Uracils barbituric acids

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, Barbituric acid deriv.s From hydrogen cyanide... 

Tsao (1940). Pollen from Antirrhinum majus. Asparagine, urea nitrate, urea,. sodium ureate, choline, adenine, guanine, uracil, barbituric acid, sodium nucleate, Ihiamine, riboflavin, pyridoxine, niacin, niacinamide, inositol, and p-amino-benzoic acid. 

Similarly Klotzer [24-26] has used the same two ethers of hydroxyurea for the preparation of iV-alkoxy and A-hydroxy derivatives of uracil, barbituric acid, cytosine, thymine, and 5-fluorouracil by condensation reactions catalyzed with sodium ethoxide. Thus, for example, the reaction of N-benzyloxyurea with ethyl cyanacetate gave l-benzyloxy-6-aminouracil which was debenzylated by heating it with hydrogen bromide in acetic acid [24]. In syntheses of 1- and 3-hydroxycytosine [24] and of l-hydroxy-5-fluorouracil the O-benzyl protective group was removed by hydrogenolysis in presence of palladium [25, 26]. 

It is the parent substance of a group of compounds which includes cytosine, thymine and uracil, which are constituents of nucleic acids and barbituric acid and its derivatives, which are important medicinally. 

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). 

There are many synthetic routes to alloxan. Probably the best is direct oxidation of barbituric acid (1004 R = H) with chromium trioxide (5208(32)6) but it may be made from barbituric acid via its benzylidene derivative by direct or indirect oxidation of uric acid from 5-chlorobarbituric acid (1004 R = C1) by nitration or from 5-nitrobarbituric acid (1004 R = N02) by chlorination, both via the intermediate (1005) (64M1057) or by permanganate oxidation of uracil (1006) under carefully controlled conditions (73BSF1167). 

The one-pot MCR of methylene active nitriles 47 has been used in the synthesis of both pyrano- and pyrido[2,3-d]pyrimidine-2,4-diones in a single-mode microwave reactor [90]. Microwave irradiation of either barbituric acids 61 or 6-amino- or 6-(hydroxyamino)uracils 62 with triethyl-orthoformate and nitriles 47 (Z = CN, C02Et) with acetic anhydride at 75 °C for 2-8 min gave pyrano- and pyrido[2,3-d]pyrimidines in excellent yield and also provided a direct route to pyrido[2,3-d]pyrimidine N-oxides (Scheme 27). 

Hayaishi O, A Kornberg (1952) Metabolism of cytosine, thymine, uracil and barbituric acid by bacterial enzymes. J Biol Chem 197 717-732. 

Although uracil possesses a structure very similar to that of barbituric acid, it is a much weaker acid (pKa 9.38) [368]. Also unlike barbituric acid, it is not... 

Both 2- and 4-hydroxyquinazolines 22 and 23 and 2-hydroxyperimidine 24 exist predominantly in the oxo forms in solution, and the same applies to uracil 25 which exists primarily as the dioxo form <2006AHC(91)1>. With barbituric acid [2,4,6(lf/,3f/,5//)-pyrimidinetrione] 26, the trione form is similarly predominant <2006IJQ(106)1338>. 

An amino or hydroxy group facilitates 5-bromination even in aqueous solution. A -bromosuccinimide (NBS) and molecular bromine are the commonest reagents used. In uracils, cytosines, and barbituric acids, products of both addition and substitution can be identified in aqueous solution, and 5,5-dibromo products are common. In the bromination of uracils, addition products, including covalent hydrates, form rapidly, and the acid-catalyzed dehydration step to 5-bromouracils is much slower. Cytosine and related compounds behave similarly <1994HC(52)1, 1996CHEC-II(6)93>. 

Supplement 1936 3458-3793 Picrolonic acid, 51. Hydantoin, 242. Uracil, 312. Indigo, 416. Barbituric acid, 467. Alloxan, 500. 

Considering tridentate sites, 2,6-diaminopyridine and uracil are complementary single site groups (see Sections 9.4.2 and 9.4.3 below). On the other hand barbituric acid (BA) and 2,4,6-triaminopyrimidine (TAP) or -triazine (TAT) are Janus molecules containing two identical recognition sites while 168 is plerotopic by virtue of its two complementary sites (see Section 9.4.4). 

Barbituric acid reacted with bromine to give in turn the 5-bromo and 5,5-dibromo derivatives. Subjection of the latter to base-induced dehydro-bromination or reduction converted it back into the monobromo species. iV-Alkylbarbituric acids behaved similarly [62HC(16)172 74JCS(P1)2095]. Uracil was brominated in aqueous solution initially in much the same way. A 5-bromo derivative was formed at first, and then (38), apparently a consequence of addition of hypobromous acid. Although quite stable, (38) can be converted back into the monobromo derivative when boiled with mineral acid. 1,3-Dimethyluracil, substituted at C-6 by chlorine, bromine, or iodine, was both mono- and di-brominated at C-5 by bromine (81S701). Cytosine and related compounds behaved similarly [59JOC11 90AHC(47)325],... 

Being an oxidizing agent, CsS04F was used to transform primary alcohols as well as aromatic aldehydes to the corresponding acyl fluorides (equation 180)309. Various N-substituted uracils and barbituric acid derivatives form, in contact with this reagent, 5-fluoro-6-alkoxyuracils accompanied by some 5,5-difluoro derivatives (equation 181)310. 

Barbituric acid and derivatives resemble uracils in their preference for... 

As in the case of electrochemical reduction, the photochemical transformation of 5-fluorouracil derivatives differs from that of the other 5-halogeno uracils. The primary photoproduct of 5-fluorouracil, its glycosides and poly(5-FU) is the photohydrate. However, at shorter wavelengths of irradiation, e.g. 254 nm where the photohydrate exhibits absorption, there is elimination of HF from the 5,6 bond and formation of barbituric acid 129 13I>. There is also some evidence for acetone photosensitized formation of cyclobutane dimers of 5-fluorouracil132), as well as dimer formation in irradiated poly(5-FU)133>. 

The analogous six-membered heterocyclic substrates also exhibit a complex behavior. Aminomethylation of the uracils 71 occurs on the N atom in position 3, although the reaction with formaldehyde alone shows an equilibrium constant for hydroxyme-thylation in position 1 which is about twice as much as the value obtained for the reaction at position 3. By contrast, in barbituric acid derivatives 72 (X = O), po.sition 5 is the most reactive when unsubstituted. Otherwi.se, the reaction is directed toward the 1 or the 3 position. " When present, the imine NH group (72, X = NH) is the last moiety to undergo attack. 

Maleic and Phthalic Hydrazides, Barbituric acid Deriv.s, Uracil Deriv.s... 

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