Pyrimidine relative aromaticity

Magnetic susceptibility anisotropy has been used for the estimation of relative aromaticity of some azines in comparison with benzene (77JCS(P2)897). If the extent of ir-electron delocalization for benzene is taken as 1.0, the corresponding values for azines are pyridine 0.7, pyridazine 0.7, pyrimidine 0.5, and 1,3,5-triazine 0.3. 

Magnetic susceptibility anisotropy has been used to estimate relative aromaticities of some azines <1977JOC897>. If the extent of -electron delocalization for benzene is taken as 1.0, the corresponding values for azines are pyridine 0.7, pyridazine 0.7, pyrimidine 0.5, and 1,3,5-triazine 0.3. Another quantitative magnetic index is the exaltation of the total magnetic susceptibility (A). All aromatic systems reveal large A values, whereas for nonaromatic compounds A is close to zero and it is assumed that aromaticity increases with A. For six-membered monocycles the following values of A have been reported (in units of cm3 mol-1 x —106) benzene (17.9), pyridine (18.3), pyridazine (8.7), pyrimidine (18.2), pyrazine (12.7), l-ethyl-2-pyridone (13.0), and 1,3,5-triazine (19.0). 

Both pynmidme and purine are planar You will see how important this flat shape is when we consider the structure of nucleic acids In terms of their chemistry pyrimidine and purine resemble pyndme They are weak bases and relatively unreactive toward elec trophilic aromatic substitution... 

The pyrimidine ring system is planar, while the purine system deviates somewhat from planarity in having a slight pucker between its imidazole and pyrimidine portions. Both are relatively insoluble in water, as might be expected from their pronounced aromatic character. 

A wide variety of other heterocyclic ring systems can conceivably serve as the conjugated backbone in nonlinear organic molecules. We will give examples from preliminary work on two of these, the thiazole and pyrimidine heterocycle derivatives 65-72 in Table VIII. These two heterocycles were chosen because the appropriate haloderivatives are commercially available as starting materials for nucleophilic aromatic substitution. The pyrimidine derivatives are of particular interest since their absorption edges ( 400 nm) are shifted hypsochromically an additional 30 nm relative even to the pyridines. 

The purines and pyrimidines are relatively stable compounds with considerable aromatic character. Nevertheless, they react with many different reagents and, under some relatively mild conditions, can be completely degraded to smaller molecules. The chemistry of these reactions is complex and is made more so by the fact that a reaction at one site on the ring may enhance the reactivity at other sites. The reactions of nucleic acids are largely the same as those of the individual nucleosides or nucleotides, the rates of reaction are often influenced by the position in the polynucleotide chain and by whether the nucleic acid is single or double stranded. The reactions of nucleosides and nucleotides are best understood in terms of the electronic properties of the various positions in the bases.26 33 Most of the chemical reactions are nucleophilic addition or displacement reactions of types that are discussed in Chapters 12 and 13. 

Fluorescence assays are considered among the most convenient, sensitive, and versatile of all laboratory techniques. However, the purine and pyrimidine bases yield only weak fluorescence spectra. Le Pecq and Paoletti (1967) showed that the fluorescence of a dye, ethidium bromide, is enhanced about 25-fold when it interacts with DNA. Ethidium bromide, which is a relatively small planar molecule (Figure El3.4), binds to DNA by insertion between stacked base pairs (intercalation). The process of intercalation is especially significant for aromatic dyes, antibiotics, and other drugs. Some dyes, when intercalated into DNA, show an enhanced fluorescence that can be used to detect DNA molecules after gel electrophoresis measurements (see Chapter 4 and Experiments 14 and 15) and to characterize the physical structure of DNA. Two analyses of DNA will be completed in this experiment ... 

It must, nonetheless, be emphasized that the products of reduction of pyrimidine have not been unequivocally identified, largely due to their instability in the presence of air (oxygen). Furthermore, the UV absorption spectra of the reduction products of waves I and II (kmax284 nm, smax 1.5 x 103) are suggestive of rapid conversion (proton-catalyzed hydration ) of the products, since both the dimer and the dihydro derivative possess a reduced system of aromatic bonds relative to the parent pyrimidine, as a result of which the UV absorption maximum should be shifted to the violet, whereas it is, in fact, shifted 44 nm to the red (from 240 nm to 284 nm) for both products. Of possible relevance to this is the fact that the reduced rings of 4-aminopyrimidine 102) and nicotinamide 103) undergo acidic hydration to form products absorbing at 280 to 290 nm. 

Calamitic compounds which exhibit a smectic and/or nematic phase usually consist of a relatively rigid central core containing co-linear six-membered rings, either aromatic rings, such as 1,4-disubstituted-phenylene, 2,5-disubstituted-pyridine, 2,5-disubstituted-pyrimidine, 3,6-disubstituted-pyridazine, and alicyc-lic rings, such as /ra j-l,4-disubstituted-cyclohexane, 1,4-disubstituted-bicy-clo[2.2.2]octane, 2,5-disubstituted-dioxane. Heteroaromatic rings tend to lead to the formation of smectic phases rather than the nematic phase unless combined with a polar terminal function, such as a cyano group. The dependence of the liquid crystalline transition temperatures on the nature of... 

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