Honors Projects

Green Chemistry Using Bismuth(III) Salts: Synthesis of Cyclic Acetals and Allylation of Tetrahydropyranyl Ethers and Aldehydes

Scott W. Krabbe — Tue, 27 Apr 2010 12:00:43 PDT

Research in our group focuses on environmentally friendly organic synthesis using bismuth compounds. With increasing environmental concerns, the need for environmentally friendly organic synthesis following Green Chemistry principles has assumed increased importance. The Pollution Prevention Act, passed in 1990, was especially important in increasing an interest in Green Chemistry, which is the design and redesign of chemical processes with a view of improving safety. Our group focuses on synthetic methodology i.e. the transformation of one functional group to another. Such transformations are of special relevance in the pharmaceutical industry for manufacture of life saving drugs. Many of the current organic synthesis methods utilize toxic and corrosive catalysts and reagents. In contrast, methods utilizing bismuth(III) salts are environmentally friendly because most bismuth compounds are non-toxic, non-corrosive, and inexpensive.

The goal of this project was to utilize bismuth(III) triflate and bismuth(III) bromide, as catalysts for the synthesis of cyclic acetals, the allylation of tetrahydropyranyl and tetrahydrofuranyl ethers, and the allylation of aldehydes. All these processes utilize many Green Chemistry principles such as the use of non-toxic reagents, room temperature reaction conditions and at times solvent-free conditions.

Complexes of Phosphine Ligands with the Main Transition Elements

Richard R. Clikeman '69 — Wed, 24 Mar 2010 14:22:00 PDT

It has been long known that ammonia as well as many primary, secondary and tertiary amines, acts as a ligand forming complexes with the main transition elements.

Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Catalyzed Allylation of Cyclic Acetals

Matthew J. Spafford, '09 — Mon, 03 Aug 2009 06:06:13 PDT

Cyclic acetals (dioxolanes, dioxanes, and dithianes) are common protecting groups in organic synthesis but they can also be converted to other useful functional groups. A bismuth(III) triflate-catalyzed multi component reaction involving the allylation of cyclic acetals followed by in situ derivatization with acid anhydrides to generate highly functionalized esters and thioesters has been developed under solvent-free conditions. Most reagents used to date for the allylation of cyclic acetals are highly corrosive or toxic and are often required in stoichiometric amounts. In contrast, the use of a relatively non-toxic and non-corrosive bismuth(III) based catalyst makes this methodology benign and attractive.

A Study of the Solvolysis Reactions of Tetrahydrofurfuryl Tosylate

Rebecca Centko '00 — Mon, 29 Sep 2008 13:52:05 PDT

The solvolysis of epoxycarbinyl substrates 1 has been the subject of several mechanistic studies. In spite of these investigations, it has not been established whether these solvolysis reactions proceed with anchimeric assistance from the epoxide oxygen and involve an oxabicyclobutonium ion intermediate or whether unassisted solvolysis occurs. Conflicting data in the literature suggest that the ability of the epoxide oxygen to provide anchimeric assistance is dependant upon structural and electronic features of the epoxycarbinyl substrate in question. The aim of this project was to study the nucleophilic substitution reactions of tetrahydrofurfuryl and tetrahydropyranyl sulfonates 2a and 2b as well as cyclopentylmethyl and cyclohexylmethyl sulfonates 3a and 3b, respectively, to probe the effect of a neighboring oxygen on solvolyses rates and product distribution. The rates of solvolyses of cyclopentylmethyl tosylate and tetrahydrofuranomethyl tosylate have been compared to determine if the oxygen lends anchimeric assistance to the leaving group in the solvolyses reactions of the latter. This research has led to an increased understanding of the role of the ether oxygen in reaction of tetrahydrofurfuryl tosylate.

