Investigating Carbocations Using High Speed Ball Milling

Home , Carbocation, Finkelstein reaction, Triphenylmethane, Triphenylmethanol, Triphenylmethyl chloride

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.

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 Br 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

H 4-methoxybenzaldhyde (anisaldhyde) 136.15 O O

benzophenone 182.22

benzopinacolone 348.44

xi O acetone 58.08

acetophenone 120.15

O 4-nitrobenzophenone 227.22

NO2

diphenylmethyl ether 350.45

O O

18-crown-6 264.32 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 H CH3 O

Cl O dihydroquinidine p- 464.98 N chlorobenzoate H CO 3

N Br

N O O N-bromosuccinimide 175.97

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

9-bromoanthracene 257.13

9-bromomethylanthracene 271.15

xiii CN

9-cyanoanthracene 203.24

9,10-dicyanoanthracene 228.26

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.

5. Safer Solvents and Auxiliaries

The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be

made unnecessary wherever possible and innocuous when used.

6. Design for Energy Efficiency

Energy requirements of chemical processes should be recognized for their

environmental and economic impacts and should be minimized. If possible, synthetic

methods should be conducted at ambient temperature and pressure.

7. Use of Renewable Feedstocks

A raw material or feedstock should be renewable rather than depleting whenever

technically and economically practicable.

8. Reduce Derivatives

Unnecessary derivatization (use of blocking groups, protection/ deprotection,

temporary modification of physical/chemical processes) should be minimized or

avoided if possible, because such steps require additional reagents and can generate

waste.

9. Catalysis

Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.

3 10. Design for Degradation

Chemical products should be designed so that at the end of their function they break

down into innocuous degradation products and do not persist in the environment.

11. Real-time analysis for Pollution Prevention

Analytical methodologies need to be further developed to allow for real-time, in-

process monitoring and control prior to the formation of hazardous substances.

12. Inherently Safer Chemistry for Accident Prevention

Substances and the form of a substance used in a chemical process should be chosen

to minimize the potential for chemical accidents, including releases, explosions, and

fires.

These principles were used to create new synthetic techniques and approaches to eliminate waste and keep the environment safe. One form of waste that can be eliminated occurs from using solvents. According to the EPA,9 thirty-five percent of the chemical waste was from organic solvents. Solvents are related to the following principles: prevention, hazardous chemical synthesis, safer solvents, and accident prevention. Prevention of solvent waste occurs through the development of solvent free reactions. Solvents like dichloromethane and chloroform are toxic and carcinogenic while other solvents like diethyl ether, hexane, and acetone are very flammable and volatile.

Solvents were previous thought to be a necessary element of a chemical reaction, however, various methods that do not use traditional solvents have been developed, such as:

solvent-free systems, water as solvent, supercritical fluids, and ionic liquids.7 Water is a

renewable resource and can be used as a solvent at high temperatures around 200-350°C.10 After

reactions are complete, simple extractions can be used to remove the water.10 Supercritical

4 fluids, like supercritical carbon dioxide, are used as a solvents to replace benzene11 and

supercritical carbon dioxide can replace phase transfer catalysts.10-11 Ionic liquids are used as

safer solvents due to their low flammability.12 Since the development of Green Chemistry,

solvent waste has generally decreased.13

High Speed Ball Milling

High Speed Ball Milling (HSBM) is an environmentally friendly technique that addresses some of the twelve principles of Green Chemistry. The major principles addressed are prevention, less hazardous synthesis, energy efficiency, and accident prevention. The major principle that is addressed by HSBM is pollution prevention. Traditional reactions utilize

solvents to enhance reactions by breaking apart intramolecular forces and facilitating

intermolecular interactions of reactants to form products. HSBM is a solvent-free system which is governed by mechanochemistry, where mechanical energy drives reactions forward.14 The

chemistry occurs when reactants are placed in a custom made 0.5 x 2.0 inch stainless steel, screw

cap vial with an eighth of an inch stainless steel ball bearing and milled at 18 Hz in a Spex

Certiprep Mixer/Mill 8000D, shown in Figures 2 and 3. The vial moves in a figure eight fashion

to move the ball and reactants. The ball facilitates the reaction by breaking the reactants down to

particle size and allowing the interaction to occur. The Spex Certiprep Mixer/Mill 8000D has

two sides were reaction vessels can be placed, as shown in Figure 3.

There is another mixer/mill called Spex Certiprep Mixer/Mill 8000M, which differs slightly from the dual mill; the single mill has one side for reactions.

Other aspects of Green Chemistry are addressed through the nature of HSBM. Reactions are carried out in closed vessels, under pressure, while these conditions would normally be very dangerous in traditional methods which use glass vessels; it is not in HSBM since the vessels are made of tougher material that can withstand the pressure. Since reactions are driven by mechanical energy, the processes are more energy efficient than traditional heating. Traditional heating does not always heat evenly and reactions typically take a long time. The vessels used in

HSBM are not easily breakable and reduce the number of accidents caused by traditional glass vessels.

6 Substitution Chemistry

Substitution reactions usually happen when solvents are used. There are two types of

substitution. Unimolecular nucleophilic substitution (SN1) depends on the substrate and typically

occurs in polar protic solvents, which stabilize carbocations that form. In solution, SN1 reactions

depend only on the concentration of substrate, and the energy diagram of an SN1 reaction is shown in Figure 5.15 Since this type of reaction depends only on the substrate, the reaction occurs through the mechanism shown in Figure 4.15

R R Nu: R' Nu -X R"

R' X R' R" R" R Nu:

R' Nu R"

rate = k[substrate]

ure . ec an sm o an e ra e aw. Fig 4 M h i f SN1 d th t l

16 Figure 5. Energy of SN1 reaction.

7 Figure 5 also shows that the rate determining step occurs when the leaving group leaves because it has the higher activation energy than the activation energy to form the products.16

Bimolecular nucleophilic substitution (SN2) depends on the substrate and the nucleophile and typically occurs in polar aprotic solvents. In solution, SN2 reactions depend on the concentration of substrate and the concentration of the nucleophile. The energy diagram of an

16 SN2 reaction is shown in Figure 7.

R R

Nu: X R' R' X Nu R" R"

- rate = k[Nu: ][substrate] ure . ec an sm o reac on an e ra e aw. Fig 6 M h i f SN2 ti d th t l

16 Figure 7. Energy of SN2 reaction.

Since this type of reaction depends on the substrate and the nucleophile, the reaction occurs through the mechanism shown in Figure 6, where the nucleophile attacks from the opposite side of the leaving group. The type of substitution depends on the nucleophiles, strong nucleophiles go through SN2, and weak or neutral nucleophiles go through SN1. The solvent lowers the

8 activation energy needed to form the transition state for SN2 reactions, and it stabilizes the

carbocation intermediate formed in SN1 reactions through hydrogen bonding.

It is not known how nucleophilic substitution reactions take place in the absence of a

solvent. Solvents play a critical role in substitution reactions. For example, the solvent

reactivity of bimolecular substitution (SN2) found that as the polarity of the solvent increases the

reactivity of the nucleophiles increase.

- Br - N3 Br + N3 +

Fi ure 8. Reaction of n-but l bromide with sodium azide.15 g y

For example, the SN2 reaction shown in Figure 8 is 200,000 times more reactive in

hexamethylphosphoramide than methanol, while the reaction in water is seven times, it is1300

times faster in dimethylsulfoxide, the reaction in dimethylformamide is 2800 times faster , and in

acetonitrile it is 5000 times faster.15

Specific nucleophiles like iodide and hydroxide can be examined in classical conditions

and HSBM conditions. Iodide has large electron density making it a good nucleophile, and it has

been used in classical solvent reactions. The Finkelstein reaction occurs when a primary or

secondary alkyl bromide reacts with sodium iodide to form an alkyl iodide and sodium bromide in acetone, as shown in Figures 9 and 10.17

Br NaI I Acetone Reflux, 1 h Figure 9. Primary Finkelstein reaction of n-pentyl bromide to n- en o e.17 p tyl i did

9 Br I NaI Acetone Reflux, 6 hrs.

Figure 10. Secondary Finkelstein reaction of 2-bromo ro ane to 2-iodo ro ane.17 p p p p

This reaction uses Le Chatelier’s Principle by the forming the salt, which is insoluble in

acetone. The reaction can also take place using alkyl chlorides and forming the chloride salt.

Another good nucleophile for substitution chemistry is hydroxide. It can attack the alkyl halide

and form the alcohol by both SN1 and SN2 mechanisms.

Since the system is solvent-free, hard soft acid base theory can work to manipulate the

reactants and form products. Pearson18 designated acids and bases into two groups; which are

soft or polarizable and hard or nonpolarizable. Pearson18 determined that hard acids and bases

are small in size, have a high oxidation state, have low polarizability, and have high

electronegativity; while soft acids and bases are larger, have a lower oxidation state, have high

polarizability, and have low electronegativity. The generalization is “hard acids prefer to

associate with hard bases, and soft acids prefer soft bases.”18 Solvents promote and change

reaction conditions and have relative hard or softness. For example, water and hydrofluoric acid

are hard solvents, which lower the basicity of anions.18 Similar results for alcohols as solvents are expected.18 Other solvents, DMSO, DMF, and acetone act to promote soft interactions.18

Bimolecular substitution has taken place through HSBM for primary alkyl halides.19 The

nucleophiles used were fluoride, chloride, iodide, and thiocyanate, and the counter ions were

sodium, potassium, and cesium.19 Various salts were mixed with 4-bromobenzylbromide, and

19 under high speed ball milling conditions the SN2 product formed, as shown in Figure 11.

10 Br X MX 1/8" ss ball & vial 16.67 hrs Br Br

19 Figure 11. Reaction of 4-bromobenzyl bromide with salts form substituted products.

The secondary alkyl halide has also been examined.20 The amount of substituted product depends on the salt. For example, if potassium iodide was used; the substituted product was formed, but if sodium iodide was used, diphenylmethane and a dimer were the majority of the products, as shown in Figure 12.20

Br KI I + HSBM

38% 37%

Br H NaI + HSBM

38%

ure . econ ar su s u on n con ons.20 50% Fig 12 S d y b tit ti i HSBM diti

Conclusions

After pollution affected people in incidents like the Love Canal and the Valley of the

Drums, the United States government started making laws. As a result, chemists created Green

Chemistry which has been used to research and develop new methods to run reactions that would

replace old methods and prevent waste. One method of focus is HSBM. HSBM has been used

to examine the SN2 reaction for primary and secondary alkyl halides. Now, we can examine SN1

reactions for tertiary alkyl halides and investigate if a carbocation intermediate can form.

11 Chapter 2

Understanding carbocation formation under ball milling conditions

Premise of thesis research

A carbocation is defined as a cation containing an even number of electrons with a

significant portion of the excess positive charge located on one or more carbon atoms.21 Due to

the fact that carbocations are electron deficient species, its stability increases when it is

surrounded by electron donating groups. As shown in Chapter 1 the ability for the formation of a

carbocation intermediate is highly dependent upon the solvent choice that is used in the reaction.

Because ball milling conditions avoid the use of a solvent we wanted to investigate whether

carbocation formation is possible under our unique conditions. Because the triphenyl methyl or

trityl carbocation is one of the most stable carbocation reported we wanted to determine if we

could detect the formation of this carbocation under ball milling conditions.22 There are two major ways to make the trityl carbocation in solution. These methods are shown in Figures 13 and 14.

H2SO4 OH

22 Figure 13. Triphenylmethanol reacts with sulfuric acid to form trityl carbocation.

AlCl3 or SnCl2 Cl

Figure 14. Triphenylmethyl chloride reacts with Lewis acids to form trityl carbocation.22

12 One method for forming the trityl ion occurs by using sulfuric acid on triphenylmethanol,

shown in Figure 13. In another method, the trityl ion is formed by reacting triphenylmethyl

chloride with a Lewis acid like aluminum chloride or tin (II) chloride, shown in Figure 14.22 Our

goal was to conduct these experiments in a solvent-free environment under ball milling conditions and compare our results to literature precedence.

Carbocation formation under Ball Milling conditions

Triphenylmethyl bromide substrate

Since the triphenylmethyl carbocation, or the trityl carbocation is very stable,

triphenylmethyl halides could be viable substrates to run substitution reactions, therefore we

used triphenylmethyl bromide as the starting material in all reactions. Triphenylmethyl bromide

was analyzed by gas chromatography coupled with mass spectrometry (GC-MS) to determine the

purity and observe what impurities are in it, as shown in Figure 15. All retention times are listed

in minutes.

13 Br

OH O

impurity

Figure 15. GC-MS of triphenylmethyl bromide to determine its purity.

Data from the chromatogram of triphenylmethyl bromide showed peaks at 7.79, 9.40,

9.96, and 11.20; these peaks were identified by mass spectrometry and were found to be

benzophenone, triphenylmethyl bromide, triphenylmethanol, and an unknown impurity,

respectively. We first wanted to know if trityl bromide was reactive at all under ball milling conditions therefore we started conducting nucleophilic reactions with varies nucleophiles. The first nucleophile examined was iodide. Iodide salts reacted with primary and secondary alkyl

halides and formed alkyl iodides. 20, 21 Iodide is a soft base, which is very polarizable.

Triphenylmethyl bromide, potassium iodide and dodecane were in 1:1:1 ratio, as shown in

Figure 16. Dodecane was added as a non-reacting standard to analyze amounts of product formed in GC-MS, which has a retention time of 5.36-5.4 minutes. Reactions occurred in a stainless steel vial with a one eighth inch stainless steel ball, and the vial was milled for 16.67 hours.

14 O

KI dodecane Br + 1/8" ss ball & vial OH 16.67 hrs

Figure 16. Triphenylmethyl bromide reacts with potassium iodide.

At the conclusion of the milling experiments the crude product was black. Analysis of 1H NMR indicated the peaks for the crude product were very small, and were in the same region as the 1H

NMR of the triphenylmethyl bromide. Analysis by GC-MS showed mostly triphenylmethanol as the product, the formation of an unknown compound at a retention time of 9.91 minutes, benzophenone, and starting material, as well as impurities from the starting materials at a retention time of 11.20 minutes. The reaction shown in Figure 16 was run again under the same system as previously mentioned with one equivalent of 18-crown-6. The purpose of the crown ether was to trap the potassium and promote the nucleophilicity of the iodide. The crude product was an orange-brown color. However, the results from 1H NMR were similar to the results of the reaction without the crown ether. The GC-MS showed mostly triphenylmethanol, starting material, benzophenone, and impurities from starting materials at a retention time of 11.20 minutes. Because we obtained the trityl alcohol as the dominant product after the reaction we wanted to investigate where the oxygen originated from. Our first thought was that the oxygen originated from water in the salt reagents however drying the potassium iodide and the vial prior to the milling experiments still did not prevent alcohol formation. Another possibility is the alcohol is generated due to air in the vial in order to investigate this the reaction was run under argon without dodecane and 18-crown-6. The 1H NMR results showed the formation of triphenylmethanol at 2.83.

15 OH O Dodecane

r Br unknown

impurity

Figure 17. GC-MS results from triphenylmethyl bromide and KI under argon.

The GC-MS showed triphenylmethanol, starting material, benzophenone, the formation of an unknown compound at 9.88, and impurities from starting material at 11.20, as shown in Figure

17.

Since sodium is a harder acid than potassium, sodium iodide is more reactive than potassium iodide because iodide is a soft base, and hard acids prefer hard bases while soft acids prefer soft bases. Therefore, the sodium cation increases the nucleophilicity of iodide and theoretically promotes the substitution reaction. Under argon, sodium iodide was reacted with triphenylmethyl bromide by HSBM to compare to the reaction with potassium iodide. The 1H

NMR of the crude product showed the formation of triphenylmethanol at 2.81. The GC-MS revealed the presence of triphenylmethanol, starting material, benzophenone, and the formation of an unknown compound at 9.89. The results from the reaction of sodium iodide were similar to the experiment with potassium iodide.

