A comparative study between para- and ortho-aminophenyl benzothiazoles using NMR and DFT calculations. G. K. Pierens, T. K. Venkatachalam and D. Reutens Centre for Advanced Imaging, The University of Queensland, St.Lucia, Brisbane 4072, Australia Abstract: Ortho- and para-substituted aminophenyl benzothiazoles were synthesized and characterized using NMR spectroscopy. A comparison of the proton chemical shift values reveals significant differences in the observed chemical shift values for the NH protons indicating the presence of a hydrogen bond in all ortho-substituted compounds as compared to the para compounds. The presence of intramolecular hydrogen bond in the ortho amino substituted aminophenyl benzothiazole forces the molecule to be planar which may be an additional advantage in developing these compounds as Alzheimer’s imaging agent since the binding to amyloid fibrils prefers planar compounds. The splitting pattern of the methylene proton next to the amino group also showed significant coupling to the amino proton consistent with the notion of the existence of slow exchange and hydrogen bond in the ortho-substituted compounds. This is further verified by density functional theory (DFT) calculations which yielded a near planar low energy conformer for all the o-aminophenyl benzothiazoles and displayed a hydrogen bond from the amine proton to the nitrogen of the thiazole ring. A detailed analysis of the 1 H, 13 C, and 15 N NMR chemical shifts and DFT calculated structures of the compounds are described. Keywords: aminophenyl benzothiazoles, hydrogen bond, 1 H NMR, 13 C NMR, 15 N NMR, DFT calculations