Organic Chemistry Commons^™

Synthesis Of A Halogenated Glyoxime For Cobalt Deposition Suppression, Liam S. Allen

Honors Theses

Dr. Qiang Huang at the University of Alabama is a chemical engineering professor and works on the electrodeposition of metals to create circuitry. During this process suppressive molecules may be added to control help the process. This project focuses on synthesizing an alpha-halogenated glyoxime to test whether the compound is a more effective suppressant in comparison to regular glyoximes. More specifically the target chemical is called bromo-dimethylglyoxime which is created in a two-stage reaction. The starting material, diacetyl monoxime, is brominated at the alpha carbon position. The product of this reaction, officially called bromodimethylglyoxalmonoxime, is then reacted with hydroxylammonium chloride …

Urea-Based Boronium Salts As Antimicrobial Agents, Gabriel Allen Merchant

Honors Theses

Quaternary ammonium compounds (QACs) are widely used in disinfectants due to their ability to inhibit the growth of and eliminate microbes. The potency, broad-spectrum activity, and low cost of QACs have made them a cornerstone of modem hygiene. In recent years, QACs have garnered many health and safety concerns due to their overuse and subsequent accumulation in the environment. The increased use of QACs has further led to an increase in antimicrobial-resistant bacteria, making the synthesis of novel antibacterial compounds vital to combat this growing threat. Recent advances in boronium salts offer a unique alternative to address these adverse effects. …

Synthesis Of Novel 1,2,3-Triarylnaphthalenes Via Intermolecular Dehydro-Diels-Alder Reaction, Ethan C. Dailey

Honors Theses

The photo-dehydro-Diels–Alder (PDDA) reaction is a useful method for the construction of substituted naphthalene derivatives from acyclic precursors. While intramolecular variants of this transformation are well established, intermolecular PDDA reactions remain rare due to challenges associated with controlling reactivity under photochemical conditions. Previous studies suggest that electron-withdrawing substituents can promote intermolecular cycloaddition by increasing alkyne polarization and stabilizing reactive intermediates. In this work, the effect of enhanced electron-withdrawing character on intermolecular PDDA reactivity was investigated through the incorporation of a 2,3,5,6-tetrafluoropyridinyl substituent. Corresponding alkyne substrates were synthesized and subjected to photochemical conditions, resulting in the formation of 1,2,3-triarylnaphthalene products. The …

Synthesis Of Piperidine Heterocycles With Specific Functional Groups Via Sn2 Reactions, Teyanna Monroe

Honors Theses

Piperidine is a heavily utilized nitrogen containing heterocycle found in numerous pharmaceutical agents, solidifying its importance as a building block in drug development. The focus of this research is to investigate different mechanisms of action for adding and replacing various functional groups utilizing readily available lab materials. These findings would lead to determining the overall influence of substitution patterns and functional groups have on stereochemistry, reactivity, and overall conformation of the piperidine ring. The synthetic approach involves the formation of 3-bromo-5-methoxy-tosylpiperidine intermediate through acid promoted cyclization, followed by nucleophilic substitution reactions to introduce various functional groups. Reaction progress and product …

Net Carbonyl Ene Reactions Of Olefins With Aldehydes, Alexandra Mock

Honors Theses

Aldehydes and olefins react in the presence of base and TMSOTf to yield homoallylic alcohols. In this net ene reaction, TMSOTf acts as a Lewis acid to activate the aldehyde, leading to a strong oxygen-silicon bond that acts as a driving force in the reaction. In the proposed mechanism, the α-methylstyrene attacks the carbonyl carbon of the TMSOTf-activated aldehyde to produce a carbocationic intermediate. Elimination using a relatively bulky base (2,6-lutidine) provides the homoallylic alcohol. This reaction has proven robust in terms of the aldehyde and olefin scope.

Effects Of Structure Of Mepegn Polymers On Hydroxide Conductivity In Anhydrous Anionic Exchange Membranes, Athan M. Gregory

Honors Theses

Anhydrous hydroxide ion (OH-) conducting polymer electrolytes composed of a 1-methyl-pyrrolidinium (1mp) head group linked to various MePEGn (n = 3, 7, 12) backbones were prepared. We have examined the structure of these anion exchange membranes to observe how the structure of the electrolyte affects the observed ionic conductivity. The structural parameters investigated were polymer length, viscosity, fractional free volume (FFV), and volume fraction of PEG (Vf,PEG), and each polymer varied in these properties. Through a comparison of the conductivity and structural parameters in the MePEGn-based anion electrolytes, we have shown that each of these structural properties weakly affects the …

