Contents

Cover

Half Title page

Title page

Copyright page

Preface

Problem 1

Problem 2

Problem 3

Problem 4

Problem 5

Problem 6

Problem 7

Problem 8

Problem 9

Problem 10

Problem 11

Problem 12

Problem 13

Problem 14

Problem 15

Problem 16

Problem 17

Problem 18

Problem 19

Problem 20

Problem 21

Problem 22

Problem 23

Problem 24

Problem 25

Problem 26

Problem 27

Problem 28

Problem 29

Problem 30

Problem 31

Problem 32

Problem 33

Problem 34

Problem 35

Problem 36

Problem 37

Problem 38

Problem 39

Problem 40

Problem 41

Problem 42

Problem 43

Problem 44

Problem 45

Problem 46

Problem 47

Problem 48

Problem 49

Problem 50

Problem 51

Problem 52

Problem 53

Problem 54

Problem 55

Problem 56

Problem 57

Problem 58

Problem 59

Problem 60

Problem 61

Problem 62

Problem 63

Problem 64

Problem 65

Problem 66

Instructor’s Guide and Solutions Manual to Organic Structures from 2D NMR Spectra

This edition first published 2015
© 2015 John Wiley & Sons Ltd

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Library of Congress Cataloging-in-Publication Data

Field, L. D.
  Instructor’s guide and solutions manual to organic structures from 2D NMR spectra /
L.D. Field, H.L. Li and A.M. Magill.
      pages cm
    ISBN 978-1-119-02725-6 (pbk.)
 1. Nuclear magnetic resonance spectroscopy–Problems, exercises, etc. 2. Spectrum analysis–Problems, exercises, etc. I. Li, H. L. (Hsiu L.) II. Magill, A. M. (Alison M.) III. Title. IV. Title: Organic structures from 2D NMR spectra. Instructor’s guide and solutions manual. V. Title: 2D NMR spectra.
   QD96.N8F54 2015b
   543′.66–dc23
   2015009524

A catalogue record for this book is available from the British Library.

ISBN: 9781119027256

PREFACE

This book is the Instructor’s Guide and Solutions Manual to the problems contained in the text Organic Structures from 2D NMR Spectra.

The aim of this book is to teach students to solve structural problems in organic chemistry using NMR spectroscopy and in particular 2D NMR spectroscopy. The basic philosophy of the book is that learning to identify organic structures using spectroscopy is best done by working through examples. This book contains a series of about 60 graded examples ranging from very elementary problems through to very challenging problems at the end of the collection.

We have assumed a working knowledge of basic structural organic chemistry and common functional groups. We also assume a working knowledge of the rudimentary spectroscopic methods which would be applied routinely in characterising and identifying organic compounds including infrared spectroscopy and basic 1D ¹³C and ¹H NMR spectroscopy.

The Instructor’s Guide contains a worked solution to each of the problems contained in Organic Structures from 2D NMR Spectra. At the outset, it should be emphasised that there are always many paths to the correct answer – there is no single process to arrive at the correct solution to any of the problems. We do not recommend a mechanical attitude to problem solving – intuition, which comes with experience, has a very important place in solving structures from spectra; however, students often find the following approach useful:

L. D. Field
H. L. Li
A. M. Magill
January 2015

Problem 1

Question:

The ¹H and ¹³C{¹H} NMR spectra of 1-iodopropane (C₃H₇I) recorded in CDCl₃ solution at 298 K and 400 MHz are given below.

The ¹H NMR spectrum has signals at δ 0.99 (H₃), 1.84 (H₂) and 3.18 (H₁) ppm.

The ¹³C{¹H} NMR spectrum has signals at δ 9.6 (C₁), 15.3 (C₃) and 26.9 (C₂) ppm.

Also given on the following pages are the ¹H–¹H COSY, ¹H–¹³C me-HSQC, ¹H–¹³C HMBC and INADEQUATE spectra. For each 2D spectrum, indicate which correlation gives rise to each cross-peak by placing an appropriate label in the box provided (e.g. H₁ → H₂, H₁ → C₁).

Solution:

1. ¹H–¹H COSY spectra show which pairs of protons are coupled to each other. The COSY spectrum is always symmetrical about a diagonal. In the COSY spectrum, there are two ³J_H–H correlations above the diagonal (H₁ → H₂ and H₂ → H₃). There are no long-range correlations.

2. The ¹H–¹³C me-HSQC spectrum shows direct (one-bond) correlations between proton and carbon nuclei, so there will be cross-peaks between H₁ and C₁, H₂ and C₂ and also between H₃ and C₃. As the spectrum is multiplicity edited, the cross-peaks corresponding to CH₂ groups are shown in red and are of opposite phase to those for CH₃ groups.

3. In HMBC spectra, remember that, for alkyl systems, both two- and three-bond C–H coupling can give rise to strong cross-peaks.

