5-Bromo-uracil

L. Pichat, J. Godbillon, and M. Herbert, Lithiation par le n-butyllithium de bromo-5 uracile nucleosides silylds. Preparation de methyl ( C-5) et methyl ( -6) uridine, de desoxy-2 -ethyl (l C-5) uridine et desoxy-2 -ethyl ( C-ti) uridine, B H. Soc. Chim. Fr. 2712 (1973). 

Orotic acid readily forms dimers even when irradiated in liquid medium [582, 583]. 5-Bromouracil (5-BrU) in DNA is dehalogenated, rather than forming cyclobutane-type dimers. Such DNA derivatives are more sensitive to ultraviolet irradiation than normal DNAs [584-594], Irradiation of 5-bromo-uracil and derivatives in aqueous medium produces 5,5 -diuracil [590, 591]. However, derivatives such as 3-sbutyl-5-bromo-6-methyluracil have been reported to yield cyclobutane dimers either by irradiation of frozen aqueous solutions, or by catalysis with free radical initiators, such as aluminium chloride, ferric chloride, peroxides or azonitriles [595]. 5-Hydroxymethyluracil is reported to dimerize very slowly in frozen water at 2537 A [596]. The fundamental research in the photochemistry of the nucleic acids, the monomeric bases, and their analogues has stimulated new experiments in certain micro-organisms and approaches in such diverse fields as template coding and genetic recombination [597-616]. 

Campbell JM, Schulte-Frohlinde D, von Sonntag C (1974) Quantum yields in the UV photolysis of 5-bromo-uracil in the presence of hydrogen donors. Photochem Photobiol 20 465-467 Chapman JD (1984) The cellular basis of radiotherapeutic response. Radiat Phys Chem 24 283-291 Chatterjee M, Mah SC, Tullius TD, Townsend CA (1995) Role of the aryl iodide in the sequence-selective cleavage of DNA by calicheamicin. Importance of thermodynamic binding vs kinetic activation process. J Am Chem Soc 117 8074-8082 Chaudry MA, Weinfeld M (1995) The action of Escherichia coli endonuclease III on multiply damaged sites in DNA. J Mol Biol 249 914-922... 

Photoreactions of Thymines etc. - The uracil derivative (184) undergoes photochemical transformation when it is irradiated in frozen benzene with added trifluoroacetic acid. Cyclodimerization occurs yielding derivatives of diaza-pentacyclo[6.4.0.0 . 0 . 0 ]dodecane derivatives such as (185). Other addition products (186) and (187) were also identified. The photoreduction of 5-bromo-uracil (188) has been studied. ... 

Branched-chain sugar nucleosides of apiose have been synthesized from the derivatives (65) and (66) and the TMS derivatives of uracil, thymine, 5-bromo-uracil, or 5-iodo-uracil using tin(iv) chloride catalysis. The synthesis of... 

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). 

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. ... 

The Suzuki coupling of 44 was utilized to prepare 5-substituted uracils as potential antiviral agents [21, 22]. Adduct 45, derived from 44 and 2-bromo-3-methylthiophene, was transformed to the corresponding uracil 46 via acidic hydrolysis. Conveniently, reversal of the coupling partners also resulted in formation of adduct 45, assembled from the Suzuki coupling of 5-bromo-2,4-di-f-butoxypyrimidine (43) and 3-methyl-2-thiopheneboronic acid. 

CASRN 314-40-9 molecular formula C9Hi3BrN202 FW 261.12 Soil Metabolites tentatively identified in soil were 5-bromo-3-(3-hydroxy-l-methylpropyl)-6-methyluracil, 5-bromo-3-5ec-butyl-6-hydroxymethyluracil, 5-bromo-3-(2-hydroxy-l-methylprop-yl)-6-methyluracil, and carbon dioxide. The presence of uracil products suggests that bromacil was degraded via hydroxylation of the side chain alkyl groups. In the laboratory, 25.3% of C-bromacil degraded in soil to carbon dioxide after 9 wk but mineralization in the field was not observed. The half-life of bromacil in a silt loam was 5-6 months (Gardiner et al, 1969). 

The uracils with herbicidal activity do not necessarily contain 5-halo substituents. 3-Cyclohexyl-5-methyluracil [354] (XLIV), l,3-di-isopropyl-6-methyl-uracil [352] (XLV) and 3-s-butyl-5-thiocyanato-6-methyluracil [353] (XLVI), for example, are cited as having this type of activity. 3-Butyl-6-methyluracil (XLlllc) possesses interesting selective activities. For instance, this pyrimidine kills many annual weed species without damage to peas and peanuts, even when applied at twice the concentration needed to kill the weeds [346]. On the other hand, the related 5-bromo derivatives, such as (XLlIlb), are useful as industrial herbicides where it is desirable to kill all plants [346]. 

At a dose of 200 mg/kg, 5-bromo-5,6-dihydrothymine (LXXXVI) retards the tumour growth of Crocker sarcoma [658]. 5-Fluorodihydrouracils (LXXXVII X = F, R = H, alkyl) are useful as germicides [659]. 5-Thiocyanato-5,6-dihydro-uracil (LXXXVII X = -SCN, R = H) shows a high level of antibacterial activity [660]. 

Uracils and related pyrimidines undergo oxidative addition to the 5,6-double bond, and the reaction with a number of oxidants to form 5,6-epoxides and 5,6-diols was discussed in CHEC-II(1996) <1996CHEC-II(6)93>. Oxidative halogenation can also occur <1996SC3583, 1998NN1125>, as shown by the formation of 5-bromo-5,6-dihydro-6-methoxyuracil 100 from uracil 99 by treatment with a mixture of potassium bromate and potassium bromide in the presence of Dowex ion-exchange resin in methanol <1996SC3583>. 

D-ribofuranosyl)-uracil-5-yl] disulfide Hydrogen-bonded complex of 2 -deoxyguanosine and 5-bromo-2 -deoxycytidine C-3 C-2 endo C-2 endo C-4 0.454 0.540 102... 

The introduction of a masked uracil moiety onto the pyridine core was achieved in the reaction of 3-tributylstannylpyridine with 5-bromo-2,4-bis(trimethylsilyloxy)pyrimidine (7.26.) The coupling proceeded in the presence of bis(triphenylphosphine)palladium dichloride to give the desired product in 42% yield (c.f 7.13.),37... 

Boyarchuk and Volkenshtein354,355 have studied the IR spectra of the crystals of 5-bromo-l-methyl-, 5-bromo-3-methyluracil, and 1-methylthymine and discussed the effect of the electronegative substituents in the pyrimidine ring on the potential energy curve of dimeric hydrogen-bonded complexes of uracil derivatives. Features of the IR spectrum of 5-bromo-l-methyluracil crystal suggested that the stability of the lactim form 28 increases owing to the influence of the substituents. 

The results presented in Table XIX are thus not very unsatisfactory. It would be interesting to calculate the changes in tautomeric equilibrium of uracil on 5- or 6-halo-substitution, particularly the 5-bromo-compound. 

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],... 

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