Because of our limited success with the iodide nucleophile we turned our attention to using hydroxide as the nucleophile. Hydroxide is a harder base than iodide, and maybe a better match in hardness with a carbocation. Triphenylmethyl bromide, potassium hydroxide, and dodecane were in a 1:1:1 ratio as shown in Figure 18.

16 KOH 1/8" ss ball & vial Br 16.67 hrs OH

Figure 18. Triphenylmethyl bromide reacts with potassium hydroxide.

The ball and vial were also dried in the oven for one hour prior to reaction. The 1H NMR of the

reaction in Figure 18 showed a small peak in the aromatic region of 7.28 to 7.31, same region as

the starting material. Characterization of the crude product was also done by GC-MS.

Dodecane

Figure 19. GC-MS results from triphenylmethyl bromide and potassium hydroxide.

The GC-MS revealed triphenylmethyl bromide at 9.38 minutes and triphenylmethanol at

9.99 minutes, as shown in the Figure 19. The majority of the starting material reacted to form

triphenylmethanol. Although triphenylmethanol formed, hydroxide may not have substituted

bromine. The oxygen from the alcohol could have come from oxygen in the air or water vapor

from air.

The reaction from Figure 18 was carried out again with one equivalent of 18-crown-6.

The crown ether was utilized to trap the potassium ion and promote nucleophilic interactions.

The 1H NMR illustrated a peak at 7.28, which could be one of many aromatic compounds.

Figure 20 show the GC-MS of the completed reaction.

17 Dodecane

18-crown-6

Figure 20. GC-MS of triphenylmethyl bromide with KOH and 18-crown-6 after HSBM.

The GC-MS depicts only triphenylmethanol and triphenylmethyl bromide or side products.

From the GC-MS results, 18-crown-6 effectively traps the potassium ion and promotes nucleophilic interactions with triphenylmethyl bromide. However, the oxygen from the alcohol could have come from oxygen in the air or water vapor from air.

Standards were done to see if triphenylmethyl bromide reacts by itself or if metal oxides from the vial reacted to form triphenylmethanol. In a stainless steel vial with a one eighth inch stainless steel ball, triphenylmethyl bromide and dodecane were milled together in a 1:1 molar ratio. The major peak from 1H NMR appeared around 7.3, which overlaps with starting material peaks. Peaks from the GC-MS showed the formation of triphenylmethanol, the formation of an unknown compound at 9.88 minutes, and triphenylmethyl bromide. Although triphenylmethanol was a peak in the triphenylmethyl bromide, the peak from triphenylmethanol after triphenylmethyl bromide was milled was larger than the peak of the triphenylmethyl bromide before it was milled. Therefore, the starting material may react with the metal oxides from the vial and Teflon® is an inert material which was used to examine triphenylmethyl bromide. To further investigate this we used a Teflon® vial instead of the stainless steel vial because Teflon® is an inert material we if the alcohol was formed it would not be from the vial surface.

Triphenylmethyl bromide and dodecane, in a 1:1 ratio, were milled in a Teflon® vial and with a

18 Teflon® ball. The 1H NMR peak from the product occurred at 7.32, close to triphenylmethyl

bromide. Data from GC-MS showed triphenylmethyl bromide, triphenylmethanol, formation of

an unknown compound at 9.87 minutes, and benzophenone. The peaks of triphenylmethanol and

benzophenone were larger with Teflon® than before triphenylmethyl bromide was milled. The

data indicates the starting material may react with air under HSBM conditions, and the role of

the vial as a metal is not significant. Triphenylmethyl bromide was run in the different vials

under argon to remove oxygen in the air as a possible reactant. A peak at around 7 and a peak at

2.82 appeared in the 1H NMR in both cases under argon. The GC-MS of the starting material under argon showed many peaks coming out after the triphenylmethyl bromide peak, which indicated the triphenylmethyl bromide degraded over 16.67 hours under HSBM conditions.

Since triphenylmethyl bromide degrades, it may not be a suitable substrate for examining the triphenylmethyl carbocation.

Triphenylmethanol substrate

Triphenylmethanol is another substrate that has been used to form the triphenylmethyl carbocation, which forms when triphenylmethanol is protonated and water is a leaving group.

Microwave irradiation has been used as a method to do substitution, as shown in Figure 21.23

I OH PTSA, KI Microwave 80 sec.

Figure 21. Triphenylmethanol, p-toluenesulfonic acid, and potassium iodide reacted in alumina bath under microwave irradiation.23

The conditions for the reaction were modified by using HSBM; however, no product was

formed.

19 Lewis acids have been used to form the carbocation from triphenylmethyl chloride.22

They can also be used to do substitution on alcohols. Triphenylmethanol was reacted with aluminum bromide in a 1:1 molar ratio. The products formed are shown in Figure 22.

AlBr3 OH 1/8" ss ball & vial Br 16.67 hrs

Figure 22. Triphenylmethanol reacts with aluminum bromide.

The GC-MS showed 19% conversion to triphenylmethyl bromide and 22% conversion to benzophenone. Triphenylmethanol was substituted. However, benzophenone was the major product which indicated that something else occurred during the reaction to form benzophenone.

20 Pinacol Rearrangement

The Pinacol rearrangement occurs through a carbocation intermediate, in solution.

However, it has not been investigated under solvent-free conditions. The Pinacol rearrangement first occurred when Fittig added pinacol and sulfuric acid together and formed pinacolane, shown in Figure 23.24

OH OH O

H2SO4

r . naco reac e w su ur c ac o rom naco ane. Figu e 23 Pi l t d ith lf i id t f pi l

The driving force of the reaction is the formation of carbon-oxygen double bond, or carbonyl.

The Pinacol Rearrangement is a classic rearrangement, where a 1, 2-diol reacts with acid and

rearranges to form a carbocation intermediate and produces ketones.25 The classical mechanism

shown in Figure 24, occurs through a carbocation intermediate.26

H OH OH OH OH2 OH -H2O

O OH O H -H

Figure 24. Classical, or carbocation, mechanism of the Pinacol Rearrangement.

Experiments can be done to disprove mechanisms. One example is by examining the kinetic

isotope effect. The kinetic isotope effect is examined by isotopic labeling of a bond formed in the

rate determining step.27 Usually hydrogen is replaced with deuterium, and the effects are found

21 by determining the rate constant (k) of both the normal isotope and the labeled isotope; once the

27 values are determined, kH/kD is the kinetic isotope effect. There are two types of kinetic

isotope effects, the primary isotope effect; which occurs at the atom labeled is directly involved

in the rate-determining step and the secondary isotope effect; which occurs on an atom next to

the atom that is involved in the rate determining step.27 Since the Pinacol Rearrangement is

thought to go through a carbocation mechanism it has been examined under the secondary

kinetic isotope effect.28 The typical secondary kinetic isotope effects are found from 1.1 to 1.2, these changes are due to the rehybridization of sp3 and sp2 hybridized carbons.27

OH OH

H2SO4

Figure 25. 1,1-diphenyl-2-methyl-1,2-propanediol reacted with sulfuric acid to from 3,3-diphenylbutanone.

Shown in Figure 25 is the rearrangement of 1,1-diphenyl-2-methyl-1,2-propanediol. Schubert and LeFevre deuderated the hydrogens on the methyl group and found the rate constants.28 They

determined the kinetic isotope effect was 1.18 when both methyls were deuterated, and the

kinetic isotope effect when one methyl was labeled was 1.07.28 They concluded that the

migration of the methyl group was not the rate determining step, which is consistent with

reported values being between 1.1 and 1.2.27-28

The concerted mechanism shown in Figure 26, does not occur through the formation of a carbocation; instead, water leaves as the methyl group migrates and the oxygen of the hydroxyl group forms the double bond.29

22 H O OH OH O H OH2 OH -H O 2 -H

e concer e mec an sm o e naco earran emen . Figure 26. Th t d h i f th Pi l R g t

The rate determining step is the migration of the group. Nakamura and Osamura29 calculated the

energies for the carbocation and the energies for the transition states for primary, secondary, and

tertiary 1,2-diols; they found the transition state was lower in energy than the carbocation.

Reactions similar to the pinacol Rearrangement are called pinacol-type rearrangements.

They occur when the leaving group is not water. They can occur and form stereo specific ketones.30 An example is shown in Figure 34, where the leaving group is methanesulfonate.30

Et3Al H

CH2Cl2 MsO H -78oC

ure . naco e rearran emen .30 Fig 27 Pi l typ g t

The inversion of the chiral center indicates that the reaction goes through the concerted

mechanism. It is also important to know which group will migrate. Different migrating groups

migrate at different rates.31 The order from fastest to slowest migrating group for the Pinacol

Rearrangement is phenyl > tertiary > primary > hydride; however, steric hindrance also plays a

role in which group would migrate, if there are larger groups like tert-butyl and a small group like hydride, the hydride would migrate because the tert-butyl would be sterically hindered by other tert-butyl groups.31

23 The Pinacol Rearrangement has occurred using other non-classical methods.32-35 The rearrangement can occur when using supercritical water, and the water acts as an acid.32 Water

also acts as an acid when microwave irradiation is used.33 Ionic liquids have been made and

used as alternatives to strong acids.34 The Pinacol Rearrangement happens when ionic liquids

are used as acid sources for pinacol and benzopinacol.34 The rearrangement has also been

examined in the solid state using benzopinacol and PTSA.35

This rearrangement can happen under HSBM conditions. Benzopinacol and p-

toulenesulfonic acid were chosen as substrates for the Pinacol Rearrangement for two major

reasons. First, both are solids, which is important in understanding how reactions occur in the

solid state. Most strong acids are aqueous, which means they are in a water solution, and the

solution can act as a solvent; however, p-toulenesulfonic acid is one of the strongest acids that is

a solid at room temperature. It has a pKa of -2.8 in water.36 Second, the benzopinacol would

form a very stable carbocation. Benzopinacol and p-toulenesulfonic acid were placed under

HSBM conditions and yielded two products, which were the tetraphenyloxirane (a) and 2,2,2-

triphenylacetophenone (b), as shown in Figure 28.

OH OH

O O H+

HSBM

a b Figure 28. Pinacol Rearrangement using benzopinacol and p-toluenesulfonic acid.

There are two mechanisms for this; one shows a carbocation intermediate, and the other is a

concerted mechanism which depends on the migratory group. It is not clear if the carbocation is

formed or the diol reacts in a concerted manner, where the rearrangement would depend on the

migration of the group. Pocker and Ronald37 monitored the reaction by thin layer

24 chromatography and concluded that epoxide formation was an intermediate to the ketone. The

reaction was done in different solvents so the results can be compared to what happens under

HSBM conditions. The solvents were toluene, ethanol, and 2,2,2-trichloroethanol. They were

picked because of their properties. Toluene is a non-polar solvent, and the rearrangement is

believed to occur under the concerted mechanism in a non-polar solution.29 Ethanol is a polar solvent, and can stabilize the carbocation. The 2,2,2-trichloroethanol is known to stabilize the carbocation.29 Results are shown in the table below, with percent conversions to each product.

O O Ph Ph Ph Ph Ph Ph Ph Ph

HSBM 4% 91% 8000M

HSBM 10% 3% 8000D

0% 100%

10% OH 0%

Cl Cl 0% 100% OH Cl

The Pinacol rearrangement was attempted with pinacol and PTSA to determine if

rearrangement occurs with alkyl groups. No product formed.

The only tertiary diols that are commercially available have symmetrical groups, and they

cannot be used to create a chiral center. There are different ways to make 1,2-diols. The first

25 way some diols were made was by modifying a known synthesis.38 Tanaka’s38 synthesis was

modified by using the ball mill instead of stirring or using a mortar and pestle. Benzopinacol

was synthesized as shown in Figure 29; however, the rearrangement occurred during the work up step.

O 1. Zn, ZnCl2 1/8" ss ball & vial 16.67 hrs OH 2. H+ work up

ure . ou n enzo enone us n n n . Fig 29 C pli g b ph i g Z /Z Cl2

Saturated ammonium chloride was used instead of 3 M HCl. The pKa of ammonium chloride is

17 39 9.24. The pKa of unprotonated diol is 12.6. However, no product was obtained. The

benzopinacol that was used in the rearrangements was also reacted with sodium hydride under

HSBM conditions to see if it could be protonated with saturated ammonium chloride; the

products are shown in Figure 30.

H O O

OH 3 NaH 1/8" ss ball & vial HO 16.67 hrs

Figure 30. Deprotonation and reprotonation of benzopinacol.

Acetophenone was used to make 2,3-diphenyl-2,3-butanediol.38 The reaction conditions

were changed by using HSBM conditions. The reaction formed multiple products, which are

shown in Figure 31.

O HO 1. Zn, ZnCl2 1/4" ss balll & viall 16.67 hrs . OH 2. NH4Cl

Figure 31.. Acetophenone coupling under HSBM condittions.

Another method attempted was shown in Figure 32, where magnesium reacts like zinc.40

Mg I2 OH Ultrasound 30 min OH

Figure 32. Benzophenone coupling with magnesium.40

Reaction conditions were modified by using HSBM conditions. A magnesium vial was used; however, no product was obtained. When a stainless steel vial and magnesium turnings were used, no product was obtained.

Since the yields were low using Tanaka’s38 method, a new method for making chiral diols was found. The new method, shown in Figure 33, used a catalytic amount of osmium tetroxide, and potassium ferricyanide and potassium carbonate were used to reoxidize the catalyst.41

dihydroquinidine p-chlorobenzoate HO OH K3[Fe(CN)6] K2CO3 OsO4

tBuOH:H2O 1:1 24 hrs RT

41 Figure 33. Oxidation of E-stilbene.

27 A chiral additive, dihydroquinidinepara-chlorobenzoate, was used to induce chirality.41 E-

stilbene was used to synthesize 1,2-diphenyl-1,2-ethanediol.

The Pinacol rearrangement of 1,2-diphenyl-1,2-ethanediol under HSBM conditions show only epoxide formation, as shown in Figure 41. However, the vial was not completely dry and some acetone also reacted with the diol in Figure 34.

O OH p-TsOH 1/8" ss ball & vial 16.67 hrs

Figure 34. 1,2-diphenyl-1,2-ethanediol and p-toluenesulfonic acid under HSBM conditions.

A stainless steel vial and 1/8” stainless steel ball was placed in the oven before use. The

reaction proceeded under the same conditions; however no product formed. The Pinacol

rearrangement of 1,2-diphenyl-1,2-ethanediol was also done in solution. It was done in toluene

under reflux conditions. According to the 1H NMR, multiple products were formed. The

reaction was also done by refluxing in ethanol. In ethanol, the GC-MS showed the only product

formed was the epoxide.

The Pinacol rearrangement has been done using triaryl substituted diols.42 Toda42

reported that the product formed when 1,1,2-triphenyl-1,2-ethanediol was reacted with three

equivalents of PTSA was 89% 2,2-diphenylacetophenone, which is shown in Figure 35.

OH O

OH 3 PTSA 60oC 2.5 hrs

Figure 35. 1,1,2-triphenyl-1,2-ethanediol reacts with p-toluenesulfonic acid to form 42 1,1-diphenylacetophenone.

28 The diol, 1,1,2-triphenyl-1,2-ethanediol, was synthesized in a three step process. The first two steps were to do a Wittig reaction, shown in Figure 36.43

PPh3 Br 1. nBuLi PPh3Br 2. Benzophenone

Figure 36. Wittig reaction using benzyl bromide, triphenyl phosphine, n-butyl lithium, and benzophenone.

The reaction to synthesize triphenylethylene was modified from one of Wittig’s papers.43 The

reaction conditions for making triphenylethylene were THF as the solvent, the reaction refluxed,

and the time was 3 days 23 hours; however Wittig used diethyl ether, the temperature of 78°C,

and the time was two days.43 Triphenylethylene was a substrate for making 1,1,2-triphenyl-1,2-

ethanediol by using the method Kwong41 used and letting it react for an hour longer.

A diol with two chiral centers can be made by changing the olefin, or alkene being made.

The olefin was made by a Wittig reaction.43 The Wittig reaction is shown in Figure 37.

