Synthesis and characterization of triazolotriazines

The Dimroth rearrangement in ring-fused 1,2,4-triazoles has been reviewed in detail in Part I and the synthesis of all known triazolo-triazines is described in Part II. Experimental investigations concerned the establishinent of the skeletal arrangement of a variety of triazolotriazines formed by several synthetic routes. Interaction of 3-amino-5-hydrazino-12,4-triazole and benzilafforded 2-amino-6, 7-diphenyl-1, 2,4-triazolo[ 5, 1-c-]-1,2,4-triazine,whereas cyclization of 5,6-diphenyl-3-hydrazino-1,2,4-triazine withcyanogen bromide resulted in the isomeric 3-amino-6,7-diphenyl,-1,2,4-triazolo [4, 3-b]-1,2,4-triazine: both amines were deaminated with amyl nitrite in boiling tetrahydrofuran without rearrangement of the heterocyclic skeleton. 6,7-Diphenyl-1,2,4-triazolo[5,1-cJ-1,2.4-triazine, synthesized from 3-hydrazino-1,2,4-triazole and benzil, formed a covalent hydrate which could be detected spectroscopically in solution, and a covalemt methanolate and ethanolate which could be isolated. A new route to 3-amino-5-hydrazino-pyrazole is described and cyclization to 7-amino-3,4-diphenyl-pyrazolo[ 5,1-.c]-1,2,4-triazine was achieved with benzil. The diazonium nitrate of 3-amino-1,2,4-triazole coupled with ethyl cyanoacetate to yield a mixture of two geometrical isomers of ethyl 2-(2H-1,2,4-triazol-3-ylhydrazono) cyanoacetate.Recrystallization of the crude coupling mixture from aqueous ethanol gave a single hydra-zone which cyclized predominantly to ethyl 7-amino-1,2,4-triazolo[5,1-c]-1,2,4-triazine-6-carboxylate in acid conditions and 6-cyano-1,2,4-triazolo[ 5,1-c]-1,2,4~triazin-7(4H)-one under basic conditions. The nature of the cyclizing medium also controlled the cyclization of .the (pyrazol-ylhydrazono) cyanoacetate hut the corresponding (tetrazol- ylhydrazono) cyanoacetate gave only ethyl 7-aminotetrazolo[ 5,1-cJ-1,2,4- -triazine-6-carboxylate. 2-( 2H-1,2,4-Triazol-3-:ylhydrazono) malonitrile cyclized unambiguously to 7-amino-6-cyano-1,2,4-triazolo-[ 5,1-c]-1,2,4- triazine. Drastic hydrolysis of ethyl 2-(2H-1,2,4-triazol-3-yllhydrazono)-cyanoacetate, ethyl 7-amino-1, 2,4-triazolo[ 5,1-c]-1,2,4-triazine-6-carboxylate, 6-cyano-1,2,4-triazolo[ 5,1-c]-1,2,4-triazin-7{ 4H)-one and 7-amino-6- cyano-1,2,4-triazolo[5,1-c]-1,2,4-triazine gave a hydrate of 1,2,4-triazo1o[5,1-c ]-1,2,4-triazin-7(4H)-one. Mass spectral fragmentations of 7-aminoazolo-[5,1-c]-1,2,4-triazinesconfirm that the azole ring is more stable than the 1,2,4-triazine ring on electron impact.

Electrospinning pH-responsive block copolymer nanofibers

Electrospinng of a fibrous triblock copolymer consisting of poly(methyl methacrylate-block-poly[2-(diethylamino) ethyl methacrylate]-block-poly(methyl methacrylate) (PMMA-b-PDEA-b-PMMA) has been discussed. A mixed co-solvent system of tetrahydrofuran (THF) and dimethylformamide (DMF) was used to electrospin fibrous PMMA-b-PDEA-b-PMMA and its influence on surface morphology and diameter of the electrospun fiber was also investigated in an attempt to control the fiber diameter. The concentration range between 20 and 40 wt % was found suitable for electrospinning of PMMA-b-PDEA-b-PMMA in a THF/DMF system. It was also observed that the average fiber diameter decreased as the content of DMF was increased. A significant decrease in fiber diameter was observed when moving from a THF solution to a THF/DMF system at a ratio of 70:30.

Controlled growth of poly(2-(diethylamino)ethyl methacrylate) brushes via atom transfer radical polymerisation on planar silicon surfaces

Progress in making pH-responsive polyelectrolyte brushes with a range of different grafting densities is reported. Polymer brushes of poly(2-(diethylamino)ethyl methacrylate) were synthesised via atom transfer radical polymerisation on silicon wafers using a 'grafted from' approach. The [11-(2-bromo-2-methyl) propionyloxy]undecyl trichlorosilane initiator was covalently attached to the silicon via silylation, from which the brushes were grown using a catalytic system of copper(I) chloride and pentamethyldiethylenetriamine in tetrahydrofuran at 80°C. X-ray reflectivity was used to assess the initiator surfaces and an upper limit on the grafting density of the polymer was determined. The quality of the brushes produced was analysed using ellipsometry and atomic force microscopy, which is also discussed.

Alquilação de tolueno com propeno, através de complexo ferro (II) ᵦ- diimina homogêneo e heterogeneizado em MCM-41, Al-MCM-41 e SBA-15

This work describes the synthesis and aplication of homogeneous and heterogenized iron catalysts in the alkylation reaction of toluene with propene, empolying experimental design. The homogenous complex was obtained trough the synthesis of the organic ligand folowed by the complexation of the iron(II) chloride. As to the heterogenized complexes, first were synthetized the inorganic supports (SBA-15, MCM-41 and Al-MCM-41). Then, it was synthetized the ligand again, that through funcionalization with chloropropyltrimethoxysilane (CPTMS), was anchored on the support previously calcinated. To these anchored ligands, was complexed the iron(II) chloride, previously solubilizated in tetrahydrofuran (THF). The organic ligand characterization was accomplished trough nuclear magnetic resonance (NMR) and Infrared spectroscopy (IV). The supports were characterized with x-ray diffraction (DRX), texture analysis with nitrogen adsorption/desorption (before and after the anchoring), termogravimetric analysis (TG) and infrared (IV). The metalic content was quantified trough the atomic absorption spectrophotometry (AAS). The complexes were tested in catalytic reactions emolying ethylaluminium sesquichloride (EASC) as co-catalyst in steel reactor, under mecanic stirring. The reaction conditions ranged from 4 to 36 ◦C, with many aluminum/iron ratios. The catalysts were actives in homogeneous and heterogenized ways. The homogenous catalytic complex showed a maximum turnover frequency (TOF) of 8.63 ×103 · h −1 , while, in some conditions, the anchored complexes showed better results, with TOF of until 8.08 ×103 · h −1 . Aditionally, it was possible to determine an equation, to the homogenous catalyst, that describes the product quantity in function of reacional temperature and aluminum/iron ratio.

Study of the kinetics and mechanism of rapid self-assembly in block copolymer thin films during solvo-microwave annealing

Microwave annealing is an emerging technique for achieving ordered patterns of block copolymer films on substrates. Little is understood about the mechanisms of microphase separation during the microwave annealing process and how it promotes the microphase separation of the blocks. Here, we use controlled power microwave irradiation in the presence of tetrahydrofuran (THF) solvent, to achieve lateral microphase separation in high- lamellar-forming poly(styrene-b-lactic acid) PS-b-PLA. A highly ordered line pattern was formed within seconds on silicon, germanium and silicon on insulator (SOI) substrates. In-situ temperature measurement of the silicon substrate coupled to condition changes during "solvo-microwave" annealing allowed understanding of the processes to be attained. Our results suggest that the substrate has little effect on the ordering process and is essentially microwave transparent but rather, it is direct heating of the polar THF molecules that causes microphase separation. It is postulated that the rapid interaction of THF with microwaves and the resultant temperature increase to 55 degrees C within seconds causes an increase of the vapor pressure of the solvent from 19.8 to 70 kPa. This enriched vapor environment increases the plasticity of both PS and PLA chains and leads to the fast self-assembly kinetics. Comparing the patterns formed on silicon, germanium and silicon on insulator (SOI) and also an in situ temperature measurement of silicon in the oven confirms the significance of the solvent over the role of substrate heating during "solvo-microwave" annealing. Besides the short annealing time which has technological importance, the coherence length is on a micron scale and dewetting is not observed after annealing. The etched pattern (PLA was removed by an Ar/O-2 reactive ion etch) was transferred to the underlying silicon substrate fabricating sub-20 nm silicon nanowires over large areas demonstrating that the morphology is consistent both across and through the film.

Fabrication of sub-10 nm lamellar structures by solvent vapour annealing of block copolymers

Fabrication of nanoscale patterns through the bottom-up approach of self-assembly of phase-separated block copolymers (BCP) holds promise for nanoelectronics applications. For lithographic applications, it is useful to vary the morphology of BCPs by monitoring various parameters to make “from lab to fab” a reality. Here I report on the solvent annealing studies of lamellae forming polystyrene-blockpoly( 4-vinylpyridine) (PS-b-P4VP). The high Flory-Huggins parameter (χ = 0.34) of PS-b-P4VP makes it an ideal BCP system for self-assembly and template fabrication in comparison to other BCPs. Different molecular weights of symmetric PS-b-P4VP BCPs forming lamellae patterns were used to produce nanostructured thin films by spin-coating from mixture of toluene and tetrahydrofuran(THF). In particular, the morphology change from micellar structures to well-defined microphase separated arrangements is observed. Solvent annealing provides a better alternative to thermal treatment which often requires long annealing periods. The choice of solvent (single and dual solvent exposure) and the solvent annealing conditions have significant effects on the morphology of films and it was found that a block neutral solvent was required to realize vertically aligned PS and P4VP lamellae. Here, we have followed the formation of microdomain structures with time development at different temperatures by atomic force microscopy (AFM). The highly mobilized chains phase separate quickly due to high Flory-Huggins (χ) parameter. Ultra-small feature size (~10 nm pitch size) nanopatterns were fabricated by using low molecular weight PSb- P4VP (PS and P4VP blocks of 3.3 and 3.1 kg mol-1 respectively). However, due to the low etch contrast between the blocks, pattern transfer of the BCP mask is very challenging. To overcome the etch contrast problem, a novel and simple in-situ hard mask technology is used to fabricate the high aspect ratio silicon nanowires. The lamellar structures formed after self-assembly of phase separated PS-b-P4VP BCPs were used to fabricate iron oxide nanowires which acted as hard mask material to facilitate the pattern transfer into silicon and forming silicon nanostructures. The semiconductor and optical industries have shown significant interest in two dimensional (2D) molybdenum disulphide (MoS2) as a potential device material due to its low band gap and high mobility. However, current methods for its synthesis are not ‘fab’ friendly and require harsh environments and processes. Here, I also report a novel method to prepare MoS2 layered structures via self-assembly of a PS-b-P4VP block copolymer system. The formation of the layered MoS2 was confirmed by XPS, Raman spectroscopy and high resolution transmission electron microscopy.

Mesure de sections efficaces absolues vibrationnelles pour la collision d’électrons de basse énergie (1-19 eV) avec le tétrahydrofurane (THF) condensé

Résumé: Ce mémoire de maîtrise est une étude des probabilités d’interactions (sections efficaces) des électrons de basse énergie avec une molécule d’intérêt biologique. Cette molécule est le tétrahydrofurane (THF) qui est un bon modèle de la molécule constituant la colonne vertébrale de l’ADN; le désoxyribose. Étant donné la grande quantité d’électrons secondaires libérés lors du passage des radiations à travers la matière biologique et sachant que ceux-ci déposent la majorité de l’énergie, l’étude de leurs interactions avec les molécules constituant l’ADN devient rapidement d’une grande importance. Les mesures de sections efficaces sont faites à l’aide d’un spectromètre à haute résolution de pertes d’énergie de l’électron. Les spectres de pertes d’énergie de l’électron obtenus de cet appareil permettent de calculer les valeurs de sections efficaces pour chaque vibration en fonction de l’énergie incidente de l’électron. L’article présenté dans ce mémoire traite de ces mesures et des résultats. En effet, il présente et explique en détail les conditions expérimentales, il décrit la méthode de déconvolution qui est utilisée pour obtenir les valeurs de sections efficaces et il présente et discute des 4 résonances observées dans la dépendance en énergie des sections efficaces. En effet, cette étude a permis de localiser en énergie 4 résonances et celles-ci ont toutes été confirmées par des recherches expérimentales et théoriques antérieures sur le sujet des collisions électrons lents-THF. En outre, jamais ces résonances n’avaient été observées simultanément dans une même étude et jamais la résonance trouvée à basse énergie n’avait été observée avec autant d’intensité que cette présente étude. Cette étude a donc permis de raffiner notre compréhension fondamentale des processus résonants impliqués lors de collisions d’électrons secondaires avec le THF. Les valeurs de sections efficaces sont, quant à elles, très prisées par les théoriciens et sont nécessaires pour les simulations Monte Carlo pour prédire, par exemple, le nombre d’ions formées après le passage des radiations. Ces valeurs pourront justement être utilisées dans les modèles de distribution et dépôt d’énergie au niveau nanoscopique dans les milieux biologiques et ceux-ci pourront éventuellement améliorer l’efficacité des modalités radiothérapeutiques.

