Submitted by Mario BC (mario@bc.ufrpe.br) on 2017-08-04T13:49:34Z No. of bitstreams: 1 Edilma Elayne da Silva.pdf: 1799072 bytes, checksum: a16d73453614482f084d66d0824fa3d9 (MD5) / Made available in DSpace on 2017-08-04T13:49:34Z (GMT). No. of bitstreams: 1 Edilma Elayne da Silva.pdf: 1799072 bytes, checksum: a16d73453614482f084d66d0824fa3d9 (MD5) Previous issue date: 2014-01-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This report describes the synthesis and structural and biological characterization of 1,2,4-oxadiazoles that are used as precursors to 2,1-unsaturated glycosides. Arilamidoximas synthesis, starting materials of interest were obtained in good yields (70-92%) compared with the results already reported. The 1,2,4-oxadiazoles are synthesized by three methods (a) heating without solvent and without a base, (b) microwave irradiation and (c) reflux solvente. Os based compounds and 3-aryl-[1 2,4-oxadiazol-5-yl]-propan-2-one (48 a-g) The obtained compounds were subjected to reduction by providing the 3-aryl-[1,2,4-oxadiazol-5-yl]-propan-2-ol (51 a-g). Compounds were brows to verify in vitro cytotoxicity against cells tumor showing moderate result. O-glycosides novel 2,3-unsaturated were obtained from the rearrangement Ferrier tri-O-acetyl-D-glucal (29) with the alcohols (51a-d) in the presence of a catalyst montimorillonita in good yields (92% -96%) to afford eight diastereomers. he range of the brine shrimp toxicity of these compounds in turn obtained satisfactory results showed high toxicity to brine shrimp was observed (LD50 ˂ 125 mg / ml) demonstrating that the compounds are promising and may have broad and diverse biological activity. The structures of the compounds obtained were elucidated by conventional spectroscopic techniques: nuclear magnetic resonance NMR and 1H and 13C. / Neste trabalho, é descrito a síntese e caracterização estrutural e biológica de 1,2,4-oxadiazóis que serão utilizados como precursores de glicosídeos 2,1-insaturados. A síntese de arilamidoximas, produtos de partida de interesse que foram obtidos em bons rendimentos (70-92%) quando comparado com resultados já descritos na literatura. Os 1,2,4-oxadiazóis foram sintetizados através da três metodologia (a) aquecimento sem solvente e sem base,(b) irradiação de micro-ondas e (c) refluxo com base e solvente.Os compostos 3-aril-[1,2,4 –oxadiazol-5-il]-propan-2-ona(48 a-g). Os compostos obtidos foram submetido a redução fornecendo os 3-aril-[1,2,4 –oxadiazol-5-il]-propan-2-ol (51 a-g).Os compostos foram testas para verificar a citoxicidade in vitro frente a células tumorais apresentando resultado moderados .Os O-glicosídeos 2,3-insaturados inéditos foram obtidos a partir do Rearranjo de Ferrier do tri-O-acetil-D-glucal(29)com os alcoóis (51a-d) em presença de montimorillonita como catalisador,com rendimentos bons (92%-96%) obtendo oito diastereoisômeros .Foi verificada a faixa de toxicidade sobre a Artemia salina estes compostos por sua vez obtiveram resultado satisfatório apresentou alta toxicidade para a Artemia salina (DL50 ˂ 125 μg/mL) o que demonstra que são promissores compostos e podem apresentar atividade biológicas vastas e diversas. As estruturas dos compostos obtidos foram elucidadas através de técnicas espectroscópicas convencionais: Infravermelho e Ressonância Magnética Nuclear de 1H e 13C.

No description available.

