TERPENOID NMR STUDIES: NMR PARAMETERS FOR BICYCLO(3.1.1)HEPTANES AND REVISED STRUCTURES FOR ARCHANGELIN AND PEREZONE Item Type text; Dissertation-Reproduction (electronic) Authors Thalacker, Victor Paul, 1941- Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 29/09/2021 07:42:31 Link to Item http://hdl.handle.net/10150/290208 This dissertation has been microfilmed exactly as received THALACKER, Victor Paul, 1941- TERPENOID NMR STUDIES: NMR PARAMETERS FOR BICYCLO[3.1.1]HEPTANES AND REVISED STRUCTURES FOR ARCHANGELIN AND PEREZONE. University of Arizona, Ph.D., 1968 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan TERPENOID NMR STUDIES: NMR PARAMETERS FOR BICYCLo[3.1.1]HEPTANES AND REVISED STRUCTURES FOR ARCHANGELIN AND PEREZONE by Victor Paul Thalacker A Dissertation Submitted to the Faculty of the DEPARTMENT OF CHEMISTRY In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 19 68 THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE I hereby recommend that this dissertation prepared under my direction by Victor Paul Thalacker entitled Terpenoid MR Studies': NMR Parameters for 6107010" [jS. 1. i] heptanes and Revised Structures for Archangelin and Perezone be accepted as fulfilling the dissertation requirement of the degree of Doctor of Philosophy 7C Dissertation Director Date After inspection of the dissertation, the following members of the Final Examination Committee concur in its approval and recommend its acceptance:* Aut.. 1.IW7 2 2 7. JU7 l?C7 *This approval and acceptance is contingent on the candidate's adequate performance and defense of this dissertation at the final oral examination. The inclusion of this sheet bound into the library copy of the dissertation is evidence of satisfactory performance at the final examination. STATEMENT BY AUTHOR This dissertation has been submitted in partial fulfillment of requirements for an advanced degree at The University of Arizona and is deposited in the University Library to be made available to bor­ rowers under rules of the Library. Brief quotations from this dissertation are allowable without special permlssiont provided that accurate acknowledgment of source is made. Requests for permission for extended quotation from or re­ production of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his judgment the proposed use of the material is in the in­ terests of scholarship. In all other instances, however, permission must be obtained from the author. SlGNEDt ACKNOWLEDGMENTS The author wishes 4to express his gratitude to Dr. Robert B. Bates for his counsel and aid throughout the course of this research and to Dr. S. K. Paknikar for his contributions to the synthesis prob­ lem. Thanks are also given to Mr. H. S. Craig for writing the plotter program. Support for this research was provided by Public Health Service Grant No. GM-11721. iii TABLE OF CONTENTS } Page LIST OF ILLUSTRATIONS vi LIST OF TABLES viil ABSTRACT ix INTRODUCTION 1 Nuclear Magnetic Resonance Spectra of Terpenoids I Archangel in 4 PsoraLens 6 Peiezone ........ 7 DISCUSSION 9 NMR Spectral Parameters in Bicyclo^3.1.llheptanes: Ot-Pinene, Myrtenal, and Verbenone •••••• 9 Chemical Shifts 10 Coupling Constants 12 Terpenoid NMR Spectral Compilation ..... 17 Archangelin 17 Psoralens 25 Perezone 27 EXPERIMENTAL 28 General Methods ..•• 28 NMR Spectral Parameters in Bicyclo^3.1.lJheptanes 28 Terpenoid NMR Spectral Compilation 29 iv V TABLE OF CONTENTS--Continued Page Synthesis of Archangelln ......... 29 2,6-Dimethyl-5-heptene-2-ol (XVII) 29 Ot-Cyclogeraniolene (XVIII) ••••«•••• 30 Acetylcyclogeranioiene (XX) , . .. 31 Regeneration of XX From Its Semicarbazone 32 ^-Cyclolavandulic Acid (XXI) . .. 32 Methyl 0-Cyclolavandulate •••••••«••• ... 33 ^Cyclolavandulol (XV) 34 0-Cyclolavandulyl Acetate .. 34 P-Cyclolavandulyl Bromide . 35 Sodium Salt of Umbelliferone (XXIV) 35 {9-Cyclolavandulyl Umbelliferonyl Ether (XXV) 36 Acetic Acid Cleavage 37 Cleavage of Archangel in ••.••••••••••••• 37 Reduction of Psoralen Mixture 38 Reduction of Linalool-ff)f-Dimethylallyl Alcohol ••••»• 39 APPENDIX A . 40 APPENDIX B 45 APPENDIX Cl NMR AND IR SPECTRA 53 LIST OF REFERENCES 68 LIST OF ILLUSTRATIONS Page Figure I. Preparation of j£»cyclolavandulyl umbelliferonyl ether .. 21 2a. Verbenone (IX) experimental spectrum (100 Mc) 54 2b. Verbenone (IX) simulated spectrum (100 Mc) 54 3a. Myrtenal (X) experimental spectrum (100 Mc) 55 3b. Myrtenal (X) simulated spectrum (100 Mc) 55 4a. 01-Pinene (XI) experimental spectrum (100 Mc) 56 4b. 0(-Pinene (XI) simulated spectrum (100 Mc), system 1 (Insert) 56 4c. 01-Pinene (XI) simulated spectrum (100 Mc), system 2.. 