Parabanic acids ureas

Fichter and Kern O first reported that uric acid could be electrochemically oxidized. The reaction was studied at a lead oxide electrode but without control of the anode potential. Under such uncontrolled conditions these workers found that in lithium carbonate solution at 40-60 °C a yield of approximately 70% of allantoin was obtained. In sulfuric acid solution a 63% yield of urea was obtained. A complete material balance was not obtained nor were any mechanistic details developed. In 1962 Smith and Elving 2) reported that uric acid gave a voltammetric oxidation peak at a wax-impregnated spectroscopic graphite electrode. Subsequently, Struck and Elving 3> examined the products of this oxidation and reported that in 1 M HOAc complete electrochemical oxidation required about 2.2 electrons per molecule of uric acid. The products formed were 0.25 mole C02,0.25 mole of allantoin or an allantoin precursor, 0.75 mole of urea, 0.3 mole of parabanic acid and 0.30 mole of alloxan per mole of uric acid oxidized. On the basis of these products a scheme was developed whereby uric acid (I, Fig. 1) is oxidized in a primary 2e process to a shortlived dicarbonium ion (Ha, lib, Fig. 1) which, being unstable, under-... 

Fig. 4. Mechanisms for decomposition of uric acid-4,S-diol to allantoin (V), alloxan (VI), urea (VII) parabanic acid (XIV) and COj...

Parabanic acid can be prepared by the condensation of urea with diethyl oxalate in an ethanolic solution of sodium ethoxide,2 by reaction of urea with an ethereal solution of oxalyl chloride,3 by oxidizing uric acid with an acid solution of perhydrol,4 or by the action of hot, concentrated nitric acid on uric acid.5 The present method gives better yields than the previously reported methods and is better adapted to larger-scale preparations. 

Parabanic Acid, the ureide of oxalic acid and oxidation product of uric acid obtained by the action of nitric acid, is converted into hydantoln and ethyl urea (Tafel and Reindl1). 

The unstable dication (261) is hydrolyzed and some products are oxidized further. From the electrolyzed solution, urea, parabanic acid (262), oxaluric acid (263), ammonia, 4-aminopurpuric acid (264), and possibly allantoin (265) were isolated. 

Oxidation of xanthine or uric acid derivatives with chromic acid gives the appropriate alloxane and urea as primary products which undergo further oxidation to corresponding parabanic acids (imidazolidine-2,4,5-triones) and purpuric acids which, on addition of ammonia, constitute the murexide test. This is positive for all purines capable of oxidation to an alloxane derivative, For a review see ref 48. 

One of the first facts observed in regard to uric acid was that on heating it yielded cyanuric acid, (OCNH)3, and ammonia, NH3. As these same products had been obtained by heating urea, OC(NH2)2, it was considered probable that a urea residue was present in uric acid. It was then shown that on oxidation with lead dioxide, one of the ureids, the di-ureid known as allantoin was obtained, together with urea, oxalic acid and carbon dioxide. With other oxidizing agents, such as nitric acid, the products were equal molecules of urea and the two ureids alloxan and parabanic acid. From alloxan there may be obtained, by reduction, two other ureids, viz., barbituric acid and... 

From the facts that uric acid yields the di-ureid allantoin and also equal molecules of alloxan, a mono-ureid, and urea it was concluded that uric acid must contain two urea residues. From the constitution of alloxan and its reduction products, barbituric and dialuric acids, uric acid must likewise contain a three carbon chain linked to a urea residue by the end carbon atoms. Also, as it yields parabanic acid or oxalyl urea, one of the urea residues must be linked to two adjacent carbon atoms in this chain. 

The splitting of the compound at the dotted line would yield alloxan and urea while splitting at the broken line would yield parabanic acid and urea. Confirmation of this constitution has been furnished in two ways (i) by Fischer s study of the methyl substitution products of uric acid and (2) by the syntheses of Horbaczewski and of Behrend and Roosen. 

In orthoesters (458 Scheme 84) one alkoxy group can be replaced by aminoacyl groups, by aminosul-fonyl groups or by the 1-imidazolyl group on reaction with ureas,imides, salicylamide, N-alkylsulfonamides in the presence of Lewis acids or with imidazoles under acid cat ysis. Excess aryl isocyanates convert orthoformates to acetals of parabanic acid. ... 

Heterocycles. Base-catalyzed condensation of urea with diethyl oxalate gives parabanic acid (Murray ) condensation with diethyl malonate gives barbituric acid (Dickey and Gray ). The first procedure uses a solution prepared from sodium... 

The diverse emissive characteristics of the triplet states of amide-containing molecules (amides, ureas, oxamides, parabanic acids, acylureas etc.) have been rationalized in terms of the amount of 3mr and 9mr character in the lowest... 

Parabanic Acid, C3H2N2O3.—Under certain conditions an acid of this formula is obtained by oxidizing uric acid with nitric acid. The structure of parabanic acid is deduced from the decomposition which results when the acid is hydrolyzed by an alkali urea and oxalic acid are formed —... 

In parabanic acid, however, the two hydroxyl groups of oxalic acid are replaced by the residue of urea. Other dibasic acids form analogous compounds, which are called ureides. Parabanic acid is, thus, oxalyl ureide it is also called oxalyl urea. 

Imidazolidine-2,4,5-trione 6 has the trivial name parabanic acid and is an even stronger NH-acid, p = 5.43. It reacts as a dibasic NH-acid. Parabanic acid is considered to be the ureide of oxalic acid. It is prepared from diethyl oxalate and urea ... 

Parabanic acid is a cyclic ureide containing a five membered ring, which on hydrolysis by alkali may regenerate the corresponding acid and urea. The cyclic ureides are acidic owing to enolization and hence, they may form metallic salts by replacing the H atom of the -OH group as shown below ... 

The reaction of thionyl chloride with 1,3-disubstituted ureas affords either N-sulfinylamines and isocyanates (R = n-alkyl), or chloroformamidine hydrochlorides (R = sec-alkyl, t-alkyl) However, the reaction of oxalyl chloride with ureas does not produce chloroformamidines, parabanic acids being the sole reaction product (51.6 5,66 ... 

After the research of Wohler and Liebig (1838, see p. 333), uric acid and its derivatives were investigated by Schlieper. The latter showed that uric acid on reduction by hydriodic acid forms glycocoll and the decomposition products of urea (NH3 and CO2). Gerhardt formulated alloxan as the mesoxalyl, and parabanic acid as the oxalyl, derivatives of urea, which he then regarded as hydrate d oxyde de cyanammonium , giving complicated formulae, which were simplified by Kekule as ... 

Ring closures with oxalyl chloride Parabanic acids from ureas... 

A soln. of 3-(3,4-dichlorophenyl)-l-isopropyl-l-(2-propynyl)urea and oxalyl chloride in benzene refluxed 8 hrs. 3-(3,4-dichlorophenyl)-l-(2-propynyl)-parabanic acid. Y 81.5%.—This is a convenient synthesis of 1,3-subst. parabanic acids from readily available 1,1,3-trisubst. ureas. F. e., also from thioureas, s. P. J. Stoffel, J. Org. Ghem. 29, 2794 (1964) f. ring closures with oxalyl chloride s. J. Org. Ghem. 29, 2796 parabanic acids from ureas and 2-iminothiazolidine-4 -diones from thioureas s. H. Ulrich and A. A. R. Sayigh, J. Org. Ghem. 30, 2781 (1965). 

---