Pyrimidine ring electronic density

Nucleophilic additions of the acetonyl anion to 6-nitrotriazolopyrimidines (91) gave CT-adducts (227), whose acidification afforded the dihydro adduct 228 (93KGS807). Direct addition of cyclic /3-diketones such as dime-done and indanedione to 91 led to the adducts 229 and 230, respectively (93ZOR622). The reactivity of this class of compounds with respect to charged and uncharged nucleophiles is determined by their aromatic character and the deficit of electron density in the pyrimidine ring, and the di-... 

In those systems where the five-membered ring contains three heteroatoms and is stable, the adjacent carbon atoms on the six-membered ring are subject to nucleophilic attack because of the reduction of electron density at these points. These reactions for l,2,3-triazolo[4,5-d]pyrimidines (7), for [l,2,5]oxadiazolo[3,4-d]pyrimidines (10), and for [ 1,2,5]thiadiazolo[3,4-d]pyrimidines (14) have been reviewed (see Table 5 for references). New reactions and reactions of other systems are discussed in the following sections. 

All positions on each of the diazines, with the sole exception of the 5-position of a pyrimidine, are a and/or y to an imine ring nitrogen and, in considering nncleophilic addition/snbstitution, it mnst be remembered that there is also an additional nitrogen that is withdrawing electron density. As a consequence, all the monohalo-diazines are more reactive than either 2- or 4-halo-pyridines. The 2- and 4-halo-pyrimidines are particularly reactive because the anionic intermediates (shown below for attack on a 2-halo-pyrimidine) derive direct mesomeric stabilisation from both nitrogen atoms. 

Pyrimidine is 7t-deficient because of electronegative A-atoms. Consequently, the electron densities at the 2- and 4-/6-positions are depleted, and these positions become strongly electrophilic, and are herein referred to as the electrophilic positions. The electron density at the 5-position is only slightly depleted the ring therefore retains benzenoid properties at this position, which is herein referred to as the benzenoid position. The electron density at the A-atoms is greatly enhanced the A-atoms constitute the basic and nucleophilic centers in pyrimidine. In quinazoline, the pyrimidine ring retains the properties of the parent heterocycle while the carbocyclic ring has benzene-like properties. 

Hiickel molecular orbital calculations have shown that the 5-position in this ring system has associated with it a greater tt-electron density than is present in the corresponding positions in s-triazolo[4,3-a]pyridine, s-triazolo[4,3-a]pyrimidine, and s-triazolo[4,3-c]pyrimidine. This fact has been used to rationalize the difficulty in rearranging this heterocycle to its s-triazolo[l,5-a] analogue, in contrast to the ease with which the other s-triazolo systems rearrange. 

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