Ureides

In a modification of the original method. Read (60) replaced a-amino acids with a-amino nitriles. This reaction is sometimes known as Strecker hydantoin synthesis, the term referring to the reaction employed for the synthesis of the a-amino nitrile from an aldehyde or ketone. The cycli2ation intermediate (18) has been isolated in some cases (61), and is involved in a pH-controUed equiUbrium with the corresponding ureide. 

Hydantoin itself can be detected ia small concentrations ia the presence of other NH-containing compounds by paper chromatography followed by detection with a mercury acetate—diphenylcarba2one spray reagent. A variety of analytical reactions has been developed for 5,5-disubstituted hydantoias, due to their medicinal iaterest. These reactions are best exemplified by reference to the assays used for 5,5-diphenylhydantoiQ (73—78), most of which are based on their cycHc ureide stmcture. Identity tests iaclude the foUowiag (/) the Zwikker reaction, consisting of the formation of a colored complex on treatment with cobalt(II) salts ia the presence of an amine (2) formation of colored copper complexes and (3) precipitation on addition of silver(I) species, due to formation of iasoluble salts at N. ... 

Although in the dry state carbon tetrachloride may be stored indefinitely in contact with some metal surfaces, its decomposition upon contact with water or on heating in air makes it desirable, if not always necessary, to add a smaH quantity of stabHizer to the commercial product. A number of compounds have been claimed to be effective stabHizers for carbon tetrachloride, eg, alkyl cyanamides such as diethyl cyanamide (39), 0.34—1% diphenylamine (40), ethyl acetate to protect copper (41), up to 1% ethyl cyanide (42), fatty acid derivatives to protect aluminum (43), hexamethylenetetramine (44), resins and amines (45), thiocarbamide (46), and a ureide, ie, guanidine (47). 

The ureide, which is stable to BuLi, was used for the protection of indole. It is cleaved with 25% NaOH in EtOH, reflux. ... 

Forty years after the initial proposal, Sweet and Fissekis proposed a more detailed pathway involving a carbenium ion species. According to these authors the first step involved an aldol condensation between ethyl acetoacetate (6) and benzaldehyde (5) to deliver the aldol adduct 11. Subsequent dehydration of 11 furnished the key carbenium ion 12 which was in equilibrium with enone 13. Nucleophilic attack of 12 by urea then delivered ureide 14. Intramolecular cyclization produced a hemiaminal which underwent dehydration to afford dihydropyrimidinone 15. These authors demonstrated that the carbenium species was viable through synthesis. After enone 13 was synthesized, it was allowed to react with N-methyl urea to deliver the mono-N-methylated derivative of DHPM 15. 

Condensation of o-phenylenediamine or xV-methyl-o-phenylcne-diamine with alloxan (8) in neutral solution gives the ureides (9) and (10), respectively However, reaction of o-phenylenediamine with 1,3-dimethylalloxan (13) yields quinoxalin-3-one-2-carboxymethyl-amide (14), rather than the dimethyl ureide. Methylation of (9) in acetone in the presence of potassium carbonate gives the spiro-hydantoin (11). 

The ureides hydantoin, parabanic acid, alloxan, barbituric acid, and 4-methyluracil show resonance energies of between 2.3 v.e. and 3.1... 

L. PAULING AND J. SHERMAN Table VIII. Ureides and purines. ... 

Reaction between ureas and malonic esters (cyclic ureides)... 

Ureides (e.g., diuron, linuron) and triazines (e.g., atrazine, simazine, ametryne) all act as inhibitors of photosynthesis and are applied to soil (see Figure 14.1 for structures). They are toxic to seedling weeds, which they can absorb from the soil. Some of them (e.g., simazine) have very low water solubility and, consequently, are persistent and relatively immobile in soil (see Chapter 4, Section 4.3, which also mentions the question of depth selection when these soil-acting herbicides are used for selective weed control). 

In 1997, the controversial mechanism of the Biginelli reaction was reinveshgated by Kappe using NMR spectroscopy and trapping experiments [94], and the current generally accepted process was elucidated (see Scheme 9.23). The N-acyliminium ion 9-112 is proposed as key intermediate this is formed by an acid-catalyzed reaction of an aldehyde with urea or thiourea via the semiaminal 9-111. Intercephon of 9-112 by the enol form of the 1,3-dicarbonyl compound 9-113 produces the open-chain ureide 9-114, which cyclizes to the hexahydropyrimidine 9-115. There follows an elimination to give the final product 9-116. 

Murray, J. S., P. Lane, T. Brinck, P. Politzer, and P. Sjoberg. 1991b. Electrostatic Potentials on the Molecular Surface of Some Cyclic Ureides. J. Phys. Chem. 95, 844. 

An access to iV-substituted 4,6-dioxo-imidazo[3,4-c]thiazoles 185 was developed considering first the reaction of 2-chloroethylisocyanate with methyl thiazolidine 4-carboxylate 183 that generated the ureide 184. Cyclization of the imidazole ring occurred in acidic medium via an addition-elimination mechanism and delivered the imidazothiazole 185 (Equation 81) <2001MI1117>. 

Barbitone (barbital, 282) was irradiated in aqueous solution at pH 10 with light of 254 nm wavelength to give the ureide (289) in 68% yield. In ethanol, the derivative (290) was formed (62%). With A-methylbarbitone (283) in buffer at pH 10, a mixture of the ureide (291) and the imidazole (292) was obtained. It was suggested that the ring-opened compounds were formed via isocyanates (288). Reaction with water would then give an acid which would spontaneously decarboxylate, but in ethanol a stable urethane (290) would form [173]. 

Photolysis of pentobarbitone (pentobarbital, 285) was achieved on a solution buffered to pH 11 with a low-pressure mercury lamp over 10 h. At this pH the mono anion was the main species present. The products identified were the dealkylated ethyl barbitone (286), the amide (294) and both diastereoisomers of the ureide (295). On more prolonged irradiation, there also appeared ethylhydroxybarbitone (287) and an unidentified dimeric compound. When ethylbarbitone (286) was photolysed in the same way, it gave (287) and 2-ethyl-2-hydroxymalonic acid. Finally, pentobarbitone was irradiated in molar sodium hydroxide solution, where the dianion would be the main form present, to give (295) with a small amount of (294) [175]. 

In an earlier report (J>), the decay of healthy yam tubers during storage was shown to be a result of catabolism of its proteins by an active a-glutamyl transpeptidase. There is also some alkaline proteolytic activity in the yam tuber (6), but little information is available on individual enzymes of the purine degradative pathway and on the properties of an alkaline proteinase that may function in yams during storage. This report describes the interrelation of five enzymes of ureide metabolism in fresh and stored yams, the release of ammonia in vitro by three of the enzymes that may provide an environment for alkaline proteinase activity in vivo, and the in vitro properties of an... 

Table 2. Effects of 12 Months Storage on Relative Activities of Ureide Enzymes in Yam Tubers.

Release of Ammonia. Of the five enzymes, three lead to release of amide/ami no nitrogen as ammonia during ureide metabolism ... 

Alkaline Proteinase Activity in Yams. The release of ammonia at several stages during ureide metabolism suggested a potential for alkaline conditions in yam tubers, rather than the usual neutral or acid conditions generally found in seeds and plants. 

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