Dissertations / Theses on the topic 'Pyrazolones'

Nitrogen-containing heterocyclic compounds are very important to the pharmaceutical and agrochemical industries, among others. Over the past few years, the Beauchemin group has been exploring reactivity of N-substituted isocyanates and as part of this has developed a metal-free alkene aminocarbonylation process relying on imino-isocyanates to form azomethine imines. The azomethine imines formed are interesting since they contain a cyclic β-aminocarbonyl motif. Catalysis of this reaction using basic additives allowed milder reaction conditions with electron-rich C=C bonds such as enol ethers. Efforts have also been made towards the derivatization of these azomethine imines into useful products. It was discovered that upon reduction and aromatization of azomethine imines, pyrazolones could be obtained. This is providing a novel modular approach to these compounds, which have relevance in pharmaceuticals and agrochemicals. This reactivity was extended to include imino-isothiocyanates.

Etude de l'effet de l'acidite de la lipophilie et effets structuraux des acyl-4 pyrazolones-5 dans l'extraction de cu, co, zu et pb divalents. Extraction de 3 types de complexes metalliques : mononucleaires de type m(l-n-lh)::(2) ou m(l-n-l) et polynucleaires (m(l-n-l))::(j). Meilleures possibilites des bis-acyl-4 pyrazolones-5

La premiere partie de ce travail concerne l'etude thermodynamique de la complexation metallique des metaux de transition divalents m#2#+, (m = cu, zn, ni), des ions lanthanides trivalents ln#3#+, (ln = la, pr, sm, eu, ho, yb) et de l'ion uranyle uo#2#+#2 par des pyrazolones. Il s'agit de la mono-(acyl-4 pyrazolone-5), hpmbp et des di-(acyl-4 pyrazolones-5) ligands constitues de deux sites complexants, l, lies par une chaine polymethylene a n motifs -ch#2, ligands symbolises par : hl-n-lh (n = 4, 5, 7, 8). L'etude a ete menee dans l'eau et dans le solvant mixte eau-acetonitrile 40-60% en poids, en presence du sel de fond naclo#4 1 mol. L##1 et a 25c. Les valeurs des constantes de stabilite des complexes formes sont determinees par spectrophotometrie couplee a la ph-metrie et traitement informatise des donnees. Les resultats obtenus montrent la formation de complexes monoligands et biligands de stoechiometrie 1:1 et 1:2 dans le cas de hpmbp et de complexes mononucleaires ou binucleaires de stoechiometrie, (metal:ligand), 1:1 ou 2:1 dans le cas des hl-n-lh. Les resultats sont interpretes en fonction de la longueur de la chaine alkyle du ligand. Les influences du milieu et du rayon ionique des cations metalliques sur la stabilite des complexes sont discutees egalement. Des structures possibles des complexes en solution sont proposees. L'etude cinetique, qui constitue la seconde partie du travail, porte sur la comprehension des cinetiques de formation, de decomposition acide et d'echange metallique des chelates de l'ion ni#2#+ et de l'ion uo#2#+#2 avec les ligands decrits precedemment. L'etude menee par spectrophotometrie a ecoulement bloque, est faite dans les conditions experimentales de la premiere partie. Pour chaque reaction etudiee, une loi de vitesse et un mecanisme sont proposes. Dans le cas des reactions de formation de complexes, les mecanismes font intervenir des etapes rapides de formation d'intermediaires qui seraient des complexes a sphere externe, suivies de reactions d'interchange de ligands controlant la vitesse. Dans le cas de la decomplexation des chelates, nos resultats sont en accord avec le mecanisme generalement admis : l'ouverture de la premiere liaison metal-ligand controle la decomposition.

Extraction de cd et zn a partir des milieux aqueux, perchlorate, nitrate et sulfate par des melanges de phenyl-1 methyl-3 benzoyl-4 pyrazolone-5 et de sels d'ammonium lipophiles. Le pyrazolonate de nh::(4) est l'agent reel de synergie. Mecanisme de transport de cuivre par des acyl-4 pyrazolones-5 a travers une membrane liquide epaisse

