Master of Science in Chemistry, Youngstown State University, 2007, Department of Chemistry

The aim of this project was the synthesis of several phosphonate esters via reaction of the salt of bis (2,2,2 trifluoroethyl) phosphite and a given alpha halo carbonyl compound in a Michealis-Becker reaction scheme. As an alternative to the use of strong base, we employed cesium carbonate as a mild reagent in hopes of successfully synthesizing our target compounds in high yields.

Committee: John Jackson (Advisor) Subjects: Chemistry, Organic

Master of Science in Chemistry, Youngstown State University, 2005, Department of Chemistry

The following work describes facile methods for the preparation of amino sugar analogs of N-acetyl-2-amino-2-deoxy-D-mannopyranose uronic acid (D-ManAcA). Two main approaches were investigated in the synthesis of N-glycosides. Staudinger and aza-Wittig approaches were used to synthesize glucosyl amides and imines. Another approach to the synthesis of N-glycosides involved the application of 1,3-dipolarcycloadditions of azides and alkynes in the presence of a Cu(I) catalyst. The synthesis of O-glycosides and C-glycosides of the methyl ester of glucuronic acid were studied in regard to the development of high yielding, stereospecific mimetic syntheses.

Committee: Peter Norris (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2000, Chemistry

Kuhr,Ida J. M.S.,Department of Chemistry,Wright State University,2000. Studies Directed at the Synthesis of Trialkoxysilyl Substituted NLO Chromophores. The synthesis of trialkoxyalkyl substituted NLO chromophores has been investigated. The chromophore 2-(7-(3-hydroxydiphenylamino)-9,9-diethyl-2-fluorenyl)-benzothiazole was prepared by a five step process. Bromination of fluorene yielded 2,7-dibromo-fluorene which could be converted to 2,7-dibromo-9,9-diethylfluorene by alkylation with ethyl iodide in DMSO.Reaction of 2,7-dibromo-9,9-diethylfluorene with one equivalent of butyl lithium followed by reaction with DMF provides 2-bromo-7-formyl-9,9-diethylfluorene. Condensation of 2-bromo-7-formyl-9,9-diethylfluorene and 2-aminobenzenethiol in DMSO results in the formation of 2-(7-bromo-9,9-diethyl-2-fluorenyl)benzothiazole. The conversion of 3-hydroxydiphenylamine to 3-benzyloxy-diphenylamine was accomplished with benzyl bromide and potassium carbonate in DMF. A palladium catalyzed coupling of 3-benzyloxydiphenylamine and 2-(7-bromo-9,9-diethyl-2-fluorenyl)benzothiazole provided 2-(7-(3-hydroxydiphenyl-amino)-9,9-diethyl-2-fluorenyl)benzothiazole. Several attempts to alkylate 2-(7-(3-hydroxydiphenylamino)-9,9-diethyl-2-fluorenyl)benzothiazole with trimethoxysilylmethyl chloride were made but the alkylation product could not be isolated and appeared to be unstable.

Committee: William Feld (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 1999, Chemistry

