In presenting the dissertation as a partial fulfillment of • the requirements for an advanced degree from the Georgia Institute of Technology, I agree that the Library of the Institute shall make it available for inspection and circulation in accordance with its regulations governing materials of this type. I agree that permission to copy from, or to publish from, this dissertation may be granted by the professor under whose direction it was written, or, in his absence, by the Dean of the Graduate Division when such copying or publication is solely for scholarly purposes and does not involve potential financial gain. It is under- stood that any copying from, or publication of, this dis- sertation which involves potential financial gain will not be allowed without written permission. 3/17/65 b LTh PART I THE RELATIVE REACTIVITIES OF COMMON NUCLEOPHILIC REAGENTS TOWARD DIFLUOROMETHYLENE--A SEARCH FOR BIFUNCTIONAL CATALYSIS PART II THE REACTIONS OF THE METHYLENE HALIDES WITH ALKOXIDES IN ALCOHOLIC SOLVENTS--A - SEARCH,FOR AN a-ELIMINATION MECHANISM AND METHYLENE INTERMEDIATES PART III THE REACTION OF METHYLMAGNESIUM BROMIDE WITH BENZOPHENONE-- THE MECHANISM OF THE GRIGNARD REACTION A THESIS Prethented .to The Faculty of the Graduate Division by 4/ Roy lAuke In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the School of Chemistry Georgia Institute of Technology April, 1967 Original Page Numbering Retained. PART I THE RELATIVE REACTIVITIES OF COMMON NUCLEOPHILIC REAGENTS TOWARD DIFLUOROMETHYLENE--A SEARCH FOR BIFUNCTIONAL CATALYSIS PART II THE REACTIONS OF THE METHYLENE HALIDES WITH ALKOXIDES IN ALCOHOLIC SOLVENTS--A SEARCH FOR AN ccELIMINATION MECHANISM AND METHYLENE INTERMEDIATES PART III THE REACTION OF METHYLMAGNESIUM BROMIDE WITH .BENZOPHENONE-- THE MECHANISM OF THE GRIGNARD REACTION Approved: ■■• - Date app ved by Chairman I 1 6 ACKNOWLEDGMENTS The author wishes to thank Drs. Jack Hine and E. C. Ashby for their guidance and encouragement throughout the course of this work. The helpful comments offered by Dr. H. M. Neumann while serving on the reading committee are also appreciated. Financial assistance from the Army Ordinance Department and the Alfred P. Sloan Foundation is gratefully acknowledged. The author also wishes to express his gratitude to his wife for her understanding and help at every step of the way. TABLE OF CONTENTS Page ACKNOWLEDGMENTS ii LIST OF TABLES. ix LIST OF ILLUSTRATIONS xviii SUMMARY xxii PART I Chapter I. INTRODUCTION 1 Background The Basic Hydrolysis of the Haloforms The Basic Hydrolysis of Difluarohalomethanes Bifunctional Capturing Agents Objectives Approach II. EXPERIMENTAL 8 Instrumentation pH Measurements and. Potentiometric Titrations Constant-Temperature Bath Nuclear Magnetic Resonance Spectra Infrared Spectra Chemicals The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Various Nucleophilic Reagents Apparatus and Procedure Analyses Hydroxide, Phenoxides, and Sulfides Chloride Fluoride Catechol Mono(Difluoromethyl) Ether ,iv Table of Contents (continued) Page Preparations Preparation of Catechol Mono(Difluoromethyl) Ether Reaction of Chlorodifluoromethane with Phenoxide in Deuterium Oxide Identification of Reaction Products III'. DISCUSSION AND RESULTS 18 The Basic Hydrolysis of Chlorodifluoromethane Determination of the Product Distribution from the Stoichiometry Determination of the Relative Rate Constants The Basic Hydrolysis of Chlorodifluoromethane Comparison of the Basic Hydrolyses of Chlorodifluoro- methane and Chloroform Rate Constants and the Appropriate Concentration Terms Carbon Monoxide as a Reaction Product The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Monofunctional Reagents The Reaction of Difluoromethylene with Fluoride The Reaction of Difluoromethylene with Azide The Reaction of Difluoromethylene with Cyanide The Relative Reactivities of Azide, Cyanide, Hydroxide, and Fluoride Summary The Reaction of Difluoromethylene with Phenoxide The Reaction of Difluoromethylene with 2,4- Dichlorophenoxide The Reaction of Difluoromethylene with p-Methyl- thiophenoxide The Relative Reactivities of Some Nucleophilic Reagents Toward Difluoromethylene The Relative Reactivities,of Water and Hydroxide toward Difluoromethylene The Reaction of Difluoromethylene with Phenoxide The Reaction of Difluoromethylene with Phenoxide in Deuterium Oxide.. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Bifunctional Reagents The Reaction of Difluoromethylene with Catechol Monoanion The Reaction of Difluoromethylene with Pyrogallol ii Table of Contents (continued) Page The Reaction of Difluoromethylene with 2-Mercaptoethanol The Basic Hydrolysis of Chlorodifluoromethane in 60 Percent Ethanol The Reaction of Difluoromethylene with Hydroxide in 60 Percent Ethanol The Reaction of Difluoromethylene with Phenoxide The Reaction of Difluoromethylene with m-Chloro- phenoxide The Reaction of Difluoromethylene with p-Chloro- phenoxide IV. CONCLUSIONS 72 APPENDIX 74 LITERATURE CITED 99 PART II I. INTRODUCTION 101 Background The Reactions of Mono-, Di, and Trihaiomethanes with Strong Bases Purpose Approach II. EXPERIMENTAL 108 Instrumentation Ultraviolet Spectra Nuclear Magnetic Resonance. Spectra Infrared Spectra Potentiometric Titrations Constant-Temperature Bath Chemicals Reaction of the Methylene Halides with Alkoxides Determination of the Rates of Formal Formation Preparation of-Di(tert-Butyl)- and Diisopropyl Formal Determination of the Stoichiometry of. the Reactions of Potassium tert-Butoxide and Isopropoxide with the Methylene Halides I 17 vi Table of Contents (continued) Page Deuterium Exchange of the Methylene Halides The Nuclear Magnetic Resonance Method The Near-Infrared Method- The Infrared Method Determination of the Deuterium Content of Exchanged Methylal Preparation of Deuterium-Exchanged. Methylal : Isolation of Deuterium-Exchanged Methylal Determination of the CH 2 /CH 3 Ratio of Deuterium- Exchanged Methylal Preparation of Methyl Alcohol-d Procedure Preparation of Isopropyl and tert-Butyl Alcohol-d Procedure ,III. DISCUSSION AND RESULTS ., . • 133 Readtions of the Methylene Halides with Alkoxides The Rates of Fotmal Formation Reaction of Chloroform with Alkoxides The Rate of Reaction Reactions of the Methylene Halides with Alkoxides The Solvent Kinetic Isotope Effect The Rates, of Deuterium Exchange Derivation of the Rate Equations for Deuterium Exchange Results of the Study of Deuterium Exchange Study of the .Deuterium Content of the Formal The Mass-Law Effect Product and Stoichiometry Studies IV• CONCLUSIONS 158 APPENDIX 160 LITERATURE CITED 231 vii Table of Contents (continued) Page PART III INTRODUCTION 234 Background The Reactive Grignard Species Association of the Grignard Reagent The Grignard-Ketone Complex Kinetics of the Grignard Reaction Reaction Mechanism Purpose Approach II. EXPERIMENTAL 243 Apparatus Instrumentation Constant-Temperature Bath Timer Inert-Atmosphere Box Reaction Flasks Chemicals Methods for Following the Grignard Reaction Kinetic Studies Preparation of the Reaction Flasks and Addition of Benzophenone Preparation of Methylmagnesium Bromide Solutions Initiating, Timing, and Quenching of the Reactions Analyses Extinction Coefficients Preparations Methylmagnesium Bromide Inert-Atmosphere Box and Purification System Purification System Preparation of Manganese(II) Oxide viii Table of Contents (continued) Page III. DISCUSSION AND RESULTS 258 Kinetic Studies The Grignard Mechanism The Meisenheimer Mechanism The Dimer Mechanism The Swain Mechanism IV. CONCLUSIONS 286 APPENDIX 288 LITERATURE CITED 321 VITA 324 ix LIST OF TABLES Table Page PART I 1. The . Basic Hydrolysis of Chlorodifluoromethane at 36° . 22 2, The Basic Hydrolysis of Chlorodifluoromethane at 36° . 32 3. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Fluoride at 36° . 33 4. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Azide at 36° 34 5. Comparison of Directly and Indirectly Determined Fractions of Difluoromethyl Azide 36 6. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Cyanide at 36° 39 7. The Relative Reactivity of Azide, Cyanide, Hydroxide, and Fluoride toward Difluoromethylene 41 8. The Basic Hydrolysis of Chlorodifluoromethane in the. Presence of Phenoxide at 36° 42- 9. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of 2,4-Dichlorophenoxide at 36° 44 10. The, Basic Hydrolysis of Chlorodifluoromethane in the Presence of p-Methylthiophenoxide at 36° 45 11. The Relative Reactivities of Some Nucleophilic Reagents Toward Difluorotethylene 46 12. The Basic Hydrolysis of Chlorodifluoromethane in the rresence of Catechol at 36° 56 13. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Catechol at 36° 56 14. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Catechol at 36° 57 15. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Catechol at 36° 57 List of Tables (continued) Table Page 16. Direct Determination of Catechol Mono(Difluoromethyl)Ether . 59 17. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of 2-Mercaptoethanol at.36° 63 18. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of Phenoxide in 60 Percent Ethanol 69 19. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of m,-.Chlorophenoxide in 60 Percent Ethanol at 25° . 69, 20. The Basic Hydrolysis of Chlorodifluoromethane in the Presence of p-Chlorophenoxide in 60 Percent Ethanol at 25° . 71 21. The Basic