Orientador: Fernando Antonio Santos Coelho
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química
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Resumo: Esse trabalho é composto de dois capítulos. No primeiro relatamos nossos esforços visando descrever a primeira síntese total da (+)-Napalilactona, um nor-sesquiterpeno clorado extraído do coral Lemnalia africana. Essa substância marinha possui quatro centros estereogênicos consecutivos em sua estrutura, dois deles quaternários, sendo que um destes centros quaternários pertence também a um anel espiro. A estratégia sintética utilizou a (S)-Carvona como material de partida, de modo que foi possível, através do centro pré-existente no monoterpeno de partida, gerar o primeiro centro existente no produto natural. A partir deste centro, utilizando metodologias já bem estabelecidas na literatura, foi possível induzir a formação de dois dos três centros restantes, de modo que 78% do esqueleto carbônico do produto natural foi construído em um total de 10 etapas, com um rendimento global de 3%. Na segunda parte desse trabalho relatamos os resultados obtidos em um estudo metodológico envolvendo a reação entre a aminoguanidinina, um bis-nucleófilo polinitrogenado, e adutos de Morita-Baylis-Hillman (MBH) sililados e acetilados. Frente aos adutos de MBH sililados, as reações com a aminoguanidina conduziram, através de um processo tandem, à formação de uma mistura diastereoisomérica de pirazolidinonas sililadas em excelentes rendimentos, sendo que o diastereoisomero syn é o favorecido em todos os casos. A diastereosseletividade dessa reação variou de 2:1 a 7:1 (syn:anti). Quando investigamos o comportamento da aminoguanidina frente aos adutos de MBH acetilados, utilizando como solvente a acetonitrila, as reações com a aminoguanidina conduziram, também através de um processo tandem, à formação exclusiva de pirazolidinonas benzilidênicas, quando um aduto oriundo de um aldeído alifático ou oriundo de um aldeído aromático substituído com grupos doadores de elétrons foram utilizados. No entanto, frente a adutos oriundos de aldeídos aromáticos com grupos retiradores de elétrons, foi observada uma tendência à formação de pirazolonas, que são regioisomeros das pirazolidinonas previamente obtidas. Estes dados indicaram que, sob estas condições, a natureza do grupo substituinte rege a seletividade destas reações. Mais tarde, observou-se que, ao submetermos as pirazolidinonas a uma solução de 2 equivalentes de K2CO3 em metanol, estas poderiam ser completamente convertidas às respectivas pirazolonas. Mostrando a influência da natureza do solvente nestas transformações químicas
Abstract: This work is composed by two chapters. In the first one we disclosed our efforts towards the first total synthesis of (+)-Napalilactone, a chlorinated nor-sesquiterpene isolated from the coral Lemnalia africana. This marine natural compound has four consecutive stereogenic centers in their structure, two of them quaternaries. One of these quaternary centers belonging to a spiro ring. Our synthetic strategy started from commercially available (S)-carvone. The asymmetric center presented in this monoterpene was used to induce the first stereogenic center exhibited by the natural product. This task was accomplished by employing a sequence of well-established synthetic metodologies. This stereogenic center has induced the formation of two of the remaining three estereogenic centers. So that 78% of the carbon skeleton of the natural product has been built in a total of 10 steps with an overall yield of 3%. In the second part of this work we described the results of a methodological study envolving the reaction between aminoguanidinine, a polynitrogenated bis-nucleophile, and silylated and acetylated Morita-Baylis-Hillman adducts (MBH). The reaction of aminoguanidine with silylated MBH adducts gave, through a tandem process, a diastereoisomeric mixture of silylated pyrazolidinones in excellent yields, in which the syn diastereoisomer is favored in all cases. The diastereoselectivity of theses reactions ranged from 2:1 to 7:1 (syn:anti). When we investigated the reaction of aminoguanidine with acetylated aliphatic and eletron rich aromatic MBH adducts, using acetonitrile as solvent, the reaction afforded exclusively benzylidenic pyrazolidinones. However, when we investigated the reaction with acetylated eletron-poor aromatic MBH adducts, we observed the formation almost exclusively of pyrazolones, which are regioisomers of the previously obtained pyrazolidinones. These data indicated that under these conditions, the nature of the substituent group governed the selectivity of these reactions. Later, it was observed that by subjecting the pyrazolidinones to a solution of 2 equivalents of K2CO3 in methanol, they were completely converted to the corresponding pyrazolones, showing the influence of the nature of the solvent in these chemical transformations
Mestrado
Quimica Inorganica
Mestre em Química

L’organocatalyse permet l’activation de réactions chimiques diverses et représente une méthode complémentaire à la catalyse métallique ou à la catalyse par les enzymes. Cette stratégie peut être moins toxique et relativement plus accessible, en plus d’être fréquemment économique et écologique. En induisant une intramolécularité temporaire, il est possible de surmonter les pénalités entropiques inhérentes aux réactions intermoléculaires. Les travaux effectués par le groupe de recherche du Pr. Beauchemin ont jusqu’à date permis d’actualiser et d’améliorer des réactions d’hydroamination, d’hydratation d’amino nitriles et d’hydrolyse d’amides organophosphoniques grâce à l’organocatalyse aux aldéhydes simples. Dans cette optique, cette thèse étudie l’application de cette méthodologie dans des réactions d’hydrolyse. Dans un premier temps, les paramètres réactionnels favorisant l’hydrolyse d’α-amino esters furent investigués. Les problèmes de labilité de divers substrats en milieu aqueux furent abordés, de même que les difficultés à effectuer un « turnover » catalytique efficace. Dans un deuxième temps, la mono-hydrolyse de 1-amino diester phosphonique fut étudiée. Les esters d’acide 1-amino phosphoniques suscitent un intérêt en raison de leurs bioactivités diverses, notamment comme analogues d’acides aminés capables d’interactions biologiques avantageuses. Il fut possible d’optimiser plusieurs conditions réactionnelles, de même que d’étendre la portée de cette méthode à la synthèse de dérivés portant des groupements alkyles. Sur un autre ordre d’idées, les hétérocycles azotés font preuve de bioactivités importantes et variées. Conséquemment, leur emploi dans les domaines pharmaceutique et agrochimique est incontournable. Les cycles de type pyrazolone sont particulièrement présents dans des composés pharmaceutiques et dans des insecticides et des herbicides, tandis que les triazolium-olates présentes des activités biologiques intéressantes. Il devient ainsi essentiel de développer des voies polyvalentes, efficaces, peu dispendieuses et plus vertes pour leur synthèse. Des travaux antérieurs du groupe Beauchemin ont élaboré la génération in situ d’isocyanates et d’isothiocyanates N-substitués, des intermédiaires rares dans la littérature. Ils furent utilisés dans des réactions de cycloaddition avec des alcènes et des imines, pour former des azométhine imines. La deuxième partie de cette thèse s’intéresse à la dérivation de ces azométhine imines en dérivés de pyrazolone et en triazolium-olates grâce à une réaction d’isomérisation. Cette approche permet une déconnexion novatrice pour synthétiser directement des hétérocycles riches en azote complexes. L’optimisation de cette réaction fut mise au point et sa portée fut étudiée. Cette méthode s’avère peu dispendieuse, n’emploie aucun catalyseur métallique, ne requière pas de préfonctionnalisation et ne génère pas de sous-produits. Finalement, l’application de cette isomérisation à la résolution cinétique des azométhines imines fut tentée.

