No description available.

No description available.

No description available.

Alkylphenols are important industrial chemicals used in a wide range of applications. In particular, 2,6-ditertbutylphenol is an indispensable building block for anti-oxidants and light protective agents. A new solid catalyst was prepared, characterised and tested for the alkylation of phenols with alkenes in an attempt to reduce the environmental hazards associated with the aqueous wastes generated by the homogeneously catalysed alkylation reactions. The new silica gel supported aluminium phenolate catalyst was prepared by a two steps procedure, first grafting of an aluminium precursor such as aluminium trichloride or triethyl aluminium onto silica mainly through reaction with the support silanol groups, then exchange of the aluminium ligand with phenol. Catalysts exhibited mainly Lewis acidity and two types of active sites were detected. The new catalyst was successfully applied in the phenol - isobutene alkylation system. Catalysts exhibited an ortho- selectivity for the introduction of the first tertbutyl group. The selectivity of the second alkylation could be tuned by varying reaction conditions (reaction temperature, catalyst amount, alkene addition methods) and catalyst characteristics (support surface pre-treatment temperature, aluminium precursor and loading). Hence high yields of 2,4-ditertbutylphenol or moderated yields of 2,6-ditertbutylphenol were obtained. Alkylation of phenol with other alkenes and cresols alkylations were successfully catalysed by the new silica gel supported aluminium phenolate catalyst with the same selectivity. However, the diorthopropylphenol was the main dialkyl products when using propene as alkylating agent. "Greening" of the catalyst preparation by reducing the amount of solvent used was carried out without changing the selectivity and the activity of the catalyst. Reusability of the catalyst was investigated and a decrease of activity was observed. Storage of the catalyst was possible for a long time but activity and selectivity were affected.

The catalytic ortho-arylation of phenols is a reaction that has been developed by our Bedford and coworkers allowing the construction of 2-hydroxybiphenyls from aryl halides and phenols. The biaryl sub-unit is important in the formation of pharmaceutically relevant products, polymers, liquid crystals, and as ligands for homogeneous transition metal catalysts. The scope of this catalytic process has been investigated by extending the technique to tackle a more biologically and pharmaceutically relevant phenol: (L)-tvrosine. The catalysis has proven successful with range of aryl bromides including electron deficient, electron neutral, and sterically hindered species. Cleavage of the tert-butyl protecting group has given rise to successful diarylation. An elegant approach to the ortho-arylation of phenols would avoid the use of a protecting group in the 2- position. We have therefore investigated the use of carbamates as masked phenols. Our results have also shown an unprecedented level of selectivity for mono-arylated product. These results will also be presented In an aim to move away from industrially disfavoured solvents, such as chlorinated DCE, and strong acid solvents, which have poor tolerance of functional groups, solvent-free C-H activation was developed. The methodology was applied to good effect on a range of C-H functionalisation reactions- palladium- catalysed ortho-arylation of carbamates and anilides, copper-mediated meta-arylation of anilides and palladium-catalysed ortho-chlorination of anilides. During this research, it was discovered that bromination was not possible via C-H activation despite claims in the published solution-phase reaction. This final discovery prompted us to investigate mild methods for artha-halogenation, as a result pTSA- mediated artha-halogenation of anilides was developed using a palladium catalyst." During the investigation into potential reactive intermediates an unusual C-H activated pTSA complex was isolated and characterised. This species was also shown to undergo facile reduction to a Pd(I)/(II) tetramer.