56 5. Myrtenal (X) experimental and simulated spectra (60 Mc; upper negative, middle J^ positive) ..... 57 6. Commercial methylheptenone (XVI) 57 7. 2,6-Dimethyl-5-heptene-2-ol (XVII) . ••• 58 8. 0t+ ^-Cyclogeraniolene (XVIII + XIX) 58 9. Commercial methylheptenone (XVI} neat) 59 10. 2,6-Dimethyl-5-heptene-2-ol (XVII; neat) . .. 59 11. <X + ^-Cyclogeraniolene (XVIII + XIX; neat) 60 12. Acetylcyclogeraniolene (XX; neat) 60 13* Acetylcyclogeraniolene (XX) ...... « .. 61 14. ^-Cyclolavandulic acid (XXI) .. 61 15. ^-Cyclolavandulic acid (XXI; KBr) .. 62 16. f-Cyclolavandulol (XV; CC14) 62 vi vil LIST OF ILLUSTRATIONS—Continued Page Figure 17. ^Cyclolavandulol (XV) . .. 63 18. f?-Cyclolavandulyl bromide (XXIII) ............ 63 19. Natural archangelln (XXVI; 60 Mc) ••...••••... 64 20. Natural archangelln (XXVI; 100 Mc) ...... 64 21. ^-Cyclolavandulyl umbelliferonyl ether (XXV; 60 Mc) ... 65 22. ^-Cyclolavandulyl umbelliferonyl ether (XXV; 100 Mc) .. 65 23. Natural archangelln (XXVI; CCl^) .. ... 66 24. ^-Cyclolavandulyl umbelliferonyl ether (XXV; CCl^) ... 66 25. Compound B 67 26. Perezone (VIII) 67 LIST OF TABLES Page Table 1. NMR ABSORPTIONS REPORTED FOR ARCHANGELIN 6 2. CHEMICAL SHIFTS (T) AT 100 Mc 11 3. COUPLING CONSTANTS IN CPS 14 4A. RESULTS OF ITERATION ON VERBENONE (IX, 60 Mc) 40 5A. ERROR VECTORS AND PROBABLE ERRORS 42 6A. TABLE OF ORDERED LINES 43 7B. LIST OF TERPENOIDS Cj-C^ 45 8B. LIST OF TERPENOIDS C15»C19 47 9B. LIST OF TERPENOIDS C. -C. 50 200 40n 10B. TERPENOIDS OVER C^ AND STEROIDS 51 vlii ABSTRACT NMR spectral parameters were derived, by computer analysis, for three bicyclo^3.1.ljheptane derivatives. As expected, the coupling constants vary little among the three compounds. A 4-bond coupling con­ stant of +5.9 to +6.5 cps was observed between bridgehead protons, and two 5-bond couplings of 1.8 cps were found in cf-pinene. The structure of archangelin, a natural furocoumarin, was re­ vised by NMR analysis and synthesis of the alkyl portion, y?-cyclolav- andulol. A new ether, ^-cyclolavandulyl umbelliferonyl ether, was synthesized and its NMR spectrum compared with that of archangelin. This is the first reported occurrence of the ^-cyclolavandulyl carbon skeleton in nature. A furocoumarin recently isolated from Hercleum candicans was shown to be a mixture of the known compounds, imperatorin and 8-geran- oxypsoralen, by stereospecific Birch reduction and NMR analysis* The structure of perezone, a natural terpenoid, was revised by inspection of its NMR spectrum. ix INTRODUCTION Nuclear Magnetic Resonance Spectra of Terpenoids In addition to charge and mass, which all nuclei have, some iso­ topes possess spin or angular momentum. Since a spinning charge gener­ ates a magnetic field, there is associated with this angular momentum a magnetic moment (fJI). Nuclei which possess spin when placed in a mag­ netic field will precess about the direction of the field. An increase in the field strength causes the nuclei to precess faster. By applying a second, much weaker, magnetic field at right angles to the first magnetic field and causing this second field to ro­ tate at exactly the precession frequency, the nuclei can be caused to align themselves with the strong magnetic.field. The frequency at which the nuclei flip can be observed by a receiver coil. Interactions of the electrons and nuclei in a molecule modify .the magnetic environment in which various nuclei are found and this leads to the observation of chemical shifts and spin coupling. The chemical shift is a result of the induced orbital motion of the elec­ trons when the molecule is placed in an external field and is propor­ 1 tional to the applied field, Hq. Ramsey' first developed a theory for the chemical shift. Nuclear spin-spin coupling, which causes the fine structure, is independent of the external field and arises from magnetic fields within 2 the molecule itself. Ramsey and Purcell developed the first successful theory to explain these interactions. 1 2 Resolution sufficient to distinguish chemical shifts of non- equivalent nuclei in the same molecule is referred to as "high resolu­ tion" nuclear magnetic resonance (NMR) spectra. By observing such spectra in liquids, where the direct magnetic dipole Interaction is averaged to zero by the rapid motion of the molecules, sufficient reso­ lution may be obtained to observe the fine structure due to nuclear spin-spin interaction. The chemical shift and spin-spin coupling parameters can com­ pletely describe high