SELECTIVE REDUCTION OF CONJUGATED NITROQLEFINS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By DEAN EVERETT LEY, B.Sc., M.Sc. The Ohio State University 1954 Approved by: / Adviser Department of Chemistry ACKNOWLEDGMENTS The author wishes to express his gratitude to Doctor Harold Shechter, who suggested this problem, for his generous guidance and advice throughout this investigation and his assistance in the preparation of this dissertation. He also acknowledges the generous spirit in which several graduate students and staff members contributed useful materials, equipment and information. The author also wishes to express his appreciation to the Office of Naval Research, who generously supplied the funds that made this research possible. TABLE OF CONTENTS Page A. STATEMENT OF PROBLEM....................... 1 B. INTRODUCTION.............................. 2 C. HISTORICAL 1. Reduction of Conjugated Nitroolefins by Dissolving Metals.................... 10 2. Catalytic Reduction of Conjugated and Unconjugated Nitroolefins............ 13 3. Reduction of Conjugated Nitroolefins With Complex Hydrides .......... 15 D. THE PRESENT INVESTIGATION, DISCUSSION OF RESULTS 1. Selective Reduction of Conjugated Nitroolefins by Sodium Trimethoxyboro- hydride............................. 22 2. Selective Reduction of Conjugated Nitroolefins by Lithium Borohydride.... 34 3. Selective Reduction of Conjugated Nitroolefins by Lithium Aluminum Hydride 43 4. Selective Reduction of Conjugated Nitroolefins by Sodium Borohydride 4& E. EXPERIMENTAL TECHNIQUE 1. Apparatus........................... 52 2. Solvents............................ 52 3. Mode of Addition.................... 54 4. Handling of Hydrides................ 54 5. Acidification of the Reaction Mixture.. 55 6. Identification of Products........... 55 F. REAGENTS.................................. 57 iii Page G. EXPERIMENTAL 1. Selective Reduction of Conjugated Nitroolefins by Sodium Trimethoxyboro- hydride............................ 65 a. Reduction of 1-nitropropene 65 b. Reduction of 2-methyl-l-nitro- propene...................... 67 c. Reduction of 2-nitro-l-butene... 70 d. Reduction of 2-nitro-2-butene... 73 e. Reduction of 4-nitro-3-heptene.. 76 f. Reduction of 3,3>3-trichloro-l- nitropropene............ 79 g. Reduction of 4j45 5, 5,6,6,6-hIepta- fluoro-2-nitro-2-hexene....... 82 h. Reduction of 5,5,6,6,7>7, 7-Kepta- fluoro-3-nitro-3“heptene....... 83 i. Reduction of omega-nitrostyrene. 8k j. Reduction of 2-(2-nitrovinyl) furan........................ 8 9 k. Attempted reduction of l-(nitro- methyl) cyclopentene........... 91 1. Reaction of Sodium trimethoxy- borohydride with 2-nitro-l-butyl acetate................ ...... 92 2. Selective Reduction of Conjugated Nitroolefins by Lithium Borohydride a. Reduction of 1-nitropropene 93 b. Reduction of 2-methyl-l-nitro- propene...................... 95 c. Reduction of 2-nitro-l-butene... 97 d. Reduction of 2-nitro-2-butene. 100 e. Reduction of 4-nitro-3-heptene.. 101 f. Reduction of 3j3>3-trichloro-l- nit r opropene.............. 104 g. Reduction of 4,4,5j5,6,6 ,6-hepta- fluoro-2-nitro-2-heptene....... 10$ h. Reduction of 5,5,6 ,o,7>7>7-hepta- fluoro-3-nitro-3-heptene........106 i. Reduction of oraega-nitrostyrene. 10$ j. Reduction of 2-(2-nitrovinyl) furan......................... 110 k. Reduction of D-arabo-tetra- acetoxy-l-nitrohexene.......... 112 1. Reaction of Lithium borohydride with 2-nitro-l-butyl acetate.... 113 iv Page 3. Selective Reduction of Conjugated Nitro­ olefins With Lithium Aluminum Hydride a. Reduction of 2-nitro-2-butene 114 b. Reduction of 3>3j3-trichloro-l- nitropropene......... 115 c. Reduction of 3,3,3-trifluoro-l- nitropropene................... 116 d. Reduction of 5j5>6,6,7,7j7-hepta- fluoro-3-nitro-3-heptene........ 118 e. Reduction of omega-nitrostyrene... 119 f. Reduction of 2-nitro-l-phenyl- propene....................... 122 g. Reduction of 2-(2-nitrovinyl)furan 124 4. Selective Reduction of Conjugated Nitroolefins With Sodium Borohydride a. Reduction of 2-nitro-2-butene 125 b. Reduction of 4-nitro-3-heptene..., 127 c. Reduction of omega-nitrostyrene... 128 d. Reduction of D-arabo-tetra- acetoxy-l-nitrohexene........... 131 e. Attempted heretrogeneous reduction of 5,5,6, 6,7,7j7-heptafluoro-3- nitro-3-heptene................ 131 5. Reaction of Omega-nitrostyrene in the Presence of Benzyltrirnethylammonium Hydroxide............... 132 6. Reaction of 2-(2-Nitrovinyl)furan in the Presence of Benzyltrirnethylammonium Hydroxide........................... 133 7. Reaction of l-Nitro-2-phenylethane and Omega-nitrostyrene................... 133 8. Reaction of 2-Nitro-l-butene and 2- Nitrobutane......................... 134 H. CONCLUSIONS............................... 