DOCTORAL DISSERTATION SERIES sWdy 4 I, A o f {he A c i i o n o f G r i qn t<L t it le k ecntinism Tfoort in iion II. t a i t o n o /? f.a c A l c o h o ls H l'S y f iih £eJ&is o f ' H y r l r n c a r h o n 6 IV. M / s c e / l c t n f t o u s I I ' AUG- Diehard \)tehL George 1343 a u th o r date State Co/h V dnid UNIVERSITY 9 * *- M £ DEGREE PUBLICATION NO. mi M l!1!1 1 1 '2 !3 |! UNIVERSITY MICROFILMS E M M ANN ARBOR - M I C HI GA N The Pennsylvania State College The Gr adua t e 8choo 1 Department of Chemistry I. A Study of the Action of Grigna,rd Reagents with Carbonyl Compounds and a Proposed Mechanism for the Reaction II. Dehydration of Tertiary Alcohols III. Synthesis of New Aliphatic Hydrocarbons IV. Miscellaneous A Thesis by Richard Stanley George Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy August 19^-3 Approved: J uly 19^3 Research Professor of Organic Chemistry July 3 a, 19^3 Head of Department of Chemistry ACKNOWLEDGEMENT The author is deeply indebted to Dr. Frank C. Whitmore who suggested and directed this research. Thanks are due to Dr. George H. Fleming for his help and advice on semi-micro fractionations and on the determinations of physical properties, to Dr. T. S. Oakwood who prepared some of the tertiary alcohols used in the dehydration study, to R. E. Meyer and N. C. Cook who did the hydro­ genations necessary for this work and to E, R, Weidlein, Jr. who has taken over the investigation of sterically hin­ dered carbonyl compounds and will thus finish some of' the studies started in this work. Thanks are also due to 'The Pennsylvania State College and the Abbott Laboratorie for fellowships which made these studies possible. TABLE OP CONTENTS Part 1 Page I. Introduction 1 p II. Historical III. Discussion 12 IV. Experimental 32 1. Description of Fra.ctj.onating Columns 32 2. Preparation of Starting Materials 32 (a) Alkyl Halides 32 (b) Dllsopropyl Ketone 33 (c) Pinaco'lone 33 (a) G-rignard Reagents 37 3« Refractive Index of Diisopropylcarbinol- DiIsopropyl Ketone Mixtures 37 k. Refractive Index of Diisopropylcarbinol- R-Diisopropylc&rbinol Mixtures 3g 5. Tbe Action of Methylmagneslum Bromide with D hi sopropyl Ketone 39 6 . The Action of Ethylmagnesium Bromide with Dilsopropyl Ketone bo 7* The Action of n-propylmagneslum Bromide with Dilsopropyl Ketone b2 S. The Action of Isopropylmagnesium Bromide with Dilsopropyl ketone il4 9 . The Action of n-Butylmagnesium Bromide with Dilsopropyl Ketone 10. The Action of Isobutylmagnesium Bromide with Dilsopropyl Ketone 4-g 11. The Action of t-Butylmagnesium Chloride with Dilsopropyl Ketone 53 12. The Action of jt-Amylmagneslum Chloride with Dilsopropyl Ketone 55 13. The Action of Neopentylmagnesium Chloride with Diisopropyl Ketone 56 1^-. The Action of Laurylraagnesium Bromide with Diisopropyl Ketone 60 15. The Action of n-Fropylmagnesium Bromide with Pinacolone 6*J- V. Summary 66 VI. Bibliography 67 Part 2 I. Introduction 70 II. Historical ?2 III. Discussion IV. Experimental 69 1. Determination of Physical Properties 69 2. Preparation and Properties of Starting Materials 3. Method for Identification and Estimation of DehydrationP roducts 92 4. Preparation of Compounds Necessary for Identification of Ozonolysis Products 92 (a.) Synthesis of n-Fropyl Isopropyl Ketone 93 (b) Synthesis of Isopropyl n-Butyl Ketone 95 Page (c) Synthesis of Isopropyl Isobutyl Ketone 9& (&) Synthesis of Isopropyl n-Amyl Ketone 96 (e) Synthesis of Isopropyl Isoamyl Ketone 97 (f) Synthesis of 3> 3"rDime'4hyl-2-hexanone 9& 5. Physical Properties of Intermediate Second­ ary Alcohols 99 6. Dehydration of Methyldlisopropylcarbinol 99 7. Dehydration of Ethyldilsopropylcarbinol 101 g. Dehydration of n-Propyldiisopropyl- cerbiriol 102 9 . Dehydration of n-Butyldiisopropylcarbinol 104 10. Dehydration of Isobutyldiisopropyl- carbinol 106 11. Dehydration of n-Amyldiisopropylcarbinol 109 12. Dehydration of Isoamyldiisooropylcarbinol 111 13. Dehydration of NeopentyldiIsopropyl­ carbinol ll4 14. Dehydration of Methyl-n-propyl-t-butyl- carbinol 116 ¥. Summary 125 ’ VI. Bibliography 126 Part 3 Page I. Introduction 12S II. Discussion 131 III. Experimental 135 1. Starting Materials 135 2. Hydrogenation of Olefins 135 3. Purification of the Saturated Hydrocarbons 135 Determination of Physical Properties 136 5. 