Etude spectrophotometrique de la stabilite des complexes de l'ion uo::(2)**(2+) et de l'ion cu**(2+), dans l'eau et eau-acetonitrile. Structures possibles des complexes 1:1, 1:2 et 2:1. Mecanismes de formation des complexes

Some new acylpyrazolone Schiff bases have been synthesized from the condensation reaction of two acylpyrazolone diketone precursors with phenylhydrazine, 2,4-dinitrophenylhydrazine and sulfanilamide. They have been fully characterized by elemental analysis and spectroscopic techniques (IR,1H and 13C NMR, and mass-spectra). The single crystal structure of the benzoyl derivative acylpyrazolone Schiff bases have been obtained and analyzed by X-ray crystallography technique. Solid state X-ray diffraction revealed a keto tautomer Schiff base in solid state. Mn(II), Co(II), Ni(II) and Cu(II) complexes with the Schiff bases have been synthesized and characterized by elemental analysis, IR and UV-VIS spectroscopy, magnetic susceptibility measurements, and thermal studies (TGA and DTG). An octahedral geometry around the transition metal ion, consisting of two bidentate Schiff base ligands bonding through the azometine nitrogen and ketonic oxygen have been proposed based on careful interpretation of available analytical and spectroscopic characterization results. Two water molecules as ligands complete the octahedral geometry in all cases. Using the invitro disc diffusion method for screening synthesized compounds against selected gram positive and gram negative bacterial at 40 mg/mL, and the DPPH free radical scavenging methods at 0.50, 0.25 and 0.13 mg/mL, the synthesized Schiff base and metal complexes showed varying biological activities. 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one sul29 fanilamide showed more activity generally, exhibiting a broad spectrum activity against all selected bacterial in some cases. Mn(II), Co(II) and Ni(II) complexes of sulfanilamide Schiff base with the acetylpyrazolone derivative 4-acetyl-3-methyl-1-phenyl-2-pyrazolin-5-one sulfanilamide, exhibited a stronger and very good DPPH radical scavenging activity as good as ascorbic acid on comparing, but not with Cu(II). As such they could be important antitumour candidates.

Extractions de co. Zu. Cd et cu divalents par les melanges phenyl-1 methyl-3 benzoyl-4 pyrazolone-5 ethers crown. La coextraction alcalins-alcalinoterreux complexes par les composes crown et des metaux divalents est possible quand la taille de la cavite de l'ether-crown est voisine de celle de l'alcalin (ou alcalino-terreux) et quand l'ion ml::(3)**(-) est suffisamment stable

La coextraction de cesium ou de strontium et de cobalt ou de cadmium par des melanges d'acyl-4-pyrazolols-5 (hl) et d'ethers-couronnes (e) a ete etudiee. Nous montrons que les extractions du cobalt a partir de milieux contenant un cation alcalin cs#+ peut entrainer l'extraction de trois types d'especes metalliques electriquement neutres: e#2cs#+, col#3# (e=b15-c-5), ecs#+, col#3# (e=db18-c-6) et col#2e (e=db24-c-8). La presence du cation alcalino-terreux sr#2#+ en phase aqueuse engendre la coextraction de deux especes col#2e et esr, 2col#3 avec e=db18-c-6, tandis qu'avec e=b15-c-5 ou db24-c-8, seule l'espece esrx, col#3 ou col#2e est extraite (x=cl ou no#3). Des resultats similaires ont ete obtenus en remplacant le cobalt par du cadmium. Ce dernier est toutefois moins bien extrait en raison d'une moins bonne complexation (formation de cdl#3#). Les extractions synergiques dependent du diluant suivant l'ordre: c#2h#4cl#2>ch#2cl#2>chcl#3 (constantes dielectriques decroissantes) et du groupe acyl de l'acyl-4-pyrazolol-5 avec benzoyl>para terbutyl benzoyl>>stearoyl (acidites decroissantes)

