There are immense efforts to install the trifluoromethyl group (CF3) into organic molecules since it significantly affects reactivity, as well as the biological and pharmaceutical properties of the molecule. The α-trifluoromethylacrylates are useful synthetic intermediates for the synthesis of trifluoromethyl-bearing nucleosides or peptides. However, methods to prepare such derivatives are scarce and suffer narrow substrate scope, lack of diastereoselectivity, use of costly reagents, and lack of user‐friendliness. Chapter 2 discusses the synthesis of α‐trifluoromethylacrylates from converting shelf-stable α‐trifluoroborylacrylates via a stereoretentive radical trifluoromethylation with inexpensive reagents NaSO2CF3 and TBHP with copper catalysis at room temperature. Under these conditions, a wide substrate scope afforded the (E)‐diastereomer exclusively in moderate to good yield. The reaction products' utility is demonstrated in synthesizing phenyl‐4H‐pyran, a potent and selective class of IKCa channel blockers. Branching out from metal-catalyzed reactions, Chapter 3 and 4 discusses metal-free organo-catalytic reactions which are more economical and greener. Boron-containing compounds are important in organic chemistry due to the different transformations that can be performed to afford useful synthetic intermediates and pharmaceuticals. Chapter 3 elaborates on the Borylation of 1,3-butadiynes, which are molecules that are widely used to synthesize biologically active molecules, polymers, and supramolecular tools under phosphine-catalyzed conditions. The reaction proceeds with both regio- and stereo-selectivity, and the boryl group is installed on the beta carbon to the alkyne in a trans fashion as established from 2D NMR and X-ray crystallography. The reaction products are converted into useful intermediates under Suzuki Miyuara, protodeborylation, etc. 31P NMR tudies were conducted to understand the mechanism of the reaction, which is supported by the DFT calculations revealing that phosphine attack is the most crucial step. A similar strategy was utilized with pinacol borane and tri-n-butyl phosphine catalyst to achieve borylation on ynamides (Chapter 4). A wide variety of ynamides underwent hydroboration to install the boron group in a regio- and stereoselective fashion. Under radical trifluoromethylating conditions, the boryl moeity was converted into the trifluoromethyl group to afford β-CF3 enamides. 31P NMR studies were conducted to elucidate the mechanism. Finally, chapter 5 provides insight into the synthesis of 1,2,4-Oxadiazoles which are privileged scaffolds in medicinal chemistry. The developed reaction occurs under metal-free conditions using sodium carbonate to couple N-hydroxylbenzenecarbonimodyl chlorides with nitriles. / Doctor of Philosophy / Installing fluorine in organic molecules significantly improves their pharmaceutical properties and the trifluoromethyl (CF3) group is one such group. Chapter 2 describes a simple, cost-effective method to synthesize trifluoromethylated compounds with readily available reagents under copper-catalyzed conditions, whereas in Chapters 3 and 4, a metal-free method is discussed. In comparison with metal catalysts, organo catalysts are less toxic, readily available, avoid contamination, and are more economic. Boron is used for different transformations in organic chemistry and for making medicinally relevant molecules. An organo-catalytic method to install boron on various substrates and potential applications of such molecules as synthetic intermediates are discussed. 1,2,4-Oxadizoles are molecules that are considered privileged scaffolds imparting pharmaceutical properties. Finally, in Chapter 5, a procedure to synthesize 1,2,4-Oxadiazoles under mild reaction conditions and readily available reagents are discussed.