Isotope Effects in NMR Spectroscopy

178 Pages·1990·3.588 MB·English

by  S. Berger, R. L. Van Etten, J. M. Risley, N. M. Sergeyev (auth.)

NMR
22
Basic Principles and Progress
Editors: P. Diehl E. Fluck H. Gunther
R. Kosfeld J. Seelig
Advisory Board: S. Forsen R.K. Harris
C.L. Khetrapal T.E. Lippmaa G.J. Martin
H. Pfeifer A. Pines B. L. Shapiro
Isotope Effects in
NMR Spectroscopy
With contributions by
S. Berger, R. L. Van Etten, J. M. Risley,
N. M. Sergeyev
With 24 Figures
Springer-Verlag Berlin Heidelberg New York
London Paris Tokyo Hong Kong
ISBN-13: 978-3-642-74837-0 e-ISBN-13: 978-3-642-74835-6
DOl: 10.1 007/978-3-642-74835-6
Library of Congress Cataloging-in-Publication Data
Isotope efTects in NMR spectroscopy/(by St. Berger ... et al.)
p. cm.-(NMR; 22)
1. Nuclear magnetic resonance spectroscopy. 2. Isotopes.
I. Berger, Stefan. II. Series: NMR (Series); v. 22.
QC490.N2 vol.22 [QD96.N8] 538.3s-dc20 [543'.0877] 89-21975 CIP
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Foreword
Isotope effects on chemical shifts and spin-spin coupling
constants in nuclear magnetic resonance spectroscopy have
found increasing attention in recent years. In particular NMR
isotope shifts have profited from the improved experimental
situation that arose through the growing use of high-field
spectrometers. Detailed theoretical treatments of NMR isotope
effects have appeared and applications of NMR isotope effect
measurements in various branches of chemistry are well
documented. The reviews collected in the present volume of
"NMR - Basic Principles and Progress", all written by experts in
the field who have themselves made excellent contributions to the
research areas they discuss, are thus believed to meet general and
widespread interest.
The first chapter, written by S. Berger, treats models which
were developed in order to rationalize deuterium induced isotope
shifts in 13C and 19F NMR for organic molecules. These
approaches are based on concepts like hybridization, hyper
conjugation and n-polarization, to name only a few, which are
important to describe structure and substituent effects in organic
chemistry. Their usefulness in the present context is convincingly
demonstrated with numerous examples.
The contribution by N. M. Sergeyev attempts a rigorous
screening of the literature for observations which are relevant
to the problem of primary and secondary isotope effects on
scalar spin-spin coupling. These effects are much smaller in
magnitude than the secondary isotope effects on chemical shifts
which are most ft:equently measured and quite a number of
experimental difficulties have to be overcome in order to get
reliable results. It is hoped that the present status report may
serve as a basis for future investigations in this area.
Finally, the impact of NMR isotope effects on studies of
structure and reactivity in organic and bio-organic chemistry as
well as in biochemistry is amply documented by the contribution
of J. M. Risley and R. L. Van Etten, who present for the first
vi Foreword
time a comprehensive collection of one-bond 180 isotope effects
on 13C and 15N chemical shifts. Numerous studies are discussed
in detail and a complete list of biosynthetic investigations where
180 isotope shifts have served as an analytical tool is given.
One formal aspect deserves a special comment: Unfortunately,
different sign conventions for NMR isotope shifts are used in
the literature and the reader will note that the articles which
follow reflect this situation faithfully. The editors felt, however,
that tolerance should be preferred to strict discipline and
apologize in advance for any inconveniences that may arise.
There seems good reason to believe that the present volume
will further promote the interest in NMR isotope effects and
their applications in various areas of chemistry.
Siegen, November 1989 H. Gi.inther
Editorial Board:
Prof. Dr. Peter Diehl Institut fiir Physik der Universitiit Basel, Klingelbergstr.
