Thèses sur le sujet « 4-oxadiazoly »

Synthesis of five-membered heteroaromatic compounds such as pyrazoles, isoxazoles and 1,2,4-oxadiazoles are important for pharmaceutical industry and material science due to their applications. Although there are many methods to prepare such compounds, new variants continue to appear since they exhibit a wide range of biological and medicinal activities. In this thesis, new methods were developed for the synthesis of 4-iodopyrazoles, pyrazoles, isoxazoles, 1,2,4-oxadiazoles and/or 1,2,4-oxadiazepines. In the first part of the study, electrophilic cyclization of &alpha
,&beta
-alkynic hydrazones by molecular iodine and copper iodide were investigated as new ways for the synthesis of 4-iodopyrazoles and pyrazoles, respectively. Initially, &alpha
,&beta
-alkynic hydrazones were prepared by the reactions of propargyl aldehydes and ketones with hydrazines. Then &alpha
,&beta
-alkynic hydrazones were treated with molecular iodine in the presence of NaHCO3, which afforded 4-iodopyrazoles in good to excellent yields. Subsequently, the same reactions were carried out with CuI in the presence of NEt3, which furnished corresponding pyrazoles in good yields. Moreover, ferrocenyl-substituted 4-iodopyrazoles and pyrazole derivatives were synthesized from corresponding

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
As espÃcies 5-(4-piridil)-1,3,4-oxadiazol-2-tiol (Hpyt) e [Fe(CN)5Hpyt]3- (FeHpyt) adsorvem espontaneamente sobre ouro formando monocamadas automontadas (SAM - "Self-Assembled Monolayers") das quais, de acordo com os dados eletroquÃmicos, apresentam defeitos ou nanoporos por onde as molÃculas de prova [Fe(CN)6]4â e [Ru(NH3)6]3+ acessam a superfÃcie do eletrodo de ouro policristalino. A partir dessas molÃculas de prova e da dependÃncia entre a corrente faradÃica e o pH do eletrÃlito, o pKa da monocamada de Hpyt foi calculada como 4,2. A partir dos resultados de microscopia de tunelamento STM (Scanning Tunneling Microscopy) obtidos para a monocamada automontada de Hpyt sobre Au(111) foi possÃvel estimar que as molÃculas de Hpyt sÃo adsorvidas em um arranjo hexagonal com um espaÃamento mÃdio entre os Ãtomo de enxofre de 5,5 Ã. Essas imagens tambÃm mostraram a presenÃa de nanoporos, do qual indica que fortes interaÃÃes laterais nÃo ocorrem efetivamente. Os parÃmetros termodinÃmicos ΔHads, ΔGads e ΔSads para o processo de adsorÃÃo das molÃculas Hpyt e FeHpyt foram calculados a partir da correlaÃÃo entre a concentraÃÃo dos adsorbatos na superfÃcie (Γ) e em soluÃÃo (C) para diferentes temperaturas. A quantidade de molÃculas adsorvidas foi calculada a partir do processo de desorÃÃo redutiva, onde R = Hpyt ou FeHpyt, observados em -555 e -566 mV versus Ag|AgCl|Cl- para as monocamadas de Hpyt e FeHpyt, respectivamente, indicando um fortalecimento da ligaÃÃo AuâS como conseqÃÃncia do efeito π-backbonding do centro metÃlico ferro para o ligante Hpyt. A reaÃÃo heterogÃnea de transferÃncia de elÃtrons da metaloproteÃna citocromo c foi satisfatoriamente acessada pelas monocamadas de Hpyt e FeHpyt, apresentando um voltamograma quasi-reversÃvel com potenciais consistentes com a forma nativa desta proteÃna.
