Differential Effects of Nitrogen Substitution in 5- and 6-Membered Aromatic Motifs.

The replacement of carbon with nitrogen can affect the aromaticity of organic rings. Nucleus-independent chemical shift (NICS) calculations at the center of the aromatic π-systems reveal that incorporating nitrogen into 5-membered heteroaromatic dienes has only a small influence on aromaticity. In contrast, each nitrogen incorporated into benzene results in a sequential and substantial loss of aromaticity. The contrasting effects of nitrogen substitution in 5-membered dienes and benzene are reflected in their Diels-Alder reactivities as dienes. 1,2-Diazine experiences a 1011 -fold increase in reactivity upon nitrogen substitution at the 4- and 5-positions, whereas a 5-membered heteroaromatic diene, furan, experiences a comparatively incidental 102 -fold increase in reactivity upon nitrogen substitution at the 3- and 4-positions.