A guide to small-molecule structure assignment through computation of (1 H and 13 C) NMR chemical shifts

341Citations
Citations of this article
325Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

This protocol is intended to provide chemists who discover or make new organic compounds with a valuable tool for validating the structural assignments of those new chemical entities. Experimental 1 H and/or 13 C NMR spectral data and its proper interpretation for the compound of interest is required as a starting point. The approach involves the following steps: (i) using molecular mechanics calculations (with, e.g., MacroModel) to generate a library of conformers; (ii) using density functional theory (DFT) calculations (with, e.g., Gaussian 09) to determine optimal geometry, free energies and chemical shifts for each conformer; (iii) determining Boltzmann-weighted proton and carbon chemical shifts; and (iv) comparing the computed chemical shifts for two or more candidate structures with experimental data to determine the best fit. For a typical structure assignment of a small organic molecule (e.g., fewer than ∼10 non-H atoms or up to ∼180 a.m.u. and ∼20 conformers), this protocol can be completed in ∼2 h of active effort over a 2-d period; for more complex molecules (e.g., fewer than ∼30 non-H atoms or up to ∼500 a.m.u. and ∼50 conformers), the protocol requires ∼3-6 h of active effort over a 2-week period. To demonstrate the method, we have chosen the analysis of the cis- versus the trans-diastereoisomers of 3-methylcyclohexanol (1-cis versus 1-trans). The protocol is written in a manner that makes the computation of chemical shifts tractable for chemists who may otherwise have only rudimentary computational experience. © 2014 Nature America, Inc.

Cite

CITATION STYLE

APA

Willoughby, P. H., Jansma, M. J., & Hoye, T. R. (2014). A guide to small-molecule structure assignment through computation of (1 H and 13 C) NMR chemical shifts. Nature Protocols, 9(3), 643–660. https://doi.org/10.1038/nprot.2014.042

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free