1.2.4- Triazolo pyrimidines electron density

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. 

The electron densities of the parent l,2,4-triazolo[4,3-c]- and [1,5-c]-pyrimidines (127 and 128) were calculated the total 77-electron density was obtained from HMO calculations and the total electron density by the complete neglect of differential overlap approximation method (CNDO-2). Whereas N6 caused C5 of both systems to be more electrophilic, N2 in the [4,3-c] system 127 decreased the 77-electron density at C5 more than N3 in the [1,5-c] system 128 at the same carbon. The calculations also indicated that the driving force for the 127-to-128 rearrangement should originate from the larger interaction between N1 and N2 in the [4,3-c] system 127 (electron densities, 5.22 and 5.09, respectively) compared to the interaction between N3 and N4 in the [1,5-c] system 128 (electron densities, 5.20 and... 

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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