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University Microfilms INFORMATION TO USERS This dissertation was produced from a microfilm copy of the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted. The following explanation of techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1. The sign or "target" fo r pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image. You will find a good image of the page in the adjacent frame. 3. When a map, drawing or chart, etc., was part of the material being photographed the photographer followed a definite method in "sectioning" the material. It is customary to begin photoing at the upper left hand corner of a large sheet and to continue photoing from left to right in equal sections with a small overlap. If necessary, sectioning is continued again — beginning below the first row and continuing on until complete. 4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation. Silver prints of "photographs" may be ordered at additional charge by writing the Order Department, giving the catalog number, title, author and specific pages you wish reproduced. University Microfilms 300 North Zeeb Road Ann Arbor, Michigan 48106 A Xerox Education Company 73-1990 FIKES, Lewis Edgar, 1943- A STUDY OF STBRIC, ELECTRONIC AND ACID- CONCENIRATION EFFECTS IN SCHMIDT REACTIONS OF ARYL M - m KETONES, DIALKYL KETONES, AND CYCLOPROPYL KETONES. The Ohio State University, Ph.D., 1972 Chemistry, organic University Microfilms, A XEROX Company, Ann Arbor, Michigan THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED. A STUDY OF STERIO, ELECTRONIC AND-ACID-CONCENTRATION EFFECTS IN SCHMIDT REACTIONS OF ARYL ALKYL KETONES, DIALKYL KETONES, AND CYCLOPROPYL KETONES ✓ DISSERTATION Presented, in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of the Ohio State University By Lewis S, Fikes, B.A., M.A.T,, M.S. ***** The Ohio State University 1972 Approved by Adviser Department of Chemistry PLEASE NOTE: Some pages may have indistinct print. FiImed as received. University Microfilms, A X e ro x Education Company DEDICATION To the memory of my Mother and Father ii ACKNOWLEDGMENTS I wish to thank Professor Harold Shechter for suggesting this study and, for his expert assistance in the preparation of this manuscript. I extend my appreciation and gratitude to ray mother-in-law, Ruth Heisel, for typing the rough draft of this dissertation. Finally, I am grateful to ray wife, Martha, for typing the final draft of this dissertation with so much care and expertise and for her constant encouragement and support during ray graduate training. iii TABLE OF CONTENTS Page DEDICATION................................. ii ACKITOWLEDGîIENTS........................... iii LIST OF T A B L E S ............................. v INTRODUCTION ............................... 1 HISTORICAL REVIEW ......................... 5 RESULTS AND DISCUSSION..................... 35 EXPERIMENTAL ............................... 113 APPENDIX A ................................. 144 APPENDIX B ................................. 146 iv LIST OF TABLES Table Page 1 Scrirnidt Reactions of para-Substituted Benzophenones............................. 17 2 Schniidt Reactions of Alkyl Phenyl Ketones . 19 3 Schr;:idt Reactions of l-Tetralones and 4-Chroraanone 21 4 Schmidt Reactions of Ohromanones ......... 22 5 Schrcidt Reactions of In d a n o n e s ....... 25 6 Schmidt Reactions of Oyclopropyl Ketones . 29 7 Schmidt Reactions of Ethyl Aryl Ketones . 38 8 Schmidt Reactions of Isopropyl Phenyl K e t o n e .................................. 47 9 Schmidt Reactions of Iscprcpyl para-Tolyl K e t o n e ............................... 56 10 3chr.iidt Reactions of Isopropyl nara-Anisyl K e t o n e ..................................... 59 11 Schmidt Reactions of Neopentyl Phenyl K e t o n e ..................................... 63 12 Schmidt Reactions of Alley 1 Methyl Ketones . 72 13 ScWidt Reactions of Neopentyl Methyl Ketone..... ............................. 75 14 Schmidt Reactions of Oyclopropyl Phenyl K e t o n e ......................... 83 15 Product Recovery Studies ................ 84 16 Schmidt Reactions of Oyclopropyl Methyl Ketone ......... ..................... 90 V 17 Schmidt Reactions of Oyclopropyl Ethyl K e t o n e ..................................... 94 18 Schmidt Reactions of Oyclopropyl Isopropyl Ketone . .............................. 