1,3-Dimethyluracils

The cross-coupling of two alkenes also takes place. Alkenes such as acrylate react regioselectively with 1,3-dimethyluracil (290) to afford 5-(l-alkenyl)ura-cils such as 291 in a high yield[260]. 

Methyl and 6-methyl-5-n-propyl substituted 2,4-dimethoxy-pyrimidines react with methyl iodide, as does the simple dimethoxy compound, to give methoxypyrimidones, but the 6-chloro-2,4-dimethoxy derivative (47) is affected only at 100°, when it gives 4-chloro-1,3-dimethyluracil (48). ... 

The 1,3-dimethyluracil derivative 109 with two reactive centers reacts with 1,2,4-tiiazine 4-oxide 58 only at the uracil fragment to afford compound 110 (96MC116). 

It has been reported that nickel catalyzed the reactions of 6-amino-1,3-dimethyluracil with substituted alkynylketones in water to give substituted 2,4-dioxopyrido[2,3-f/ pyrimidine derivatives in quantitative yields at room temperature (Eq. 4.70).134 The products have potential pharmacological and biological activities. The reaction may have proceeded through an ionic process. 

The photodimerization of pyrimidine bases continues to attract attention, undoubtedly because of the biological implications of such transformations. 1,3-Dimethyluracil affords four [ 2 + 2] dimers on irradiation in an ice-matrix.192 Analogous dimeric species have been obtained under a variety of conditions from dimethylthymine,193 tetramethyluracil,194 5-methyloro-... 

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

The availability of different metal ion binding sites in 9-substituted purine and pyrimidine nucleobases and their model compounds has been recently reviewed by Lippert [7]. The distribution of metal ions between various donor atoms depends on the basicity of the donor atom, steric factors, interligand interactions, and on the nature of the metal. Under appropriate reaction conditions most of the heteroatoms in purine and pyrimidine moieties are capable of binding Pt(II) or Pt(IV) [7]. In addition, platinum binding also to the carbon atoms (e.g. to C5 in 1,3-dimethyluracil) has been established [22]. However, the strong preference of platinum coordination to the N7 and N1 sites in purine bases and to the N3 site in pyrimidine bases cannot completely be explained by the negative molecular electrostatic potential associated with these sites [23], Other factors, such as kinetics of various binding modes and steric factors, appear to play an important role in the complexation reactions of platinum compounds. 

When 1,3-dimethylorotic acid (233) was heated at 198 °C in benzyl bromide for 3h, 6-benzyl-1,3-dimethyluracil (236) was formed in 10% yield together with the product of decarboxylation, 1,3-dimethyluracil (235). This finding supports the involvement of a carbon-6-centred nucleophilic intermediate in the decarboxylation reaction a carbanion (234) could be involved or a carbene (237)." ... 

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

Other interesting examples of intermolecular N-C-N transfragment replacement are the ones being found when 1,3-dimethyluracil (113, R = R" = H) and several of its C-5/C-6 mono-substituted or C-5,6 di-substituted derivatives react with different 1,3-ambident nucleophiles (77JHC537 84H(2)89). Reaction of (113, R = R" = H) with guanidine gives isocytosine 115 (R = R = H) in reasonable-to-good yields. 

A theoretical interpretation of this different behavior is not yet available. In any case, the most obvious possibility that all sulfenyl halides attack initially at the nitrogen as the most electron abundant site 160), and that the CF3S compound is then converted to the more stable 5-substi-tuted product, is to be disregarded, since 1,3-dimethyluracil, with both nitrogen atoms blocked, gives with CF3SCI the 5-substituted compounds in high yield. 

The addition of organometaiiics to unactivated pyrimidines normally produces unstable dihydro derivatives which readily oxidize back to the pyrimidine oxidation level, although successful conjugate addition to pyrimidinone derivatives can occur. Thus, the addition of lithium trimethylsilyldiazomethane [TMSC(Li)N2] to 1,3-dimethyluracil 418 occurred at the 6-position to produce a mixture of the two pyrazolo[4,3-rf]pyrimidine-5,7-diones 419 and 420, where the initial addition had been accompanied by cyclization <1997T7045>. 

Silicon nucleophiles have also been investigated with uracil derivatives, and thus the addition of dimethylphe-nylsilyllithium to 5-substituted 1,3-dimethyluracils 459 was found to give stable products of addition at the 6-position 460, although products arising from addition at the 5-position were also observed with some 6-substituted derivatives <1998H(48)2601>. 

Irradiation of air-free solutions of pyrimidines can give products resembling some of those produced by ultraviolet light, but probably by a quite different mechanism. Irradiation of 1,3-dimethyluracil with 200 kV X-rays produces not only the expected 5,6-glycol, but also 6-hydroxyl-l,3-dimethyl-5-hydrouracil, the same isomer as the UV-produced hydrate discussed elsewhere in this chapter. The yield of the hydroxy compound is low, G = 0.35 molecules/100 eV absorbed. Cytosine glycol is formed in gamma-irradiated cytosine solutions, and this deaminates completely to the uracil glycol. These products are probably formed by addition of an OH to the 6-position of the pyrimidine and then dismutation of hydroxy radical. The major products formed in the radiolysis of air-free solutions of pyrimidines or purines have not yet been identified. 

Rare C-nucleosides were observed via cyclocondensation of the glycosyl enaminone 508 with 6-amino derivatives of uracil, thioxouracil, and 1,3-dimethyluracil to give the 7-(2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl)pyrido[2,3-r/ pyr-imidine derivatives 509-511, respectively (Equation 40) <1996GAR71>. 

Pyrimidine-2,4(1//,3//)-dione (uracil) does not react with 7V-fluorobis(trifluoromethylsul-fonyl)amine (Id) at 22 C in acetic acid, probably due to its insolubility, but when heated at 45 CC for 12 hours it gives a difluorinated acetoxy derivative which could not be isolated.114 1,3-Dimethyluracil reacts with two equivalents of 1 d at 22 °C to give 6-acetoxy-5,5-difluoro-l, 3-dimethyl-5,6-dihydrouracil in 85% yield while with one equivalent of Id 5-fluoro-l, 3-dimethyl-uracil (mp 132-134°C) is also obtained.114... 

Comparatively little was previously known about photoaddition reactions to unsaturated substrates of different structure. Elements of water add to the A5 6 in the pyrimidine ring of 1,3-dimethyluracil (CXXXYII)301 and probably of nucleosides and nucleotides of cytosine261,307 upon irradiation with ultraviolet light to give products such as CXXXVIII. CXXXVIII reverts to CXXXVII under the influence of acid, alkali, or heat. 

N-, 0-, and S-heterocyclic ligands also form [Os(NH3)5 t)2-(C,C)-L ]2+ complexes [L = 2,6-lutidine, 2,6-lutidinium, pyridinium, N-methylpyridinium, and lV-methyl-4-picolinium (85, 167), NJV -dimethylimidazolium (90), pyrrole (90, 179), IV-methylpyrrole (90, 179), thiophene (90,179), furan (90,179), and 1,3-dimethyluracil (72, 73)]. On oxidation to Os(III), arene ligands are rapidly lost from the coordination sphere, or in the case of the substituted arene ligands with good a donors, rapid linkage isomerization reactions occur (Section V,D). 

From the relative kinetic acidities of the 0-7 and 0-8 protons of 1,3-dimethyluracil dication, Poulter and Anderson331 have concluded that the monocation derived from protonation at 0-8 is considerably more stable (as least 3.9 kcal/mole) than its 0-7 (38) protonated isomer. 

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