Characterizing Conformational Changes Along the Dimerization Helix of the Global Regulator, FNR, Using Fluorescence Spectroscopy

Melanie Zupancic '03 — Mon, 29 Sep 2008 13:52:03 PDT

The FNR protein is a transcription factor that allows Escherichia coli to undergo anaerobic cellular respiration. It is known to positively regulate the expression ofseveral genes required for anaerobic respiration as well as negatively regulate genes responsible for aerobic respiration. Consequently, FNR is active under anaerobic conditions and inactive under aerobic conditions. Although the tertiary structure ofFNR is unknown, previous studies have indicated that FNR is inactive in the monomeric state and active in the dimeric state. Thus, it is believed that in anaerobic conditions, FNR undergoes a confonnational change from the monomeric to dimeric state. The mechanism involved in going from the monomeric to dimeric state is not completely understood, but it is thought to be triggered by the acquisition ofa [4Fe-4S]2+ cluster in the N-tenninal region ofFNR. The acquisition ofthe cluster causes a confonnational change to be transmitted through the allosteric domain to the dimerization helix resulting in the active dimeric species. Infonnation regarding the environment of amino acid residues in the dimerization helix in both the active and inactive fonns of FNR could be helpful in eliciting a better understanding ofthe dimerization mechanism. Such environmental conditions can be detennined by the fluorescent properties ofthe amino acid, tryptophan. Surface exposed tryptophan residues are expected to have a longer Amax than those buried in the hydrophobic core. In order to gain insight into the environment ofthe amino acids on the dimerization helix we have created tryptophan mutants (LWI46, MW147, MW157, KW163, and KW164) that either lay on or near the helix. The mutants KW163 and KW164 all lie on the periphery ofthe helix while LW146, MW147 and MW157 lie on the helix. Ofthe five mutants, KW163 retained anaerobic activity most similar to that of the wild type indicating that its structure is similar to the wild type protein with the exception ofthe single amino acid substitution. By comparing the fluorescence ofthe active and inactive forms of KW163, we hope to gain a better understanding ofthe dimerization mechanism ofFNR.

Synthesis and Nucleophilic Reactions of Bifunctional Thiourea S,S,S-Trioxides

Dan Webb '89 — Mon, 29 Sep 2008 13:51:59 PDT

The synthesis of bifunctional thioureas and the corresponding thiourea S,S,S-trioxides has been examined. Two methods for the synthesis of the bisthioureas were employed. One involved the treatment of a diamine with silicon tetraisothiocyanate in benzene. The second involved treatment of the amine with ammonium thiocyanate in dilute acid. This latter synthesis was superior because of the ease of its use, the high yields obtained, and the purity of the products. Though this synthesis worked well for the preparation of phenylene-l,4-bis(thiourea), it yielded only bisthiocyanate salts in the synthesis of aliphatic thioureas. The oxidation of the bisthioureas was carried out using peracetic acid or hydrogen peroxide to give the corresponding thiourea S,S,S-trioxides.

Photochemistry of Nitrous Acid and Nitrite Ion

Christopher L. Exstrom '90 — Mon, 29 Sep 2008 13:51:57 PDT

Aqueous solutions of HONO (ranging from 0.010M to 0.057M) and NO2 (ranging from 0.025M to 0.035M) were each photolyzed with nm ultraviolet (UV) light. In the presence of benzene scavenger, DH radical intermediate was indicated by formation of p-nitrosophenol (PNP). Ultraviolet/visible (UV/vis) absorption spectra of photolyzed aqueous HONO/benzene solutions showed the presence of PNP by its characteristic absorption at 298 nm. UV/vis absorption spectra of photolyzed aqueous NO -benzene solutions showed no evidence of PNP formation. Other compounds such as scavengers were toluene, benzoic acid, and terephthalic acid. UV/vis spectra of photolyzed aqueous HOND/scavenger solutions showed an Int n e road peak in the 295-310 nm range, Indicating that the scavenger was hydroxylated by OH, formed from HONO photolytic dissociation, and subsequently nitrostated by reaction with excess HONO. Hydrugen peroxide, a known OH producer, was photolyzed in the presence of benzene to verify the proposed OH-scavenging sequence under varying pH condItions. UV/vis spectra showed evidence of hydrocybenzene formation upon photolysis. The thermal decomposition of HONO was studied and a kinetic order with respect to HONO, of 0.5+-0.5 was determined. Quantitative data concerning the photochem cal de omposition of HONO was too inconsistent to make reasonable comparisons to thermal decomposition data.