Made available in DSpace on 2015-05-14T13:21:26Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 8587505 bytes, checksum: 3dc99b05c6b4e46c71e2ec550261f7cf (MD5) Previous issue date: 2013-01-18 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Among the heterocyclic compounds, 1,3,4-oxadiazole represents an important unit for the development of new drugs, since compounds containing this unit present a broad spectrum of biological activities such as antibacterial, antifungal, analgesic, anti- inflammatory, antiviral, antitumor, antihypertensive, anticonvulsant, etc. We describe the synthesis, characterization and antimicrobial activity of heterocyclic compounds of class 2,3-dihydro- 1,3,4-oxadiazole, specifically, 3-acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazole, that were obtained as racemic mixture from the reaction of cyclization of N-acylhydrazones using acetic anhydride. Compounds were divided into three sets congeners as follows: series 1 (2-aryl-3- acetyl-5-(pyridin-4-yl)-2,3-dihydro-1,3,4-oxadiazol), series 2 (2-(5-nitrofuran-2-yl)-3-acetyl- 5-aryl-2,3-dihydro-1,3,4-oxadiazol) and series 3 (2-(4-acetoxyphenyl)-3-acetyl-5- aryl-2,3- dihydro-1,3,4-oxadiazol). All compounds were characterized by spectroscopic techniques IR, 1H-NMR, 13C-NMR and mass spectrometry. In the evaluation of the in vitro antimicrobial activity, compounds of the series 2 exhibit efficient activity against several strains of Staphylococcus aureus with minimum inhibitory concentration in the range of 8 to 32μg/mL, being more potent than the standard drug chloramphenicol, and good antifungal activity against six Candida strains with minimum inhibitory concentration values ranging from 64 to 512 μg/mL. / Entre os compostos heterocíclicos, 1,3,4-oxadiazol representa uma importante unidade de construção para o desenvolvimento de novos fármacos, uma vez que compostos que contém esta unidade possuem um amplo espectro de atividades biológicas tais como: antibacteriana, antifúngica, analgésica, anti-inflamatória, antiviral, antitumoral, antihipertensiva, anticonvulsivante, etc. Neste trabalho, descreve-se a síntese, caracterização e atividade antimicrobiana de compostos heterocíclicos da classe 2,3-diidro-1,3,4-oxadiazol, especificamente, 3-acetil-2,5-diaril-2,3-diidro-1,3,4-oxadiazol, que foram obtidos como mistura racêmica a partir da reação de ciclização de N-acilhidrazonas usando anidrido acético. Os compostos foram divididos em três séries congêneres como: série 1 (2-aril-3-acetil-5- (piridin-4-il)-2,3-diidro-1,3,4-oxadiazol), série 2 (2-(5-nitrofuranil)-3-acetil-5-aril-2,3-diidro- 1,3,4-oxadiazol) e série 3 (2-(4-acetoxifenil)-3-acetil-5-aril-2,3-diidro-1,3,4-oxadiazol). Todos os novos compostos foram devidamente caracterizados por técnicas espectroscópicas de IV, RMN de 1H e 13C e espectrometria de massa. Na avaliação da atividade antimicrobiana in vitro, os compostos da série 2 exibiram eficiente atividade frente a diversas linhagens de Staphylococcus aureus ensaiadas com concentração inibitória mínima na faixa de 8-32μg/mL, sendo mais potente do que o fármaco padrão cloranfenicol, e boa atividade antifúngica contra seis linhagens de Candida com concentração inibitória mínima na faixa de 64 a 512μg/mL.

Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2017-09-06T12:10:14Z No. of bitstreams: 1 2017 - Paulo Pitasse Santos.pdf: 13320307 bytes, checksum: b714828ac2a5d9a1d2ab188470e04e9a (MD5) / Made available in DSpace on 2017-09-06T12:10:14Z (GMT). No. of bitstreams: 1 2017 - Paulo Pitasse Santos.pdf: 13320307 bytes, checksum: b714828ac2a5d9a1d2ab188470e04e9a (MD5) Previous issue date: 2017-02-20 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Chagas disease was studied and described by the Brazilian sanitarist and physician Carlos Chagas in 1909. It is caused by the protozoan Trypanosoma cruzi and presents complex clinical manifestations. However, since its discovery, little progress has been made in the chemotherapeutic treatment of Chagas' disease. The only available drug for its treatment (benzonidazole) is not completely efficient and is associated with the development of several side effects. From the knowledge of the antiparasitic activity of the natural amidic alkaloid piperine, this work focused on the proposition of new structurally-similar molecules with trypanocidal potential. From the principles of bioisosterism, a series of new 1,2,4-oxadiazoles were proposed. Its synthesis was designed from the corresponding 3-arylacrylic acids to give the respective acyl chlorides by reaction with oxalyl chloride. The subsequent step involves O-acylation of the properly substituted benzamidoxime following the cyclization reaction of the oxadiazolic ring, which occurs in solid support (silica gel) using microwave irradiation. The characterization of the products was done by determination of melting points, 1H and 13C NMR, infrared espectrometry and high and low resolution mass spectrometry. The present work also presents information about the biological activity profile of the molecules synthesized against epimastigote forms of the T. cruzi protozoan and against primary mammalian cells, allowing the calculation of their selectivity indexes. Investigations about the possible mechanisms of action of the derivatives on T. cruzi indicate that there are no influences on the enzymatic action of the protease cruazain, on the cell cycle of the parasite or on the biosynthesis of membrane sterols catalyzed by the enzyme CYP51. The developed sinthetic methodology can be applied in the expansion of the series of analogues derivatives. The perspectives of this work also include the biological evaluation against amastigote and trypomastigote forms of the parasite. / A doen?a de Chagas foi estudada e descrita pelo m?dico sanitarista e cientista brasileiro Carlos Chagas, em 1909. ? causada pelo protozo?rio Trypanossoma cruzi, apresentando manifesta??es cl?nicas complexas. No entanto, desde sua descoberta, pouco se avan?ou no tratamento quimioter?pico da doen?a de Chagas, sendo o f?rmaco dispon?vel (benzonidazol) pouco eficiente e associado ? manifesta??o de diversos efeitos colaterais. A partir do conhecimento da atividade antiparasit?ria da amida natural piperina, este trabalho focou-se na proposi??o de novas mol?culas estruturalmente semelhantes com potencial tripanocida. A partir dos princ?pios do bioisosterismo, foi proposta uma s?rie de novos 1,2,4-oxadiaz?is diferentemente substitu?dos. Sua s?ntese foi concebida partir dos ?cidos 3-arilacr?licos correspondentes, obtendo-se os respectivos cloretos de acila, atrav?s da rea??o com cloreto de oxalila. A etapa posterior envolve a O-acila??o da benzamidoxima adequadamente substitu?da, seguida do fechamento do anel oxadiaz?lico, que se d? em em suporte s?lido (s?lica-gel) empregando-se irradia??o de micro-ondas. A caracteriza??o dos produtos foi feita atrav?s de ponto de fus?o, RMN 1H e 13C, espectrometria no infravermelho e espectrometria de massas de alta e baixa resolu??o. O presente trabalho ainda traz informa??es quanto ao perfil de atividade biol?gica das mol?culas sintetizadas frente a formas epimastigotas do protozo?rio