Design and Development of Carbon-Carbon and Carbon-Heteroatom Bond Forming Reactions” is divided into two sections. Section-A, contains two chapters, describes the catalytic ability of iodine for cross coupling reactions. Section-B, divided into three chapters, presents the azidation of organic scaffolds under oxidative conditions. Section A Chapter 1 presents a C-H functionalization of tetrahydroisoquinolines using iodine as a catalyst under aerobic conditions.1 This methodology employs Cross Dehydrogenative Coupling (CDC) strategy as a key step, which is highly atom economical as it doesn’t require pre-functionalized starting materials.2 Owing to the importance of tetrahydroisoquinoline moiety which is present in the umpteen natural products, considerable attention has been put up to functionalize tetrahydroisoquinoline scaffold.3 Iodine a non-metal which is non-toxic was found to catalyze the C-H functionalization of tetrahydroisoquinolines with a variety of nucleophiles such as coumarin, alkyl phosphite, phenols, indoles, acetone and dialkyl malonoates were coupled to it. Significant mechanistic study has been carried out to find the possible intermediate and support the mechanistic proposal. A few representative examples are highlighted in Scheme 1.1 Synopsis Scheme 1: A CDC coupling of tetrahydroisoquinoline with variety of nucleophiles Chapter 2 describes the Cross Hetero Dehydrogenative Coupling (CHDC) reactions of amines, alcohols and sulfoximines with various phosphites.4 Phosphoramidates and phosphate esters are structural scaffolds that are present in a variety of biologically active molecules.5 The conventional methods for synthesizing phosphoramidates/phosphate esters largely involve treating alcohol/amine with appropriate phosphorus halides which generates stoichiometric amount of halogen waste.6 Due to the usage of stoichiometric reagents and difficulties associated with the reported methods, there is a need for developing a protocol which is catalytic and mild. Therefore, we developed a method which employs catalytic amount of iodine and aq. H2O2 as a sole oxidant under milder conditions. Using this methodology, variety of phosphoramidates, phosphorous triesters and sulfoximine derived Synopsis Scheme 2: Phosphorylation of amines, alcohols and sulfoximines phosphoramidates have been synthesized with great efficiency and environmentally benign conditions. A few representative examples are highlighted in Scheme 2.4 Section B Chapter 1 of Section B demonstrates a mild way of synthesizing quaternary azides from α-substituted active methylene compounds which will serve as surrogates for several unnatural amino acid derivatives.7 Azidation has emerged as one of the efficient methods to introduce nitrogen atom in to the organic molecules.8 Azides are versatile functional groups which can be converted to amine, amide, and nitro compounds by simple modification. Moreover, azides are potential handle for “click” chemistry and provide late stage modifications in drug candidates, biomolecules and polymers, etc.9 Azidation of 1,3-dicarbonyl compounds is challenging, as both azides and 1,3-dicarbonyl compounds are nucleophilic in nature. In this section of the thesis, azidation of 1,3-dicarbonyl compounds has been carried out using tetrabutyl ammonium iodide (TBAI) as a catalyst, aq. TBHP as an oxidant and TMSN3 as a azide source. This method uses water as a solvent under mild reaction conditions to generate Synopsis quaternary azides in good to excellent yields. This operationally simple, practical, mild and green method provides an opportunity for synthesizing a variety of azidated β-keto esters, amides and ketones in good yields, Scheme 3.7 The application of this methodology has been demonstrated by synthesising a few triazole and pyrazolone derivatives. Scheme 3: Azidation of 1,3-dicarbonyl compounds Chapter 2 of Section B comprises the azidation and peroxidation of β-napthol derivatives using dearomatization strategy. Azidation and peroxidation are efficient ways to introduce nitrogen and oxygen into organic molecules, which serve as surrogates for amines and alcohol functional groups. In the present study, the azidative or peroxidative dearomatization of naphthol derivatives have been described. The azidation of β-napthol derivatives has been achieved by using CuBr (5 mol %) as a catalyst, TMSN3 as an azide source and aq. TBHP as an oxidant. Whereas, the peroxidation β-napthol derivatives has been accomplished using CuBr (5 mol %) in the presence of aq. TBHP at ambient reaction conditions.10 The products obtained are naphthalenone derivatives, which serve as valuable Synopsis