Mechanistic Studies on the Oxidation of Alkyl Substituted
Total Page：16
File Type：pdf, Size：1020Kb
Mechanistic studies on the oxidation of alkyl substituted tetrahydrobenzofurans with m-chloroperbenzoic acid by Samuel Beryl Gingerich A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry Montana State University © Copyright by Samuel Beryl Gingerich (1983) Abstract: The reaction of a series of alkyl substituted tetrahydrobenzo-furans with m-chloroperbenzoic acid has been explored. The furan substrates used included 3-methyl-4,5,6,7-tetrahydrobenzofuran, 1,2,3,4,5,6,7,8-octahydrodibenzofuran, 2-methy1-4,5,6,7-tetrahydro-benzofuran and 2,3-dimethyl-4,5,6,7-tetrahydrobenzofuran. The products arising from the oxidation of these substrates have been isolated and their structures determined. These substrates have also been prepared labeled with oxygen-18. These labeled substrates were also oxidized and the position of the label in the products determined by carbon-13 NMR spectroscopy. On the basis of the data obtained from these experiments, a detailed mechanistic scheme was developed. Initial attack of the furan moiety by m-chloroperbenzoic acid occurs to form an epoxide which subsequently undergoes ring openings to form a cis-enedione. These compounds are postulated as intermediates in all the reactions studied even though such a compound was isolated in only one case. These enediones undergo rapid Baeyer-Villiger oxidation with a second equivalent of m-chloroperbenzoic acid. In certain cases, the reaction with a third equivalent of m-chloroperbenzoic acid has been observed and, again, this is viewed as a Baeyer-Villiger oxidation. MECHANISTIC STUDIES ON THE OXIDATION OF ALKYL SUBSTITUTED TETRAHYDROBENZOFURANS WITH m-CHLOROPERBENZOIC ACID by Samuel Beryl Gingerich A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry MONTANA STATE UNIVERSITY Bozeman, Montana March 1983 Archives ii d o p . I APPROVAL of a thesis submitted by Samuel Beryl Gingerich This thesis has been read by each member of the thesis committee and has been found to be satisfactory regarding content, English usage, format, citations, bibliographic style, and consistency, and is ready for submission to the College of Graduate Studies. Date Chairperson, graduate Commipcee Approved for the Major Department 3//r/g3 H Date Head, Major Department Approved for the College of Graduate Studies 7 - '2 %' F Z ? ____________ — Date Graduate Dean iii STATEMENT OF PERMISSION TO USE In presenting this thesis in partial fulfillment of the require ments for a doctoral degree at Montana State University, I agree that the Library shall make it available to borrowers under rules of the Library. I further agree that copying of this thesis is allowable only for scholarly purposes, consistent with "fair use" as prescribed in the U.S. Copyright Law. Requests for extensive copying or repro duction of this thesis should be referred to University Microfilms International, 300 North Zeeb Road, Ann Arbor, Michigan 48106, to whom I have granted "the exclusive right to reproduce and distribute copies of the dissertation in.and from microfilm and the right to reproduce and distribute by abstract in any format." Signature Date I 5» ^ 19 V ACKNOWLEDGEMENT The author wishes to express his gratitude to Dr. P.W. Jennings for the direction given and the support offered during his sojourn here at Montana State University. The author also wishes to thank the colleagues in his research group for the encouragement they offered professionally and personally during his graduate career. Gratitude is also expressed to the other members of the chemistry department for numerous helpful and stimulat ing discussions. A note of thanks to J.A. Campbell and Dr. C.F. Campana for their efforts on the x-ray crystallographic work. Gratitude is expressed to Montana State University for financial support in the form of teaching and research assistantships. The author thanks Joan Pribanic for the assistance freely given in so many aspects of this work. And finally, the author wishes to thank his family for the love and the support they have offered over the years. Without their care, this project would have been so much more difficult. vi TABLE OF CONTENTS Page 1. V I T A ................ .............. .................... iv 2. ACKNOWLEDGEMENT.......................... .............. V 3. TABLE OF CONTENTS.............................. .. vi 4. LIST OF TABLES ......................... • .............. vii 5. LIST OF FIGURES......................................... viii 6. ABSTRACT............................................... ix 7. INTRODUCTION........................................... I 8. STATEMENT OF THE P R O BLEM.......... 20 9. DISCUSSION . ....................................... 