Bottom-Up Mechanochemical Synthesis Of Nanographene, Sarah Kerr

Honors Theses

This research explores the application of mechanochemistry in the bottom-up synthesis of nanographene, specifically focusing on the mechanochemical Diels-Alder (DA) reaction. The study investigates the effect of different reaction conditions and dienophiles on the mechanochemical DA reaction, aiming to optimize reaction efficiency and yield using a ball mill. The initial trials with a sterically hindered dienophile (2) and an electron-deficient diene experienced repeated failure, while reactions using dienophile (B), a terminal alkyne showed more promising results. Various variables were examined, including reaction time, jar size, ball size, ball number, shaking frequency, liquid-assisted grinding (LAG), heating, and diene to dienophile ratio, …

Synthetic Efforts Towards An Analog Of Ly426965, Macy Sproles

Honors Theses

The 5-hydroxytryptamine_1A (5-HT_1A) receptor is a key target in the treatment of various neuropsychiatric conditions, and the development of selective antagonists offers promising therapeutic potential.²⁴ This study aimed to develop a synthetic analog of LY426965, a selective 5-HT_1A receptor antagonist. The synthetic route was initiated from dimethyl-2-phenylmalonate, employing pig liver esterase (PLE) as an enantioselective biocatalyst to achieve regioselective hydrolysis of one ester moiety in the malonic diester intermediate.¹⁷ Through a series of stereochemically controlled transformations, a new intermediate was successfully synthesized. Although the target molecule was not obtained, a new compound was synthesized …

Synthesis And Analysis Of A Novel Magnetic Surfactant, Donovan Turpin

Honors Theses

Researchers in the University of Mississippi Chemical Engineering Department have suggested that chelation of a large magnetic transition metal, namely dysprosium, into the large polar head group of a surfactant could result in a magnetic surfactant. This project was aimed at synthesizing a surfactant with a large enough head group and negative charge (specifically EDTA) to support this ion and demonstrating that the chelation process was successful. If so, the molecule would ideally be capable of forming micelles which could extract oily substances from water using a strong magnet—possibly applicable to environmental crises like oil spills.

NMR analysis has suggested, …

Phenanthrene Jamboree, Alexander D. Roth

Honors Theses

Using cyclopropanated and cyclobutanated phenanthrene precursors, our hero embarks on a mission to find as many reactive intermediates as possible. Fraught with danger, romance, and mangosteens, Anderson calls this work 'monstrous' and 'alarming.'

A Synthetic Approach To The Optimization Of Silicon-Rosindolizine Swir Fluorophores, Timothy Lewis

Honors Theses

Fluorophores emitting within the near-infrared (700 – 1000 nm) or shortwave-infrared (1000 – 1700 nm) regions of the electromagnetic spectrum are of particular interest for their potential to supplement or even outright replace commonly used biological imaging techniques, such as magnetic resonance imaging and computed tomography scanning. Various characteristics make these molecules particularly appealing to researchers, such as their ease of synthetic tunability, generally low toxicity, and high solubility in biological media in comparison to other NIR- and SWIR-emissive fluorophores. Different molecular skeletons have been examined for use as the core of these imaging agents, such as squaraine, cyanine, and …

Design And Synthesis Of Dinucleating Phthalazine-Based Ligands Toward Bimetallic Ruthenium Catalysts For Water Oxidation, Alex Bromley

Honors Theses

Two synthetic pathways were developed to construct dinucleating ligands towards the synthesis of bimetallic ruthenium-based water oxidation catalysts. The motivation for this work stems from earlier observations of related ligands that are susceptible to oxidative decomposition. The design pursued here incorporates a phthalazine core into the dinucleating ligand, which, we hypothesize, will prevent the previously established cleavage of a pyridazine unit at the same position. The ligand precursors involved in the multi-step syntheses are characterized by Nuclear Magnetic Resonance (NMR) spectroscopy. Synthetic protocols were refined to ensure reproducibility. In addition, our hypothesis for which of the two target ligands will …

Separating The R Vs. S Enantiomers Of A Quinoline Aimed At Inhibiting The Allosteric Binding Pocket Of Hiv-1 Integrase, Madison Canfield

