Fluorophenyl)-7-azaindole (1d), 1-(3,5-dimethylphenyl)-7-azaindole (1f), thienyl)-
Fluorophenyl)-7-azaindole (1d), 1-(three,5-dimethylphenyl)-7-azaindole (1f), thienyl)-7-azaindole (1g) and 1-(3-pyridyl)-7-azaindole (1h). 1-(2-thienyl)-7-azaindole (1g) and 1-(3-pyridyl)-7-azaindole (1h).Because thiophene is also a five-membered heteroaromatic prone to SE Ar, it was interesting to consider the iodination of 1-(2-thienyl)-7-azaindole (1g). Certainly, the calculations carried out as ahead of showed a maximum HOMO coefficient as well as a most damaging C charge in the 5-position from the thienyl ring (Compound 48/80 Biological Activity Figure ten). Experimentally, we obtained the 5-iodinated derivative 3g (Table 3, entry eight), which is the compound already formed by deprotometalation-iodolysis (Table 2, entry 4). With regard to 1-pyridyl-7-azaindoles 1h-1j, Figure ten. Calculated C BSJ-01-175 Formula charges (in brackets) and C3 is expected (Figure 10).by utilizing the HuLiS calculator [73]) for 1direct iodination at HOMO coefficients (obtained As assumed, by carrying out the reac(4-methoxyphenyl)-7-azaindole (1b), 1-(4-fluorophenyl)-7-azaindole (1d), 1-(3,5-dimethylphenyl)-7-azaindole (1f), 1-(2tion in the 3- and 2-pyridyl substrates, we observed the formation on the 3-iodinated thienyl)-7-azaindole (1g) and 1-(3-pyridyl)-7-azaindole (1h). derivatives 4h and 4i because the only reaction solutions (Table 3, entries 92). Therefore, it seems that HOMO coefficients and carbon atomic charges might be applied to predict the regioselectivity of SE Ar iodination reactions. Throughout this study, the regioselectivity was established by NMR and confirmed for the solutions 4c, 4e, 4h and 4i by X-ray diffraction (Figure 11). For 4c, brief intermolecular contacts have been observed at the solid state involving the nitrogen of the azaindole pyridine plus the hydrogen at C2 (2.734 , at the origin of a linear chain, whilst these chains are linked by short chlorine-iodine contacts (3.569 (Figure 12A). The molecular networks of 4e, 4h and 4i all exhibit intermolecular halogen bonds [58] in which the iodine atoms are connected to the pyridine nitrogens. For 4e (Figure 12B) and 4h (Figure 12C), these weak interactions bind the heavy halogen plus the nitrogen of the azaindole pyridine and hence produce linear chains (with iodine-nitrogen distances alternating involving 3.137 and 3.158 for the very first and 3.497 for the second). Inside the case of 4i, the iodine is instead linked for the 2-pyridyl attached towards the azaindole core, this time establishing a zig-zag chain (iodine-nitrogen distance of 3.283 (Figure 12D).Molecules 2021, 26,chains are linked by short chlorine-iodine contacts (three.569 (Figure 12A). The molecular networks of 4e, 4h and 4i all exhibit intermolecular halogen bonds [58] in which the iodine networks of 4e, 4h and 4i all exhibit intermolecular halogen bonds [58] in which the iodine atoms are connected towards the pyridine nitrogens. For 4e (Figure 12B) and 4h (Figure 12C), atoms are connected to the pyridine nitrogens. For 4e (Figure 12B) and 4h (Figure 12C), these weak interactions bind the heavy halogen as well as the nitrogen with the azaindole pyridine these weak interactions bind the heavy halogen and also the nitrogen in the azaindole pyridine and thus build linear chains (with iodine-nitrogen distances alternating among three.137 and thus develop linear chains (with iodine-nitrogen distances alternating involving 3.137 and 3.158 for the first and three.497 for the second). Within the case of 4i, the iodine is rather 14 of 33 and 3.158 for the very first and three.497 for the second). Inside the case of 4i, the iodine is rather linked for the 2-pyridyl attached for the.