Oxalyl urea

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. 

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. 

Commercially important arenesulfonyl isocyanates are not directly accessible from the corresponding sulfonamides via phosgenation due to lack of reactivity or by-product formation at elevated temperatures. A convenient method for their preparation consists of the reaction of alkyl isocyanates with sulfonamides to produce mixed ureas which, upon phosgenation, yield a mixture of alkyl and arenesulfonyl isocyanates. The desired product can be obtained by simple distillation (16). Optionally, the oxalyl chloride route has been employed for the synthesis of arenesulfonyl isocyanate (87). 

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. 

Preparatively useful procedures based on acetic anhydride,20 trifluoroacetic anhydride,21 and oxalyl chloride22 have been developed. The latter method, known as Swern oxidation, is currently the most popular and is frequently preferred to Cr(VI) oxidation. Scheme 12.3 gives some representative examples of these methods. Entry 4 is an example of the use of a water-soluble carbodiimide as the activating reagent. The modified carbodiimide facilitates product purification by providing for easy removal of the urea by-product. 

Richter et al. prepared /V-benzoyl-/V -(/V-aryloxamoyl) ureas 138 (R = Ph R = H, Me) by using a sequence of reactions involving ben-zoylation, reaction with oxalyl chloride, and, finally, reaction with anilines (Scheme 5) (78JOC4150). Karparov et al. found, in broad-spectrum antiviral screening, that Mannich bases 139 (m = 4,5) showed some activity, but that the parent urea (104) and thiourea (105) did not (84AF9). However, a later study revealed the two Mannich bases were inactive toward alphavi-rus models (86MI1). 

The possibility of crosslinking natural macromoleculcs, such as cellulose and proteic materials, via the Mannich reaction has also been inve.stigatcd. Cellulose derivatives, however, are mostly subjected to the analogous amidomcthylation reaction, " usually employing bis-methylol amides (urea, oxalyl, adipoyl derivativas, etc.) capable of reacting with the cellulose hydroxy groups. 

Direct introduction of the carboxyl group into an aromatic ring is accomplished with urea hydrochloride, phosgene, oxalyl chloride, or carbon dioxide. Carboxylation of benzene is effected in 15-58% yields by treating with liquid phosgene and aluminum chloride. No catalyst is required in the conversion of dimethylaniline and phosgene to p-dimethyl-aminobenzoic acid (50%). 9-Anthroic acid (67%) is prepared from anthracene by heating to 240° with oxalyl chloride and nitrobenzene. ... 

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). 

The following section highlights some selected recent applications of the use of phosgene equivalents in the preparation of Vilsmeier-type chlorinated derivatives of amides and ureas. Thionyl chloride, carbonyl bromides, phosphorus oxychloride, phosgene, triphosgene, oxalyl chloride, and p-toluenesulfonyl chloride are all efficient oxophilic promoters capable of generating Vilsmeier-type chloro imi-nium ion intermediate 1770 by reaction with formamides, particularly dimethyl-formaraide, and ureas. 

A very useful group of procedures for oxidation of alcohols to ketones have been developed that involve dimethyl sulfoxide (DMSO) and any one of a number of electrophilic molecules, particularly dicyclohexylcarbodiimide, acetic anhydride, trifluoroacetic anhydride, oxalyl chloride, and sulfur trioxide. The initial work involved the DMSO-dicyclohexylcarbodiimide system.The utility of the method has been greatest in the oxidation of molecules that are highly sensitive to more powerful oxidants and therefore cannot tolerate alternative methods. The mechanism of the oxidation involves formation of intermediate A by nucleophilic attack of DMSO on the carbodiimide, followed by reaction of this species with the alcohol. A major part of the driving force for the reaction is derived from the conversion of the carbodiimide to a urea, with formation of an amide carbonyl. ... 

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