Organic structure determination using 2 d NMR spectroscopy a problem based approach

Organic Structure Determination Using 2-D NMR Spectroscopy A Problem-Based Approach Second Edition Jeffrey H Simpson Department of Chemistry Massachusetts Institute of Technology Cambridge, Massachusetts, USA AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD PARIS • SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 525 B Street, Suite 1900, San Diego, CA 92101-4495, USA 225 Wyman Street, Waltham, MA 02451, USA Radarweg 29, PO Box 211, 1000 AE Amsterdam, The Netherlands The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK Second edition 2012 Copyright Ó 2012 Elsevier Inc All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone (+44) (0) 1865 843830; fax (+44) (0) 1865 853333; email: permissions@elsevier.com Alternatively you can submit your request online by visiting the Elsevier web site at http://elsevier.com/locate/permissions, and selecting Obtaining permission to use Elsevier material Notice No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made Library of Congress Cataloging-in-Publication Data Simpson, Jeffrey H Organic structure determination using 2-D NMR spectroscopy : a problem-based approach / Jeffrey H Simpson e 2nd ed p cm ISBN 978-0-12-384970-0 (pbk.) Molecular structure Organic compoundseAnalysis Nuclear magnetic resonance spectroscopy I Title QD461.S468 2012 547’.122edc23 2011038670 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN: 978-0-12-384970-0 For information on all Academic Press publications visit our web site at elsevierdirect.com Printed and bound in USA 12 13 14 15 10 Dedicated to Edward Worcester teacher, coach, philosopher 1935e2011 Preface The second edition of this book comes with a number of new figures, passages, and problems Increasing the number of figures from 290 to 448 has necessarily impacted the balance between length, margins, and expense It is my hope that the book has not lost any of its readability and accessibility I firmly believe that most of the concepts needed to learn organic structure determination using nuclear magnetic resonance spectroscopy not require an extensive mathematical background It is my hope that the manner in which the material contained in this book is presented both reflects and validates this belief The second edition owes much of its improvement to the efforts of others Most notably, Letitia Yao of the University of Minnesota labored mightily to improve the 2nd edition manuscript A number of researchers at the Massachusetts Institute of Technology assisted in generating samples and collecting some of the data that appear in this edition In this regard, I wish to thank Jason Cox, Rick Danheiser, John Essigmann, Shaun Fontaine, Tim Jamison, Deyu Li, Ryan Moslin, Julia Robinson, and Tim Swager As before, a number of Elsevier personnel have also assisted in bringing this edition to fruition Those at Elsevier who helped with this edition include Gavin Becker, Joy Fisher Williams, Anita Koch, Emily McCloskey, Mohanapriyan Rajendran, Linda Versteeg-Buschman, and Rick Williamson I thank those who reviewed the 1st edition and shared their comments I thank my family for supporting me during manuscript preparation, editing, and proofing Since the publication of the first edition, I have received many emails from readers These emails have been overwhelmingly positive, gratifyingly suggesting that the book fills a niche in the near continuum of NMR books available today I am interested in finding out how I may have erred in presenting any material contained herein so that I may correct errors and thereby improve the book As always, I encourage readers to send me email with comments and suggestions My email address is jsimpson@mit.edu Lastly, I cannot resist suggesting how best to digest the material contained in this book (this philosophy can also be applied to other learning endeavors) If we have the luxury of not having to read and work continuously (i.e., if we are not working to satisfy a deadline), we will be well served by taking breaks in between reading and working problems We balance our work with other interests and try not to let our friendships languish Despite the rigors of work, xiii xiv Preface I still find time to be with my family, to garden, to camp in winter in the White Mountains of New Hampshire (sometimes below À20  F/À29  C), to draw a still life with oil pastels, to play the electric guitar, to drink beer and throw a FrisbeeÔ, to troll for landlocked salmon and togue on Sebec Lake, and to occasionally pull an all-nighter while anchored near the Isles of Shoals six miles off the coast of Maine and New Hampshire Life is hurtling by; we must make the most of it Jeff Simpson Epping, NH, USA July, 2011 Preface to the First Edition I wrote this book because this book did not exist when I began to learn about the application of nuclear magnetic resonance spectroscopy to the elucidation of organic molecular structure This book started as 40 two-dimensional (2-D) nuclear magnetic resonance (NMR) spectroscopy problem sets, but, with a little cajoling from my original editor (Jeremy Hayhurst), I agreed to include problem-solving methodology in chapters and 10, and after that concession was made, the commitment to generate the first chapters was a relatively small one Two distinct features set this book apart from other books available on the practice of NMR spectroscopy as applied to organic structure determination The first feature is that the material is presented with a level of detail great enough to allow the development of useful ‘NMR intuition’ skills, and yet is given at a level that can be understood by a junior-level chemistry major, or a more advanced organic chemist with a limited background in mathematics and physical chemistry The second distinguishing feature of this book is that it reflects my contention that the best vehicle for learning is to give the reader an abundance of real 2-D NMR spectroscopy problem sets These two features should allow the reader to develop problem-solving skills essential in the practice of modern NMR spectroscopy Beyond the lofty goal of making the reader more skilled at NMR spectrum interpretation, the book has other passages that may provide utility The inclusion of a number of practical tips for successfully conducting NMR experiments should also allow this book to serve as a useful resource I would like to thank D.C Lea, my first teacher of chemistry, Dana Mayo, who inspired me to study NMR spectroscopy, Ronald Christensen, who took me under his wing for a whole year, Bernard Shapiro, who taught the best organic structure determination course I ever took, David Rice, who taught me how to write a paper, Paul Inglefield and Alan Jones, who had more faith in me than I had in myself, Dan Reger who was the best boss a new NMR lab manager could have and who let me go without recriminations, and, of course, Tim Swager, who inspired me to amass the data sets that are the heart of this book I thank Jeremy Hayhurst, Jason Malley, Derek Coleman, and Phil Bugeau of Elsevier, and Jodi Simpson, who graciously agreed to come out of retirement to copyedit the manuscript I also wish to thank those who xv xvi Preface to the First Edition reviewed the book and provided helpful suggestions Finally, I have to thank my wife, Elizabeth Worcester, and my children, Grant, Maxwell, and Eva, for putting up with me during manuscript preparation Any errors in this book are solely the fault of the author If you find an error or have any constructive suggestions, please tell me about it so that I can improve any possible future editions As of this writing, e-mail can be sent to me at jsimpson@mit.edu Jeff Simpson Epping, NH, USA January, 2008 CHAPTER Introduction Chapter Outline 1.1 What Is Nuclear Magnetic Resonance? 1.2 Consequences of Nuclear Spin 1.3 Application of a Magnetic Field to a Nuclear Spin 1.4 Application of a Magnetic Field to an Ensemble of Nuclear Spins 1.5 Tipping the Net Magnetization Vector from Equilibrium 12 1.6 Signal Detection 13 1.7 The Chemical Shift 14 1.8 The 1-D NMR Spectrum 14 1.9 The 2-D NMR Spectrum 16 1.10 Information Content Available Using NMR Spectroscopy 18 Problems for Chapter One 19 1.1 What Is Nuclear Magnetic Resonance? Nuclear magnetic resonance (NMR) spectroscopy is arguably the most important analytical technique available to chemists From its humble beginnings in 1945, the area of NMR spectroscopy has evolved into many overlapping subdisciplines Luminaries have been awarded several recent Nobel prizes, including Richard Ernst in 1991, John Pople in 1998, and Kurt Wuăthrich in 2002 Nuclear magnetic resonance spectroscopy is a technique wherein a sample is placed in a homogeneous1 (constant) magnetic field, irradiated, and a magnetic signal is detected Photon bombardment of the sample causes nuclei in the sample to undergo transitions2 (resonance) between their allowed spin states In an applied magnetic field, spin states that differ energetically are unequally populated Perturbing the equilibrium distribution of the spin-state population is called excitation.3 The excited nuclei emit a magnetic signal called a free induction decay4 (FID) which we detect with analog electronics and capture digitally The Homogeneous Constant throughout Transition The change in the spin state of one or more NMR-active nuclei Excitation The perturbation of spins from their equilibrium distribution of spin-state populations Free induction decay, FID The analog signal induced in the receiver coil of an NMR instrument caused by the xy component of the net magnetization Sometimes the FID is also assumed to be the digital array of numbers corresponding to the FID’s amplitude as a function of time Organic Structure Determination Using 2-D NMR Spectroscopy DOI: 10.1016/B978-0-12-384970-0.00001-6 Copyright Ó 2012 Elsevier Inc All rights reserved Chapter digitized FID(s) is(are) processed computationally to (we hope) reveal meaningful things about our sample Although excitation and detection may sound very complicated and esoteric, we are really just tweaking the nuclei of atoms in our sample and getting information back How the nuclei behave once tweaked conveys information about the chemistry of the atoms in the molecules of our sample The acronym NMR simply means that the nuclear portions of atoms are affected by magnetic fields and undergo resonance as a result 1.2 Consequences of Nuclear Spin Observation of the NMR signal5 requires a sample containing atoms of a specific atomic number and isotope, i.e., a specific nuclide such as protium, the lightest isotope of the element hydrogen, also commonly referred to as simply a proton A magnetically active nuclide will have two or more allowed nuclear spin states.6 Magnetically active nuclides are also said to be NMR-active Table 1.1 lists several NMR-active nuclides in approximate order of their importance to chemists An isotope’s NMR activity is caused by the presence of a magnetic moment7 in its nucleus The nuclear magnetic moment arises because the positive charge prefers not to be well located, as described by the Heisenberg uncertainty principle (see Figure 1.1) Instead, the nuclear charge circulates Because the charge and mass are both inherent to the particle, the movement of the charge imparts movement to the mass of the nucleus The motion of all rotating masses is Table 1.1: NMR-active nuclides Nuclide H C 15 N 19 F 31 P H (or 2D) 13 Element-Isotope Spin Natural Abundance (%) Frequency Relative to 1H Hydrogen-1 Carbon-13 Nitrogen-15 Fluorine-19 Phosphorus-31 Deuterium-2 ½ ½ ½ ½ ½ 99.985 1.108 0.37 100 100 0.015 1.00000 0.25145 0.10137 0.94094 0.40481 0.15351 Signal An electrical current containing information Spin state Syn spin angular momentum quantum number The projection of the magnetic moment of a spin onto the z-axis The orientation of a component of the magnetic moment of a spin relative to the applied field axis (for a spin-½ nucleus, this can be +½ or e½) Magnetic moment A vector quantity expressed in units of angular momentum that relates the torque felt by the particle to the magnitude and direction of an externally applied magnetic field The magnetic field associated with a circulating charge Introduction Figure 1.1: The structure of an atom with the positive charge unequally distributed in the nucleus inside the electron cloud expressed in units of angular momentum In a nucleus, this motion is called nuclear spin.8 Imagine the motion of the nucleus as being like that of a wild animal pacing in circles in a cage Nuclear spin (see column three of Table 1.1) is an example of the motion associated with zero-point energy in quantum mechanics, whose most well-known example is perhaps the harmonic oscillator The small size of the nucleus dictates that the spinning of the nucleus is quantized; that is, the quantum mechanical nature of small particles forces the spin of the NMR-active nucleus to be quantized into only a few discrete states Nuclear spin states are differentiated from one another based on how much the axis of nuclear spin aligns with a reference axis (the axis of the applied magnetic field, see Figure 1.2) We can determine how many allowed spin states there are for a given nuclide by multiplying the nuclear spin number (I) by and adding For a spin-½ nuclide, there are therefore (1/2) ỵ ẳ allowed spin states In the absence of an externally applied magnetic field, the energies of the two spin states of a spin-½ nuclide are degenerate9 (the same) The circulation of the nuclear charge, as is expected of any circulating charge, gives rise to a tiny magnetic field called the nuclear magnetic moment (m) e also commonly referred to as a spin (recall that the mass puts everything into a world of angular momentum) Magnetically active nuclei are rotating masses, each with a tiny magnet, and these nuclear magnets interact with other magnetic fields according to Maxwell’s equations Nuclear spin The circular motion of the positive charge of a nucleus Degenerate Two spin states are said to be degenerate when their energies are the same 560 Index Compound X in D2O aliphatic hydrocarbons and, 224, 225f aromatic hydrocarbons and, 224, 225f cross-peak of, 229, 233e234 examination methodology for, 224 gCOSY of, 231f, 233f HMBC of, 234f HMQC and, 227e229, 228f, 229f initial inspection of, 224e227 resonances of, 227t, 228t signal-to-noise ratio of, 224 structure of, 235f, 236f Console computer, 34 Continuous wave (CW), 15, 129, 144 Continuous wave decoupling (CW decoupling), 144 Continuous wave RF (CW RF), 129, 180 Contour line See Successive contour line CooleyeTukey algorithm, 69 Corduroy pattern, 72 Correlation spectroscopy (COSY), 17e18, 37 cross peaks of, 149, 195 PFGs and, 151 as phase-sensitive or non-phase-sensitive, 149e150 using J-coupling, 149e151 Correlation time, 189f decrease of, 188e189 spectral density function and, 172e173, 173f T1 relaxation and, 188 T2 relaxation and, 188 COSY See Correlation spectroscopy CPMG experiment See Carr-Purcell-Meiboom-Gill CRC Handbook of Chemistry and Physics, 202 Cross product, 6e7, 7f Cross-peak, 93e94 of compound X in D2O, 229, 233e234 of COSY, 149, 195 of HMBC, 164e165, 220e221 of HMQC, 161 of HSQC, 214 information provided by, 182 intensity of, 209 irreversible reaction, 195 overlapping, 216 ROESY generation of, 181e182 strength of, 98e99 Cryogenically cooled probe, 49e50 costs of, 50 requirements and weaknesses of, 49e50 CSA See Chemical shift anisotropy a-Cubebene resonance assignment problem, 427e432 13 C NMR spectrum, 428f gCOSY, 429f gHMBC, 431f H NMR spectrum, 428f HSQC, 430f structure of, 427f CW See Continuous wave CW decoupling See Continuous wave decoupling CW RF See Continuous wave RF Cyclic hydrocarbons, saturated, 106 Cyclohexane ring, 139f J-coupling in, 138e139 Newman projection of, 138e139, 140f D d See Chemical shift Dach effect, 128f, 130, 131f absence of, 131e132 Darling Models, 116 Data collection acquisition time for, 65e66 backward linear prediction and, 77e78 baseline correction and, 81e83 chemical shift and J-coupling measurement, 87e92 data representation and, 92e100 forward linear prediction and, 75e77 integration of, 83e87 one-dimensional NMR point acquisition, 67e68 phase correction and, 78e81 point acquisition and, 66e67 pulse rind down and, 77e78 resolution enhancement and, 75 truncation error and apodization, 71e72 two-dimensional NMR point acquisition, 69e71 zero filling and digital resolution, 67e68 Data point, 69e70, 76e77, 209 13 C, 213e214 complex, 87e88 digital, 71 recording of, 66e67 t2, 213e214 Data representation, 92e100 colored plots and, 92 Decoupling See also Continuous wave decoupling effect of, 174, 175f gated, 144 HMQC and HSQC, 157 Index as homonuclear or heteronuclear, 142e143 mechanism of, 143 methods for, 142e145 simplest type of, 144 timing of, 144 Degenerate, Dephasing, 64 Depolarization, 64 DEPT See Distortionless enhancement through polarization transfer Deshielded group, 103e104, 106 Detection period, 18 Deuterium lock channel, 31e32, 39 Diastereotopic group, 113e114 anisochronous of, 117e118 Diastereotopicity, 117e120 classification of, 118 Newman projections of, 118 Digital data point, 71 Digital resolution, 67e68 accuracy and, 89 effect of, 68f importance of, 87e88 limitations of, 68 variations of, 89 Digitization, 77, 144e145 of FID, 67, 71e72, 74, 76e77, 79, 86e87 signal, 53e57, 161 Dihedral angle, 119, 164e165 orbital geometries of, 138, 139f Dimethyl sulfoxide (DMSO), 25 1,3-Dimethylcyclohexane, 116e117, 116f Dipolar interaction, 190 resonance intensities influenced by, 170 Dipolar relaxation pathway, 169e170 Dipolar relaxation rate constant (W), 170e171 Distortionless enhancement through polarization transfer (DEPT), 145, 148, 148f of longifolene, 148, 148f, 291f DMSO See Dimethyl sulfoxide DNP See Dynamic nuclear polarization Double quantum filtered COSY (DQF-COSY), 150 Double quantum pathway, rapid relaxation via, 174e177 Double quantum spin flip rate constant (W2), 186 shut down of, 177 Doublet, 127, 128f Doublet of doublets, 136e137, 137f Downfield, 70e71, 86, 103e104, 106e107, 109f DQF-COSY See Double quantum filtered COSY 561 Dummy scans See Steady-state scans Dwell time, 54, 66e67, 144e145, 178e179 Dynamic nuclear polarization (DNP), 8, 49 E Ea See Activation energy (-)-Eburnamonine complex resonance assignment problem, 316e320 13 C NMR spectrum, 317f gCOSY, 318f gHMBC, 320f gHSQC, 319f H NMR spectrum, 316f structure of, 316f EDGs See Electron-donating groups Einstein, Albert, 4e5 Electron-donating groups (EDGs), 103 Electronegativity, 102, 105, 111, 204 of nearby atoms, 101, 200, 211e212 resonance and, 218e219 Electron-withdrawing groups (EWGs), 103 Enantiotopic atoms, anisochronous of, 116e117 Enantiotopicity, 116e117 chemical shifts and, 117 design of, 117 Energetics of isolated heteronuclear two-spin system, 170e172 of spin-state combinations, 171f Enhancement (NOE enhancement), 175e176, 180 Ensemble, 11 Entry points, 199e200 identification of, 200e201 of unknown molecular structure, 230 (-)-Epicatechin complex resonance assignment problem, 311e315 13 C NMR spectrum, 312f gCOSY, 313f gHMBC, 315f H NMR spectrum, 312f HSQC, 314f structure of, 311f Epimer, 120 Equilibrium, M tipping, 12e13, 62 Ernst, Richard, Ernst angle, 62e63 Ethanol, 131e132 structure of, 132f Ethernet card, 34 Ethernet connection, 34 562 Index Ethyl nipecotate, 202e203, 202f bookkeeping on, 203t chemical shift of, 204 examination of, 205 gCOSY of, 208e209, 208f HMQC of, 214, 215f one-dimensional NMR spectrum of, 205f, 212, 213f resonances of, 211 (1S*, 4S*, 10S*)-1-Ethyl-4-(hydroxyethyl)quinolizidine, resonance assignment problem, 432e436 13 C NMR spectrum, 433f gCOSY, 434f gHMBC, 436f H NMR spectrum, 433f HSQC, 435f 6-ethyl-3-formylchromone, 217 13 C NMR spectrum of, 218f examination of, 219 HMBC of, 219f, 220 structure of, 218f Evolution time, t1, 17e18, 75e76, 152e153, 160e161 EWGs See Electron-withdrawing groups Excitation, 1e2 efficiency cutoffs, 47t RF frequency limits, 47t Exponentially damped sinusoid, 76e77, 79 EXSY spectrum, 195, 196f of compound 119, 477 F F1 frequency axis, 75e76, 82e83, 82f, 210 F1 frequency domain, 18, 75e76 F1 projection, 99e100, 163, 167 F2 frequency axis, 18, 82e83, 213e214 F2 frequency domain, 18, 69, 149e150 F2 projection, 18, 82e83, 99e100, 213e214 Fast-exchange limit, 174 (1R)-endo-(+)-Fenchyl alcohol simple resonance assignment problem, 246e251 13 C NMR spectrum, 247f gCOSY, 248f H NMR spectrum, 246f HMBC, 250f HSQC, 249f NOESY, 251f structure of, 246f FID See Free induction decay Field gradient pulse, 49, 64, 64f, 155e156 Field heterogeneity, 28e29 Field homogeneity, 27e28, 33, 149 Field lock, 31 Field strength, J-coupling and, 130e131 Filter attenuation, 52e53, 53f RF, 156 Filtering, of RF, 37e39 First-order multiplet prediction, 135t J-coupling and, 131e137 rule for, 133e134 First-order phase correction, 77e80 Flip-flop transition, 173e174 See also Zero quantum spin flip rate constant Flow-through probe, 49 Folding, 55, 60e61, 61f Forward linear prediction, 75e77 rule of thumb for, 76e77 two-dimensional NMR spectrum and, 75e76 use of, 76 Forward power, 37 Fourier ripples, 72 Fourier transform (FT), 15e16, 67e68, 72, 161 Frame of reference relationship between static and rotating, 42f sample excitation and, 41e42 static compared to rotating, 42f Free induction decay (FID) acquisition time of, 67e68, 85, 156 clipped, 56, 56f definition, 1e2, 66 digitization of, 67, 71e72, 74, 76e77, 79, 86e87 signal-rich portion of, 75 Frequency calculation of, determining, 173e174 J-coupling altering, 125e126 measurement of, 89 Frequency domain, 14e15, 54, 72e74, 201 F1, 18, 75e76 F2, 18, 69, 149e150 Frequency measurement, accuracy of, 89 Frequency spectrum, chemical exchange and, 193 Frequency synthesizer, 35 FT See Fourier transform Full cannon homospoil method, 65 Fuptet, 134e135, 136f G g See Gyromagnetic ratio Gated decoupling, 144 Gaussian function, 71e72, 75 Index Gaussian line broadening, 71e72 gCOSY See Gradient-selected correlation spectroscopy Geminal bond angle, 164e165 gHMBC See Gradient-selected heteronuclear multiple bond correlation gHSQC See Gradient-selected heteronuclear single quantum correlation Gradient probe See Pulsed-field gradients Gradient pulse See Field gradient pulse Gradient-selected correlation spectroscopy (gCOSY), 150e151 aliphatic side of, 232 chemical shift identification from, 211 complex resonance assignment problem (-)-ambroxide, 338f L-cinchonidine, 302f cis-myrtanol, 328f (-)-eburnamonine, 318f (-)-epicatechin, 313f (+)-limonene, 297f of longifolene, 292f naringenin, 333f (3aR)-(+)-sclareolide, 308f trans-myrtanol, 323f of compound X in D2O, 231f, 233f distortion of, 209 of ethyl nipecotate, 208e209, 208f examination of, 209 of menthol, 82f, 98f reading of, 210e211 resonance assigning based on, 207e209, 216e217 artemisinin, 444f melatonin, 464f piperine, 459f resonance assignment problems brucine, 454f compound 119, 474e477, 476f compound 119, 469f a-cubebene, 429f (1S*, 4S*, 10S*)-1-ethyl-4-(hydroxyethyl)quinolizidine, 434f sinomenine, 439f vincamine, 449f simple resonance assignment problem 2-acetylbutyrolactone, 239f N-acetylhomocysteine thiolactone, 260f (-)-bornyl acetate, 253f guaiazulene, 265f 563 2-hydroxy-3-pinanone, 270f 7-methoxy-4-methylcoumarin, 280f (R)-(+)-perillyl alcohol, 275f sucrose, 285f a-terpinene, 243f symmetry and, 210 unknown structure elucidation problems complex unknown, 382f, 387f, 392f, 396f, 401f, 406f, 410f, 415f, 420f, 424f simple unknown, 343f, 348f, 352f, 355f, 358f, 362f, 365f, 369f, 373f, 376f unknown, 481f, 486f, 487f, 492f, 497f, 501f, 506f, 510f, 514f, 518f, 522f Gradient-selected heteronuclear multiple bond correlation (gHMBC), 80 complex resonance assignment problem (-)-ambroxide, 340f L-cinchonidine, 304f, 305f cis-myrtanol, 330f (-)-eburnamonine, 320f (-)-epicatechin, 315f (+)-limonene, 299f naringenin, 335f (3aR)-(+)-sclareolide, 310f, 311f trans-myrtanol, 325f plot threshold variation and, 93f, 94f, 95f of progesterone, 166f resonance assignment problems artemisinin, 446f, 447f brucine, 456f compound 142, 472f, 473f (1S*, 4S*, 10S*)-1-ethyl-4-(hydroxyethyl) quinolizidine, 436f melatonin, 466f piperine, 461f sinomenine, 441f vincamine, 451f simple resonance assignment problem (1R)-endo-(+)-fenchyl alcohol, 247f 2-hydroxy-3-pinanone, 272f 7-methoxy-4-methylcoumarin, 282f (R)-(+)-perillyl alcohol, 277f sucrose, 287f a-terpinene, 245f unknown structure elucidation problems complex unknown, 384f, 389f, 394f, 398f, 408f, 412f, 417f, 422f simple unknown, 367f, 371f, 374f, 378f unknown, 483f, 489f, 490f, 494f, 495f, 499f, 503f, 504f, 508f, 512f, 516f, 520f, 524f, 525f 564 Index Gradient-selected heteronuclear single quantum correlation (gHSQC) complex resonance assignment problem cis-myrtanol, 329f (-)-eburnamonine, 319f trans-myrtanol, 324f simple resonance assignment problem 2-hydroxy-3-pinanone, 271f 7-methoxy-4-methylcoumarin, 281f (R)-(+)-perillyl alcohol, 276f unknown structure elucidation problems complex unknown, 397f, 402f, 407f, 411f, 416f, 421f simple unknown, 370f, 377f Guaiazulene, simple resonance assignment problem, 263e267 13 C NMR spectrum, 264f gCOSY, 265f H NMR spectrum, 263f HMBC, 267f HSQC, 266f Gyromagnetic ratio (d) definition of, signal strengths influencing, 11 H H chemical shift, 66e67, 203e204 of aliphatic hydrocarbons, 105 of aromatic hydrocarbons, 108e109 axis, 167, 229 heteroatom effects of, 110t isotopic effect on, 125 H coil, 51e52 Heisenberg uncertainty principle, 3f, 4e5 Helical array of vectors, 64 HETCOR See Heteronuclear correlation Heteroatom effects, 110e111 Heteronuclear correlation (HETCOR), 155e156 Heteronuclear decoupling, 142e143 Heteronuclear experiment, utilizing J-coupling, 155e167 HMBC, 163e167 HMQC and HSQC, 155e163 Heteronuclear multiple bond correlation (HMBC), 37, 70e71, 163e167, 165f complex resonance assignment problem, of longifolene, 294f of compound X in D2O, 234f cross peaks of, 164e165, 220e221 of 6-ethyl-3-formylchromone, 219f, 220 feature of, 164 methodology of, 163e164 plotting of, 167 practicality of, 167 resonance assignment based on, 217e221 scans required for, 164 simple resonance assignment problem N-acetylhomocysteine thiolactone, 262f (-)-bornyl acetate, 255f, 256f guaiazulene, 267f unknown structure elucidation problems, complex unknown, 403f, 426f Heteronuclear multiple quantum correlation (HMQC), 70e71, 135e136, 155e163 complex resonance assignment problem, of longifolene, 293f compound X in D2O and, 227e229, 228f, 229f cross peaks of, 161 decoupling and, 157 of ethyl nipecotate, 214, 215f examination of, 215 M and, 159f plotting of, 163 pulse sequence of, 158f, 159f, 160f resonances and, 213e217 setup of, 162e163 simple resonance assignment problem 2-acetylbutyrolactone, 240f N-acetylhomocysteine thiolactone, 261f (-)-bornyl acetate, 254f unknown structure elucidation problems, simple unknown, 344f, 349f, 350f, 353f, 356f, 359f, 360f, 363f Heteronuclear single quantum correlation (HSQC), 37, 70e71, 97f, 135e136, 155e163, 162f complex resonance assignment problem (-)-ambroxide, 339f L-cinchonidine, 303f (-)-epicatechin, 314f (+)-limonene, 298f naringenin, 334f (3aR)-(+)-sclareolide, 309f cross peaks of, 214 decoupling and, 157 normalized volume integrals of, 163t plotting of, 163 resonance assignment problem artemisinin, 445f brucine, 455f Index compound 142, 470f, 471f a-cubebene, 430f (1S*, 4S*, 10S*)-1-ethyl-4-(hydroxyethyl) quinolizidine, 435f melatonin, 465f piperine, 460f sinomenine, 440f vincamine, 450f resonances and, 213e217 setup of, 162e163 simple resonance assignment problem (1R)-endo-(+)-fenchyl alcohol, 246f guaiazulene, 266f sucrose, 286f a-terpinene, 244f unknown structure elucidation problems, 515f complex unknown, 383f, 388f, 393f, 425f simple unknown, 366f unknown, 482f, 488f, 493f, 498f, 502f, 507f, 511f, 519f, 523f Heteronuclear splitting, 136 Heteronuclear two-spin system decoupling one of, 174 energetics of, 170e172 Highband channel, 38 High-performance liquid chromatography (HPLC), 25 HMBC See Heteronuclear multiple bond correlation HMQC See Heteronuclear multiple quantum correlation Homogeneous, 1e2 Homonuclear experiment, utilizing J-coupling, 149e155 absolute-value COSY, including gCOSY, 150e151 COSY, 149e151 INADEQUATE, 154e155 phase-sensitive COSY, 150 TOCSY, 151e153 Homonuclear single-frequency decoupling, 142e145 Homospoil method, 63 Homotopicity, 115e116, 115f testing for, 115 Host computer, 34e35, 69 HPLC See High-performance liquid chromatography HSQC See Heteronuclear single quantum correlation Hydrocarbons acetylenic, 107 aliphatic, 104e105, 105f aromatic, 108e109, 109f 565 cyclic, 106 olefinic, 106e107 2-Hydroxy-3-pinanone simple resonance assignment problem, 268e272 13 C NMR spectrum, 269f gCOSY, 270f gHMBC, 272f gHSQC, 271f H NMR spectrum, 268f structure of, 268f I Impurity, 86 Incredible natural abundance double-quantum transfer experiment (INADEQUATE), 154e155 mechanism of, 154 sample concentration needed for, 155 Instrument architecture of, 34e39 evolution of, 22 Integrals, 60e61, 66, 81, 83e84 accuracy of, 84e86 prediction of, 201 Integration, 18e19, 62, 83e87 accuracy of, 84e85 application of, 83e84 Intensities of cross-peak, 209 of multiplet, 207 prediction of, 201, 212 Interferogram, examination of, 17e18 Interleaving, 152 Intermediate chemical exchange, 193e195 as amendable, 193 Internuclear distance, 180 Isochronous, 114 Isopropyl cyclohexane, 116e117, 116f J J-coupling, 123e168 consistency of, 126 in cyclohexane rings, 138e139 decoupling methods, 142e145 doublet of doublet and, 137f facts regarding, 128e129 field strength variation and, 130e131 first-order multiplet prediction, 131e137 frequency altered by, 125e126 geometries of, 125f, 126f 566 Index J-coupling (Continued ) as independent field, 126 Karplus relationship spins separated by three bonds, 137e139, 138f spins separated by two bonds, 139e141 long range, 142 measurement of, 87e92 multiplet intensity skewing and, 128e131 occurrence of, 124 one-dimensional experiments using, 145e148 origin of, 124e128 pentet pattern and, 136f quartet pattern and, 134f shifts caused by, 124 spin state and, 130 splitting pattern of, 134f as through-bond effect, 123e124 triplet pattern and, 136f two-dimensional experiments utilizing, 148e167 heteronuclear experiment, 155e167 HMBC, 163e167 HMQC and HSQC, 155e163 homonuclear experiment, 149e155 absolute-value COSY, including gCOSY, 150e151 COSY, 149e151 INADEQUATE, 154e155 phase-sensitive COSY, 150 TOCSY, 151e153 use of, 124 Johnson noise, 49e50 K Karplus diagram, 164e165, 218e219 Karplus relationship, 218e219 spins separated by three bonds, 137e139, 138f spins separated by two bonds, 139e141 L Larmor frequency, 6e7, 12 Lattice, 11e14 Leaning, definition of, 89e90 Leg, 127 (+)-Limonene complex resonance assignment problem, 295e299 13 C NMR spectrum, 296f gCOSY, 297f gHMBC, 299f H NMR spectrum, 295f HSQC, 298f structure of, 295f Line broadening See Apodization Line broadening function See Lorentzian line broadening function Line width See Observed line width Linear prediction See Backward linear prediction; Forward linear prediction Lock channel See Deuterium lock channel Lock frequency See Larmor frequency Locking, 31e32 field, 31 Long range J-coupling, 142 Longifolene complex resonance assignment problem, 148, 148f, 289e294 13 C NMR spectrum, 290f DEPT-135 NMR spectrum, 291f gCOSY, 292f H NMR spectrum, 290f HMBC, 294f HMQC, 293f structure of, 289f Lorentzian line broadening function, 71e72 M M See Net magnetization vector m See Nuclear magnetic moment Magnet bore tube, 32, 35, 48 Magnetic field, fluctuations of, 189 Magnetic moment, 2e3 vector summation of, 10f Magnetic susceptibility, 28 Magnetically equivalent, 120 Malonic acid, 115, 115f Melatonin resonance assignment problem, 462e466 13 C NMR spectrum, 463f gCOSY, 464f gHMBC, 466f H NMR spectrum, 462f HSQC, 465f structure of, 462f The Merck Index, 202 Mesitylene, 115, 115f Metal ion, T1 relaxation influenced by, 86 Methine group, APT of, 146, 146f, 147f 7-Methoxy-4-methylcoumarin simple resonance assignment problem, 278e282 13 C NMR spectrum, 279f gCOSY, 280f gHMBC, 281f Index gHSQC, 281f H NMR spectrum, 278f structure of, 278f 2-Methyl Malonic acid, 116e117, 116f Methylene spin state of, 132e133 splitting of, 133 Mixing definition of, 17e18 down, 52 NOESY and, 181 sample, 25 TOCSY and, 153 Molecular dynamics, 185e197 cursory understanding of, 185e186 intermediate chemical exchange and, 193e195 NMR spectroscopy influenced by, 185 rapid chemical exchange, 190e191 relaxation and, 186e190 slow chemical exchange and, 191e192 Molecular geometry, distortions in, 141 Molecular SieveÔ, 27 Molecular site stoichiometry, 113e114 Molecular Visions, 116 Multiple resonance, irradiation of, 178 Multiplet analysis of, 207 intensities of, 207 overlap resonance and, 92 prediction of, 201e202 skewing of, 89e91, 90f, 128e131 terminology for, 201 Multiplicities analysis of, 205 basis of, 204e207 identification of, 232 N Naringenin complex resonance assignment problem, 331 13 C NMR spectrum, 332f gCOSY, 333f gHMBC, 335f H NMR spectrum, 331f HSQC, 334f structure of, 331f Narrow resonances, truncation error and, 72 Net magnetization vector (M), 41 behavior of, 12 567 definition of, 11 division of, 79 equilibrium tipping from, 12e13, 62 HMQC and, 159f phase correction and, 78 pulse rolloff and, 65 split of, 42e43 tipping of, 43f Newman projections of cyclohexane ring, 138e139, 140f of diastereotopicity, 118 6-Nitrochrysene, 178, 179f NMR See Nuclear magnetic resonance spectroscopy NMR time scale, 190e191 No-bond resonance, 109 Node, 45 NOE See Nuclear Overhauser effect NOE enhancement See Enhancement (NOE enhancement) NOESY See Nuclear Overhauser effect spectroscopy Noise floor, 94e96 Non-first-order effects, 89e90 Normal coil configuration, 51e52, 155 Nuclear magnetic moment (m), cancellation of, 10 Nuclear magnetic resonance (NMR) spectroscopy, 1e2 information from, 18e19 molecular dynamics influencing, 185 Nuclear Overhauser effect (NOE), 169e184 of 6-nitrochrysene, 179f dipolar relaxation pathway and, 169e170 efficiency of, 180 enhancement variation of, 175e176, 180 irradiation and, 178e179 loss of, 177 one-dimensional experiment utilizing, 177e180 relaxation mechanisms and, 180 spectral density function and, 172e174 as through-space effect, 177 two-dimensional experiment utilizing, 181e183 Nuclear Overhauser effect spectroscopy (NOESY), 37, 63 experiment of, 181 mixing time and, 181 showing chemical exchange, 195 simple resonance assignment problem, (1R)-endo-(+)-fenchyl alcohol, 251f unknown structure elucidation problems, simple unknown, 345f 568 Index Nuclear shielding, 14 Nuclear spin, 9f consequences of, 2e3 magnetic field forcing, 4e7 magnetic field forcing ensemble of, 7e12 Nuclides, magnetically active, 2t Nyquist sampling theorem, 54 O Observed line width, T*2 relaxation and, 73e74 Occam’s razor, 223e226 Off-resonance, 42e45 Offset, 60 Olefinic hydrocarbons, 106e107 One-dimensional 1H NMR spectrum complex resonance assignment problem (-)-ambroxide, 336f L-cinchonidine, 300f cis-myrtanol, 326f (-)-eburnamonine, 316f (-)-epicatechin, 312f (+)-limonene, 295f of longifolene, 290f naringenin, 331f (3aR)-(+)-sclareolide, 306f trans-myrtanol, 321f resonance assignment problem artemisinin, 442f brucine, 452f compound, 119, 475f compound, 142, 467f a-cubebene, 428f (1S*, 4S*, 10S*)-1-ethyl-4-(hydroxyethyl)quinolizidine, 433f melatonin, 462f piperine, 457f sinomenine, 437f vincamine, 448f simple resonance assignment problem 2-acetylbutyrolactone, 238f N-acetylhomocysteine thiolactone, 258f (1R)-endo-(+)-fenchyl alcohol, 246f guaiazulene, 263f 7-methoxy-4-methylcoumarin, 278f (R)-(+)-perillyl alcohol, 273f sucrose, 283f a-terpinene, 241f unknown structure elucidation problems complex unknown, 380f, 385f, 386f, 390f, 395f, 399f, 409f, 413f, 418f, 423f simple unknown, 341f, 346f, 351f, 353f, 357f, 361f, 363f, 368f, 372f, 374f unknown, 480f, 484f, 491f, 496f, 500f, 505f, 509f, 513f, 517f, 521f One-dimensional 13C NMR spectrum complex resonance assignment problem (-)-ambroxide, 337f L-cinchonidine, 301f cis-myrtanol, 327f (-)-eburnamonine, 317f (-)-epicatechin, 312f (+)-limonene, 296f of longifolene, 290f naringenin, 332f (3aR)-(+)-sclareolide, 307f trans-myrtanol, 322f of compound X in D2O, 226f of 6-ethyl-3-formylchromone, 218f resonance assignment problem artemisinin, 443f brucine, 453f compound 142, 468f a-cubebene, 428f (1S*, 4S*, 10S*)-1-ethyl-4-(hydroxyethyl)quinolizidine, 433f melatonin, 463f piperine, 458f sinomenine, 438f vincamine, 448f simple resonance assignment problem 2-acetylbutyrolactone, 238f N-acetylhomocysteine thiolactone, 259f (1R)-endo-(+)-fenchyl alcohol, 247f guaiazulene, 264f 7-methoxy-4-methylcoumarin, 279f (R)-(+)-perillyl alcohol, 274f sucrose, 284f a-terpinene, 242f time periods of, 16, 16f unknown structure elucidation problems complex unknown, 381f, 386f, 391f, 395f, 400f, 405f, 409f, 414f, 419f, 423f simple unknown, 342f, 347f, 351f, 354f, 357f, 361f, 364f, 368f, 372f, 375f unknown, 480f, 485f, 491f, 496f, 500f, 505f, 509f, 513f, 517f, 521f using NOE, 177e180 utilizing J-couplings, 145e148 One-dimensional NMR pulse sequence, 16e17, 16f, 17f Index One-dimensional NMR spectrum of cedryl acetate, 23, 24f central peak of, 127f chemical shift influencing, 70f of ethyl nipecotate, 205f of 1-ethyl-2-pyrrolidone, 85f examination of, 205, 207 2-hydroxy-3-pinanone, 268f, 269f initial inspection of, 224e227 of menthol, 191f overview of, 14e16 points acquired in, 66e67 pulse sequence of, 15 of S-(-)-1-(2-methoxybenzoyl)-2-methoxy-methyl) pyrrolidine, 192f One-pulse NMR experiment, 40f On-resonance, 26f, 42e43, 44f, 45 Optimal solute concentration, 29e30 Optimal wait between scans, 62e65 Orbital geometries, 141f of dihedral angle, 138, 139f four-bond, 143f Overlap resonance, 90e91, 91f multiplet intensity and, 92 Oversampling, 34 P Paramagnetic relaxation agent, 63 Paramagnetic species, 