Investigating carbocations using high speed ball milling A thesis submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirements for the degree of Master of Science in the Department of Chemistry of the McMicken College of Arts and Sciences by Meghan R. Wagner B. S. Chemistry Otterbein College June 2009 Committee Chair: James Mack, Ph.D. i Abstract of Thesis Carbocations are typically formed in solution, where the solvent stabilizes the carbocation and mixes the reaction allowing the particles to interact and form products. However, in the absence of solvent it is unknown if the carbocation will form. Previous literature has shown that SN2 reactions can occur under high speed ball milling conditions; the results were that primary alkyl halides undergo substitution reactions, while the reactions of secondary alkyl halides depend on the nucleophile. However, reactions that form a carbocation intermediate, such as, SN1 reaction and pinacol rearrangement have not been explored, until now. ii iii Acknowledgements I would like to acknowledge and thank everyone that has helped me reach my goals thus far. iv Table of Contents Chapter Page 1. Introduction and Background………………………………………..……1 Green Chemistry……………………………………………….…….…....2 High Speed Ball Milling………………………………………………...…5 Substitution Chemistry……………………………………………………..7 2. Understanding carbocation formation under ball milling conditions…..…12 Carbocation formation under Ball Milling conditions...................................13 Pinacol Rearrangement………………………………………………...….21 Conclusions and Future Work……………………………………………..29 3. Experimental Methods…………………………………………,………….31 4. References…………………………………………………………………63 5. Appendix A Other Investigations……………………………………….…71 6. Appendix B Spectra………………………………………………………..79 v List of Figures Figure Page 1 – Valley of the Drums 2 2 –Vials and Balls 6 3 – High Speed Ball Mill 6 4 – Mechanism of SN1 reaction and the rate law 7 5 – Energy of SN1 reaction 7 6 – Mechanism of SN2 and the rate law 8 7 – Energy of SN2 reaction 8 8 – Reaction of bromobutane with sodium azide 9 9 – Primary Finkelstein reaction of n-pentyl bromide to n-pentyl iodide 9 10 – Secondary Finkelstein reaction of 2-bromopropane to 2-iodopropane 10 11 – Reaction of 4-bromobenzyl bromide with salts to form substituted 11 products 12 – Secondary bimolecular substitution in HSBM conditions 11 13 – Triphenylmethanol reacts with sulfuric acid to form trityl carbocation 12 14 – Triphenylmethyl chloride reacts with Lewis Acids to form trityl 13 carbocation 15 – GC-MS of triphenylmethyl bromide 14 16 – Triphenylmethyl bromide reacts with potassium iodide 15 17 – GC-MS results of triphenylmethyl bromide and KI under argon 16 18 – Triphenylmethyl bromide reacts with KOH 17 19 – GC-MS results from triphenylmethyl bromide and potassium hydroxide 17 vi 20 – GC-MS of triphenylmethyl bromide with KOH and 18-crown-6 18 after HSBM 21 – Triphenylmethanol, p-toluenesulfonic acid, and potassium iodide 19 reacted in alumina bath under microwave irradiation 22 – Triphenylmethanol reacts with aluminum bromide 20 23 – Pinacol reacted with sulfuric acid to from pinacolane 21 24 – Classical, or carbocation, mechanism of the Pinacol Rearrangement 21 25 – 1,1-diphenyl-2-methyl-1,2-propanediol reacted with sulfuric acid to from 22 3,3-diphenylbutanone 26 – The concerted mechanism of the Pinacol Rearrangement 23 27 – Pinacol type rearrangement 23 28 – Pinacol Rearrangement using benzopinacol and p-toluenesulfonic acid 24 29 – Coupling benzophenone using Zn/ZnCl2 26 30 – Deprotonation and reprotonation of benzopinacol 26 31 – Acetophenone coupling under HSBM conditions 27 32 – Benzophenone coupling with magnesium 27 33 – Oxidation of E-stilbene 27 34 – 1,2-diphenyl-1,2-ethanediol and p-toluenesulfonic acid under HSBM 28 conditions 35 – 1,1,2-triphenyl-1,2-ethanediol reacts with p-toluenesulfonic acid to form 28 1,1-diphenylacetophenone 36 – Wittig reaction using benzyl bromide, triphenyl phosphine, n-butyl lithium, 29 and benzophenone vii 37 – Wittig reaction using benzyl bromide, triphenyl phosphine, n-butyl lithium, 29 and 4-nitobenzophenone 38 – 1,2-diphenyl-1,2-ethanediol, acetone, and p-toluenesulfonic acid formed 71 ketal 39 – Ethylene glycol reacts with benzophenone and acid to form a ketal 72 40 – Ethylene glycol reacts with anisaldehyde and acid to form an acetal 72 41 – Diphenylmethyl bromide reacted with sodium iodide under liquid nitrogen 73 42 – Diphenylmethyl bromide reacted with sodium borohydride to form 73 diphenylmethane 43 – Diphenylmethyl bromide reacted with sodium iodide and 1-hexene 74 44 – Diphenylmethyl bromide reacted with sodium iodide and 74 1,4-cyclohexadiene 45 – Reaction of benzyl bromide with metal iodide forms benzyl iodide 75 46 – Friedel-Crafts alkylation