4. H₁ correlates to C₂ and C₃. H₂ correlates to C₁ and C₃. H₃ correlates to C₁ and C₂.

5. The INADEQUATE spectrum shows one-bond ¹³C–¹³C connectivity. There are correlations between C₁ and C₂, and C₂ and C₃.

Problem 2

Question:

The ¹H and ¹³C{¹H} NMR spectra of 2-butanone (C₄H₈O) recorded in CDCl₃ solution at 298 K and 400 MHz are given below.

The ¹H NMR spectrum has signals at δ 1.05 (H₄), 2.14 (H₁) and 2.47 (H₃) ppm.

The ¹³C{¹H} NMR spectrum has signals at δ 7.2 (C₄), 28.8 (C₁), 36.2 (C₃) and 208.8 (C₂) ppm.

Also given on the following pages are the ¹H–¹H COSY, ¹H–¹³C me-HSQC, ¹H–¹³C HMBC and INADEQUATE spectra. For each 2D spectrum, indicate which correlation gives rise to each cross-peak by placing an appropriate label in the box provided (e.g. H₁ → H₂, H₁ → C₁).

Solution:

1. ¹H–¹H COSY spectra show which pairs of protons are coupled to each other. The COSY spectrum is always symmetrical about a diagonal. In the COSY spectrum, there is only one ³J_H–H correlation above the diagonal (H₃ → H₄). There are no long-range correlations.

2. The ¹H–¹³C me-HSQC spectrum shows direct (one-bond) correlations between proton and carbon nuclei, so there will be cross-peaks between H₁ and C₁, H₃ and also between C₃ and H₄ and C₄. As the spectrum is multiplicity edited, the cross-peaks corresponding to CH₂ groups are shown in red and are of opposite phase to those for CH₃ groups.

3. In HMBC spectra, remember that, for alkyl systems, both two- and three-bond coupling can give rise to strong cross-peaks. There are no one-bond C–H correlations.

4. H₁ correlates to C₂ and C₃. H₃ correlates to C₁, C₂ and C₄. H₄ correlates to C₂ and C₃.

5. The INADEQUATE spectrum shows one-bond ¹³C–¹³C connectivity. There are correlations between C₁ and C₂, C₂ and C₃ and C₃ and C₄.

Problem 3

Question:

Identify the following compound.

Molecular Formula: C₆H₁₂O

IR: 1718 cm⁻¹

Solution:

1. The molecular formula is C₆H₁₂O. Calculate the degree of unsaturation from the molecular formula: ignore the O atom to give an effective molecular formula of C₆H₁₂ (C_nH_m) which gives the degree of unsaturation as (n − m/2 + 1) = 6 − 6 + 1 = 1. The compound contains one ring or one functional group containing a double bond.

2. The ¹³C{¹H} spectrum establishes that the compound contains a ketone (¹³C resonance at 209.3 ppm). There can be no other double bonds or rings in the molecule because the C=O accounts for the single degree of unsaturation.

3. 1D NMR spectra establish the presence of three CH₂ groups and two CH₃ groups. The multiplicities of the signals can be verified using the me-HSQC spectrum.

4. The COSY spectrum shows a single spin system –H₃ → H₄, H₄ → H₅ and H₅ → H₆ for a –CH₂CH₂CH₂CH₃ fragment.

5. H₁ does not couple to any of the other protons in the molecule and therefore does not show any correlations in the COSY spectrum.

5. The ¹H–¹³C me-HSQC spectrum easily identifies the protonated carbon resonances: C₆ at 13.9, C₅ at 22.4, C₄ at 26.0, C₁ at 29.9 and C₃ at 43.5 ppm.

6. The HMBC spectrum confirms the structure with correlations from H₁ and H₃ to C₂ indicating that the ketone group is located between C₁ and C₃. All other correlations are consistent with the structure.

Problem 4

Question:

The ¹H and ¹³C{¹H} NMR spectra of ethyl propionate (C₅H₁₀O₂) recorded in CDCl₃ solution at 298 K and 300 MHz are given below.

The ¹H NMR spectrum has signals at δ 1.14 (H₁), 1.26 (H₅), 2.31 (H₂) and 4.12 (H₄) ppm.

The ¹³C{¹H} NMR spectrum has signals at δ 9.2 (C₁), 14.3 (C₅), 27.7 (C₂), 60.3 (C₄) and 174.5 (C₃) ppm.

Use this information to produce schematic diagrams of the COSY, HSQC and HMBC spectra, showing where all of the cross-peaks and diagonal peaks would be.

Solution:

1. The molecule contains two independent spin systems – one for each CH₂CH₃ fragment. Each spin system is made up of two unique spins – one CH₂ and one CH₃.

2. The COSY spectrum has peaks on the diagonal for each unique spin, so the spectrum will contain four diagonal peaks.

3. COSY spectra show cross-peaks (off-diagonal peaks) at positions where a proton whose resonance appears on the horizontal axis is directly coupled to another whose resonance appears on the vertical axis.

4. For ethyl propionate, the CH₂ of each spin system will couple to the CH₃ of the same spin system, so two cross-peaks would be expected – one between H₄ and H₅, and another between H₁ and H₂.

5. Remember that a COSY spectrum is symmetrical about the diagonal, so the two peaks above the diagonal must also be reflected below the diagonal.

