Uracil reaction

Excitation of a ground state UH+ or U" can be easily eliminated as the responsible process for uracil photohydration. In the first place, the midpoint of the uracil curve in Figure 7, at about 4.5 does not agree with either of the known pK values of uracil, Reactions 8a and 8b. 

Two routes are known by which the free base, uracU, can enter the ribonucleotide pool. One proceeds by the sequential actions of uridine phosphorylase and uridine-cytidine kinase (reactions 5 and 6, Fig. 12-1) this route is discussed below. The other route is by way of a single-step phosphoribosyltransferase reaction specific for uracil (reaction 4, Fig. 12-1) ... 

Reaction of / fZ-amyl alcohol with urea in the presence of sulfuric acid gives a monoalkylated urea (61,62). Monoalkyl ureas are used to prepare uracil derivatives which are useful as herbicides, fungicides, and plant growth regulators (61). 

The direct formation of dipyrimidin-5-yl sulfides occurs on treatment of appropriate 5-unsubstituted pyrimidine substrates with sulfur mono- or di-chloride. Thus, reaction of uracil (83 R = H) with sulfur monochloride in boiling formic acid gives diuracil-5-yl sulfide in good yield sulfur dichloride gives a poor yield. Simple derivatives of uracil and barbituric acid undergo similar reactions but not cytosine, isocytosine, 2,4-bismethylthiopyrimidine or pyrimidine-4,6-dione (59). The mechanism is unknown (72AJC2275). 

In contrast, the photochemistry of uracil, thymine and related bases has a large and detailed literature because most of the adverse effects produced by UV irradiation of tissues seem to result from dimer formation involving adjacent thymine residues in DNA. Three types of reaction are recognizable (i) photohydration of uracil but not thymine (see Section 2.13.2.1.2), (ii) the oxidation of both bases during irradiation and (iii) photodimer formation. 

As mentioned above (Section 2.13.2.1.3), bipyrimidine photoproducts can arise, probably by reaction between two radicals. Thus, irradiation of an aqueous solution of 5-bromouracil (ill R=Br) in the absence of oxygen produces a variety of products including uracil, barbituric acid, 5-carboxyuracil (111 R = CO2H), several non-pyrimidine compounds and, as a stable end-product, the biuracil (114 R = H). A similar product (114 R = Me) is formed from 5-bromo-l,3-dimethyluracil (ilS). When two such related uracil derivatives are irradiated together, a mixed bipyrimidine product is formed, inter alia (B-76MI21302). 

Uracil reacts with hydrazine to give pyrazol-3(2if)-one (944) and urea N-methyl- and dimethyl-hydrazine behave similarly to give the 2-methyl- and 1,2-dimethyl derivatives. The reactions of hydrazines with uridine and related nucleosides and nucleotides is well studied (67JCS(C)1528). The tautomerism and predominant form of uracil are discussed in Section 2.13.1.8.4. 

Having a 5-methyl group, thymine is not nitrated or halogenated normally, but with aqueous bromine it does give the dihydropyrimidine (948) (25JBC(64)233) its other reactions parallel those of uracil although its behavior on irradiation is somewhat different (Section 2.13.2.1.4). 

For unsubstitUted or lower alkylated dioxotriazines, it is advantageous to cyclize semicarbazones by sodium ethylate in ethylene glycol as described by Chang and XJlbricht. In this reaction 6-aza-uracil is obtained in 66% yield. The procedure was used for the preparation of labeled 6-azauracil ° and later for the synthesis of a number of 6-alkyl derivatives including 6-azathymine. °... 

Azauridine was also synthesized using the knowledge of the course of alkylation of 6-azauracil 2-methylmercapto derivatives (e.g., Section II,B,4,b). The 1-ribofuranosyl derivative obtained by reaction of the mercury salt of the 2-methylmercapto derivative with tri-O-benzoyl-jS-D-ribofuranosyl chloride on removal of the methyl-mercapto and then benzoyl groups yielded crystalline 6-azauridine, The main difference between uracil and 6-azauracil nucleosides consists in the preparation of cyclic nucleosides. It is known that uridine can be readily converted to cyclic nucleosides by the reaction of 2 (50-O-mesyl derivatives with nucleophilic agents, Analogous... 

Direct bromination readily yields the 6-bromo derivative (111), just as with uracil. Analogous chlorination and iodination requires the presence of alkalies and even then proceeds in low yield. The 6-chloro derivative (113) was also obtained by partial hydrolysis of the postulated 3,5,6-trichloro-l,2,4-triazine (e.g.. Section II,B,6). The 6-bromo derivative (5-bromo-6-azauracil) served as the starting substance for several other derivatives. It was converted to the amino derivative (114) by ammonium acetate which, by means of sodium nitrite in hydrochloric acid, yielded a mixture of 6-chloro and 6-hydroxy derivatives. A modified Schiemann reaction was not suitable for preparing the 6-fluoro derivative. The 6-hydroxy derivative (115) (an isomer of cyanuric acid and the most acidic substance of this group, pKa — 2.95) was more conveniently prepared by alkaline hydrolysis of the 6-amino derivative. Further the bromo derivative was reacted with ethanolamine to prepare the 6-(2-hydroxyethyl) derivative however, this could not be converted to the corresponding 2-chloroethyl derivative. Similarly, the dimethylamino, morpholino, and hydrazino derivatives were prepared from the 6-bromo com-pound. ... 

It may be said in conclusion that the reactivity of position 5 (i.e., 6 of the triazine ring) is similar to that of uracil. The only difference seems to be in the failure to prepare 5-nitro-6-azauracil although this reaction proceeds readily with uracil. 

On reaction with aged phosphoroxychloride, 6-azauracil formed 3,5-dichlorotriazine (117) in only a 10% yield. " A somewhat higher yield (30%) was obtained from the reaction of 6-bromodioxotriazine which gave 3,5,6-trichloro-l,2,4-triazine. Similar reactions take place much more readily with uracil and in better yield. " Thus,... 

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