synthetic intermediates and has potential handle for further functionalization.11 Several α-amino or α-peroxy naphthalenones are synthesized using this method in good yields. The usefulness of the methodology has been illustrated by synthesizing a few chiral azides and peroxides in good yields and with moderate enantioselectivity Scheme 4.10 Scheme 4: Dearomatizative azidation and peroxidation of 2-naphthols Chapter 3 reveals the azidation of indole at C-2 position by employing CuBr (10 mol %) as a catalyst and aq. TBHP as an oxidant in acetonitrile under reflux conditions (Scheme 5).12 The C-H functionalization of indole at C-2 position is one of pivotal methods, since it paves a way for synthesizing a variety of indolo-alkaloids.13 Azide is a versatile functionality which can be converted to several other nitrogen containing functional groups such as Synopsis Scheme 5: Azidation of indoles amine, amide, triazole, etc.9 A variety of functional groups were tolerated under the reaction conditions, and furnished the azidated product in good to excellent yields. Through radical inhibition study, we presume that the reaction may be proceeding through radical mechanism. In Scheme 5, a few representative examples are depicted.

Cette thèse porte sur la conception, la synthèse et la caractérisation de nouveaux dérivés accepteurs d'électrons. Elle se concentre sur l’étude des dérivés de la 1,2,4,5-tétrazine, mais contient également l’étude de dérivés du benzonitrile, précurseurs typiques de la préparation des 1,2,4,5-tétrazines et de dérivés de la pyridazine, les produits dérivés de la réaction de Diels – Alder à Demande Inverse (IEDDA) des dérivés de la tétrazine. De plus, les dérivés de 1,2,3,4-thiatriazole, en tant que produits imprévus de la synthèse de Pinner modifiée, sont également étudiés de manière approfondie. En raison des états de transfert de charge (CT) introduits dans le système donneur-accepteur, les dérivés préparés accepteur d'électrons présentent en général des propriétés photophysiques et électrochimiques intéressantes, et ont donc un intérêt particulier pour l'électronique organique.Le point culminant de cette thèse est le développement de méthodologies synthétiques dans chaque chapitre. En résumé, le chapitre 2 met en évidence une nouvelle approche synthétique sans métal pour les 1,2,4,5-tétrazines 3-monosubstituées, qui sont très utiles pour la chimie du click bioorthogonal. Le chapitre 3 décrit une stratégie de synthèse élaborée pour de nouveaux dérivés de benzonitrile donneur-accepteur qui présentent de la TADF, de l’ AIE et du mécanochromisme. Le chapitre 4 présente une étude détaillée de la réaction de couplage croisé Buchwald – Hartwig en tant que méthodologie de synthèse importante dans la synthèse de molécules de tétrazine. Le chapitre 5 décrit l'étude de la réaction à l'IEDDA comme un outil synthétique utile pour préparer des dérivés de pyridazine. Le chapitre 6 présente une nouvelle synthèse pratique de 1,2,3,4-thiatriazoles à partir de composés nitriles. / This PhD thesis deals with the design, synthesis and characterization of novel electron-acceptor derivatives. It is focused on the study of 1,2,4,5-tetrazine derivatives, but also involves the study of benzonitrile derivatives which are the typical precursors for the preparation of 1,2,4,5-tetrazines, and pyridazine derivatives which are the products derived from Inverse Electron Demand Diels–Alder (IEDDA) reaction of tetrazine derivatives. Moreover, 1,2,3,4-thiatriazole derivatives, as unpredicted products from modified Pinner synthesis, are also elaborately investigated. Due to the charge-transfer (CT) states introduced in the donor-acceptor system, the prepared electron-acceptor derivatives exhibit interesting photophysical and electrochemical properties, and therefore are of particular interest in organic electronics.The highlight of this thesis is the development of synthetic methodologies in each chapter. To sum up, Chapter 2 demonstrates a novel metal-free synthetic approach to 3-monosubstituted 1,2,4,5-tetrazines, which are highly useful for bioorthogonal click chemistry. Chapter 3 describes an elaborative synthetic strategy for novel donor-acceptor benzonitrile derivatives which exhibit TADF, AIE and mechanochromism. Chapter 4 presents a detailed study of Buchwald–Hartwig cross-coupling reaction as an important synthetic methodology in the synthesis of tetrazine molecules. Chapter 5 described the study of IEDDA reaction as a useful synthetic tool to prepare pyridazine derivatves. Chapter 6 presented a novel convenient one-pot synthesis of 1,2,3,4-thiatriazoles directly from nitrile compounds.

