Academic literature on the topic '1,2,4,5-tétrazine'

Cette thèse se compose de deux parties. La première traite de la synthèse et des études électrochimiques et de fluorescence de nouveaux dérivés de la 1,2,4,5 tétrazine en tant que sondes moléculaires pour des anions et des composés riches en électrons. La seconde traite de la synthèse et des études électrochimiques préliminaires de sels de ferrocène à base de pyridinium. Dans la partie I, une vue d'ensemble de la chimie des 1,2,4,5 tétrazine (s tétrazines) est présentée. Les stétrazines ont déjà trouvé des applications dans beaucoup de domaines, mais leur capacité à se lier avec des anions ou des composés riches en électrons par interactions anion n ou empilement n n n'a été démontrée que très récemment. Dans ce contexte, une série de nouvelles sondes moléculaires contenant des noyaux tétrazine servant d'unités liantes et de détection a été conçue, comprenant des pinces tétrazines, des trépied tétrazines, des cyclophane tétrazines, et des calices tétrazines. Parmi eux, un trépied tétrazine (86), deux cyclophane tétrazines (90, 93) et deux calices tétrazines (94, 95) ont été synthétisés avec succès en se basant sur des réactions de type SNAr avec la 3,6 dichloro s tétrazine (23). Les études photophysiques prouvent que la fluorescence de 86, 90, 94 et 95 peut être efficacement éteinte par les composés riches en électrons tels que la triphénylamine (TPA), la tris (4 bromophényl) amine, le pyrrole, le tétrathiafulvalène (TTF) et le 1,3,5 triméthoxybenzène. Les études électrochimiques indiquent également la présence d'interactions entre les sondes de tétrazine et ces composés électron donneurs. Les mécanismes d'extinction de fluorescence sont étudiés dans certains cas, et des calculs d'orbitales moléculaires sont présenter pour expliquer le rapport entre les structures et les propriétés moléculaires de fluorescence. Dans la partie II, la synthèse d'un sel de pyridinium à deux branches contenant des ferrocènes (45j) et de deux analogues à trois branches (46h, 46j) obtenus par condensations du 1,2,6 triméthylpyridinium ou 1,2,4,6tétraméthylpyridinium avec des aldéhydes aromatiques est présentée. Une nouvelle voie de synthèse est également développée pour les deux intermédiaires importantes, le trans 5 (2 ferrocényl vinyl) 2 carbaldéhydethiophène (47), et l'aldéhyde du ferrocényléthényl bithiophényle (48). Les études électrochimiques préliminaires prouvent que les sousunités bithiophène influencent considérablement le comportement redox des molécules<br>This thesis consists of two parts. The first one deals with the synthesis and electrochemical and fluorescence studies of new 1,2,4,5 tetrazine derivatives as molecular sensors for anions and electron rich compounds, and the second one with the synthesis and preliminary electrochemical studies of ferrocene containing pyridinium salts. In part 1, a short overview of 1,2,4,5 tetrazine chemistry (s tetrazine) is presented. S Tetrazines have already found applications in many fields, but their ability to bind anions or electron rich compounds through anion n interaction or n n stacking bas not been noticed until very recently. In this context, a series of novel molecular sensors containing tetrazine moieties as both binding units and sensing units are designed, including tweezer tetrazines, tripodetrazines, cyclophane tetrazines, and calycular tetrazines. Among them, a tripod tetrazine (86), two cyclophaneetrazines (90, 93) and two calycular tetrazines (94, 95) have been successfully synthesized based on SNAr reactions of 3,6 dichlorotetrazine (23). Fluorescence studies show that the fluorescence of 86, 90, 94 and 95 can be efficiently quenched by electron rich compounds such as triphenylamine (TPA), tris(4 bromophenyl)amine, pyrrole, tetrathiafulvalene (TTF) and 1,3,5 trimethoxybenzene. Electrochemical studies also indicate the interactions between the tetrazine sensors and these electron rich compounds. The fluorescence quenching mechanisms are investigated in some cases, and calculations on molecular obitals are carried out to investigate the relationship between molecular structures and fluorescence properties. In part II, the synthesis of a dibranched ferrocene containing pyridinium salt (45j) and two tri branched ones (46h, 46j) through the condensations of 1,2,6 trimethyl pyridinium or 1,2,4,6 tetramethyl pyridinium with aromatic aldehydes is presented. A new synthetic route is also developed for the two important intermediates, trans 5 (2errocenyl vinyl) 2 carbaldehyde thiophene (47), and ferrocenylethenyl bithiopheneyl aldehyde (48). Preliminary electrochemical studies show that bithiophene units influence greatly the redox behaviors of the molecules