Honors Theses

HIV-1 is a retroviral disease that infects CD4+ T cells in the body. Once inside the body, HIV-1 uses human cell machinery to replicate and reproduce using several enzymes to reverse transcribe viral RNA to DNA and integrate the viral DNA into the human genome to reproduce. Several drugs, such as NRTIs, INSTIs, NNRTIs, and PIs, have been created to inhibit specific parts of the viral life cycle and are used in combination to fight HIV-1. However, these medications face challenges of viral mutation and resistance, which increases the importance of creating more potent and effective drugs. Recently, a new …

Separating The R Vs. S Enantiomers Of A Quinoline Aimed At Inhibiting The Allosteric Binding Pocket Of Hiv-1 Integrase, Madison Canfield

Honors Theses

HIV-1 is a retroviral disease that infects CD4+ T cells in the body. Once inside the body, HIV-1 uses human cell machinery to replicate and reproduce using several enzymes to reverse transcribe viral RNA to DNA and integrate the viral DNA into the human genome to reproduce. Several drugs, such as NRTIs, INSTIs, NNRTIs, and PIs, have been created to inhibit specific parts of the viral life cycle and are used in combination to fight HIV-1. However, these medications face challenges of viral mutation and resistance, which increases the importance of creating more potent and effective drugs. Recently, a new …

Modeling Surface Structures For The Capture Of Carbon Dioxide, Paige Freyre

Honors Theses

Our research utilized a modified graphene surface model to simulate capture of carbon dioxide and nitrogen gas based on van der Waals forces and hydrogen bonding. We completed an extensive review of the literature for model and experimental surfaces used to trap carbon dioxide and nitrogen gas into structures and pores with varying functional groups, pore sizes, and pore structures. We replicated the design of selected published models and compared their and our calculated binding energies. We used Scigress (Fujitsu) software with the Molecular Mechanics MM3 parameter set to perform calculations to analyze a proposed graphene surface pore lined with …

Synthetic Investigations In Chemical Probe Development Part 1: Design And Synthesis Of Novel Triton X-405 Adenosine Conjugates; Part 2: Synthesis Of 2,8-Dihydroxychrysene, Rachel Irene Hammond

Honors Theses

Although not drugs themselves, chemical probes are a necessary tool in biomedical research for the interrogation of biological systems. In the present synthetic investigation, two chemical probes were developed – a Triton X-405 adenosine conjugate (TX-405A) and 2,8-dihydroxychrysene. The designed TX-405A conjugate was generated in four steps through tosylation and amination of TX-405 such that EDC-coupling of TX-amine with 2’,3’-Isopropylidene adenosine-5’-carboxylic acid afforded TX-405A following acetonide deprotection. The development of TX-405A represents the first report of the synthesis and utilization of a detergent-linked dosimeter. The synthesis of 2,8-dihydroxychrysene provided an in-depth exploration on the unique reactivity of chrysene. The desired …

Dicyanobenzothiadiazole-Based Organic Dye As A Visible Light Absorbing Strong Photoinduced Oxidant With A 16 Microsecond Long-Lived Excited State, Ivy Li

Honors Theses

Strong photoinduced oxidants are important to organic synthesis and solar energy conversion to chemical fuels or electric. For these applications, visible light absorption is important to solar energy conversion and long-lived excited states are needed to drive catalysis. With respect to these desirable qualities, a series of five 5,6-dicyano[2,1,3]benzothiadiazole ((CN)₂BTD) dyes are examined as organic chromophores that can serve as strong photooxidants in catalytic systems. The series utilizes a ((CN)₂BTD) core with aryl groups on the periphery varying electron donation strengths relative to the core. The dyes are studied via both steady-state and transient absorption and …

Synthesis And Study Of Unsymmetrical Bidentate Bis(Phosphino)Pyrrole Ligands And Their Transition Metal Complexes, Julia F. Vidlak

Honors Theses

Our laboratory has reported the synthesis and characterization of a broad library of unsymmetrical bidentate bis(phosphino)pyrrole (BPP) ancillary ligands for use in nickel-catalyzed cross-coupling reactions. The electronic and steric properties of nickel complexes bearing these ligands are examined, and our data support the hypothesis that these ligands produce nickel complexes with electron-deficient metal centers. The syntheses of (BPP)Ni(o-tolyl)Cl precatalysts for utilization in nickel-catalyzed Buchwald-Hartwig Amination are described, and preliminary reactivity studies reveal that (BPP)Ni(o-tolyl)Cl precatalysts are effective in promoting C–N cross-coupling reactions. Finally, we report steric measurements and electronic properties obtained from computed (BPP)NiCl2 and (BPP)Ni(CO)2 complexes, respectively. Additional reactivity …