Title: Palladium catalysts deposited over novel siliceous supports Author: Pavlína Křečková Department: Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague Supervisor: prof. RNDr. Petr Štěpnička, Ph.D. Supervisor's e-mail address: stepnic@natur.cuni.cz Advisor: prof. Ing. Jiří Čejka, DrSc. Advisor's e-mail address: jiri.cejka@jh-inst.cas.cz Abstract Keywords: palladium; deposited catalysts; siliceous supports; C-C coupling reaction. The aim of this work was to prepare a deposited palladium catalyst from Pd2+ and twodimensional zeolite ITQ-2 bearing ≡SiCH2CH2CH2NHCH2CH2NEt2 groups at the surface. This catalys has been evaluated in the Heck reaction between n-butyl-acrylate and brombenzene to give n-butyl-cinnamate. Influence of the reaction temperature, the solvent, base and hydrate water on the progress of the Heck reaction was investigated. This work also deals with the possibility of recycling the catalyst and, due to its nature, with the quantity of leached palladium into the reaction mixture. Furthermore, the work describes differences in morphology between the fresh and a recycled catalyst.

This PhD thesis reports the development of novel C-H activation strategies and aqueous-phase Suzuki-Miyaura cross-coupling reactions for the synthesis of modified deazapurine nucleobases. The methodologies of chemo- and regioselective synthesis of highly functionalized deazapurines have been developed by using modern C-H activation chemistry. Various functional groups such as amino-, imido-, silyl- and phosphonyl- were introduced by C-H activation reactions. Amino deazapurine derivatives were synthesized by developed Pd/Cu-catalyzed direct C-H amination and C-H chloroamination of 6-substituted 7-deazapurines with N-chloro-N- alkyl-arylsulfonamides. C-H imidation reactions of pyrrolopirimidines were performed under ferrocene catalysis with N-succinimido- or N-phtalimidoperesters. In order to obtain silylated derivatives, Ir-catalyzed C-H silylations of phenyldeazapurines with alkyl silanes were designed. Highly interesting deazapurine phosphonates were prepared by using Mn-promoted C-H phosphonation method and were further transformed into the corresponding phosphonic acids. All of the developed direct C-H functionalization reactions proceeded regioselectively at position 8 in deazapurine core, except for C-H silylation where reaction undergoes mainly as directed ortho C-H silylation on phenyl ring,...