La détection de faibles quantités de petites molécules volatiles, qu’elles soient polluantes, utilisées comme armes chimiques ou encore explosives présente un intérêt sociétal certain. Les polymères de coordination poreux (PCPs) ou ’Metal-Organic Frameworks‘ (MOFs) sont des solides poreux qui peuvent être décrits par l’association de ligands organiques et de briques inorganiques interagissant par liaisons fortes et définissant une structure cristalline avec des pores de différentes tailles et formes. La large gamme d'application de ces solides (séparation, stockage, biomédecine...) repose sur leurs diversités chimique et structurale. Par exemple, il est possible de synthétiser des MOFs luminescents en utilisant un ligand organique lui-même luminescent. Le coeur tétrazine et ses dérivés sont des bons candidats pour cet objectif, puisqu'ils présentent des propriétés de fluorescence remarquables : émission dans le visible (λem~560 nm), bon rendement quantique. De plus, cette fluorescence peut être modifiée par la présence de molécules riches en électrons, ce qui laisse envisager son utilisation comme capteur moléculaire. Nos travaux se sont de plus focalisés sur des métaux à haut degré d'oxydation (Al(III), Zr(IV)) susceptibles de conférer aux solides une stabilité en milieu aqueux adéquate pour les applications envisagées. Deux acides carboxyliques à base de tétrazine, adaptés à la préparation de MOFs, ont tout d'abord été synthétisés. Le premier a été utilisé pour préparer un MOF à base de zirconium.La structure du solide, et entre autres son caractère flexible, ainsi que ses propriétés optiques ont été étudiées. Particulièrement, ses performances en tant que capteur d'amines aromatiques et de phénol ont été évaluées. La réactivité du second ligand avec les ions lanthanides a aussi été explorée et plusieurs solides ont été isolés, leur structure, caractérisée. Leurs propriétés optiques ont été évaluées, afin d'établir des relations entre la structure du MOF et la fluorescence de la tétrazine. Ensuite, avec ce même ligand, une stratégie de synthèse à ligand mixte a été adoptée pour incorporer la tétrazine dans des MOFs. Il s'agit de partir d'une structure aux propriétés avantageuses (stabilité, porosité) et de substituer une partie de ses ligands organiques ‘inactifs’ par des tétrazines. Ceci peut s'effectuer pendant la synthèse ou via un traitement post-synthétique. Les propriétés optiques des solides obtenus ont été enfin étudiées et leur efficacité en tant que capteur évaluées<br>Detection of low concentrations of small organic molecules, which can be hazardous, polluting or used as chemical weapons, represents a societal problem worth addressing. Metal-Organic Frameworks (MOFs) are a class of porous crystalline materials that can be described as an association of inorganic subunits and organic ligands defining an ordered structure with accessible cavities of various size and shape. The wide range of potential applications for these materials (biomedicine, gas separation, catalysis...) relies on their chemical and structural diversity, which allows combining porosity with additional properties. For example, it is possible to synthesize luminescent MOFs through the use of a luminescent organic ligand. The tetrazine core and its derivatives appear as good candidates for such a purpose, as they have a fluorescent emission in the visible spectrum (λem~560 nm) with a good quantum yield. In addition, this fluorescence can be affected by the presence of electron rich molecules, making their use possible as sensors for ions or organic molecules. Our work focused mainly on the design of MOFs based on tetrazine and cations of high charge density (Al(III), Zr(IV)) in order to ensure their stability in water, which is desirable in this field.Two different tetrazine dicarboxylic acids suitable for the preparation of MOFs were first synthesized. The first one was used to prepare a new MOF based on zirconium. The structure of this solid, together with its flexible character and its optical properties were investigated. Especially, its use for the sensing of aromatic amines and phenol was evaluated. The reactivity of the second ligand with lanthanide ions was then investigated and few solids were isolated and structurally characterized. Their optical properties have been studied, in order to establish some relationship between their structure and their fluorescence. Then, with the same ligand, a mixed-ligand strategy has been developed in order to incorporate the tetrazine into MOFs. This involves starting from a non-fluorescent MOF with interesting properties (stability, porosity) and substituting some of the 'inactive' ligands with these tetrazines. This was performed either during the synthesis or as a post-synthetic treatment. The spectroscopic properties of these solids were finally investigated and their efficiencies as sensors evaluated

