La synthèse de nitriles gras à partir de ressources renouvelables est un domaine qui attire depuis quelques temps les industries de la parfumerie, des polymères et des biocarburants pour avion. Ce travail de thèse s’est plus particulièrement intéressé à réduire de 100°C la température de travail pour les procédés en phase liquide et gaz, au moyen de catalyseurs plus efficaces. Le procédé en phase liquide a été étudié en terme de catalyse homogène et les formes actives à base de zinc ou indium ont été plus particulièrement détaillées ; des conditions ont été établies pour obtenir une réduction de 50°C de la température de travail. Le procédé en phase gaz a été étudié en terme de catalyse hétérogène, les catalyseurs obtenus ou synthétisés étant caractérisés par microcalorimétrie d’adsorption ; des corrélations entre la conversion de l’ester et l’acidité du lit catalytique ont été trouvées à 300°C, et des conditions expérimentales ont été développées pour obtenir une conversion totale à une température réduite de 100°C sur des catalyseurs choisis / The production of fatty nitriles from renewable sources has lately become attractive for the perfume, polymer and aviation biofuel industry. The present work investigated both liquidand gas-phase processes in the aim of developing catalysts working at 200°C, this is 100°C lower than the state-of-the-art. Homogeneous catalysis was described with zinc and indium based species for the liquid-phase process, succeeding in reducing by 50°C the operating temperature. Heterogeneous catalysts with acid-base features were characterized by adsorption calorimetry and tested in the gas-phase process, leading to correlations between acidity and ester conversion at 300°C, while conditions were found on selected catalysts in order for the process to perform the complete conversion of esters into nitriles at 200°C

Thesis (MScEng (Process Engineering))--Stellenbosch University, 2008. / Nitriles are precursors of important amides and organic acids (e.g. acrylamide, nicotinamide, mandelic acid and acrylic acid) which are used, inter alia, as food additives, in plasticisers, detergents, make-up, medicine and as chemical intermediates in the production of various important polymers. Traditionally, chemical processes are used to convert nitriles to amides and organic acids but these processes are non-specific causing various by-products to form. Chemical processes are also environmentally unfriendly and require harsh conditions. Nitrile conversions through an enzymatic route, on the other hand, have the distinct advantages of excellent chemo-, regio- and stereo selectivities, mild process conditions and reduced downstream processing costs. The enzymatic process is mediated via an initial nitrilase catalysed conversion to amide, followed by an amidase catalysed conversion to acid. This research focused on the latter part of the enzymatic transformation of nitriles, which is the amidase catalysed biotransformation of an amide to an acid, specifically with respect to the development of a membrane immobilised amidase continuous process which has the major advantage of enzyme retention coupled with product separation. The research was conducted in three parts namely the characterisation of the free amidase, the development of the experimental bioreactor system and the quantification of the membrane immobilised amidase process.

