2, 6-Diaminouracil

Caution This procedure should be conducted in a good hood. The slurry is stirred while being heated on a steam bath, and solid sodium hydrosulfite is added until the red color of the nitroso compound is completely bleached (Note 5). Then an additional 30 g. of sodium hydrosulfite is added the light tan suspension is stirred with heating for 15 minutes more and is then allowed to cool. The dense diaminouracil bisulfite is filtered from the cooled solution, washed well with water, and partially dried. 

The crude product is readily purified by conversion to its hydrochloride salt. The bisulfite salt is transferred to a wide-mouthed 1-1. flask, and concentrated hydrochloric acid is added until the consistency of the resulting mixture is such as to permit mechanical stirring (100 to 200 ml. of acid). The slurry is heated on a steam bath with stirring for 1 hour Hood ). The tan diaminouracil hydrochloride is filtered on a sintered glass funnel, washed well with acetone, and vacuum-dried over phosphorus pentoxide. The yield of diaminouracil hydrochloride is 104-124 g. (68-81%) (Notes 6 and 7). 

If placed in a preheated melting-point block, the product melts with decomposition in the range 300-305°. Diaminouracil hydrochloride in 0.1 N hydrochloric acid has a well-defined absorption peak at 260 mju, log e = 4.24. Satisfactory analyses for nitrogen and chlorine are difficult to obtain with this type of compound although good results are obtained for carbon and hydrogen. 

The procedure for the formation of diaminouracil bisulfite is slightly modified from that of Cain, Mallette, and Taylor,2 which in turn is derived from preparations of Bogert and Davidson,8 and Traube.4 The sulfate salt may be formed in lower yield than the hydrochloride described here by dissolving the bisulfite salt in aqueous base and precipitating with sulfuric acid.8-4 The hydrochloride is appreciably soluble in water, while the sulfate salt is only slightly soluble. 

Bredereck, Hennig, and Pfleiderer 6 describe a method for the formation of diaminouracil from uric acid which involves acetylation and subsequent hydrolysis of the acetyl derivative. This preparation was attempted on a large scale by the submitters without success (even when the acetylation step was carried out twice on the same material). 

Treatment of certain uracils, such as l-methyl-6-amino-,3-methyl-6-amino- or 1,3-dimethyl-5,6-diaminouracil with formaldehyde gave compounds containing between 10—30 per cent by weight of reversibly bonded formaldehyde. These new compounds were claimed to be useful as disinfectants or antiseptics [413]. 

The Schiff base derivative 65, prepared from the respective 5,6-diaminouracil 63 and aldehydes 64, can be converted into the C-8 substituted xanthines 66 through an oxidative cyclization with m-chloroperbenzoic acid <99H29>. 

Diaminouracil bisulfite, 37, 16 Diaminouracil hydrochloride, 37,15 Diamylamine, 32, 2 Di-n-amyl ketone, 31, 71... 

Starting from 5,6-diaminouracils and boronic acid derivatives, some purine analogues were prepared, e.g. (60) (67AF607, 70CR(C)(27l)754). 

The oxidation of 5,6-diaminouracil provides a good example of the use of thin-layer spectroelectrochemistry to determine the rate constant of an electrogenerated intermediate [34]. The reaction sequence is as follows ... 

Figure 3.15 Thin-layer chronoabsorptometry of electrogenerated reactant in an optically transparent thin-layer electrode. (A) Variation of the absorbance of the intermediate species (A320 nm) during the electrooxidation of 10 mM 5,6-diaminouracil in Mcllvaine buffer pH 5 at 0.35 V. Arrow indicates time at which all 5,6-diaminouracil has been electrolyzed. (B) Kinetic plot of time versus the absorbance at 330 nm of intermediate species. Absorbance data were taken from curve A. Setting time = 0 at the point where the concentration of 5,6-diaminouracil was zero. [From Ref. 34.]...

On the basis of the literature data [53,56,57] of the synthesis of dihydrodiazepine and dihydrotriazepine derivatives by chalcone reaction with diamines such as 1,3-dimethyl-5,6-diaminouracil and diaminotetrazole, the suggested structure of the products of these interactions was later proved to be erroneous [61, 62,63]. Analysis of the reaction paths actually observed under such conditions is presented in Sect. 4.5. 

As in the case of 0-PDA, ambiguity in the structure of the products is also observed in the reaction of diaroylethylenes with heterocyclic 0r /i0-diamines. For example, one of the products of l,3-dimethyl-5,6-diaminouracil 55 condensation with 4,4-dimethyldibenzoylethylene 190 at first was considered to have the structure of diazepine 196 [136] (Scheme 4.54). 

The readiness of amidine formation in reactions of lactim ethers with amines has been used in the synthesis of 8,9-poly methylene-purines.97 Attempts to condense 2 (R = Me) with uramil and l,3-dimethyl-4,5-diaminouracil failed.97 Lactim ethers were also found not to react with derivatives of 5-aminouracil, probably due to the low basicity of the latter.97... 

A transribosylase which exchanges the hypoxanthine of inosine with adenine, guanine, xanthine, thymidine, 4,5-diaminouracil, 5-bromouracil, and 4,6-diaminouracil has been found in Escherichia coli. - ... 

Diaminouracil derivatives 599 react with cinnamic acids (R = NO2, OCH3, Br), in the presence of EDCCl to give carboxamido compounds 600. ... 

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