Interest in linear peptides and peptidomimetics experienced rapid growth within the pharmaceutical industry due to their ability to disrupt protein-protein interactions; and their ability to modulate protein function by allosteric regulation and competitive binding. However, many linear peptides that show therapeutic potential cannot be readily developed into bioavailable pharmaceuticals due to their poor lipophilicity and protease stability; and their unpredictable secondary structures. Macrocyclic peptides show increased lipophilicity and protease stability; and their constrained secondary structures often lead to improved target binding affinity and selectivity. Consequently, there has been a resurgence of interest within the pharmaceutical industry towards peptide based therapeutics and increased research towards novel peptide macrocyclisation strategies. Progress towards a novel solid-phase peptide macrocyclisation strategy based on the inverse electron demand Diels-Alder reaction of 1,2,4,5-tetrazines is reported in this thesis. The solid-phase oxidation activation peptide macrocyclisation strategy uses the in situ oxidation of a dihydro-1,2,4,5-tetrazine to trigger the inverse electron demand Diels-Alder reaction of a 1,2,4,5,-tetrazine and therefore peptide macrocyclisation. Also, the solid-phase oxidation activation peptide macrocyclisation strategy enables selective late stage incorporation of the dihydro-1,2,4,5-tetrazine moiety onto the peptide backbone in the presence of a dienophile. A successful proof of concept in situ oxidation and inverse electron demand Diels-Alder reaction of a dihydro-1,2,4,5- tetrazine was achieved. However, the poor stability of a strained dienophile towards an oxidant was also highlighted. To overcome this problem a library of alternative oxidants and a library of unstrained dienophiles were screened to successfully optimise the proof of concept in situ oxidation and inverse electron demand Diels-Alder reaction of a dihydro-1,2,4,5-tetrazine. The optimised in situ oxidation and inverse electron demand Diels-Alder reaction of a dihydro-1,2,4,5-tetrazine was successfully transferred onto solid-phase using resin-bound dienophiles. However, attempts to synthesise resin-bound dihydro-1,2,4,5-tetrazine derivatised amino acids were unsuccessful. Therefore, an alternative dihydro-1,2,4,5-tetrazine was selected for future development of the solid-phase oxidation activation peptide macrocyclisation strategy.

Les travaux présentés dans ce mémoire de thèse portent sur la synthèse et l'étude des propriétés spectroscopiques et électrochimiques de systèmes donneur-accepteur conçus pour des applications variées telles que l'électrofluorochromisme, l'absorption à deux photons et le photovoltaïque. La s-tétrazine a été choisie comme accepteur pour sa forte affinité électronique, ses propriétés émissives remarquables et sa capacité à s'organiser via des interactions intermoléculaires de type &#61552--stacking. La triphénylamine a été sélectionnée comme donneur pour son faible potentiel d'ionisation, ses propriétés spectroscopiques (fortes absorption et émission) et la modulation facile de ses propriétés par changement de substituants. Sept dérivés de triphénylamine ont été synthétisés ainsi que dix-huit nouveaux composés multichromophoriques à base de tétrazine et de triphénylamine présentant cinq liens différents et des substituants variés. Ils ont été caractérisés par électrochimie et spectroscopie (stationnaire et résolue en temps). L'étude de la modulation de leurs propriétés photophysiques par le changement de l'état rédox a ensuite été réalisée. Dix composés présentant un lien permettant la conjugaison entre la triphénylamine et la tétrazine ont été synthétisés et caractérisés par électrochimie et spectroscopie. Compte-tenu de leurs propriétés, six d'entre eux ont été testés en absorption à deux photons et deux ont étés retenus pour être utilisés comme donneurs dans une cellule photovoltaïque organique. Par ailleurs, deux réactions ont été étudiées en détail pour expliquer la formation des produits obtenus, inattendus à un premier abord.