PPh3 1. nBuLi Br Br PPh3Brr

2. O

NO2 Figure 37.. Wiittig reaction using benzyl bromiide, triphenyl phosphine, n-butyll lithiium, and 4-nitobenzophenone. O2N The percent conversion was 43.9% 1-(4-nitro-phenyl)-1,2-diphenylethene according to the GC-

MS.

Conclusions and Future Work

It is unclear if tertiary alkyl halides can be used in substitution reactions. However,

further investigation can be done by examining the reaction time, as well as the reaction in

Teflon. Triphenylmethyl bromide and sodium or potassium iodide should also be explored in

29 solution to compare it to HSBM conditions. Triphenylmethanol can undergo substitution with

Lewis acids; however, most of it is left unreacted. The Pinacol Rearrangement occurs under

HSBM conditions. However, the mechanism needs to be investigated further. The only tertiary

diols that are commercially available have symmetrical groups, and they cannot be used to create

a chiral center. Therefore, diols with two different chiral centers should be synthesized, and run the diols with p-toluenesulfonic acid under HSBM conditions. If the rearrangement occurs under a concerted mechanism, one of the chiral centers will be inverted. However, if a carbocation is formed, the product will be a racemic mixture. The products will be analyzed by 1H and 13C

NMR and GC-MS, and chiral induction will be analyzed by chiral HPLC.

30 Experimental Methods

Instrumentation and Materials

Ball milling reactions were done in an 8000D Spex Certiprep Mixer/Mill. Ball bearings

were purchased from Small Parts incorporated. Custom made ½” x 2” screw-capped stainless steel vials were made by the machine shop at the University of Cincinnati with metal rods purchased from ESPICorp Inc. All column separations were done on a Combiflash Companion

Instrument by Teledyne using 4, 12, and 25 g silica columns. All GC-MS were recorded on a

Hewlett Packard (Agilent) 6890 Series GC coupled with 5972A MS Detector. All NMR spectra were recorded on a Bruker Advance 400 spectrometer. Deuterated NMR solvents were obtained from Cambridge Isotope Laboratories, Inc., Andover MA, and used without further purification.

All products were confirmed by comparison to literature.20, 44-76

Triphenylmethyl chloride, triphenylmethyl bromide, 2-methyl-2-bromopropane, 4-

bromo-benzylbromide, benzyl bromide, 9-bromoanthracene, 9-methylanthracene, N-

bromosuccinimide, dodecane, triphenylmethanol, benzopinacol, pinacol, acetophenone, 4-

chloroacetophenone, 1,4-cyclohexadiene, 1-hexene, E-stilbene, zinc dust, lithium iodide, sodium

hydride, 1.6 M n-butyl lithium (nBuLi) in hexanes, 2.8 M phenyl magnesium bromide in ether,

aluminum chloride and aluminum bromide were purchased from Acros Organics and used

without further purification, unless otherwise mentioned. Benzophenone, 2-methyl-2-propanol

(tBuOH), potassium iodide, potassium carbonate, potassium hydroxide, sodium iodide, sodium

borohydride, sodium sulfite, magnesium turnings, anhydrous magnesium sulfate, zinc (II)

chloride, and iodine were purchased from Fisher and used without further purification.

Potassium ferricyanide was purchased from Baker and used without further purification.

Anthracene was purchased from Eastman and used without further purification. Maleic

31 anhydride, 4-methoxybenzaldehyde, benzoin, p-toulenesulfonic acid, and carbon tetrachloride

were purchased from Matheson, Coleman and Bell and were used without further purification.

Diphenylmethyl bromide was purchased from MP Biomedical and used it without further

purification. Ethylene glycol was purchased from Pharmaco and was used without purification.

Copper powder, 18-crown-6, osmium tetroxide, 2.5 wt.% osmium tetroxide in tBuOH,

dihydroquinidine 4-chlorobenzoate, triphenylphosphine, 4-nitrobenzophenone, 9-

cyanoanthracene, 9,10-dicyanoanthracene, benzoyl peroxide and 2,2,2-trichloroethanol were

purchased from Sigma Aldrich and used without further purification. Diethyl ether,

tetrahydrafuran (THF), ethyl acetate, toluene, and dichloromethane were purchased from Tedia

Company and used without further purification.

Reactions with primary alkyl halides

Reaction of benzyl bromide with sodium iodide

In a clean dry stainless steel vial, benzyl bromide (208.0 mg, 1.2 mmol) and sodium iodide (87.2 mg, 0.6 mmol) was added with a ⅛” stainless steel ball. The sodium iodide was in the oven prior to use. The reaction ran for 16.67 hours. The crude product was black slurry.

1HNMR and GC-MS confirmed that benzyl bromide and benzyl iodide20 were the only products.

The peaks in the 1H NMR occurred at 4.5 and 7-8. The GC-MS showed 50.9% conversion, which had benzyl bromide44 at 4.47 minutes that had m/z peaks at 170, 91, and 65.The product, benzyl iodide,20 came out at 5.38 minutes and had m/z peaks at 254, 91, and 65. After

characterization, the slurry was extracted with ethyl acetate and distilled water. The ethyl acetate

layer was poured through anhydrous magnesium sulfate and rotavaped. The mass of the mixture

of benzyl bromide and benzyl iodide was 128.5 mg.

Reaction of benzyl bromide with lithium iodide

32 In a clean dry stainless steel vial, benzyl bromide (279.1 mg, 1.6 mmol) and lithium

iodide (96.7 mg, 0.7 mmol) was added with a ⅛” stainless steel ball. The reaction ran for 16.67

hours. The reaction smoked when opened. The crude product was black slurry. 1H NMR and

GC-MS confirmed that benzyl bromide and benzyl iodide20 were the only products. The peaks

in the 1H NMR occurred at 1.5, 3.5, 4.5, and 6.5-8. Water45 occurred at 1.5. The GC-MS

showed 81.3% conversion to benzyl iodide.20 The starting material, benzyl bromide44, came out

at 4.38 minutes and had m/z peaks at 170, 91, and 66. The benzyl iodide20 had a retention time

of 5.29 minutes and had m/z peaks at 218, 91, and 66. There was also a small peak in the GC-

MS that had a retention time of 9.16 minutes with m/z peaks at 181, 165, and 77. After

characterization, the slurry was extracted with ethyl acetate and distilled water. The ethyl acetate

layer was poured through anhydrous magnesium sulfate and rotavaped. The mass of the mixture

of benzyl bromide and benzyl iodide was 297.5 mg.

Reactions with secondary alkyl halides

Diphenylmethyl Bromide

Cold Experiment in 8000M Mixer/Mill

For doing a cold experiment under HSBM conditions, a ⅛” stainless steel ball and a

stainless steel vial were placed in liquid nitrogen for five minutes. Then diphenylmethyl

bromide (207.7 mg, 0.9 mmol) and sodium iodide (126.3 mg, 0.8 mmol) were added to the vial

and it was left under liquid nitrogen for five minutes. The reaction was closed up and milled in

the 8000M Mixer/Mill by itself for ten minutes. Then it was cooled in liquid nitrogen for five

minutes. The previous two steps were repeated until the reaction was milled for total of one

hour. A light green solid was obtained. The peaks in the 1H NMR occurred at 1.54, 6.28, 6.57, and 7-8. The peaks are consistent with starting material.20

33 Reaction of diphenylmethyl bromide with sodium borohydride (NaBH4)

In a stainless steel vial a⅛” stainless steel ball, diphenylmethyl bromide (207.0 mg, 0.9

mmol) and sodium borohydride (70.0 mg, 2.2 mmol) were combined. The reaction was milled

for 16.67 hours. Clear liquid and white solid were left in the vial. The major product formed was

diphenylmethane20, which according to the GC-MS showed 50.1% conversion,

bis(dipenylmethyl)ether20 showed 15.5% conversion, tetraphenylethane20 showed 2.3%

conversion, and p-benzyltriphenylmethane20 showed 13.6% conversion. The retention times, in

minutes, were 6.84, 7.78, 8.21, 11.30, 11.60, 11.75, and 12.10. Diphenylmethane20 had a retention time of 6.84 minutes and m/z peaks at 167, 152, 91, and 77. Diphenylmethanol45l had a

retention time of7.78 minutes and m/z peaks at 184, 105, and 77. The peak at 8.21 minutes had

m/z peaks at 167, 152, 91, and 77. Tetraphenylethane20 had a retention time of 11.30 minutes

and m/z peaks at 334, 167, and 152. The peak at 11.60 minutes had m/z peaks at 272, 183, and

167; which was consistent with bis(dipenylmethyl)ether20. The peak at 11.75 minutes was p- benzyltriphenylmethane20 and had m/z peaks at334, 243, 165, and 91. The peak at 12.10 minutes

was p-benzyltriphenylmethane20 and had m/z peaks at 334, 243, 165, and 91.In the 1H NMR,

peaks occurred at 1.54, 3.98, 5.5, and 6.75-7.75.

Reaction of diphenylmethyl bromide with sodium iodide and 1-hexene

In a stainless steel vial a⅛” stainless steel ball, diphenylmethyl bromide (207.3 mg, 0.9

mmol), sodium iodide (133.4 mg, 0.9 mmol), and 1-hexene (84.1 mg, 1.0 mmol) were combined.

The vial was closed and milled for 16.67 hours. A gooey white substance remained in the vial.

The peaks in the 1H NMR occurred at 1.25, 2.03, 3.97, 4.10, 4.77, 5.39, and 7-7.5. The peaks at

1.25, 2.03, 3.97, 4.10, 4.77, and 5.39 were from 1-hexene47. The peaks at 7-7.5 were from

diphenylmethane.20 The GC-MS indicated there were five peaks at different retention times (in

34 minutes), which were: 6.81, 7.80, 7.83, 11.31, and 11.58. At 6.81 minutes, the m/z peaks were

at 168, 152, 91, and 77; they were from diphenylmethane.20 At 7.80 minutes, the m/z peaks were

at 182, 105, and 77; which was benzophenone48. At 7.83 minutes, the m/z peaks were at 184,

105, and 77; which was diphenylmethanol46a. At 11.31 minutes, the m/z peaks were at 334, 167,

and 152. At 11.58 minutes, bis(dipenylmethyl)ether21 had m/z peaks were at 272, 183, 167, 105,

and 77. The GC-MS showed 53% conversion of diphenylmethyl bromide to diphenylmethane20,

6% was benzophenone48, and 8% was diphenylmethanol46a, 27% was tetraphenylethane20, and

6% was bis(dipenylmethyl)ether20.

Reaction of diphenylmethyl bromide with sodium iodide and 1,4-cyclohexadiene

In a stainless steel vial a⅛” stainless steel ball, diphenylmethyl bromide (208.2 mg, 0.9

mmol), sodium iodide, (126.3 mg, 0.8 mmol) and 1,4-cyclohexadiene (64.8 mg, 0.9 mmol) were

combined. The vial was closed and milled for 16.67 hours. The retention times from the GC-MS

were in minutes and at 6.83, 7.80, 11.31, and 11.59.At 6.83 minutes, diphenylmethane20 had m/z

peaks were at 167, 152, 91, and 77. At 7.80 minutes, the m/z peaks were at182, 105, and 77;

which was benzophenone48. At 11.31 minutes, the m/z peaks were at 334, 167, and 152, which

was tetraphenylethane20. At 11.59 minutes, the m/z peaks were at 272, 183, 167, 105, and 77,

which was bis(dipenylmethyl)ether20. The GC-MS showed 63% conversion to

diphenylmethane20, 21% conversion to tetraphenylethane20, 12% conversion to

bis(dipenylmethyl)ether20, and 3% conversion to benzophenone48. The peaks in the 1H NMR occurred at 1.47, 2.65, 3.98, 4.76, 5.39, 5.68, and 7-7.5. The 1,4-cyclohexadiene49 peaks are

2.65 and 5.68.

Reactions with tertiary alkyl halides

Triphenylmethyl chloride

35 Initial experiments were done using an old bottle of triphenylmethyl chloride, which had

impurities. It was recrystallized by adding boiling toluene and once the crystals dissolved, after

it cooled, a few drops of cyclohexane was added.

Reaction of triphenylmethyl chloride with sodium iodide

In a stainless steel vial a ⅛” stainless steel ball, triphenylmethyl chloride (215.3 mg, 0.8 mmol) and sodium iodide (185.9 mg,1.2 mmol)were combined. The vial was closed and milled for 16.67 hours. Orange solid remained after the reaction. The 1H NMR showed peaks at 1.54

and 7.30.

Reaction of triphenylmethyl chloride with potassium hydroxide

In a stainless steel vial a ⅛” stainless steel ball, triphenylmethyl chloride (206.1 mg, 0.7

mmol), of potassium hydroxide (95.3 mg, 1.7 mmol), and dodecane(129.4 mg, 0.8 mmol) were

combined. The vial was closed and was milled for 16.67 hours. Orange and white solid

remained after the reaction. The 1H NMR showed peaks at 0.88, 1.30, and 7.29. The peaks at

0.88 and 1.30 were from dodecane50.

18-crown-6

In a stainless steel vial a ⅛” stainless steel ball, triphenylmethyl chloride (204.5 mg, 0.7 mmol), potassium hydroxide (102.9 mg, 1.8 mmol), dodecane (124.3 mg, 0.7 mmol), and 18- crown-6 (189.6 mg, 0.7 mmol) were combined. The vial was closed and milled for 16.67 hours.

Pale yellow solid remained after the reaction. The 1H NMR showed peaks at 0.88, 1.28, 3.67,

and 7.30. The peaks at 0.88 and 1.28 were from dodecane50.

36 Reaction of triphenylmethyl chloride with potassium iodide

In a stainless steel vial a ⅛” stainless steel ball, triphenylmethyl chloride (154 mg, 0.6

mmol), dodecane (91.3 mg, 0.5 mmol), and potassium iodide (94.1 mg, 0.6 mmol) were

combined. The vial was closed and milled for 16.67 hours. Black solid with nasty odor

remained. The 1H NMR showed peaks at 0.88, 1.29, 1.54, 2.79, and 7.31. The peaks at 0.88 and

1.29 were from dodecane50. The peak at 1.54 was from water45.

Reaction of triphenylmethyl bromide with potassium iodide

In a stainless steel vial a ⅛” stainless steel ball, triphenylmethyl bromide (211.6 mg, 0.7

mmol), potassium iodide (102.2 mg, 0.6 mmol), and dodecane (106.7 mg, 0.6 mmol) were

combined. The vial was closed and milled for 16.67 hours. Black solid remained after the

reaction. The 1H NMR and GC-MS showed the major product was triphenylmethanol51. The

peaks in the 1H NMR occurred at 0.86, 1.28, and 7.30. The peaks at 0.86 and 1.28 were from dodecane50. The GC-MS showed peaks at 5.34 minutes, 7.80 minutes, 9.39 minutes, 9.90

minutes, and 10.03 minutes. Dodecane had a retention time of 5.34 minutes. At 7.80 minutes,

the m/z peaks were 182, 105, and 77; which was benzophenone48. At 9.39 minutes, the m/z

peaks were 244, 165, 152, and 77; which was triphenylmethyl bromide52. At 9.90 minutes, m/z

peaks were at 288, 243, 211, 183, 165, 105, and 77. At 10.03 minutes, m/z peaks were at 260,

183, 154, 105, and 77; which indicated triphenylmethanol51 was present.

Argon

In a stainless steel vial a ⅛” stainless steel ball, triphenylmethyl bromide (205 mg, 0.6

mmol) and potassium iodide (166 mg, 1.0 mmol) were combined in the dry box. The vial was

closed and milled for 16.67 hours. Black solid remained after the reaction. The 1H NMR and

GC-MS showed the major product was triphenylmethanol51. The peaks in the 1H NMR occurred

37 at 2.77 and 7-7.75, which indicated triphenylmethanol51 was present. The GC-MS showed peaks

at (in minutes) 5.42, 7.82, 9.43, 9.88, and 10.05. Dodecane had a retention time of 5.42 minutes.