A funcionalização régiosseletiva e quimiosseletiva de arenos utilizando reagentes organometálicos têm sido uma ferramenta importante na síntese de novas moléculas de interesse científico e tecnológico, principalmente para a Química Medicinal. Neste contexto, o objetivo deste trabalho foi investigar a reatividade de amidetos metálicos na funcionalização de benzonitrilas, uma vez que o grupo ciano é um importante intermediário sintético e pode ser transformado em diversos grupos funcionais. Para tanto, inicialmente, cianofenóis foram convertidos aos respectivos pivalatos, carboxilatos e fosforodiamidetos, sendo estes grupos estudados como grupos orto-dirigentes de metalação. Com o objetivo de desenvolver metodologias para funcionalização dos substratos, diferentes amidetos de lítio e mistos de magnésio e lítio foram estudados sob diferentes condições reacionais, sendo iodo o eletrófilo padrão para monitoramento das reações. De maneira geral, observou-se pouca reatividade das bases mistas TMPMgCl?LiCl e TMP2MgCl?2LiCl frente aos substratos estudados. Por outro lado, a base TMPLi se mostrou efetiva na funcionalização dos substratos, sendo que os produtos de rearranjo de Fries foram sempre majoritários em detrimento aos produtos de iodólise. Com isso, diferentes benzonitrilas funcionalizadas de estrutura inédita na literatura puderam ser sintetizadas de maneira regiosseletiva, sendo os produtos caracterizados por meio de análises de RMN bidimensionais. Similarmente, na etapa final do projeto, a reatividade das mesmas bases foi investigada em reações com metóxi-benzonitrilas, sendo que neste caso os iodetos esperados foram obtidos em bons rendimentos pelo uso das bases mistas de magnésio e litio. Adicionalmente, os intermediários organometálicos demostraram boa reatividade frente a diversos eletrófilos, proporcionando o isolamento de benzonitrilas substituídas com diferentes grupos funcionais, sendo estas de grande interesse sintético e medicinal. / The regioselective and chemoselective functionalization of arenes using organometallic reagents has been an important tool for the synthesis of new molecules of scientific and technologic interest, especially for the Medicinal Chemistry. In this context, the objective of this work was to investigate the reactivity of metallic amides in the functionalization of benzonitriles once the cyano group is an important synthetic intermediate and can be transformed in several different functional groups. Thus, initially, cyanophenols were converted to the respective pivalates, carboxylates and phosphodiamides which were studied as ortho directing metalation groups. With the goal of developing methodologies for the functionalization of the cited substrates, different lithium amides and mixed lithium-magnesium amides were studied under different reaction conditions being iodide the standard electrophile for reaction monitoring. In general, it was observed little reactivity of the mixed bases TMPMgCl?LiCl and TMP2MgCl?2LiCl against the studied substrates. On the other hand, the TMPLi base has proved to be effective in the functionalization of the substrates though the Fries\' rearrangement products were always observed in majority compared to the iodolysis products. By using this strategy, several novel functionalized benzonitriles could be synthetized in a regioselective way with the products being characterized by bidimensional NMR techniques. Similarly, in the final stage of the project the reactivity of the same bases was investigated in reactions employing methoxi-benzonitriles where the mixed lithium-magnesium afforded the expected iodides in good yields. Additionally, the organometallic intermediates demonstrated good reactivity against several electrophiles providing the isolation of substituted benzonitriles of great synthetic and medicinal interest.