Electrostatically Paired Porphyrin and Phthalocyanine: Equilibria and Electrochemical Oxidation

Libin Ho '91 — Mon, 29 Sep 2008 13:51:55 PDT

A synthetic model system for the special pair in the photosynthetic reaction center of bacteria has been prepared from electrostatically paired porphyrin and phthalocyanine molecules. Use of rigorously dry propylene carbonate as the solvent allowed complex fonnation to occur between tetra-(N-methyl-4-pyridyl)porphyrin hexafluorophosphate (H2TMPyP(PF6)4) and tetraphenylphosphonium tetrasulfatophthalocyanine (Ph4P)4H2TSPc molecules. The stoichiometry of the complex was determined to be 1:1 by Job's method and the pair formation constant K1 was estimated to be 1x108.T he dependence of K1 on ionic strength was studied at various concentrations of tetra-n-butylammonium tetrafluoroborate BU4NBF4. With increasing ionic strength K1 decreases as expected according to the Debye-Huckellimiting law. Using an ionic strength of 2 mM (BU4NBF4) in PC, the extent of pairing was found to be almost 100%. Under these conditions tetrasulfatophthalocyanine and the electrostatically paired complex were oxidized at E1/2's of 0.453 and 0.350 V vs SCE (aq), respectively. From evaluation by the Nemst equation of the measured potential difference between paired and unpaired tetrasulfatophthalocyanine, the ratio of [C]K2 / [C+]K1 is estimated to be 55. K2 is the equilibrium constant for the formation of the singly-oxidized pair. The significance of the value of the ratio leads to an estimate of K2 = 6 x 109 at an ionic strength of 2.0 mM.

The Reactions of N-Phenylaminoiminomethanesulfonic Acid (PAIMSO) with Meldrum's Acid

Milana-Minja Maletic '91 — Mon, 29 Sep 2008 13:51:54 PDT

Synthesis of Aliphatic Bis(Thioureas)

Donald G. McEwen IV '91 — Mon, 29 Sep 2008 13:51:51 PDT

The synthesis of aliphatic bifunctional thioureas have been attempted using several nucleophilic displacement reactions. The first method involved treatment of an aliphatic diamine with ammonium thiocyanate, under two different sets of reaction conditions. The first set of reaction conditions utilized water as the solvent, while second employed acetone as the solvent. Both of the reactions utilizing l,2-ethylenediamine and ammonium thiocyanate did not afford the desired bis(thioureas). In particular, the crystalline solid obtained from the reaction carried out in water was 57.8 ± 0.05 % thiocyanate by mass. The second nucleophilic addition method involved the treatment of both 1,2-ethylenediamine and 1,6-hexanediamine diamine with silicon tetraisothiocyanate in anhydrous benzene. The product from the reaction of l,6-hexanediamine with silicon tetraisothiocyanate in anhydrous benzene was found to be 40.3 ± 2.07 % thiocyanate by mass. The third set of reaction conditions involved treatment of 1,6hexanediamine with silver thiocyanate in concentrated ammonium hydroxide. As a result of the presence characteristic thiocyanate IR absorbance peak at 2100 cm-1 in the product, it was found to contain thiocyanate ions. It was concluded that the product was composed of mainly the 1,6 hexanediamine thiocyanate salts. The final set of reaction conditions involved treatment of 1,6hexanediamine with silver thiocyanate and thiourea, in concentrated ammonium hydroxide. Upon analysis of the resulting reaction mixtures, it was determined that each fraction contained no thiocyanate anion or starting thiourea. Further work needs to be carried out in order to determine the products.

Synthesis of New Reagents for the Detection of Fingerprints and Amino Acids

Bjorn Borup '92 — Mon, 29 Sep 2008 13:51:49 PDT

DFO (1,8-Diazafluoren-9-one) is a new reagent for the detection of latent fingerprints. It reacts with amino acids present in fingerprints to give a fluorescent product, and is an improvement over ninhydrin which has been used in forensic laboratories for years. The object of this work was to synthesize new analogs of ninhydrin and DFO. The preparation of 9-Hcyclopenta[1,2-b:3,4-b'] dipyrazine-9-one (A) was attempted but was not successful. Currently the synthesis of 7H-cyclopenta[b]pyridine-S,6,7-trione (B) is being completed. The compound 9H-cyclopenta[1,2-b]pyrazine[3,4b] pyridine-9-one (C) will then be made from (B), an analog of ninhydrin.