Cette thèse se divise en trois parties. La première concerne le développement d'une nouvelle voie d'accès à des hétérocycles azotés. Cette synthèse est basée sur deux étapes: l'addition radicalaire d'un xanthate, portant une fonction 1,2-dione, sur diverses oléfines suivie de sa condensation sur une diamine. Cette étude a permis de préparer des composés présentant un intérêt biologique certain tels que des pyrazines. De plus, une nouvelle méthodologie permettant l'accès à des structures imidazoles a été mise en évidence. La seconde partie a été consacrée à la préparation d'un support soluble à l'aide du procédé Madix. La dernière étude porte sur le développement de nouveaux agents modérateurs de la polymérisation radicalaire. Cette étude nous a amenés tout d'abord à synthétiser une large gamme de composés originaux de type dihydro-pyrazolone. Par la suite, la mise en place d'une étude modèle nous a permis de mesurer l'aptitude à se dissocier de ces composés puis de sélectionner les meilleurs candidats. Enfin, une étude poussée en polymérisation des agents sélectionnés a permis de mieux comprendre leur mécanisme d'action. Nous sommes en présence d'un système de type initer original. Ce système de polymérisation n'est cependant pas vivant du fait de l'irréversibilité de l'addition du contre radical dihydro-pyrazolone sur la chaîne polymère.

Etude de la reduction chimique de sels (nitrate et acetate) d'uranyle et des complexes (phenyl-1 methyl-3 acyl-4 pyrazolones-5) et beta-cetophosphonates d'uranyle en milieu organique et en presence de perchlorate d'ammonium sur une electrode de mercure

碩士
國立臺灣科技大學
纖維及高分子工程系
90
In this study, the reaction of ethyl acetoacetate with hydrazine hydrate , Methylhydrazine or phenyhydrazine is show to give pyrazolone derivatives ,First a solution of pyrazolone derivative in ethanol was condensed with aromatic aldehyde derivatives by presence of basic catalyst was shown to give compounds 9a~9d .The pyrazolone intermediate was condense with some aromatic primary amines were coupled with pyrazolone to give a series of yellow-coloured monoazo pyrazolone dyes11a~11j and 12a~12d Finally, these compound were determined the structure by spectrometry(IR、UV、1H-NMR) and element analysis (EA)

碩士
中國醫藥大學
藥物化學研究所碩士班
97
An efficient and convenient method for the bromination of pyrazolones and 5-hydroxypyrazoles was developed by used of N-bromobenzamide or dibromoisocyanuric acid in THF at room temperature. A safe bromination has been developed for pyrazolones and 5-hydroxypyrazoles to give the corresponding di-brominated pyrazolones in excellent yields (≥ 90%).

First part is focused on finding suitable reaction conditions for organocatalytic domino Michael/Michael reaction of ethyl (E)-3-(2-thiophenyl)acrylate with α,β-unsaturated aldehydes. Second part deals with the preparation of pyrazolone derivatives from commercially available compounds and describes effects of various substituents in α-position on chemical efficiency and stereoselectivity of amination with azodicarboxylate catalyzed by quinine.