-(4-pyridinyl)-1,3,4-oxadiazole-2-thiol (Hpyt) and [Fe(CN)5Hpyt]3- (FeHpyt) species spontaneously adsorbed on gold forming SAM (Self-Assembled Monolayers) that, based on electrochemical data, contain pinholes through which [Fe(CN)6]4â and [Ru(NH3)6]3+ probe molecules access the underlying gold electrode. From the former molecule and the dependence of the faradaic current on the pH value of the electrolyte solution, the surface pKa of the Hpyt SAM was evaluated as 4.2. Taking into account the STM (Scanning tunneling Microscopy) results obtained for the Hpyt SAM on Au(111), it was possible to estimate that the Hpyt molecules are adsorbed in an hexagonal arrangement with an average distance between the sulfur atoms of 5.5 Ã. These images also showed the presence of pinholes, which indicate that a strong lateral interaction does not effectively happen. The thermodynamics parameters ΔHads, ΔGads and ΔSads of the Hpyt and FeHpyt adsorption process were calculated from the correlation between the concentration of the adsorbates on the surface (Γ) and in solution (C) at different temperatures. The surface coverage data were obtained from the reductive desorption process RS-Au + e- �� RS- + AuÂ, where R = Hpyt or FeHpyt, observed at -555 and -566 mV vs Ag|AgCl|Cl- for Hpyt and FeHpyt SAM, respectively, indicating an enhancement of the AuâS bond as consequence of the π-backbonding interaction from iron metal center toward the Hpyt moiety. The heterogeneous electron transfer reaction of cytochrome c metalloprotein was successfully assessed by Hpyt and FeHpyt and SAM, presenting a quasi-reversible voltammograms with potentials consistent with the native form of the protein.

PAULO, T. F.; DIÓGENES, I. C. N. 5-(4-PIRIDIL)-1,3,4-(OXADIAZOL)-2-TIOL E Na3[Fe(CN)5Hpyt].3H2O: Síntese, caracterização e estudos de formação de monocamadas automontadas. 2007. 85 f. Dissertação (Mestrado em Química Inorgânica) - Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2007.
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-(4-pyridinyl)-1,3,4-oxadiazole-2-thiol (Hpyt) and [Fe(CN)5Hpyt]3- (FeHpyt) species spontaneously adsorbed on gold forming SAM (Self-Assembled Monolayers) that, based on electrochemical data, contain pinholes through which [Fe(CN)6]4– and [Ru(NH3)6]3+ probe molecules access the underlying gold electrode. From the former molecule and the dependence of the faradaic current on the pH value of the electrolyte solution, the surface pKa of the Hpyt SAM was evaluated as 4.2. Taking into account the STM (Scanning tunneling Microscopy) results obtained for the Hpyt SAM on Au(111), it was possible to estimate that the Hpyt molecules are adsorbed in an hexagonal arrangement with an average distance between the sulfur atoms of 5.5 Å. These images also showed the presence of pinholes, which indicate that a strong lateral interaction does not effectively happen. The thermodynamics parameters ΔHads, ΔGads and ΔSads of the Hpyt and FeHpyt adsorption process were calculated from the correlation between the concentration of the adsorbates on the surface (Γ) and in solution (C) at different temperatures. The surface coverage data were obtained from the reductive desorption process RS-Au + e- �� RS- + Au°, where R = Hpyt or FeHpyt, observed at -555 and -566 mV vs Ag|AgCl|Cl- for Hpyt and FeHpyt SAM, respectively, indicating an enhancement of the Au–S bond as consequence of the π-backbonding interaction from iron metal center toward the Hpyt moiety. The heterogeneous electron transfer reaction of cytochrome c metalloprotein was successfully assessed by Hpyt and FeHpyt and SAM, presenting a quasi-reversible voltammograms with potentials consistent with the native form of the protein.
As espécies 5-(4-piridil)-1,3,4-oxadiazol-2-tiol (Hpyt) e [Fe(CN)5Hpyt]3- (FeHpyt) adsorvem espontaneamente sobre ouro formando monocamadas automontadas (SAM - "Self-Assembled Monolayers") das quais, de acordo com os dados eletroquímicos, apresentam defeitos ou nanoporos por onde as moléculas de prova [Fe(CN)6]4– e [Ru(NH3)6]3+ acessam a superfície do eletrodo de ouro policristalino. A partir dessas moléculas de prova e da dependência entre a corrente faradáica e o pH do eletrólito, o pKa da monocamada de Hpyt foi calculada como 4,2. A partir dos resultados de microscopia de tunelamento STM (Scanning Tunneling Microscopy) obtidos para a monocamada automontada de Hpyt sobre Au(111) foi possível estimar que as moléculas de Hpyt são adsorvidas em um arranjo hexagonal com um espaçamento médio entre os átomo de enxofre de 5,5 Å. Essas imagens também mostraram a presença de nanoporos, do qual indica que fortes interações laterais não ocorrem efetivamente. Os parâmetros termodinâmicos ΔHads, ΔGads e ΔSads para o processo de adsorção das moléculas Hpyt e FeHpyt foram calculados a partir da correlação entre a concentração dos adsorbatos na superfície (Γ) e em solução (C) para diferentes temperaturas. A quantidade de moléculas adsorvidas foi calculada a partir do processo de desorção redutiva, onde R = Hpyt ou FeHpyt, observados em -555 e -566 mV versus Ag|AgCl|Cl- para as monocamadas de Hpyt e FeHpyt, respectivamente, indicando um fortalecimento da ligação Au–S como conseqüência do efeito π-backbonding do centro metálico ferro para o ligante Hpyt. A reação heterogênea de transferência de elétrons da metaloproteína citocromo c foi satisfatoriamente acessada pelas monocamadas de Hpyt e FeHpyt, apresentando um voltamograma quasi-reversível com potenciais consistentes com a forma nativa desta proteína.