The war between human and malaria has never stopped, and the development and application of antimalarial drugs has not eradicated this terrible disease. To fight drug-resistant malaria, many leads have been studied over the years. (1S,3R)-MMV008138 and MMV1803522 are two compounds that have been studied in the Carlier Group. My research focused on the structural variation of each of these compounds, in the hope that greater potency could be realized. Chapter 2 describes my work on (1S,3R)-MMV008138, which inhibits the enzyme PfIspD in the methylerythritol phosphate (MEP) pathway. This compound shows good in vitro potency against the drug resistant Dd2 strain of Plasmodium falciparum. However, this lead showed no activity in mouse models. This lack of activity may be due to poor metabolic stability of the compound. However, a significant increase in in vitro potency could also improve in vivo activity. Towards that end, I focused on further variation of the D-ring and A-rings. With the regard to the D-ring, we made five analogs of MMV008138 that replaced the 2,4-dichlorophenyl ring with dihalogenated thiophen-3-yl and thiophen-2-yl rings. We also explored the effect of installing a cyano group on the A-ring of MMV008138. Unfortunately, none of these new compounds were potent growth inhibitors of Dd2 strain P. falciparum. We conclude that the lead goes into a well-defined pocket within the PfIspD enzyme that only accommodates 2,4-dihalogenated phenyl D-rings. This pocket also cannot accept any substitution larger than F on the A-ring. Interestingly, the crystal structure of 5-cyano-substituted MMV008138 was obtained ((±)-2-50c). This is the first compound out of more than 100 analogs of MMV008138 family to be amenable to crystallization. The solid state conformation of the (±)-2-50c revealed that the C3-carboxyl group was in a pseudoequatorial orientation, and the C1-aryl group was thus in a pseudoaxial orientation. 1H NMR spectroscopic studies in CD3OD-D2O were carried out to determine the solution conformation. As expected from previous studies of ester derivatives of MMV008138, these studies indicated that in solution, 2-5 would adopt both the C3-carboxyl pseudoequatorial and pseudoaxial conformations. In Chapter 3, I describe the synthesis of analogs of the antimalarial drug candidate MMV1803522. This β-carboline-3-carboxamide shows good in vitro growth inhibition potency of Dd2 strain P. falciparum, operating by a still unknown mechanism. To investigate the pharmacophore of this lead, I first sought to determine whether the pyridine N (i.e. N2) of the β-carboline was important for in vitro potency. I prepared series of carbazole analogs of MMV1803522, which replace N2 with a CH. These compounds potently inhibited the growth of Dd2 strain P. falciparum. These results suggest that N2 of MMV1803522 is not involved in any energetically significant interactions with its target protein. To further identify the pharmacophore, we prepared truncated analogs lacking the A- and B- rings (biphenyl analogs), and tricyclic analogs that feature a reversed indole moiety. Unfortunately, the biphenyl analogs and reversed indole analogs show no growth inhibition at 10,000 nM the highest concentration tested. Lastly, I describe analogs of MMV1803522 in which the 3,4-dichlorophenyl ring of MMV1803522 was replaced with halogenated thiophene. This substitution was tolerated, but compounds were roughly half as potent as MMV1803522. / Doctor of Philosophy / Malaria, mainly caused by the infection of P. falciparum, is a serious worldwide disease. In 2020, there were 241 million cases of malaria infections and over 600,000 deaths from malaria. Combinations of commercially available antimalarial compounds, such as chloroquine, mefloquine and artemisinin, are commonly used as combination therapies to treat malaria. Since different antimalarial compounds have different mechanisms of action, this combination strategy can greatly slow down the spread of drug-resistant parasites. However, multiple drug-resistant strains of P. falciparum have been reported. Therefore, there is an urgent need for new antimalarial compounds with novel mechanisms of action. This dissertation involves my research on the investigation and optimization of two novel antimalarial compounds, MMV008138 and MMV1803522. MMV008138 is an inhibitor of the MEP pathway, which is an essential metabolic pathway and attractive target for antimalarial therapies, in malaria parasites. The parasites cannot survive, with the MEP pathway inhibited. Since the MEP pathway is not present in human, the MMV008138 molecule is unlikely to have toxicity to human. The MMV008138 molecule has been demonstrated to have great in vitro performance of inhibiting the MEP pathway in several studies, however, the in vivo performance in mouse models is yet to improve. This may be due to the poor metabolic stability of this compound. The compound decomposes in the mouse body before it takes effect. To enhance the metabolic stability and potency, I performed chemical modifications on the A- and D-rings of the MMV008138 compound. An X-ray crystal structure was obtained to help elucidate the conformer distribution of MMV008138. This crystal structure can be used to guide our understanding of the docking of this compound to the target enzyme in the future. MMV1803522 is another compound that shows great potency in vitro and in vivo. This compound is fully oxidized and contains four aromatic rings. However, the target enzyme and the mechanism of action of MMV1803522 is yet to be discovered, and the structure-activity relationship between the chemical structure and the biological activity of this molecule is still unknown. Therefore, I have developed synthetic methods to synthesize a series of compounds that are structurally similar to the MMV1803522 and found that potency of this molecule is not due to the nitrogen on the C-ring. Also, the number and size of the ring structures in the MMV1803522 may be crucial for this molecule to exhibit great potency in vitro and in vivo.