A funcionalização regiosseletiva e quimiosseletiva de arenos e heterociclos utilizando reagentes organometálicos têm sido uma ferramenta importante na síntese de novas moléculas bioativas, assim como na química de materiais. Neste contexto, o objetivo deste trabalho foi investigar a reatividade de novos reagentes mistos de magnésio e de lítio na funcionalização de nitrilas aromáticas (dicianobenzeno) e heteroaromáticas (furano, tiofeno, piridina e pirazina), uma vez que o grupo ciano é um importante intermediário sintético e pode ser transformado em diversos grupos funcionais. Para todos os substratos, foram realizados testes metodológicos, a fim de obter a melhor condição reacional de metalação utilizando a base organometálica TMPMgCloLiCl na presença ou ausência de aditivos, como ZnCl2. Após a formação do intermediário magnesiado, diferentes eletrófilos foram testados, levando aos produtos desejados em bons rendimentos. Por outro lado, após reações de transmetalação com cloreto de zinco, os intermediários puderam ser arilados através de reações de acoplamento cruzado de Negishi. Além disso, o estudo de metalação dirigida de nitrilas contendo furano e tiofeno em sua estrutura resultou na síntese de nitrilas heterocíclicas funcionalizadas em bons rendimentos. De forma similar, na sequência do trabalho, as funcionalizações de uma série de piridinas e pirazinas foram avaliadas utilizando a base TMPMgCloLiCl , tanto em condições convencionais, quanto pelo uso de irradiação de micro-ondas na etapa de metalação. Após as reações dos reagentes organomagnésio correspondentes com diversos eletrófilos, foram obtidos pirazinas e piridinas funcionalizadas com interessantes quimio- e regiosseletividades, e em rendimentos moderados. Finalmente, a reatividade de cianobenzenos e dicianobenzenos frente à base TMPMgCloLiCl foi também avaliada, e neste caso os reagentes de lítio se mostraram mais eficientes para funcionalização destes compostos. / The regio- and chemoselective functionalization of arenes and heterocycles using organometallic reagents has been an important synthetic tool in the synthesis of new bioactive molecules, as well as in materials chemistry. In this context, the objective of this study was to investigate the reactivity of new mixed magnesium-lithium reagents in the functionalization of aromatic nitriles (dicyanobenzene) and heteroaromatic (furan, thiophene, pyridine and pyrazine), whereas the cyano group is an important synthetic intermediate and can be transformed into various functional groups. For all substrates, methodological trials were performed in order to stablish the best reaction conditions of metalation using organometallic base TMPMgCloLiCl in the presence or absence of additives such as ZnCl2. After formation of the magnesiated intermediated, reactions were quenched with several electrophiles, leading to the desired products in good yields. Following a transmetalation step with ZnCl2, intermediates could be arylated using Negishi cross-coupling reactions. Moreover, the metalation study using nitrile-substituted furan and thiophene substrates resulted in functionalized heterocyclic nitriles in good yields. Similarly, the functionalization of pyridines and pyrazines with TMPMgCloLiCl were also evaluated using both conventional conditions and under microwave irradiation in the metalation step. After that, the treatment of the corresponding organomagnesium intermediates with various electrophiles provided functionalized pyrazines and pyridines with interesting chemo- and regioselectivity and in moderated yields. Finally, the reactivity of cyano- and dicyanobenzenes against the base TMPMgCloLiCl was also evaluated, however in this case the organolithium reagents appeared to be more efficient for the functionalization of this class of compounds