Trypanosoma cruzi e frente a c?lulas prim?rias de mam?feros, permitindo que se calculasse o seu ?ndice de seletividade. Investiga??es quanto a poss?veis mecanismos de a??o dos derivados sobre o T. cruzi indicam n?o haver influ?ncias sobre a a??o enzim?tica da protease cruza?na, sobre o ciclo celular do parasito, nem sobre a bioss?ntese de ester?is de membrana, catalisada pela enzima CYP51. A metodologia qu?mica desenvolvida poder? ser aplicada na s?ntese de outros an?logos. As perspectivas deste trabalho incluem ainda a avalia??o biol?gica frente a formas amastigota e tripomastigota do parasito

Made available in DSpace on 2015-05-14T12:59:39Z (GMT). No. of bitstreams: 1 Arquivototal.pdf: 1442527 bytes, checksum: 9d12b86569a24dac4080acc552110564 (MD5) Previous issue date: 2012-02-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / It was observed the pharmacological effects of OXDINH, a 1,3,4-oxadiazole derivative obtained by organic synthesis, on the cardiovascular system and the involvement of K+ channels in this response, were studied in rats using techniques combined in vivo and in vitro. In the superior mesenteric artery rings isolated from rats with functional endothelium, OXDINH (10-10 - 10-4 M) induced relaxation of contractions induced by phenylephrine (1 μM) (pD2 = 5.33 ± 0.16, Emax = 117.03 ± 6.49%, n = 7) concentration dependent manner and this effect was not attenuated after removal of the vascular endothelium (pD2 = 5.15 ± 0.09; Emáx = 108.58 ± 6.03%, n = 6). These results suggest that the response induced by vasorelaxant OXDINH seems to be independent of the vascular endothelium. Based on these initial observations, the subsequent experiments were performed with preparations without endothelium. In the preparations incubated with KCl 20mM, a modulator of the efflux of K+, the vasorelaxant effect induced OXDINH was changed (pD2 = 4.67 ± 0.08; Emáx = 57.71 ± 1.72%, n = 5), which is a characteristic of substances that act by activating K+ channels. This effect was corroborated after the use of tetraethylammonium (TEA) 3 mM (Emáx = 44.26 ± 2.41%) that this concentration does not selectively block K+ channels. In addition, the vasodilating effect OXDINH was significantly attenuated after incubation with 4- aminopyridine (1 mM) (Emáx = 61.17 ± 5.55%), glibenclamide (10 μM) (Emáx = 57.00 ± 4.07%), or BaCl2 (30 μM) (Emáx = 61.87 ± 7.52%), selective blockers of KV, KATP and KIR, respectively. By using TEA (1 mM), which at this concentration is more selective for the BKCa, vasodilatation was also found to be significantly attenuated (Emáx = 47.31 ± 5.75%), suggesting the involvement of these channels in this effect. Additionally, when OXDINH (10-5 and 10-4 M) was incubated in depolarizing medium nominally without Ca2+, CaCl2 induced contractions were not changed. However, these contractions were significantly attenuated concentration dependent manner when OXDINH (10-4 M) was incubated in saline without Ca2+ and nominally in the presence of phenylephrine (10μM). In non-anesthetized normotensive rats, OXDINH (1, 5 and 10 mg.kg-1 iv, randomly) produced hypotension accompanied by tachycardia. Interestingly, the highest dose (30 mg.kg-1) of OXDINH, the pressor and tachycardic response was, probably by a direct effect of the compound in the heart. In conclusion, these results suggest that the biological effects induced by OXDINH seem to directly involve the participation of K+ channels, probably by repolarization / hyperpolarization of the membrane and consequent closure of Cav, preventing the influx of Ca2+ through these channels. / Os efeitos farmacológicos de OXDINH, um derivado 1,3,4-oxadiazol obtido por síntese orgânica, sobre o sistema cardiovascular e a participação dos canais para K+ nesta resposta, foram estudados em ratos usando técnicas combinadas in vivo e in vitro. Em anéis de artéria mesentérica superior isolada de rato, com endotélio funcional, OXDINH (10-10 10-4 M) induziu relaxamento das contrações induzidas por fenilefrina (1 μM) (pD2 = 5,33 ± 0,16, Emáx= 117,03 ± 6.49 %, n = 7) de maneira dependente de concentração e esse efeito não foi atenuado após remoção do endotélio vascular (pD2=5,15 ± 0,09, Emáx= 108,58 ± 6.03 %, n = 6). Esses resultados sugerem que a resposta vasorelaxante induzida pela OXDINH parece ser independente do endotélio vascular. Baseado nessas observações iniciais, os experimentos subseqüentes foram realizados com preparações sem endotélio vascular. Em preparações incubadas com KCl 20 mM, um modulador do efluxo de K+, o efeito vasorelaxante induzido por OXDINH foi alterado (pD2= 4,67 ± 0,08, Emáx= 57,71 ± 1.72%, n = 5), sendo esta uma característicade substâncias que agem por ativar canais para K+. Este efeito foi corroborado após utilização de tetraetilamônio (TEA) 3 mM (Emáx= 44,26 ± 2.41%), que nesta concentração bloqueia não seletivamente os canais para K+. Além disso, o efeito vasodilatador do OXDINH foi significativamente atenuado após incubação com 4- aminopiridina 1 mM (Emáx= 61,17 ± 5,55%), glibenclamida 10 μM (Emáx= 57,00 ± 4,07%), ou BaCl2 30 μM (Emáx= 61,87 ± 7.52%), bloqueadores seletivos dos KV, KATP e KIR, respectivamente. Ao utilizar TEA 1 mM, que nesta concentração é mais seletivo para os BKCa, a vasodilatação também foi atenuada de modo significante (Emáx= 47,31 ± 5.75%), sugerindo a participação destes canais neste efeito. Adicionalmente, quando OXDINH (10-5 e 10-4M) foi incubado em meio despolarizante nominalmente sem Ca2+, as contrações induzidas por CaCl2 não foram alteradas. Porém, estas contrações foram significativamente atenuadas, de maneira dependente de concentração, quando OXDINH (10-4M) foi incubado em solução fisiológica nominalmente sem Ca2+ e na presença de fenilefrina (10μM). Em ratos normotensos não anestesiados, OXDINH (1; 5 e 10 mg.kg-1 i.v., randomicamente) produziu uma hipotensão acompanhada por taquicardia. Interessantemente, na maior dose administrada (30 mg.kg-1) de OXDINH, a resposta foi pressora e taquicárdica, provavelmente por um efeito direto do composto no coração. Em conclusão, esses resultados sugerem que os efeitos biológicos induzidos por OXDINH parecem envolver diretamente a participação de canais para K+, provavelmente pela repolarização/hiperpolarização da membrana e, consequente fechamento dos Cav, impedindo o influxo de Ca2+ através desses canais.

Submitted by Maike Costa (maiksebas@gmail.com) on 2017-06-21T12:11:13Z No. of bitstreams: 1 arquivototal.pdf: 5280829 bytes, checksum: 081debefa3f10398a1c9461855ba5b9d (MD5) / Made available in DSpace on 2017-06-21T12:11:14Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 5280829 bytes, checksum: 081debefa3f10398a1c9461855ba5b9d (MD5) Previous issue date: 2015-07-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Two series based on the structure of 2,5-diaryl-1,3,4-oxadiazole were synthesized, 2-aryl-5-methyl-1,3,4-oxadiazole (1a,h) and 2-aryl-5- trifluoromethyl-1,3,4-oxadiazole (2a,e), and their biological activity were investigated. These compounds had their chemical structures characterized with spectrometric methods such as IR, 1H and 13C NMR. To characterize the compound 2-(2-acetoxyphenyl)-5-methyl-1,3,4- oxadiazole, it was necessary the use of two-dimensional NMR techniques (COSY, HMQC and HMBC) and his structural arrangement was analyzed by the crystallographic X-ray technique. Mass spectrometric investigation, unprecedented for this class of compound, was also performed. All compounds were tested against eight strains of Staphylococcus aureus, Escherichia coli and also against strains of Aspegilles fumigatus, Aspegilles flavus, Candida albicans, Candida albicans and Candida tropicalis. The results showed that compounds 1b, 1c, 1e, 1g, 2a and 2c, produced inhibition on the growth of species of bacteria and fungi, where the MIC was set between 512 to 1224 mg mL-1. While the compounds 