No description available.

MSc dissertation School of Chemistry Faculty of Science 0004984F / Many azapolycyclic aromatic ring systems, whether they are naturally occurring or synthetically made, display important biological activities. One important class of naturally occurring azapolycyclic aromatic ring systems are the dibenzopyrrocoline alkaloids, which contain an indole ring fused to an isoquinoline moiety, where they share a common nitrogen. The basic skeleton of these alkaloids is the indolo[2,1-a]isoquinoline nucleus. Both the dibenzopyrrocoline alkaloids and the indolo[2,1-a]isoquinolines have been found to inhibit tubulin polymerization and thus possess antitumour and antileukemic activities. In our laboratories, a variety of indolo[2,1-a]isoquinolines, for example 5,12- dimethyl-6-phenylindolo[2,1-a]isoquinoline, have been synthesized using the Suzuki-Miyaura cross coupling reaction and reaction conditions for the formation of aromatic rings (KOBut in DMF and a light source – developed in our laboratories) as key steps. In this dissertation we discuss the synthesis of (±)-5,6-dihydro-6-phenylindolo[2,1-a]isoquinolin-5-ol and ethyl indolo[2,1- a]isoquinoline-6-carboxylate using these reaction conditions as our key steps. The syntheses commenced with the N-protection of isatin with a benzyl and an ethyl acetate group to afford 1-benzylindoline-2,3-dione and ethyl 2-(2,3- dioxoindolin-1-yl)acetate respectively. The next step was the synthesis of the brominated compounds 1-benzyl-2-bromo-1H-indole and ethyl 2-(2-bromo- 1H-indol-1-yl)acetate by means of a functional group interconversion of the oxygen in the 3-position to two chlorine atoms, followed by hydrodehalogenation, using zinc in AcOH, and then bromination, using POBr3 in CH2Cl2. Having obtained the brominated compounds we went on and coupled them with 2-formylphenylboronic acid using the Suzuki-Miyaura cross coupling reaction to obtain the coupled products 2-(1-benzyl-1H-indol-2- yl)benzaldehyde and ethyl 2-(2-(2-formylphenyl)-1H-indol-1-yl)acetate in 92 and 77% yield, respectively. Aromatisation of ethyl 2-(2-(2-formylphenyl)-1Hindol- 1-yl)acetate to ethyl indolo[2,1-a]isoquinoline-6-carboxylate occurred smoothly in 2 minutes using 10 mol % KOBut in DMF at room temperature. Using the same reaction conditions on 2-(1-benzyl-1H-indol-2- yl)benzaldehyde to form 6-phenylindolo-[2,1-a]isoquino-line resulted in (±)- 5,6-dihydro-6-phenylindolo[2,1-a]iso-quinolin-5-ol being obtained in 75% yield (7:3 ratio of anti:syn). An attempt to dehydrate this compound using p-TSA in CH2Cl2 in the presence of molecular sieves was not successful. Time constraints prevented any further attempts at dehydrating (±)-5,6-dihydro-6- phenylindolo[2,1-a]iso-quinolin-5-ol. In conclusion, we managed to synthesize (±)-5,6-dihydro-6-phenylindolo[2,1- a]isoquinolin-5-ol and ethyl indolo[2,1-a]isoquinoline-6-carboxylate using the Suzuki-Miyaura cross coupling reaction and specific reaction conditions, using the base KOtBu, for the formation of aromatic rings, both as key steps.