Analysis of Carbon across the Cenomanian-Turonian Boundary

Andrew J. Carr '92 — Mon, 29 Sep 2008 13:51:48 PDT

Following the work of Wolbach et al., who studied reduced carbon across the 65 Ma-old Cretaceous-Tertiary extinction boundary, a study was conducted to analyze reduced carbon across the 92 Ma-old Cenomanian-Turonian (C-T) extinction horizon, in the hope that evidence could be gathered which might support a particular mechanism for these extinction events. Currently two sample sites are being analyzed for reduced carbon content at the C-T boundary: Red Wash, New Mexico and Chispa Summit, Texas. Both sample sites are from the Western Interior Basin of North America. During the time of the extinctions 92 million years ago, the basin was an inland sea. Preliminary data suggest a decrease in the amount of carbonaceous residue found at the boundary at both sample sites. This would indicate that the extinction event was not rapid, as lower amounts of reduced carbon are generally more characteristic of extinctions caused by slow changes in climate vs sudden changes caused by catastrophic events. Slow climate changes would allow microorganisms time to digest (oxidize) the carbon in dead plankton before sedimentation, thus decreasing the amount of reduced carbon preserved in the rock. A mechanism for the C-T extinctions consistent with previous data as well as preliminary results obtained in this study is the opening of deep sea fissures at the ocean floor, increasing certain metal concentrations in seawater, and, more importantly, increasing water temperatures. Plankton unable to adapt to these new conditions would become extinct.

Photochemistry of Nitrous Acid and Nitrite Ion

Jane A. Johnson '92 — Mon, 29 Sep 2008 13:51:46 PDT

A study of the solution phase photochemistry of the nitrous acid/nitrite ion system in both water and non-aqueous solvents has been undertaken. Photolysis at 366nm of the aqueous system is known to form hydroxyl radical and nitric oxide. The relative contributions of the molecular and ionic forms to the photochemical production of radicals is unknown. Scavenging reactions of the hydroxyl radicals in aqueous and nonaqueous solution are used to determine the relative production of OH. formed by photolysis of HONO and N02-. Molecular nitrous acid is isolated from its conjugate base by extraction into benzene from water. The thermal decomposition of HONO in the extraction mixture was measured and it was found to be second order with respect to nitrous acid. The product of the photolysis of this benzene solution, PNP, indicates hydroxyl radical formation. Nitrite ion dissolves in aprotic solvents, such as DMF and DMSO, without the formation of nitrous acid. Photolysis of these solutions appears to result in the formation of phenol only. The quantum yield for the formation of phenol was determined to be 1.8 ± 0.3 x 10-2 mol/eins.

The Development of an Improved Extraction Method for the Determination of Cocaine Metabolite in Human Urine

Leanne M. Nieukirk '92 — Mon, 29 Sep 2008 13:51:44 PDT

Benzoyl ecgonine (BE) is the primary metabolite of cocaine. Detection of BE in urine is therefore an indication of cocaine usage. The goal of this research is to improve the extraction efficiency in order to increase the sensitivity of the method of determining cocaine usage through urine analysis. A technique was developed to efficiently extract BE from aqueous solution. Ultraviolet/Visible Spectroscopy was used to determine the extraction conditions for which optimum extraction of BE into organic solvent occurred.

Photochemistry of Nitrous Acid and Nitrite Ion

Kathryn E. Shanks '93 — Fri, 26 Sep 2008 13:50:31 PDT

Research is currently underway to elucidate the photochemical decomposition mechanism of nitrous acid and nitrite ion in aqueous and non-aqueous media. The quantum yield of the photochemical disappearance of nitrous acid and nitrite, as a function of pH and nitrous acid/nitrite ion concentration ratios, was examined. Spectroscopic studies have been done with nitrite ion in various aprotic organic solvents. Similar work has been started with molecular nitrous acid that was produced in aqueous solution and then extracted into organic solvents. These organic solvents were employed in order to study the quantum yield with respect to NO2- and HONO without the complications of the acid dissociation equilibrium seen in aqueous solutions. Other work includes the product analysis of hydroxyl radical scavenging reactions.

Organochlorine Pesticide Residues in the Neotropical Migratory Passerine Birds

Birthe Borup '94 — Fri, 26 Sep 2008 13:50:30 PDT

In 1874 Othmar Ziedlert a German chemist was working on the synthesis and characterization of substituted aromatic hydrocarbons. In the process of his work he synthesized dichloro-diphenyl-trichloro-ethane commonly known as DDT. It was not until 1930 that its use as an insecticide was detected by Paul Muller who found that it was effective against potato beetles (Leptinotarsal declineata) and clothes moths, (Tineola besselliella ) (Dunlap 1981). Pure DDT is a white crystalline solid with a melting point of 109 C, and a vapor pressure of 0.025mPa at 20 C. Technical grade DDT is a white amorphous powder, consisting of a mixture of active 4,4'-DDT(65-80%), inactive 2,4'-DDT(14-21%), up to 4% DDD (1,1'-(2,2-dichloroethylidene) bis (4-chlorobenzene), and traces of 2,2'DDT. This mixture readily dissolves in xylene and tetraline (600 g/L), moderately dissolves in mineral oil and kerosene (50-80g/L), and is practically insoluble in water (1.2ug/ml) (Elvers et al. 1989).

