50 and More Essential NMR Experiments

A Detailed Guide

Matthias Findeisen, Stefan Berger

• Publisher: Wiley-VCH
• Year: 2013
• Print ISBN: 9783527334834
• eBook ISBN: 9783527336944
• Edition: 1
• Topic: Sciences physiques
• Subtopic: Spectroscopie et analyse du spectre

This book is the perfect link for learning how to perform the experiments after only having studied theory. In eight chapters more than 50 essential NMR experiments are described in detail. Special focus is put on the organic set of NMR spectra (1H, 13C-APT, COSY, NOESY, HSQC and HMBC). Different chapters deal with advanced organic NMR, selective methods, heteronuclear NMR, relaxation and diffusion measurements, organic applications and maintenance. Every experiment has a section providing the reader with the purpose and scope of the specific experiment. Every experiment is concluded with the spectrum as it is obtained under the conditions described. Questions
and comments enable the reader to check their understanding. The authors are very experienced and the whole book is in full color, which enhances the reading experience and makes the spectra and other figures easier to understand.

This book is strongly recommended for all students and researchers who are involved in the structural elucidation of chemical compounds both in practical education and in pursuing research, in particular if they handle an NMR spectrometer.

Chapter 1

The Organic Set of NMR Spectra

There are six NMR spectral methods, which are usually first measured on a routine basis if an organic chemist has produced a new compound. Usually, this organic set is sufficient for a complete structural elucidation, especially if additional support comes from mass spectrometry and IR-or UV-spectroscopy.

These six methods are:

1.1 ¹H-NMR

1.2 APT-¹³C-NMR [Attached Proton Test]

1.3 COSY [COrelation SpectroscopY]

1.4 NOESY [Nuclear Overhauser Effect SpectroscopY]

1.5 HSQC [Heteronuclear Single Quantum Coherence]

1.6 HMBC [Heteronuclear Multiple Bond Correlation]

We describe therefore in this first chapter these six methods in some detail using strychnine as an example. Strychnine with its rather complicated molecular structure provides all the typical problems encountered during spectral assignments in organic chemistry. With concurrent instrumentation and about 20 mg of substance having a molecular weight around 500 Da, the total recording time of these techniques will be about 5 h.

Of course, this book offers much more, but this organic set comprises the most essential of all our essentials.

taken from TAMU NMR Letters, 1975, 199, 49.

Experiment 1.1 ¹H NMR Experiment

1. Purpose

The aim of the standard ¹H NMR experiment is to record a routine proton NMR spectrum in order to get structure-related information for the protons of the sample, i. e. chemical shifts, spin–spin couplings, and intensities. Here we apply this standard procedure to strychnine and discuss different weighting functions and problems of integration.

The prospect of measuring very rapid reaction rates by NMR provided the inspiration for getting an affirmative response from Linus Pauling [then chairman of the division of Chemistry and Chemical Engineering at California Institute of Technology] that “with NMR, we could investigate the borderline between resonance and tautomerism”. For example, investigating the NMR spectrum of cycloheptatriene with temperature to see if it existed as a rapidly equilibrating mixture of cycloheptatriene and norcaradiene, or was what later would be called a “monohomobenzene”. The argument was persuasive and we soon ordered a 30-MHz Varian proton and fluorine spectrometer.

J. D. Roberts, * 1918 “A Personal NMR Odyssey” Enyclopedia of NMR, 1996, 1, 590–598.

2. Variants

Variants of this form of NMR spectroscopy include first of all excitation with different pulse angles.

However, since recent NMR instruments are sensitive enough, usually one 90° scan is sufficient to obtain a spectrum. Therefore no considerations about reduced pulse angles are necessary. Second, if a strong solvent signal is present, different forms of signal suppression are available. These are discussed in chapter 3.

3. Pulse Scheme and Phase Cycle

Scheme 1.1-1

Common values:

p1: 90° ¹H transmitter pulse

d1: relaxation delay

4. Acquisition

Special values used for the spectrum shown:

Sample: 3% strychnine in CDCl₃.

Time requirement: 1 min

Spectrometer: Bruker DRX-600 with 5-mm-TBI-probe

td:	64K
sw:	15 ppm
aq:	3.6 s
o1:	middle of ^1H NMR spectrum
d1:	2 s
ns:	1

These data will lead to an FID digital resolution of 0.28 Hz/point for the real or imaginary part of the FID.

