This thesis describes the development of a more economical catalytic system for the N-alkylation of amines by “borrowing hydrogen” and its application in the synthesis of a variety of amines including the dopamine agonist Piribedil and the antihistamine agents Antergan and Tripelennamine. <b>Chapter 2</b> describes the development of the ruthenium-catalysed N-alkylation of primary amines with primary alcohols by “borrowing hydrogen”. <b>Chapter 3</b> describes the application of the ruthenium-catalysed N-alkylation of secondary amines with primary alcohols by “borrowing hydrogen”. The ruthenium-catalysed synthesis of dimethylamines by “borrowing hydrogen” is also described and a mechanistic proposal for the N-alkylation of alcohols with amines has been proposed. <b>Chapter 4</b> describes the role of amines in pharmaceuticals and the ruthenium-catalysed synthesis of Piribedil, Antergan and Tripelennamine by “borrowing hydrogen”.

Transition metals are known to be the essential part in most of the catalysts, the heterogeneous and the homogenous catalysts; however, the ligands that attached to the metal centers can also alter the reactivity of the catalyst, and that is widely observed in nature. In our project, we are interested in the metal-ligand cooperation of a special type of ligand called the pincer ligand. Our focus is mainly on the tridentate Pincer Ligands with a pyridine backbone. Also, it contains a spacer that could be deprotonated and protonated during the aromatization and dearomatization process. Aromatization and dearomatization of the pincer ligand are responsible for the unique reactivity of the pincer complexes, especially in the hydrogenation and dehydrogenation reactions. Recently, huge developments have been made in the dehydrogenative coupling of aniline and benzyl alcohol via manganese pincer complexes. The most recent papers on that subject have been done by Beller in 2016[1], Kempe 2018 [2], and Hultzsch 2019 [3]. However, rhenium complexes have not been studied enough even though it is in the same seventh row of the transition metal. Therefore, the rhenium was studied as a possible alternative. Then, the synthesis of a well-defined PN3 rhenium complex was performed from the bipy-tBu ligand and the metal precursor Re(CO)5Cl. The ligand has a unique deformity as the phosphine sidearm is not attached to the metal center. Further investigation of the aniline and benzyl alcohol dehydrogenative coupling via PN3 rhenium pincer complex has been done. An optimal reaction condition was achieved, and the substrate scope was further examined with various alcohols and amines, and the result shows good to moderate conversion with decent selectivity towards the imine. Except for the secondary alcohols.

When speciality chemicals are manufactured within the pharmaceutical industry, they are often produced in stirred batch/semi-batch reactors. A ‘methodology’ was explored, to help with the development of continuous fixed-bed catalytic reactors for this sector. This was tested on two different types of model reactions: (a) In the first, the viability of producing tertiary amines via ‘borrowing hydrogen’ was explored, and the reaction of morpholine and benzyl alcohol was studied, on Ru and Pt catalysts. This provided an opportunity for an early involvement in small-scale batch testing of catalysts, and then experiments were performed with the catalyst supported on granules in a packed bed (i.d. = 7 mm, length = 300 mm). Although it was shown that continuous processing is viable, and that high conversions (e.g. 73 to 98%, at 150 ºC) could be achieved, unfortunately further work was necessary to identify a more robust catalyst system, before moving on to pilot-scale trials. (b) In the second, the partial oxidation of benzyl alcohol to benzaldehyde was studied, using a Pt catalyst on a carbon support. This proved to be successful, and the reaction was finally demonstrated at pilot-scale. Carbon monoliths were used as catalyst supports (monolith o.d. = 19 mm; length = 50 mm long; square 0.7 mm x 0.7 mm channels; catalyst loading 2.5 and 2.7 wt% Pt). With a liquid flow of 1 L h-1 and a reactant concentration of ~1 mol L-1, operating at 110 ºC, conversion ranged from 80 to 90% and selectivity from 65 to 99%. The catalyst system was tested for 160 h of operation, and retained its performance. While testing the 2nd reaction, a pilot-scale reactor was also developed, which could be used for a variety of novel reactions. The design was flexible and it was easy to insert and remove the catalytic monoliths.

Nos travaux ont porté sur la mise au point de nouvelles stratégies de synthèse de la nicotianamine (molécule naturelle ubiquitaire chez les plantes et impliquée dans le transport du fer in planta) qui ont été appliquées à la préparation de nouveaux analogues naturels et non-naturels inédits. Les propriétés chélatrices d'un de ces analogues naturels, la thermonicotianamine, ont été mises en évidence par spectrométrie de masse.Ce manuscrit est organisé en quatre chapitres : la première partie présente un point bibliographique sur le rôle central de la nicotianamine dans l'homéostasie du fer chez la plante. Puis, nous avons décrits, après un aperçu de l'état de l'art sur les synthèses de la nicotianamine et de ses analogues naturels et non-naturels, notre nouvelle stratégie de synthèse de la basée sur la réaction de N-alkylation. Afin de répondre à un besoin de nouvelles molécules et de réduire leur temps de fabrication nous avons développé la première synthèse de la NA et de ses analogues sur support. Enfin, après une vue de l'état de l'art sur les méthodes d'analyse des phytosidérophores et de leurs complexes avec les métaux, les propriétés chélatrices de la tNA avec les métaux ont été étudiées par spectrométrie de masse. / Our work focused on developing new strategies for synthesis of nicotianamine (a natural molecule ubiquitous in plants and involved in iron transport in planta) which have been applied to the preparation of new natural and unnatural analogues. The chelating properties of a natural analogue, the thermonicotianamine, were investigated by mass spectrometry.This manuscript is organized into four chapters: the first part presents a literature review on the central role of nicotianamine in iron homeostasis in plants.After an overview of the state of the art in the synthesis of nicotianamine and its natural and non-natural analogues, we described our new synthetic strategy based on the N-alkylation reaction.To meet the need for new molecules and reduce manufacturing time we developed the first synthesis of nicotianamine and its analogues on solid phase.Finally, after a view of the state of the art on methods for analyzing phytosiderophores and their complexes with metal, chelating properties of thermonicotianamine with metals have been studied by mass spectrometry.