The thesis entitled “Design and Development of Metal-Free Cross Dehydrogenative Coupling Reactions for the construction of C-S, C-O and C-C bonds” is divided into three Chapters. Chapter 1 is presented in five parts, which reveals the cross dehydrogenative coupling (CDC) strategies for the C–S bond forming reactions through C–H functionalization strategy using heterocyclic thiols and thiones. Chapter 2 presents tetrabutyl ammonium iodide (TBAI) catalyzed chemoselective α-aminoxylation of ketones with N-hydroxyimidates using TBHP as oxidant under cross dehydrogenative coupling (CDC) strategy. Chapter 3 describes a transition metal-free Minisci reaction for the acylation of isoquinolines, quinolines, and quinoxaline. Chapter 1 Iodine Promoted C-S Bond Forming Reactions using Dimethyl Sulfoxide as an Oxidant Chapter 1 reveals the utility of cross dehydrogenative coupling (CDC) reactions for the formation of C–S bonds by employing C–H functionalization strategies.1 The direct functionalization of C–H bonds to form C–C and C–X (N, O, S and P) bonds using metal-free reaction conditions is an interesting research topic in recent years.2 Use of dimethyl sulfoxide as an oxidant is emerging as one of the research topics of great interest and utility.3 Heterocyclic thiols and thiones are important precursors for synthesizing a variety of pharmaceuticals and biologically active compounds.4 Therefore it is useful to develop CDC reactions using heterocyclic thiols and thiones as precursors. In this chapter, we describe CDC reactions of heterocyclic thiols and thiones for the sulfenylation of ketones, aldehydes, α, β unsaturated methyl ketone derivatives, pyrazolones, enaminones and imidazoheterocycles using DMSO as an oxidant Chapter 1: Part 1 Iodine Promoted Regioselective α-Sulfenylation of Carbonyl Compounds using Dimethyl Sulfoxide as an Oxidant: In this chapter, a rare regioselective C–H sulfenylation of carbonyl compounds with heterocyclic thiones and thiols have been described using iodine and dimethyl sulfoxide as reagents. Thus, dimethyl sulfoxide (as an oxidant) and stoichiometric amount of iodine have been used for the sulfenylation of ketones using heterocyclic thiones. Whereas the sulfenylation of ketones with heterocyclic thiols required catalytic amount of iodine. This protocol offers a rare regioselective sulfenylation of (i) methyl ketones in the presence of more reactive α-CH2 or α-CH groups, and (ii) aldehydes under CDC method. A few representative examples are highlighted in Scheme 1.5 The application of this methodology has been demonstrated by synthesizing a few precursors for Julia-Kocienski olefination intermediates. Scheme 1. Iodine promoted rare regioselective α-sulfenylation of ketones and aldehydes Siddaraj , Y.; Prabhu, K. R. Org. Lett. 2016, 18, 6090 Chapter 1: Part 2 Regioselective Sulfenylation of α’-CH3 or α’-CH2 Groups of α, β Unsaturated Ketones using Dimethyl Sulfoxide as an Oxidant: In this chapter, an interesting regioselective sulfenylation of α’-CH3 or α’-CH2 groups of α, β unsaturated ketones using dimethyl sulfoxide as an oxidant and catalytic amount of aq. HI (20 mol %) as an additive has been described. This eco-friendly method uses readily available, inexpensive I2 or HI and DMSO. This methodology exhibits a high regioselectivity without forming Michael addition product in the presence of strong acid such as aq. HI or iodine, which is difficult to achieve under cross dehydrogenative coupling (CDC) conditions. Current methodology exhibits a broad substrate scope. A few examples are shown in Scheme 2.6 Scheme 2. HI and DMSO promoted α’-sulfenylation of α, β unsaturated ketones Siddaraju, Y.; Prabhu, K. R. (Manuscript submitted) Chapter 1: Part 3 Iodine Catalyzed Sulfenylation of Pyrazolones using Dimethyl Sulfoxide as an Oxidant: In this chapter, a sustainable and efficient strategy for the sulfenylation of pyrazolones has been described using metal-free conditions by employing DMSO as an oxidant and iodine as a catalyst. A variety of heterocyclic thiols, heterocyclic thiones and disulfides undergo C–H functionalization reaction with pyrazolone derivatives furnishing the corresponding sulfenylated products in short time. Most of the products are isolated in pure form without column purification. A few examples are presented in Scheme 3.7 Scheme 3. Iodine promoted sulfenylation of pyrazolones Siddaraju, Y.; Prabhu, K. R. Org. Biomol. Chem. 2017, 15, 5191 Chapter 1: Part 4 Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: Sulfenylation of Enaminones using Dimethyl Sulfoxide as an Oxidant: In this chapter, synthesis of poly functionalized aminothioalkenes has been described using substoichiometric amount of iodine and DMSO as an oxidant. This metal-free methodology enables a facile sulfenylation of enaminones with heterocyclic thiols and thiones. This methodology is one of the simple approaches for the sulfenylation of enaminones under cross dehydrogenative coupling method. A few examples are highlighted in Scheme 4.8 Scheme 4. Cross-dehydrogenative coupling approach for sulfenylation of enaminones Siddaraju, Y.; Prabhu, K. R. J. Org. Chem. 2017, 82, 3084 Chapter 1: Part 5 Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: A Regioselective Sulfenylation of Imidazoheterocycles using DMSO as an Oxidant: In this chapter, a simple synthetic approach for the regioselective sulfenylation of imidazoheterocycles using iodine as a catalyst and DMSO as an oxidant under cross dehydrogenative coupling (CDC) reaction conditions has been demonstrated. This protocol provides an efficient, mild and inexpensive method for coupling heterocyclic thiols and heterocyclic thiones with imidazoheterocycles. This is the first report on sulfenylation of imidazoheterocycles with heterocyclic thiols and heterocyclic thiones under metal-free conditions. A few examples are shown in Scheme 5.9 Scheme 5. Cross-dehydrogenative coupling approach for sulfenylation of imidazoheterocycles Siddaraju, Y.; Prabhu, K. R. J. Org. Chem. 2016, 81, 7838 Chapter 2 Chemoselective α-Aminoxylation of Aryl Ketones: Cross Dehydrogenative Coupling Reactions Catalyzed by Tetrabutyl Ammonium Iodide: In this chapter, chemoselective α-aminoxylation of ketones with N-hydroxyimidates catalyzed by tetrabutyl ammonium iodide (TBAI) has been presented. The coupling reaction of a variety of ketones with N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI), N-hydroxybenzotriazole (HOBt) or 1-hydroxy-7-azabenzotriazole (HOAt) using TBHP as oxidant has been investigated. This α-aminoxylation of ketones is chemoselective as aryl methyl ketones, aliphatic ketones as well as benzylic position are inactive under the reaction condition. A few examples are highlighted in Scheme 6.10 The application of this method has been demonstrated by transforming a few coupled products into synthetically useful vinyl phosphates. Scheme 6. Chemoselective α-aminoxylation of ketones with N-hydroxyimidates Siddaraju, Y.; Prabhu, K. R. Org. Biomol. Chem. 2015, 13, 11651 Chapter 3 A Transition Metal-Free Minisci Reaction: Acylation of Isoquinolines, Quinolines, and Quinoxaline: In this chapter, transition metal-free acylation of isoquinoline, quinoline and quinoxaline derivatives with aldehydes has been described by employing TBAB (tetrabutyl ammonium bromide, 30 mol %) and K2S2O8 as an oxidant under cross dehydrogenative coupling (CDC) reaction. This intermolecular acylation of electron-deficient heteroarenes provides an easy access and a novel acylation method of heterocyclic compounds. The application of this CDC strategy has been illustrated by synthesizing isoquinoline-derived natural products. A few representative examples are shown in Scheme 7.11 Scheme 7. CDC reactions of heteroarenes with aldehydes Siddaraju, Y.; Lamani, M.; Prabhu, K. R. J. Org. Chem. 2014, 79, 3856