6. The HSQC spectrum contains cross-peaks at positions where a proton whose resonance appears on the horizontal axis is directly bound to a carbon atom whose resonance appears on the vertical axis. There are four cross-peaks in the HSQC spectrum.

7. The HMBC spectrum contains cross-peaks at positions where a proton whose resonance appears on the horizontal axis is separated by two or three bonds from a carbon atom whose resonance appears on the vertical axis.

Problem 5

Question:

The ¹H and ¹³C{¹H} NMR spectra of ethyl 3-ethoxypropionate (C₇H₁₄O₃) recorded in CDCl₃ solution at 298 K and 600 MHz are given below.

The ¹H NMR spectrum has signals at δ 1.18 (H₁), 1.26 (H₇), 2.56 (H₄), 3.50 (H₂), 3.70 (H₃) and 4.15 (H₆) ppm.

The ¹³C{¹H} NMR spectrum has signals at δ 14.2 (C₇), 15.1 (C₁), 35.3 (C₄), 60.4 (C₆), 65.9 (C₃), 66.4 (C₂) and 171.7 (C₅) ppm.

Also given on the following pages are the ¹H–¹H COSY, ¹H–¹³C me-HSQC and ¹H–¹³C HMBC spectra. For each 2D spectrum, indicate which correlation gives rise to each cross-peak by placing an appropriate label in the box provided (e.g. H₁ → H₂, H₁ → C₁).

Solution:

1. ¹H–¹H COSY spectra show which pairs of protons are coupled to each other. The COSY spectrum is always symmetrical about a diagonal. In the COSY spectrum, there are three ³J_H–H correlations above the diagonal (H₂ → H₁, H₃ → H₄ and H₆ → H₇). There are no long-range correlations.

2. The ¹H–¹³C me-HSQC spectrum shows direct (one-bond) correlations between proton and carbon nuclei, so there will be cross-peaks between H₁ and C₁, H₂ and C₂, H₃ and C₃, H₄ and C₄, H₆ and C₆ and H₇ and C₇. As the spectrum is multiplicity edited, the cross-peaks corresponding to CH₂ groups are shown in red and are of opposite phase to those for CH₃ groups.

3. In HMBC spectra, remember that, for alkyl systems, both two- and three-bond couplings can give rise to strong cross-peaks.

4. H₁ correlates to C₂ only. H₂ correlates to C₁ and C₃. H₃ correlates to C₂, C₄ and C₅. H₄ correlates to C₃ and C₅. H₆ correlates to C₅ and C₇. H₇ correlates to C₆ only.

Problem 6

Question:

The ¹H and ¹³C{¹H} NMR spectra of 4-acetylbutyric acid (C₆H₁₀O₃) recorded in CDCl₃ solution at 298 K and 600 MHz are given below.

The ¹H NMR spectrum has signals at δ 1.81, 2.08, 2.31, 2.47 and 10.5 ppm.

The ¹³C{¹H} NMR spectrum has signals at δ 18.5, 29.8, 32.9, 42.2, 178.8 and 208.6 ppm.

The 2D me-¹H–¹³C HSQC and ¹H–¹³C HMBC spectra are given on the following pages. Use these spectra to assign the ¹H and ¹³C{¹H} resonances for this compound.

Solution:

1. The methyl group (H₆, singlet at 2.08 ppm) and the –OH proton (10.5 ppm, exchangeable) may be easily identified from the ¹H NMR spectrum. The triplet resonances (at 2.31 and 2.47 ppm) correspond to H₂ and H₄ but cannot be assigned by inspection. The more complex resonance at 1.81 ppm must correspond to H₃ since the multiplet structure shows it has more than two neighbouring protons.

2. The signals corresponding to the ketone (C₅, 208.6 ppm) and the carboxylic acid (C₁, 178.8 ppm) in the ¹³C{¹H} NMR spectrum can be assigned by inspection.

3. The ¹H–¹³C me-HSQC spectrum easily identifies the protonated carbon resonances: C₃ at 18.5, and C₆ at 29.8 ppm. The proton resonance at 2.31 ppm correlates to the ¹³C resonance at 32.9 ppm, and the ¹H resonance at 2.47 ppm correlates to the ¹³C resonance at 42.2 ppm.

4. Remember that, in HMBC spectra, two- and three-bond correlations are generally strongest in aliphatic systems.

5. In the ¹H–¹³C HMBC spectrum, H₆ correlates to the ketone carbon (C₅, a two-bond correlation), as well as the resonance at 42.2 ppm. This correlation must be the three-bond correlation to C₄, and so we can assign the resonances at 2.47 and 42.2 ppm to H₄ and C₄, respectively. The newly assigned H₄ shows a strong correlation to C₅, confirming its assignment.

6. H₂ must therefore be the resonance at 2.31 ppm, and C₂ the resonance at 32.9 ppm.

7. In the HMBC spectrum, H₂ correlates strongly to C₁, confirming its assignment.

Problem 7

Question:

Identify the following compound.

Molecular Formula: C₅H₉ClO₂

Solution: