Structure Elucidation by Modern NMR: A Workbook PDF
Preview Structure Elucidation by Modern NMR: A Workbook
Duddeck . Dietrich· T6th • Structure Elucidation by Modern NMR H. Duddeck, W. Dietrich, G. T6th Structure Elucidation by Modern NMR A Workbook Third, Revised and Updated Edition Springer Prof.Dr.HelmutDuddeck UniversityofHannover,InstituteofOrganicChemistry Schneiderberg 1B,0-30167Hannover,Germany Dr.WolfgangDietrich RuhrUniversityBochum,FacultyofChemistry P.O.Box102148,0-44780Bochum,Germany Prof.Dr.GaborT6th TechnicalAnalyticalResearchGroupoftheHungarianAcademyofSciences TechnicalUniversityBudapest,lnstituteforGeneralandAnalyticalChemistry SzentGellérttér4,H-llll Budapest,Hungary DieDeutscheBibliothek- CIP-Einheitsaufnahme Duddeck,Helmut: StructureelucidationbymodernNMR:aworkbook/H.Duddeck; W.Dietrich;G.T6th.-3.,rev.andupdateded.-Darmstadt: Steinkopff; NewYork:Springer,1998 Dt.Ausg.u.d.T.:Duddeck,Helmut:Strukturaufklârungmitmoderner NMR-SpcktroskopieDietrich,Wolfgang:Strukturaufklârungmit modernerNMR-SpcktroskopieToth,Gabor:Strukturaufkliirungmit modemcrNMR-Spcktroskopic Thisworkistsubjecttocopyright.Alirightsarereserved,whetherthewholeorpartofthematcrialisconcerned, specificallythe rightsoftranslation.reprinting.re-useofillustrations. recitation,broadcasting, reproductionon microfilmorinotherways.andstorageindatabanks.Duplicationofthispublicationorpartsthereofisonlyper mittedundertheprovisionsoftheGermanCopyrightLawofSepternber9. 1965.initsversionofJune24. 1985. andacopyrightfeemustalwaysbepaid.Violationsfull undertheprosecutionactoftheGermanCopyrightLaw. ISBN 978-3-7985-1111-8ISBN 978-3-642-88310-1 (eBook) DOI 10.1007/978-3-642-88310-1 © 1998bySpringer-VerlagBerlinHeidelberg OriginallypublishedbyDr.DietrichSteinkopffVerJagGmbH&Co.KG,Darmstadtin1998. ChemistryEditor:Dr.MariaMagdaleneNabbe- CopyEditing:Dr.MaryK.Gossen Production:HeinzJ.Schafer Theuseofrcgisterednarnes,trademarks,etc.inthispublicationdoesnotimply.evenintheabsenceofaspecifie staternent,thatsuchnarnesarcexemptl'romtherelevantprotective lawsand regulationsandthereforefree for generaluse. Foreword In 1988, our first workbook (Strukturaujklärung from the Technical University in Budapest, Hunga mit moderner NMR-Spektroskopie, Steinkopff, ry, to contribute significantly to this new edition. Darmstadt) appeared in the German language He is among the most prominent NMR specialists based on our experience in organizing seminars in his country and abroad, and has been teaching and workshops on the application of modem one spectroscopy and its application in organic chemi and two-dimensional NMR methods. Many of the stry for more than 20 years. exercises described in the workbook have been This book cou1d not have been written in the used in these courses and some of them have been present form without the help of a number of shaped to a great extent by the participants. The colleagues; therefore, we gratefully acknowledge response of readers and discussions with collea generous gifts of sampies from and useful discus gues from many countries encouraged us two years sions with B. Abegaz (Addis Ababa, Ethiopia), U. later to produce an English translation in order to H. Brinker (Vienna, Austria), E. Dagne (Addis make the book accessible to a wider audience. In Ababa, Ethiopia), M. H. A. Elgamal (Cairo, 1992 a revised and expanded second edition Egypt), M. Gonzalez-Sierra (Rosario, Argentina), appeared. 1. Harangi (Debrecen, Hungary), I. Hermecz (Bu During the last few years, however, routine dapest, Hungary), Gy. Horvath (Budapest, Hun applications of NMR techniques have been further gary), A. Levai (Debrecen, Hungary), M. Michal developed. Spectrometers of the latest generation ska (Lodz, Poland), P. S. Rao (Warangal, India), E. offer new types of experiments, such as spin-lock A. Ruveda (Rosario, Argentina), P. Schreiber and inverse-detected methods, which were not yet (Budapest, Hungary), G. Snatzke (Bochum, Ger mentioned in the earlier editions. So, we believed many), H. S. M. Soliman (Cairo, Egypt), and L. that it was again time to revise the book by intro Szilagyi (Debrecen, Hungary). ducing this new methodology and by incorporating We also thank A. Simon and B. Balazs (Buda it into new exercises. Although the general scheme pest), S. Rockitt (Hannover), and M. Gartmann is unchanged - presenting spectra and guiding the (Bochum) for their comrnitted cooperation and as reader to their solution - Chapter 2 (methodology) sistance in the measurements. has been completely revised and updated. Some Inspite of painstaking efforts, mistakes can hardly exercises have been newly introduced, whereas be avoided. We are always grateful for any re some others were removed. In ISaBddNit io9n7,8 -3a -6n4e2w- 883s1p0o-n1s e( eBfrooomk )readers to correct or improve the chapter has been introduced which demonstrates book. Comrnents may be directed to the e-mail ad the fully detailed interpretation of two typical dress: [email protected]. examples. We have changed the names of the two If we have been successful in conveying an im casy spectra and adopted the more widely used pression of the wealth of information offered by designations "casy" replacing H,H casy and modem NMR, then the book has satisfied its goal. HETcaR replacing H,C casy. The authors of the former editions are proud to welcome their friend and colleague Gabor T6th Hannover, Bochum, Budapest Helmut Duddeck March 1998 Wolfgang Dietrich Gabor T6th Dedicated to the memory of Prof. Dr. Dr.h.c.(H) Günther Snatzke (1928 - 1992) on the occasion of his 70th birthday anniversary He was an outstanding expert in stereochemistry and spectroscopy and taught one to love the architecture of three-dimensional molecular structures. Contents Foreword Introduction .......................................................... 1 2 Methodology .......................................................... 7 2.1 High Magnetic Fields ............................................ 8 2.2 One-Dimensional IH and 13C NMR Spectra (INEPT, DEPT) ............. 10 2.3 Two-Dimensional IH,IH Correlation (COSY, Linear Prediction, Pulsed Field Gradients, TOCSY) ............. 15 2.4 Two-Dimensional 13C, IH One-Bond Correlation (HETCOR, Inverse Detection, HSQC, HMQC, HMQC-TOCSY) ......... 23 2.5 Two-Dimensional 13C,IH Long-Range Correlation (COLOC, HMBC) ...... 29 2.6 I3C,13C-Correlation (INADEQUATE) ............................... 32 2.7 Dipolar Coupling Experiments (NOE difference, NOESY, ROESY) ....... 35 2.8 Appendix: IH and 13C NMR Data ofQuinidine ........................ 42 3 Demonstration Examples ............................................... 44 3.1 Formation of a Novel Benzothiazoline Derivative by Ring Contraction ..... 44 3.2 Structure Elucidation of a Triterpene Saponin ........................ 54 4 Exercises. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 71 5 Strategies ........................................................... 161 6 Solutions 167 Explanation of Acronyms ............................................. 203 Subject Index ....................................................... 204 Compound Index .................................................... 206 1 Introduction 1 Introduction Since the early 1980s modem NMR spectroscopy in the bibliography. The minimum condition for - especially the two-dimensional methodology - successfully working with this book is simply a has become an extraordinarily useful tool in the degree of knowledge about conventional IH and structural elucidation of unknown organic com \Je NMR spectroscopy with which chemistry stu pounds. Nowadays, the latest generation spectro dents should be familiar and that chemists can re meters with their increasingly powerful pulse pro view in many textbooks or exercise collections. grammers, computers, and data storage devices en Our book is different from most other books or able the user to perform routinely many multipulse articles cited in the bibliography. We have de experiments with a time expenditure no longer liberately restricted the number of methods used to significantly exceeding that of most traditional those techniques that in the course of our daily techniques, as for instance, multiple selective de laboratory routine have proved executable at the coupling. On the other hand, much more informa spectrometer without much experimental effort tion can be extracted from multipulse than from and that are relatively easy to interpret. This is the conventional measurements. reason why we refrain completely from some im Modem NMR techniques have revolutionized portant but highly advanced techniques, as for the structure elucidation of organic compounds and example three- or even four-dimensional NMR natural products. This, however, is not yet fully re spectroscopy which play an important role in pro cognized by chemists who do not work with these tein NMR. We wish to demonstrate the great po methods routinely. Numerous review articles and tential of the basic experiments, but without over monographs published during the last few years burdening the novice with a large number of ex may give the impression that these methods are ex perimental variants that would be difficult to sur traordinarily complicated and difficult to evaluate, vey. thus, deterring many potential users. Our experi This book has been arranged so that it may serve ence in a number of workshops and seminars with as both a book for seminars and a self-study text graduate students and researchers, as weil as with for chemists who do not have access to courses. In the routine service in our NMR laboratories, has offering a realistic picture of everyday laboratory demonstrated that in the presence of the beauty and routine, we have not attempted to plot all spectra in elegance of the modem one- and two-dimensional an optimal fashion, and therefore, we have not NMR methodology, spectroscopists te nd to over tried to eliminate all artifacts. Generally, the per estimate the readiness of their "customers" to get son recording the spectra is not the same person acquainted with the underlying physical theory. who orders them (and often the spectroscopist does Therefore, in this book we address chemists for not know be forehand exactly what kind of infor whom structure elucidation is an educational or oc mation is to be extracted). Therefore, we want to cupational concem. By means of exercises taken support the reader's ability to evaluate spectra from everyday practice, we demonstrate that the critically so that, for instance, he or she can diffe use of spectra from multipulse NMR experiments rentiate "real" signals from artifacts. For technical is often straightforward and does not necessarily reasons the spectra depicted in this book had to be require insight into the underlying methodology reduced in size from the original plots. and pulse sequences. For the same reason we re Seminars on modem NMR spectroscopy have frain from a discussion of the physical back often shown that novices have a strong tendency to ground; the reader may find appropriate references solve problems containing two-dimensional spec- 2 1 Introduction tra by first and nearly exelusively evaluating the overwhelming. In such cases only through study one-dimensional IH and llC NMR spectra and experience, and perhaps the advice of a skilled developing a structural proposal in the conventio colleague, can wrong conelusions be avoided. nal way taught in basic courses. Later, they may In the choice of compounds and problems we try to confmn their ideas by tracing appropriate have remained elose to actual practice and offer a evidence from two-dimensional spectra. This ap broad range of chemical elasses representative of proach is not essentially wrong but it is often im the chemistry for organic and natural products. The practical and leads to a strict adherence to esta 25 exercises presented here cannot be all inelusive; blished structural proposals without consideration because nature is unsurpassable in her variety, na of alternatives. For instance, one often ignores the tural products play an important role in this book. fact that a cross peak in a COSY spectrum is un In Chapter 2 the NMR experiments used in the equivocal prooffor the existence of a coupling and exercises are discussed and explained by simple, not just a probability. The observation of a signal straightforward examples. Readers without any ex in an NOE difference spectrum or a cross peak in a perience in multipulse NMR spectroscopy should NOESY or ROESY spectrum proves the spatial begin with this section. proximity of the respective nuclei. The novice has Teaching modem state-of-the-art NMR spectro to learn the difference between such hard proof scopy faces a problem which increases year by and soft hints. year and with each newly invented experiment. It is amazing to see how easy it is to establish The wealth of information available becomes lar structural fragments by simple evaluation of one ger and larger and thereby the complexity of pro and two-dimensional NMR spectra in a "jigsaw blems which can be tackled also increases. On the puzzle" fashion. Such an approach should always other hand, education as exemplified in seminars be the start of a structural elucidation. In this way, or self-study exercise books like this has to be re the objectivity necessary for considering all possi stricted to easy to survey examples in order to not ble alternative structures is retained. overburden the novice. In order to fill this gap, we Two-dimensional spectra gene rally contain a decided to introduce a novel section (Chapter 3) in wealth of information which may sometimes cause the third edition of this exercise book in which the the inexperienced to become lost. The argumenta procedure of evaluating and interpreting NMR tion for solving a problem should therefore be spectra is demonstrated step by step for two ex structured. Preferably, one should begin with the amples that are more complex than most of the 25 assemblage of molecular fragments, which can la exercises in the following chapters. In the first ter be combined into a constitution formula. There example (Sect. 3.1) we present a chemical problem after, if necessary, the stereochemistry of the com where an unexpected ring contraction reaction is pound can be investigated. In most cases this stra elucidated by inspecting a variety of NMR spectra tegy leads to a quick and safe solution and an im of the reaction product. A study on the conforma portant objective of this book is to help the reader tional behavior of the product is ineluded which is develop a feeling for this kind of approach. assisted by a molecular modelling calculation. The However, we warn the unwary to be cautious. second example (Sect. 3.2) is the structure deter Two-dimensional NMR methods may give rise to mination of a rather complex natural product con artifacts and the inexperienced tend to overinter sisting of a pentacyelic triterpene aglycone with a pret such spectra. For example, the temptation to monosaccharide moiety. Although we cannot offer draw conelusions about the magnitude of a coupl general rules, we simultaneously present ways of ing constant from the size of a cross peak is often arranging documentation in graphical and tabular 1 Introduction 3 form, since novices often face the problem of A complete signal assignment is not always ne lucidly documenting results from the spectra in a cessary in order to ans wer the question in an exer report or publication. cise; occasionally, the information in the one-di Chapter 4 contains 25 exercises comprising si mensional spectra suffices. This is intentional to gnal assignments for given structures or structures show that multipulse techniques - although ex known only in part, as weil as for the elucidation tremely helpful tools - are not always necessary of unknown chemical structures. In addition, ex and that even complex problems can be solved by amples have been chosen where different confor conventional methods. We do not wish to elicit a mations or configurations of a molecule can be blind and overly faithful adherence to modem monitored. As in the previous edition we begin NMR techniques. with rather simple single spectrum interpretations In the NMR literature we find ab initio or a (exercises 1 -8). Then, in exercises 9 - 11 aseries priori signal assignments in an increasing number, of single spectrum problems is presented, all from denoting spectral interpretations that are based the same compound, in wh ich each one is based on exclusively on experimental evidence, i.e., "hard" what has been found in the preceding. Thereby, the proof, and that refrain completely from the use of user is guided step-by-step to the multi spectra any empirical parameters or experience, such as problems. chemical shifts, magnitudes of coupling constants, There are two levels of assistance offered by this or substituent effects. Of course, in cases of doubt workbook: if the reader [mds him- or herself un such assignments are preferable. Such a rigorous able to solve the problems without assistance, attitude, however, is coupled with a high demand there is a strategy for each exercise in the respec for spectrometer time and familiarity with preten tive section in Chapter 5, i.e., hints about how to tious pulse programs, which not all NMR laborato approach the problem. The solutions themselves ries can afford and are often not required for solv are described explicitly in the respective section in ing a problem. Therefore, we have selected ex Chapter 6, and in many cases there are additional amples that allow chemists to make use of their information and references. Of course, the propos previous experience in NMR spectroscopy. ed strategy is not necessarily the only possibility. As in our lectures and seminars it is our aim to With some experience the reader should be able to convey something of the satisfaction that one can develop his or her own strategy independent of the find in using modem NMR techniques. Fans of descriptions in this book, which is exactly the brainteaser problems will find a field of enjoyable objective we wish to achieve. activity.
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