The thesis entitled “Design and Development of Metal-Free Cross Dehydrogenative Coupling Reactions for the construction of C-S, C-O and C-C bonds” is divided into three Chapters. Chapter 1 is presented in five parts, which reveals the cross dehydrogenative coupling (CDC) strategies for the C–S bond forming reactions through C–H functionalization strategy using heterocyclic thiols and thiones. Chapter 2 presents tetrabutyl ammonium iodide (TBAI) catalyzed chemoselective α-aminoxylation of ketones with N-hydroxyimidates using TBHP as oxidant under cross dehydrogenative coupling (CDC) strategy. Chapter 3 describes a transition metal-free Minisci reaction for the acylation of isoquinolines, quinolines, and quinoxaline. Chapter 1 Iodine Promoted C-S Bond Forming Reactions using Dimethyl Sulfoxide as an Oxidant Chapter 1 reveals the utility of cross dehydrogenative coupling (CDC) reactions for the formation of C–S bonds by employing C–H functionalization strategies.1 The direct functionalization of C–H bonds to form C–C and C–X (N, O, S and P) bonds using metal-free reaction conditions is an interesting research topic in recent years.2 Use of dimethyl sulfoxide as an oxidant is emerging as one of the research topics of great interest and utility.3 Heterocyclic thiols and thiones are important precursors for synthesizing a variety of pharmaceuticals and biologically active compounds.4 Therefore it is useful to develop CDC reactions using heterocyclic thiols and thiones as precursors. In this chapter, we describe CDC reactions of heterocyclic thiols and thiones for the sulfenylation of ketones, aldehydes, α, β unsaturated methyl ketone derivatives, pyrazolones, enaminones and imidazoheterocycles using DMSO as an oxidant Chapter 1: Part 1 Iodine Promoted Regioselective α-Sulfenylation of Carbonyl Compounds using Dimethyl Sulfoxide as an Oxidant: In this chapter, a rare regioselective C–H sulfenylation of carbonyl compounds with heterocyclic thiones and thiols have been described using iodine and dimethyl sulfoxide as reagents. Thus, dimethyl sulfoxide (as an oxidant) and stoichiometric amount of iodine have been used for the sulfenylation of ketones using heterocyclic thiones. Whereas the sulfenylation of ketones with heterocyclic thiols required catalytic amount of iodine. This protocol offers a rare regioselective sulfenylation of (i) methyl ketones in the presence of more reactive α-CH2 or α-CH groups, and (ii) aldehydes under CDC method. A few representative examples are highlighted in Scheme 1.5 The application of this methodology has been demonstrated by synthesizing a few precursors for Julia-Kocienski olefination intermediates. Scheme 1. Iodine promoted rare regioselective α-sulfenylation of ketones and aldehydes Siddaraj , Y.; Prabhu, K. R. Org. Lett. 2016, 18, 6090 Chapter 1: Part 2 Regioselective Sulfenylation of α’-CH3 or α’-CH2 Groups of α, β Unsaturated Ketones using Dimethyl Sulfoxide as an Oxidant: In this chapter, an interesting regioselective sulfenylation of α’-CH3 or α’-CH2 groups of α, β unsaturated ketones using dimethyl sulfoxide as an oxidant and catalytic amount of aq. HI (20 mol %) as an additive has been described. This eco-friendly method uses readily available, inexpensive I2 or HI and DMSO. This methodology exhibits a high regioselectivity without forming Michael addition product in the presence of strong acid such as aq. HI or iodine, which is difficult to achieve under cross dehydrogenative coupling (CDC) conditions. Current methodology exhibits a broad substrate scope. A few examples are shown in Scheme 2.6 Scheme 2. HI and DMSO promoted α’-sulfenylation of α, β unsaturated ketones Siddaraju, Y.; Prabhu, K. R. (Manuscript submitted) Chapter 1: Part 3 Iodine Catalyzed Sulfenylation of Pyrazolones using Dimethyl Sulfoxide as an Oxidant: In this chapter, a sustainable and efficient strategy for the sulfenylation of pyrazolones has been described using metal-free conditions by employing DMSO as an oxidant and iodine as a catalyst. A variety of heterocyclic thiols, heterocyclic thiones and disulfides undergo C–H functionalization reaction with pyrazolone derivatives furnishing the corresponding sulfenylated products in short time. Most of the products are isolated in pure form without column purification. A few examples are presented in Scheme 3.7 Scheme 3. Iodine promoted sulfenylation of pyrazolones Siddaraju, Y.; Prabhu, K. R. Org. Biomol. Chem. 2017, 15, 5191 Chapter 1: Part 4 Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: Sulfenylation of Enaminones using Dimethyl Sulfoxide as an Oxidant: In this chapter, synthesis of poly functionalized aminothioalkenes has been described using substoichiometric amount of iodine and DMSO as an oxidant. This metal-free methodology enables a facile sulfenylation of enaminones with heterocyclic thiols and thiones. This methodology is one of the simple approaches for the sulfenylation of enaminones under cross dehydrogenative coupling method. A few examples are highlighted in Scheme 4.8 Scheme 4. Cross-dehydrogenative coupling approach for sulfenylation of enaminones Siddaraju, Y.; Prabhu, K. R. J. Org. Chem. 2017, 82, 3084 Chapter 1: Part 5 Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: A Regioselective Sulfenylation of Imidazoheterocycles using DMSO as an Oxidant: In this chapter, a simple synthetic approach for the regioselective sulfenylation of imidazoheterocycles using iodine as a catalyst and DMSO as an oxidant under cross dehydrogenative coupling (CDC) reaction conditions has been demonstrated. This protocol provides an efficient, mild and inexpensive method for coupling heterocyclic thiols and heterocyclic thiones with imidazoheterocycles. This is the first report on sulfenylation of imidazoheterocycles with heterocyclic thiols and heterocyclic thiones under metal-free conditions. A few examples are shown in Scheme 5.9 Scheme 5. Cross-dehydrogenative coupling approach for sulfenylation of imidazoheterocycles Siddaraju, Y.; Prabhu, K. R. J. Org. Chem. 2016, 81, 7838 Chapter 2 Chemoselective α-Aminoxylation of Aryl Ketones: Cross Dehydrogenative Coupling Reactions Catalyzed by Tetrabutyl Ammonium Iodide: In this chapter, chemoselective α-aminoxylation of ketones with N-hydroxyimidates catalyzed by tetrabutyl ammonium iodide (TBAI) has been presented. The coupling reaction of a variety of ketones with N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI), N-hydroxybenzotriazole (HOBt) or 1-hydroxy-7-azabenzotriazole (HOAt) using TBHP as oxidant has been investigated. This α-aminoxylation of ketones is chemoselective as aryl methyl ketones, aliphatic ketones as well as benzylic position are inactive under the reaction condition. A few examples are highlighted in Scheme 6.10 The application of this method has been demonstrated by transforming a few coupled products into synthetically useful vinyl phosphates. Scheme 6. Chemoselective α-aminoxylation of ketones with N-hydroxyimidates Siddaraju, Y.; Prabhu, K. R. Org. Biomol. Chem. 2015, 13, 11651 Chapter 3 A Transition Metal-Free Minisci Reaction: Acylation of Isoquinolines, Quinolines, and Quinoxaline: In this chapter, transition metal-free acylation of isoquinoline, quinoline and quinoxaline derivatives with aldehydes has been described by employing TBAB (tetrabutyl ammonium bromide, 30 mol %) and K2S2O8 as an oxidant under cross dehydrogenative coupling (CDC) reaction. This intermolecular acylation of electron-deficient heteroarenes provides an easy access and a novel acylation method of heterocyclic compounds. The application of this CDC strategy has been illustrated by synthesizing isoquinoline-derived natural products. A few representative examples are shown in Scheme 7.11 Scheme 7. CDC reactions of heteroarenes with aldehydes Siddaraju, Y.; Lamani, M.; Prabhu, K. R. J. Org. Chem. 2014, 79, 3856

