A CASE (Computer-Assisted Structure Elucidation) for Bench-Top NMR Systems in the Undergraduate Laboratory for De Novo Structure Determination: How Well Can We Do?

Abstract

The recent popularity of benchtop (BT) NMR systems has prompted its applications in undergraduate laboratories around the world. Owing to their low maintenance cost, due to the lack of a superconducting magnetic core, and simple operation, these BT NMR systems can fulfill many of the learning objectives outlined in the undergraduate organic chemistry curricula. With a variety of BT NMR systems currently available (e.g., 43, 60, 80, and 100 MHz), it can be overwhelming for instructors to determine which system is appropriate for their needs. When used as a structure elucidation tool, the focus is often placed solely on solving chemical structures, prompting the eventual question of the magnetic field strength requirements for de novo structure elucidation. To answer this question, two artificial intelligence (AI) software packages, namely Structural Elucidator (v.2020.1.2) from ACD/ Laboratories and Mnova Structure Elucidation (v 14.2.3) from Mestrelab Research, were used. These software provide an unbiased, yet separate, metric to gauge the effect of magnetic field strength on the accuracy of the determined structures. For comparison purposes, results from these two BT magnetic field strengths will be compared to those obtained from a high field NMR (500 MHz) spectrometer, providing a complete overview of the advances, as well as limitations in current BT systems for undergraduate education. In addition, the spectral data presented in this work can be used as a practical example in class to illustrate the effect of spectral resolution on the accuracy of determined structures, which is fundamental to understanding structure elucidation within organic chemistry.

Brewing alcohol 101: An undergraduate experiment utilizing benchtop NMR for quantification and process monitoring

“…In addition, most often at the undergraduate level, NMR is used as a structure elucidation tool in courses such as Organic Chemistry. 2 In this experiment, students gained a different set of NMR processing skills by quantifying peaks and monitoring reaction kinetics. In the course context, the low-field NMR experiment acted as a complementary addition to the high-field experiment in our curriculum, where students learned about the power of NMR as a structure elucidation tool and about various types of NMR experiments such as 1D 1 H and 13 C and 2D COSY and HSQC for mixture analysis.…”

“…In this experiment, we challenged students to develop their NMR skills as they had to set up and collect quantitative data. In addition, most often at the undergraduate level, NMR is used as a structure elucidation tool in courses such as Organic Chemistry 2 . In this experiment, students gained a different set of NMR processing skills by quantifying peaks and monitoring reaction kinetics.…”

“…Firstly, the lower frequency magnets reduce spectral dispersion thereby increasing overlap. 2 The spectral dispersion scales linearly with the field, therefore when comparing 500 MHz to an 80 MHz magnet, there is a $6-fold reduction in peak dispersion. Secondly, sensitivity is greatly reduced, as the signal-to-noise ratio (SNR) of an NMR signal is proportional to B 0 3/2 , where B 0 is the strength of the magnetic field.…”

“…Though benchtop NMR is a powerful analytical tool, it has two main limitations in contrast to high‐field NMR. Firstly, the lower frequency magnets reduce spectral dispersion thereby increasing overlap 2 . The spectral dispersion scales linearly with the field, therefore when comparing 500 MHz to an 80 MHz magnet, there is a ~6‐fold reduction in peak dispersion.…”

Scaffolded Structure Determination Activities Utilizing 2D NMR Spectroscopy of Simple Organic Molecules

“…Notably, analysis of 2D NMR spectroscopy has been incorporated into this series of assessments. Over the past several years, laboratory experiments have reported the use of 2D NMR spectroscopy in undergraduate chemistry laboratories. − With the increasing availability of high-field and benchtop NMR spectrometers, 2D experiments such as 1 H– 1 H correlation spectroscopy (COSY) and 1 H– 13 C heteronuclear single quantum coherence spectroscopy (HSQC) are accessible for undergraduate students to utilize. The determination of an unknown organic molecule is a traditional organic chemistry laboratory experiment and has been previously adapted to include 2D NMR spectroscopy. , Both experiments describe the incorporation of 2D NMR with a small set of molecules utilized for a single assignment.…”