2,2,3-Trlmethylhexane 136 (a) Hydrogenation of Olefins 136 (To) Rehydrogenation 137 (c) Refractionation of Nonane I3S (d) Physical Properties of 2,2,3“ Trlmethylhexane l4l 6. 2-Methyl-3“Isopropylhexane l4l (a) Hydrogenation of Olefins l4l (b) Refractionation of Decane 14-2 (c) Physical Properties of 2-Methyl~3- i sopropylhexane 143 7. 2“Methyl“3“isopropylheptane 144 (a) Hydrogenation of Olefins 144 (b) Refractionation 144 (c) Physical Properties of 2-Methyl-3- isopropylheptane l46 S. 2,6“Dimethyl-3-isopropylheptane 147 (a) Hydrogenation of Olefins 147 Page (b) Refractionation l4g (c) Physical Properties of 2,6-Dimethyl- 3-isopropylheptane 150 IV. Bibliography 151 Part 4 I. Introduction 152 II. Discussion 15^ III. Experimental 165 1. Purification of Methyl-t-butylneopentyl- Chloride 165 2. Purification of Dineopentylacetyl Chloride 166 3. Preparation of Me thy1-t-bu t ylne op e n t yl - acetaldehyde 16b K. Preparation of Isopropyl Me thy l-_t-butyl- neopentylcarbinyl Ketone 16B E. Preparation of Ethyl Dineopentylcarblnyl Ketone 170 6 . Addition of Acetyl Chloride to the Bromo­ ms, gne slum Enolate of Ethyl Dineopentyl- ctC etyl Ketone ■ 172 7. Attempt to Cleave 1-Acetyl-1-dineopentyl- acetyl-ethane with Methylmagneslum Bromide 176 6 . Preparation of 3 > 5 > rimethyl-3-t- butylhexahol-2 179 9. Oxidation of 3,5, E-Trimethyl-3-t- butylhexanol-2 ISO 10. Attempts to Isolate the Coordination' Com­ plex from t-Butylmagneslum Chloride and Me thy1-jfc-b ut y1neope nty1ac e t aid ehy d e 162 IV. Bibliography 186 PART I a study of the action of g-rig-nard reagents with carbonyl COMPOUNDS AND A PROPOSED MECHANISM FOR THE REACTION INTRODUCTION In the preparation of a series of tertiary alcohols for dehydration studies the action of several Grlgnard reagents with dilsopropyl ketone was investigated* With increasing com­ plexity of the alkyl group of the Grignard reagent the yield of addition product, the tertiary alcohol, was markedly decreased. When branched Grignard reagents, such as the 1 isopropyl reagent, were used no tertiary alcohol could be found Mpst of the Grignard reagents gave the reduction product and the enollzation product, but in no case could any condensation product be found. The close relationship between the structure of the Grignard reagents and the yields of reaction products soon became apparent. While the relation of the structure of the carbonyl compound to the products of the Grignard reaction has received adequate attention by workers in this field, the influence of the Grignard reagent on The reaction products has been somewhat neglected. Thus, the above series of reactions was run with the study of this influence as a primary objective. In several cases the experiments were planned to give optimum conditions for throvring some light on the mechanism of the addition, reduction and enolization reactions. HISTORICAL 2 The Grignard reaction, first reported in 1900 , is one of the most important reactions in organic chemistry. Count­ less studies have been made on this reaction and recorded in the literature. However, because of the failure of many invest! gators to recognize the possibility of obtaining a mixture of several reaction products, and because adequate fractionating equipment for a complete investigation of these products has only recently become available, much of this work is of question able value. Thus, in the only recorded investigations of the enolization of carbonyl compounds by different G-rignard reagents 3, 4- 9 done by G-rignard and coworkers , reduction was mistaken for enolization in many of their experiments. The failure to distinguish between enolization and reduction products from Grignard reactions has resulted in an erroneous observation regarding the enolization of ketones by Grignard reagents which seems to be generally accepted today. This observation may be stated as follows: '‘Enolization of ketones by Grignard reagents is primarily a function of hindrance in the ketone and branching of the chain In the reagent Is of relatively 6 minor importance in this reaction" . The studies on the reduction of carbonyl compounds by 1, 7, S, 9, 10 e-rignard reagents nave been more numerous, and they have contributed substantially to the chemistry of the