THE PREPARATION OF HIGHLY FLUORINATED GRIGNARD REAGENTS AND THEIR APPLICATION TO THE SYNTHESIS OF ORGANIC FLUORIDES ' DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohi.o State University By William Connett Francis, B.S. The Ohio State University 1952 Approved fay: Adviser ACKNOWLEDGMENT The author wishes to express his sincere grati­ tude to Professor Albert L, Henna for his indispensable guidance and encouragement throughout the course of this work, and for his very valuable contributions towards continued opportunities for me in this field. Financial assistance in the form of Research Fellowships from the General Motors and Dupont de Nemours Companies is also gratefully acknowledged. SSOSVG 11 TABLE OF COHTENTS INTRODUCTION 1 HISTORICAL 2 PURPOSE AND SCOPE 3 RESULTS PREPARATION AND REACTIONS OF CFnCHgBr A. Synthesis of CFaCBgBr 1. Preparation of CBrClg-CB^Br 6 2. Fluorlnatlon of CBrCla-CHsBr 7 3. Preparation of CBrCIF-CHaBr 8 4 . Fluorlnatlon of CBrClF-CHsBr 9 5. Preparation of CFgSCEBr 9 6. Preparation of CFaCEaBr 10 B, Reactions of CFgCl^Br 1. Attempted Reaction of CFsCHgBr with Mercury and Amalgams 11 2. Attempted Reaction of CFgCEsBr with Magnesium 12 3. Attempted Conversion of CFgCHsBr to CF3CE2I 13 II SYNTHESIS AND REACTIONS OF BEPTAFLUORO-n-PROPTL IODIDE A. Synthesis of n-CaFrl 14 B, Reactions of n-CgFyl 1, Reaction of n-CsFyl with Magnesium In Various Solvents 15 2, Formation of n-Cgl^'^jgl at Room Temperature (a) Determination of Grignard Formation hy Titration and Gas Analysis 15 (h) Carbonation of n-CgFyl - Magnesium Reaction Mlxtrures 16 (c) Reaction of n-C^yl with Magnesium In the Presence of Carbonyl Compounds 17 (d) Side Products from the Reaction of n-CsFyl with Magnesium 19 ill 5 » Low Temperature Reactions of n-CaFTi with Magnesium (a) Carbonation of n-CaFyl-Magnesium Reaction Mixtures 20 4 . Reaction of n-CaF-Mgl vlth Carbonyl Compounds at Low Temperatures (a) Reaction of n-CaF-^Mgl vlth Acetone 22 (b) Reaction of n-CsFvMgl -with n-Butyralde- hyde 25 (c) Reaction of n-CaF^Mgl with Ethyl Formate 25 (d) Attempted Reaction of n-CsP-TMgl with Heptafluorobutyraldehyde 29 (e) Reaction of n-C^-yMgl with Perfluoro Esters 53 (f) Reaction of n-CgF-^Mgl with Perfluoro Acid Chlorides 59 (g) Conclusions Concerning Reactions of Grignard Reagents with Carbonyl Functions Adjacent to Perfluoroalkyl Groups 4 l 5 , Side Products from the Reaction of n-CgF?! with Magnesium at Low Temperatures 42 III PERFLGûRCALKn. CARBINOLS A, Preparation of C^7~GH(0H)~C3F7 45 B. Acidity and Infrared Absorption Characteristics of CaFTCEfeOH» C3F7-CE(OS) , and SGMMAET AND CONCLUSIONS I PREPARATION AMD REACTIONS OF CFaCE^Br 49 II SYNTHESIS AMD REACTIONS OF BEPTAFLUORO-n- PROPYL IODIDE A. Synthesis of n-CgFrl 50 B. Formation of CaF^Mgl 5I C. Low-temperature Reactions of CsFyMgl 51 D. General Conclusions Concerning Reaction Conditions and Experimental Procedures 54 III PERFLUOROALKYL CARBINOLS 55 iv EXPEEIMENTAL I PREPARATION AMP BEACTIONS OF CFctCHpBr A, Synthesis of GFaCRgBr 1. Preparation of CBrClg-CB^Br 56 2, Fluorination of CBrCle-CHeBr 57 5. Preparation of CBrClF-CBgBr 58 4 . Fluorination of CBrClP-CHaBr 59 5. Preparation of CFa-CHBr 60 6« Preparation of CFaCBgBr 60 B. Reactions of CFaCBgBr 1. Attempted Reaction of CFaCBgBr with Mercury and Amalgams 6l 2. Reaction of CFaCBgBr with Magnesium 62 5. Attempted Conversion of CFaCBgBr to CFaCB^I 65 II SYNTHESIS AND REACTIONS OF BBPTAELUDRO-n- PBOFYL IODIDE A. Synthesis of n-CaPyl 64 B. Reactions of n-CaFyl 1. Formation of n-CaFyMgl at Room Temperature (a) Determination of Grignard Formation by Titration and Gas Analysis 66 (b) Carbonation of n-CaFyl - Magnesium Reaction Mirfcures 68 (c) Reaction of n-CaFyl with Magnesium in the Presence of Carbonyl Compounds 71 (d) Side Products from the Reaction of n-CaFyl with Magnesium 71 2 8 Dow-temperature Reaction of d-C^tI with Magnesium; Carbonation of Reaction Mixtures 73 3. Reactions of n-CgPTMgl with Carbonyl Compounds at Low Temperatures (a) Reactions of n-CgFyMgl with Acetone 78 (b) Reaction of n-CgF-^I with n-Butyralde- hyde 78 (c) Reaction of n-CgFyMgl with Ethyl Formate 80 (d) Attempted Reaction of n-CgFTMgl with Beptafluoro-n-butyraldehyde 85 (e) Reaction of n-CgPyMgl with Ethyl Hepta- fluoro-n-hutyrate 89 (f) Reaction of n-C^T^ligl with Eeptafluoro- n-hutyryl Chloride 92 III fERELUOROALm. CARBINOLS A. Preparation of C3F7-CE(OE)-C3F7 94 BIBLIOGEAPHÏ 96 ADTOBIOGRAEHY 9 9 1 THE PREPARATION OF HIGHLY FLUORINATED GEIGNARD REAGENTS AND THEIR APPLICATION TO THE SYNTHESIS OF ORGANIC FLUORIDES INTRODUCTION There has heen a growing interest in recent years in the use and study of fluorine-containing organic compounds. This interest arises from the fact that the replacement of hydrogen hy fluorine in organic molecules results, in most cases, in more stable compounds which have new and interesting physical and chemical properties. These compounds are also generally convenient to handle and study. Theoretically, as many carbon - fluorine ocmpounds are possible as there are organic compounds containing carbon and hydrogen. Thus the chemistry of organic fluorides could well develop into a new and distinct branch of chemistry of considerable importance both from the standpoint of technical and practical applications, and from the standpoint of the theoretical significance of effects resulting from the highly electronegative nature of the fluorine atom. However, the development of this field of chemistry is dependent upon the extent to which the fluorine analogues of organic compounds can be synthesized, and there are at present certain limitations due to the difficulty of introducing fluorine into organic molecules. Thus much of the current work in the field of organic fluorine chemistry is directed towards convenient methods of synthesizing compounds which contain fluorine atoms at known positions within the molecule. It is inevitable that such a program of research should include an investigation of the possibility of extending the widely applicable and extremely useful Grignard synthesis to the field of organic fluorides, HI3T0BICAL Studies involving the reaction of fluorinated organic halides vith magnesium and other metals have shown, as in the case of other types of fluorinated compounds, that the fluorine atoms have little effect upon the seat of reaction when separated from this function by two or more methylene groups. For example, the Grignard reagent of CFaCEgCBgCl has been prepared in good yield, and it is oxidized and carbonated in the usual manner to yield the respective trifluoro- substituted primary alcohol and carboxylic acid (1,2), However, when the fluorine atoms are situated alpha to the reactive halogen atom a different type of behavior is exhibited. Thus CHPsCBgl, CEFgCBgBr, and CF3CH2I react with metals such as magnesium, sodium, and potassium to yield the respective olefins resulting frcm the elimination of a fluorine atan and the adjacent halogen atom (3,4 ), No information concerning this type of reaction with CFaCHsCl or CFsCEgBr is to be found in the literature other than the general statement that they do not form a Grignard reagent (5), However, Huh (6) reports that CFsCHJaBr reacts with normal butyl lithium to yield the olefin, CFg^CHs, and n-butyl bromide, Among the fluorinated halo-methanes, Henne (3) found CClgFs, CHCIF2, and CHBrF2 to be unaffected even when passed through molten sodium. In ether or benzene solvents CF3CI fails to react with magnesium or lithium, A reaction takes place with both of these metals when trimethyl amine is used as the solvent, but there is no Indication of Grignard formation (T), Emeleus and Haszeldine (5 ) carried out an extensive series of reactions between CF3I and certain metals under 5 varying conditions. There was no reaction with magnesium in ether except at elevated temperatures or when irradiated with ultra-violet light. Under these conditions they observed only decomposition and formation of fluoroform. They succeeded, however, in preparing CFsHgl and (CF3)2Hg in good yields hy reacting CF3I with mercury and various amalgams under free radical conditions in the absence of protonic solvents. Attempts to convert these mercury derivatives to zinc or magnesium organometallic cimpounds were not successful (8), The reaction of CF3CF2I with magnesium was also found only to result in decomposition (5), POBFOSE AMD SCOPE The purpose of this research has been to study the synthesis of fluorinated organic halides, their reaction with metals, particuJarly magnesium, and the application of such organometallic derivatives to the synthesis of various fluorinated compounds, A particular aim of this investigation has been to develop through the Grignard type of reaction a method of introducing fluorinated clusters at certain specified positions within an organic molecule. The preparation and utilization of perfluoroalkyl Grignard reagents is considered especially desirable in that it would make possible the introduction of fluorinated clusters, such as a CFs- or homologous fluoro group, in a position directly adjacent to a functional group. This would thus constitute a method of synthesizing organic fluorides in which there is exerted a maximum inductive effect by such fluorinated clusters upon a functional group such as carbonyl, hydroxyl, etc. The initial efforts were directed towards the synthesis and reactions of CFsCBeBr, No successful preparation of a Grignard reagent 14. (CFsCHaMgX) from this type of compound has heen reported in the literature. However, there is no evidence of other than superficial examination of the behavior of this type of molecule with active metals. At the outset of this research no practical or convenient method for obtaining perfluoroalkyl halides such as CF3I appeared to be available. Later, Henne and Finnegan (9) developed a very convenient method for the preparation of perfluoroalkyl iodides from the readily available perfluoro carboxylic acids.