Many cancer drugs are inherently cytotoxic, leading to severe toxicity towards healthy tissues and organs. One effective strategy to circumvent these side effects is to mask a cytotoxic drug with a “caging group” which, once at the target tissues, releases the masked drug upon an appropriate trigger. In this study, 1,2,4,5-tetrazines which undergo bioorthogonal inverse electron demand Diels-Alder cycloadditions, were used as “chemical triggers” to unmask a “caged cargo”. The vinyl carbamate bond was successfully used as a caging group to ‘cage coumarin’ and was decaged with trigger ‘dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate’. However the trigger underwent hydrolysis under physiological conditions. Various 1,2,4,5- tetrazines were synthesized and hydrolytic stable 1,2,4,5- tetrazines were evaluated for decaging of caged coumarin but with no success. In depth stability of 1,2,4,5-tetrazines under physiological conditions was investigated before exploration alternative caging groups. The results obtained showed basic and physiological conditions had a deteriorating impact on the stability of 1,2,4,5-tetrazine with rapid degradation (t1/2 5– 50 min) in culture medium. The half-lives were significantly increased in acidic pH compared to basic pH (with up to a 187-fold increase from pH 9 to pH 5). Exploration of ketene-N,S-acetals, enamides, thioether-norbornene, enolethernorbornene and vinyl ether as caging groups was conducted. Only vinyl ethers proved to be a success with caging of two fluorophores i.e. fluorescein and resorufin. Two 1,2,4,5-tetrazines were effective in the decaging of the vinyl ether caged fluorophores in water and PBS. Bis-vinyl fluorescein was successfully decaged in HeLa cells showing the potential of vinyl ethers as a caging groups. In future, the vinyl ether would be used to cage a cytotoxic drug and its activation by 1,2,4,5-tetrazine functionalised with tumor targeting peptide or antibodies would result in localised and selective drug release.

This thesis describes the synthesis and properties of a number of novel substituted 1 ,2,4,5-tetrakis(amino )benzenes for which synthetic methods have only recently become available. Similar compounds have previously been observed as very electron rich systems; this thesis therefore explores some of the behaviour of these compounds that stems from this observed property. Chapter 1 details a proposed architecture for using single organic molecules as storage or processing units for single bits of binary data. This involves a bottom-up approach of creating single molecules, which could be used to fulfil the role of components in an integrated circuit. The design criteria that a molecule would need to fulfil in order to perform this task are discussed and substituted 1,2,4,5- tetrakis(amino )benzenes are suggested as possible candidates. Chapter 2 reports the results of a theoretical and computational study into the effects of ion-pairing on the observed electrochemical behaviour of tertiary 1,2,4,5-tetrakis(amino)benzenes. Compounds 1 - 6 are modelled using Density Functional Theory in the gas phase, in solution and as ion-pairs with [PF6] and [CI04] anions. The results of this study provide some insight as to why some of the tertiary tetrakis( amino )benzenes exhibit two-electron oxidation processes under certain conditions. Chapter 3 goes on to explore the synthesis of a selection of novel secondary tetrakis(amino)benzenes 9a - 11a based on recently published methods employing palladium catalysis. These new compounds have aromatic substituents on the nitrogen atoms and methyl or methoxy groups on the 3 and 6 positions of the central benzene ring. The ease with which these compounds can be oxidised to the corresponding benzoquinonediimines 9 - 11 is noted. Chapter 4 reports the discovery that these benzoquinonediimines can be oxidatively cyclised to produce the novel riminophenazines 12 and 13 or tetra(aza)pentacenes 14 and 15. The oxidative synthesis of these compounds is optimised and the tetra(aza)pentacenes are observed to be stable with regard to further oxidation and can form dications. Chapter 5 explores the ability of the benzoquinone diimines to form stable coordination compounds with a variety of rhodium-containing fragments producing a selection of binuclear complexes. These compounds were observed to be redox active. The effect on the redox potentials caused by changes to substituents on the central ring as well as the ancilliary ligands was investigated. Chapter 6 summarises the conclusions drawn in each of the preceding chapters to give an overall picture of the properties and behaviour of the compounds studied. These observations are linked to the electron rich nature of these compounds. Some comments are offered regarding how the compounds studied would meet the specification laid out for 'molecular bits'. A number of interesting observed properties are highlighted. Potential future applications of the compounds detailed herein are explored, and a range of derivative compounds which would be worthy of further study are highlighted.