1d, 1e, 1f, 1h, 2a and 2b were inactive, the compounds 1d, 1e, 1f, 1h, 2a and 2b reported a broad spectrum. / Duas séries do heterocíclico 1,3,4-oxadiazol foram sintetizadas, a 2-aril-5-metil-1,3,4-oxadiazol (1a, h) e a 2-aril-5-trifluormetil-1,3,4- oxadiazol (2a, e), obtendo cinco moléculas inéditas (1a, 1e, 2a, 2c e 2e). Todas as moléculas obtidas foram caracterizados pelas técnicas espectroscópicas de 1D de RMN 1H e 13C, IV e realizado o estudo inédito de espectroscopia de Massas. Para a caracterização do composto 2-(2- acetoxifenil)-5-metil-1,3,4-oxadiazol se fez necessário a utilização das técnicas bidimensionais de RMN COSY, HMQC e HMBC, bem como seu arranjo estrutural foi analisado pela técnica cristalográfica de Raios-X. Os oxadiazóis obtidos foram avaliadas frente a oito cepas de Staphylococcus aureus e Escherichia coli e oito cepas, incluindo, Aspegilles fumigatus ATCC 16913, Aspegilles flavus, Candida albicans, Candida albicans e Candida tropicalis. Os ensaios para avaliações da atividade biológica dos produtos foram realizados pela técnica de microdiluição em meio líquido, onde foi determinada a concentração Inibitória Mínima (CIM). Os resultados mostraram que os compostos (1b), (1c), (1e), (1g), (2a) e (2c), produziram inibição sobre o crescimento de espécies de bactérias e de fungos, onde a CIM ficou estabelecida entre 512 a 1224 mg/ml. Enquanto que os compostos 1d, 1e, 1f, 1h, 2a e 2b se apresentaram inativos. Já os compostos 1d, 1e, 1f, 1h, 2a e 2b relataram um amplo espectro.

Diese Arbeit befasst sich mit dem Einfluss der molekularen Struktur von 2,5-Diphenyl-1,3,4-Oxadiazol-Derivaten auf die Präparierung dünner Schichten mittels Vakuumdeposition. Dünne Schichten von diesen Substanzen wurden auf Si/SiO2 aufgedampft und ihre Struktur systematisch mittels XSR, AFM und IR untersucht. Das Ergebnis zeigt, dass die Schichtstrukturen offenbar von Substratetemperatur (Ts) abhängig sind. Im untersuchten Ts-Bereich bilden etherverbrückte Oxadiazole immer geordnete Schichten und die Schichtperiodicität hängt linear von der Längen der aliphatischen Ketten, während sich bei den amidverbrückten Oxadiazolen nur bei hohen Ts geordnete Schichten bilden können. Diese Unterschiede sind auf die intermolekularen Wasserstoffbrücken zurückzuführen. Der Tilt-Winkel der Moleküle ist durch die Wechselwirkung zwischen dem aromatischen Teil bestimmt. Die Wechselwirkungen zwischen den Kopfgruppen können durch Tempern abgeschwächt werden und führen zur Strukturumwandlung von Schichten, die auf etherverbrückten Oxadiazolen basieren. Alle Schichten von etherverbrückten Oxadiazolen haben Doppelschicht-Struktur, aber amidverbrückte Oxadiazole bilden nur Doppelschicht-Strukturen, wenn die Moleküle eine Kopfgruppe besitzen. / The correlations between the chemical structures of the 2,5-diphenyl-1,3,4-oxadiazole compounds and their corresponding vapour deposited film structures on Si/SiO2 were systematically investigated with AFM, XSR and IR for the first time. The result shows that the film structure depends strongly on the substrate temperature (Ts). For the compounds with ether bridge group, the film periodicity depends linearly on the length of the aliphatic chain. The films based on those oxadiazols have ordered structure in the investigated substrate temperature region, while die amide bridged compounds form ordered film only at high Ts due to the formation of intermolecular H-bond. The tilt angle of most molecules is determined by the pi-pi complexes between the molecules. The intermolecular interaction between head groups leads to the structural transformation during the thermal treatment after deposition. All the ether bridged oxadiazoles form films with bilayer structure, while amide bridged oxadiazole form film bilayer structure only when the molecule has a head group.

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.

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.