At 7.82 minutes, the m/z peaks were 182, 105, and 77; benzophenone48 was present. At 9.43

minutes, the m/z peaks were 244, 165, 152, and 77; which was triphenylmethyl bromide52. At

9.88 minutes, m/z peaks were at 289, 243, 211, 183, 165, 105, and 77. At 10.05 minutes, m/z

peaks were at 260, 183, 154, 105, and 77; triphenylmethanol51 was present.

18-crown-6

In a stainless steel vial a ⅛” stainless steel ball, triphenylmethyl bromide (200 mg, 0.6 mmol), potassium iodide (102.7 mg, 0.6 mmol), dodecane (105.4 mg, 0.6 mmol), and 18-crown-

6 (163.6 mg, 0.6 mmol) were added. The vial was closed and milled for 16.67 hours. Brownish

orange sludge remained after the reaction. The 1H NMR and GC-MS showed the major product

was triphenylmethanol51. The peaks in the 1H NMR occurred at 0.88, 1.28, 3.74, and 7.30. The peaks at 0.88 and 1.28 were from dodecane50. The peaks in the GC-MS had retention times (in

minutes) at 5.33, 7.79, 8.94, 9.39, 10.02, and 11.20. Dodecane had a retention time of 5.33 minutes, and 18-crown-6 had a retention time of 8.94 minutes. At 7.79 minutes, the m/z peaks

were 182, 105, and 77; benzophenone48 was present. At 9.39 minutes, the m/z peaks were 244,

165, 152, and 77; which was triphenylmethyl bromide52. At 10.02minutes, m/z peaks were at

260, 183, 154, 105, and 77; which was triphenylmethanol51. At 11.20 minutes, the m/z peaks were at 259, 105, 77, and 65.

Reaction of triphenylmethyl bromide with potassium hydroxide

In a stainless steel vial a ⅛” stainless steel ball, of triphenylmethyl bromide (215.4 mg,

0.7 mmol), potassium hydroxide (96.1 mg, 1.7 mmol), and dodecane (107.2 mg, 0.6 mmol) were combined. The vial was capped and milled for 16.67 hours. Yellow mustard colored solid

38 remained after the reaction. The 1H NMR and GC-MS showed the major product was

triphenylmethanol51. The peaks in the 1H NMR occurred at 0.88, 1.30, and 7.29. The peaks at

0.88 and 1.30 were from dodecane50. The retention times of the peaks in the GC-MS were 5.36

minutes, 9.38 minutes, and 9.98 minutes. Dodecane had a retention time of 5.36 minutes.

Triphenylmethyl bromide52 had a retention time of 9.38 minutes with m/z peaks at 244, 165, 152,

and 77. The peak at 9.98 minutes was triphenylmethanol51, which had m/z peaks at 260, 183,

154, 105, and 77.

18-crown-6

In a stainless steel vial a ⅛” stainless steel ball, triphenylmethyl bromide (201.2 mg, 0.6 mmol), potassium hydroxide (93.3 mg, 1.7 mmol), dodecane (110.1 mg, 0.6 mmol), and18- crown-6 (167.3 mg, 0.6 mmol) were combined. The vial was closed and milled for 16.67 hours.

Grey solid remained after the reaction. The 1H NMR and GC-MS showed the major product was

triphenylmethanol51. The peaks in the 1H NMR occurred at 0.88, 1.30, 3.68, and 7.29. The

peaks at 0.88 and 1.30 were from dodecane50, and the peak at 3.68 was from 18-crown-653a. The

GC-MS indicated there were three peaks from the GC at 5.36 minutes, 8.91 minutes, and 9.97

minutes. The peak at 5.36 minutes was from dodecane, and the peak at 8.91 minutes was from

18-crown-653b. The peak at 9.97 minutes was from triphenylmethanol51 and had m/z peaks at

260, 183, 154, 105, and 77.

Reaction of triphenylmethyl bromide with sodium iodide

In a stainless steel vial a ⅛” stainless steel ball, triphenylmethyl bromide (205 mg, 0.6

mmol), sodium iodide (98 mg, 0.7 mmol), and dodecane (103.1 mg, 0.6 mmol) were combined

in the dry box. The vial was capped and milled for 16.67 hours. Black solid remained after the

reaction. The 1H NMR and GC-MS showed the major product was triphenylmethanol51. The

39 peaks in the 1H NMR occurred at 1.51, 2.78, 4.58, and 7-7.75. The retention times of the peaks

(in minutes) in the GC-MS were 5.41, 7.82, 9.42, 9.89, and 10.06. The peak at 5.41 minutes was

dodecane. At 7.82 minutes, the m/z peaks were 182, 105, and 77; benzophenone48 was present.

Triphenylmethyl bromide52 had a retention time of 9.42 minutes with m/z peaks at 244, 165, 152,

and 77. At 9.89 minutes, the m/z peaks were 288, 243, 211, 183, 165, 105, and 77. At 10.06

minutes was triphenylmethanol51, which had m/z peaks at 260, 183, 154, 105, and 77.

Controlled reactions

Controlled reactions were done to determine what would happen to starting material if it was ball milled alone, or with dodecane. These standards were done using Teflon® or stainless

steel.

Stainless steel

Dodecane

In a stainless steel vial, triphenylmethyl bromide (201.5 mg, 0.6 mmol) and dodecane

(102.9 mg, 0.6 mmol) were added with a ⅛” stainless steel ball. The reaction was milled for

16.67 hours. Red-orange solid remained. The peaks in the 1H NMR occurred at 0.88, 1.26, and

7.29. Peaks at 0.88 and1.26 were from dodecane50. GC-MS showed four peaks at retention

times 5.37, 9.38, 9.88, and 9.98 (in minutes). Dodecane had a retention time of 5.37 minutes. At

9.38 minutes, the m/z peaks were 244, 165, 152, and 77, which indicated triphenylmethyl

bromide52 remained. At 9.88 minutes, the m/z peaks were 288, 243, 211, 183, 165, 105, and 77.

At 9.98 minutes, the m/z peaks were 260, 183, 154, 105, and 77, triphenylmethanol51 was

present.

40 Alone

Triphenylmethyl bromide, a⅛” stainless steel ball, and a stainless steel were placed in the dry box. In the vial, triphenylmethyl bromide (212 mg, 0.7 mmol) was added. The reaction was milled for 16.67 hours. Bright neon orange solid remained. The peak in the 1H NMR occurred at

7.29. GC-MS showed six peaks at retention times 7.82, 9.61, 9.99, 10.22, 10.67, and 10.78, in minutes. At 7.82 minutes, m/z peaks were 182, 105, and 77, the same as benzophenone48. At

9.61 minutes, m/z peaks were at 244, 165, 152, and 77, which was triphenylmethyl bromide52.

At 9.99 minutes, m/z peaks were at 286, 242, 165, 119, and 77. At 10.22 minutes, m/z peaks

were at 341, 243, 165, and 77. At 10.67 minutes, m/z peaks were at 348, 243, 165, and 72. At

10.78 minutes, m/z peaks were at 348, 314, 268, 237, 191, 178, 165, 152, 105, and 77.

Teflon®

Dodecane

In a stainless steel vial, triphenylmethyl bromide (206.3 mg, 0.6 mmol) and dodecane

(105 mg, 0.6 mmol) were added with a ⅛” stainless steel ball. The reaction was milled for 16.67

hours. White solid remained. The peaks in the 1H NMR occurred at 0.88, 1.28, and 7.26; which

the first two were identified as dodecane50 and the last one was chloroform45. GC-MS showed five peaks at retention times 5.38, 7.80, 9.40, 9.87, and 9.97 (in minutes). Dodecane had a retention time of 5.38 minutes. At 7.80 minutes, the m/z peaks were 182, 105, and 77,

benzophenone48 was present. At 9.40 minutes, the m/z peaks were 244, 165, 152, and 77, which

indicated triphenylmethyl bromide remained. At 9.87 minutes, the m/z peaks were 288, 243,

211, 183, 165, 105, and 77. At 9.97 minutes, the m/z peaks were 260, 183, 154, 105, and 77,

triphenylmethanol51 was present.

41 Alone

Triphenylmethyl bromide, a⅛” stainless steel ball, and a stainless steel were placed in the dry box. In the vial, triphenylmethyl bromide (200.4 mg, 0.6 mmol) was added. The reaction was milled for 16.67 hours. White solid remained. The 1H NMR showed a peak at 7.28, which

was in the aromatic region. GC-MS showed ten peaks at retention times 7.81, 9.47, 9.94, 10.02,

10.14, 10.20, 10.52, 10.58, 12.95, and 14.18, in minutes. At 7.81 minutes was benzophenone48.

At 9.47 minutes, m/z peaks were at 244, 165, 152, and 77, which was triphenylmethyl bromide52.

At 9.94 minutes, m/z peaks were at 242, 165, and 119. At 10.02 minutes, m/z peaks were at 260,

183, 154, 105, and 77, which was the same as triphenylmethanol51. At 10.14 minutes, m/z peaks

were at 243 and 165. At 10.20 minutes, m/z peaks were at 268, 252, 189, and 165. At 10.52

minutes, m/z peaks were at 348, 243, 165, and 78. At 12.95 minutes, m/z peaks were at 328,

319, 252, 243, 165, 152, and 77. At 14.18 minutes, m/z peaks were at 328, 317, 239, and 165.

Reactions with tertiary alcohols

Reaction of triphenylmethanol with potassium iodide

In a stainless steel vial, triphenylmethanol (261.4 mg, 1.0 mmol), PTSA (285.7 mg, 1.5

mmol), and potassium iodide (339.9 mg, 2.0 mmol) were added with a ⅛” stainless steel ball.

The reaction was ball milled for 16.67 hours. The peaks in the 1H NMR occurred at 2.5, 3.5, and

7.0-7.5.

Reaction of triphenylmethanol with aluminum bromide

The reaction was done by placing triphenylmethanol (200.7 mg, 1.3 mmol) in a stainless steel vial. Then, aluminum bromide (204.9 mg, 1.3 mmol) was added. A ⅛” stainless steel ball was added and the reaction was milled for 16.67 hours. The solid was white and orange. Two products formed and they were triphenylmethyl bromide and benzophenone. The peaks in the

42 GC-MS occurred at 7.80, 9.39, 9.87, and 9.98. The first peak was benzophenone48, which had

m/z peaks at 182, 105, and 77. The second peak was triphenylmethyl bromide52. The third peak

had m/z peaks at 288, 243, 211, 183, 165, 105, and 77. The last peak, at 9.98 minutes, had m/z

peaks at 260, 183, 154, 105, and 77; it was triphenylmethanol51. According to the GC-MS, the percent conversion for each was 19% triphenylmethyl bromide52 and 22% benzophenone48. The

peaks in the 1H NMR occurred at 7.25-7.32.

Electrophilic Aromatic Substitution

Alone

In a stainless steel vial, toluene (74.1 mg, 0.8 mmol) and 4-bromobenzyl bromide (200

mg, 0.8 mmol) were added with a ⅛” stainless steel ball. The reaction was milled for 16.67

hours. The peaks in the 1H NMR occurred at 1.56, 2.30, 4.44, and 7.48. Only starting materials

were in the GC-MS and no reaction occurred. Two mass specs were obtained; one occurred at

5.98 minutes, and the other at 6.55 minutes. At 5.98 minutes, the mass spectrum showed

splitting at 206, 169, and 89, which was 4-bromobenzyl chloride54. At 6.55 minutes, the mass

spectrum showed splitting at 250, 169, and 90, which was 4-bromobenzyl bromide55. A mass

spectrum was taken of 4-bromobenzyl bromide, and it indicated that there were the same two

peaks and the compound contained 4-bromobenzyl chloride.

Lewis Acid

In a stainless steel vial, 4-bromobenzyl bromide (554.1 mg, 2.2 mmol), toluene (221.1

mg, 2.4 mmol), and aluminum chloride (197.3 mg, 1.5 mmol) were added with a ⅛” stainless

steel ball. The reaction was milled for 16.67 hours. Dark red liquid remained, which fumed

when open. The peaks in the 1H NMR occurred at 1.54, 2.13, 2.85, 3.75-4.25, and 7-7.5. The

GC-MS indicated there were multiple products and multiple reactions occurred.

43 Pinacol Rearrangement of benzopinacol

Benzopinacol under HSBM conditions

In a stainless steel vial, benzopinacol (200 mg, 0.5 mmol) and a ⅛” stainless steel ball

were added. The reaction vial was placed in the 8000M mixer/mill. The reaction was milled for

16.67 hours. Then, a crude 1H NMR showed benzopinacol56 only. The peaks in the 1H NMR

occurred at 1.54, 3.02, 7.18, and 7.30.

HSBM in 8000M Mixer/Mill

The ball milled reaction was done by placing benzopinacol (203.1 mg, 0.6 mmol) in a

stainless steel vial. Then PTSA (109.3mg, 0.6 mmol) was added and a ⅛” stainless steel ball was

added. The reaction vial was placed alone in the center of the plates in an 8000M mixer/mill.

The reaction was milled for 16.67 hours. Crude GC-MS showed that the majority of the product

was benzopinacolone57. Peaks from the GC occurred (in minutes) at 7.78, 8.05, 11.26, and

12.06. The peaks at 7.78 minutes and 8.05 minutes were from benzopinacol58. The peak at 11.26

minutes was tetraphenyloxirane59a, which had m/z peaks at 348, 165, 105, and 77. The peak at

12.06 minutes was benzopinacolone57, which had m/z peaks at 243, 165, 105, and 77. The

product was extracted with distilled water and ethyl acetate.

HSBM in 8000D Mixer/Mill

1 hour

The ball milled reaction was done by placing benzopinacol (199.7 mg, 0.5 mmol) in a

stainless steel vial. Then PTSA (104.5 mg, 0.5 mmol) was added and a ⅛” stainless steel ball

was added. The reaction vial was placed in the 8000D mixer/mill. The reaction was milled for 1

hour. The solid was extracted with 10% sodium bicarbonate and ethyl acetate. Both 1H NMR

and GC-MS showed only benzopinacol56, 58. The peaks in the 1H NMR occurred at 1.55, 2.04,

44 3.03, 7.18, and 7.30. The GC-MS had only one peak at 8.04 minutes, which was the same time as benzopinacol58.

8 hours

The ball milled reaction was done by placing benzopinacol (206.6 mg, 0.6 mmol) in a stainless steel vial. Then PTSA (115.4 mg, 0.6 mmol) was added and a ⅛” stainless steel ball was added. The reaction vial was placed in the 8000D mixer/mill. The reaction was milled for 8 hours. The solid was extracted with 10% sodium bicarbonate and ethyl acetate. Both 1H NMR and GC-MS showed benzopinacol56, 58 and tetraphenyloxirane59. The peaks in the 1H NMR occurred at 2.01, 3.03, 7.18, and 7.30. Three peaks in the GC-MS were show at retention times of 8.02, 9.19, and 11.21, in minutes. At 8.02 minutes, m/z peaks were at 182 and 77, which was benzopinacol58. At 11.21 minutes, m/z peaks were at 348, 165, 105, and 77, which was tetraphenyloxirane59a.

16.67 hours

The ball milled reaction was done by placing of benzopinacol (199.9 mg, 0.6 mmol) in a stainless steel vial. Then PTSA (107.5 mg, 0.6 mmol) was added and a ⅛” stainless steel ball was added. The reaction vial was placed in the 8000D mixer/mill. The reaction was milled for

16.67 hours. Crude GC-MS showed that the majority of the product was benzopinacolone57.

The product was extracted with distilled water and ethyl acetate. The peaks in the 1H NMR occurred at 2.02, 3.03, 7.18, and 7.30. The peaks in the 13C NMR occurred at 83.1, 126.7, 127.0,

127.1, 127.3, 127.6,127.6, 127.8, 128.3, 128.7, 130.9, 131.1, 138.6, and 144.2. The GC-MS had four peaks at 8.01, 8.05, 11.31, and 11.97, in minutes. The peaks at 8.01 minutes and 8.05 minutes were from benzopinacol58. At 11.31 minutes, m/z peaks were at 348, 165, 105, and 77,

45 which indicated tetraphenyloxirane59a formed. At 11.97 minutes, m/z peaks were at 243, 165,

105, and 77, which was benzopinacolone57.