86 Pascal’s triangle, 133e134 Pattern, sinusoidal, 41, 41f Pauli electronegativities, 101 Peak symmetry, 80e81 Peak-picking, 88f definition of, 87 3-Pentanone, 115, 115f Pentet, 134e135, 136f (R)-(+)-Perillyl alcohol simple resonance assignment problem, 273e277 13 C NMR spectrum, 274f gCOSY, 275f gHMBC, 277f gHSQC, 276f H NMR spectrum, 273f structure of, 273f PFGs See Pulsed-field gradients Phase character, 17e18, 164 Phase correction, 78e81 M and, 78 phase-sensitive receiver detection mode for, 78 pulse ring down and, 79 requirement of, 78 two-dimension NMR spectrum and, 80 zero-order, 79 Phase cycling, 63, 81, 213e214 Phaseable, 216 Phase-sensitive COSY, 150 minimum phase cycle for, 150 Phase-sensitive NMR spectrum, 54e55 Phase-sensitive receiver detection mode, 78 Piperine resonance assignment problem, 457e461 13 C NMR spectrum, 458f gCOSY, 459f gHMBC, 461f H NMR spectrum, 457f HSQC, 460f structure of, 457f Plot threshold school of thought on, 94e96 variation of, 92e93, 93f, 94f, 95f Point See Data point Pople, John, Positive rotation, Precession frequency See Larmor frequency Probe delivery, 35 temperature recommendations for, 185 tuning, 36e37 poorly, 36 timing of, 37 variation, 47e52 cryogenically cooled, 49e50 flow-through, 49 normal versus inverse coil configuration in, 51e52 sizes, 50e51 small-volume, 48 Protic solvent, 224, 283 Protium, Proton channel See Highband channel Pulse calibration, 39e41, 40f RF and, 37 time periods in, 39, 40f Pulse ring down, 77e78 cause of, 77 delay of, 77e78 negative effects of, 77 phase correction and, 79 569 570 Index Pulse rolloff, 13, 42e46 definition of, 45 M and, 65 on-resonance, 44f Pulse sequence, 149 acquisition time in, 157 for APT, 145f, 147 of HMQC, 158f, 159f, 160f of one-dimensional NMR spectrum, 15 powerful nature of, 147e148 of two-dimensional NMR spectrum, 17 Pulsed-field gradients (PFGs), 47, 63, 64f, 185 COSY and, 151 Purity, sample, 23 Q Quantum mechanical nature, Quartet, 130 pattern of, 134f Quintet, 134e135 R Radiofrequency electromagnetic radiation (RF), 12 excitation limits, 47t filter, 156 filtering of, 37e39 generation of, 35 pulse calibration and, 37 Rapid chemical exchange, 190e191 definition of, 190e191 Recovery time, 187f Relaxation See also T1 relaxation; T1 r relaxation; T2 relaxation; T*2 relaxation definition of, 186e190 occurrence of, 13e14 spin-lattice, 186 spin-spin, 186 studies of, 190 Relaxation delay, 66, 144 Residual magnetization, elimination of, 63 Resistor-inductor-capacitor (RLC) circuit, 13 Resolution enhancement, 75 consequence of, 75 Resonance assigning of, 199e221 based on gCOSY, 207e209, 216e217 of chemical shifts, 211e213 HMBC, 217e221 of compound X in D2O, 227t, 228t differentiation of, 23e24 electronegativity and, 218 of ethyl nipecotate, 211 HSQC/HMQC spectrum, 213e217 identification of, 205 intensities of, 170 multiplicities and, 204e207 overlap of, 90e92, 91f phasing of, 80, 80f splitting pattern of, 206e207 T1 relaxation unknown, 85e86 Resonance assignment problem See also Complex resonance assignment problem; Simple resonance assignment problem artemisinin, 442e447 brucine, 452e456 compound, 119, 474e477 compound, 142, 467e473 a-cubebene, 427e432 gHMBC, 431f (1S*, 4S*, 10S*)-1-ethyl-4-(hydroxyethyl)quinolizidine, 432e436 melatonin, 462e466 piperine, 457e461 sinomenine, 437e441 vincamine, 447e451 Resonance broadening, 194e195, 220 Resonance line width, 186e187 RF See Radiofrequency electromagnetic radiation RF channel, 37e39, 51 Ring current, 104e105, 108 aromatic, 108 RLC See Resistor-inductor-capacitor circuit ROESY See Rotational Overhauser effect spectroscopy rof2, 77e78 Rolloff See Pulse rolloff Roof effect, 128f Room-temperature (RT) shim set, 32, 48 Rotamer, 119 Rotating frame of reference, 41e42 static frame of reference relationship with, 42f Rotational isomerism, 81 Rotational Overhauser Effect Spectroscopy (ROESY) analysis of, 183 cross peak generation and, 181e182 disadvantage of, 182 Index simple resonance assignment problem, (-)-bornyl acetate, 257f TOCSY compared to, 182 unknown structure elucidation problems, simple unknown, 367f RT See Room-temperature shim set S Sample degradation, for air- and water-sensitive compounds, 30e31 Sample excitation, frame of reference rotation and, 41e42 Sample preparation, 22e31 concentration, 155 degradation minimizing, 30e31 heating of, 155 impurities, 86 locking, 31e32 mixing, 25 purity, 23 shimming, 32e33 solute concentration, 27e29 excess, 27 limited, 29 optimal, 29e30 solvent selection, 23e24 tube selection, 22e23 volume, 26e27 Sampling rate, of A/D, 60, 66e67 Satellite peak, 124e125, 127f Saturation, 142e143 Scalar coupling See J-coupling (3aR)-(+)-sclareolide complex resonance assignment problem, 300e311 13 C NMR spectrum, 307f gCOSY, 308f gHMBC, 310f, 311f H NMR spectrum, 306f HSQC, 309f structure of, 305f Sensitivity, 22 Serial phase-sensitive sampling method, 55 Shielding variation, chemical shift and, 107 Shifted sine bell function, 71e72 Shifted square sine bell function, 71e72 Shimming, 32e33 Signal cancellation mechanism for, 8e9 detection of, 13e14 analog, 52e53 571 digitization, 53e57, 161 division of, 114 Signal decay, 65 Signal-to-noise ratio, 11 of compound X in D2O, 224 Simple resonance assignment problem 2-acetylbutyrolactone, 237e240 N-acetylhomocysteine thiolactone, 258e262 (-)-bornyl acetate, 251e257 guaiazulene, 263e267 2-hydroxy-3-pinanone, 268e272 (R)-(+)-perillyl alcohol, 273e277 sucrose, 283e287 a-terpinene, 240e245 Simple unknown molecular structure elucidation problems, 341e378 H NMR spectrum, 341f, 346f, 351f, 353f, 357f, 361f, 363f, 368f, 372f, 374f 13 C NMR spectrum, 342f, 347f, 351f, 354f, 357f, 361f, 364f, 368f, 372f, 375f gCOSY, 343f, 348f, 352f, 355f, 358f, 362f, 365f, 369f, 373f gHMBC, 367f, 371f, 374f, 378f gHSQC, 370f, 377f HMQC, 344f, 349f, 350f, 353f, 356f, 359f, 360f, 363f HSQC, 366f NOESY, 345f ROESY, 367f Single quantum spin flip rate constant (W1), 186 Single-channel probe, 51 Sinomenine resonance assignment problem, 437e441 13 C NMR spectrum, 438f gCOSY, 439f gHMBC, 441f H NMR spectrum, 437f HSQC, 440f structure of, 437f Sinusoid See Exponentially damped sinusoid Sinusoidal pattern, 41, 41f Slow chemical exchange, 191e192 Small-volume probe, 48 Solute concentration excess, 27 limited, 29 optimal, 29e30 Solvent selection, 23e24 Spectral density