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-04-18T17:37:33Z No. of bitstreams: 1 wiliamcaneschi.pdf: 24031147 bytes, checksum: 55a6b3c64e0dad5d05212886301c8aa2 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-04-19T11:42:35Z (GMT) No. of bitstreams: 1 wiliamcaneschi.pdf: 24031147 bytes, checksum: 55a6b3c64e0dad5d05212886301c8aa2 (MD5) / Made available in DSpace on 2017-04-19T11:42:35Z (GMT). No. of bitstreams: 1 wiliamcaneschi.pdf: 24031147 bytes, checksum: 55a6b3c64e0dad5d05212886301c8aa2 (MD5) Previous issue date: 2016-12-20 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os heterociclos oxadiazólicos estão presentes em inúmeras estruturas com diversas propriedades biológicas, por esse motivo, o interesse nessa pesquisa. Desse modo, este trabalho encontra-se dividido em dois capítulos: o primeiro refere-se a síntese de oxadiazóis com intuito de verificar seu potencial biológico, enquanto o segundo, baseia-se no desenvolvimento de novas metodologias para síntese dos derivados 1,2,4 e 1,3,4oxadiazólicos. No primeiro capítulo, vinte e uma substâncias derivadas do heterociclo 1,2,4oxadiazólico foram obtidas por meio de reações de substituição nucleofilica de segunda ordem e trinta e dois novos derivados 1,3,4-oxadiazólicos foram obtidos a partir de reações do tipo Mannich. Os compostos foram testados quanto as suas propriedades citotóxicas e antibacteriana. De um modo geral, os derivados 1,2,4-oxadiazólicos não apresentaram interessantes atividades biológicas. Por outro lado, os regioisômeros 1,3,4- demonstraram um perfil de atividade interessante, sendo mais ativas que aquelas moléculas contendo o grupo piperazina alquilado com doze átomos de carbono. Para a atividade antitubercular, foi verificada uma melhor atividade para os 1,3,4-oxadiazóis alquilados com quatorze átomos de carbono. A busca cada vez maior por metodologias mais simples e eficientes na síntese de novas substâncias, propiciou, neste segundo capítulo, a síntese de uma série de derivados 1,2,4- e 1,3,4-oxadiazólicos obtidos por reações de aminocarbonilação catalisadas por paládio. Vários nucleófilos hidrazidas e amidoximas foram passíveis de reação com diferentes brometos de arila e monóxido de carbono produzido ex situ, em uma reação multicomponente, possibilitando a formação desses heterociclos em altos rendimentos. Essa metodologia se mostrou eficaz na marcação isotópica de ¹³C para diferentes compostos bem como permitiu a síntese do fármaco ataluren com rendimento global de 43%. / Oxadiazoles heterocycles are present in many structures with different biological properties, therefore, the interest in this research. So, this work is divided in two chapters: the first refers to the synthesis of these heterocycles in order to verify its biological potential, while the second is based on the development of new methodologies for synthesis of derivatives 1.2, 4 and 1,3,4-oxadiazoles. In the first chapter, twenty one 1,2,4-oxadiazoles derivatives were obtained by nucleophilic substitution reactions of second order and thirty two new 1,3,4oxadiazoles derivatives were obtained through Mannich-type reactions. The compounds were tested for their anticancer and antibacterial properties. In general, 1,2,4-oxadiazoles derivatives did not show interesting activity against the tested pathologies. On the other hand, 1,3,4-regioisomers demonstrated interesting activity profile, being most active those molecules containing the alkylated piperazine group with twelve carbons chain. For the antitubercular activity, a better activity was verified for the alkylated 1,3,4oxadiazoles with fourteen carbon chain. The search for efficient and simple methods for the synthesis of new molecules, allowed in the second chapter, the synthesis of a number of 1,2,4- and 1,3,4-oxadiazoles derivatives obtained by reactions palladium-catalyzed aminocarbonylation reactions. Various nucleophiles hydrazides and amidoximes were able of reaction with different aryl bromides and carbon monoxide produced ex situ in a multicomponent reaction, enabling the formation of such heterocycles in high yields. This methodology was effective for isotopic ¹³C labeling for different compounds as well as allowed the synthesis of the drug ataluren in an 43% overall yield.

