Development of a Teaching Approach for Structure Elucidation Using 1D and 2D Homonuclear and Heteronuclear NMR Spectra

Abstract

A frequent challenge that graduate and undergraduate students in chemistry, biology, and pharmacy laboratories face is accurately assigning proton and carbon peaks in the 1D and 2D Nuclear Magnetic Resonance (NMR) spectra of organic and pharmaceutical molecules. We propose a consistent, step-by-step approach to effectively assist students in simultaneously interpreting a variety of 1D and 2D NMR spectra. According to this approach, the anticipated NMR peaks are initially predicted based on the compound’s molecular structure, followed by the interpretation of the actual spectra. The novelty of this teaching approach lies in the simultaneous use of experimental data from 1D and 2D homonuclear and heteronuclear spectra to validate or enhance the theoretical approach derived solely from the molecule’s two-dimensional structure. The integrations obtained from 1D ¹H NMR spectrum and bond and spatial correlations from homonuclear and heteronuclear 2D NMR spectra are the experimental data used for every structure elucidation. A special notation using arrows is adduced in order to indicate the bond and spatial correlations and to schematically present the proposed teaching approach in an easy and comprehensive way. The proposed notation could offer a new way to visualize and conceptualize the theoretical approach, potentially making it easier for students to apply. This methodology begins with predicting proton, carbon, and proton-carbon correlations based solely on the molecular structure, followed by listing the expected signals for all available spectra. The approach then emphasizes comparing these predicted correlations and signals with those observed in 1D and 2D NMR spectra. This methodology is only applicable when the synthesis of a particular product is anticipated, which is a typical scenario for students engaged in organic synthesis laboratories or conducting research in organic and medicinal chemistry.