Hutson, Leslie K. M.S. Department of Chemistry, Wright State University, 1999. Synthesis of Benzoxazoles Containing Allyl Crosslinking Sites via Claisen Rearrangements. The reaction of diethyl 2,5-dihydroxyterephthalate with allyl bromide/K2CO3 in DMF followed by hydrolysis provided 2,5-di(allyloxy)terephthalic acid. The conversion of 2,5-di (allyloxy)terephthalic acid to 1,4-di(2-benzoxazolyl)-2,5-di(allyloxy)benzene in PPSE was unsuccessful. However, the reaction of 1,4-di(2-benzoxazolyl)-2,5- dihydroxybenzene with allyl bromide/K2CO3 provided 1,4-di(2-benzoxazolyl)-2,5- di(allyloxy)benzene. DSC analysis indicated that 1,4-di(2-benzoxazolyl)-2,5- di(allyloxy)benzene undergoes a Claisen rearrangement to the corresponding diallyl product. The synthesis of 2-allyloxy-1,4-di(2-benzoxazolyl)benzene was carried out using 2-hydroxy-1,4-di(2-benzoxazolyl)benzene as starting material. DSC analysis was inconclusive with respect to a Claisen rearrangement. The reaction of 2-allyloxybenzoic acid with 2,2-bis(3-amino-4-hydroxyphenyl)-1,1,1,3,3,3-hexafluoropropane in PPSE was unsuccessful but the reaction of 2,2-bis(2-(2-hydroxyphenyl)-5-benzoxazolyl)-1,1,1,3,3,3-hexafluoropropane with allyl bromide/K2CO3 in DMF provided 2,2-bis(2-(2- allyloxyphenyl)-5-benzoxazolyl)-1,1,1,3,3,3-hexafluoropropane. DSC analysis of 2,2- bis(2-(2-allyloxyphenyl)-5-benzoxazolyl)-1,1,1,3,3,3-hexafluoropropane was inconclusive as to the presence of a Claisen rearrangement.

Committee: William Feld (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2007, Chemistry

In the present work, a synthetic route to the formation of a sydno[3,4- a]indolone was explored in the hope of attaining the first example of a fused-ring sydnone with an sp2-hybridized bridge. Formation of this product and exploration of its chemical behavior was anticipated to be of particular interest to the formation of NO-releasing prodrugs. A direct synthetic pathway to yield the target sydnoindolone starting from 3-(2-methoxycarbonylphenyl)sydnone and reaction with a base was proposed and explored. Attempted formation and isolation of the target sydnoindolone proved impossible under a variety of different conditions, undoubtedly due to the instability of this intermediate. To "work around" this proposed instability, a “trapping” protocol for the sydnoindolone was explored. Thus, the ester starting material was treated with LDA (or LHMDS) at -78°C for 10 minutes whereupon another organolithium base was added, with the expectation that the latter would intercept the intermediate sydnoindolone. Indeed, when this approach was utilized with methyl, phenyl and butyl lithium, the corresponding fused-ring sydnoindoles were formed in yields ranging from 15-44%. A brief exploration of optimization of the process was explored using methyl lithium as the second base / nucleophile. The relative success of this approach led to extension to other nucleophiles such as a Wittig and three Grignard reagents. The former did not provide the desired alkenyl product but the latter did form the corresponding fused-ring sydnoindoles, albeit (where comparison could be made) in lower yield than from the use of the organolithium species. With this new avenue to the fused-ring sydnoindoles in hand, it was elected also to further test their reactivity. Unfortunately, reactions (acids, base followed by alkyl halide) carried out upon 5-hydroxy-5-methylsydno[3,4- a]indole as the test molecule in attempts to affect the alcohol moiety proved to be futile as recovery of the sydnoindole resulted (open full item for complete abstract)

Committee: Kenneth Turnbull (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2007, Chemistry

Some years ago, we reported that 3-phenylsydnone underwent dilithiation to yield the dilithio species, upon treatment with n-butyllithium. Subsequent reactions with electrophiles led to variously substituted aryl sydnones, dependent on the nature of the electrophile employed. Sydnonimines, exocyclic nitrogen analogs of sydnones, exhibit interesting biological properties and, accordingly, it was of value to explore whether or not the dilithiation approach could be extended to such species. In the present work a series of N-6-ethoxycarbonyl-3-arylsydnonimines were synthesized from the corresponding sydnonimine hydrochlorides in moderate yields (22-77%). Attempted dilithiations of N-6-ethoxycarbonyl-3-arylsydnonimines and trapping with iodine proved to be problematic, yielding only the mono substituted (at the 4-position) iodosydnonimine and not the desired disubstituted sydnonimine in a model study with N-6-ethoxycarbonyl-3-phenylsydnonimine. The 4-iodo species was extremely unstable, decomposing to the parent sydnonimine on standing or exposure to moisture, however, by careful chromatography, it was possible to isolate the N-6-ethoxycarbonyl-4-iodo-3-phenylsydnonimine in a very low yield (1.6%). Further lithiations with different reagents and substrates led to many unidentified reaction products, none of which appeared to be a sydnonimine. Reactions of N-6-ethoxycarbonyl-3-arylsydnonimines with brominating agents (potassium bromate and N-bromosuccinimide) showed that the preference was for substitution on the sydnonimine ring (yields of the 4-bromo congeners ranged from 32-90%). With the latter, it was discovered that removal of the bromine at the 4-position could be effected cleanly using sodium borohydride. The chlorinating agent potassium chlorate also showed a preference for substitution on the sydnonimine ring, however, other chlorinating agents (N-chlorosuccinimide and (dichloroiodo)benzene) did not effect chlorination on the aryl ring or sydnonimine ring in mo (open full item for complete abstract)