Fast Photochemical Oxidation And Footprinting Of Proteins Via Trifluoromethyl Radical Chemistry, Elaine Morrow

Honors Theses

Fast photochemical oxidation of proteins (FPOP) is a useful tool in proteomics because of the ability for modifications to occur on the scale of microseconds which reduces the modifications to tertiary and quaternary structure allowing for more accurate labeling of the protein. Labels for FPOP are generated from various radicals in our experiments which include hydroxyl radicals and trifluoromethyl radicals. Hydroxyl radicals are easily generated by using an excimer laser (KrF laser, 248 nm) or a UV flash lamp (as a part of the Fox™ System) by the photolysis of hydrogen peroxide. Trifluoromethyl radicals, however, need hydroxyl radicals to be …

Techniques For The Enantioselective Asymmetric Synthesis Of Benzyl Substituted Malonic Acid Esters, Madison Hansen

Honors Theses

A popular method for the enantioselective synthesis of substituted malonic half esters is hydrolysis via Pig Liver Esterase (PLE), however some substrates produce low enantiomeric excess, namely benzyl-substituted malonic esters. Presented here are alternative methods explored for this synthesis, the first being phase-transfer catalyzed hydrolysis via N-benzyl quaternary ammonium salts derived from cinchona alkaloids. The second method utilized chiral auxiliary directed benzylation with auxiliaries including menthol and oxazolidinones. Though unsuccessful, this research provided valuable groundwork in the investigation for the enantioselective asymmetric synthesis of benzyl-substituted malonic acid esters.

Keywords: Pig Liver Esterase, Enantioselectivity, Phase-Transfer Catalysis, Cinchona Alkaloids, Quaternary Ammonium …

Investigation Of N-Sulfonyliminium Ion Triggered Cyclizations For The Synthesis Of Piperidine Scaffolds, Kaitlyn Birkhoff

Honors Theses

In consideration of the on-going global pandemic, immediate access to Food and Drug Administration approved pharmaceutical medications and vaccines is a matter of utmost priority to our national healthcare system. One significant modality in managed care is the dispensation of prescription drugs for the prevention or treatment of illnesses and diseases. According to the Centers for Disease Control and Prevention, physicians order and provide over 2.9 billion prescriptions each year with analgesics, antihyperlipidemics, and dermatological agents being the most prescribed therapeutic classes. Within those classes exists a disparate variety of chemical structures that must be prepared on a metric ton …

One-Pot Synthesis Of Disubstituted Primary Amines From Nitriles Via Grignard Addition And Metal-Alcohol Reduction, Joshua Peltan

Honors Theses

The process of developing a working base case procedure for a novel one-pot-two-step synthesis of primary amines from Grignard reagents, nitriles, sodium metal or alkali metal loaded silica gel, and alcohol is described. Initial steps towards applying the process broadly are detailed. The process has the potential to be an affordable, convenient, safer, greener, and more accessible alternative to exiting methods of accomplishing the same transformation. The reaction scheme has been proven to provide yields and purity comparable to existing methods for certain pairs of substrates; however, its utility as a general-purpose method for transforming arbitrary pairs of Grignard reagent …

End Group Modification Of Linear Dendritic Block Copolymers (Ldbcs), Chinwe Udemgba

Honors Theses

Linear dendritic block copolymers are amphiphilic molecules that consist of a dendritic hydrophilic portion and a linear hydrophobic portion. Its unique ability to self-assemble into spherical nanoaggregates while having the potential to uptake and transport both hydrophilic and hydrophobic drugs makes these polymers an item of interest in regard to the drug delivery field. The synthesis of polyamidoamine-polylactide linear dendritic block copolymers was designed to address the common issues in drug delivery systems, including problems in permeability, solubility, stability, specificity, and retention. Though this linear dendritic block copolymer has previously been synthesized in our lab with cationic amine surface functionalities, …

Applications Of Sodium Azide In The Synthesis Of Tetrazines And Hydrolysis Reactions, My Le

Honors Theses

The inverse electron demand Diels−Alder cycloadditions of heterocyclic azadienes have provided a robust methodology for synthesizing highly substituted and functionalized heterocycles. It is widely used in organic synthesis and the pharmaceutical industry in the divergent construction of screening libraries and bioorthogonal conjugation. Each heterocyclic azadiene was found to possess a unique reactivity toward different classes of dienophiles, display predictable modes of cycloaddition, and exhibit substantial substituent electronic effects impacting their intrinsic reactivity and cycloaddition regioselectivity. Synthesis of 1,2,4,5-tetrazine has been reported in the literature since the late 19th century, showing scientists' tremendous interest in its application.