碩士
國立臺灣科技大學
纖維及高分子研究所
86
The pyrazolone derivatives were prepared from ethyl acetoacetate with hydrazine hydrate , methylhydrazine and phenylhydrazine, respectively.In this study , three types of heterocyclic methine、aza-methine and azo disperse dyes were prepared by pyrazolone intermediates.The pyrazolone intermediates were condensed with aromatic aldehyde in basic solution to obtain a series of yellow to red-coloured methine pyrazolone dyes，with nitrosoaniline derivatives to obtain a series of garnet to petunia-coloured aza-methine pyrazolone dyes， with some aromatic primary amines to give a series of yellow-coloured monoazo pyrazolone dyes. The structure of the dyes was confirmed by,IR,MS, -NMR spectral analysis.The absorption maximum of dyes in acetone and DMF were measured.We found that the λmax of dyes in DMF solvent is longer than in acetone.By changing of pH value , p-Dimethylaminobenzylidene pyrazolone methine dyes have strong hypsochromic shifts in basic solution,but p-hydroxybenzylidene pyrazolone methine dyes have bathochromic shifts. N,N-dimethylaniline methyleneamino pyrazolone aza-methine dyes have strong hypsochromic shifts both in basic and acid solution,but phenylamine methyleneamino pyrazolone aza-methine dyes have bathochromic shifts in the basic solution. Pyrazolone azo dyes have bathochromic shifts in the basic solution.These dyes were applied to dyeing on polyester fabrics in different pH and shown yellow to petunia hues. The sublimation fastness、the lightfastness and washfastness of dyes on polyester fabrics were in the range between 2~5 grade, 4~7 grade and 4~5 grade,respectively.

碩士
國立臺灣科技大學
纖維及高分子研究所
86
The pyrazolone derivatives were prepared by the reaction of ethyl acetoacetatewith hydrazine hydrate,methylhydrazine and phenylhydrazine,respectively.Theazamerocarbocyanine dyes were synthesised from pyrazolone intermediates and1,3,3-trimethyl-2-methylene indoline.The structure of the dyes was confirmedby E.A,IR,MS,H-NMR spectral analysis.Azamerocarbocyanine dyes were applied to dying on polyester fabrics and shown red to reddish-purple hues.The sublimation and light fastness of dyes on pol-yester fabrics were measured and shown in the range among 3-5 grade and 3-7grade,respectively.The photofading rate of the dyes shown 1 and 2 order respectively.