Committee: Kenneth Turnbull (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2007, Chemistry

In this research, 5-methylsydno-[3,4-a]quinazoline was synthesized via multiple methodologies, the best of which yielded the target compound in 50 % overall yield for the six steps. Synthesis of this compound in reasonable yields and exploration of its chemical behavior is of particular interest as a putative NO-prodrug. As an initial approach to the synthesis and accumulation of the compound of interest, attempts were made to optimize the existing synthetic pathway to its precursors. The starting material, 3-(2-acetylphenyl)sydnone, was prepared in 3 steps from commercially available starting material in good yields. This sydnone compound was then converted to the versatile intermediate, 3-(2-acetylphenyl)sydnone oxime. This conversion was accomplished by two distinct means, one of which was a novel microwave-assisted synthesis. Following its synthesis, 3-(2-acetylphenyl)sydnone oxime was converted to several reactive intermediates (O-acetate, O-tosylate, O-mesylate) in order to evaluate their utility with regards to cyclization to the aforementioned sydnoquinazoline. With respect to cyclization, 3-(2-acetylphenyl)sydnone oxime was treated with trifluoroacetic acid, which resulted in the target sydnoquinazoline in low yields. The reactive intermediates were also treated under thermal conditions, with the O-tosylate and O-mesylate species resulting in the target fused-ring sydnone in very low yields. These more reactive sydnones were exposed also to lithiation conditions to explore the possibility of base-induced cyclization to the desired sydnoquinazoline. Under these conditions, the O-tosylate and O-mesylate were treated with lithium diisopropyl amide. The O-tosylate resulted in the formation of the target quinazoline in moderate yields, while the O-mesylate resulted in formation of the target compound in good yields. Indeed, by adjustment in the amount of base employed, an up to 80% yield of the desired fused-ring sydnone could be realized; a considerable improve (open full item for complete abstract)

Committee: Kenneth Turnbull (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2007, Chemistry

The goal of this research was to synthesize the natural product epibatidine, a non-opiate analgesic and nicotinic acetylcholine agonist isolated from Epipedobates tricolor. A synthetic pathway utilizing a Diels-Alder cycloaddition of a 3-pyridyl substituted pyrrole and tosylacetylene was conceived based upon the original mass spectral fragmentation pathway of epibatidine determined by Daly. Although this pathway had been previously attempted using 1-(triisopropyl)-3-[5-(2-chloropyridyl)]pyrrole in the key Diels-Alder step, the lack of cycloadduct suggested that a pyrrole with a more electron withdrawing protecting group was required for this step. Therefore, synthesis of 1-(phenylsulfonyl)-3-[5-(2-chloropyridyl)]pyrrole via a palladium catalyzed cross-coupling reaction of 1-(phenylsulfonyl)-3-pyrroline and 2-chloro-5-iodopyridine was set as a synthetic goal and accomplished. The Diels-Alder reaction required further investigation to determine the extent to which 1-(phenylsulfonyl)pyrrole would undergo cycloaddition with dimethyl acetylenedicarboxylate and tosylacetylene. Once this was completed, the Diels-Alder reaction of 1-(phenylsulfonyl)-3-[5-(2-chloropyridyl)]pyrrole was attempted with tosylacetylene but the desired cycloadduct could not be found.