Ce manuscrit porte sur la synthèse et les applications d'une nouvelle série de composés hétéroaromatiques : les 4H-pyrido[e][1,3]oxazin-4-ones. La première partie de ce manuscrit présente la préparation de ces squelettes via une réaction d'O-arylation intramoléculaire. La seconde partie du manuscrit repose sur la réactivité de ces entités chimiques et de leur utilisation en tant qu'intermédiaires de synthèse. La fonctionnalisation des 4H-pyrido[e][1,3]oxazin-4-ones, via des réactions de couplage pallado-catalysées, a permis d'obtenir des systèmes polyfonctionnalisés plus complexes. Les pyrido-oxazinones ont également été transformées, en une étape, en divers petits hétérocycles d'intérêt : les 1,3,5-triazines, les 1,2,4-triazoles et les 1,2,4-oxadiazoles. La dernière partie du manuscrit est consacrée à l'utilisation des molécules synthétisées comme potentielles sondes fluorescentes pour la détection de protéines oxydées
This work focused on the synthesis and applications of a novel series of heteroaromaticcompounds: the 4H-pyrido[e][1,3]oxazin-4-ones. The first part of this thesis presents thepreparation of these pyrido-oxazinones via an intramolecular O-arylation reaction. The secondpart of this work relies on the reactivity of these chemical entities and their use as buildingblocks. The functionalization of the 4H-pyrido[e][1,3]oxazin-4-ones has been studied viacross-coupling reactions to obtain more elaborated structures. The pyrido-oxazinones werealso converted, in one step, into other diverse small molecules of interest: 1,3,5-triazines,1,2,4-triazoles and 1,2,4-oxadiazoles. The last part of this thesis was devoted to the use of theobtained heterocycles as potential fluorescent probes for the detection of carbonylatedproteins

A introdução de um grupo substituinte na molécula de um fármaco promove alterações químico-estruturais que, por sua vez, modificam suas propriedades físicoquímicas. O arranjo espacial de átomos ou grupos de átomos, em especial grupos funcionais, na molécula de um fármaco, expressos por meio de suas propriedades físico-químicas, influenciam direta ou indiretamente na interação fármaco-receptor. Esta, por sua vez, determina aspectos farmacológicos e farmacocinéticos que influem na eficácia terapêutica do medicamento. Assim, uma série de compostos 2-[5-nitro-tiofen-2-il]-3-acetil-5-[4-fenil-substituído]-2,3-diidro-1,3,4-oxadiazolínicos foi planejada e os análogos foram sintetizados, identificados estruturalmente e avaliados in vitro quanto a atividade antimicrobiana frente a Staphylococcus aureus (cepa ATCC 25923), expressa pela determinação da concentração inibitória mínima. Cepas desta bactéria são comuns em infecções hospitalares e frequentemente apresentam caráter de multi-resistência, portanto, alternativas aos fármacos comumente empregados na terapia antibacteriana, especialmente em infecções multi-resitentes, são alvo de estudos e desenvolvimento. Relações entre mudanças estruturais de 2-[5-nitro-tiofen-2-il]-3-acetil-5-[4- fenil-substituído]-2,3-diidro-1,3,4-oxadiazolinas e suas respectivas concentrações inibitórias mínimas podem fornecer informações sobre a influência de propriedades físico-químicas na ação antibacteriana destes compostos, informações estas que podem contribuir para o entendimento das relações entre a estrutura química e a atividade biológica desta classe de compostos, visando a identificação qualitativa e quantitativa das propriedades físico-químicas que influenciam no perfil farmacológico desta classe de compostos. Os grupos substituintes introduzidos nos derivados de 2,3-diidro-1,3,4-oxadizolinas-2,3,5-substituídas contribuem para alterações em suas propriedades físico-químicas, sendo representadas por parâmetros físico-químicos que descrevem a natureza e intensidade da alteração observada. O presente trabalho objetivou identificar, partindo das propriedades físico-químicas, fatores da estrutura química que favoreçam a atividade antimicrobiana dos compostos estudados. A atividade antimicrobiana, expressa pela concentração inibitória mínima, foi determinada pelo