23 Oxidation of F u r a n ................................... 24 Studies with 3-Methyl-4,5,6,7-tetrahydrobenzofuran . 25 Studies with I,2,3,4,5,6,7,8-Octahydrodibenzofuran . 34 Studies with 3-Methyl-4,5,6,7-tetrahydrobenzo- Ig furan- O and I,2,3,4,5,6,7,8-Octohaydrodibenzo- furan-^O........................................... 39 Attempted Synthesis of Enediones ............ .... 57 Studies with 2 ,5-Dimethylfuran.................. 60 Studies with 2-Methyl-4,5,6,7-tetrahydrobenzofuran . 61 Studies with 2,3-Dimethy1-4,5,6,7-tetrahydro benzofuran ......................................... 75 Low Temperature NMR Studies with 3-Methyl- 4,5,6,7-tetrahydroenzof uran........................ 82 Discussion of the Proposed Mechanism ................ 85 10. SUMMARY................................................. 93 11. EXPERIMENTAL.......................... 95 12. REFERENCES 134 vii LIST OF TABLES Page IQ Table I. O Content for Studies Involving 3-Methyl- 4.5.6.7- tetrahydrobenzofuran..................... 46 Table 2. 0 Content for Studies Involving Perhydro- dibenzofuran. ..................................... 52 18 Table 3. O Content for Studies Involing 2-Methyl- 4,5 ,6,7-tetrahydrobenzofuran.................. .. 73 18 Table 4. O Content for Studies Involving 2,3-Dimethyl- 4.5.6.7- tetrahydrobenzofuran..................... 81 viii LIST OF FIGURES Page Figure I. Synthetic scheme followed for preparation of 3-methyl-4,5,6,7-tetrahydrobenzofuran ...... 26 Figure 2. Proposed mechanism for the oxidation of 3-methyl-4,5,6,7-tetrahydrobenzofuran via a diepoxide intermediate.......................... 32 Figure 3. Synthetic scheme followed for preparation of perhydrodibenzofuran............................ 35 Figure 4. Proposed mechanism for the oxidation of perhydrodibenzofuran via a diepoxide inter mediate ......................................... 37 Figure 5. Perspective view of the molecular structure of 78 .... ............................... 38 Figure 6. Synthetic scheme followed for preparation of Ig 3-methyl-4,5,6,7-tetrahydrobenzofuran- 0 . 44 Figure 7. Proposed mechanism for the cyclization of p,y-epoxy ketals to furans...................... 48 Figure 8. Synthetic scheme followed for preparation of 18 perhydrodibenzofuran- 0 ........................ 50 Figure 9. NMR spectrum of 96a . ....................... 51 13 Figure 10. C NMR spectrum of 7 7 a ........................ 53 Figure 11. NMR spectrum of 7 8 a ........................ 54 Figure 12. Proposed mechanism for the oxidation of 18 perhydrodibenzofuran- 0 via an enedione intermediate..................................... 55 Figure 13. Proposed mechanism for the oxidation of 18 3-methyl-4,5,6,7-tetrahydrobenzofuran- 0 via an enedione type intermediate.............. 56 ix LIST OF FIGURES— Continued Page Figure 14. Synthetic scheme followed for preparation of 2-methyl-4,5,6,7-tetrahydrobenzofuran........ 62 13 Figure 15. C NMR analysis of carbonyl resonances of HO .................................. 64 Figure 16. Initially proposed mechanism for the oxida tion of 2-methyl-4,5,6,7-tetrahydrobenzofuran . 67 Figure 17. Proposed mechanism for the oxidation of 2-methyl-4,5,6,7-tetrahydrobenzofuran via an enedione intermediate................ 75 Figure 18. Proposed mechanism for the oxidation of 2,3-dimethyl-4,5,6,7-tetrahydrobenzofuran via an enedione intermediate........... 83 X ABSTRACT The reaction of a series of alkyl substituted tetrahydrobenzo- furans with m-chloroperbenzoic acid has been explored. The furan substrates used included 3-methyl-4,5,6,7-tetrahydrobenzofuran, I,2,3,4,5,6,7,8-octahydrodibenzofuran, 2-methy1-4,5,6,7-tetrahydro- benzofuran and 2,3-dimethyl-4,5 ,6,7-tetrahydrobenzofuran. The products arising from the oxidation of these substrates have been isolated and their structures determined. These substrates have also been prepared labeled with oxygen-18. These labeled substrates were also oxidized and the position of the label in the products deter mined by carbon-13 NMR spectroscopy. On the basis of the data obtained from these experiments, a detailed mechanistic scheme was developed. Initial attack of the furan moiety by m-chloroperbenzoic acid occurs to form an epoxide which subsequently undergoes ring openings to form a cis-enedione. These compounds are postulated as intermediates in all the reactions studied even though such a compound was isolated in only one case. These enediones undergo rapid Baeyer-Villiger oxidation with a second equivalent of m-chloro perbenzoic acid. In certain cases, the reaction with a third equiva lent of m-chloroperbenzoic acid has been observed and, again, this is viewed as a Baeyer-Villiger oxidation. I INTRODUCTION The chemistry of furans has attracted the interest of many researchers over the years. However,