Cette thèse se compose de deux parties. La première traite de la synthèse et des études électrochimiques et de fluorescence de nouveaux dérivés de la 1,2,4,5 tétrazine en tant que sondes moléculaires pour des anions et des composés riches en électrons. La seconde traite de la synthèse et des études électrochimiques préliminaires de sels de ferrocène à base de pyridinium. Dans la partie I, une vue d'ensemble de la chimie des 1,2,4,5 tétrazine (s tétrazines) est présentée. Les stétrazines ont déjà trouvé des applications dans beaucoup de domaines, mais leur capacité à se lier avec des anions ou des composés riches en électrons par interactions anion n ou empilement n'a été démontrée que très récemment. Dans ce contexte, une série de nouvelles sondes moléculaires contenant des noyaux tétrazine servant d'unités liantes et de détection a été conçue, comprenant des pinces tétrazines, des trépieds tétrazines, des cyclophane tétrazines, et des calices tétrazines. Parmi eux, un trépied tétrazine (86), deux cyclophane tétrazines (90, 93) et deux calices tétrazines (94, 95) ont été synthétisés avec succès en se basant sur des réactions de type SNAr avec la 3,6 dichloros tétrazine (23). Les études photophysiques prouvent que la fluorescence de 86, 90, 94 et 95 peut être efficacement éteinte par les composés riches en électrons tels que la triphénylamine (TPA), la tris (4 bromophényl) amine, le pyrrole, le tétrathiafulvalène (TTF) et le 1,3,5 triméthoxybenzène. Les études électrochimiques indiquent également la présence d'interactions entre les sondes de tétrazine et ces composés électrodonneurs. Les mécanismes d'extinction de fluorescence sont étudiés dans certains cas, et des calculs d'orbitales moléculaires sont présentés pour expliquer le rapport entre les structures et les propriétés moléculaires de fluorescence. Dans la partie II, la synthèse d'un sel de pyridinium à deux branches contenant des ferrocènes (45j) et de deux analogues à trois branches (46h, 46j) obtenus par condensations du 1,2,6 triméthylpyridinium ou 1,2,4,6tétraméthylpyridinium avec des aldéhydes aromatiques est présentée. Une nouvelle voie de synthèse est également développée pour les deux intermédiaires importantes, le trans 5 (2 ferrocényl vinyl) 2 carbaldéhydethiophène (47), et l'aldéhyde du ferrocényléthényl bithiophényle (48). Les études électrochimiques préliminaires prouvent que les sousunités bithiophène influencent considérablement le comportement redox des molécules.