procedimento de microdiluição sucessiva, no qual diferentes concentrações de composto a ser analisado foram incubadas em presença de inóculo de Staphylococcus aureus, em meio de cultura líquido. As microdiluições originam concentrações decrescentes a fim de se determinar a menor concentração do composto testado onde o crescimento microbiano foi inibido. Foram realizadas comparações entre as concentrações inibitórias mínimas dos compostos analisados e destas com parâmetros estruturais que representam as propriedades físico-químicas dos compostos. Baseado nas análises comparativas, identificou-se tendências que evidenciam a preponderância de propriedades físicoquímicas sobre a atividade antimicrobiana desempenhada. Constatou-se que a hidrofobicidade influi significativamente na atividade antimicrobiana. Observou-se também que o efeito eletrônico por indução e o volume do grupo substituinte em posição para-fenila também influenciam a ação antimicrobiana, mas estas ainda não foram conclusivas, carecendo de estudos mais aprofundados que levem à compreensão dos fatores estruturais que mais influenciam a ação antimicrobiana de 2-[5-nitro-tiofen-2-il]-3-acetil-5-[4-fenilsubstituído]- 2,3-diidro-1,3,4-oxadiazolinas, de forma a fundamentar o planejamento de futuros candidatos a fármacos antimicrobianos a partir desta classe de compostos.
The introduction of a substitute group within a drug molecule promotes chemical-structure shifts, which by consequence, alters its physical-chemical properties. The atomic special design, particularly the one related to functional groups, assumed in a drug molecule, expressed by the physical-chemical properties, interferers directly or indirectly on drug-receptor interaction. Theses effects collaborate to pharmacologic and pharmacokinetics aspects of drugs, interfering with its therapeutic efficient. Therefore, a set of 2-[5-nitro-thiophen-2-yl]-3-acetyl-5-[4- substitued-phenyl]-3,4-dihydro-1,3,4-oxadiazolines compounds was designed and its analogs synthesized, structurally identified, and in vitro assayed due to its antimicrobial activity against ATCC 25923 Staphylococcus aureus strains, through the determination of minimum inhibitory concentration. Strains of such bacterial species are commonly present within hospital infections, and frequently appear as multi-resistant variant. Consequently, alternatives to the agents usually applied in antimicrobial chemotherapy, particularly to multi-resistant infections, are target for drug research and development. Relations among structural shifts on 2-[5-nitro-thiophen-2-yl]-3-acetyl-5-[4-substitued-phenyl]-3,4-dihydro-1,3,4-oxadiazolines compounds and its respective minimum inhibitory concentration may lead to information about the influence of physical-chemical properties in antimicrobial activity. Continually, such information might contribute to the elucidation of chemical structure-biological activity relationship of these compounds. The substitutes groups inserted on 2,3,5-substituted-3,4-dihydro-1,3,4-oxadiazolines derivates contribute to differs the molecule physical-chemical properties, which is represented by its physical-chemical parameters, which describe the nature and intensity of the observed modification. Therefore, the following study aimed to identify, throughout physical-chemical properties, chemical structure factors that favor the antimicrobial activity of the synthesized compounds. The antibacterial activity, expressed as the minimum inhibitory concentration, was quantified by the microdilution method, where gradual concentrations of the tested conpound were incubated within ATCC 25923 Staphylococcus aureus cells suspended in broth medium. The microdilutions originated descending concentrations, in order to spot the minimum concentration whose microbial growth was inhibited. The minimum inhibitory concentration regarded to each compound was correlated to its physical-chemical parameters. Based on observed relations, it could be identified evidences assuming the physical-chemical properties relevance on antimicrobial assay. It was