Towards the total synthesis of amphidinolides C and F

The amphidinolides are marine macrolides extracted from dinoflagellates of the genus Amphidinium. To date, 37 amphidinolides have been isolated and identified, most of them possessing cytotoxicity against human cancer cell lines. Among these, amphidinolides C, F, C2 and C3 represent synthetic targets of interest owing to their scarcity, structural complexity and promising biological activities. This thesis describes the work realised towards the total synthesis of amphidinolides C and F, with a focus on the different strategies investigated and the key fragments synthesised. In the first approach, the C18−C29 fragment of amphidinolide F was prepared using an intramolecular etherification of an epoxide under acidic catalysis to produce the 2,5-trans-disubstituted tetrahydrofuran ring featured in the natural product. Unfortunately, dithiane alkylation with the C1−C17 iodide counterpart generated the desired coupling product in low yield. A second approach proposing to build the C17−C18 bond by a silicon-tethered RCM proved unsuccessful, because the requisite diene could not be obtained. It was then envisioned to form the C18−C19 bond by displacement of a triflate with an alkyne and install the ketone at C18 by a protoborylation/oxidation sequence. To this end, the C19−C29 triflate precursor was synthesised. Displeasingly, the C1−C18 alkyne counterpart (work by Dr Filippo Romiti) could not be prepared and coupling of the two fragments was not attempted. In the latest approach, the C10−C29 fragment of amphidinolide F was obtained employing a boron-mediated aldol condensation and a dithiane alkylation to form the C13−C14 and C18−C19 bonds. Several endgame strategies were examined including the successful Yamaguchi esterification of the C13-epi C10−C29 fragment and the C1−C9 acid. A challenging Stille crosscoupling was then effected to close the macrocycle but only yielded the desired macrolactone in trace amounts after global desilylation.

Copper Nanoparticles in Click Chemistry

Conspectus: The challenges of the 21st century demand scientific and technological achievements that must be developed under sustainable and environmentally benign practices. In this vein, click chemistry and green chemistry walk hand in hand on a pathway of rigorous principles that help to safeguard the health of our planet against negligent and uncontrolled production. Copper-catalyzed azide–alkyne cycloaddition (CuAAC), the paradigm of a click reaction, is one of the most reliable and widespread synthetic transformations in organic chemistry, with multidisciplinary applications. Nanocatalysis is a green chemistry tool that can increase the inherent effectiveness of CuAAC because of the enhanced catalytic activity of nanostructured metals and their plausible reutilization capability as heterogeneous catalysts. This Account describes our contribution to click chemistry using unsupported and supported copper nanoparticles (CuNPs) as catalysts prepared by chemical reduction. Cu(0)NPs (3.0 ± 1.5 nm) in tetrahydrofuran were found to catalyze the reaction of terminal alkynes and organic azides in the presence of triethylamine at rates comparable to those achieved under microwave heating (10–30 min in most cases). Unfortunately, the CuNPs underwent dissolution under the reaction conditions and consequently could not be recovered. Compelling experimental evidence on the in situ generation of highly reactive copper(I) chloride and the participation of copper(I) acetylides was provided. The supported CuNPs were found to be more robust and efficient catalyst than the unsupported counterpart in the following terms: (a) the multicomponent variant of CuAAC could be applied; (b) the metal loading could be substantially decreased; (c) reactions could be conducted in neat water; and (d) the catalyst could be recovered easily and reutilized. In particular, the catalyst composed of oxidized CuNPs (Cu2O/CuO, 6.0 ± 2.0 nm) supported on carbon (CuNPs/C) was shown to be highly versatile and very effective in the multicomponent and regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles in water from organic halides as azido precursors; magnetically recoverable CuNPs (3.0 ± 0.8 nm) supported on MagSilica could be alternatively used for the same purpose under similar conditions. Incorporation of an aromatic substituent at the 1-position of the triazole could be accomplished using the same CuNPs/C catalytic system starting from aryldiazonium salts or anilines as azido precursors. CuNPs/C in water also catalyzed the regioselective double-click synthesis of β-hydroxy-1,2,3-triazoles from epoxides. Furthermore, alkenes could be also used as azido precursors through a one-pot CuNPs/C-catalyzed azidosulfenylation–CuAAC sequential protocol, providing β-methylsulfanyl-1,2,3-triazoles in a stereo- and regioselective manner. In all types of reaction studied, CuNPs/C exhibited better behavior than some commercial copper catalysts with regard to the metal loading, reaction time, yield, and recyclability. Therefore, the results of this study also highlight the utility of nanosized copper in click chemistry compared with bulk copper sources.