La réaction de cyclisation de type Wacker, de composés polyols et aminopolyols insaturés constitue un outil puissant et efficace pour la synthèse d’hétérocycles oxygénés ou azotés.Dans ce travail de thèse, nous proposons l’étude d’une réaction catalysée par un complexe de palladium(II) de type domino-cyclisation, mettant en jeu une réaction de couplage. Cette séquence catalytique revient à une fonctionnalisation d’un hétérocycle par une chaîne latérale, tout en créant deux centres stéréogènes en une seule étape. L’influence de la nature des réactifs mis en jeu, ainsi que des conditions expérimentales sur l’activité et la diastéréosélectivité de la réaction sont discutées. Les applications vers la synthèse de produits naturels (anisomycine) ou d’analogues (varitriol) sont présentées.La réaction d’oxycarbonylation catalysée par un complexes de palladium(II) est une transformation intéressante de polyols insaturés en lactones bicycliques, présentant un motif de type tétrahydrofurane avec une excellente stéréosélectivité-cis. Le premier exemple de réaction d’oxycarbonylation catalysée par des complexes de palladium chiraux dans les liquides ioniques est décrit. Une étude approfondie de la nature des ligands démontre que les bis(oxazolines) chirales constituent les meilleurs ligands du palladium pour la cyclisation du pent-4-ène-1,3-diol racémique 69a. Le dédoublement cinétique du composé 69a sous atmosphère de monoxyde de carbone, en présence d’un complexe chiral de palladium(II) et de p-benzoquinone employant l’acide acétique ou le liquide ionique [bmim]NTf2 comme solvant, a permis d’isoler le 2,6-dioxabicyclo-[3.3.0]octane-3-ones avec jusqu’à 57% d’excès énantiomérique pour l’énantiomèrede configuration (R,R)-70a, et jusqu’à 80% d’excès énantiomérique pour l’énantiomèrede configuration (S,S)-70a. / Intramolecular Wacker-type cyclization of unsaturated polyols and aminopolyols represents a powerful method in the synthesis of oxygen- or nitrogen-containing heterocycles. The thesis offers an insight into the systematic study of domino intramolecular palladium(II)-catalyzed cyclization and coupling reaction allowing the implementation of side chains into heterocyclic skeletons along with the formation of two stereocenters in a single step. Different types of coupling partners and reaction conditions were examined, the influence of substrate substituents on diastereoselectivity is discussed. The applications in the synthesis of naturally occuring compounds or their analogs are outlined (anisomycin, varitriol). Palladium(II)-catalyzed oxycarbonylation represents an interesting transformation of unsaturated polyols into bicyclic lactones with tetrahydrofuran structural motif with excellent cis-stereoselectivity. The first example of the use of ionic liquids as reaction media in the asymmetric Pd(II)-catalyzed oxycarbonylation is described. Based on a ligand screening, the chiral bis(oxazoline)-type ligands were successfully used in the Pd(II)-promoted bicyclisationof racemic pent-4-ene-1,3-diol (±)-69a. The kinetic resolution of (±)-69a in the presenceof chiral catalyst and p-benzoquinone under carbon monoxide atmosphere using acetic acid and/or ionic liquid as solvent afforded enantioenriched 2,6-dioxabicyclo[3.3.0]octane-3-ones(R,R)-70a (57% ee) and (S,S)-70a (80% ee), respectively.

