Valorisation de molécules biosourcées en flux continu

Dans le contexte actuel d’une conscientisation forte du grand public quant à l’empreinte globale associée à la production des produits du quotidien, le développement de procédés industriels alternatifs aux procédés pétrosourcés devient une réalité de plus en plus marquée. La bioraffinerie vise à la transformation de matières premières naturelles et renouvelables (non fossiles) afin d’alimenter alternativement les filières chimiques traditionnellement exclusivement pétrosourcées. L’utilisation de ressources renouvelables pour alimenter les différentes filières chimiques est motivée à la fois par une volonté de réduire l’impact environnemental et de palier à la diminution des réserves de ressources fossiles. Dans ce travail, des matières premières biosourcées, comme le glycérol, l'érythritol, l'acide shikimique et l'acide quinique ont été transformés en produits à haute valeur ajoutée d’utilité particulière pour l'industrie chimique. Ces transformations ont été réalisées en flux continu dans des microréacteurs spécifiquement construits pour ces applications. Nous avons développé une application unique de la réaction de désoxydéshydratation (DODH) pour la préparation d’oléfines, produits typiquement pétrosourcés, à partir de composés biosourcés. L’application de la réaction de DODH en conditions microfluidiques a permis d’obtenir des très bons rendements en alcool allylique (84%) à partir du glycérol commercial. De même que le glycérol non purifié, issu de la synthèse du biodiesel que nous avons réalisée à partir de l'huile de Jatropha curcas a donné 86% d’alcool allylique. Un profil varié des produits (3-butène-1,2-diol, 1,3-butadiène, 2,5-dihydrofurane et crotonaldéhyde) dont les proportions sont liées aux conditions de réaction a été obtenu à partir de l'érythritol, avec des rendements modérés à quantitatifs. Le 3-butène-1,2-diol obtenu (56%), non purifié, a été transformé lors d'une synthèse subséquente, en vinyléthylène carbonate (71%), un produit à haute valeur ajoutée pour l’industrie des polymères. L'acide shikimique et l'acide quinique ont été transformés en acide benzoïque (60% et 6% respectivement). Les mécanismes et sélectivités sont également étudiés afin de pouvoir orienter les réactions. Ce travail fournit un outil efficace et original pour la transformation des molécules issues de la biomasse, facile à mettre en œuvre, avec les avantages d'opérer à des temps de réaction brefs, et avec une sécurité inhérente à haute température

Upgrading of glycerol towards allyl alcohol under continuous-flow conditions

Our group is active in the valorization of biomass-derived small platform molecules, among which glycerol occupies a special place. Glycerol is increasingly attracting attention for upgrading into high value bio-based chemicals due to its wide availability related to the current growth of the biodiesel industry. Glycerol can be upgraded in a variety of important chemicals such as bio-allyl alcohol through the deoxydehydration (DODH) reaction. The DODH of glycerol can be performed using either metal-catalyzed or formic acid-assisted strategies, but these methods often require prolonged exposure times to high temperatures, thus leading to variable purity profiles. This work presents the most recent advances from our group for the implementation of a DODH reaction of glycerol towards allyl alcohol under continuous-flow conditions. The combination of a unique reactive dynamic feed solution approach and short exposure (1-6 min) to high temperature (250 °C) through a microfluidic reactor gave high yield (up to 97%) and excellent selectivity in the presence of formic acid, triethyl orthoformate, or a combination of both

Revisiting the deoxydehydration of glycerol towards allyl alcohol under continuous-flow conditions

peer reviewedThe deoxydehydration (DODH) of glycerol towards allyl alcohol was revisited under continuous-flow conditions combining a microfluidic reactor setup and a unique reactive dynamic feed solution approach. Short reaction times, high yield and excellent selectivity were achieved at high temperature and moderate pressure in the presence of formic acid, triethyl orthoformate, or a combination of both. Triethyl orthoformate appeared as a superior reagent for the DODH of glycerol, with shorter reaction times, lower reaction temperatures and more robust conditions. In-line IR spectroscopy and computations provided different perspectives on the unique reactivity of glycerol O,O,O-orthoesters

