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A pilot scale plant at Technology Readiness Level (TRL) 6 comprising an electrochemical ex-cell continuous production of sodium peroxodicarbonate and a thermal depolymerization plug flow reactor for kraft lignin conversion is established. Due to the labile nature of the "green" oxidizer peroxodicarbonate, special attention must be paid to the production parameters in order to optimize its use. A simplified design model describing steady-state and transient operations is formulated and finally validated against experimental data from the electrolysis setup. Design trade-offs are visualized, and their impact on specific energy consumption is evaluated. The pilot plant was operated for a 20-month period for more than 1200 h on-stream. Optimized process conditions result in vanillin yields of 8 wt % and thus prove the successful scale-up.
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Iminophosphoranes are commonly used reagents in organic synthesis and are, therefore, of great interest. An efficient and sustainable iodide-mediated electrochemical synthesis of N-sulfonyl iminophosphoranes from readily available phosphines and sulfonamides is reported. This method features low amounts of supporting electrolytes, inexpensive electrode materials, a simple galvanostatic setup, and high conversion rates. The broad applicability could be demonstrated by synthesizing 20 examples in yields up to 90%, having diverse functional groups including chiral moieties and biologically relevant species. Furthermore, electrolysis was performed on a 20 g scale and could be run in repetitive mode by recycling the electrolyte, which illustrates the suitability for large-scale production. A reaction mechanism involving electrochemical mediation by the iodide-based supporting electrolyte is proposed, completely agreeing with all of the results.
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The direct anodic conversion of alkali carbonates in aqueous media provides access to peroxodicarbonate, which is a safe to use and green oxidizer. Although first reports date back around 150 years, its low concentrations and limited thermal stability have consigned this reagent to oblivion. Boron-doped diamond anodes, novel electrolyser concepts for heat dissipation, and the mixed cation trick allow record breaking peroxodicarbonate concentrations >900 mM. The electrochemical generation of peroxodicarbonate was already demonstrated on a pilot scale. The inherent safety is ensured by the limited stability of the peroxodicarbonate solution, which decomposes under ambient conditions to oxygen and facilitates subsequent downstream processing. This peroxide has, in particular at higher concentrations, an unusual reactivity and seems to be an ideal reagent when peroxo-equivalents in combination with alkaline base are required. The conversions with peroxodicarbonate include the Dakin reaction, epoxidation, oxidation of amines (aliphatic and aromatic) and sulfur compounds, deborolative hydroxylation reactions, and many more. Since the base equivalents also represent the makeup chemical for pulping plants, peroxodicarbonate is an ideal reagent for the selective degradation of lignin to vanillin. Moreover, peroxodicarbonate can be used as a halogen-free bleaching agent. The emerging electrogeneration and use of this green platform oxidizer are surveyed for the first time.
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The electrochemical reduction of nitroarenes allows direct access to manifold nitrogen containing heterocycles. This work reports the simple and direct electro-organic synthesis of 18 different examples of 2H,4H-4-hydroxy-1,4-benzoxazin-3-ones in up to 81% yield. The scalability of the method was demonstrated on a gram-scale.
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A new and practical method for the thermal degradation of technically relevant bio-based lignin is presented. By heating a solution of lignin in highly concentrated caustic potash, vanillic acid is almost exclusively obtained in yields up to 10.6â wt %. By altering the reaction parameters, the selectivity of the reaction can be shifted towards the demethylation product, protocatechuic acid, which is obtained in a yield of 6.9â wt %. Furthermore, the procedure was applicable to different types of Kraft and organosolv lignin. To create an economically feasible process, ion exchange resins were used for the work-up of the highly caustic reaction media without neutralizing the complete mixture. By the selective removal of the desired vanillic acid from the caustic potash, this alkaline media could directly be reused for at least 5 further lignin degradations without significant loss of yield.
