Synthèse de carbo-benzènes, carbo-cyclohexadiènes et carbo-butadiènes à substituants chromophores

La thématique de recherche développée pour ce doctorat est centrée sur la synthèse et la caractérisation de molécules hautement insaturées et enrichies en carbone de type carbo-mères, portant des substituants chromophores, notamment de type polycyclique et hétérocyclique azoté. La première partie concerne la synthèse de carbo-benzènes quadripolaires portant des fluorophores hydrocarbonés de type fluorène, soit directement connectés au noyau carbo-benzénique, soit séparés de ce dernier par l'intermédiaire d'un lien acétylénique. La deuxième partie porte sur la synthèse de carbo-benzènes para-disubstitués par des fluorophores hétérocycliques azotés (indoles et carbazoles) et de deux types d'analogues : des carbo-cyclohexadiènes, macrocycliques mais non-macro-aromatiques, et des carbo-butadiènes, références acycliques présentant un enchaînement conjugué commun aux deux autres séries. Des représentants de ces trois sous-familles de molécules carbo-mères ont été préparés, et une étude comparative de leurs caractéristiques physico-chimiques a été réalisée. Enfin, le dernier chapitre porte sur la synthèse et la fonctionnalisation d'isoindoles dans le but de les accrocher à un cœur carbo-benzénique. Ce travail a permis de mettre en évidence le caractère électrophile particulier du 3-chloro-2-phénylisoindole-1-carbaldéhyde conduisant notamment à un réarrangement original du noyau isoindole en dérivé amino-isochromanone. Les résultats présentés dans cette thèse ouvrent des perspectives inédites en chimie des hétérocycles azotés et en chimie des carbo-mères, et plus généralement des polyacétyléniques aromatiques (notion de " p-frustration "). De plus, l'étude préliminaire de propriétés photophysiques de deux des carbo-benzènes décrits dans ce manuscrit laisse entrevoir des possibilités d'applications en optique non-linéaire du troisième ordre, et notamment en absorption à deux photonsThe project developed for this PhD thesis is focused on the synthesis and characterization of highly unsaturated and carbon-enriched molecules called carbo-mers, substituted by polycyclic and heterocyclic chromophoric groups. The first part of the work concerns the synthesis of quadrupolar carbo-benzenes bearing purely hydrocarbon fluorene substituents, which are either directly connected to the carbo-benzene ring or separated from it by acetylenic linkers. The second part deals with the synthesis of carbo-benzenes substituted by nitrogen-containing heterocycles (indoles or carbazoles) and of two series of analogs: macrocyclic but non macro-aromatic carbo-cyclohexadienes, and carbo-butadienes, which can be viewed as the acyclic references of the two other series. Selected representatives of these three sub-families of carbo-mers were prepared, and a comparative study of their physico-chemical properties was conducted. The last chapter addresses the synthesis and functionalization of isoindoles in view of anchoring them to a carbo-benzene ring. This work has highlighted the peculiar electrophilic character of 3-chloro-2-phenylisoindole-1-carbaldehyde, leading to an original rearrangement of the isoindole core into an amino-isochromanone. The results presented in this thesis open unprecedented perspectives in both the chemistry of nitrogen-containing heterocycles and carbo-mers, and more generally of aromatic polyacetylenics (notion of "p-frustration"). Finally, the study of photophysical properties of two carbo-benzenes described in this manuscript suggests potential applications in third order nonlinear optics, and in particular in two-photon absorptio

Towards fluorescent indolyl-carbo-benzenes

The C18 macro-aromatic carbo-benzene core is a strong chromophoric unit resembling the porphine ring which is prone to quench the emission of fluorophoric substituents. Within the aim of preparing fluorescent carbo-benzenes (and carbo-cyclohexadiene parents) for measurement of their two-photon absorption cross-section by the TPEF method, several indole derivatives were devised and anchored to the C18 macrocycle either directly, p-phenylogously or ethynylogously. Synthesis methodology and spectroscopical measurements are presented in a comparative prospec

A difluorenyl-carbo-cyclohexadiene: prospective chromophore for two-photon absorption

For the purpose of outlining structure-property relationships for two-photon absorption (2PA), a "s-locked" carbo-cyclohexadiene with two fluorenyl substituents has been envisaged for comparison with previously studied aromatic carbo-benzene and non-aromatic carbo-quinoid congeners. A representative where the C10-π-conjugated fluorenyl moieties are also connected by a C8-π-insulating 3,6‐dimethoxy‐3,6‐bis(trifluoromethyl)octa‐1,4,7‐triyn-1,8-diyl edge has thus been synthesized in four steps from known C8F triyne and C10 triynyldial, through a [8F+10] cyclization process. In spite of a relatively strong absorbance (e = 84 800 L.mol-1.cm-1 at 634 nm), the non-vanishing green fluorescence (at 533 nm) of the chromophore should allow measurements of the 2PA cross section by both the TPEF and Z-scan methods