Pinacol Rearrangement of benzopinacol in toluene

In a 100 ml round bottom, 30 ml toluene was added with a stir bar. Then, benzopinacol

(206.5 mg, 0.6 mmol) was added. Then, PTSA (108.8 mg, 0.6 mmol) was added to the round bottom. The reaction was attached to water condenser and refluxed for 16 hours. After 16 hours, it was cooled to room temperature and rotavaped. Then,1H NMR of the crude product was taken. 1H NMR showed only benzopinacolone59a, where the peaks were at 7.25 and 7.66.

The 13C NMR showed peaks at 71.1, 126.7, 127.6, 127.8, 130.7, 131.1, 131.7, 137.4, 143.2, and

198.8; which are the same as benzopinacolone59a. The crude product was extracted with distilled water and ethyl acetate. The ethyl acetate layer was poured over anhydrous magnesium sulfate, and it was rotavaped and a GC-MS was taken. The GC-MS had one peak at 11.94 minutes with m/z peaks at 243, 165, 105, and 77, which indicated only benzopinacolone57 formed. It was purified using a silica plug, and running cyclohexane through the plug.

Pinacol Rearrangement of benzopinacol in ethanol

In a 100 ml round bottom, 30 ml ethanol was added with a stir bar. Then, benzopinacol

(201.2 mg, 0.6 mmol) was added. Then, PTSA (112.1 mg, 0.6 mmol) was added to the round bottom. The reaction was attached to water condenser and refluxed for 16 hours. After 16 hours, it was cooled to room temperature and rotavaped. Then 1H NMR of the crude product was taken, and peaks occurred at 2.73 and 7-7.75.The product was extracted with distilled water and ethyl acetate. The ethyl acetate layer was poured over anhydrous magnesium sulfate, and it was rotavaped and a GC-MS was taken. According to the GC-MS, the only product formed was

46 tetraphenyloxirane59a. The retention time was 11.25 minutes and the m/z peaks were 348, 165,

105, and 77, which indicated tetraphenyloxirane59a formed.

Pinacol Rearrangement of benzopinacol in 2,2,2-trichloroethanol

In a 100 ml round bottom, 30 ml 2,2,2-trichloroethanol was added with a stir bar. Then, benzopinacol (201.1 mg, 0.5 mmol) was added. Then, PTSA (104.4 mg, 0.5 mmol) was added to the round bottom. The reaction was attached to water condenser and refluxed for 16 hours.

After 16 hours, it was cooled to room temperature and rotavaped. The GC-MS of the crude product showed a peak at 11.94 minutes which had m/z peaks 243, 165, 105, and 77, these GC-

MS results indicated that the only product formed was benzopinacolone57. It was extracted with

10% sodium bicarbonate and ethyl acetate. The ethyl acetate layer was poured over anhydrous magnesium sulfate. It was recrystallized with absolute ethanol. 1H NMR showed only benzopinacolone59a. The peaks in the 1H NMR occurred at 7.25 and 7.66.

Pinacol Rearrangement of pinacol

The ball milled reaction was done by placing pinacol (202.4 mg, 1.7 mmol) in a stainless steel vial. Then PTSA (332.4 mg, 1.7 mmol) was added and a ⅛” stainless steel ball was added.

The reaction vial was placed in the 8000M mixer/mill. The reaction was milled for 16.67 hours.

Then, crude 1H NMR showed pinacol60 only. The peaks in the 1H NMR occurred at 1.25 and

2.00.

47 Synthesis of diols using Zn/ZnCl2

Modifications were made to Tanaka’s37 synthesis for coupling aromatic aldehydes and aromatic ketones. The reaction was done under HSBM conditions.

Benzophenone

In a stainless steel vial, benzophenone (205.0 mg, 1.1 mmol) and zinc dust (590.0 mg, 9.0 mmol) were added. Then, a ⅛” stainless steel ball was added and the reaction was milled for 1 hour. The reaction was extracted with 1 ml of 3 M HCl and ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and rotavaped. A column was run, using a gradient starting with cyclohexane and ending with dichloromethane. Three fractions were collected; the first fraction was a mixture of benzophenone and benzopinacol, and the second fraction was benzopinacol. The second fraction had peaks in the 1H NMR at 0.88, 1.29, 1.55,

3.03, 7.17, and 7.28. The peaks at 0.88 and 1.29 were from grease45. The peak at 1.55 was from water45. However, the rest of the peaks were benzopinacol56 peaks; at 3.03 was the hydrogen of the alcohol, and the peaks at 7.17 and 7.28 were from the aromatic rings.

Acetophenone

In a stainless steel vial, acetophenone (209.0 mg, 1.7 mmol), zinc dust (869.7 mg, 13.3 mmol), and zinc (II) chloride (235.8 mg, 1.7mmol) were combined. Then, a ¼” stainless steel ball was added and the reaction was milled for 16.67 hours. The reaction was extracted with saturated ammonium chloride and ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and rotavaped. A 4 g column was run, using a gradient starting with cyclohexane and ending with dichloromethane. Four fractions were collected. The first two were the E and Z isomers of 2,3-diphenyl-2-butene61. The 1H NMR had peaks at 0.88, 1.30,

1.52, 2.40, 6.74, 6.95-7.19, and 7.24-7.39. The 13C NMR had peaks at 19.7, 29.6, 31.1, 67.3,

48 125.0, 125.9, 127.5, 127.5, 127.9, and 129.9. The GC-MS had two peaks for 2,3-diphenyl-2-

butene were at 7.63 minutes and 8.09 minutes, and 2,3-diphenyl-2-butene61 m/z peaks were 208,

193, 178, 130, 115, 91, and 77 for both retention times. The fourth fraction was 2,3-diphenyl-

2,3-butanediol58. The 1H NMR had peaks at 0.88, 1.26, 1.51, 1.58, 2.57, 7.21, and 7.26.The 13C

NMR had peaks at 14.1, 22.7, 25.0, 25.1, 29.4, 29.7, 31.9, 78.6, 78.9, 126.9, 127.0, 127.1, 127.3,

127.4, and 143.4. The GC-MS had two peaks. The first was at 4.00 minutes and had m/z peaks

at 120, 105, and 77. The second was at 9.06 minutes and had m/z peaks at 121, 105, and 77. The diol, 2,3-diphenyl-2,3-butanediol58, breaks apart at the carbon-carbon bond where the diols are

before it hits the detector, which is why the major peak is at 9.06 minutes and has a major m/z

peak of 121. The yield obtained for the 2,3-diphenyl-2,3-butanediol58 was 42.8%.

Synthesis of diols using Mg/I2

Synthesis was modified from Wangab’s40 magnesium induced pinacol synthesis.

However, it didn’t work because the reaction did not reach the temperature to make magnesium

iodide.

Magnesium vial

In a stainless steel vial, benzophenone (211.2 mg, 1.2 mmol), magnesium turnings (208.9

mg, 8.6 mmol), and iodine (102.0 mg, 0.4 mmol) were combined. Then, a ⅛” stainless steel ball

was added and the reaction was milled for 16.67 hours. The reaction was extracted with

saturated ammonium chloride and ethyl acetate. The solid was worked up by extracting with

10% HCl and ethyl acetate. Then, it was extracted with distilled water and ethyl acetate three

times. The dark red solution was poured over anhydrous magnesium sulfate and it was

rotavaped. The peaks in the 1H NMR occurred at 1.25, 2.04, 2.08, 4.12, 7.25, 7.50, 7.60, and

7.80. The retention times of the GC-MS were 8.06, 8.28, 8.48, 8.55, 8.66, and 11.98 (in

49 minutes). At 8.06 minutes, the m/z peaks were 182, 105, and 77; the molecule was

benzophenone48. At 8.28 minutes, the m/z peaks were 210, 167, 152, and 77. At 8.48 minutes,

the m/z peaks were 222, 181, 165, 103, and 77. At 8.55 minutes, the m/z peaks were 183, 105, and 77. At 8.66 minutes, the m/z peaks were 121, 105, and 77. At 11.98 minutes, the m/z peaks were 243, 165, 105, and 77.

Stainless Steel

In a stainless steel vial, of benzophenone (207.7 mg, 1.1 mmol), magnesium turnings

(59.7 mg, 2.5 mmol), and iodine (164.0 mg, 0.6 mmol) were combined. Then, a ¼” stainless steel ball was added and the reaction was milled for 16.67 hours. The reaction was extracted with saturated ammonium chloride and ethyl acetate. 1H NMR had peaks at 7.26, 7.51, 7.60, and

7.80, which indicated only benzophenone62 was present. The dark gray solid was worked up by extracting with 10% HCl and ethyl acetate. Then, it was extracted with distilled water and ethyl acetate three times. The ethyl acetate solution was poured over anhydrous magnesium sulfate and it was rotavaped.

Cleavage of Benzopinacol

In a stainless steel vial, benzopinacol (207.0 mg 0.6 mmol) was added, and the vial and a

⅛” stainless steel ball were placed in the dry box. Then, sodium hydride (46.0 mg, 1.9 mmol) was added to the vial, along with the ball. The reaction was capped in the dry box. The reaction was under HSBM conditions for 16.67 hours. The solid was put in a solution of saturated ammonium chloride and ethyl acetate. The reaction stirred for 13 hours and 45 minutes. The ethyl acetate layer was poured over anhydrous magnesium sulfate and rotavaped. 1H NMR and

GC-MS indicated diphenylmethanol46 and benzophenone,62, 48 were the products. The peaks in the 1H NMR occurred at 0.88, 1.22, 2.12, 2.58, 5.80, 6.87, 7.28, 7.45, 7.55, and 7.77. The peaks

50 at 0.88 and 1.22 were from grease45, and the peak at 2.12 was unknown. The peaks at 2.58, 5.80,

7.28, 7.45, 7.55, and 7.77 were from diphenylmethanol46b. The GC-MS had three peaks at 8.02

minutes, 8.11 minutes, and 8.26 minutes. The peak at 8.02 minutes had m/z peaks at 182, 105,

and 77; benzophenone48 was present. The peak at 8.11 minutes had m/z peaks at 182, 105, and

77; which indicated benzophenone48 was present. The peak at 8.26 minutes had m/z peaks at

228, 184, 165,105, and 77.

Synthesis of 1,2-diphenyl-1,2-ethanediol

The synthesis of 1,2-diphenyl-1,2-ethanediol was prepared using Kwong’s method.41 In

a 100 ml round bottom flask, 0.0065 g osmium tetroxide was added with 0.5 ml tBuOH. Then,

15 ml tBuOH was added to the round bottom flask. After that, 15 ml distilled water was added.

Then, potassium carbonate (0.8332 g, 6.0 mmol), dihydroquinidine 4-chlorobenzoate (0.4671 g,

1.0 mmol), and potassium ferricyanide(1.9835 g, 6.0 mmol) were added to the flask one at a

time. The last thing added was E-stilbene (0.3684 g, 2.0 mmol). The alkene must be added

last.41 Reaction stirred for 24 hours; then, 1.5228 g sodium sulfite was added. The reaction

stirred for an hour. The product was extracted out with ether three times. The ether layer was

poured over anhydrous magnesium sulfate and rotavaped. A 12 g column was run using a ramp,

which started with dichloromethane and ending with ethyl acetate. The product was obtained in

the second fraction collected. The solution was placed in a round bottom flask, and 66.6% yield

was obtained. The peaks of1,2-diphenyl-1,2-ethanediol63 in the 1H NMR occurred at 2.94, 4.69,

7.13, and 7.21. The GC-MS had one peak at 8.91 minutes, and it had m/z peaks at 196, 150,

107, and 79; which was 1,2-diphenyl-1,2-ethanediol63.

Modifications were made by using 0.31 ml of 2.5 wt.% osmium tetroxide in tBuOH and

adding 0.18 ml tBuOH, which made it easier to measure the amount of osmium tetroxide.

51 Pinacol Rearrangement of 1,2-diphenyl-1,2-ethanediol in HSBM conditions

The ball milled reaction was done by placing 1,2-diphenyl-1,2-ethanediol (106.3 mg, 0.5 mmol) in a stainless steel vial. Then PTSA (98.5mg, 0.5 mmol) was added and a ⅛” stainless steel ball was added. The reaction was milled for 16.67 hours. The crude product was extracted with distilled water and ethyl acetate. The ethyl acetate layer was poured over anhydrous magnesium sulfate, and it was rotavaped. The peaks in the 1H NMR occurred at 4.75, 7.13, and

7.26. Peaks in the 13C NMR were at 21.2, 29.7, 79.1, 80.1, 126.9, 127.0, 127.1, 127.3, 127.9,

128.1, 128.2, 128.2,136.8, 139.8, and 170.3. The GC-MS had retention times at 9.04, 9.25,

10.93, and 12.68, in minutes. At 9.04 minutes the m/z peaks were 214, 107, and 79, which were

the same as 1,2-diphenyl-1,2-ethanediol63. At 9.25 minutes, the m/z peaks were 256, 150, 107,

and 79. At 10.93 minutes, the m/z peaks were 196, 178, 167, 105, 89, 77, which was the same as

1,2-diphenyloxirane64. At 12.68 minutes, the m/z peaks were 225, 197, 180, 167, 105, which

was unknown.

Pinacol Rearrangement of 1,2-diphenyl-1,2-ethanediol in dry HSBM conditions

The ball and vial were placed in the oven at 120°C one hour before use. The ball milled reaction was done by placing 1,2-diphenyl-1,2-ethanediol (100.5 mg, 0.5 mmol) in a stainless steel vial. Then PTSA (90.1 mg, 0.5 mmol) was added and a ⅛” stainless steel ball was added.

The reaction was milled for 16.67 hours. The crude product was extracted with 10% sodium bicarbonate and ethyl acetate. The ethyl acetate layer was poured over anhydrous magnesium sulfate, and it was rotavaped. Then, 1H NMR and GC-MS were taken and revealed only 1,2-

diphenyl-1,2-ethanediol63. The peaks in the 1H NMR occurred at 0.89, 1.27, 2.90, 4.70, 7.13, and

7.21. Peaks in the 13C NMR were at 29.3, 79.1, 126.9, 127.9, 128.1, 128.2, and 139.8.

52 Pinacol Rearrangement of 1,2-diphenyl-1,2-ethanediol in toluene

In a 100 ml round bottom, 15 ml toluene was added with a stir bar. Then, 1,2-diphenyl-

1,2-ethanediol (100.5 mg, 0.5 mmol) was added to the round bottom. Then, PTSA (90.1 mg, 0.5

mmol) was added to the round bottom. The reaction was attached to water condenser and

refluxed for 16 hours. After 16 hours, it was cooled to room temperature and rotavaped. Then,

1H NMR of the crude product was taken. The peaks in the 1H NMR occurred at 2.24, 2.38, 4.90,

6.5-7.5, 7.75, 9.91, and 11.00. The 13C NMR peaks were at 83.1, 126.7, 127.0, 127.1, 127.3,

127.6, 127.6, 127.8, 128.3, 128.7, 130.9, 131.1, 138.6, and 144.2. The NMR data indicated

multiple products were formed. The crude product was extracted with 10% sodium bicarbonate

and ethyl acetate. The ethyl acetate layer was poured over anhydrous magnesium sulfate, and it

was rotavaped. However, products were different than before.

Pinacol Rearrangement of 1,2-diphenyl-1,2-ethanediol in ethanol

In a 100 ml round bottom, 15 ml ethanol was added with a stir bar. Then, 1,2-diphenyl-

1,2-ethanediol (102.5 mg, 0.5 mmol) was added to the flask. Then, PTSA (90.4 mg, 0.5 mmol)

was added to the round bottom. The reaction was attached to water condenser and refluxed for

16 hours. After 16 hours, it was cooled to room temperature and rotavaped. It was extracted

with 10% sodium bicarbonate and ethyl acetate. The ethyl acetate layer was poured over

anhydrous magnesium sulfate, and it was rotavaped and a GC-MS was taken. According to the

GC-MS, the only product formed was 1,2-diphenyloxirane64.Three peaks were in the GC-MS.