verified that hydrophobic effects interferes with antimicrobial activity, as well as inductive electronic effects and molecular volume of substitute group in para-phenyl position. These factors contribute to physical-chemical properties shifts and therefore play a role on the antimicrobial action. However, these latest two influences were enable to conclude, suggesting the need of more extensive studies. So that, a more profound comprehension about structure factors that interfere with 2,3,5-substitued-3,4-dihydro-1,3,4-oxadiazolines derivates might lead to the rational design of potential antimicrobial agents among this class of compounds.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
In the present work, a series of 2-alkyl/arylchalcogenide-N-(4-aryl-1,3-thiazol-2-yl)acetamide was prepared via addition of aryl or alkyl chalcogenides. This methodology allowed the preparation of new derivatives of 2-amino-1,3-thiazoles in good yields. The compound synthesized is intended to evaluate the biological potential from the antioxidant activity by scavenging capacity of the assay by ABTS and DPPH. Was also developed a methodology for obtaining the compounds (S)-N-(alkyl-1-(3-aryl-1,2,4-oxadiazol-5-yl)-2-(phenylchalcogenide)acetamide derived from (S)-2-(2-(phenylchalcogenide)acetamido)alkanoic acids and arylamidoximes employing microwave irradiation. This synthesis was carried out in three conditions by varying the reaction time, temperature and solvent. The reactions employing microwave irradiation exhibit advantages against reactions using conventional method. These compounds were characterized by 1H NMR, 13C NMR and techniques high resolution mass spectrometry.
No presente trabalho, uma série de 2-alquil/arilcalcogeno-N-(4-aril-1,3-tiazol-2-il)acetamidas foi preparada via adição de calcogenetos de alquila ou arila. Essa metodologia permitiu a obtenção de derivados de 2-amino-1,3-tiazois em bons rendimentos. A proposta dessa síntese tem a finalidade de avaliar o potencial biológico a partir da atividade antioxidante por meio da capacidade sequestradora dos compostos sintetizados através de ensaios de ABTS e DPPH. Também foi desenvolvido uma metodologia para a obtenção dos compostos (S)-N-(1-(3-aril-1,2,4-oxadiazol-5-il)alquil)-2-(calcogenofenil)acetamidas derivados de ácidos (S)-2-(2-(calcogenofenil)acetamido)alcanoicos e arilamidoximas, empregando irradiação de micro-ondas. Para essa síntese foram desenvolvidas três condições reacionais variando o tempo reacional, temperatura e solvente. As reações conduzidas em micro-ondas apresentaram vantagens frente às reações em método convencional. Estes compostos foram caracterizados por técnicas de RMN 1H, RMN 13C e por espectrometria de massas de alta resolução.

4,5-Dihydro-1,2,3-oxadiazoles are postulated to be key intermediates in the synthesis of ketones from alkenes on an industrial scale, alkylation of DNA in vivo, decomposition of N-nitrosoureas (potent carcinogens), and are also a subject of great interest for theoretical chemists. In this thesis, formation of the parent compound and decay into secondary products has been studied by NMR monitoring analysis. The elusive properties and the intermediacy of the parent compound, 4,5-dihydro-1,2,3-oxadiazole, in the decomposition of suitably substituted N-nitrosoureas using Tl(I) alkoxides as bases, have been confirmed by the characterisation of its decay products viz., ethylene oxide, acetaldehyde, and especially diazomethane, at very low temperatures by 1H NMR, 13C NMR, 15N NMR, and relevant 2D NMR methods. Moreover, it has been shown that the methylation of nucleophilic molecules by 3-methyl-4,5-dihydro-1,2,3-oxadiazolium salts, which are considered to be activated forms of β−hydroxyalkylnitrosamines, does not involve 4,5-dihydro-1,2,3-oxadiazole as an intermediate, as has been reported in literature; instead, nucleophilic substitution leading to synthesis of open-chain products dominates the reaction