95 19 Schmidt Reactions of Oyclopropyl Alkyl Ketones ............................ 96 20 Product Recovery Studies of Brackenridge's W o r k ..................................... 145 VI INTRODUCTION The acid-catalysed reaction of unsyiTUDetrical ketones with hydrogen aside, the Schmidt reaction,^ (l) For reviews see: H. V/olff, Org, Reactions, 3.» Chapter S (1946) and P. A, S. Smith in Mayo, "Molecular Rearrangements," Vol. 1, Interscience Publishers, Inc., New York, 1963. yields as principal products two isomeric amides (Eq 1), HR^ R-CO-R‘ — R-NH-CO-R' + R-CO-NH-R' (l) the ratio of which is profoundly influenced by the structure of the starting ketone. Early investigations indicated this structural influence was primarily steric in nature, the more bulky R group migrating preferentially. Accordingly, the early mechanistic formulations for the Schmidt reaction reflected this steric factor. However, subsequent scattered investigations have shovm additional factors (eg, electrical and acid concentration effects) may be operative in Schmidt reactions of ketones, and thus modifications of earlier proposed mechanisms may be necessary. The effect of the concentration of the acid 1 catalyst on the course of the Schmidt reaction of ketones 2 has received little study. However, Brackenridge has (2) B, R, Brackenridge, Ph.D. Thesis, The Ohio State University, Columbus, Ohio, 1966. reported that the concentration of sulfuric acid affects the ratio of isomeric amides produced in Schmidt reactions of meta-substituted benzophenones. At elevated acid concentrations he reported that preferential migration of electron-deficient phenyl groups occurred. This was a surprising result. Perhaps equally surprising have been the results of the few Schmidt reactions which have been carried % out on oyclopropyl ketones. F o r instance, Bunce and (5) S. C. Bunce and J. B. Cloke, J. Am. Cham. Soc,, 76, 2244 (1954). % Cloke^ have reported that in the Schmidt reaction of oyclopropyl methyl ketone (Eq 2), the sterically smaller [^CO-CH^ - P>-CO-NH-CH^ + [>-NH-CO-CH^ (2) " 77fo methyl group migrates preferentially. Since this was the opposite result one would expect on steric grounds, Bunce and Cloke concluded that electronic effects must be of importance. However, the nature of such electronic effects was not specified. The initial phase of the present study was con­ cerned with the investigation of Schinidt reactions of a number of alkyl aryl ketones in order to see; 1. whether in Schmidt reactions of alkyl aryl ketones there is an acid-concentration effect on the amide ratios, similar to that observed p by Brackenridge for Schmidt reactions of meta-substituted benzophenones; 2, whether various electron-withdrawing and -dona­ ting substituents on the aryl moiety of these allcyl aryl ketones might result in amide ratios indicating the operation of electronic factors in the Sctoidt reactions of these ketones. In this initial phase, Schmidt reactions were effected on. the following: ethyl phenyl ketone, ethyl meta-tolyl ketone, ethyl nara-bromophenyl ketone, ethyl meta-nitrophenyl ketone, ethyl para-tolyl ketone, ethyl para-anisyl ketone, isopropyl phenyl ketone, isopropyl para-tolyl ketone, isopropyl para-anisyl ketone, and neopentyl phenyl ketone. The second phase of the present study involved study of Schmidt reactions of various cyclopropyl ketones to see: 1, whether the amide ratios are a function of acid concentration; 2, whether the cyclopropyl group gives rise to any electronic effects in Schmidt reactions of cyclopropyl ketones. Accordingly, Schmidt reactions were carried out on the following: cyclopropyl phenyl ketone, cyclopropyl methyl ketone, cyclopropyl ethyl ketone, and cyclopropyl isopropyl ketone. To assist interpretation of the results of reactions of hydrogen aside with cyclopropyl ketones and allcyl aryl ketones, Schmidt reactions were effected on the following dialley 1 ketones : methyl ethyl ketone, methyl isopropyl ketone, and methyl neopentyl ketone. ■ In summary, the present investigation involves study of steric, electrical, and acid concentration effects on the products and mechanism of Schmidt reactions of alkyl aryl ketones, cyclopropyl ketones, and dialkyl ketones. HISTORICAL REVIEW The acid-catalyzed reaction of hydrogen azide (HN^) with ketones and aldehydes was discovered by Karl Friedrich Schmidt^ while investigating the decomposition (4) K. P.
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