82, CH -4056 Basel
Prof. Dr. EHehard Fluck Gmelin-Institut, Varrentrappstr. 40/42, 0-6000
Frankfurt am Main 90
Prof. Dr. H. Gunther Universitiit Siegen, Organische Chemie II,
Postfach 101240,0-5900 Siegen
Prof. Dr. Robert Kosfeld Universitiit-Duisburg, Physikalische Chemie,
Postfach 101629,0'4100 Duisburg 1
Prof. Dr. J. Seelig Biozentrum der Universitiit Basel, Abt. Biophysikalische
Chemie, Klingelbergstr. 70, CH-4056 Basel
Advisory Board:
Prof. Dr. Stute Forsen Department of Physical Chemistry, Chemical Centre,
University of Lund, P.O.B. 740, S-22OO7 Lund
Prof. Dr. Robin K. Harris University of Durham, Department of Chemistry,
Science Laboratories, South Road,
GB-Durham DHI 3LE
Prof. C. L. Khetrapal Sophisticated Instruments Facility, Indian Institute of
Science, Bangalore-560012, India
Prof. Dr. T. E. Lippmaa Institute of Chemical Physics and Biophysics,
Academy of Sciences of the Estonian SSR, Lenini
paiestee 10, Tallinn 200001, USSR
Prof. Dr. G. J. Martin Universite de Nantes, U,E.R. de Chimie, Resonance
Magnetique Nucleaire et Reactivite Chimique,
UA-CNRS No 472, 2, rue de la Houssini';re,
F-44072 Nantes-Cedex
Prof. Dr. Harry Pfeifer Sektion Physik, Karl-Marx-Universitiit, Linnestral3e 5,
DDR-7010 Leipzig
Prof. Dr. Alex Pines University of California, Berkeley, Department of
Chemistry, Berkeley, CA 94720, USA
Prof. Dr. Bernard L. Shapiro 966 Elsinore Court, Palo Alto, CA 94303, USA
Table of Contents
Chemical Models for Deuterium Isotope Effects in
13C_ and 19F -NMR
S. Berger. . . . . . . . . . . . . .
Isotope Effects on Spin-Spin Coupling Constants:
Experimental Evidence
N. M. Sergeyev. . . . . . . . . 31
Properties and Chemical Application of
180 Isotope Shifts in 13C and 15N Nuclear
Magnetic Resonance Spectroscopy
J. M. Risley, R. L. Van Etten. . . . . 81
Appendix to Isotope Effects on Spin-Spin
Coupling Constants . . . . . . . . . . . . . 169
Author Index Volume 21-22
Chemical Models for Deuterium Isotope Effects in
t3C_ and -NMR
19F
S. Berger
Fachbereich Chemie der Universitiit Marburg, Hans Meerwein StraBe, D-3550 Marburg, FRG
Table of Contents
Introduction . 2
1.1 Scope and Aim of the Review 2
1.2 Definition and Sign Convention. 3
2 Polarization of x-Systems 3
2.1 Long Range Isotope Effects 8
2.2 MO-Calculations. 9
3 Isotope Effects and Hyperconjugation 10
3.1 Isotope Effects in Aromatic Compounds. 10
3.2 Isotope Effects Involving a Carbonyl Group 14
3.3 Isotope Effects in Cations. 16
4 Stereospecificity of Isotope Effects 21
4.1 Isotope Effects in Rigid Molecules. 22
4.2 Perturbation of Conformational Equilibria. 25
5 Conclusions . 27
6 Acknowledgement 27
7 References. 27
Deuterium isotope effects on DC_ and 19F-NMR spectra are reviewed from the point of view of
substituent induced chemical shifts. In three sections, similarities between deuterium isotope effects
and substituent behaviour are discussed. It is shown that the concepts of increment systems, substituent
parameters, 1t-polarization, dihedral angle dependence, and hyperconjugation apply with equal success
to deuterium isotope effects.
NMR Basic Principles and Progress, Vol. 22
© Springer-Verlag, Berlin Heidelberg t990
2 S. Berger
1 Introduction
The research on isotope effects in organic chemistry is based on the vibrational
theory [1]. Kinetic isotope effects in chemical reactions and equilibrium isotope
effects have been dealt with on the basic assumption that the only important
difference between isotopes is their mass and any effects from isotopic substitution
ultimately should be traced back to this difference. Thus, within the Born
Oppenheimer approximation the electronic potential of a C-D bond is believed
to be identical with the potential of a C-H bond. Isotope effects therefore are
thought to stem from the anharmonicity of this potential and the different zero
point energy of the heavier isotope within this potential.