The Photochemistry of the Nitrite Ion

Deborah Anna Cull '94 — Fri, 26 Sep 2008 13:50:29 PDT

The photolysis of aqueous nitrite ion, N02-, yields the free radicals nitric oxide, NO*, and hydroxyl radical, *OH. It has been found by Treinin and Hayon and supported in this laboratory that no net reaction occurs when nitrite is photolyzed in pure water. Zafiriou has extensively studied the solar photolysis of nitrite-containing seawater, and has detected increased partial pressures of NO* during the day, as well as decreased nitrite concentrations, which both suggest that net photolysis of nitrite has occurred. In pure water, the *OH and NO* radicals produced from the photolysis of NO2- presumably recombine and ultimately reproduce NO2-. In the presence of benzene, a known radical scavenger, this process is interrupted and net photolysis of nitrite is observed. This particular scavenging process is of primary interest to this research. Aqueous nitrite saturated with benzene has been photolyzed at 366nm, a wavelength present in solar radiation at which nitrite absorbs. The effect of varying the pH as well as the solvent for maximal extraction of the scavenger product has been studied. Ideally, the identity of the product will be obtained, leading to the quantification of the scavenging process. The reaction has been monitored both spectrophotometrically as well as by a nitrite-specific electrode. In addition to the photochemical reaction, the thermal reaction of nitrite in the presence of benzene has been tested. The scavenging of the hydroxyl radical by benzene has also been studied by producing *OH via hydrogen peroxide and a catalyst. Long range goals include the determination of the quantum yield with respect to nitrite disappearance, with the results compared to the photolysis of nitrous acid, a process that occurs in polluted atmospheres.

A Synthetic Study of an Organophosphorous Compound as an Acetylcholinesterase Inhibitor

Sulay Jhaveri '94 — Fri, 26 Sep 2008 13:50:28 PDT

Acetylcholinesterase is the enzyme that catalyzes the hydrolysis of acetylcholine. Based on the transition state of the catalysis, and what is known about the structure of the enzyme, a synthetic study has been conducted on an organophosphorous inhibitor which is capable of probing into the stereospecificity of the enzyme. The asymmetric synthesis was initiated with I-proline, and several methods were employed in phosphorylation in order to get the desired product.

Ignition and Environmental Effects of Wildfires as Related to Giant Impacts

Gregory S. Kufner '94 — Fri, 26 Sep 2008 13:50:27 PDT

Soot has been discovered by Wolbach et al. at the Cretaceous-Tertiary boundary in various geographic locations, supporting the theory that worldwide wildfires were ignited by the impact of a giant meteorite which caused the mass extinction 65 million years ago. This project examines a deep sea core sample from the North Central Pacific Ocean for evidence of soot. Soot discovery at this site, the only deep ocean site to be studied, supports the theory that soot distribution from the fires was worldwide.

In another project, samples from the suevite breccia of the Kara Ust-Kara craters in Russia (unrelated to the KT impact) were examined for' soot to find evidence of fires triggered by a different impact. After demineralization to remove the minerals in the rock, reduced carbon was found in both the core and crater samples. Oxidation in dichromate solution removed the organic carbon (kerogen) form the samples. Analysis of the post-oxidation residues under a scanning electron microscope confirmed the presence of soot in both the core and crater samples.

Pursuit of a Chiral Amino Aldehyde Intermediate in the Synthesis of (+)-Obafluorin, a B-Lactone Antibiotic

Jim Cwik '96 — Fri, 26 Sep 2008 13:50:23 PDT

This research is focused on synthesizing a chiral amino aldehyde from L-Serine. The proposed synthesis of the amino aldehyde would yield a stereochemically pure product working through an L-Serine beta-lactone intermediate. The amino aldehyde is a proposed intermediate in the synthesis of (+)-obafluorin, a beta-lactone antibiotic of interest. The proposed synthesis might provide a simpler, more versatile way to synthesize obafluorin.