The first peak had a retention time of 8.47 minutes and m/z peaks at 135, 107, and 79. The

second peak had a retention time of 8.92 minutes and m/z peaks at107 and 79. The third peak at

12.70 minutes had m/z peaks at 225, 197, 180, 167, and 105. Peaks in the 1H NMR occurred at

53 1.25, 2.03, 2.97, 4.71, 6.11, and 6.90-7.50. Peaks in the 13C NMR were at 127.1, 127.9, 128.1,

128.2, 128.2, 128.4, 129.8, 129.9, 136.2, 138.1, 139.8, 139.9, and 140.0.

Protecting Groups

Acetone

In a stainless steel vial, 1,2-diphenyl-1,2-ethanediol (101.6 mg, 0.5 mmol), PTSA (90.3 mg, 0.5 mmol), and acetone (36.3 mg, 0.6 mmol) were added with a ⅛” stainless steel ball. The reaction took 16.67 hours. It was worked up by extracting the solid with 10% sodium bicarbonate and ethyl acetate. The ethyl acetate was poured into a round bottom flask over anhydrous magnesium sulfate, and rotavaped. Peaks in the 1H NMR occurred at 1.67, 4.65, 4.74,

7.10, 7.20, and 7.30. Peaks in the 13C NMR were at 27.2, 29.7, 79.1, 79.1, 85.5, 109.4, 126.7,

127.0, 127.9, 128.1, 128.3, 128.4, 136.7, and 139.9. The NMR data indicated the diol was

protected. The GC-MS had two peaks. The first peak was at 8.69 minutes and had m/z peaks at

197, 179, 148, 133, 119, 105, 90, and 77. The second peak was at 8.92 minutes and had m/z

peaks at 197, 107, and 79. The product obtained was 90.4 mg, with a 71.1% yield.

Ethylene glycol

Benzophenone

In a stainless steel vial, benzophenone (586.4 mg, 3.2 mmol), of PTSA (608.3 mg, 3.2 mmol), and ethylene glycol (0.20 ml, 3.6 mmol) were added with a ⅛” stainless steel ball. The reaction took 16.67 hours. It was worked up by extracting the solid with 10% sodium bicarbonate and ethyl acetate. The ethyl acetate was poured into a round bottom flask over anhydrous magnesium sulfate, and rotavaped. 1H NMR peaks at 1.24, 1.42, 2.03, 4.11, 7.47,

7.58, and 7.80 indicated no reaction took place.

54 4-methoxybenzaldehyde

In a stainless steel vial, 4-methoxybenzaldehyde (0.50 ml, 4.1mmol), PTSA (685.1 mg,

3.6 mmol), and ethylene glycol (0.20 ml, 3.6 mmol) were added with a ⅛” stainless steel ball.

The reaction took 16.67 hours. It was worked up by extracting the solid with 10% sodium

bicarbonate and ethyl acetate. The ethyl acetate was poured into a round bottom flask over

anhydrous magnesium sulfate, and rotavaped. 1H NMR peaks occurred at 3.86, 6.99, 7.80, and

9.86; which were from 4-methoxybenzaldehyde62.

Preparation of triphenylethene

Triphenylethene was prepared by modifying a Wittig synthesis.43 First, the phosphonium salt was prepared by adding about 120 ml toluene from solvent system to 250 ml round bottom flask. Then, 2.80 ml (23.5 mmol) benzyl bromide was pipetted out into a 10 ml graduated cylinder and poured into the round bottom flask. The flask was rinsed out graduated cylinder with some solvent from another flask. Then, triphenylphosphine (6.0823 g, 23.2 mmol) was added to the round bottom flask. The flask was swirled to get triphenylphosphine to dissolve.

Then a stir bar was added to the flask and a reflux condenser was attached. The water was turned on. The oil bath was placed under the flask and heated the solution under reflux for 16 hrs. The reaction was cooled to room temperature for 20 min. The product was collected by vacuum filtration; the 250 ml flat round bottom flask, the universal adapter, and the fritted funnel with neoprene adapter were attached and clamped together. The pressure tubing connected to vacuum pump from Schlenk line was attached to universal adapter. The knob on the Schlenk line for vacuum to apparatus was turned on. The vacuum was turned on and a fine white powder

(product) remained on top; solvent and soluble starting materials went into the flat round bottom flask. Once gas started to evolve, the vacuum was turned off. The product was placed on a

55 watch glass and let dry. Then it was placed in the oven for 5 min to remove residual toluene.

After 5 min in the oven, the watch glass with product was cooled to room temperature. The

product was weighed, and 9.9200 g was obtained, which gave a 98.7% yield.

Two flasks were placed in oven at least 1 hour before use, and they were a 250 ml 3 neck flask and a 50 ml cone bottom flask. The 3 neck flask was taken out and let cool to room temperature. Septa were placed on either ends of the 3 neck flask, or reaction flask. A one inch stir bar was added to the reaction flask. Approximately 150 ml THF from solvent system

(already under argon) was added to the reaction flask. Then, about 100 ml THF was placed in a

100 ml round bottom. All of the triphenylphosphine salt was added to reaction flask by funneling in. The funnel was rinsed with 2-3 1 ml portions of THF. Then the reaction flask was rinsed with THF. A reflux condenser was attached to the reaction flask. Air was purged out by having a septa and a needle on the top of the condenser, and placing a needle connected to

Schlenk line with argon on. A syringe was primed by taking argon out of reaction flask and

dumping it out into the air (3 times). The 1.6 M nBuLi was placed under argon by attaching an

out needle and an in needle connected to argon from Schlenk line on to it. Then, 18 ml nBuLi in

hexanes, and ~2 ml argon was syringed out and added to reaction flask. The syringe was cleaned

out by flushing with ethanol or isopropanol and rinsing with acetone. The reaction flask was

stirred at room temperature for 30 min, and the solution turned dark red. The cone flask was

taken from the oven and benzophenone (4.1820 g, 23.0 mmol) to cone flask and the remaining

THF was added. Septa was placed over the cone flask and placed under argon. The flask

containing benzophenone solution was swirled until benzophenone dissolved. The

benzophenone solution was syringed into reaction flask. Then the out and in was removed from

benzophenone flask and reaction flask. The reaction flask heated to reflux for 93 hours. After

56 93 hours, the solution was transferred to a 250 ml round bottom flask, and the THF was rotavaped off. A light pink solid remained. The product was purified by trituration with cyclohexane; white solid remains in the round bottom and product is in cyclohexane. The product in cyclohexane was transferred to another round bottom and rotavaped off. It was further purified by recrystallization with methanol, and a 46.5% yield was obtained. The peaks in the 1H NMR occurred at 1.25, 1.54, 6.9-7.6. The peak at δ 1.25 was from methanol45, and the peak at 1.54 was from water45. The peak at 6.9-7.6 is triphenylethylene65a. The GC-MS indicated that triphenylethylene65b has a retention time of 10.04 minutes, with m/z peaks at 256,

239, 178, 165, 126, 113, and 77.

Preparation of 1-(4-nitro-phenyl)-1,2-diphenylethene

1-(4-nitro-phenyl)-1,2-diphenylethene was prepared by a Wittig synthesis.43 The phosphonium salt was prepared as described in the Preparation of Triphenylethylene. The phosphonium salt (8.4428 g, 19.5 mmol) was dissolved in ether in a 250 ml three-neck flask with stir bar. The middle opening was attached to a reflux condenser, and the other two openings were cover with septa. Septum was placed in the top of the condenser, and the system was flushed with argon. It stirred overnight. Then 15 ml of 1.6 M nBuLi, was added and the reaction stirred for 25 minutes, then more ether was added. The reaction was placed in an ice bath. Then,

4-nitrobenzophenone (4.4309 g, 19.5 mmol) in ether was added. However, not all of the ketone dissolved in ether, and it was rotavaped, and scraped out of the flask and added into the reaction flask. The reaction stirred for two days at room temperature. The reaction was then placed in an oil bath and heated to 75°C and refluxed 10 hours. Reaction was cooled to room temperature and transferred to a round bottom flask. It was rotavaped and a brown solid was obtained. The product was purified by running a column. The peaks in the 1H NMR occurred at 1.23, 2.04,

57 3.48, 4.12, 4.71, 5.40, 5.44, and 7.0-7.8. The percent conversion was 43.9% 1-(4-nitro-phenyl)-

1,2-diphenylethene66 according to the GC-MS. The starting material, 4-nitrobenzophenone67,

had a retention time of 9.24 minutes and had m/z peaks at 277, 106, and 77. Two products of 1-

(4-nitro-phenyl)-1,2-diphenylethene66 occur in this reaction, one at 11.48 minutes and 11.65

minutes; both peaks have m/z peaks at 301, 253, 178, and 126. There was also a peak at 11.21

minutes that had m/z peaks at 277, 199, 183, and 77.

For future reference, it would be better to use THF, because the ketone is soluble in THF.

Preparation of 1,1,2-triphenyl-1,2-ethanediol

With dihydroquinidine 4-chlorobenzoate

The synthesis of 1,1,2-triphenyl-1,2-ethanediol was prepared using Kwong’s method.41

In a 100 ml round bottom flask, 15 ml distilled water and 15 ml tBuOH were added. Then, 0.31 ml of 2.5 wt.% osmium tetroxide in tBuOH and 0.18 ml tBuOH were added to the round bottom.

Then, potassium ferricyanide (1.9843 g, 6.0 mmol), potassium carbonate (0.8319 g, 6.0 mmol) and dihydroquinidine 4-chlorobenzoate (0.4677 g, 1.0 mmol) were added to the flask one at a time. The last thing added was triphenylethylene (0.5222 g, 2.0 mmol). The alkene must be added last.41 Reaction stirred for 25 hours; then, 1.50 g sodium sulfite was added. The reaction

stirred for an hour. The product was extracted out with ether three times. The ether layer was

poured over anhydrous magnesium sulfate and rotavaped. A column was run using a ramp,

which started with dichloromethane and ending with ethyl acetate. The 1,1,2-triphenyl-1,2- ethanediol68 was obtained in the second fraction collected. The solution was placed in a round bottom flask, and 66.6% yield was obtained. The peaks in the 1H NMR occurred at 2.10, 3.13,

5.65, 7-7.25, 7.41, and 7.71. Peaks in the 13C NMR were at 76.7, 78.0, 126.2, 126.7, 127.0,

127.4, 127.5, 127.6, 127.7, 128.1, and 128.5.

58 Without dihydroquinidine 4-chlorobenzoate

The synthesis of 1,1,2-triphenyl-1,2-ethanediol was attempted by modifying Kwong’s

method.41 In a 100 ml round bottom flask, 15 ml distilled water and 15 ml tBuOH were added.

Then, 0.31 ml of 2.5 wt.% osmium tetroxide in tBuOH and 0.18 ml tBuOH were added to the

round bottom. Then, potassium ferricyanide (1.9806 g, 6.0 mmol) and potassium carbonate

(0.8306 g, 6.0 mmol) were added to the flask one at a time. The last thing added was

triphenylethylene (0.5193 g, 2.0 mmol). The alkene must be added last.41 Reaction stirred for

25 hours; then, 1.58 g sodium sulfite was added. The reaction stirred for an hour. The product

was extracted out with ether three times. The ether layer was poured over anhydrous magnesium

sulfate and rotavaped. The peaks in the 1H NMR occurred at 1.54, 2.13-2.40, 3.75-4.12, and 7-

7.5, which indicated no reaction occurred without the chiral compound.

Preparation of 1,1,2-triphenyl-1,2-ethanediol via Grignard

Two 250 ml round bottom flasks, a claisen head condenser, and a drying tube were placed in the oven an hour before use. The drying tube was filled with calcium sulfate and attached to the curved part of the claisen head. The straight part of the claisen head was capped, attached to the round bottom with stir bar, and put under argon. Then 20 ml of 2.8 M phenylmagnesuim bromide (56 mmol) in diethyl ether was added to the round bottom. In the other round bottom flask, 100 ml of diethyl ether was obtained from the solvent system. In a clean dry cone flask, benzoin (736.6 mg, 3.5 mmol) was added. Diethyl ether was added to the cone flask. The solution was syringed into the round bottom flask. However, not all of the benzoin dissolved in ether, and what did not dissolve was scraped out and added to the round bottom. Solution stirred for 2 hours. Then it was extracted with 1.5 M HCl. The ether layer poured through anhydrous magnesium sulfate and then the ether was rotavaped off. The solid

59 was triturated twice with hexane, and 16.3 % yield was obtained. The 1H NMR and GC-MS

indicated the major product was 1,1,2-triphenyl-1,2-ethanediol45o. The peaks in the 1H NMR

occurred at 1.57, 2.45, 3.15, 5.29, 5.62, 7.15, 7.30, 7.40, and 7.70. The GC-MS had five peaks at7.86 minutes, 9.89 minutes, 10.18 minutes, 10.40 minutes, and 10.80 minutes. At 7.86 minutes, the m/z peaks were182, 105, and 77. At 9.89 minutes, the m/z peaks were 256, 178, and 165. At 10.18 minutes, the m/z peaks were243 and 165. At 10.40 minutes, the m/z peaks were 346, 239, 165, 105, and 77.At 10.80 minutes, the m/z peaks were 183, 105, and 77. All the peaks in the GC-MS are from how the molecule hits the detector; the diol breaks apart at the carbon-carbon bond where the diols are before it hits the detector, which is why the major peak is at 7.86 minutes and has a major m/z peak of 182.

Bromination of 9-methylanthracene

In a 100 ml round bottom, 30 ml of carbon tetrachloride was added with a stir bar. Then

9-methylanthracene (1.0012 g, 5.2 mmol) was added. Another 20 ml of carbon tetrachloride was added to the round bottom. Then, benzoyl peroxide (37.8 mg, 0.2 mmol) was added to the flask.

The flask was swirled and placed in an oil bath and stirred. Then NBS (0.9266 g, 5.2 mmol) was added slowly. The water condenser was attached and turned on. The flask was heated, and the

lamp was also attached. Foil was placed around the reaction with the shiny side in so the

reaction can reflect more light. The lamp was turned on, and the reaction proceeded for one

hour. The reaction cooled to room temperature, and the carbon tetrachloride was rotavaped off.

Distilled water was added to the flask. The product was extracted out of the distilled water with

dichloromethane three times. The dichloromethane was poured over anhydrous magnesium

sulfate and rotavaped. The product, 9-bromomethylanthracene, was obtained with a 99.3 %

yield. Peaks in the 1H NMR were at 1.42, 2.73, 5.29, 5.52, 7.49, 7.63, 8.01, 8.27, and 8.47. The

60 peak at 1.42 was from residual water45 after the work up. The peak from 2.73 was succinimide69.

The peak at 5.29 was dichloromethane45. The rest of the peaks in the 1H NMR were from 9-

bromomethylanthracene70.

Diels-Alder Reactions with Maleic Anhydride

These reactions were done in the 8000D Mixer/Mill. Two vials were placed in opposite sides in a 4 vial holder. The vial holder was placed in a metal holder, which was placed on one side of the dual mill. Another set of two vials, and vial holder, and metal holder was placed on the other side of the dual mill to act as a counter balance.

Diels-Alder Reactions with Anthracene

In a stainless steel vial, anthracene (200.4 mg, 1.1 mmol) and maleic anhydride (110.0 mg, 1.1 mmol) were added with a⅛” stainless steel ball. The reaction was the only reaction milled and ran for 16.67 hours. 1H NMR had peaks at 6.96, 7.45, 8.00, and 8.42, in which the

first peak was from maleic anhydride71 and the rest were from anthracene72 and indicated no

product formed.

Diels-Alder Reactions with 9-methylanthracene

In a stainless steel vial, 9-methylanthracene (201.6 mg, 1.0 mmol) and maleic anhydride

(107.3 mg, 1.1 mmol) were added with a ⅛” stainless steel ball. The reaction was milled with

four other reactions and ran for 16.67 hours. 1H NMR occurred at 2.23, 3.12, 3.56, and 6.5-7.75,

which indicated the Diels-Alder product, 9-methyl-9,10-dihydro-9,10-ethano-anthracene-11,12- dicarboxylic acid-anhydride73, formed. The mass obtained was 235.0 mg.