The synthesis of calix[4]arene derivatives, 5,11,17,23-tetra-tert-butyl[25,27-bis(hydroxy)-26,28-bis(ethylthioethoxy)]-calix[4]arene, L3, and 5,11,17,23-tetra-tert-butyl[25,27-bis(ethylethanoate)oxy-26,28-bis(ethylthioethoxy)]-calix[4]arene, L4, are reported. These ligands are structurally (1H, 13C NMR and X-ray crystallography) and thermodynamically (solubility, calorimetry) characterised. In addition to L3 and L4, 5,11,17,23-tetra-tert-butyl[25,26,27,28-tetrakis(ethylethanoate)- calix[4]arene, L1 and 5,11,17,23-tetra-tert-butyl[25,26,27,28-tetrakis(methylketonemethoxy)-calix[4]arene, L2, are included in this study. Therefore, ligands L1, L2, L3 and L4 were investigated by 1H NMR technique to obtain information regarding their conformation in solution and the active sites of interaction with metal cations in different deuterated solvents at 298 K. Conductance measurements were performed to establish the composition of the metal-ion complexes with L1, L3 and L4 in acetonitrile, methanol, N,N-dimethylformamide and propylene carbonate at 298.15 K. Weak or non-existing interaction was observed in the latter solvent. However, complexes of 1:1 stoichiometry are formed in all cases. Potentiometric and calorimetric measurements were carried out to establish the thermodynamic parameters of complexation of these ligands in acetonitrile, methanol, and N,N-dimethylformamide at 298.15 K. L1 and L2 behaved in a parallel fashion in acetonitrile, with a peak selectivity for Ca2+ relative to other bivalent metal cations investigated. Complexation was absent in other media. On the other hand, L4 showed higher discrimination ability towards metal cations relative to L1 in acetonitrile, methanol and N,N-dunethylformamide. In moving to L3, the selectivity of the ligand was improved with respect to L1 and L4 to recognize only Ag+ and Hg2+. The ligand and the medium effects on the complexation process are quantitatively assessed. Solution and transfer thermodynamic parameters for the reactants and the product involved in the complexation of Ag+, Hg2+ with L3 and L4 in acetonitrile (as a reference solvent), methanol and N,N-dimethylformamide (as receiving solvents) are discussed. The complexation and solution data for the reactants and the product were used to calculate the standard enthalpies of coordination as a means of checking the reliability of the data. Extraction affinity of L3 for Ag+ was investigated in the water-dichloromethane saturated system. Crystals of several ligands and their metal-ion complexes were isolated and characterized by X-ray diffraction studies. Conclusions and suggestions for further work in this area are given.

Synthesis of novel broader rim calix[4]arene derivatives has been carried out, initially, using palladium coupling reactions. Further derivatisation and investigation into host-guest chemistry of these novel compounds has also been accomplished. Conditions have been optimised for the coupling of both aromatic and aliphatic acrylates. Stereospecific formation of the all trans coupled product of an exclusively beta Heck coupling has been observed throughout. All compounds (of the type II) have been obtained in good yield. Synthetic methodology for the generation of receptor libraries (be they static or dynamic) via the coupling of both tertiary and secondary aciylamide species using a palladium catalyst has been accomplished. Some of the secondary aciylamides possess the capacity (by virtue of pre-arrangement of amidic hydrogen bonding motifs) to form dimers via H-bonding in non-polar solution. The binding of a commercial pesticide (TMTD) by an acrylamidocalix[4]arene is reported and corroborated by NMR and ESI-MS data. The ability to couple formyl functionalised acrylates to the broader rim has allowed the preparation of a small library of deep cavity receptors in the form of tetra-transimines. These deep cavity calix[4]arene receptors could be obtained and are folly characterised. In the case of dynamic combinatorial libraries the principle of utilising a guest molecule to template or at least effect a specific outcome of imine forming reactions at four aldehydic sites on the broader rim of the calix[4]arene has also been illustrated. This provides support for the principles of formation of dynamic combinatorial libraries and further proposes calix[4]arene building blocks as being useful in their construction.

Les parfums sont constitués de molécules sujettes à l'autoxydation au contact de l’air. Cette dégradation oxydante peut entraîner une perte des propriétés olfactives, l’apparition d’odeurs désagréables et la formation de substances irritantes ou allergisantes. L’ajout d’antioxydants est donc nécessaire pour stabiliser les formules. Cependant, les antioxydants synthétiques tels que le BHA ou le BHT suscitent la méfiance des consommateurs et sont ou seront interdits par les futures directives européennes. Des solutions alternatives doivent donc être trouvées en cherchant parmi les antioxydants naturels les plus efficaces et les plus inoffensifs et en exploitant au mieux les synergies, souvent constatées mais rarement comprises, entre les antioxydants et les autres ingrédients de la formule. C'est dans ce contexte que ce travail de thèse a été réalisé avec un triple objectif : élucider les mécanismes de fonctionnement des antioxydants, seuls ou en association, comprendre les effets de matrices sur leur activité et, identifier et rationaliser les effets de synergie. La cible moléculaire était une fragrance aldéhydique (décanal) connue pour être très sensible à l’oxygène et difficile à stabiliser. Quant aux antioxydants, le choix s’est porté sur les phénols (synthétiques, naturels ou « parfumés ») qui inhibent les processus d’oxydation radicalaire en chaîne en transférant un H• aux radicaux oxygénés intermédiaires. / Perfumes are composed of molecules which are prone to autoxidation in the presence of oxygen. This oxidative degradation can lead to the loss of olfactory properties, the appearence of off-odours or colors and the formation of irritant or allergenic substances. The antioxidants addition is necessary to stabilize formulas. However, consumers distrust the synthetic antioxidants such as BHA or BHT which are or will be banned by future European directives. New alternatives must be found either by identifying the most efficient and the most harmless natural antioxidants, or by taking benefits from the synergies between antioxidants and other ingredients in the formula which are often observed but rarely understood. In this context, the three aims of this work were: to establish mechanisms of antioxidant action, alone or in mixture, to indentify the matrix effects on their efficiency and to rationalize synergies. The target molecule was a fragrant aldehyde (decanal) known to be very sensitive to oxygen and difficult to stabilize. Concerning antioxidants, the choice fell on phenols (synthetic, natural or "fragrant") which inhibit the free radical chain oxidation by transferring a H• to oxygen radical intermediates.