This work first describes the synthesis of the starting materials, the 1,2,4- and 1,3,4-oxadiazoles, from arylamidoximes and arylhydrazides derivatives, respectively. These two precursors were previously reacted with the 2-chloroacetyl chloride, and after cyclodehydration formed the desired heterocycles in satisfactory yields (10 examples, 67-99 %). The heterocyclic starting materials were submitted to aliphatic nucleophilic substitution reactions (SN2) against calcogenolates derived from arylic and alkylic disselenides and thiols. The selenolates were obtained in reducing medium of NaBH4 and anhydrous ethanol, whereas the thiolates were formed by treatment of thiols in basic medium of Et3N, so that the products from these substitutions were obtained in good yields (41 examples, 25-99 %). Some aspects of the methodologies employed were also studied, and some statements are possible, because when using tellurium don’t occurred the formation of the desired products, and also the formation of by-products unwanted. Secondly, the heterocyclic starting materials were re-subsumed to the SN2 reactions, but now, against potassium chalcogenocyanates (KSCN and KSeCN) in acetonitrile and the presence of an ammonium salt (TBAB), which aimed to catalyze reactions of aliphatic substitutions. The molecules from these reactions were obtained in excellent yields (12 examples, 69-92 %), which were subsequently submitted to the cycloaddition reactions (3+2) with NaN3, in a solution of toluene and Et3N.HCl, to form the respective 1H-tetrazoles (12 examples, 49-99 %). The products obtained contain, in the same molecule, the oxadiazolic, tetrazolic and chalcogen core. Chalcogencyanates and tetrazoles were further evaluated in vitro for their antioxidant properties by reducing the DPPH radical and Mo (VI) to Mo (V), so that two chalcogencyanates and one tetrazole presented good results for the phosphomolibidenium test. The cyclic voltammetry technique was also used to evaluate the redox potential of these compounds. Some compounds obtained in the first stage of this work are under evaluation of their antioxidant properties, but preliminary tests presented promising results for the molecules in question. / Este trabalho descreve, inicialmente, a síntese dos materiais de partida, os 1,2,4- e 1,3,4-oxadiazóis, derivados de arilamidoximas e arilhidrazidas, respectivamente. Estes dois precursores reagiram previamente com o cloreto de 2-cloroacetila e após ciclodesidratação formaram os heterociclos desejados em rendimentos satisfatórios (10 exemplos, 67-99%). Os materiais de partida heterocíclicos foram submetidos às reações de substituição nucleofílica alifática (SN2) frente aos calcogenolatos derivados de disselenetos e tióis arílicos e alquílicos. Os selenolatos foram obtidos em meio redutor de NaBH4 e etanol anidro, já os tiolatos formam-se pelo tratamento de tióis em meio básico de Et3N, de modo que os produtos provenientes destas substituições foram obtidos em bons rendimentos (41 exemplos, 25-99%). Foram ainda, estudados alguns aspectos das metodologias empregadas, e algumas afirmações são possíveis, pois quando se utilizaram reagentes de telúrio não ocorreu a formação dos produtos desejados, e ainda se constatando a formação de subprodutos indesejados. Em um segundo momento, os materiais de partida heterocíclicos foram submetidos novamente às reações SN2, porém agora frente à calcogenocianatos de potássio (KSCN e KSeCN), em acetonitrila e na presença de um sal de amônio (TBAB), que teve como finalidade catalisar as reações de substituições alifáticas. As moléculas provenientes destas reações foram obtidas em excelentes rendimentos (12 exemplos, 69-92%), sendo que estes foram posteriormente submetidos às reações de cicloadição (3+2) com NaN3, em uma solução de tolueno e Et3N.HCl, formando os respectivos 1H-tetrazóis (12 exemplos, 49-99%). Os produtos obtidos contêm, em uma mesma molécula, os núcleos oxadiazólico, tetrazólico e calcogênio. Os calcogenocianatos e os tetrazóis foram ainda submetidos à avaliação de suas propriedades antioxidantes in vitro, por meio da redução do radical DPPH e do Mo (VI) à Mo (V), de forma que dentre os compostos avaliados, dois calcogenocianatos e um tetrazol exibiram bons resultados para o teste de fosfomolibidênio. Foi ainda utilizada a técnica de voltametria cíclica com o intuito de avaliar o potencial redox desses compostos. Alguns compostos obtidos, na primeira etapa deste trabalho, estão sob avaliação de suas propriedades antioxidantes, porém testes preliminares apresentaram resultados promissores para as moléculas em questão.