Barbituric acid separation

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. 

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. 

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. 

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. 

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). 

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.

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. 

In a 2-litre round-bottomed flask, fitted with a double surface reflux condenser, place 11.5 g (0.5 mol) of clean sodium. Add 250 ml of absolute ethanol in one portion if the reaction is unduly vigorous, immerse the flask momentarily in ice. When all the sodium has reacted, add 80 g (76 ml, 0.5 mol) of diethyl malonate, followed by a solution of 30 g (0.5 mol) of dry urea in 250 ml of hot (c. 70 °C) absolute ethanol. Shake the mixture well, fit a calcium chloride guard-tube to the top of the condenser and reflux the mixture for 7 hours in an oil bath heated to 110°C. A white solid separates. Treat the reaction mixture with 450 ml of hot (50 °C) water and then with concentrated hydrochloric acid, with stirring, until the solution is acid (about 45 ml). Filter the resulting almost clear solution and leave it in the refrigerator overnight. Filter the solid at the pump, wash it with 25 ml of cold water, drain well and then dry at 100 °C for 4 hours. The yield of barbituric acid is 50 g (78%). It melts with decomposition at 245 °C. 

Enantiomer separation of various compounds such as barbituric acids, benzoin, MTH-proline, glutethimide, a-methyl-oc-phenyl-succinimide, y-phenyl-y-butyrolac-tone, methyl-mandelate, l-(2-naphthyl)ethanol, mecoprop methyl, diclofop methyl and fenoxaprop methyl by pressure supported CEC on a permethyl-P-cyclodextrin modified stationary phase was described by Wistuba and Schurig [42-44]. Three different separation beds were used (i) permethyl-P-cyclodextrin was covalently attached via a thioether to silica (Chira-Dex-silica) [42], permethyl-P-cyclodextrin was linked to a dimethylpolysiloxane and thermally immobilized (ii) on silica (Chirasil-Dex-silica) [43] or (iii) on a silica monolith (Chirasil-Dex-monolith) [44], respectively. 

One such way is a precipitation of the furfural with barbituric acid to form furfural barbituric acid [113]. To this end, 0.5 g of barbituric acid is dissolved in 25 ml of 12 % aqueous hydrochloric acid, and this solution is added to the mixture containing the furfural. After a standing period of 18 hours to permit the crystallization to take place, the precipitate is separated by a dried and weighed glass filter, washed twice with distilled water, and drained by a vacuum. Then the filter is dried at 130 °C until a constant weight is reached. 

Much higher acetonitrile contents are required to elute the most important barbiturates i.e., barbital, phenobarbital, and hexobarbital. Their separation is depicted in Fig. 5-32. Barbiturates are derived from barbituric acid (p/fa = 3.9 [40]) which is quite acidic because of its activated methylene group in 5-position. 

Thiocyanate is separated from cyanide by distilling off HCN from a weakly acid medium. With bromine and chloramine-T, thiocyanate is converted into cyanogen bromide and cyanogen chloride, respectively, and determined as a polymethine dye by the benzidine-pyridine method or pyridine—barbituric acid method [38—40]. The latter method has been applied for continuous determination of thiocyanate in blood plasma and in urine [40]. 

Ethyl malonate (320 g) is stirred into a solution of sodium (48 g) in anhydrous methanol (400 ml), and the mixture is then boiled for 10 min, after which a hot solution of urea (120 g) in anhydrous methanol (300 ml) is added this affords a thick slurry. To complete the condensation the mixture is heated for a further 5 h under reflux. It is then poured into water (3 1) and acidified with concentrated hydrochloric acid (200 ml), which causes first dissolution of the solid material and then separation of barbituric acid in beautiful crystals. After re-crystallization from water and drying for 2 days at 100° these have m.p. above 260° with decomposition. The yield is 210 g. 

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