Diels-Alder Reactions with 9-cyanoanthracene

In a stainless steel vial, 9-cyanoanthracene (255.4 mg, 1.3 mmol) and maleic anhydride

(125.9 mg, 1.3 mmol) were added with a⅛” stainless steel ball. The reaction was milled with

61 another other reaction (each reaction was placed on opposite sides of the dual mill) and ran for

16.67 hours. 1H NMR peaks were at 1.85, 7.04, 7.60, 7.73, 8.09, 8.44, and 8.69,which indicated

no product formed. The peak at 1.85 was from grease45. The peak at 7.04 was maleic

anhydride71. The peaks at 7.60, 7.73, 8.09, 8.44, and 8.69 were from 9-cyanoanthracene74.

Diels-Alder Reactions with 9,10-dicyanoanthracene

In a stainless steel vial, 9,10-dicyanoanthracene (251.4 mg, 1.1 mmol) and maleic anhydride (109.7 mg, 1.1 mmol) were added with a⅛” stainless steel ball. The reaction was milled with four other reactions and ran for 16.67 hours. 1H NMR indicated no product formed.

The peaks in the 1H NMR occurred at 1.65, 7.04, 7.85, and 8.53. The peak at 1.65 was from

some residual water45 after the vial was cleaned. The peak at 7.04 was from maleic anhydride71,

and the peaks at 7.85 and 8.53 were from 9,10-dicyanoanthracene75.

Diels-Alder Reactions with 9-bromoanthracene

In a stainless steel vial, 9-bromoanthracene (255.9 mg, 1.0 mmol) and maleic anhydride

(94.5 mg, 1.0 mmol) were added with a⅛” stainless steel ball. The reaction was the only

reaction milled and ran for 16.67 hours. The peaks in the 1H NMR occurred at 6.93, 7.49, 7.95,

8.30, which were from 9-bromoanthracene76.

Diels-Alder Reactions with 9-bromomethylanthracene

In a stainless steel vial, 9-bromomethylanthracene (271.0 mg, 1.0 mmol) and maleic

anhydride (98.6 mg, 1.0 mmol) were added with a⅛” stainless steel ball. The reaction was the

only reaction milled and ran for 16.67 hours. 1H NMR had peaks at 2.25, 2.75, 3.60, 4.77, 5.52,

6.5-9.0.

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70 Appendix A

Other Investigations

Protecting Groups

Protecting groups are used when a reaction needs to occur at a specific site in a

multifunctional compound and the other sites need to be blocked to allow the reaction to

happen.77 Diols can serve as protecting groups for aldehydes and ketones, and aldehydes and

ketones can serve as protecting groups for diols. 77 It has been found that the formation of acetals

and ketals usually use these three diols:2,2-dimethyl-1,3-propanediol, ethylene glycol, and 1,3-

propanediol. 77 These diols are listed from greatest to least reactivity. 77 The classical reaction conditions involve using a catalytic amount of acid, and refluxing the reaction in toluene while it is attached to a Dean-Stork trap. The Dean-Stork trap is used to drive off water, a side product of

the reaction. However, diols and aldehydes and ketones could be protected under HSBM

conditions.

Acetone

If acetone is present during a pinacol rearrangement, the products formed could be

different. When 1,2-diphenyl-1,2-ethanediol, acetone and PTSA were reacted under HSBM

conditions, the product formed was confirmed by 1H NMR and is shown in Figure 38.

O O O OH p-TsOH 1/8" ss ball & vial 16.67 hrs

Figure 38. 1,2-diphenyl-1,2-ethanediol, acetone, and p-toluenesulfonic acid formed ketal.

This may be of interest if there are specific diols or ketones that need to be protected.

Ethylene glycol

71 Ethylene glycol is a specific diol that is often used to protect aldehydes and ketones. It

was used with benzophenone, and the reaction in Figure 39 shows theoretical product.

OH O O H+ OH

Figure 39. Ethylene glycol reacts with benzophenone and acid to form a ketal.

However, under HSBM conditions no product is seen. This is supported by the 1H NMR.

Ethylene glycol and 4-methoxybenzaldhyde, shown in Figure 40, were placed under HSBM

conditions. The product shown in Figure 40 is the theoretical product.

O O O OH H+ H OH H

H3CO H3CO Figure 40. Ethylene glycol reacts with anisaldehyde and acid to form an acetal.

According to the 1H NMR, no product was formed, which indicates that protecting aldehydes,

ketones, and diols cannot always occur.

Bimolecular Substitution

In order to understand how HSBM works it is important to examine what is already known, which is that bimolecular substitution reaction occurs with primary and secondary alkyl halides. The mechanism for the substitution of secondary alkyl halides has been speculated to

predict the formation of carbon-carbon bonds. The bonds form depending on which salt is

used.20

Diphenylmethyl bromide

72 Further experiments were done using diphenylmethyl bromide to explain formation of

specific products. When diphenylmethyl bromide was reacted with sodium iodide under cold

conditions by placing the vial in liquid nitrogen for five minutes then milling for ten minutes,

after a total of one hour, a light green solid was obtained. 1H NMR indicated no reaction occurred, as shown in Figure 41. These reaction were done with liquid nitrogen to determine

Br Br

NaI 1/8" ss ball & vial 1 hr COLD

Figure 41. Diphenylmethyl bromide reacted with sodium iodide under liquid nitrogen. if the temperature can be used to manipulate which product forms.

Diphenylmethyl bromide was reacted with sodium borohydride, in a ratio of 1:1, to

determine if substitution would take place, as shown in Figure 42.

NaBH4 1/8" ss ball & vial 16.67 hrs

Figure 42. Diphenylmethyl bromide reacted with sodium borohydride to form diphenylmethane.

The reaction was done under HSBM conditions. The product formed was diphenylmethane, which according to the GC-MS showed 50.1% conversion, bis(dipenylmethyl)ether showed8.3% conversion, 2.3% was converted to tetraphenylethane, and 13.6% converted to p-

benzyltriphenylmethane.

Diphenylmethyl bromide was reacted with sodium iodide. An alkene was added to see if

the reaction proceeds through a radical mechanism. If it does, there would be multiple products,

including diphenylmethane. The reaction scheme is shown in Figure 43.

73 Br NaI 1-hexene 1/8" ss ball & vial 16.67 hrs

Figure 43. Diphenylmethyl bromide reacted with sodium iodide and 1-hexene.

The GC-MS showed 53% conversion of diphenylmethyl bromide to diphenylmethane at 6.81,

6% was benzophenone at 7.80, 8% was diphenylmethanol at 7.83, 27% wastetraphenylethane at

11.31, and 6% was bis(dipenylmethyl)ether.

Diphenylmethyl bromide was placed under HSBM conditions with sodium iodide and

1,4-cyclohexadiene. The 1,4-cyclohexadiene is known as a radical quencher. If the secondary reaction goes through a radical mechanism, then the resulting products would be benzene and diphenylmethane. The reaction shown in Figure 44 indicates the results under HSBM conditions.

Br NaI 1,4-cyclohexadiene 1/8" ss ball & vial 16.67 hrs

Figure 44. Diphenylmethyl bromide reacted with sodium iodide and 1,4-cyclohexadiene.

The GC-MS shows that diphenylmethane is at 6.83 and 63% was converted to it; while there is a

3% conversion to benzophenone at 7.60 minutes, 22% conversion to tetraphenylethane at 11.31 minutes, and 12% conversion to bis(dipenylmethyl)ether at 11.59 minutes.

Benzyl bromide

The substitution of the benzyl bromide is believed to go through an SN2 reaction.

However, the secondary reaction yields a dimer. Therefore, the reaction conditions were changed by using 0.5 equivalence of the iodide salt to see if a carbon-carbon bond would form.

74 Br I 0.5 equivalence MI 1/8" ss ball & vial 16.67 hrs

Figure 45. Reaction of benzyl bromide with metal iodide forms benzyl iodide. Metal is sodium or lithium.

Reaction conditions are shown in Figure 45. The only product formed was the substituted product.

Although substitution occurs for primary and secondary alkyl halides, the only product in the tertiary alkyl halide is the tertiary alcohol. It is not clear where the alcohol comes from.

Some substitution occurred when Lewis acids were used on tertiary alcohols, as mentioned in

Figure 44. However, there was another product formed and it was the majority of the product.

Electrophilic Aromatic Substitution

Another type of substitution is electrophilic aromatic substitution, which occurs when an electrophile reacts with electrons from the aromatic ring to form a bond. Some examples of electrophilic aromatic substitution are aromatic nitration, aromatic halogenation, aromatic sulfonation, Friedel-Crafts alkylation, and Friedel-Crafts acylation. Friedel-Crafts alkylation was explored under HSBM conditions to determine if the metal vial could act as a Lewis acid.

Toluene, 4-bromobenzyl bromide, and aluminum chloride were reacted under HSBM conditions for 16.67 hours, as shown in Figure 46.

Br AlCl3 1/8" ss ball & vial 16.67 hours Br r - r n n r n n . Figure 46. F iedel C afts alkylatio u de HSBM co ditio s

Figure 47. GC-MS of Friedel-Crafts alkylation of toluene and 4-bromobenzyl bromide.

Multiple products were formed according to the GC-MS in Figure 29. No products formed

without aluminum chloride, which indicated that the vial cannot act as a Lewis acid.

Diels-Alder

The Diels-Alder reaction was named after Otto Paul Hermann Diels and Kurt Alder.

They discovered the correct product formed in reactions that involve a diene and an alkene.42

They did experimental studies to support their claims, and made the reaction more generalized.42

Diels and Alder78 also outlined preparations for other reactions. The reaction occurs between a

conjugated 1,3-diene or diene and an alkene or dienophile (Figure 48).79 The mechanism of the

Diels-Alder is shown in Figure 48. 79

∆

43 Figure 48. Diels-Alder mechanism.

Since this reaction occurs through thermal energy, the energy of the ball mill can be

determined by experimental methods. The energy of the Diels-Alder reaction can be computationally calculated. A specific Diels-Alder reaction of interest occurs when anthracene and maleic anhydride react with each other to form9,10-dihydroanthracene-9,10-α,β-succinic

acid anhydride, shown in Figure 49. 79

76 O O O

8 9 1 O 7 2 ∆ O

6 3 5 10 4 O

43 Figure 49. Diels-Alder reaction of anthracene and maleic anhydride.

This Diels-Alder reaction normally takes place under solvent conditions by refluxing in xylene for 30 minutes. 79

Anthracene and its derivatives were examined as different substrates under HSBM conditions. In the 8000M mill, the Diels-Alder reaction was examined using anthracene and maleic anhydride; and 9-methylanthracene and maleic anhydride.80 The results from the 8000M

mill indicate, that the 1/8” stainless steel ball provides the best force per surface area. 80

The transition states were calculated and yields using the 8000M mill are shown in Figure 50. 80

They indicate that the energy of the 8000M mill is between 20 and 35 kcal/mol. 80

77 These reactions were done in the 8000D. The difference between the two mills is that the

8000D requires a counter balance for reactions. Another difference was found when no product

was formed in a reaction with anthracene and maleic anhydride, when they were ball milled

under the same conditions as the reaction in the 8000M. However, the Diels-Alder with maleic

anhydride and 9-methylanthracene did occur. Thus, the energy of the 8000D mill is between 17

and 20 kcal/mol. 80

The energetics of the Diels-Alder reaction was changed by having deactivating or

electron withdrawing groups on the 9 and 10 positions of anthracene. Having groups in those

positions increases the energy of the HOMO of the diene, which increases the energy needed to

form the carbon-carbon bonds. The cyano or nitrile group is a deactivating group.16 When 9- cyanoanthracene and maleic anhydride were under HSBM conditions in the 8000D mill, no reaction occurred. When 9,10-dicyanoanthracene and maleic anhydride were under HSBM conditions in the 8000D mill, no reaction occurred. Halogens also act as deactivating groups on the aromatic ring.16 Then, 9-bromoanthracene and maleic anhydride were under HSBM

conditions in the 8000D mill, no reaction occurred. Although this reaction did not work, it lead to modifying the methyl group on 9-methylanthracene by brominating it. Once 9- methylanthracene was brominated, it formed 9-bromomethylanthracene, which has a moderate

deactivating group on it. Then, maleic anhydride and 9-bromomethylanthracene were under

HSBM conditions in the 8000D mill, no reaction occurred.

78 Appendix B

Spectra 1H NMR 0.5 equiv. NaI Br 1/8" ss ball & vial I 16.67 hrs

79 GC-MS 0.5 equiv. NaI Br 1/8" ss ball & vial 16.67 hrs

80 GC-MS 0.5 equiv. NaI Br 1/8" ss ball & vial 16.67 hrs

81 GC-MS 0.5 equiv. NaI Br 1/8" ss ball & vial 16.67 hrs

82 1H NMR 0.5 equiv. LiI Br 1/8" ss ball & vial 16.67 hrs

83 GC-MS 0.5 equiv. LiI Br 1/8" ss ball & vial 16.67 hrs

84 GC-MS 0.5 equiv. LiI Br 1/8" ss ball & vial 16.67 hrs

85 GC-MS 0.5 equiv. LiI Br 1/8" ss ball & vial 16.67 hrs

86 GC-MS 0.5 equiv. LiI Br 1/8" ss ball & vial 16.67 hrs

87 1H NMR Br Br NaI 1/8" ss ball & vial 1 hr, COLD

88 1H NMR Br

NaBH4 1/8" ss ball & vial 16.67 hrs

89 GC-MS Br

NaBH4 1/8" ss ball & vial 16.67 hrs

90 GC-MS Br

NaBH4 1/8" ss ball & vial 16.67 hrs

91 GC-MS Br

NaBH4 1/8" ss ball & vial 16.67 hrs

92 GC-MS Br

NaBH4 1/8" ss ball & vial 16.67 hrs

93 GC-MS Br

NaBH4 1/8" ss ball & vial 16.67 hrs

94 GC-MS Br

NaBH4 1/8" ss ball & vial 16.67 hrs

95 GC-MS Br

NaBH4 1/8" ss ball & vial 16.67 hrs

96 GC-MS Br

NaBH4 1/8" ss ball & vial 16.67 hrs

97 1H NMR Br

NaI, 1-hexene 1/8" ss ball & vial 16.67 hrs

98 GC-MS Br

NaI, 1-hexene 1/8" ss ball & vial 16.67 hrs

99 GC-MS Br

NaI, 1-hexene 1/8" ss ball & vial 16.67 hrs

100 GC-MS Br

NaI, 1-hexene 1/8" ss ball & vial 16.67 hrs

101 GC-MS Br

NaI, 1-hexene 1/8" ss ball & vial 16.67 hrs

102 GC-MS Br

NaI, 1-hexene 1/8" ss ball & vial 16.67 hrs

103 GC-MS Br

NaI, 1-hexene 1/8" ss ball & vial 16.67 hrs

104 1H NMR Br

NaI, 1,4-cyclohexadiene 1/8" ss ball & vial 16.67 hrs mrwI141a 1000 -0.00 1.47 HDO 2.65 2.66 3.94 3.98 4.76 5.39 5.67 5.69 7.07 7.09 7.11 7.15 7.17 7.17 7.18 7.19 7.26 7.27 7.29 7.29 7.30 7.35 7.37 7.79 7.81

900

800

700

600

500

400

300

200

100

0 3.11 0.86 2.99 15.03

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 f1 (ppm)