<p>For decades there has been interest in understanding early prebiotic Earth, including its atmospheric chemistry. Saturn’s moon Titan is the only other body in our Solar System with an atmosphere thought to resemble that of early Earth’s, and for this reason it has garnered a lot of attention over the years. Much is now known about the smaller molecules present in that atmosphere, starting with the most abundant, N₂ and CH₄, and going up to slightly larger molecules such as cyanoacetylene and benzene. As the molecules get larger, however, so does the gap in knowledge, especially as it pertains to nitriles. This dissertation aims to add to the story of Titan’s nitriles by first characterizing a molecule thought to be the photochemical product of the reaction between cyanoacetylene and benzene, 3-phenyl-2-propyne-nitrile (PPN). The UV spectra of PPN proved immensely interesting due to the strong presence of in-plane and out-of-plane vibrations of b₂ and b₁ symmetry, respectively. This is possibly a result of strong vibronic coupling between several excited electronic states or Coriolis coupling between complementary b₁ and b₂ vibrational levels. The multi-layer extension of the multi-configuration time dependent Hartree (ML-MCTDH) algorithm was used to understand how the excited states and the vibrational levels might interact, and emission and absorption spectra were modeled and compared to the experimental spectra. The second group of molecules studied included the <i>ortho</i>-, <i>meta</i>-, and <i>para</i>-methyl PPN. Strong methyl rotor activity is seen in the <i>m</i>-methyl PPN, with some activity in the <i>p</i>-methyl PPN. The methyl rotor activity in the <i>m</i>-methyl PPN is similar to other <i>meta</i>-substituted toluenes, and allows us to describe the methyl rotor barrier height in both ground and excited electronic state. Additionally, in all three methylated PPNs we see evidence for strong vibronic coupling in the abundance of out-of-plane vibrations, as had been seen in PPN.</p>

by Fung Chun-wah. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 117-119). / Abstracts in English and Chinese. / Table of Contents --- p.i / Acknowledgments --- p.v / Abbreviations --- p.vi / Abstract --- p.vii / Chapter PART I: --- ACTIVATION OF CARBON-CARBON BONDS OF NITRILES BY RHODIUM PORPHYRIN RADICAL / Chapter CHAPTER 1 --- General Introduction --- p.1 / Chapter 1.1.1 --- Activation of Carbon-Carbon Bond (CCA) by Transitional Metals --- p.1 / Chapter 1.1.1.1 --- Potential Application of C-C Bond Activation --- p.1 / Chapter 1.1.1.1.1 --- Cracking --- p.1 / Chapter 1.1.1.1.2 --- Depolymerization --- p.2 / Chapter 1.1.1.2 --- Thermodynamic and Kinetic Considerations in CCA --- p.3 / Chapter 1.1.1.3 --- C-C Bond Activation in Strained System --- p.3 / Chapter 1.1.1.4 --- C-C Bond Activation facilitated by Aromatization --- p.7 / Chapter 1.1.1.5 --- C-C Bond Activation of Carbonyl Compounds --- p.9 / Chapter 1.1.1.6 --- C-C Bond Activation of the Nitriles --- p.13 / Chapter 1.1.1.7 --- Selective C-C Bond Activation on a Multimetallic Site --- p.16 / Chapter 1.1.1.8 --- Intramolecular sp2 -sp3 C-C Bond Activation in PCP System --- p.17 / Chapter 1.1.1.9 --- CCA in N-Heterocyclic Carbene --- p.18 / Chapter 1.1.1.10 --- CCA in Pt(0) complexes bearing Chelating P´ةN- and P´ةP- Ligands --- p.19 / Chapter 1. 1.1.11 --- CCA of Alkyne via Hydroiminoacylation by Rh(I) Catalyst --- p.20 / Chapter I. 1.1.12 --- CCA in Homoallylic Alcohol by β-Allyl Elimination --- p.21 / Chapter I. 1.1.13 --- C-C Bond Activation by Metathesis of Alkanes --- p.23 / Chapter I.1.2 --- Structural Features of Rhodium Porphyrins --- p.25 / Chapter I.1.3 --- Objective of the Work --- p.27 / Chapter CHAPTER 2 --- Carbon-Carbon Bond Activation (CCA) of Nitriles by Rhodium Porphyrin Radical --- p.28 / Chapter I.2.1 --- Introduction --- p.28 / Chapter I.2.1.1 --- CCA of Nitroxides by Rhodium(II) Porphyrin Radical Rh(por) --- p.28 / Chapter I.2.2 --- CCA of Nitriles by Rh(tmp) Radical --- p.29 / Chapter I.2.2.1 --- Synthesis of Rh(tmp)Me --- p.29 / Chapter I.2.2.2 --- Synthesis of Rh(tmp) Radical --- p.30 / Chapter I.2.2.3 --- Ligand effect on CCA --- p.31 / Chapter I.2.2.3.1 --- Synthesis of Phosphines --- p.31 / Chapter I.2.2.3.2 --- Reactions between Rh(tmp) and Phosphines --- p.32 / Chapter I.2.2.3.3 --- Synthesis of Alkyl Rh(tmp) --- p.35 / Chapter I.2.2.4 --- CCA of Nitriles by Rh(tmp) with PPh3 added --- p.36 / Chapter I.2.2.4.1 --- Synthesis of Nitrile --- p.36 / Chapter I.2.2.4.2 --- Reactions between Rh(tmp) and Nitriles --- p.37 / Chapter I.2.3.4 --- Proposed Mechanism of CCA --- p.44 / Chapter CHAPTER 3 --- Experimental Section --- p.46 / Conclusion --- p.63 / References --- p.64 / Chapter PART II --- ACTIVATION OF CARBON-SILICON BONDS OF NITRILES BY RHODIUM PORPHYRIN RADICAL --- p.71 / Chapter CHAPTER 1 --- General Introduction --- p.71 / Chapter II. 1.1 --- Carbon-Silicon Bond Activation by Transitional Metals --- p.71 / Chapter II. 1.1.1 --- Potential Application of C-Si Bond Activation --- p.72 / Chapter II.l. l.2 --- C(sp3)-Si Bond Activation --- p.73 / Chapter II. 1.1.2.1 --- Intermolecular C(sp3)-Si Bond Activation in Strained System --- p.73 / Chapter II. 1.1.2.2 --- Intermolecular C(sp3)-Si Bond Activation in Unstrained System --- p.76 / Chapter II. 1.1.3 --- C(sp2)-Si Bond Activation --- p.78 / Chapter II. 1.1.3.1 --- Intermolecular C(aryl)-Si Bond Activation --- p.78 / Chapter II. 1.1.3.2 --- Intramolecular C(aryl)-Si Bond Activation --- p.84 / Chapter II. 1.1.3.3 --- C(vinyl)-Si Bond Activation --- p.87 / Chapter II. 1.1.4 --- C(sp)-Si Bond Activation --- p.89 / Chapter II. 1.2 --- Objective of the Work --- p.92 / Chapter CHAPTER 2 --- Carbon-Silicon Bond Activation (CSA) of Nitriles --- p.93 / Chapter II.2.1 --- Introduction --- p.93 / Chapter II.2.2 --- Reactions between Rh(tmp) Radical and Silylnitriles --- p.93 / Chapter II.2.2.1 --- Investigation the CSA of Trimethylsilylcyanide by Rh(tmp) --- p.93 / Chapter II.2.2.1.1 --- Synthesis of Rh(tmp)SiMe3 --- p.93 / Chapter II.2.2.1.2 --- Synthesis of Rh(tmp)CN --- p.94 / Chapter II.2.2.1.3 --- Reactions between Rh(tmp) and Trimethylsilylcyanide --- p.95 / Chapter II.2.2.1.4 --- Ligands effect on CSA of Trimethylsilylcyanide by Rh(tmp) --- p.98 / Chapter II.2.2.1.5 --- Temperature effect on CSA --- p.101 / Chapter II.2.2.2 --- Reactions between Rh(tmp) and other Silylnitriles --- p.102 / Chapter II.2.3 --- Mechanism of CSA of Trimethylsilylcyanide --- p.103 / Chapter II.2.3.1 --- Proposed Mechanism of CSA of Trimethylsilylcyanide by Rh(tmp) --- p.104 / Chapter II.2.4 --- A Comparison of CSA and CCA of Nitriles --- p.105 / Chapter CHAPTER 3 --- Experimental Section --- p.107 / Conclusion --- p.116 / References --- p.117 / List of Spectra --- p.120 / Spectra --- p.121

Mechanistic investigation has been carried out for the reaction between Rh(tmp) and the nitroxide, 2,2,6,6-tetramethyl-piperidine-1-oxyl (TEMPO). Mechanistically, Rh(tmp) at first coordinated with one molecule of TEMPO to produce a 1:1 adduct. Through this complex, parallel major carbon-carbon bond activation (CCA) and minor carbon-hydrogen bond activation (CHA) occurred. CCA was more favorable at higher reaction temperatures. The CHA product Rh(tmp)H further reacted with excess TEMPO to produce Rh(tmp) again for further CCA and CHA. The overall activation reaction was found to follow second order kinetics, rate = k [Rh(tmp)] [TEMPO]. / Rhodium(II) meso-tetramesitylporphyrin (Rh(tmp)) has been prepared successfully by photolysis of Rh(tmp)Me under anaerobic conditions at low temperature. / The activation of carbon-carbon bond with high reactivity and selectivity has attracted many organometallic chemists due to its fundamental importance in basic chemical research and potential utility in organic synthesis. / The aliphatic, unstrained carbon-carbon bonds of a series of nitroxides 1,1,3,3-tetraalkylisoindolin-2-oxyl have been activated by Rh(tmp). In long chain alkyl substituted nitroxides, regioselective carbon-carbon bond activations were observed. This was attributed to the cooperative effects of the bond dissociation energy and the steric hindrance of alkyl groups in nitroxides. While PPh3 was used as the fifth ligand, the yields of regioselective CCA changed. For sterically less hindered nitroxides, the