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We present an analysis of a set of molecular, electrical, and electronic properties for a large number of the cations of quaternary ammonium salts usually employed as supporting electrolytes in cathodic reduction reactions. The goal of the present study is to define a measure for the quality of a supporting electrolyte in terms of the yield of the reaction considered. We performed a principal component analysis using the normalized values of the properties in order to lower the number of relevant reaction coordinates and find that the integral variance of 13 properties can well be represented by three principal components. The yield of the electrochemical hydrodimerization of acrylonitrile employing different quaternary ammonium salts as supporting electrolytes was determined in a series of experiments. We found only a very weak correlation between the yield and the values of the properties but a strong correlation between the yield and the values of the most important principal component. Very similar results are obtained for two further existing systematic experimental studies of the impact of the supporting electrolyte on the yield of cathodic reductions. For all three example reactions, a supervised regression using the two most important principal components as variables yields excellent values for the coefficients of determination. For comparison, we also applied our methodology to sets of purely structure-based features that are usually employed in cheminformatics and obtained results of almost similar quality. We therefore conjecture that our methodology in combination with a small number of experiments can be used to predict the yield of a given cathodic reduction on the basis of the properties of the supporting electrolyte.
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A novel synthesis of sitagliptin based on a redox-active ester derived from the chiral pool is reported. The key step is an electrochemical nickel-catalyzed sp2-sp3 cross-coupling reaction using inexpensive nickel foam in an undivided cell. It was successfully applied to 21 examples in up to 88% yield. These sitagliptin-analogue precursors could potentially interact with the DPP4 enzyme. A full synthesis based on our new reaction pathway provided sitagliptin in an overall yield of 33%.
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An intramolecular electrochemical dehydration reaction of dicarboxylic acids to their cyclic anhydrides is presented. This electrolysis allows dicarboxylic acids as naturally abundant, inexpensive, safe, and readily available starting materials to be transformed into carboxylic anhydrides under mild reaction conditions. No conventional dehydration reagent is required. The obtained cyclic anhydrides are highly valuable reagents in organic synthesis, and in this report, we use them in-situ for acylation reactions of amines to synthesize amides. This work is part of the recent progress in electrochemical dehydration, which - in contrast to electrochemical dehydrogenative reactions for example - is an underexplored field of research. The reaction mechanism was investigated by 18O isotope labeling, revealing the formation of sulfate by electrochemical oxidation and hydrolysis of the thiocyanate-supporting electrolyte. This transformation is not a classical Kolbe electrolysis, because it is non-decarboxylative, and all carbon atoms of the carboxylic acid starting material are contained in the carboxylic anhydride. In total, 20 examples are shown with NMR yields up to 71 %.
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A dynamic thermodynamic resolution method for converting (R/S)-BINOL (1,1'-binaphthyl-2,2'-diol) into (R)-BINOL in 100% theoretical yield is reported. This technique involves mixing (R/S)-BINOL with N-benzyl cinchonidinium bromide (1 equiv) and a [Cu2(tmeda)2(µ-OH)2]Br2 (2.5 mol %) redox catalyst in acetonitrile. In the background of this process is the observation that the energy for atropoisomerization decreases significantly when an electron is removed from BINOL. Therefore, it is possible to convert both enantiomers into the thermodynamically favorable [N-benzyl cinchonidinium bromide·(R)-BINOL] adduct.
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Electrochemically generated green platform oxidizers like peroxodicarbonate (PODIC) constitute a game-changing technology in terms of sustainable chemistry while serving as an alternative counterreaction in the electrochemical hydrogen evolution. Peroxodicarbonate avoids the storage and shipping of concentrated hydrogen peroxide solution. We herein disclose an efficient method for the N-oxidation of quinolines, pyridines, and complex tertiary amines. The use of phenoyloxy succinimide (POSI) is the decisive factor for obtaining N-oxides (28 examples) in isolated yields of up to 98%.