105 GC-MS Br

NaI, 1,4-cyclohexadiene 1/8" ss ball & vial 16.67 hrs

106 GC-MS Br

NaI, 1,4-cyclohexadiene 1/8" ss ball & vial 16.67 hrs

107 GC-MS Br

NaI, 1,4-cyclohexadiene 1/8" ss ball & vial 16.67 hrs

108 GC-MS Br

NaI, 1,4-cyclohexadiene 1/8" ss ball & vial 16.67 hrs

109 GC-MS Br

NaI, 1,4-cyclohexadiene 1/8" ss ball & vial 16.67 hrs

110 1H NMR

NaI 1/8" ss ball & vial Cl 16.67 hrs

111 1H NMR

KOH dodecane Cl 1/8" ss ball & vial 16.67 hrs

112 1H NMR

KOH, 18-c-6 dodecane Cl 1/8" ss ball & vial 16.67 hrs

113 1H NMR

KI dodecane Cl 1/8" ss ball & vial 16.67 hrs

114 1H NMR

KI dodecane Br 1/8" ss ball & vial 16.67 hrs

115 GC-MS

KI dodecane Br 1/8" ss ball & vial 16.67 hrs

116 GC-MS

KI dodecane Br 1/8" ss ball & vial 16.67 hrs

117 GC-MS

KI dodecane Br 1/8" ss ball & vial 16.67 hrs

118 GC-MS

KI dodecane Br 1/8" ss ball & vial 16.67 hrs

119 GC-MS

KI dodecane Br 1/8" ss ball & vial 16.67 hrs

120 1H NMR

KI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

121 GC-MS

KI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

122 GC-MS

KI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

123 GC-MS

KI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

124 GC-MS

KI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

125 GC-MS

KI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

126 1H NMR

KI, 18-c-6 dodecane Br 1/8" ss ball & vial 16.67 hrs

127 GC-MS

KI, 18-c-6 dodecane Br 1/8" ss ball & vial 16.67 hrs

128 GC-MS

KI, 18-c-6 dodecane Br 1/8" ss ball & vial 16.67 hrs

129 GC-MS

KI, 18-c-6 dodecane Br 1/8" ss ball & vial 16.67 hrs

130 GC-MS

KI, 18-c-6 dodecane Br 1/8" ss ball & vial 16.67 hrs

131 GC-MS

KI, 18-c-6 dodecane Br 1/8" ss ball & vial 16.67 hrs

132 1H NMR

KOH dodecane Br 1/8" ss ball & vial 16.67 hrs

133 GC-MS

KOH dodecane Br 1/8" ss ball & vial 16.67 hrs

134 GC-MS

KOH dodecane Br 1/8" ss ball & vial 16.67 hrs

135 GC-MS

KOH dodecane Br 1/8" ss ball & vial 16.67 hrs

136 1H NMR

KOH, 18-c-6 dodecane Br 1/8" ss ball & vial 16.67 hrs

137 GC-MS

KOH, 18-c-6 dodecane Br 1/8" ss ball & vial 16.67 hrs

138 KOH dodecane Br 1/8" ss ball & vial 16.67 hrs

139 1H NMR

NaI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

140 GC-MS

NaI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

141 GC-MS

NaI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

142 GC-MS

NaI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

143 GC-MS

NaI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

144 GC-MS

NaI, Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

145 1H NMR

dodecane 1/8" ss ball & vial r B 16.67 hrs

146 GC-MS

dodecane 1/8" ss ball & vial r B 16.67 hrs

147 GC-MS

dodecane 1/8" ss ball & vial r B 16.67 hrs

148 GC-MS

dodecane 1/8" ss ball & vial r B 16.67 hrs

149 GC-MS

dodecane 1/8" ss ball & vial r B 16.67 hrs

150 1H NMR

Argon dodecane Br 1/8" ss ball & vial 16.67 hrs

151 1H NMR

Argon 1/8" ss ball & vial r B 16.67 hrs

152 GC-MS

Argon 1/8" ss ball & vial r B 16.67 hrs

153 GC-MS

Argon 1/8" ss ball & vial r B 16.67 hrs

154 GC-MS

Argon 1/8" ss ball & vial r B 16.67 hrs

155 GC-MS

Argon 1/8" ss ball & vial r B 16.67 hrs

156 GC-MS

Argon 1/8" ss ball & vial r B 16.67 hrs

157 GC-MS

Argon 1/8" ss ball & vial r B 16.67 hrs

GC-MS

158 Argon 1/8" ss ball & vial r B 16.67 hrs

159 1H NMR

dodecane Teflon Br 16.67 hrs

160 GC-MS

dodecane Teflon Br 16.67 hrs

161 dodecane Teflon Br 16.67 hrs

162 GC-MS

dodecane Teflon Br 16.67 hrs

163 GC-MS

dodecane Teflon Br 16.67 hrs

164 GC-MS

dodecane Teflon Br 16.67 hrs

165 1H NMR

Argon dodecane Br Teflon 16.67 hrs

166

1H NMR

Argon Teflon Br 16.67 hrs

167 GC-MS

Argon Teflon Br 16.67 hrs

168 GC-MS

Argon Teflon Br 16.67 hrs

169 GC-MS

Argon Teflon Br 16.67 hrs

170 GC-MS

Argon Teflon Br 16.67 hrs

171 GC-MS

Argon Teflon Br 16.67 hrs

172 GC-MS

Argon Teflon Br 16.67 hrs

173 GC-MS

Argon Teflon Br 16.67 hrs

174 GC-MS

Argon Teflon Br 16.67 hrs

175 GC-MS

Argon Teflon Br 16.67 hrs

176 1H NMR

PTSA OH KI 1/8" ss ball & vial 16.67 hrs

177 1H NMR

AlBr3 1/8" ss ball & vial OH 16.67 hrs

178 GC-MS

AlBr3 1/8" ss ball & vial OH 16.67 hrs

179 GC-MS

AlBr3 1/8" ss ball & vial OH 16.67 hrs

180 GC-MS

AlBr3 1/8" ss ball & vial OH 16.67 hrs

181 GC-MS

AlBr3 1/8" ss ball & vial OH 16.67 hrs

182 1H NMR

Br 1/8" ss ball & vial Br 16.67 hours Br Br

183 GC-MS

Br 1/8" ss ball & vial Br 16.67 hours Br Br

184 GC-MS

Br 1/8" ss ball & vial Br 16.67 hours Br Br

185 GC-MS

Br 1/8" ss ball & vial Br 16.67 hours Br Br

186 GC-MS

Br 1/8" ss ball & vial Br 16.67 hours Br Br

187 1H NMR

Br AlCl3 1/8" ss ball & vial 16.67 hours Br

188 GC-MS

Br AlCl3 1/8" ss ball & vial 16.67 hours Br

189

190 1H NMR

OH OH OH OH

1/8" ss ball & vial 16.67 hrs

191 GC-MS

OH OH

PTSA 1/8" ss ball & vial Single Mill 16.67 hrs

192 GC-MS

OH OH

PTSA 1/8" ss ball & vial Single Mill 16.67 hrs

193 GC-MS

OH OH

PTSA 1/8" ss ball & vial Single Mill 16.67 hrs

194 GC-MS

OH OH

PTSA 1/8" ss ball & vial Single Mill 16.67 hrs

195 GC-MS

OH OH

PTSA 1/8" ss ball & vial Single Mill 16.67 hrs

196 1H NMR

OH OH

PTSA 1/8" ss ball & vial Single Mill 16.67 hrs

197 13C NMR

OH OH

PTSA 1/8" ss ball & vial Single Mill 16.67 hrs

198 1H NMR

OH OH OH OH

PTSA 1/8" ss ball & vial 1 hr

199 GC-MS

OH OH OH OH

PTSA 1/8" ss ball & vial 1 hr

200 1H NMR

OH OH

PTSA 1/8" ss ball & vial 8 hrs

201 GC-MS

OH OH

PTSA 1/8" ss ball & vial 8 hrs

202 GC-MS

OH OH

PTSA 1/8" ss ball & vial 8 hrs

203 GC-MS

OH OH

PTSA 1/8" ss ball & vial 8 hrs

204 GC-MS

OH OH

PTSA 1/8" ss ball & vial 8 hrs

1H NMR

205 OH OH

PTSA Dual Mill 1/8" ss ball & vial 16.67 hrs

206 13C NMR

OH OH

PTSA Dual Mill 1/8" ss ball & vial 16.67 hrs

207 GC-MS

OH OH

PTSA Dual Mill 1/8" ss ball & vial 16.67 hrs

208 GC-MS

OH OH

PTSA Dual Mill 1/8" ss ball & vial 16.67 hrs

209 GC-MS

OH OH

PTSA Dual Mill 1/8" ss ball & vial 16.67 hrs

210 GC-MS

OH OH

PTSA Dual Mill 1/8" ss ball & vial 16.67 hrs

211 OH OH O

PTSA toluene 16 hrs

1H NMR

212 13C NMR

OH OH O

PTSA toluene 16 hrs

213 GC-MS

OH OH O

PTSA toluene 16 hrs

214 GC-MS

OH OH O

PTSA toluene 16 hrs

215 1H NMR

OH OH O

PTSA EtOH 16 hrs

216 GC-MS

OH OH O

PTSA EtOH 16 hrs

217 GC-MS

OH OH O

PTSA EtOH 16 hrs

218 GC-MS

OH OH O

PTSA EtOH 16 hrs

219 1H NMR

O OH OH

PTSA Cl3CH2OH 16 hrs

220 GC-MS

O OH OH

PTSA Cl3CH2OH 16 hrs

221 1H NMR OH OH OH OH 1/8" ss ball & vial 16.67 hrs

222 1H NMR

O OH OH

Zinc dust 1/8" ss ball & vial 1 hr

223 1H NMR

224 13C NMR

225 GC-MS

226 GC-MS

227 GC-MS

228 1H NMR

OH OH

229 13C NMR OH OH

230 GC-MS

OH OH

231 GC-MS

OH OH

232 GC-MS

OH OH

233 1H NMR O O

Mg, I2 1/8" ss ball & Mg vial 16.67 hrs

234 GC-MS O O

Mg, I2 1/8" ss ball & Mg vial 16.67 hrs

235 GC-MS O O

Mg, I2 1/8" ss ball & Mg vial 16.67 hrs

236 GC-MS O O

Mg, I2 1/8" ss ball & Mg vial 16.67 hrs

237 GC-MS O O

Mg, I2 1/8" ss ball & Mg vial 16.67 hrs

238 GC-MS O O

Mg, I2 1/8" ss ball & Mg vial 16.67 hrs

239 GC-MS O O

Mg, I2 1/8" ss ball & Mg vial 16.67 hrs

240 GC-MS O O

Mg, I2 1/8" ss ball & Mg vial 16.67 hrs

241 O O

Mg, I2 1/4" ss ball & vial 16.67 hrs 1H NMR

242 1H NMR O

OH OH 3 NaH 1/8" ss ball & vial 16.67 hrs OH NH4Cl

243 GC-MS O

OH OH 3 NaH 1/8" ss ball & vial 16.67 hrs OH NH4Cl

244 GC-MS O

OH OH 3 NaH 1/8" ss ball & vial 16.67 hrs OH NH4Cl

245 GC-MS O

OH OH 3 NaH 1/8" ss ball & vial 16.67 hrs OH NH4Cl

246 GC-MS O

OH OH 3 NaH 1/8" ss ball & vial 16.67 hrs OH NH4Cl

247 1H NMR dih dro uinidine -chlorobenzoate y q p HO OH K3[Fe(CN)6] K2CO3 OsO4 tBuOH:H2O 1:1 24 hrs RT

248 GC-MS dih dro uinidine -chlorobenzoate y q p HO OH K3[Fe(CN)6] K2CO3 OsO4 tBuOH:H2O 1:1 24 hrs RT

249 1H NMR HO OH HO OH PTSA 1/8" ss ball & vial 16.67 hrs

250 13C NMR HO OH HO OH PTSA 1/8" ss ball & vial 16.67 hrs

251 HO OH HO OH PTSA 1/8" ss ball & vial 16.67 hrs

GC-MS

252 HO OH HO OH PTSA 1/8" ss ball & vial 16.67 hrs

GC-MS

253 HO OH HO OH PTSA 1/8" ss ball & vial 16.67 hrs

GC-MS

254 HO OH HO OH PTSA 1/8" ss ball & vial 16.67 hrs

GC-MS

255 GC-MS HO OH HO OH PTSA 1/8" ss ball & vial 16.67 hrs

256 1H NMR HO OH HO OH PTSA Dry 1/8" ss ball & vial 16.67 hrs

257 HO OH HO OH PTSA Dry 1/8" ss ball & vial 16.67 hrs

13C NMR

258 1H NMR HO OH

PTSA toluene 16 hrs

259 13C NMR HO OH

PTSA toluene 16 hrs

260 1H NMR HO OH O PTSA EtOH 16 hrs

261 13C NMR HO OH O PTSA EtOH 16 hrs

262 GC-MS HO OH O PTSA EtOH 16 hrs

263 GC-MS HO OH O PTSA EtOH 16 hrs

264 GC-MS HO OH O PTSA EtOH 16 hrs

265 GC-MS HO OH O PTSA EtOH 16 hrs

266 1H NMR

HO OH O O PTSA Acetone 1/8" ss ball & vial 16.67 hrs

267 13C NMR

HO OH O O PTSA Acetone 1/8" ss ball & vial 16.67 hrs

268 GC-MS

HO OH O O PTSA Acetone 1/8" ss ball & vial 16.67 hrs

269 GC-MS

HO OH O O PTSA Acetone 1/8" ss ball & vial 16.67 hrs

270 GC-MS

HO OH O O PTSA Acetone 1/8" ss ball & vial 16.67 hrs

1H NMR

271 O O

PTSA 1/8" ss ball & vial 16.67 hrs

HO HO

OH OH

272 1H NMR HO HO

OH OH PTSA O O 1/8" ss ball & vial 16.67 hrs

H H

e MeO M O

273 1H NMR

PPh Br 3 1. nBuLi 2. Benzophenone

274 GC-MS

PPh Br 3 1. nBuLi 2. Benzophenone

275 GC-MS

PPh Br 3 1. nBuLi 2. Benzophenone

276 1H NMR

O2N PPh Br 3 1. nBuLi 2. 4-nitrobenzophenone

NO2

277 GC-MS

O2N PPh Br 3 1. nBuLi 2. 4-nitrobenzophenone

NO2

278 GC-MS

PPh Br 3 1. nBuLi 2. 4-nitrobenzophenone

O2N NO2

279 PPh Br 3 1. nBuLi 2. 4-nitrobenzophenone

GC-MS O2N NO2

280 GC-MS

O2N NO2

281 GC-MS

O2N NO2

282 1H NMR dihydroquinidine p-chlorobenzoate K3[Fe(CN)6] OH OH K2CO3 OsO4 tBuOH:H2O 1:1 25 hrs RT

283 13C NMR

dihydroquinidine p-chlorobenzoate OH OH K3[Fe(CN)6] K2CO3 OsO4 tBuOH:H2O 1:1 25 hrs RT

284 1H NMR

K3[Fe(CN)6] K2CO3 OsO4 tBuOH:H2O 1:1 25 hrs RT

285 1H NMR

OH OH

1. PhMgBr 2. 1.5 M HCl HO

286 GC-MS

OH OH

1. PhMgBr 2. 1.5 M HCl HO

287 GC-MS

OH OH

1. PhMgBr 2. 1.5 M HCl HO

288 GC-MS

OH OH

1. PhMgBr 2. 1.5 M HCl HO

289 GC-MS

OH OH

1. PhMgBr 2. 1.5 M HCl HO

290 GC-MS

OH OH

1. PhMgBr 2. 1.5 M HCl HO

291 GC-MS

OH OH

1. PhMgBr 2. 1.5 M HCl HO

292 1H NMR Br

NBS, Benzoyl peroxide Light CCl4, 1 hr

293 1H NMR O O

O 1/8" ss ball & vial O 16.67 hrs

O O

294 1H NMR O O O

O 1/8" ss ball & vial O 16.67 hrs

295 1H NMR CN CN O O

O 1/8" ss ball & vial O 16.67 hrs

O O

296 1H NMR CN CN O O

O 1/8" ss ball & vial O 16.67 hrs

O O CN CN

297 1H NMR Br Br O O

O 1/8" ss ball & vial O 16.67 hrs

O O

298 1H NMR Br Br

O O

O 1/8" ss ball & vial O 16.67 hrs

O O

299