Magister Scientiae - MSc (Chemistry) / This work involves the synthesis of copper telluride-polypropylenimine tetra(5-(2-thienyl) salicylaldimine) (CuTe@PPI) and copper antimonide-polypropylenimine tetra(5-(2-thienyl) salicylaldimine) (CuSb@PPI) core-shell nanoparticles (NPs), using two-pots and one-pot synthesis methods, respectively. Their morphology was studied by X-ray diffraction spectroscopy (XRD), high resolution transmission electron microscopy (HRTEM) and high resolution scanning electron microscopy (HRSEM); while their structures were characterized by Fourier transform infrared spectroscopy (FTIR) and elemental analysis. Photophysical properties of the core-shell NPs were determined from ultraviolet-visible absorption spectroscopy (UV-Vis) and photoluminescence spectroscopy (PL). For core-shell NPs produced via two-pots method only CuTe@PPI exhibited ? ? ?* and n ? ?* which indicate that CuSb@PPI produced via two-pots method was unsuccessfully synthesized. The ? ? ?* and n ? ?* transitions indicate the presence of polypropylenimine tetra(5-(2-thienyl) salicylaldimine) (PPI) on the surface of CuTe NPs and CuSb NPs. FTIR confirmed coordination of PPI on the surface of CuTe NPs and CuSb NPs by showing a shift in wavenumber of C=N group bands from PPI. HR-TEM showed that the CuTe@PPI synthesized via one-pot method have a wide particles sizes distribution with an average particles size of 13.60 nm while for CuTe@PPI synthesized via two-pots it was impossible to determine the particles size due to aggregation. CuSb@PPI synthesized via twopots method and one-pot method has a wide particles sizes distribution with an average size of 7.98 nm and 11.61 nm respectively. The average particles sizes determined by HR-SEM were found to be 35.24 nm (CuTe@PPI two-pots method), 33.90 nm (CuTe@PPI one-pot method), 18.30 nm (CuSb@PPI two-pots method), and 16.18 nm (CuSb@PPI one pot method). / 2021-08-31

Nanophase-separated hydrophilic-hydrophobic multiblock copolymers are promising proton exchange membrane (PEM) materials due to their ability to form various morphological structures which enhance transport. Four arylene chlorides monomers (2,5-Dichlorobenzophenone and its derivatives) were first successfully synthesized from aluminum chloride-catalyzed, Friedel-Crafts acylation of benzene and various aromatic compounds with 2,5-dichlorobenzoyl chloride. These monomers were then polymerized via Ni (0)-catalyzed coupling reaction to form various high molecular weight substituted poly(2,5-benzophenone)s. Great care must be taken to achieve anhydrous and inert conditions during the reaction. A series of poly(2,5-benzophenone) activated aryl fluoride telechelic oligomers with different block molecular weights were then successfully synthesized by Ni (0)- catalyzed coupling of 2,5-dichloro-benzophenone and the end-capping agent 4-chloro-4'-fluorobenzophenone or 4-chlorophenly-4′-fluorophenyl sulfone. The molecular weights of these oligomers were readily controlled by altering the amount of end-capping agent. These telechelic oligomers (hydrophobic) were then copolymerized with phenoxide terminated disulfonated poly (arylene ether sulfone)s (hydrophilic) by nucleophilic aromatic substitution to form novel hydrophilic-hydrophobic multiblock copolymers. A series of novel multiblock copolymers with number average block lengths ranging from 3,000 to 10,000 g/mol were successfully synthesized. Two separate Tgs were observed via DSC in the transparent multiblock copolymer films when each block length was longer than 6,000 g/mol (6k). Tapping mode atomic force microscopy (AFM) also showed clear nanophase separation between the hydrophilic and hydrophobic domains and the influence of block length, as one increased from 6k to 10k. Transparent and creasable films were solvent-cast and exhibited good proton conductivity and low water uptake. These PAES-PBP multiblock copolymers also showed much less relative humidity (RH) dependence than random sulfonated aromatic copolymers BPSH 35 in proton conductivity, with values that were almost the same as Nafion with decreasing RHs. This phenomenon lies in the fact that this multiblock copolymer possesses a unique co-continuous nanophase separated morphology, as confirmed by AFM and DSC data. Since this unique co-continuous morphology (interconnected channels and networks) dramatically facilitates the proton transport (increase the diffusion coefficient of water), improved proton conductivity under partially hydrated conditions becomes feasible. These multiblock copolymers are therefore considered to be very promising candidates for high temperature proton exchange membranes in fuel cells. / Ph. D.