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-05-22T14:02:19Z No. of bitstreams: 1 karinebragaenes.pdf: 7466338 bytes, checksum: 0e0ed747f5f8a7f155224bc895ca8db6 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-22T17:37:37Z (GMT) No. of bitstreams: 1 karinebragaenes.pdf: 7466338 bytes, checksum: 0e0ed747f5f8a7f155224bc895ca8db6 (MD5) / Made available in DSpace on 2017-05-22T17:37:37Z (GMT). No. of bitstreams: 1 karinebragaenes.pdf: 7466338 bytes, checksum: 0e0ed747f5f8a7f155224bc895ca8db6 (MD5) Previous issue date: 2017-03-06 / O câncer é uma das maiores causas de morte no mundo e, por consequência, é uma questão de saúde pública. Desse modo, a especialidade oncológica tem despertado o interesse de muitos, devido à deficiência de um arsenal terapêutico abrangente e eficaz. Tendo em vista a gravidade dessa doença e, com o intuito de desenvolver moléculas ativas, este trabalho descreve a síntese de 1,2,4-oxadiazóis acoplados a diaminas, o que resultou na obtenção de vinte compostos inéditos, dentre eles: um oxadiazol intermediário e dezenove derivados acoplados a diaminas, sendo três deles alquilados. Foram obtidos quatro oxadiazóis, após duas etapas de síntese, a partir da reação de benzonitrilas com hidroxilamina seguida por reação com brometo de bromo acetila. Para a obtenção das estruturas finais, os oxadiazóis foram condensados às diaminas, gerando vinte e quatro compostos. Além disso, três oxadiazóis inéditos foram obtidos pela condensação do respectivo heterociclo com a piperazina alquilada a partir dos brometos ou cloretos de alquila. As estruturas dos compostos obtidos foram elucidadas por espectroscopia na região do infravermelho e RMN de 1H e de 13C. Os derivados oxadiazólicos finais foram submetidos à avaliação da atividade citotóxica, como proposto inicialmente, porém nenhum deles se mostrou ativo frente às células testadas. Além disso, os compostos foram testados quanto a sua atividade antibacteriana, sendo que três compostos se mostraram ativos frente a duas cepas de bactérias, e antitubercular, porém, nenhum dos derivados mostrou atividade frente à cepa Mycobacterium tuberculosis. / One of the biggest causes of death in the world is cancer, and therefore it is a public health concern. In this way, the oncology field is of great interest to many researches, due to the deficiency of a comprehensive and effective therapeutic arsenal. Considering the severity of this disease, and in order to develop active molecules, in this work we describe the synthesis of 1,2,4-oxadiazoles coupled to diamines, which resulted in the obtaining of twenty novel compounds, among them: an intermediate oxadiazole and nineteen derivatives coupled to diamines, three of them being alkylated. Four oxadiazoles were obtained after two steps of synthesis, from the reaction of benzonitriles with hydroxylamine followed by reaction with bromine acetyl bromide. In order to obtain the final structures, the oxadiazoles were condensed to the diamines, generating twenty-four compounds. In addition, three novel oxadiazoles were obtained by condensing the respective heterocycle with the alkylated piperazine from the alkyl bromides or chlorides. The structures of the obtained compounds were elucidated by infrared spectroscopy and 1H NMR and 13C. The final oxadiazolic derivatives were submitted to evaluation of cytotoxic activity, as initially proposed, but none of them were active against the cells tested. In addition, the compounds were tested for their antibacterial activity, and three compounds were active against two strains of bacteria, and antitubercular, but none of the derivatives showed activity against the strain Mycobacterium tuberculosis.