under HSBM conditions 75 47 – GC-MS of Friedel-Crafts alkylation of toluene and 4-bromobenzyl 76 bromide 48 – Diels-Alder mechanism 76 49 – Diels-Alder reaction of anthracene and maleic anhydride 77 50 – Energy diagrams by B3PLY/6-31G* Theory 77 viii List of Structures Structure Compound MW g/mol diphenylmethane 168.23 tetraphenylethane 334.45 p-benzyltriphenylmethane 334.45 dodecane 170.34 toluene 92.14 1-hexene 84.16 1,4-cyclohexadiene 80.13 E-stilbene 180.25 Triphenylethylene 256.34 O2N 1-(4-nitro-phenyl)-1,2- diphenylethene 301.34 O2N 2,3 diphenyl-2-butene 208.3 ix H C H dichloromethane 84.93 Cl Cl Br benzyl bromide 171.03 I benzyl iodide 218.03 Br 4-bromobenzyl bromide 249.03 r B Cl 4-bromobenzyl chloride 205.48 Br Br diphenylmethyl bromide 241.13 Cl 278.78 triphenylmethyl chloride Br triphenylmethyl bromide 323.23 OH diphenylmethanol 184.23 OH triphenylmethanol 260.33 x OH benzopinacol 366.45 HO OH pinacol 118.18 HO OH 2,3 diphenyl-2,3-butanediol 242.31 HO HO OH 1,2-diphenyl-1,2-ethanediol 214.26 OH HO ethylene glycol 62.03 OH OH 1,1,2-triphenyl-1,2- ethanediol 290.36 O H 4-methoxybenzaldhyde (anisaldhyde) 136.15 O O benzophenone 182.22 O benzopinacolone 348.44 xi O acetone 58.08 O acetophenone 120.15 O 4-nitrobenzophenone 227.22 NO 2 O diphenylmethyl ether 350.45 O O O 18-crown-6 264.32 O O O O 1,2-diphenyloxiraine 196.24 O tetraphenyloxiraine 348.44 O O trans-2,2-dimethyl-4,5- 254.32 diphenyl-1,3-dioxolane p-toulenesulfonic acid 172.20 O S O OH xii CH3 O Cl O dihydroquinidine p- 464.98 N chlorobenzoate H3CO N Br N O O N-bromosuccinimide 175.97 H N O O succinimide 97.07 O O O O benzoyl peroxide 242.43 O O O maleic anhydride 98.06 anthracene 178.23 9-methylanthracene 192.26 Br 9-bromoanthracene 257.13 Br 9-bromomethylanthracene 271.15 xiii CN 9-cyanoanthracene 203.24 CN 9,10-dicyanoanthracene 228.26 CN xiv Chapter 1 Introduction and Background Throughout history scientific advances have had an adverse effect on the environment. For example, as a result of the industrial revolution, increased manufacturing led to an increase in air pollution. In order to limit the amount of pollution the Clean Air Act was passed to limit pollution from factories.1 Rachel Carson’s book Silent Spring shed light on the effects of dichlorodiphenyltrichloroethane (DDT) to the environment.2 She observed that DDT, a powerful pesticide was responsible for the thinning of egg shells which had an adverse effect on the population of the American Bald Eagle leading the Bald Eagle to be an endangered species. 2 In part due to the findings in this book the Environmental Protection Agency (EPA) was established by President Richard M. Nixon.3 The EPA banned DDT two years later3 and now the American Bald Eagle is no longer endangered. Although pollution and pesticides were regulated in the 1960’s chemical waste disposal was not regulated. One of the main environmental tragedies that demonstrated poor chemical disposal was the infamous Love Canal incident. The “Love Canal” was originally created by William T. Love who wanted to create an ideal community by a canal that was between the upper and lower Niagara Rivers; however, it was turned into a chemical waste dump site.4 The Love Canal was then used to store chemical waste, and the Hooker Chemical Company buried the waste and sold it back to the city.4 When the chemicals began leeching into the soil and water, the chemicals effected humans by causing birth defects, miscarriages, and other health issues.4 In 1980, The Superfund was created, to clean up the most hazardous waste sites, and it has cleaned up 1,080 sites from its creation to 2009.5 One of the first sites cleaned up was the Valley of Drums, in Bullitt County, Kentucky, 1 where about 4,000 drums were rusting and leaking, causing waste to be dumped, shown in Figure 1.6 Figure 1. Valley of the Drums.6 The pollution from the drums caused health problems for people who lived in the area.6 After sites like the Valley of the Drums and Love Canal were cleaned up, pollution prevention was a way to prevent the sites from existing and becoming a problem. In 1990, the Pollution Prevention Act was passed.3 As a result, Green Chemistry was established. Green Chemistry Green Chemistry was formed to reduce and eliminate the creation of hazardous materials.7 Twelve principles were founded to guide Green Chemistry. They are:8 1. Prevention It is better to prevent waste than to treat or clean up waste after it has been created. 2. Atom Economy Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product. 2 3. Less Hazardous Chemical Syntheses Wherever practical, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment. 4. Designing Safer Chemicals Chemical products should be designed to affect their desired function while minimizing their toxicity.