Ureides hydrolysis

Amides from Esters Hydrolysis of Ureides Hydrolysis of Carbamates Hydrolysis of Carboxamides Decarboxylation ... 

The cyclization of a-halo carboxylic acid ureides can be complicated with products from different modes of cyclization. For example, bromination of 70 at low pH affords the 2-amino-4(5//)-oxazolone 71 in excellent yield, whereas bromination at pH 5-6 generates a mixture of hydantoins 72 and 73 in poor yield (Scheme 6.19)." Japanese workers" reported that cyclization of a-bromoisovaleryl-urea with 28% aqueous ammonia yields 2-amino-5-isopropyl-4(5H)-oxazolone 74, not 75 or 76. The structure of 74 was established spectroscopically and confirmed by hydrolysis to 77 (Scheme 6.20). 

Alkyl hypochlorites and N-halo amides add to isocyanides to give, after hydrolysis, carbamates and N-acylureas (ureides), respectively.806... 

Plants also form the ureides allantoin and allantoic acid, and in some legumes, such as soy beans, these compounds account for 70-80% of the organic nitrogen in the xylem. They appear to function in nitrogen transport.337 As indicated in Fig. 25-18, the hydrolysis to glyoxylate, NH4+, and C02 follows a different pathway than in animals. See also Chapter 24, Section C. 

Bundgaard, H. and M. Johansen. 1982. Kinetics of hydrolysis of tpHiaJe (An ureid J-Mannich base with platelet antiaggregant activity) in aqueous solution and in plasfon ]. Pharm. Chem., Sci. Ed. 10 139-145. 

Many kinds of enzymes with different substrate specificities are involved in hydantoin hydrolysis. Ogawa et al. [10] found two hydantoin-hydrolyzing enzymes in Blastobacter sp. A17p-4. These enzymes were purified to homogeneity and characterized (Table 1). One hydrolyzed dihydropyrimidines and 5-monosubstituted hydantoins to the corresponding AT-carbamoyl amino acids. Since the hydrolysis of 5-substituted hydantoins by this enzyme was D-stereo-specific, this enzyme was identified as D-hydantoinase, which is identical with dihydropyrimidinase. The other one preferably hydrolyzed cyclic imide compounds such as glutarimide and succinimide more than cyclic ureide compounds such as dihydrouracil and hydantoin. Because there have been no reports on enzymes which show same substrate specificity as this enzyme, it is considered to be a novel enzyme, which should be called imidase [10]. 

Addition of isocyanates and isothiocyanates, followed by hydrolysis, yields amides, thioamides,274-277 or ureides of j8-ketoacids 82 and 83 are examples of typical intermediates in this reaction. 

Further confirmation of the structures assigned is nevertheless desirable, especially for those ureides whose detailed chemical properties are only little known. Since the periodate-oxidation method (which has been used so effectively by Todd and coworkers - in the determination of glycosyl ring structures) was of little value in this case (see Table II), some other approach to this problem, such as methylation followed by hydrolysis, should be investigated. 

Our results provide a basis for predicting the relative hydrolytic tendencies of the cyclic ureides 25-32. Susceptibility toward hydrolysis is expected to increase roughly as Vs becomes more positive. However, we anticipate that the number of C=0 groups in the molecule is also an important factor in determining its reactivity, since each of them is a potential site for nucleophilic interaction. 

Early work" " on the reaction of 2-substituted amino-3-amino-pyridines (54) with alloxan (55) in neutral solution has been corrected. The initial yellow product from the condensation is a ureide of formula 56, which readily rearranges to the colorless spirohydantoin 57 on treatment with acid or base. Tire isomeric pyridine 49 yields a second series of ureides and hydantoins. When 2,3-diaminopyridine itself is used, a mixture of products is obtained in which the 3-oxo compound 56 (R = H) predominates over its 2-oxo isomer. Alkaline hydrolysis followed by decarboxylation and methylation served to confirm the orientation (see Section II2B). If the reaction with alloxan is carried out in alkaline solution, the only product obtained is the 3-oxo-2-carboxylic acid." ... 

Treatment of the ureide 129 or its 4-methyl derivative with diazomethane results in the formation of the monomethylated, and then the dimethylated spirohydantoin 131. This also demonstrates the ease of cyclization of these ureido derivatives. Similar reactions occur with 1,2-dihydro-2-oxo-3-ureidopyrido[2,3-h]pyrazine. If the methylated hydantoin 131 is treated with nitrous acid, the 1-nitroso compound 132 is formed. On alkaline hydrolysis this yields the 2-methylamino compound 133. The corresponding reactions with the 2-oxo isomer of 131 failed as... 

Alloxan, C4H2N2O4, is shown by its hydrolysis to be the ureide of mesoxalic acid —... 

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 ... 

Hexobarbital is prepared by reacting together methyl urea and methyl-a-methyl-a-cyclo-hexen-1-yl-a-cyano acetate when an open-chain ureide is formed as an intermediate with the elimination of a molecule of methanol. This upon hydrolysis affords spontaneous closure of the ring thereby resulting into the formation of hexobarbital. 

Example. Phenobarbital [Gardinal ]. The following scheme vividly explains the base hydrolysis of phenobarbital wherein the cyclic ureide ring (in barbiturate) undergoes cessation. Besides, it may also be seen that the aforesaid cessation strategically takes place either between C-l/C-2 and/or C-l/C-6 locations in the structure of barbiturate. However, the cleavage between C-1 and C-6 is considered to be the most preferred pathway prevailing in the ionized barbiturates , such as aqueous solutions of sodium salts. 

Another enzyme, barbiturase, which catalyzed the hydrolysis of barbituric acid to urea and malonic acid (Fig. 13), has been partially purified and freed of urease activity. The mechanism involved in this reaction has not yet been established. It seems most plausible that the initial cleavage would yield a half ureide of malonic acid, since it is not likely that a single enzyme could simultaneously cleave two linkages in the same molecule. So far there has been no evidence to support the formation of a half ureide of malonic acid. 

When human urine was treated with ethyl ether, the majority of carbonyls were able to be detected in the aqueous fraction, with only a small amount in soluble in the organic (ethyl ether) phase. Further, when human urine was distilled by steam, a large amount of carbonyls fractionated into the non-volatile fraction. However a small but detectable amount remained in the volatile fraction. Importantly, it is generally recognized that most simple carbonyls are soluble in ethyl ether and volatiles. By contrast, ureides are insoluble in ethyl ether and not volatile. Base on these facts, we hypothesized that many carbonyls in urine might be derivatized in vivo with urea. Furthermore, these considerations imply that DNPH analysis of total urinary carbonyls may partly reflect hydrolysis of ureides as well as free dicabonyls. 

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