Herein we attempt to …

Effects Of Halogen Bonding On 13c Nmr Shifts Of Various Tolan Species, Anthony Lybrand

Honors Theses

Halogen bonding is slowly becoming a more and more useful part of the world of chemistry and is beginning to be incorporated into various aspects of the chemical industry. This study’s purpose is to determine whether or not halogen bonding can cause any effect in the 13C NMR shifts. The specific purpose of this study is to determine whether these chemical shifts change when a Lewis Base is added to the dissolved sample. In order to do this, the tolan species (4-iodotolan and 4-chlorotolan) had to be synthesized. Once synthesized, the tolan species were analyzed via NMR. NMR data indicated …

Synthesis Of A Dd-Π-Aa Organic Dye For Dye-Sensitized Solar Cells, Hope Lovell

Honors Theses

This project investigates the synthesis of a DD-π-AA (dual donor/dual acceptor) organic dye as a potential sensitizer for dye-sensitized solar cells (DSCs). The design of this dye was based off previous research that found dual donor/dual acceptor dyes exhibited promising results when used in a DSC. The donor groups, acceptor groups, and π-bridge were chosen for their stability, ability to absorb in the near-infrared (NIR) region, and intramolecular charge transfer (ICT) abilities.

While many components of the dye were synthesized, the final stages of the synthetic scheme were not completed due to the loss of time from COVID-19. Had the …

Preparation Of Perylene Bisimide Acceptors With Ethylcarboxyl And Pyrenylcyclohexyl Imide Groups, Michael Cashen Stark

Honors Theses

Multiple attempts were made to deprotect TBDMS-protected (tert-butyldimethylsilyl protected) serinol and swallowtailed PBI (Compound 2), synthesized by past researcher Tarrah Frederick, to generate Compound 1. The theoretical Compound 1 product is intended for use in molecular rectification of electricity because the perylene core acts as a good acceptor with high electron affinity, and it does not require an electron donor group. Many rectification molecules are amphiphilic Donor-σ-Acceptor compounds, which allow for electron transfer through localized molecular orbitals when placed between electrodes (Langmuir-Blodgett Method). However, PBIs can transfer electrons from one electrode, through the LUMO of perylene, and to the other …

Indolizine Donor-Based Dyes For Applications In Fluorescence Biological Imaging, William Meador

Honors Theses

NIR emissive fluorophores are intensely researched due to their potential to replace modern imaging procedures. Many molecular strategies have been employed in the literature to optimize fluorophores for deeper NIR absorption and emission, biocompatibility, and higher fluorescence quantum yields. Amongst the fluorophores studied to date, proaromatic indolizine donors are attractive alternatives to traditional alkyl amine and indoline based donors due to their 1) lower energy absorption and emission facilitated by proaromaticity, 2) large Stokes shifts due to increased dihedral angles about the π-system, 3) ease of functionalization and capacity for bioconjugation at the phenyl ring, and 4) potential for further …

Synthesis Of Fluorinated Pyrazoles Via Intra- And Intermolecular Cyclization Reactions, Matthew Saucier

Honors Theses

Pyrazole-based pharmaceuticals treat a wide array of diseases and conditions including obesity, diabetes, cancer, microbial and viral infections, pain and inflammation, and many neurological disorders. Syntheses for this biologically significant substrate have been well developed, but current methods to afford fluorinated pyrazoles are limited by variability and selectivity. By 2013, over 25% of all drugs available on the market contained the element fluorine due to its unique characteristics leading to improved target protein binding, bioavailability, and metabolic stability. In order to harness these pharmaceutical benefits of fluorine and overcome its difficulty in handling and stability, we set out to develop …

Silver-Catalyzed Synthesis Of Disubstituted Fluorinated Isoxazoles, Micah Stewart

Honors Theses

The presence of fluorine can provide organic compounds with useful biological properties, such as increased metabolic stability and drug uptake. Because of these advantages, fluorinated compounds make up about 30% of the drug industry. However, fluorination of complex molecules is difficult due to fluorine’s high electronegativity.

Fluorinated isoxazoles are of particular interest in the pharmaceutical industry. Isoxazoles are five-membered heterocycles with oxygen and nitrogen in the 1, 2 positions that are able to engage in interactions unavailable to other ring structures, conferring advantageous biological properties upon compounds containing them. However, there are limited synthetic routes for fluorinated isoxazoles, and those …