation of crystals and is then poured into 30 parts of benzene, whereupon a thick crystalline pulp is forthwith formed which, after being cooled to room temperature, is centrifuged off. The so-obtained 5-allyl-5-( 3-hydroxypropyl)-barbituric acid is dried at 70°C under reduced pressure and can be used for therapeutic purposes without further purification. Melting point 164 °C to 165°C. Yield 5 parts. 

Propyl-methyl-carbinyl allyl barbituric acid (also called allyl 1-methyl-butyl barbituric acid) may be prepared as follows 1 mol of propyl-methyl-carbinyl barbituric acid is dissolved in a suitable vessel In a 10 to 35% aqueous solution of 1 mol of potassium hydroxide. To this are added somewhat in excess of 1 mol of allyl bromide, and alcohol equal to about 10% of the total volume of the solution. The vessel Is agitated for 50 to 75 hours. At the end of this time, the solution, which may still exhibit two layers, is concentrated to about one-half its volume to remove the excess allyl bromide and the alcohol. On cooling, an oily layer, which is propyl-methyl-carbinyl allyl barbituric acid, separates out as a sticky viscous mass. It is dried, washed with petroleum ether, and dissolved in the minimum amount of benzene. Any unreacted propyl-methyl-carbinyl barbituric acid, which does not dissolve, is filtered off. The addition of petroleum ether to the clear filtrate causes the propyl-methyl-carbinyl allyl barbituric acid to precipitate as an oily mass. 

In a 2-1. round-bottomed flask fitted with a reflux condenser protected by a calcium chloride tube 11.5 g. (0.5 gram atom) of finely cut sodium is dissolved in 250 cc. of absolute alcohol. To this solution is added 80 g. (0.50 mole) of ethyl malonate followed by 30 g. (0.50 mole) of dry urea dissolved in 250 cc. of hot (70°) absolute alcohol. After being well shaken the mixture is refluxed for seven hours on an oil bath heated to 1 io°. A white solid separates rapidly. After the reaction is completed, 500 cc. of hot (50°) water is added and then enough hydrochloric acid (sp. gr. 1.18) to make the solution acidic (about 45 cc.). The resulting dear solution is filtered and cooled in an ice bath overnight. The white product is collected on a Buchner funnel, washed with 50 cc. of cold water, and then dried in an oven at 105-1 io° for three to four hours. The yield of barbituric acid is 46-50 g. (72-78 per cent of the theoretical amount). 

Superheated water at 100°-240 °C, with its obvious benefits of low cost and low toxicity, was proposed as a solvent for reversed-phase chromatography.59 Hydrophobic compounds such as parabens, sulfonamides, and barbiturates were separated rapidly on poly(styrene-divinyl benzene) and graphitic phases. Elution of simple aromatic compounds with acetonitrile-water heated at 30°-130 °C was studied on coupled colums of zirconia coated with polybutadiene and carbon.60 The retention order on the polybutadiene phase is essentially uncorrelated to that on the carbon phase, so adjusting the temperature of one of the columns allows the resolution of critical pairs of... 

It is sometimes possible to improve detection by changing the pH of the eluent, or by the use of photochemical reactions. The common barbiturates used in therapy are weak acids that are easily separated in their acid (unionised) forms. Because the conjugate bases are much stronger chromophores than the acids, barbiturates have been detected by post-column mixing with a pH 10 borate buffer followed by uv absorption at 254 nm. An example of the second approach is the detection of cannabis derivatives in body fluids involving the conversion of cannabis alcohols to fluorescent derivatives on subjecting the column effluent to intense uv radiation. 

In order to determine the applicability of retention indices, based on the alkyl arylketone scale, as the basis of a reproducible method of reporting retentions, the separation of 10 barbiturates and a set of column test compounds were examined on an octadecylsilyl bonded silica (ODS-Hypersil) column with methanol-buffer of pH 8.5 as eluent [100]. The effects on the capacity factors and retention indices, on changing the eluent composition, pH, ionic strengthened temperature, showed that the retention indices of the barbiturates were much less susceptible to minor changes in the eluent than the capacity factors. 

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.)... 

Cyclic amines (including local anesthetic drugs) and amides were among the first classes of chiral compounds investigated in the early stages of the application of macrocyclic antibiotics as chiral selectors therefore, they were screened on vancomycin [7], teicoplanin [30], and ristocetin A [33] CSPs, under RPmode systems. Cyclic imides (including barbiturates, piperidine-2,6-diones, and mephenytoin) have been separated on a vancomycin CSP [157], under NP and RP mobile phase conditions. 

CEC separation of barbiturates Determination of barbiturates in human serum... 

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. 

Figure 6.7 Illustration of multipoint hydrogen bonding based self-assembly (a) hydrogen bond formation between barbituric acid functionalized gold nanoparticles and Hamilton receptor functionalized block copolymers and (b) selective deposition of nanoparticles on a microphase-separated block copolymer film. Reprinted with permission fi om Binder et al. (2005). Copyright 2005 American Chemical Society.

A significant advantage of the benzodiazepines over other central nervous system depressants (e.g., the barbiturates) is that they possess a much greater separation between the dose that produces sleep and the dose that produces death. This increased margin of safety has been one of the major reasons benzodiazepines have largely replaced the barbiturates and other types of sedative-hypnotics in the treatment of anxiety and insomnia. In addition, benzodiazepine aclministration is associated with few side effects. 

This technique can be also applied when the water-miscible acetonitrile is added to the serum sample for extracting the analytes. Following the addition of acetonitrile, the solution is saturated with potassium chloride so that the water and acetonitrile phases separate and derivatization is performed in the acetonitrile layer. Such alkylating procedures have been applied for prechromatographic derivatization of various drug residues with carboxylic groups, including penicillins (252) and barbiturates (253). 

Separation selectivity was demonstrated by extraction of salicylic acid from pH 2 solutions in the presence of a 60-fold excess of ethanol and sixfold excesses of barbituric acid and caffeine. No measurable interference was observed. Experiments showed that the principal selectivity is in the extraction rather than the back extraction step. This finding indicated that the polar and/or ionic nature of these interferences prevents retention by polymer. Preconcentration of analyte was examined by means of extraction from a flowing stream and back extraction into a minimum volume. The extractor tube length was 4.3 m, and the sample was 10 mL of 1 mM oxine with an extraction time of 2.0 min. The back extractant was 80 pL of 0.2 M NaOH. A sevenfold increase in concentration was observed. Enhanced preconcentration can be expected with smaller tubing diameter-to-length ratios, larger sample volumes, and repetitive use of back extractant. 

Electrophoretic Methods. Several electrophoretic procedures have been developed to fractionate or purify the various caseins (McKenzie 1971C Thompson 1971 Whitney 1977). Wake and Baldwin (1961) fractionated whole casein by zone electrophoresis on cellulose powder in 7 M urea and 0.02 ionic strength sodium phosphate buffer at pH 7 and 5°C. Payens and co-workers employed several somewhat different electrophoretic conditions for the fractionation and purification of the caseins on cellulose columns (Payens 1961 Schmidt and Payens 1963 Schmidt 1967). Three fractions, as-, k-, and /3-caseins, were separated at pH 7.5 and 30°C with 4.6 M urea-barbiturate buffer. The purification of asi-casein and the separation of the genetic variants of K-casein were accomplished by altering the electrophoretic conditions. Manson (1965) fractionated acid casein on a starch gel column stabilized by a density gradient at 25 °C. 

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