Les oméga-3 sont reconnus comme étant des acides gras essentiels pour la santé. Ils sont particulièrement sensibles à l’oxygène et sont donc sujets à une dégradation oxydante conduisant à la détérioration de leurs propriétés organoleptique et nutraceutique. Il est donc crucial de protéger les huiles oméga-3 contre l’oxydation par l’ajout d’antioxydants, mais sans danger pour les consommateurs. Afin de retarder l’oxydation, des antioxydants phénoliques synthétiques tels que le BHA et le BHT sont largement utilisés mais suscitent la méfiance des consommateurs. La tendance actuelle est donc de les remplacer par des composés naturels (seuls ou en mélange) conduisant à des effets synergiques, souvent observés mais rarement compris, permettant une meilleure inhibition de l’oxydation. En ajoutant à ceci des mécanismes complexes se produisant lors de la dégradation des acides gras polyinsaturés, ce travail de thèse a été réalisé avec un triple objectif : la détection et l’identification des traces de produits oxydés dans les huiles, la mise en évidence des conditions relatives à la structure chimique des phénols performants et la clarification des mécanismes de fonctionnement des mélanges d’antioxydants. La spectrométrie de masse couplée à une ionisation par électronébulisation (ESI-MS) apparaît être la technique la plus appropriée pour l’ionisation sélective et sensible d’hydroperoxydes intacts identifiés comme les produits d’oxydation primaires. De plus, l’huile de lin, étant l’huile végétale la plus riche en oméga-3, a été notre substrat d’étude. Plus de 70 phénols inhibant l’oxydation radicalaire en chaîne par transfert d’hydrogène aux radicaux péroxyles ont été testés. / Omega-3 has been known as essential fatty acids to health. They are particularly sensitive to oxygen leading to a deterioration of their organoleptic and nutraceutical properties. Protecting omega-3 oils against oxidation is then crucial and requires the addition of highly effective antioxidants but safe for consumers. In order to prevent oxidative degradation, synthetic phenolic antioxidants such as BHT and BHA are widely used but they provoke safety concern from the consumer side. Therefore, the current tendency is to replace them by natural compounds used alone or in mixture, which leads to synergistic effects, often observed but rarely understood. Adding this to the complex mechanism occurring in the degradation of polyunsaturated fatty acids, this thesis was composed by 3 objectives: the detection and identification of traces of oxidation products in oils, the highlight of the requirements of the chemical structures of efficient phenols and the clarification of the mechanisms of action between antioxidants. The electrospray mass spectrometry (ESI-MS) appears as the most suitable technique for the selective and sensitive ionization of intact hydroperoxides which are the primary oxidation products. In addition, the linseed oil, known as the richest vegetable oil in omega-3, was our substrate of study. Over than 70 phenols which inhibit the radical chain oxidation by hydrogen transfer to peroxyl radicals were tested.

This thesis describes the chemistry developed during a study of novel transition metal-catalysed reactions. Chapter 2 describes a novel procedure for the synthesis of 2,5-disubstituted furans via the isomerisation of 1,4-alkyne diols, avoiding the pitfalls of the traditional Paal-Knorr reaction. The initial ruthenium catalysed isomerisation is followed by an in situ cyclocondensation reaction using an acid co-catalyst in a one step route to furan derivatives. In addition the synthesis of the 1,4-dicarbonyl surrogates, 1,4-alkyne diols, is detailed. The methodology detailed in chapter 2 is then used in the synthesis of pyrrole derivatives in Chapter 3. Replacement of the acid co-catalyst with 2 equivalents of amine allow various pyrrole derivatives to be synthesised using the 1,4-alkynediols as starting materials. Various amines can also be used from anilines, benzylamines and aliphatic amines, allowing access to a wide range of products.