The effect of small substituents on the properties of indole. An ab initio 6-31G* study

The effect of small substituents (the isoelectronic series F, OH, NH2, CH3) in position 5 and 6 of indole on its electronic distribution has been examined using molecular electrostatic potential (MEP) maps and NMR properties. To clarify the nature of the effects observed the NO2, COO- and O- substituents have also been considered. The geometries of each conformer have been optimised at the HF/6-31G* level. The anti conformers are slightly more stable (by about 0.5 kcal/mol) than the syn conformers for 5,OH and 5 or 6,CH3-indole, while for 6,OH-indole the two forms are almost equal in energy. The 6-31G* Mulliken charges are stronger than those produced by the STO-3G minimal basis set computed on the 6-31G* geometry, as expected. The Merz-Kollman (MK) charges, derived from the best-fit to both the ab-initio 6-31G* and STO-3G MEP around the molecule, differ one from the other slightly less than the corresponding net Mulliken populations and re-equilibrate the strong charge displacement between the ring N and C-3, observed in the 6-31G*: Mulliken charges. By comparing the MEP produced, the Gasteiger-Huckel charges are of about the same quality as the Pullman charges, even though they are somewhat worse than the MK charges, whose MEP is hardly distinguishable from the ab initio one; they are, however, decidedly better than the Gasteiger-Marsili charges, as expected, because the latter are devised for non conjugated pi systems. The methyl group has no effect on the MEP outside of the condensed ring plane. The F and OH lone pairs produce a noticeable negative potential, enhancing the polarity of the N proton. The rr density is increased by the presence of the NH2 group which, however, reduces the positive potential at the proton linked to the ring N. The chemical shift at the N proton turns out to be correlated to its MK charge. The bond length change with respect to indole is very limited (0.01 Angstrom at most, and on average below 0.005 Angstrom). The pyrrole ring has a more localised charge distribution than the benzene ring. (C) 1998 Elsevier Science B.V. All rights reserved.