碩士
國立臺灣科技大學
高分子系
95
This research is taking Hydrazine with the Ethyl acetoacetate as the intermediate preparation (3a) 5-amino-2,4-dihydro-3H -pyrazol-3-one, again after includes derivative of the different substituted group aniline to give the diazonium to carry on the coupling reaction, forms a series of pyrazolone[ 1,5-a ] pyrimidine compounds, we discuss dye’s tautomerism by changing different polar solvents and the pH value in acetone solvent, and then measures its λ max absorption, dye of the synthesis passes through IR, Mass, the 1H-NMR spectrum determines its chemical constitution.

M. Tech. (Department of Chemical Engineering, Faculty of Engineering and Technology): Vaal University of Technology
The arylation and alkenylation of alkenes under the influence of a palladium catalyst, commonly referred to as the Heck reaction, has been extensively exploited by synthetic chemists since its debut in the late 1960’s. A traditional Heck coupling is based on an aryl iodide or bromide as the electrophilic partner and a terminal alkene as the nucleophilic partner. Academic and industrial interest in this reaction has increased in recent years, fueled by the development of more active catalyst systems, the discovery of waste-free versions, and the desire to put the vast empirical data on a sound mechanistic basis. In this study, we wish to report the use of commercially available substituted pyrazolones (1-(4-Sulfophenyl)-3-methyl-5-pyrazolone (L1), 1-(2,5-Dicloro-4-sulfophenyl)-3-methyl-5-pyrazolone (L2) and 5-oxo-1-phenyl-2-pyrazolin-3-carboxylic acid (L3)) and pyrazoles (α-[(2-Ethoxy-2-oxoethoxy)imino]-3-pyrazole acetic acid (L4) and 3.5 dimethyl pyrazole (L5)) as auxiliary ligands in the Heck coupling reaction. These ligands were used either with PdCl2 or Pd(OAc)2 to catalyze the Heck reaction of iodobenzene with ethyl acrylate or butyl acrylate. GC-MS was used to monitor the reaction, percentage (%) conversions were determined based on the consumption of iodobenzene. Different reaction parameters such as ligands, temperature, base, solvent and influence of time were investigated. It was observed that the lower conversion was obtained for ethyl acrylate and conversions above 80% were obtained for butyl acrylate. Ligand effect proved to be very crucial during the Heck coupling reactions of iodobenzene with butyl acrylate and ethyl acrylate. For instance in the absence of ligands with PdCl2, the conversions were 29 % and 44 % for butyl acrylate and ethyl acrylate, respectively. When Pd(OAc)2 was used in the absence of ligands the conversions were 25 % and 36 % for butyl acrylate and ethyl acrylate, respectively. In the study for the effect of temperature, 80 ◦C was observed as the best temperature since promising conversions were obtained with little or no sign of deactivation of the catalysts. On the other hand, increasing the temperature to 120 ◦C and above high percent conversions are observed; however deactivation of the catalysts occurs as observed from the precipitation of palladium black at the bottom of the vial. From the results obtained it is clear that pyrazolone and pyrazole ligands/palladium systems are important at very low catalyst loadings and mild temperatures. Based on the employed reaction conditions the influence of base suggested that the organic base triethylamine was the reagent of choice since better conversions were obtained compared to inorganic bases. The inhomogeneity of the inorganic base proved to be a disadvantage in the reaction of iodobenzene with butyl acrylate at employed reaction conditions. It was also found that parameters such as solvents and time effects were important in the Heck reaction. Polar aprotic solvents proved to be solvents of choice rather than non-polar solvents, from the investigated solvents DMF gave better conversions under the used reaction conditions giving average conversions of 78 % and 75 % for all the ligands in the presence of PdCl2 and Pd(OAc)2, respectively. During the investigation of time effect, it was noteworthy to observe that L4 had a slow initiation rate, for instance after 0.5 h conversions of 2 % and 10 % were obtained for catalytic systems, PdCl2 and Pd(OAc)2 respectively. Also it was observed that under the investigated parameters there was no need to run the reaction for 24 h because after 4 h not much of a difference in conversions was observed. In comparing the influence of these two different auxiliary ligands, pyrazolone based ligands were more efficient than pyrazole based ligands under the investigated parameters. The fully detailed information supporting this has been discussed in Chapter 4.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Anna Břečková Supervisor: Přemysl Mladěnka, Ph.D. Title of Thesis: Iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group II Iron deficiency and iron overload play important roles in the pathophysiology of certain human diseases. Administration of iron chelators is a suitable therapy in iron overload conditions, especially in cases of hematological diseases treated with blood transfusions. Iron- chelating therapy appears as well as a promising tool for other diseases (acute myocardial infarction, tumor, etc.). Several factors should be considered according to expected indications: 1) oral efficiency, 2) activity in acidic environment, 3) ability to reduce ferric ions to ferrous ions (risk of pro-oxidation). The aim of this thesis was to verify the iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group by use of UV-VIS spectrophotometric methods. From this group, p-terc.butyl- and p-nitroderivatives of the basic structure and the derivatives marked as H2Q3Q and H2QPy, which are double molecules of the basic structure, were chosen. All of the tested substances had some potential to chelate ferrous ions and were also devoid of...