Revisiting the deoxydehydration (DODH) of glycerol towards allyl alcohol under continuous-flow conditions

The deoxydehydration (DODH) of glycerol towards allyl alcohol was revisited under continuous-flow conditions combining a microfluidic reactor setup and a unique reactive dynamic feed solution approach. Short reaction times, high yield and excellent selectivity were achieved at high temperature and moderate pressure in the presence of formic acid, triethyl orthoformate, or a combination of both. Triethyl orthoformate appeared as a superior reagent for the DODH of glycerol, with shorter reaction times, lower reaction temperatures and more robust conditions. In-line IR spectroscopy and computations provided different perspectives on the unique reactivity of glycerol O,O,O-orthoesters

Ruthenium-Arene Complexes Bearing a Carbonate Ligand: Evaluation of their Catalytic Activity in the Synthesis of Enol Esters

Ruthenium-arene complexes are versatile and efficient catalyst precursors for various important organic transformations such as olefin metathesis, atom transfer radical reactions, transfer hydrogenation of ketones, and isomerization of allylic alcohols. Ruthenium-arene complexes also catalyse the addition of carboxylic acids to terminal alkynes affording vinyl esters in high yields and excellent selectivities. In particular, we found that the synthesis of vinyl esters was greatly accelerated when the reaction was performed in water-saturated toluene. Since 2006, ruthenium-arene complexes bearing a carbonate ligand, [Ru(η2-O2CO)(η6-arene)(PR3)], are known to be easily synthesized. However, their catalytic activity has never been reported. As part of our research program directed toward the synthesis of vinyl esters, we decided to investigate the catalytic activity of complexes [Ru(η2-O2CO)(η6-arene)(PPh3)] and [Ru(η2-O2CO)(η6-arene)(PCy3)] for the title reaction. Ruthenium-carbonate complexes are found to be excellent catalytic species in enol esters synthesis. Indeed, kinetics and selectivities of the reaction were very good wathever the used acid. Moreover, the reaction could successfully be carried out at 40 °C. Finally, the dilution of those complexes was investigated; while the time required for reaching completion increased significantly, a TON of 1500 could be achieved

Catalytic activity of ruthenium-arene complexes bearing a carbonate ligand on the synthesis of enol esters

Ruthenium-arene complexes are versatile and efficient catalyst precursors for various important organic transformations such as olefin metathesis, atom transfer radical reactions, transfer hydrogenation of ketones, and isomerization of allylic alcohols. Ruthenium-arene complexes also catalyse the addition of carboxylic acids to terminal alkynes affording vinyl sters in high yields and excellent selectivities. Particularly, we found that the synthesis of vinyl esters was greatly accelerated when the reaction was performed in water-saturated toluene. Since 2006, ruthenium-arene complexes bearing a carbonate ligand, [Ru(η2-O2CO)(η6-arene)(PR3)], are known to be easily synthesized. However, their catalytic activity has never been reported. As part of our research program directed toward the synthesis of vinyl esters, we decided to investigate the catalytic activity of complexes [Ru(η2-O2CO)(η6-arene)(PPh3)] and [Ru(η2-O2CO)(η6-arene)(PCy3)] for the title reaction. Ruthenium-carbonate complexes are found to be excellent catalytic species in enol esters synthesis. Indeed, kinetics and selectivities of the reaction were very good wathever the used acid. Moreover, the reaction could successfully be carried out at 40 °C. Finally, the dilution of those complexes was investigated; while the time required for reaching completion increased significantly, a TON of 1500 could be achieved

Ruthenium-arene complex bearing a pta ligand. Evaluation of its catalytic activity in the synthesis of enol esters