No description available.

Amines are ubiquitous in nature and serve a variety of functions in living organisms. Because of this fact amines are of great biological and pharmaceutical interest. The iridium catalyst (pentamethylcyclopentadienyl) iridium dichloride dimer ([Cp*IrCl2]2) has been used in a number of ways to synthesize new carbon-nitrogen bonds. These studies were directed toward the development of a method for the iridium catalyzed N-alkylation of alpha-amino acid esters as well as the development of a strategy for synthesis of the natural product 275A. We have optimized a method for the N-alkylation for alpha-amino acid esters. Using this method, we have N-alkylated a series of alpha-amino acid esters with a variety of alcohols. We have shown that the N-alkylation of the alpha-amino acid esters works consistently and gives the desired products in moderate to high yields. We have examined the effect of this method on the chiral center of the obtained products by analyzing their optical rotation. Evaluation of these specific rotations indicated racemization was occurring but it is believed that any loss of the chiral center is due to the reaction conditions. Amphibian alkaloids are of great interest to the pharmaceutical and academic communities due to their biological activities. Unfortunately, they are not naturally available in large quantities which makes total synthesis the most common method of generating these compounds for evaluation. One amphibian alkaloid class of interest to us are the Lehmizidines. These are bicyclic ring structures consisting of a 7-member and 5-member ring with a nitrogen bridgehead. The alkaloid, 275A, was selected as a target for a general synthetic approach. This synthetic approach required the synthesis of novel diols. The construction of these diols along with a method for the synthesis of the azepane ring is presented here.

The focus of these studies was directed towards the synthesis of novel N-heterocyclic compounds and pharmacological evaluation of these compounds for activity at monoamine transporters. A series of novel piperidine and pyrrolidine analogues were prepared from commercially available starting material with a three and four step synthetic method, respectively. A variety of substituents on the aromatic ring were incorporated to achieve a diverse library of compounds. The preliminary binding studies of piperidine molecules showed strong affinity towards serotonin transporters and moderate affinity towards dopamine transporters. The focus of further studies was directed towards utilization of iridium catalysis for the development of new synthetic methods for biologically important molecules. This research has led to the development of a new synthetic strategy for the construction of nicotine and its analogues. In addition, the iridium catalysis was also used for alkylation of amides with primary and secondary alcohols under microwave conditions.

The solvent-free (Cp*IrCl2)2 catalyzed N-alkylation of urea with benzyl alcohol has been studied. A variety of reaction conditions were studied and optimized to produce a high yield (82%) of N,N-dibenzylurea. A series of substituted benzyl alcohols were examined at the optimal reaction conditions. However, the preparation of substituted benzyl urea derivatives using conditions optimized for benzyl alcohol gave poor yields or intractable mixtures.

The pyrrolidine and piperidine ring systems are present in a variety of different classes of amphibian alkaloids. We have found the iridium catalyzed N-heterocylization reaction of diols with amines to be very useful for the construction of novel pyrrolidine, piperidine and piperazine derivatives. The scope and utility of the iridium catalyzed N-heterocyclization reaction for the construction of novel anuran scaffolds using amino diols and triols are presented. Studies directed towards the total synthesis of 4,6-disubstituted quinolizidine and (±)-epiquinamide are discussed. The second study is focused on the selective conversion of terminal dienes to primary diols. This conversion has always had problems with regioselectivity and low yields due to polymer formation with carbon chains having more than 7 carbon atoms. An improvement in the yield and regioselectivity was observed with disiamylborane prepared in situ using 2-methyl-2-butene and BH3•DMS. The scope of this method with 7, 8 and 9 carbon chains and different alcohol protecting groups for synthesis of triols is presented.

This diploma thesis describes organic pigments of diketopyrrolopyrroles (DDPs) possessing properties applicable in attractive and perspective areas of organic electronics and photonics. The modification of the DPP skeleton was performed by nucleophilic substitution by various alkyl chains and 5 series of DPP derivatives were prepared. The regioselectivity of N-alkylation and also the photophysical properties of the prepared derivatives were studied. A key product of this work is the N,N'-ethyladamantyl derivative of DPP, which exhibited ambipolar characteristic with excellent electron mobility of 0.2 cm2 V–1 s–1. Further, the -conjugation of the above-mentioned DPP derivative was extended by 1 and 2 thiophene units at positions 3,6 and the effect of this modification on optical properties of the resulting derivatives was investigated. A new modified N,N'-unsubstituted DPP derivative was also prepared. The last point of this thesis was the study of the incorporation of formyl functional groups into the skeleton of key N,N'-ethyladamantyl DPP derivative.