4,5-Dihydro-1,2,3-oxadiazole wurden als Schlüsselintermediate in der industriellen Synthese von Ketonen aus Alkenen, der in vivo Alkylierung von DNA und der Zersetzung von N-Nitrosoharnstoffen (potente Karzinogene) postuliert. Sie sind ebenso von großem Interesse in der theoretischen Chemie. Im Rahmen dieser Arbeit wurde die Bildung der Stammverbindung und deren Zersetzung in sekundäre Produkte mittels NMR-Verfolgung studiert. Die ausgesprochene Kurzlebigkeit der Stammverbindung 4,5-Dihydro-1,2,3-oxadiazol wurde durch die Charakterisierung der Produkte bei der Zersetzung geeignet substituierter N-Nitrosoharnstoffe mit Tl(I)-Alkoxiden bestätigt. Die Zersetzungsprodukte Ethylenoxid, Acetaldehyd und besonders Diazomethan wurden bei sehr niedrigen Temperaturen mittels 1H-NMR, 13C-NMR, 15N-NMR und relevanten 2D-NMR-Methoden charakterisiert. Des Weiteren konnte gezeigt werden, dass die Methylierung nucleophiler Spezies mit 3-Methyl-4,5-dihydro-1,2,3-oxadiazoliumsalzen, welchen als aktivierte Äquivalente der β−Hydroxyalkylnitrosamine verstanden werden, nicht zur Bildung von 4,5-Dihydro-1,2,3-oxadiazol als Intermediat führt, so wie dies in der Literatur berichtet wurde. Stattdessen wird die Bildung offenkettiger Produkte durch nukleophile Substitution bevorzugt

碩士
國立中央大學
化學學系
103
In the first series, a new system of isoxazole containing function group of aldehyde, performed reaction of Schiff Base then exhibition mesomorphic properties was synthesize and examined. 2b exhibited SmC phase. The control group 2a with N、SmC phase and 2c exhibited SmC phase. Results indicated that increasing the rigid cores would raise the isotropic temperatures and increasing the OH functional group would supply hydrogen bonds for molecular arrangement regularity. Using variable temperature IR spectroscopy observed the change of interaction. 1b、1c performed reaction of cyclization exhibited N, SmC and/or SmA phase. 1d was extended from 1b, and exhibited N phase. Two single crystallographic structures(1b、1d) were determined by X-ray crystallographic analysis. These mesomorphic properties were studied and identified by polarization microscopy, differential scanning calorimetry, and X-ray diffraction methods. In the second series, we succeed to synthesize three heterocyclic symmetric structure, 1e, characterization and their mesomorphic properties investigated. One single crystallographic structures were determined by X-ray crystallographic analysis. Compare with other similar example, results indicated that isoxazole effected upon the molecular arrangement more than 1, 3, 4-oxadiazole but mesomorphic properties were no difference.

碩士
國立成功大學
化學系專班
96
Using conducting materials as emission layer (EML), Organic light-emitting diode (OLEDs) has been applied on monitors. Its contribution has drawn more and more attention from academic and industrial circles. Currently the components of electroluminescent are composed in the way of multi-layers, that means to paint a coating of electron transport layer (ETL) and hole transport layer (HTL) separately between electrode and emission layer, so as to control the injection balance of electron and hole and manufacture best luminous element. This study focuses on synthesizing 1,3,4-oxadiazole ring that has electron transport capacity to be the main frame, and finding out the effect of its 2,5 positions to the derivatizing reaction of non-aromatic substituent and various reagents to its productive rate. This report uses 4-nitrobenzoyl chloride and various benzohydrazide of substitutional group to carry out condensation reaction and obtained dicarboxylic hydrazide compound, then through various cyclization reagents to carry out cyclization reaction to form 2,5-aromatic base oxadiazole derivate. There after , following up the study of various nitro- hydrogenation reduction reaction and synthesized 1,3,4-oxadiazole derivate that contains aminopheny. Finally, using amino group, ketones, diphenyl ketone, methyl iodide, and benzoyl chloride to carry out various condensation and substitution reactions, so as to prepare various derivatives of 2,5-aromatic base, -1,3,4- oxadiazole (2,5-diaryl-1,3,4- oxadiazole) ring organic luminous materials.