Committee: Daniel Ketcha (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2006, Chemistry

Carbonic anhydrases (CAs) are metalloenzymes that catalyze the reversible interconversion of CO2 and bicarbonate. We recently initiated a screen of a broad range of indoles and pyrroles possessing acyl-, carboxyl-, amido-, sulfonyl-, sulfamyl- and oxime- functionalities as potential inhibitors of a-CA II isozyme. As slight inhibition was observed in the case of 2-carboxamido-1-(phenylsulfonyl)pyrrole, and aware that pyrrole carboxamide derived sulfonamides had been previously demonstrated to possess CA inhibition, we sought to prepare a series of 1-(phenylsulfonyl)pyrrole-2-carboxamides but lacking a sulfonamide moiety to ascertain if the activity in our case might be due to a hitherto unrecognized pyrrole pharmacophore. To this end, we examined synthetic routes to such derivatives and found optimal results when employing a microwave-assisted, polymer-supported amidation reaction of 1-(phenylsulfonyl)pyrrole-2-carboxylic acid. Additionally, we examined the microwave-assisted Beckmann rearrangement of the oximes of acyl-1-(phenylsulfonyl)pyrroles and observed optimal results using montmorillonite as catalyst under solventless conditions.

Committee: Daniel Ketcha (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2005, Chemistry

Fisher, Jennifer A., M.S., Department of Chemistry, Wright State University, 2005.Bismuth Triflate Catalyzed Friedel-Crafts Acylations of Sydnones. In the present work, suitably functionalized arylsydnones were used to synthesize a variety of 4-acylsydnones and diacyl sydnones, both as potential precursors to novel sydnoquinolines.The approach to the diacyl species is based on the discovery that activated sydnonesbrominate in both the 4 position of the sydnone ring and on the phenyl ring. Thus, it seemed likely that Friedel-Crafts reactions on an activated sydnone would give diacylated species for McMurray coupling to sydnoquinolines. Friedel-Crafts acylations on the 4 position of the sydnone ring have been achieved in high yields using 4 equivalents of various alkyl anhydrides, 25 mol % of bismuth triflate and lithium perchlorate inanhydrous acetonitrile at 95 °C. Various parasubstituted phenyl sydnones with differentelectron withdrawing and electron donating substituents were used to explore the effect of the attachment on the reaction time and yields of the acylation with acetic anhydride. Additionally, four other alkyl anhydrides were employed to test their utility with phenylsydnone. The reaction times were consistent with the electron withdrawing or donating nature of the para substituents. Thus, electron-donating groups appeared to speed up the process, whereas the reactions were slower in the presence of electron-withdrawing moieties. The reaction times involving phenylsydnone and other alkyl anhydrides were consistent with the steric hindrance of the anhydride; bulkier species leading to longer reaction times. With optimized conditions available for the monoacylation process, it was of interest to explore diacylation using the activated sydnone, 3-(3, 5dimethoxyphenyl) sydnone. Many attempts were made to prepare the diacyl sydnone,but no methods thus far have given only the desired diacyl product. For example, when the activated sydnone was reacted under th (open full item for complete abstract)

Committee: Kenneth Turnbull (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2003, Chemistry