Ruthenium-arene complexes are widely used as efficient catalysts in various chemical reactions such as olefin metathesis, atom transfer radical reactions, isomerization of allylic alcohols and the addition of carboxylic acids to terminal alkynes. Ruthenium-arene complexes bearing a PTA ligand (PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane), are known as water soluble complexes and extensively studied for anticancer activity due to their high selectivity towards cancer cells. As part of our research program directed toward the synthesis of vinyl esters, we decided to investigate the catalytic activity of [RuCl2(η6-p-cymene)(PTA)]. To the best of our knowledge, the catalytic activity of this complex has never been reported for the synthesis of vinyl esters. Compared to [RuCl2(η6-arene)(PR3)] complexes, [RuCl2(η6-p-cymene)(PTA)] was much less efficient for the synthesis of vinyl esters through the addition of carboxylic acids to terminal alkynes. The selectivity for the Markovnikov isomer was quite good at 60°C, but decreased with the temperature. A maximum TON of around 1500 was obtained as for corresponding [RuCl2(η6-arene)(PR3)] catalytic systems

A versatile biobased continuous flow strategy for the production of 3-butene-1,2-diol and vinyl ethylene carbonate from erythritol

A versatile, tunable and robust continuous flow procedure for the deoxydehydration (DODH) of biobased erythritol toward 3-butene-1,2-diol is described. The procedure relies on specific assets of multistep continuous flow processing. Detailed mechanistic and computational studies on erythritol show that either 3-butene-1,2-diol or butadiene are obtained in high selectivity and yield on demand, as a function of the DODH reagent/substrate ratio and of the process parameters. Short reaction times (1-15 min) at high temperature (225-275 °C) and moderate pressure are reported. 3-Butene-1,2-diol is then further converted downstream into its corresponding carbonate, i.e. 4-vinyl-1,3-dioxolan-2-one (vinyl ethylene carbonate), an important industrial building block. The carbonation step uses a supported organocatalyst, and could be directly concatenated to the first DODH step. This unprecedented procedure also relies on a unique combination of on- and off-line analytical protocols for reaction monitoring and product quantification, and offers a biobased strategy toward important industrial building blocks otherwise petrosourced

Microwave-Assisted Olefin Metathesis as Pivotal Step in the Synthesis of Bioactive Compounds

Over the last two decades, olefin metathesis has emerged as a new avenue in the design of new routes for the synthesis of natural products and active pharmaceutical ingredients. In many cases, syntheses based on olefin metathesis strategies provide elegant routes in terms of increasing the overall yields, improving the synthesis scope, and decreasing the number of steps. On the other hand, over the last decade, microwave-assisted chemistry has experienced an incredible development, which rapidly opened new vistas in organic synthesis and in homogeneous catalysis. In this review article, we highlight applications of microwave-heated olefin metathesis reactions as pivotal steps in the total synthesis of biologically active compounds. By drawing selected examples from the recent literature, we aim to illustrate the great synthetic power and variety of metathesis reactions, as well as the beneficial effects of microwave irradiation over conventional heating sources. The majority of the selected applications of microwave-assisted olefin metathesis cover the synthesis of medium-ring cycles, macrocycles, and peptidomimetics by means of ring-closing metathesis (RCM) and cross-metathesis (CM) routes

Continuous Flow Organic Chemistry: Successes and Pitfalls at the Interface with Current Societal Challenges

This review intends to provide the reader with a clear and concise overview of how preparative continuous flow organic chemistry could potentially impact on current important societal challenges. These societal challenges include health/well-being and sustainable development. Continuous flow chemistry has enabled significant advances for the manufacturing of pharmaceuticals, as well as for biomass valorization toward a biosourced chemical industry. Examples related to pharmaceutical production are herein focused on (a) the implementation of flow chemistry to reduce the occurrence of drug shortages, (b) continuous flow manufacturing of orphan drugs, (c) continuous flow preparation of active pharmaceuticals listed on the WHO list of essential medicines and (d) perspectives for the manufacturing of peptide-based pharmaceuticals. Examples related to sustainable development are focused on the valorization of biosourced platform molecules. Besides positive impacts on societal challenges, this review also illustrates some of the potentially most threatening perspectives of continuous flow technology within the actual context of terrorism and drug abuse