5- barbituric acid

Ethyl malonate condenses with urea in the presence of sodium ethoxide to yield barbituric acid (malonylurea)  

In a 2 litre round-bottomed flask, fitted with a double surface reflux condenser, place 11 5 g. of clean sodium. Add 250 ml. of absolute alcohol 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.) of ethyl malonate (Section 111,153), followed by a solution of 30 g. of dry urea in 250 ml. of hot (ca. 70°) absolute alcohol. Shake the mixture well, fit a calcium chloride (or cotton wool) guard tube to the top 

The condensation of 1 mol of ethyl malonate with two mols of ethyl iodide in the presence of two mols of sodium ethoxide gives a good yield of ethyl diethylmalonate. Upon allowing the latter to react with the theoretical quantity of urea in the presence of an alcoholic solution of sodium ethoxide, veronal (diethylbarbituric acid or diethylmalonylurea) is produced. 

Diethylbarbituric acid. In a dry 250 ml. distilling flask, fitted with a thermometer reaching to within 3-4 cm. of the bottom and a condenser, place 5-1 g. of clean sodium and add 110 g. (140 ml.) of super-dry ethyl alcohol (Section 11,47,5). When all the sodium has reacted, introduce 20 g. of ethyl diethylmalonate and 7 0 g. of dry urea (dried at 60° for 4 hours). Heat the flask in an oil bath and slowly distil off the ethyl alcohol. As soon as the temperature of the liquid reaches 110-115°, adjust the flame beneath the bath so that the contents of the flask are maintained at this temperature for at least 4 hours. Allow the flask to cool somewhat, add 100 ml. of water and warm until the solid (veronal-sodium) dissolves. Pour the solution into a beaker, and add a further 100 ml. of water but containing 7 0 ml. of concentrated sulphuric acid this will liberate the veronal from the sodium derivative. The veronal usually crystallises out if it does not, add a few more drops of dilute sulphuric acid until the solution is acid to Congo red. Heat the contents of the beaker, with stirring and the addition of more water if uecessarv, until all the veronal dissolves at the boding poiut. Allow the hot solution to cool, filter off the crystals of veronal and dry in the air. The yield is 12 g., m.p. 190°. 

Ethyl diethylmalonate. Equip a 1 litre three-necked flask with a 

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White crystals, m.p. 191°C. A barbituric acid derivative. The sodium salt is administered orally as a sedative. 

It is the parent substance of a group of compounds which includes cytosine, thymine and uracil, which are constituents of nucleic acids and barbituric acid and its derivatives, which are important medicinally. 

Barbituric acid and 2-thiobarbituric acid are readily prepared by the condensation of diethylmalonate with urea and thiourea respectively, in the presence of sodium ethoxide. The use of substituted derivatives of urea and thiourea and of diethyl malonate will clearly lead to a wide range of barbituric and thiobarbituric acids having substituents in the i, 3, or 5 positions. 

Uramll (aminobarbituric acid) (III) may be prepared by the oxidation of barbituric acid (I) to nitrobarbiturlc acid (II), followed by reduction of the latter ... 

Barbituric acid was first pre pared in 1864 by Adolf von Baeyer (page 112) A histori cal account of his work and the later development of barbiturates as sedative-hypnotics appeared in the October 1951 issue of the Journal of Chemical Education (pp 524-526)... 

Diethyl malonate has uses other than m the synthesis of carboxylic acids One particu larly valuable application lies m the preparation of barbituric acid by nucleophilic acyl substitution with urea... 

Barbituric acid is the parent of a group of compounds known as barbiturates The bar biturates are classified as sedative-hypnotic agents meaning that they decrease the responsiveness of the central nervous system and promote sleep Thousands of deriva lives of the parent ring system of barbituric acid have been tested for sedative-hypnotic activity the most useful are the 5 5 disubstituted derivatives... 

These compounds are prepared m a manner analogous to that of barbituric acid itself Diethyl malonate is alkylated twice then treated with urea... 

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... 

Section 21 8 Alkylation of diethyl malonate followed by reaction with urea gives derivatives of barbituric acid called barbiturates, which are useful sleep promoting drugs... 

Urea and malonic acid give barbituric acid (7), a key compound in medicinal chemistry (see also Hypnotics, SEDATIVES, AND anticonvulsants) ... 

More conveniently, compound (13) was directly condensed with barbituric acid (14) in acetic acid (28) or in the presence of an acid catalyst in an organic solvent (29). The same a2o dye intermediate (13) and alloxantin give riboflavin in the presence of palladium on charcoal in alcohoHc hydrochloric acid under nitrogen. This reaction may involve the reduction of the a2o group to the (9-phenylenediamine by the alloxantin, which is dehydrogenated to alloxan (see Urea) (30). 

Cyanide compounds are classified as either simple or complex. It is usually necessary to decompose complex cyanides by an acid reflux. The cyanide is then distilled into sodium hydroxide to remove compounds that would interfere in analysis. Extreme care should be taken during the distillation as toxic hydrogen cyanide is generated. The cyanide in the alkaline distillate can then be measured potentiometricaHy with an ion-selective electrode. Alternatively, the cyanide can be determined colorimetricaHy. It is converted to cyanogen chloride by reaction with chloramine-T at pH <8. The CNCl then reacts with a pyridine barbituric acid reagent to form a red-blue dye. 

A number of other heterocycHc diazo components such as thiazole, iadazole, thiophenes, and thiadiazole types (see Fig. 1), as well as heterocycHc couplers, ie, 6-hydroxy-2-pyridinone [626-06-2] barbituric acid [67-52-7] and tetrahydroquiaoline [25448-04-8] h.2L e been cited ia the Hterature (90,91). Reviews on disperse dyes have been pubUshed (92,93). 

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