Синтез 1-(триетилсиліл)-3-[4-(гетарил)феніл]- 5-(триметилсиліл)пента-1,4-діїн-3-олів

The method of synthesis of 1-(triethylsilyl)-3-[4-(hetaryl)phenyl]-5-(trimethylsilyl)penta-1,4-diyn-3-ols based on the interaction between 1-(triethylsilyl)-5-(trimethylsilyl)penta-1,4-diyn-3-one and lithium derivatives of 1-(4-bromophenyl)-1H-indole or 9-(4-bromophenyl)-9H-carbazole has been developed.Разработан метод синтеза 1-(триэтилсилил)-3-[4-(гетарил)фенил]-5-(триметилсилил)пента-1,4-диин-3-олов, основанный на взаимодействии литиевых производных 1-(4-бромфенил)-1Н-индола и 9-(4-бромфенил)-9Н-карбазола с 1-(триэтилсилил)-5-(триметилсилил)пента-1,4-диин-3-оном.Розроблено метод синтезу 1-(триетилсиліл)-3-[4-(гетарил)феніл]-5-(триметилсиліл)пента-1,4-діїн-3-олів, що базується на взаємодії літієвих похідних 1-(4-бромофеніл)-1Н-індолу та 9-(4-бромофеніл)-9Н-карбазолу з 1-(триетилсиліл)-5-(триметилсиліл)пента-1,4-діїн-3-оном

Combining incompatible processes for deracemization of Praziquantel derivative under flow conditions

An efficient deracemization method for conversion of the racemate to the desirable (R)-enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. By a library approach, a derivative that crystallizes as a conglomerate has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 °C, whereas deracemization is achieved by alternating crystal growth/dissolution steps with temperature cycling between 5–15 °C. These incompatible processes are combined by means of a flow system resulting in complete deracemization of the solid phase to the desired (R)-enantiomer (98 % ee). Such an unprecedented deracemization by a decoupled crystallization/racemization approach can readily be turned into a practical process and opens new opportunities for the development of essential enantiomerically pure building blocks that require harsh methods for racemization

1-Ethyl-2-phenyl-3-[2-(trimethylsilyl)ethynyl]-1H-indole

The title compound, C21H23NSi, was synthesized by Sonogashira-type reaction of 1-ethyl-3-iodo-2-phenyl-1H-indole with trimethylsilylacetylene. The indole ring system is nearly planar [maximum atomic deviation = 0.0244 (15) Å] and is oriented at a dihedral angle of 51.48 (4)° with respect to the phenyl ring. The supramolecular aggregation is completed by weak C—H...π interactions of the methylene and phenyl groups with the benzene and pyrrole rings of the indole ring system. The methyl groups of the trimethylsilyl unit are equally disordered over two sets of sites

Performance Analysis and Model-Free Design of Deracemization via Temperature Cycles

Solid-state deracemization via temperature cycles is a technique that has been shown to be effective to isolate the pure enantiomer of a conglomerate-forming compound. This process has a large number of operating parameters that can be adjusted according to system-specific properties. On the one hand, this feature makes the process flexible and prone to optimization. On the other hand, the design space is so large that experimental optimization of the process can become long and cumbersome. In this work, we achieve two results. First, we show that deracemization via temperature cycles works very effectively for two new experimental systems, namely, the chiral compounds 2-(benzylideneamino)-2-(2-chlorophenyl)acetamide (CPG) and 3,3-dimethyl-2-((naphthalen-2-ylmethylene)amino)butanenitrile (tLEU). Second, we propose a new approach for the design of an effective deracemization process via temperature cycles for a new compound. Therefore, in this work, we investigate the effect of different operating conditions, namely, the initial enantiomeric excess, the cooling rate, the temperature range, and the catalyst concentration, on the performance of deracemization via temperature cycles for the new compounds CPG and tLEU and for N-(2-methylbenzylidene)phenylglycine amide (NMPA), which was already studied in a previous paper. On the basis of these outcomes, we conclude by proposing a model-free screening strategy for the design of an effective deracemization process via temperature cycles for a new compound.ISSN:1083-6160ISSN:1520-586