High-Resolution NMR Techniques in Organic Chemistry

Timothy D.W. Claridge

• Publisher: Elsevier Science
• Year: 2016
• ISBN:
  9780080999937
• Edition: 3
• Topic: Ciencias físicas
• Subtopic: Espectroscopia y análisis de espectro

High-Resolution NMR Techniques in Organic Chemistry, Third Edition describes the most important NMR spectroscopy techniques for the structure elucidation of organic molecules and the investigation of their behaviour in solution. Appropriate for advanced undergraduate and graduate students, research chemists and NMR facility managers, this thorough revision covers practical aspects of NMR techniques and instrumentation, data collection, and spectrum interpretation. It describes all major classes of one- and two-dimensional NMR experiments including homonuclear and heteronuclear correlations, the nuclear Overhauser effect, diffusion measurements, and techniques for studying protein–ligand interactions. A trusted authority on this critical expertise, High-Resolution NMR Techniques in Organic Chemistry, Third Edition is an essential resource for every chemist and NMR spectroscopist.

Chapter 1

Introduction

Abstract

This chapter provides a brief overview of the book contents. It begins with a brief historical perspective on the development of high-resolution nuclear magnetic resonance (NMR) spectroscopy. It then explains the broad contents of each chapter and describes the nomenclature and graphical representations used throughout the text for the description of NMR techniques. It finishes with guidance on how one might employ these techniques.

Keywords

history

pulse sequence

structure elucidation

structure verification

Chapter Outline

1.1 The Development of High-Resolution NMR 1

1.2 Modern High-Resolution NMR and This Book 3

1.2.1 What This Book Contains 4

1.2.2 Pulse Sequence Nomenclature 5

1.3 Applying Modern NMR Techniques 7

References 10

From the initial observation of proton magnetic resonance in water [1] and in paraffin [2], the discipline of nuclear magnetic resonance (NMR) has seen unparalleled growth as an analytical method and now, in numerous different guises, finds application in chemistry, biology, medicine, materials science and geology. The founding pioneers of the subject, Felix Bloch and Edward Purcell, were recognised with a Nobel Prize in 1952 ‘for their development of new methods for nuclear magnetic precision measurements and discoveries in connection therewith’. The maturity of the discipline has since been recognised through the awarding of Nobel Prizes to two of the pioneers of modern NMR methods and their application, Richard Ernst (1991, ‘for his contributions to the development of the methodology of high resolution NMR spectroscopy’) and Kurt Wüthrich (2002, ‘for his development of NMR spectroscopy for determining the three-dimensional structure of biological macromolecules in solution’). Despite its inception in the laboratories of physicists, it is in chemical and biochemical laboratories that NMR spectroscopy has found greatest use. To put into context the range of techniques now available in the modern chemical laboratory, including those described in this book, we begin with a short overview of the evolution of high-resolution (solution-state) NMR spectroscopy and some of the landmark developments that have shaped the subject.

1.1. The development of high-resolution NMR

It is almost 70 years since the first observations of NMR were made in both solid and liquid samples, from which the subject has evolved to become the principal structural technique of the research chemist, alongside mass spectrometry. During this time, there have been a number of key advances in high-resolution NMR that have guided the development of the subject [3–5] (Table 1.1) and consequently the work of chemists and their approaches to structure elucidation. The seminal step occurred during the early 1950s when it was realised that the resonant frequency of a nucleus is influenced by its chemical environment, and that one nucleus could further influence the resonance of another through intervening chemical bonds. Although these observations were seen as unwelcome chemical complications by the investigating physicists, a few pioneering chemists immediately realised the significance of these chemical shifts and spin–spin couplings within the context of structural chemistry. The first high-resolution proton NMR spectrum (Fig. 1.1) clearly demonstrated how the features of an NMR spectrum, in this case chemical shifts, could be directly related to chemical structure and it is from this that NMR has evolved to attain the significance it holds today.

Table 1.1

A Summary of Some Key Developments that have had a Major Influence on the Practice and Application of High-Resolution NMR Spectroscopy in Chemical Research

Decade	Notable Advances
1940s	First observation of NMR in solids and liquids (1945)
1950s	Development of chemical shifts and spin–spin coupling constants as structural indicators
1960s	Use of signal averaging for improving sensitivity Application of the pulse FT approach The NOE employed in structural investigations
1970s	Use of superconducting magnets and their combination with the FT approach Computer-controlled instrumentation
1980s	Development of multipulse and 2D NMR techniques Automated spectroscopy
1990s	Routine application of pulsed field gradients for signal selection Development of coupled analytical methods (eg LC-NMR)
2000s	Use of high-sensitivity helium-cooled cryogenic probes Routine availability of actively shielded magnets for reduced stray fields Development of microscale tube and flow probes
2010+	Adoption of fast data acquisition methods Use of high-sensitivity nitrogen-cooled cryogenic probes Use of multiple receivers…?

Figure 1.1 The first ‘high-resolution’ proton NMR spectrum, recorded at 30 MHz, displaying the proton chemical shifts in ethanol. (Source: Reprinted with permission from Ref. [6], Copyright 1951, American Institute of Physics.)

The 1950s also saw a variety of instrumental developments that were to provide the chemist with even greater chemical insight. These included the use of sample spinning for averaging to zero field inhomogeneities which provided a substantial increase in resolution, so revealing fine splittings from spin–spin coupling. Later, spin decoupling was able to provide more specific information by helping the chemists understand these interactions. With these improvements, sophisticated relationships could be developed between chemical structure and measurable parameters, leading to such realisations as the dependence of vicinal coupling constants on dihedral angles (the now well-known Karplus relationship). The inclusion of computers during the 1960s was also to play a major role in enhancing the influence of NMR on the chemical community. The practice of collecting the same continuous wave spectrum repeatedly and combining them with a CAT (computer of average transients) led to significant gains in sensitivity and made the observation of smaller sample quantities a practical realisation. When the idea of stimulating all spins simultaneously with a single pulse of radiofrequency, collecting the time domain response and converting this to the required frequency domain spectrum by a proces...