Weisner, Andrew J. M.S., Department of Chemistry, Wright State University, 2003. Sonogashira Coupling Routes to ortho-Alkynyl- and Fused-Ring Sydnones. In the present work, suitably functionalized arylsydnones were used to synthesize a variety of ortho-alkynyl sydnones both as potential precursors to novel sydnoquinolines and to provide non-linear optical (NLO) species of interest to Wright-Patterson Air Force Base (WPAFB). The versatile intermediate, 3-(2-(trimethylsilylethynyl)phenyl)sydnone, was prepared in good yield by the coupling of 3-(2-iodophenyl)sydnone with trimethylsilyl acetylene under Sonogashira conditions. From this intermediate, several ortho-alkynyl sydnones were prepared via a one-pot desilylation with tetrabutylammonium fluoride and Sonogashira coupling with para-substituted aryl iodides. In addition, a three-reaction-in-one-pot procedure was developed to access some of these species directly from 3-(2- iodophenyl)-sydnone. Subsequent reaction of these species with electrophiles has been examined as an avenue to novel sydnoquinolines. For example, there is evidence that the electrophile phenylselenyl chloride has induced cyclization of 3-(2- (phenylethynyl)phenyl)sydnone and 3-(2-(4-methoxyphenylethynyl)phenyl)sydnone in moderate yield. Similarly, concentrated sulfuric acid has effected cyclization of 3-(2- (phenylethynyl)phenyl)sydnone and 3-(2-(4-bromophenylethynyl)phenyl)sydnone, also in low yield. In contrast, trifluoroacetic acid and trifluoromethanesulfonic acid transform these species into novel cinnolines, presumably via sydnone ring cleavage followed by acid-induced cyclization. Sonogashira coupling routes were used to add additional para-alkynylphenyl moieties to the above-mentioned ortho-alkynyl sydnones and generate oligomeric alkynyl sydnones. The aim of this endeavor was to fulfill an interest of the United States Air Force in these species as ligands for the preparation of platinum-centered NLO materials. 3-(2-Ethynylphenyl)sydnone (open full item for complete abstract)

Committee: Kenneth Turnbull (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2001, Chemistry

Sawyer,James R. M.S.,Department of Chemistry,Wright State University,2001. The Functionalization of Thermally Stable Third-Order NLO Chromophores. There is a need to functionalize NLO chromophore systems to incorporate them into polymeric matricies by covalent attachment.The functionalization of a series of NLO chromophores based on the N,N-diphenyl-N-[7-(2-benzothiazolyl)-9,9-diethyl-2- fluorenyl ]amine structure has been investigated.All the chromophores were synthesized from the intermediate chromophore N-phenyl-N-[4-(4-bromophenyl)phenyl ]-N-[7-(2- benzothiazolyl)-9,9-diethyl-2-fluorenyl ]amine which was prepared by a six-step process. Bromination of fluorene yielded 2,7-dibromo-fluorene which could be converted to 2,7- dibromo-9,9-diethylfluorene by alkylation with ethyl iodide in DMSO.Reaction of 2,7- dibromo-9,9-diethylfluorene with one equivalent of butyl lithium followed by reaction with DMF provides 2-bromo-7-formyl-9,9-diethylfluorene.Condensation of 2-bromo-7- formyl-9,9-diethylfluorene and 2-aminobenzenethiol in DMSO results in the formation of 7-(2-benzothiazolyl)-2-bromo-9,9-diethylfluorene.The palladium catalyzed reaction of 7- (2-benzothiazolyl)-2-bromo-9,9-diethylfluorene with aniline afforded N-phenyl-N-[7-(2- benzothiazolyl)-9,9-diethyl-2-fluorenyl ]amine which was subjected to a second palladium catalyzed reaction with 4,4 '-dibromobiphenyl to yield N-phenyl-N-[4-(4- bromophenyl)phenyl ]-N-[7-(2-benzothiazolyl)-9,9-diethyl-2-fluorenyl ]amine.Further reactions have yielded a series of thermally stable NLO chromophores in which the functional group is located in the para position to the amine nitrogen.