Submitted by Marco Antônio de Ramos Chagas (mchagas@ufv.br) on 2016-05-12T09:00:32Z No. of bitstreams: 4 texto completo.pdf: 8315275 bytes, checksum: 9dd2106d4ac2f94ab959f96f25772c27 (MD5) Artigo 1.pdf: 1151286 bytes, checksum: 7e033f3b0a18d0bb5f1bc4b0b53dafd4 (MD5) Artigo 2.pdf: 2870615 bytes, checksum: e6ddb0194ef5633caaabbb8a6e1b0ab8 (MD5) Patente.pdf: 18231116 bytes, checksum: 3f6356bf0781afa63bd3222f1a33ba48 (MD5)<br>Made available in DSpace on 2016-05-12T09:00:32Z (GMT). No. of bitstreams: 4 texto completo.pdf: 8315275 bytes, checksum: 9dd2106d4ac2f94ab959f96f25772c27 (MD5) Artigo 1.pdf: 1151286 bytes, checksum: 7e033f3b0a18d0bb5f1bc4b0b53dafd4 (MD5) Artigo 2.pdf: 2870615 bytes, checksum: e6ddb0194ef5633caaabbb8a6e1b0ab8 (MD5) Patente.pdf: 18231116 bytes, checksum: 3f6356bf0781afa63bd3222f1a33ba48 (MD5) Previous issue date: 2015-01-05<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior<br>Os 1,2,4,5-tetraoxanos correspondem a compostos que apresentam em sua estrutura geral anel de 6 membros com 4 oxigênios, sendo sua síntese descrita como fácil, rápida e que utiliza reagentes de baixo custo. Os tetraoxanos têm comprovada ação na área farmacológica, especialmente para o tratamento da malária e apesar da facilidade sintética, não há qualquer registro na literatura sobre a avaliação dessa classe de compostos como herbicidas. Diante da semelhança estrutural dos tetraoxanos com os 1,2,4- trioxolanos (ozonídeos) por apresentarem em sua estrutura a porção peróxido, comprovadamente responsável pela atividade fitotóxica nos ozonídeos, além de ambos serem eficientes no combate à malária. O presente trabalho teve por objetivo sintetizar uma série de novos 1,2,4,5-tetraoxanos, visando a avaliação de sua atividade herbicida. Buscou-se ainda, realizar estudos teóricos de correlação estrutura-atividade (QSAR) visando compreender os fatores estruturais mais importantes para a atividade herbicida e assim prosseguir no processo de otimização da estrutura e produção de compostos mais ativos. Nesse sentido, os tetraoxanos foram preparados inicialmente a partir da conversão de aldeídos aromáticos (e/ou cetonas cíclicas e lineares) em 1,1- dihidroperóxidos na presença de peróxido de hidrogênio em meio ácido com rendimentos variando de 50% a 91%. Os hidroperóxidos então, reagiram com novos compostos carbonílicos em meio ácido para a formação de (20) vinte 1,2,4,5-tetraoxanos com rendimentos entre 10% e 52%. Os compostos sintetizados foram completamente caracterizados, utilizando-se as técnicas de espectroscopia no IV, espectroscopia de RMN de H e de 13 C, além de espectrometria de alta resolução. A atividade fitotóxica foi avaliada inicialmente in vitro em plantas indicadoras com rápida resposta, sorgo (Sorghum bicolor) para a classe das monocotiledôneas e pepino (Cucumis sativus) para as dicotiledôneas. Todos os compostos apresentaram alta taxa de inibição do crescimento radicular e parte aérea em ambas as plântulas, de modo que, procedeu-se análise estatística de agrupamento (análise de Cluster) por similaridade no tocante à fitotoxicidade. Sete tetraoxanos apresentaram resultados comparáveis ou superiores aos herbicidas comerciais, glyphosate e imazethapyr, utilizados como controle neste trabalho. Os compostos mais ativos foram então submetidos a testes in vivo com 4 espécies de plantas daninhas: monocotiledôneas Brachiaria brizantha (braquiária), Sorghum arundinaceum (falso-massambará) e dicotiledôneas Bidens pilosa (picão- preto), Euphorbia heterophylla (leiteiro). O resultado mais importante foi para o tetraoxano [39], que apresentou valores de inibição do crescimento radicular e da parte aérea estatisticamente superiores aos herbicidas testados, causando inclusive amarelecimento das folhas em plantas de Brachiaria brizantha. Além da atividade biológica supracitada, todos os compostos foram submetidos a estudos de QSAR e ainda foram estudadas uma série de propriedades teóricas que se avalia a partir dos dados obtidos se um determinado composto pode se tornar um novo herbicida. Procedeu-se também, devido a semelhança estrutural já citada, análise cristalográfica por difração de raios-x de sete ozonídeos (1,2,4-trioxolanos) preparados anteriormente (trabalho de Mestrado) e cinco deles cristalizam com sistema