However, more than 20 years ago, Halevi [2] summarized in perhaps
provocative statements a different line of thought applying the language of physical
organic chemistry to the study of isotope effects: "Although these effects are
vibrational in origin, and can be dealt with in vibrational terms to a limited extent,
they can be regarded as genuine substituent effects for all practical purposes. Thus
the effect of CD relative to CH on a given property is of qualitatively the same
3 3
nature as that of ethyl or tert-butyl, and may discussed in similar terms." Thus
"one can attempt to correlate secondary isotope effects empirically in terms of the
electrical influences that have proved valuable in interpreting the effects of a
non-isotopic substituent" [3].
1.1 Scope and Aim of the Review
It is the aim of this review to report on nuclear magnetic resonance results.
Especially the work on intrinsic deuterium isotope effects in 13C_ and 19F-NMR
spectroscopy was influenced by the above line of reasoning. This review will
therefore not, or only to a small extent, deal with deuterium isotope effects in
equilibrating molecules, a topic which was comprehensively reviewed by Siehl [4].
It is equally not the aim of this review article to report on all intrinsic deuterium
isotope effects which have been measured recently, because this has been done well
in recent years by the review articles of Hansen [5] and Forsyth [6] following the
initial review by Batiz-Hernandez and Bernheim [7]. We will not mention papers
which report on isotope effects investigated mainly for assignment purposes.
Instead, we will focus on selected papers where experiments were designed in light
of the arguments outlined above. We will see whether the ideas of Halevi and other
early workers in this field were fruitful and may still be valid in the area of high-field
NMR, which provides detailed insight into the electronic properties of molecules.
We will therefore not enlarge on the conventional theory of intrinsic isotope effects
reviewed recently by Jameson [8]. In her approach all deuterium isotope effects
are viewed from and explained by the vibrational model, applying the theory of
the temperature dependence of chemicals shifts. However, this approach, although
physically rigorous (within the accepted model) is hardly able to describe or even
to predict intrinsic isotope effects in molecules of the typical size used in Organic
Chemical Models for Deuterium Isotope Effects 3
Chemistry (MW 200-600), for which isotope effects can be measured over a large
number of chemical bonds.
We will describe here mainly three lines of current experimental research. The
first can be titled with "polarization of n-systems", where deuterium is attached
directly to a n-system such as benzene; the deuterium isotope effects are interpreted
in terms of the analysis of substituent effects in l3C_ NM R spectroscopy. The second
part, closely related to the first part, should be headed with "isotope effects and
hyperconjugation"; experiments are described in which the different hyper
conjugational ability of deuterated alkyl groups is investigated. The third part
describes intrinsic isotope effects as conformational probes and will report on
experiments where deuterium isotope effects are investigated as a tool for
conformational analysis.
1.2 Definitions and Sign Convention
Intrinsic deuterium isotope effects in NMR spectroscopy belong to the class of
secondary isotope effects in which no bond involving the deuterium atom is broken.
We follow the notation given by Hansen [5J by, for example, writing 2~ when the
isotope effect exerted on the chemical shift of a carbon atom comes from a deuterium
atom two bonds away. However, we will not follow the sign convention given by
Hansen and the review article of Batiz-Hernandez [6]. There was a debatel [9,10J
in the literature about this sign convention. Since it is the aim of this review article
to exemplify the similarities between deuterium isotope effects and substituent
effects it is appropriate to adopt the same sign for both effects. Therefore we define
~ = 6deu,cra,cd - 6paren" This means, that a negative ~ implies greater screening in
the de ute rated compound. In all formulas the isotope effects are given in ppb; at
positions where no values are given the isotope effects have not been resolved.
2 Polarization of 1t-Systems
Perhaps the first paper on deuterium isotope effects on chemical shifts with
deuterium directly attached to a n-system was the work by Young and
Yannoni [11]. This contribution was entitled "Deuterium as an aromatic
substituent" and in principle already contained all the basic ideas which were later
described in more detail. The authors took advantage of the large chemical shifts
range of 19F-NMR. Since l3C-NMR was not yet a feasable method, they measured
the deuterium isotope effects in ortho-, meta- and para-deuterofluorobenzenes
(la-c). They found - 285 ppb for the ortho-, - 8 ppb for the meta- and - 11 ppb
for the para-compound.
, It is the experience of this author that referees of different journals tend to argue about the proper
sign of these effects and have papers rewritten mainly for this purpose.