Committee: William Feld (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2002, Chemistry

Matuszewski, Michael J. M.S., Department of Chemistry, Wright State University, 2002. The Synthesis of Bromoethoxy and Vinylbenzyloxy Substituted NLO Chromophores. Multiphoton-absorption processes have recently attracted growing interest because of the potential impact on a wide spectrum of applications, ranging from data storage to photodynamic therapy. From the materials standpoint, particular interest is centered in designing chromophores that exhibit a large two-photon cross-section. The current research is focused on establishing synthetic routes that lead to the formation of derivatives of N,N-diphenyl-(7-benzothiazol-2-yl)-9,9-diethyl-9H-fluoren-2-ylamine which contain meta functionalization. A bromoethoxy functionalized chromophore, N-phenyl-N-(3-(2-bromoethoxy)phenyl)-7-(benzothiazol-2-yl)-9,9-diethyl-9H-fluoren- 2-ylamine , was synthesized and used as a polymer pendent while a vinylbenzyloxy chromophore, N-phenyl-N-(3-(4-vinylbenzyloxy)phenyl)-7- (benzothiazol-2-yl)-9,9-diethyl-9H-fluoren-2-ylamine, was synthesized as a hydrosilation substrate. A compound containing three chromophores, 1,3,5-tris(3-(N-phenyl- 4-(7-(benzothiazol-2-yl)-9,9-diethyl-9H-fluoren-2- ylanilino)phenoxymethyl)benzene, has been synthesized to determine if a larger two-photon cross-section (s 2') could be obtained by increasing the number of chromophore units in a single molecule.

Committee: William Feld (Advisor) Subjects: Chemistry, Organic

Master of Science (MS), Wright State University, 2002, Chemistry

Fauley, Stacey M. M.S., Department of Chemistry, Wright State University, 2002. Selected Synthetic Studies of NLO pi-Bridges and Thermally Stable Monomers. The molecular weights of two series of PEEK polymers were determined using gel permeation chromatography (GPC). The first series contains oxyalkylene linkages. The other series contains oxyethylene linkages. The synthesis of several thermally stable monomers has been investigated. These monomers include 9,9-dihexylfluorene-2,7-dicarboxaldehyde, 2,7-bis(bromomethyl)-9,9- dibutylfluorene and 2,7-bis(hydroxymethyl)-9,9-diethylfluorene. These monomers can be used to form polymers that will contain short conjugated segments separated by nonconjugated segments. The synthesis of 50 g of each of the following monomers was accomplished: bis(3-methylphenyl) phenylphosphine oxide, bis(4-methylphenyl)phenylphosphine oxide, bis(3- carboxyphenyl)phenylphosphine oxide and bis(4-carboxyphenyl)phenylphosphine oxide. These monomers will be used in a polymerization to form polybenzoxazoles. The synthesis of the NLO pi-bridge 2,10-dibromo-5,6-diphenyl-11,12- dihydroindeno[2.1-a] was accomplished. Alkylation of this compound was attempted, but the results were inconclusive. This project was abandoned due to the consistently low yields. Another NLO pi-bridge that was attempted contained the c-fused system, however, the initial steps also showed consistently low yields. Because of low yields, this project was also abandoned.

Committee: William Feld (Advisor) Subjects: Chemistry, Organic

PhD, University of Cincinnati, 2001, Arts and Sciences : Chemistry

PAMAM dendrimers have been synthesized using two separate acrylamide monomer compounds, (2-acryloylamino-ethyl)-carbamic acid tert-butyl ester (1) and N-cyanomethyl-acrylamide (18). These monomer units allow for facile synthesis of PAMAM dendrimers with decreased opportunity of defects. Zero and first generations dendrimers have been synthesized with compound 1 and zero through second generation dendrimers have been synthesized with compound 18. Various amine-terminated compounds were used as initiator cores from which the dendrimers were grown. Dendrimers were also grown using 3-[(2-tert-butoxycarbonylamino-ethyl)-(2-methoxycarbonyl-ethyl)-amino]-propionic acid methyl ester (9). After selective deprotection of this compound, normal amino acid coupling procedures were used to produce the next higher half-generation dendrimer.