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-25T12:04:02Z No. of bitstreams: 1 williamcaneschi.pdf: 11580354 bytes, checksum: d5186d98d0e023e595e7509f1a08efff (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-25T13:32:21Z (GMT) No. of bitstreams: 1 williamcaneschi.pdf: 11580354 bytes, checksum: d5186d98d0e023e595e7509f1a08efff (MD5) / Made available in DSpace on 2017-05-25T13:32:21Z (GMT). No. of bitstreams: 1 williamcaneschi.pdf: 11580354 bytes, checksum: d5186d98d0e023e595e7509f1a08efff (MD5) Previous issue date: 2013-02-22 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Diversos análogos 1,3,4-oxadiazóis tem sido reportados na literatura uma vez que possuem grande espectro de atividade biológica, como: antiviral, antibacteriano, antitumoral, antioxidante, anti-inflamatório, anticonvulsivante, antimalarial, antifúngica e analgésica. Com o intuito de desenvolver moléculas ativas e seletivas a certas doenças, este trabalho descreve a síntese de derivados N-acilidrazonas e seus respectivos 2,3-diidro-1,3,4-oxadiazóis, o que resultou na obtenção de vinte e sete derivados inéditos, dentre eles: nove derivados de Nacilidrazonas e dezoito derivados 2,3-diidro-1,3,4-oxadiazóis. Foram obtidos vinte e oito derivados N-acilidrazonas a partir de uma reação de adição de aldeídos aromáticos e heteroaromáticos com a isoniazida. Para a obtenção das N-acilidrazonas com cadeia longa, foi proposto, inicialmente, a alquilação do 4-hidroxibenzaldeído com haletos de alquila com: 1-cloroexano, 1-cloro-octano, 1-bromononano, 1-clorodecano, 1-clorododecano, 1-lorotetradecano e 1-bromo-propargila. Foi proposta também a síntese de dois derivados sulfonados, sintetizados pela mesma metodologia de alquilação com os cloretos de mesila e tosila. Em seguida, os aldeídos alquilados e sulfonados sintetizados e dezenove aldeídos comerciais foram condensados a isoniazida gerando os derivados N-acilidrazonas, que por sua vez, foram ciclizados, em reação com anidrido acético, que gerou vinte e sete derivados 2,3-diidro-1,3,4-oxadiazólicos. As estruturas dos compostos obtidos foram elucidadas por espectroscopia na região do infravermelho, RMN de 1H e de 13C, técnicas de RMN 2D, espectrometria de massas. Os análogos oxadiazólicos foram submetidos a teste de citotoxicidade, antibacteriano, antioxidante e antimalarial. Os compostos se mostraram bastantes ativos contra células cancerígenas, com índices de seletividade superiores ao composto padrão utilizado. / Several analogs 1,3,4-oxadiazoles have been reported in the literature due to wide range biological activity, such as: antiviral, antibacterial, antitumoral, antioxidant, anti-inflammatory, anticonvulsivant, antimalarial, antifungal e analgesic activity. With the aim to develop molecules active and selective for some illness, this work describe the synthesis of some N-acyl-hydrazones derivatives and the respective 2,3-dihydro-1,3,4-oxadiazoles, that resulted the obtainment twenty seven inedited derivatives, among them: nine N-acyl-hydrazones derivatives and eighteen 2,3-dihydro-1,3,4-xadiazoles derivatives. At this work were obtainment twenty e eight N-acylhydrazones derivatives through the addition reaction of aromatics and heteroaromatics aldehydes with isoniazid. For the obtainment of N-acyl-hydrazones of long chain, the 4-hydroxybenzaldehyde was alkylated with several alkyl halides: 1-chlorohexane, 1-chlorooctane, 1-bromononane, 1-chlorodecane, 1-chlorododecane, 1-hlorotetradecane and 1-bromopropargyl. It was also proposed the synthesis of two sulfa derivatives, synthesized by the same alkylation methodology with the mesyl and tosyl chloride. These alkylated aldehydes and nineteen commercials aldehydes were condensed to the isoniazid that gave the N-acyl-hydrazones derivatives, which in turn were cyclized to obtain the 2,3-dihydro-1,3,4-oxadiazoles derivatives in reaction with acetic anhydride. The structures of the compounds were elucidated by in infrared, ¹H NMR, ¹³C NMR, 2D NMR techniques, mass spectrometry. The oxadiazoles analogs were submitted to citotoxicity, antibacterial, antioxidant and antimalarial activity. The compounds showed great activity against tumor cells, with selectivity index higher than standard compound used.