total yield of CCA increased. For sterically more hindered nitroxides, the total yield of CCA decreased. These can be attributed to the cooperation of steric and electronic effects in the rhodium porphyrin complexes and nitroxides. / The C(sp3)-C(sp3) bonds of a series of alpha-alkylphenylacetonitriles have been activated by Rh(tmp) using PPh3 as the optimized fifth ligand. The activation was not regioselective. The CCA yield was affected by bond energy and steric hindrance of the nitriles. The optimal reaction temperature was 130 &deg;C. / Under same reaction conditions, CCA between Rh(tmp) and 2-alkylbenzonitriles also was carried out. Only C(sp3)-C( sp3) bond was activated. CCA yield depended on the BDE of C-C bond in alkyl substituents. / by Li Xinzhu. / "June 2006." / Adviser: Kin Shing Chan. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6396. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 197-210). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Five novel compounds were synthesized and characterized. Crystal structures were determined using Rigaku Mercury 375/MCCD(XtaLAB mini) diffractometer with graphite monochromated MoKα radiation. The crystal structures of [Rh2(NPhCOCH3)4•xNCC6H4R where x = 1 or 2 and R=H, 2-CH3,3-CH3 and 4-CH3 were solved to an R1 value of less than 5 (R1= Σ||Fo| - |Fc|| / Σ |Fo|). In each of the nitrile complexes, the rhodium is five or six coordinate and possesses pseudo D4h symmetry. The complexes were also characterized by NMR and IR spectroscopy. [Rh2(CO2CCH3)(PhCOCF3)3] was also synthesized. In this complex, each rhodium atom is six coordinate, thus each rhodium is in an octahedral environment. Details of each synthesized complex are discussed.

A new method for running the Knoevenagel condensation in high yields has been developed and tested in eleven reactions with malononitrile. The dimer from cyclopentylidenemalononitrile was characterized and its structure was deduced from spectroscopy data. Reactions of the monomers with isoprene were carried out in sealed tubes and the ratio and yields of the isomeric products were determined by gas liquid partition chromatography. A para relationship of the cyano and methyl groups is favored in the products.Ball State UniversityMuncie, IN 47306

La réaction de Kulinkovich, découverte en 1989, permet la transformation d'esters encyclopropanols par réaction avec un complexe oléfinique de titane. Cette réaction a étéappliquée en 2001 à la conversion des nitriles en cyclopropylamines primaires.Nous avons tout d'abord effectué une étude de la cyclopropanation asymétrique d'uncyanoester par un complexe chiral de titane. Une méthode d'évaluation rapide de l'inductionasymétrique de ligands chiraux a été mise au point, et a permis de réaliser un screening dediols chiraux. Les meilleurs résultats ont été obtenus avec le TADDOL, qui a fourni des excèsénantiomériques moyens, mais notre méthode d'évaluation reste un atout pour l'évaluationd'autres types de ligands chiraux.Une méthode originale de formation de 1,4-dicétones via un complexe oléfinique detitane a été découverte puis optimisée, et ses limites ont été explorées. La préparation des 1,4-dicétones s'effectue en deux étapes à partir d'acides carboxyliques avec des rendementsmodestes à satisfaisants. L'utilisation de réactifs peu coûteux et peu toxiques ainsi que lagrande diversité structurale accessible rendent notre méthode de synthèse compétitive vis-àvisde celles décrites dans la littérature.Plusieurs études réalisées précédemment par notre équipe ont permis de synthétiser defaçon exclusive les isomères (Z) de divers 2,3-méthanoaminoacides. Nous avons développé aucours de cette thèse une voie de synthèse des isomères (E) et (Z) de la 2,3-méthanolysineprotégés de façon orthogonale, via la cyclopropanation diastéréosélective d'une cyanhydrinebenzylée. La flexibilité de cette stratégie permet d'envisager la préparation des isomères (E)et (Z) de nombreux autres analogues contraints d'acides aminés.