碩士
國立交通大學
應用化學系碩博士班
99
We report here the design and synthesis of a series of highly selective fluorescent chemodosimeters 45－49 for Fe3+, where 1,2,4-oxadiazoles were introduced to the lower-rim of calix[4]arene by using 1,3-dipolar cycloaddtion of aryl nitrile oxides with nitrile groups. Control compound 50 and isoxazole 51 were also synthesized for comparison. Structures of anthryl-1,2,4-oxadiazolyl cailx[4]arenes 45 and 50 were confirmed by X-ray diffraction analysis. 　　Anthryl-1,2,4-oxadiazole substituted calix[4]arenes 45－49 all showed a high selectivity and strong fluorescence quenching toward Fe3+ among 17 other metal perchlorate salts in CH3CN. Moreover, in the presence of Cu2+, the metal based oxidant, phenolic-OH of calix[4]arenes 45－47 were oxidized and their fluorescence was turned off. 　　Results from the 1H NMR titration of 46, 50 and 51 showed that all proton signals were significantly shifted and the anthryl-H10 signal disappeared. Because Fe2+ could be easily detected by ferrozine, the irreversible chemical reaction between anthryl-1,2,4-oxadiazole group and Fe3+ was confirmed to be a redox reaction. 　　The oxidation of the control compounds 50 led to the formation of products X1, where the anthryl-C10 was found to be oxidized into a carbonyl group. Based on X1 molecular ion from Mass we propose the possible structures of the unknown X1. Two other by-products 63 and 64, resulting from the oxidation of the control compound 50, were confirmed by single crystal X-ray analysis. 　　Upon addition of different amounts of Fe3+, the oxidation of lower- rim bis-anthryl-1,2,4-oxadiazoly calix[4]arene 46 led to the formation of products X2－X4. From 1H, 13C NMR, and IR spectra of X3－X4, we found that the anthryl-C10 was oxidized into carbonyl group (C=O). Moreover, the lower rim phenol of calix[4]arene was oxidized into carbonyl group (C=O) which formed the oxidation product X2.

碩士
國立中央大學
化學學系
103
This thesis is devided into four different series. In series 1, two new structures of unsymmetric 1, 3, 4–oxa(thia)–diazoles 1a–b and 2 containing both quinoxaline and naphthalene moieties were prepared and their mesomorphic properties were investigated. The mesomorphic behavior of compounds 1–2 was studied by DSC analysis and polarized optical microscopy. All compounds 1a and 2 exhibited hexagonal columnar phases (Colh), which were also confirmed by powder XRD diffractometer. Ncell and Rar values equal to 5.23 and 22.73 Å within a slice of 9.0 Å thick were also obtained for 1a (n=16), indicating that a more disc-like structure constructed by two molecules lying side-by-side was correlated in Colh phases. In contrast, all compounds 1b were not mesogenic, and the lack of mesomorphic properties in 1b might be due to their unfavorable conformations. The PL spectra of all compounds 1a, b showed one intense peak at λmax = 509–512 nm, and these photoluminescent emissions originated from quinoxaline moiety. In series 2, four new series of quinoxaline with four kind of 1, 3, 4–oxadiazoles spacer 1a–d were designed and prepared. Their mesomorphic properties were investigated. The mesomorphic behavior of compounds 1a–1d was studied by DSC analysis and polarized optical microscopy. All compounds 1a and 1d exhibited hexagonal columnar phases (Colh), which were also confirmed by powder XRD diffractometer. Ncell values equal to 2.85 and 2.16, Rar values are 20.49 and 22.74 Å within a slice of 9.0 Å thick were also obtained for 1a (n=12) and 1d (n = 12), indicating that a single molecule was packed within the columns in Colh phases. In contrast, all compounds 1c were not mesogenic, and the lack of mesomorphic properties in 1c might be due to their unfavorable conformations. The PL spectra of all compounds 1a–1d showed one intense peak at λmax = 517–529 nm, and these photoluminescent emissions originated from quinoxaline moiety. In series 3, three new materials of catenar liquid crystals 1a–c derived from heterocyclic bisoxazoles and bisthiazoles exhibiting columnar phases were reported. All compounds 1a–c exhibited hexagonal columnar phases, which were also confirmed by powder XRD diffractometer. Compounds 1a have a slightly wider temperature range of columnar phases than those of compounds 1b, which might be attributed to higher core dipole polarized in 1a. A Ncell and Rar value equal to 2.54–2.76 and 19.99–20.45 Å within a slice of 9.0 Å thick were obtained for three derivatives 1a–c (all n = 12), indicating that a single molecule was packed within the columns in Colh phases. All derivatives showed good stabilities at temperature below T = 408.8 C on TGA analysis. The PL spectra of all compounds 1a–c showed one intense peak at λmax = 505–510 nm, and these photoluminescent emissions originated from quinoxaline moiety. In series 4, three new series of multiple heterocyclic compounds 1a–c constructed by bis–pyrazoles, bis–1, 3, 4–oxadiazoles and thiophene exhibiting mesophases were reported. Crystallographic data showed that the crystal 1a (n = 8) is a linear–shaped molecule with a molecular length of ca. 40.57 Å. However, three heterocyclic rings were not coplanar. All compounds 1a formed smectic A/C phases, and all compounds 1c exhibited columnar phases, which were confirmed by powder XRD diffractometer. A Ncell and Rar value equal to 3.91 and 18.29 Å within a slice of 9.0 Å thick were obtained for derivatives 1c (n = 8), indicating that two molecule was correlated within columns in Colh phases. All derivatives showed good stabilities at temperature below T = 383–426 C on TGA. The PL spectra of all compounds 1b–c (n = 8) showed one intense peak at λmax = 418–496 nm, and these photoluminescent emissions originated from 1, 3, 4–oxadiazole moiety.