5. Processing

Use zero filling to si = 64K and exponential weighting with lb = 0.1 Hz, phase correction and referencing to internal TMS, which is the only acceptable reference scheme. The digital resolution of the spectrum will be with these data sw/si = 0.14 Hz/point. Before integration, perform phase and baseline correction on the spectrum accurately. A comparison of the spectra in Fig. 1.1-3 and 1.1-4 shows how a Gaussian weighting function with lb = −1 Hz and gb = 0.3 makes additional small spin couplings visible.

The appearance of an unsplit methyl signal in a CH₃CH moiety, where the chemical shift difference was large compared to the vicinal coupling constant, expected to be about 7 Hz, subsequently impressed on me the importance of MR spectral analysis. When I understood what was going on, I wrote a paper which was published in 1961 on the nature of the signals of C-methyl groups, and this explained many anomalous “coupling constants” involving methyl groups in steroids and other compounds; it anticipated later research by others on virtual coupling. Although spectral analysis is becoming almost a lost art in the midst of so-called “modern NMR”, it is in fact just as useful and necessary as it has ever been, in my own experience.

F. A. L. Anet, * 1926 “A lapsed organic chemist in the wonderland of NMR” Enyclopedia of NMR, 1996, 1, 187–190.

6. Result

The figures show two expansions of the 600 MHz ¹H NMR spectrum of strychnine.

A closer inspection of the integrals reveals that the integral of H-4 is too small as compared to all other integrals of the compound. Although the spectrum was recorded with only one scan, the waiting time after the receiver gain adjust command before and the actual measurement was appartently too short (see Question A).

Fig. 1.1-1 Expansion of the ¹H-NMR spectrum in the aromatic region

Scheme 1.1-2

Fig. 1.1-2 Expansion of the ¹H-NMR spectrum in the aliphatic region

Fig. 1.1-3 Edited with lb = 0.1 Hz (zoom of Fig. 1.1-2)

Fig. 1.1-4 Edited with gb = 0.3, lb = −1

7. Comments

The excitation pulse p1 converts the equilibrium magnetization of the ¹H nuclei into a transverse magnetization as shown in Equation (1). During the acquisition time chemical shifts and spin-spin couplings develop in the x,y plane, as shown separately in Equations (2) and (3), and are detected by the receiver in the x,y plane in quadrature mode.

(1)

(2)

(3)

8. Questions

A. Suggest a reason why the integral of H-4 is considerable smaller than the others.

B. How would one classify the aromatic spin system?

C. The intensity pattern of the signals between 4.2 and 4.0 ppm has a special name?

D. The signals at 2.35 and 1.27 ppm both belong to the methylene group of C-15 and are spin coupled to each other; however, only one has an additional spin coupling. Why?

9. Own Observations

[1] T. D. W. Claridge, “Highresolution NMR techniques in organic chemistry”, Pergamon, Oxford, 1999.

[2] I. K. M. Sanders, B. K. Hunter, “Modern NMR spectroscopy”, 2nd Edition, Oxford University Press, Oxford, 1993.

[3] H. Friebolin, “Basic one-and two-dimensional NMR spectroscopy”, 3rd Edition, Wiley-VCH, Weinheim, 1998.

[4] H. Gunther, “NMR Spectroscopy”, 2nd Edition, Wiley, Chichester, 1995.

Experiment 1.2 ATP-¹³C NMR

1. Purpose

The aim of a routine ¹³C NMR experiment is to record a ¹³C NMR spectrum with proton broad-band decoupling and data accumulation in order to get chemical shift information for structure determination. At the same time one wants to have multiplicity information. From the many schemes proposed we feel the APT (Attached Proton Test) technique is the most useful and convenient method available, especially if carried out with a chirp 180° pulse on the carbon channel to avoid phase problems at high field spectrometers.

2. Variants

Alternative methods that give information about the multiplicities are INEPT, DEPT, DEPTQ, and PENDANT, and the historic off-resonance ¹H-decoupling technique. Unlike INEPT or DEPT, the APT method yields ¹³C NMR spectra th...

Table of contents

• Cover
• Contents
• Title Page
• Copyright
• Preface
• Chapter 1 The Organic Set of NMR Spectra
• Chapter 2 Advanced Organic NMR Spectroscopy
• Chapter 3 Selective Methods
• Chapter 4 Heteronuclear NMR
• Chapter 5 Experiments in Physical Organic Chemistry
• Chapter 6 Organic Chemistry Applications
• Chapter 7 An Excursion to the Solid State and to Structural Biology
• Chapter 8 Maintenance and Calibration
• Answer
• Pulse Programs
• Elementary Product Operator Formalism Rules
• Chemical Shift and Spin-Coupling Data for Strychnine
• Picture Credits
• Index