Committee: Prof. Allan Pinhas (Advisor); Prof. William Heineman (Other); Prof. H. Halsall (Other); Prof. R. Wilson (Other) Subjects: Chemistry, Organic

PhD, University of Cincinnati, 2001, Arts and Sciences : Chemistry

A series of Dihydrodioxins has been synthesized as part of a research program investigating the development of 2,2,3-triaryl- and 2,3-diaryl-2,3-dihydrophenanthro[9,10-b]-1,4-dioxins (dihydrodioxins) as efficient DNA cleaving agents. The dihydrodioxins are unique, photochemical, masked o-quinone DNA cleaving agents. When used in combination with DNA sequence-recognizing groups, they have the potential to be an important tool in the fight against cancer, and /or genetic disease. The focus of this research was the synthesis of chiral dihydrodioxins, utilizing the Schonberg-Mustafa reaction, a 2+4 photocyclization of phenanthroquinone (PAQ) and an appropriate alkene. The products of this reaction involving a variety of different alkenes is reported, and their use, and / or potential use, as chiral DNA cleaving agents is evaluated. The chiral resolution of a selected 2,3-diaryl-dihydrodioxin, followed by an examination of the DNA cleaving potential of the enantiomers is reported.

Committee: R. Wilson (Advisor) Subjects: Chemistry, Organic

PhD, University of Cincinnati, 2001, Arts and Sciences : Chemistry

The application of lasers to photochemical studies has resulted in the ability to produce high-intensity, multiple-photon, photochemical reactions. The absorption of two or more photons by a molecule, or transient intermediate, can result in the production of a higher excited state in an intratransient reaction. The production of higher concentrations of transient intermediates, such as radicals, biradicals, carbene, or nitrenes, can also be achieved using this technique. The higher concentrations increase the likelihood for an intertransient reaction to occur between two such intermediates. Both of the aforementioned cases can lead to the formation of photochemical products that previously had not been observed under conventional, low-intensity, conditions. High-intensity reactions have been investigated in this laboratory using the argon-ion, laser-jet apparatus. A number of compounds were chosen for this research to possibly provide answers to questions resulting from previous observations under high-intensity conditions. The types of reactions studied were symmetry-governed reactions: 3,4-benzocoumarin (11) and bifluorenylidene (22); and intertransient reactions: 1,8-naphthalic anhydride (26), 2,3-naphthalic anhydride (31), N-phenyl-1,8-naphthalimide (37), N-phenyl-2,3-naphthalimide (38), and N-phenyl-phthalmide (39). The application of the laser-jet technique to photo-induced electron transfer reactions was also investigated. Two classes of compounds were investigated as possible targets for this type of reaction: diphenylalkanediones; 1,6-diphenyl-1,6-hexanedione (41), 1,8-diphenyl-1,8-octanedione (42), 1,10-diphenyl-1,10-decanedione (43), and 1,12-diphenyl-1,12-dodecanedione (44); and N-(phenylalkyl)phthalimides; N-(3-phenylpropyl)phthalimide (68) and N-(4,4,4-triphenylbutyl)phthalimide (71). The incorporation of an excimer laser in the laser-jet technique, along with the required modifications of the laser-jet apparatus, also is reported.

Committee: R. Wilson (Advisor) Subjects: Chemistry, Organic

PhD, University of Cincinnati, 2008, Arts and Sciences : Chemistry

Solventless high speed ball milling (HSBM) technique has over the years gained the attention of organic chemists in particular from the viewpoint of green chemistry, because harmful organic solvents are not involved in the reaction process. Moreover, some novel products can also be obtained only from solvent-free reactions under the HSBM conditions rather than from the liquid-phase reactions. We looked to apply the HSBM technique towards the improvement of multi-component reactions (MCR). Based on their usefulness in organic synthesis and in pharmaceutical industry, the Baylis-Hillman reaction, the Gewald, and the Ugi-4-component reaction (U-4CR) were chosen for investigation. For these three reactions we were able to observe a rate enhancement and an increase in the product yields. Herein, we report the utility of HSBM to provide a rate enhancement and increased yields for the following multi-component reactions: The Baylis- Hillman, the Gewald reactions and the U-4-CR.