Ondřej Kučera Charles University in Prague, Faculty of Pharmacy in Hradec Králové Synthesis and study of 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)hexanoic acid derivatives as transdermal permeation enhancers Transdermal permeation enhancers are used to increase absorption of drugs through skin or, more importantly, through the stratum corneum, which is the uppermost layer of the skin. Mechanism of action of enhancers is not fully understood. In general the most active enhancers consist of hydrophilic and hydrophobic parts. In this work, we prepared and studied fluorescent permeation enhancers. Fluorescent dye NBD (7-nitrobenzo[c][1,2,5]oxadiazol) is fairly hydrophilic, so we used it as a hydrophilic head of potential enhancers based on dodecyl 6- (dimethylamino)hexanoate (DDAK). Such fluorescent enhancers could help us understand more about the mechanism of action. It enables determination of this enhancer and imaging of its penetration pathways in the skin. We synthesized three esters of 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-hexanoic acid (NBD-acid) with ester-linked C8-C12 alkyls. 6-Aminocaproic acid reacted with 4-chloro- NBD and then with a series of alcohols to give us different lengths of alkyl chains. We applied these enhancers to human skin in Franz diffusion cells using two...

碩士
國立交通大學
應用化學系碩博士班
101
In part 1, we successfully synthesized 1,2,4-oxadiazloe derivatives 24, 30a, 30b and 30c using 1,3-dipolar cycloaddtion reaction of anthryl nitrile oxide with a nitrile group. Compound 24 was found to show a high selectivity toward Fe3+ (among 18 different metal ions) in CH3CN with a strong fluorescence quenching. Compound 24 underwent a Fe3+-induced irreversible oxidation to afford compound X1 as the major product and compounds 25 and 26 as minor products. Compounds X1, 25 and 26 were isolated and characterized by organic spectroscopic data; furthermore, they were also confirmed by single crystal X-ray crystallography analysis.Three other analogues of 3-aryl-1,2,4-oxadiazoles 30a-30c were synthesized, however, they did not undergo Fe3+-induced irreversible oxidation in CH3CN as analyzed by NMR and UV-vis spectroscopy. Among the 3-aryl-1,2,4-oxadiazoles derivatives, we found that only compound 24 with anthracene as a fluorophore is a chemodosimeter for Fe3+. We also found that anthracene alone was oxidized by Fe3+ to afford oxanthrone, which proves that anthracene moiety is the key component of 24 as a Fe3+ selective chemodosimeter. In part 2, we report the synthesis of 1,3-alternate calix[4]arene derivative 57 using click reaction to get methyl triazoliumpyrene at the lower rim, and crown[5] ether at the upper rim. Compound 57 was found to show a high selectivity toward K+ (among 17 different metal ions) and I- (among 13 different anions) in CHCl3/MeOH (1/3, v/v) with fluorescence quenching. The pre-complex 57．K+ improved its binding ability toward I- by roughly 2 fold as compared to 57 alone. It exhibits a positive heteroditropic sensing effect toward KI. Interestingly, compound 57 was found to exhibit self-assembly behaviour in 1H NMR and DOSY spectra under various concentrations (0.2 to 30 mM in CHCl3).