136 I. BIBLIOGRAPHY.............................. 139 J. AUTOBIOGRAPHY............................. 144 o o SELECTIVE REDUCTION OF CONJUGATED NITROOLEFINS A. STATEMENT OF PROBLEM The present investigation is primarily a study of the reduction of conjugated nitroolefins with lithium borohydride, sodium borohydride, sodium trimethoxyborohydride and lithium aluminum hydride, respectively. It is the purpose of this study to develop satisfactory laboratory methods for synthesis of primary and secondary nitroalkanes from their corresponding conjugated nitroalkenes; it is also desirous that the methods developed be applicable for preparation of complex and highly functionally-substituted primary and secondary mononitroalkanes. 1 2 B. INTRODUCTION During the past decade the chemistry of aliphatic nitro compounds has been a subject of renewed interest; excellent reviews of the earlier chemistry of nitroalkanes 1 2 have been written by Gabriel in 1939 and 1940 , Hass and Riley^ in 1943, Degering in 1945^, Levy and Rose'* in 194$> 6 7 Shechter and Kaplan in 1952, and Hass, Riley and Shechter' in 1953. Examination of the extensive literature of nitro- paraffin chemistry reveals, however, that there are very few methods for synthesis of pure nitroalkanes by satisfactory • methods. Most of the methods that have been developed suffer the limitations that they are not general, the yields of reaction product are poor, the processes are tedious and involve complex and unavailable reactants, and mixtures which are difficultly separated are obtained. A survey, appropriate for the present discussion, of laboratory methods, and their limitations, for preparing mononitro- alkanes will now be summarized. The most important method for preparation of lower nitroalkanes involves nitration of alkanes in the vapor- 8 phase with nitric acid. Vapor-phase nitration is usually conducted as a continuous process at temperatures ranging from 350-450° and exposure times up to one second. Under these conditions, any primary, secondary, or tertiary hydrogen atom or any alkyl group of an alkane may be 3 replaced by a nitro group to yield mononitroalkanes. Thus, nitration of propane, a process now being operated tech- 9 nically by the Commercial Solvents Corporation, yields nitromethane, nitroethane, 1-nitropropane, and 2-nitro- propane. The vapor-phase method, although quite satis­ factory for commercial adaptation, suffers from the facts: (1 ) the experimental conditions are either too drastic or are inaccessible for ready laboratory use, (2 ) the reactions are relatively non-specific in that oxidation is an important competitive process, and (3 ) the nitration products are those derived by all possible hydrogen and alkyl-substitu­ tion processes. At present, for the laboratory chemist, the most significant aspect of the vapor-phase method is that it offers large quantities of lower mononitroalkanes very economically; these lower mononitro compounds then serve as convenient reagents for synthesis of more complex mononitro compounds. Nitration of hydrocarbons in the liquid-phase has been widely studied"^’ ^ in an attempt to develop adequate methods for preparing mononitroalkanes. The principal liquid-phase nitration reaction is replacement of hydrogen atoms by nitro groups; a nitration reaction involving replacement of alkyl groups does not occur as in the vapor-phase process. The order of reactivity of hydrogen atoms of alkanes or cycloalkanes is tertiary > O 4 secondary> primary. The liquid-phase method; offers the disadvantages that (1 ) most organic substances are in­ soluble in nitric acid or in nitrating mixtures, (2 ) mixtures of primary, secondary, and tertiary mononitro compounds which are separated with great difficulty are always obtained, (3 ) excessive oxidation-reduction usually accompanies nitration, (4 ) hydrolysis and oxidation of the primary and secondary nitroalkanes yield carboxylic acids and ketones, respectively, which then undergo further oxi­ dation, and (5) continued nitration of mononitroalkanes results in formation of polynitroalkanes. The principal laboratory uses for liquid-phase nitration are therefore usually limited to preparation of simple tertiary nitro compounds (separable from acidic nitro compounds by alkaline extraction), simple nitrocycloalkanes, and certain stable and unique primary and secondary mononitroalkanes. The most important general method for preparing unsubstituted mononitroalkanes has been reaction of alkyl halides with metallic nitrites. Reaction of silver nitrite with primary, secondary, or tertiary halides is known as the Victor Meyer method; the reaction may lead to the formation of alkyl nitrites and nitrates and various 11 12