cristalino monoclínico e grupo espacial P2 1 /c. O composto [46] cristalizou de maneira incomum com grupo espacial centrossimétrico R m, representando apenas 0,04% do total de moléculas com estrutura conhecida. A estrutura supramolecular deste composto forma infinitas cadeiras no formato hexagonal, resultando em uma estrutura no formato de favo de mel. Utilizou-se ainda, cálculos teóricos, como o método semi-empírico PM6 e cálculos DFT utilizando o funcional B3LYP e o conjunto de bases 6- 31G(d) para otimizar a geometria das moléculas e calcular parâmetros estruturais como comprimento de ligação e ângulo, assim como ângulo diedro e comparar os resultados com os obtidos a partir da estrutura cristalina refinada. Os resultados mostraram correlação satisfatória entre os valores experimentais e teóricos.<br>The 1,2,4,5-tetraoxanes correspond to compounds having in their general structural 6-membered ring with 4 oxygen atoms, their synthesis being described as easily, quickly and using reagents with low economic value. The tetraoxanes have proven action in the pharmaceutical field, especially for the treatment of malaria and even synthetic ease, there is no report in the literature on the evaluation of this class of compounds as herbicides. Since the structural similarity of tetraoxanes with 1,2,4-trioxolanes (ozonides), having in their structure a portion peroxide responsible for phytotoxic activity in ozonides, and both are effective against malaria, the present study was order to synthesize a series of new 1,2,4,5-tetraoxanes and evaluate its herbicidal activity. Aimed to further conduct theoretical studies of structure-activity (QSAR) seeking to understand the most important structural factors for herbicide activity and thus proceed to the optimization of structure and production more active compounds. Accordingly, the tetraoxanes were initially prepared from the aromatic aldehyde conversion (and/or linear and cyclic ketones) in 1,1-hydroperoxides in the presence of hydrogen peroxide in an acid medium with yields ranging from 50% to 91%. Hydroperoxides then reacted with new carbonyl compounds in an acid medium to form twenty (20) 1,2,4,5-tetraoxanes with yields between 10% and 52%. The synthesized compounds were fully characterized using the techniques of IR spectroscopy, 1 H NMR spectroscopy and 13 C, in addition to High-Resolution Mass Spectrometry. The phytotoxic activity was initially assessed in vitro with plants of Sorghum bicolor for the class of monocotyledonous and Cucumis sativus for dicotyledons, where all compounds showed high inhibition rate of root growth and shoot in both the seedlings so that proceeded statistical analysis (Cluster analysis) with regard to the similarity phytotoxicity. Seven tetraoxanes showed results comparable or superior to commercial herbicides, glyphosate and imazethapyr used as a control in this study. The most active compounds were then subjected to in vivo tests with four weed species: monocots Brachiaria brizantha, Sorghum arundinaceum, and dicotyledons Bidens pilosa, Euphorbia heterophylla and as a result more importantly, tetraoxane [39] presented values of inhibition of root growth and shoot higher than to herbicides, including causing yellowing of leaves in plants of Brachiaria brizantha. Besides the biological activity, all compounds were been subjected to QSAR studied. Crystal structure analysis by X-ray was performed in seven ozonídeos due to the aforementioned structural similarity. Five of them crystallize in monoclinic crystal system and space group P21/c. The compound [46] crystallized unusually centrosymmetric space group R m, representing appended 0.04% of molecules with known structure. The supramolecular structure of this compound seats in endless form hexagonal shape, resulting in a structure in honeycomb form. Theoretical calculations were used, such as the semi-empirical method PM6 and DFT calculations using the B3LYP functional and the basis set 6-31G(d) for optimizing the geometry of the molecules and structural parameters as calculated bond and angle length, as dihedral angle and comparing the results with those obtained from the refined crystal structure. The results show good correlation between the theoretical and experimental values.