Committee: Dr. James Mack (Advisor) Subjects: Chemistry, Organic

PhD, University of Cincinnati, 2007, Arts and Sciences : Chemistry

We have investigated the photochemical reactivity and applications of the following triplet biradicals:(a) Triplet alkyl nitrenes, their selective formation and reactivity. (b) Selective generation and detection of triplet imine radicals. (c) Applying triplet imine radical mechanism for the rapid and effective photolysis of alcohols. (d) Understanding the formation of photoenols from 1,4-triplet biradicals of benzophenone and acetophenone derivatives and their application to photorelease of alcohols. (e) Generation of persistent carbon centered radicals by thermolysis. We have demonstrated that triplet alkyl nitrenes can be selectively generated in the photolysis of 1-azidoethanophenones I-1b. However, the triplet alkyl nitrenes I-2b, a long-lived intermediate (lifetime ≈ 2 ms), undergoes secondary photochemical alpha-cleavage to form benzoyl and imine radicals (see Chapter 1). We have shown a simple and elegant way of generating triplet imine radicals from the photolysis of 4-azidobutyrophenone II-1, and from [2-(azidomethyl) phenyl](phenyl) methanone III-1, detect them using transient spectroscopy. We used product studies and density functional theory (DFT) computational methods to establish the reaction mechanism (see Chapters 2 and 3). Employing the imine radical mechanism, we demonstrate the rapid, solvent independent, and efficient photorelease of alcohol from 2-(2'-azidomethylbenzoyl) benzoic acid methyl ester IV-1 (Chapter 4). Our DFT computational studies allowed us to understand why the photorelease of alcohol from certain Methyl 2-(2'-alkylbenzoyl) benzoic acid esters fail (for example, ester V-4) and why others (esters V-1 and V-5) photoreleased alcohols in inert atmosphere. We similar establish the mechanism of photo-oxidation of the benzylic carbon in esters V-4 and V-1 in the presence of molecular oxygen (see Chapters 5a and 5b). We show how intramolecular hydrogen bonding is used to favor the formation of triplet biradicals VI-2bB which intersystem c (open full item for complete abstract)

Committee: Dr. Anna Gudmundsdottir (Advisor) Subjects: Chemistry, Organic

PhD, University of Cincinnati, 2007, Arts and Sciences : Chemistry

Rotaxanes are a class of interlocked compounds that have been extensively investigated for their potential utility as switches or sensors. We recently demonstrated that Rotaxanes have further application as agents that transport material into cells. This novel finding prompted our investigation into the mechanism by which Rotaxanes are involved in transmembrane transport. Presented in the following dissertation are four major research focus areas in the development of host-Rotaxanes and investigation of their binding abilities and intracellular transport mechanism of the host-Rotaxanes. The first chapter is about the mechanism study of a cleft-[2]Rotaxane as a intracellular transport agent. Two-dimensional NMR analysis showed that a cleft-containing rotaxane exists in two dominant conformations (‘closed' and ‘open'). The rotaxane was chemically modified to lock it in the closed conformation in order to determine the importance of conformational flexibility on the ability of the rotaxanes to bind guests and transport material into cells. Charged guests interact less favorably with the locked rotaxane, as compared to the unmodified rotaxane, in both an aqueous solution and in DMSO. The locked rotaxane exhibited a reduced capacity to transport a fluoresceinated peptide into cells, whereas, the unmodified rotaxane efficiently delivers the peptide. Flow cytometry experiments demonstrated that a high percentage of the cells contained the delivered peptide, the level of delivery is concentration dependent, and the rotaxanes and peptide have low toxicity. Cellular uptake of the peptide was largely temperature and ATP independent, suggesting that the rotaxane-peptide complex passes through the cellular membrane without requiring active cell-mediated processes. The results show that the sliding motion of the wheel is necessary for the delivery of materials into cells and can enhance the association of guests. The second chapter is about the synthesize, binding study, and in (open full item for complete abstract)

Committee: Dr. David Smithrud (Advisor) Subjects: Chemistry, Organic