function, 172e174 correlation times and, 172e173, 173f 572 Index Spectral density function (Continued ) definition of, 172 importance of, 177 in liquid-state sample, 172 transition rate and, 174 Spectral window (SW) control over, 60 folding caused by, 61, 61f setting of, 59e61 Spin lock, 152 Spin pair, 171, 173 Spin state definition of, determination of, energy gap between, 5e6 J-coupling and, 130 magnetic field effect thereon, 4f of methylene, 132e133 parallel compared to antiparallel, Spin-lattice relaxation See T1 relaxation Spinner, diagram of, 26f Spin-spin coupling See J-coupling Spin-spin relaxation See T2 relaxation Spin-tickling experiment, 129 Splitting, 126 heteronuclear, 136 J-coupling pattern and, 134f of methylene, 133 resonances and, 206e207 Static frame of reference, rotating frame of reference relationship with, 42f Steady-state scans, 152 Stereochemistry, of sugar ring, 235f, 236, 236f Successive contour line limit of, 98e99 spacing of, 96 Sucrose simple resonance assignment problem, 283e287 13 C NMR spectrum, 284 gCOSY, 285 gHMBC, 287 H NMR spectrum, 283 HSQC, 286 structure of, 283 Sugar ring, stereochemistry of, 235f, 236, 236f SW See Spectral window (SW) Sweep width, 59e60 Symmetry, 113e121, 209 of gCOSY, 210 T T1 relaxation, 62e63, 186 correlation time and, 188 definition of, delay in, 62 dipolar interaction and, 190 metal ion influencing, 86 temperature influencing, 86 unknown resonances, 85e86 t1 time See Evolution time, t1 T1r relaxation, 188 T2 relaxation, 29, 186 correlation time and, 188 definition of, reliance of, 188 T*2 relaxation, 72 definition of, 66, 186 observed line width and, 73e74 time influencing, 74f t2 time, 54 apodization and, 74 Temperature probes and, 185 T1 relaxation influenced by, 86 Temperature regulation, 33 a-Terpinene simple resonance assignment problem, 240e245 13 C NMR spectrum, 241f gCOSY spectrum of, 243f H NMR spectrum, 241f structure of, 240f tert-Butylcyclohexane, 115, 115f Tetramethylsilane (TMS), chemical shift in, 102 Tetrasubstituted methanes, 13C chemical shift trends in, 111t TFA See Trifluoroacetic acid TFE See Trifluoroethanol Thermal noise See Johnson noise TMS See Tetramethylsilane TOCSY See Total correlation spectroscopy Topicity, 113e121 definition of, 114e115 signal division according to, 114 Total correlation spectroscopy (TOCSY), 37, 151e153 of cpd36, 154f efficiency of, 152e153 mechanism of, 151e152 mixing and, 153 power of, 153 ROESY compared to, 182 Index showing chemical exchange, 195 spin lock and, 152 timing of, 153 X-shaped profile of, 152e153 Transition rate, spectral density function and, 174 trans-Myrtanol complex resonance assignment problem, 321 13 C NMR spectrum, 322f gCOSY, 323f gHMBC, 325f gHSQC, 324f H NMR spectrum, 321f structure of, 321f Trifluoroacetic acid (TFA), 28 Trifluoroethanol (TFE), 28 Triplet, 136f Truncation error, 71e72, 73f Tube cleaning of, 24e25 diameter of, 50e51 drying of, 25 selection of, 22e23 spinner diagram of, 26f Tuning, of probe, 36e37 Two-channel probe, 51 Two-dimensional NMR spectrum forward linear prediction and, 75e76 overlapping resonances and, 90e91, 91f overview of, 16e18 phase correction and, 80 points acquired in, 69e71 pulse sequence of, 17 showing chemical exchange, 195 time periods of, 17e18, 17f utilizing J-coupling, 148e167 utilizing NOE, 181e183 NOESY, 181 ROESY, 181e183 U Unknown molecular structure elucidation, 223e236 accounting practices for, 227e230 assignment completion and, 230e236 complex unknown, 379e426 13 C NMR spectrum, 381f, 386f, 391f, 395f, 400f, 405f, 409f, 414f, 419f, 423f gCOSY, 382f, 387f, 392f, 396f, 401f, 406f, 410f, 415f, 420f, 424f gHMBC, 384f, 389f, 394f, 398f, 408f, 412f, 417f, 422f 573 gHSQC, 397f, 402f, 407f, 411f, 416f, 421f H NMR spectrum, 380f, 385f, 386f, 390f, 395f, 399f, 409f, 413f, 418f, 423f HMBC, 403f, 426f HSQC, 383f, 388f, 393f, 425f entry point identification and, 230 multiple interpretations for, 223 simple unknown, 341e378 13 C NMR spectrum, 342f, 347f, 351f, 354f, 357f, 361f, 364f, 368f, 372f, 375f gCOSY, 343f, 348f, 352f, 355f, 358f, 362f, 365f, 369f, 373f gHMBC, 367f, 371f, 374f, 378f gHSQC, 370f, 377f H NMR spectrum, 341f, 346f, 351f, 353f, 357f, 361f, 363f, 368f, 372f, 374f HMQC, 344f, 349f, 350f, 353f, 356f, 359f, 360f, 363f HSQC, 366f NOESY, 345f ROESY, 367f simplicity for, 223e224 unknown, 479e525 13 C NMR spectrum, 480f, 485f, 491f, 496f, 500f, 505f, 509f, 513f, 517f, 521f gCOSY, 481f, 486f, 487f, 492f, 497f, 501f, 506f, 510f, 514f, 518f, 522f gHMBC, 483f, 489f, 490f, 494f, 495f, 499f, 503f, 504f, 508f, 512f, 516f, 520f, 524f, 525f H NMR spectrum, 480f, 484f, 491f, 496f, 500f, 505f, 509f, 513f, 517f, 521f HSQC, 482f, 488f, 493f, 498f, 502f, 507f, 511f, 515f, 519f, 523f V Valence shell electron pair repulsion (VSEPR), 141 Variable temperature (VT), 33, 185 results from, 193 stacked plot of, 194f Vector helical array of, 64 magnetic moment summation of, 10f Vicinal bond angle, 165 Vincamine resonance assignment problem, 447e451 13 C NMR spectrum, 448f gCOSY, 449f gHMBC, 451f 574 Index Vincamine (Continued ) H NMR spectrum, 448f HSQC, 450f structure of, 447f Volume, sample, 26e27 VSEPR See Valence shell electron pair repulsion VT See Variable temperature Window function See Apodization Wuăthrich, Kurt, W z4 hump, 80e81 Zeeman effect, 5, 5f, 170 Zero filling, 67e68 definition of, 68 Zero quantum spin flip rate constant (W0), 170e171, 186e188 Zero-order phase correction, 79 W See Dipolar relaxation rate constant (W) W0 See Zero quantum spin flip rate constant W1 See Single quantum spin flip rate constant W2 See Double quantum spin flip rate constant Water-sensitive compounds, sample degradation minimizing for, 30e31 X X-shaped profile, of TOCSY, 152e153 Z ... medical sciences, in particular, independent verification of diagnoses and drug dosages should be made Library of Congress Cataloging-in-Publication Data Simpson, Jeffrey H Organic structure determination. .. sinusoidal wave with a particular frequency Because a single sinusoid25 has a constant phase26 and amplitude, a number of components within the NMR console are dedicated to controlling the phase and... found in an NMR instrument: a highband channel (for 1H and 19F, and may be 3H), a broadband channel, for all nuclides with Larmor frequencies at that of 31P and lower, a lock channel (devoted exclusively