ELECTROPHILIC SUBSTITUTION IN THE BENZOFURAN SERIES - A THEORETICAL (AM1) STUDY

The electrophilic substitution in a series of 5-aminobenzofurans was investigated by all-valence electron AM1 molecular orbital calculations. Various molecular properties of the reactants, intermediates, and products were computed and compared with available experimental data. The results indicate that while calculated ground-state charge densities cannot be used to predict reactivity and orientations, the relative thermodynamic stabilities of the reaction intermediates (arenium ions, sigma-complexes) reflected by calculated heats of formation (DELTA-H(f)) accurately indicated the isomers resulting from the kinetically controlled substitutions. The relative stabilities of the reaction products could be used to predict reaction preferences for the thermodynamically controlled electrophilic substitutions. Positions 4 for both aniline and 5-aminobenzofurans were the most susceptible toward electrophilic attack. The calculated DELTA-H(f) of the reaction intermediates, in good agreement with the experimental data, were capable of distinguishing between slightly nonequivalent positions such as the ortho and ortho prime to a substituent. Calculated AM1 DELTA-H(f) may represent practical guides in the prediction of sites of electrophilic aromatic substitutions for molecules with complex structures.