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2012-2013. / Une nouvelle classe d'agent de déoxofluoration a été développée en 2009 par la compagnie OmegaChem en vue d'être des analogues alternatifs beaucoup plus stables que les réactifs standards DAST et Déoxo-Fluor®. En effet, ces réactifs cristallins de type aminodifluorosulfinium, connus sous le nom XtalFluor, ont démontré une excellente réactivité à l'égard de nombreux dérivés alcools et carbonyles fonctionnalisés lorsque ceux-ci sont accompagnés d'une source externe de fluorure. Ces sels sulfiniums ont du même coup montré une propriété d'activation intéressante au cours de cette transformation, ce qui fût le point de départ d'une investigation plus approfondie de ces réactifs. Ainsi, le sujet de ce mémoire porte sur l'étude de la réactivité du XtalFluor-E à titre d'agent d'activation potentiel dans d'autres réactions connues en synthèse organique. Une mise en contexte générale de la réaction de déoxofluoration, ainsi que les propriétés du réactif XtalFluor-E seront exposés dans un premier temps (Chapitre 1). Par la suite, les travaux portant sur l'utilisation de ce réactif en tant qu'agent de cyclodéshydratation pour la synthèse de composés N-hétérocycles, grandement utilisés entre autres en chimie médicinale, seront abordés. En effet, d'une part, le développement d'une nouvelle méthode de synthèse des motifs 1,3,4-oxadiazoles fonctionnalisés sera montré (Chapitre 2), qui sera suivi de l'expansion de cette nouvelle méthode pour la préparation de dérivés 2-oxazolines, 2-thiazolines et 2-benzooxazoles (Chapitre 3). Finalement, la grande réactivité du XtalFluor-E a permis de s'intéresser à son utilisation dans les réactions d'halogénations (chloration, bromation, iodation) à partir de divers composés alcools. Cette nouvelle méthodologie de synthèse sera présentée au Chapitre 4.

The structural, electronic, and optical properties of a series of organic pi-conjugated polymer, oligomer, or molecular materials of interest for applications in organic electronics are described. For this purpose, quantum-chemical techniques ranging from Density Functional Theory to Hartree-Fock ab initio and semiempirical methods are used to evaluate the charge-transport, charge-transfer, and electroluminescence properties of pi-conjugated organic materials. First, the effect of electronic polarization on the charge-transport parameters of organic semiconductors is discussed. A generalized methodology based on a basis set orthogonalization procedure is developed to determine reliable charge-transport characteristics. The charge-transport parameters of a number of organic semiconductors such as oligoacenes and derivatives are studied with this methodology. Then, triplet emitters, in particular iridium complexes, that achieve high efficiency electroluminescence in organic light-emitting diodes are discussed. The effects of ligand substitution and orientation on the luminescent properties of iridium compounds are investigated in order to develop structure-properties relationships. The emission properties of these complexes are found to be governed by an interplay between metal-to-ligand charge transfer excitations and ligand-centered and/or interligand excitations. The extent of mixing of these various excitations turns out to be highly dependent on the nature of the substituents. Design strategies to shift the emission color towards deep blue are proposed. Finally, several classes of materials acting as hosts for phosphorescent emitters are studied. It is shown that restricting the conjugation length leads to high energy gap host materials suitable for blue phosphorescent emitters.

Title: Phosphinoferrocene amides and hydrazides Author: Hana Solařová Department: Department of Inorganic Chemistry Supervisor: doc. RNDr. Petr Štěpnička, Ph.D. Abstract: While studying functionalized phosphinoferrocene ligands, we recently turned to phosphinoferrocene carboxamides. These donors already proved to be versatile ligands for coordination chemistry and catalysis. This led us to synthesize and study the archetypal representative, 1'-(diphenylphosphino)-1-carbamoylferrocene (5), and the corresponding hydrazide 6. PPh2 COOH Fe Hdpf PPh2 CONH2 Fe 5 PPh2 CONHNH2 Fe 6 This work describes the preparation of primary amide 5 and hydrazide 6 from 1'- (diphenylphosphino)-1-ferrocenecarboxylic acid (Hdpf) via the corresponding acylbenzo- triazole derivative. The hydrazide was alternatively obtained from Hdpf methylester and hydrazine hydrate. Both newly synthesized compounds were characterized by spectroscopic methods (NMR, IR, and MS) and elemental analysis, and their crystal structures were determined by single-crystal X-ray crystallography. The amide was further utilized in the preparation of several palladium complexes, which were characterized in a similar manner including X-ray crystallography. One palladium complex was obtained also from the hydrazide. However, the hydrazide was used mainly as a...