A brief analysis of 2D and 13 C-NMR at low field

Importance of the topic

Benchtop nuclear magnetic resonance (NMR) instruments have grown in accessibility and affordability, promising routine structural analysis in laboratories outside of advanced research facilities. However, their low magnetic field strength (<90 MHz) imposes sensitivity and resolution constraints that can limit their ability to perform heteronuclear and two-dimensional (2D) experiments. Understanding these limitations and exploring complementary analytical approaches are essential for ensuring efficient workflows and accurate molecular characterization in quality control, teaching, and small-molecule research settings.

Objectives and Overview

This application note examines the practical utility of 2D and 13C NMR experiments on benchtop spectrometers and contrasts them with an orthogonal strategy combining 1H NMR and infrared spectroscopy. Two common pharmaceutical compounds, ibuprofen and lidocaine, serve as case studies to illustrate how much information can be obtained from simple proton spectra, when advanced NMR experiments add value, and when alternative techniques offer faster, equally reliable structural confirmation.

Methodology

A series of experiments was conducted on benchtop devices at concentrations ranging from 0.1 to 2 M. Proton (1H), carbon (13C), and 2D NMR (COSY, HSQC, HMBC) experiments were performed on a 60 MHz benchtop NMR system. Infrared spectra were recorded in parallel using an attenuated total reflectance (ATR) accessory. Acquisition times and spectral clarity were compared across methods and concentrations to evaluate throughput advantages and information content.

Used Instrumentation

• Benchtop NMR spectrometer (60–90 MHz) performing 1H, 13C, COSY, HSQC, HMBC experiments
• Thermo Scientific Nicolet iS5 FT-IR spectrometer with iD5 ATR accessory

Main Results and Discussion

Case Study 1 – Ibuprofen:
• 1H NMR acquired in under 15 seconds at 2 M yielded unambiguous structural assignments despite moderate line overlap.
• HSQC (≈1 hour) and HMBC (≈2 hours) offered no additional structural insight beyond the 1H spectrum.

Case Study 2 – Lidocaine:
• 1H NMR at 2 M identified nearly all proton environments, but left the amide carbonyl position ambiguous.
• A 13C NMR experiment required 10–18 minutes at 2 M and over 2 hours at 0.1 M to resolve the carbonyl resonance.
• Infrared spectroscopy detected the amide carbonyl band (~1660 cm⁻¹) and N–H absorption (~3243 cm⁻¹) in under 30 seconds at concentrations down to 100 mM.
• Combining 1H NMR and IR provided a full structural picture in less than one minute for 2 M samples and under two minutes at 0.1 M—offering a 14– to 121-fold time saving compared to 13C NMR alone.

Benefits and Practical Applications

• Many small-molecule structures can be confidently assigned using only 1H NMR on benchtop systems, eliminating the need for time-consuming heteronuclear or 2D experiments.
• Parallel acquisition of IR and 1H NMR data provides rapid confirmation of functional groups, reducing instrument time and improving sample throughput in teaching labs and routine QC.
• The combined NMR-IR workflow extends reliable structural analysis to lower analyte concentrations and more complex matrices where benchtop 13C NMR is impractical.

Future Trends and Opportunities

• Development of enhanced sensitivity probes or cryogenic cooling for benchtop NMR could narrow the gap with high-field instruments, enabling faster heteronuclear experiments at lower concentrations.
• Integration of automated data fusion and machine-learning algorithms will further streamline orthogonal spectral interpretation, guiding users to optimal combinations of techniques.
• Expansion of compact, hybrid analytical platforms combining NMR, IR, and MS modules may become standard for rapid, on-site structural screening in industrial and field applications.

Conclusion

While benchtop NMR spectrometers can technically perform 2D and 13C experiments, practical limitations in sensitivity, sample concentration, and acquisition time often outweigh their benefits. Straightforward 1H NMR analysis combined with infrared spectroscopy delivers equivalent structural information far more quickly and across a broader range of sample conditions. Adopting such complementary approaches enhances lab productivity and makes routine structural confirmation accessible in non-specialist settings.