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A novel electrochemical approach to access alkyl alkenesulfonates via a multicomponent reaction was developed. The metal-free method features easy-to-use SO2 stock solution forming monoalkylsulfites from alcohols with an auxiliary base in-situ. These intermediates serve a dual role as starting materials and as supporting electrolyte enabling conductivity. Anodic oxidation of the substrate styrene, radical addition of these monoalkylsulfites and consecutive second oxidation and deprotonation preserve the double bond and form alkyl ß-styrenesulfonates in a highly regio- and stereoselective fashion. The feasibility of this electrosynthetic method is demonstrated in 44 examples with yields up to 81 %, employing various styrenes and related substrates as well as a diverse set of alcohols. A gram-scale experiment underlines the applicability of this process, which uses inexpensive and readily available electrode materials.
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Electrochemical transformations are a subject of increasing interest in early drug discovery due to its ability to assemble complex scaffolds under rather mild reaction conditions. In this context, we became interested in electrochemical decarboxylative cross-coupling (DCC) protocols of redox-active esters (RAEs) and halo(hetero)arenes. Starting with the one-step electrochemical synthesis of novel methylamino-substituted heterocycles we recognized the potential of this methodology to deliver a novel approach to ß- and γ- amino acids by starting from the corresponding RAEs. Our work finally resulted in the delivery of novel and highly valuable trifunctional building blocks based on ß- and γ-amino-acid scaffolds.
Assuntos
Aminoácidos , Ésteres , Eletroquímica , Estrutura Molecular , Aminoácidos/química , Ésteres/química , OxirreduçãoRESUMO
Important improvements have been achieved in developing the coupling of electrochemical CO2 reduction to formate with its subsequent microbial conversion to polyhydroxybutyrate (PHB) by Cupriavidus necator. The CO2 based formate electrosynthesis was optimised by electrolysis parameter adjustment and application of Sn based gas diffusion electrodes reaching almost 80 % Faradaic efficiency at 150â mA cm-2. Thereby, catholyte with the high formate concentration of 441±9â mmol L-1 was generated as feedstock without intermediate downstream processing for semi-automated formate feeding into a fed-batch reactor system. Moreover, microbial formate conversion to PHB was studied further, optimised, and successfully scaled from shake flasks to semi-automated bioreactors. Therein, a PHB per formate ratio of 16.5±4.0â mg g-1 and a PHB synthesis rate of 8.4±2.1â mg L-1 OD-1 h-1 were achieved. By this process combination, an almost doubled overall process yield of 22.3±5.5 % was achieved compared to previous reports. The findings allow a detailed evaluation of the overall CO2 to PHB conversion, providing the basis for potential technical exploitation.
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Although electro-organic synthesis is currently receiving renewed interest because of its potential to enable sustainability in chemical processes to value-added products, challenges in process development persist: For reductive transformations performed in protic media, an inherent issue is the limited choice of metallic cathode materials that can effectively suppress the parasitic hydrogen evolution reaction (HER) while maintaining a high activity toward the targeted electro-organic reaction. Current development trends are aimed at avoiding the previously used HER-suppressing elements (Cd, Hg, and Pb) because of their toxicity. Here, this work reports the rational design of highly porous foam-type binary and ternary electrocatalysts with reduced Pb content. Optimized cathodes are tested in electro-organic reductions using an oxime to nitrile transformation as a model reaction relevant for the synthesis of fine chemicals. Their electrocatalytic performance is compared with that of the model CuSn7Pb15 bronze alloy that has recently been endorsed as the best cathode replacement for bare Pb electrodes. All developed metal foam catalysts outperform both bare Pb and the CuSn7Pb15 benchmark in terms of chemical yield and energetic efficiency. Moreover, post-electrolysis analysis of the crude electrolyte mixture and the cathode's surfaces through inductively coupled plasma mass spectrometry (ICP-MS) and scanning electron microscopy (SEM), respectively, reveal the foam catalysts' elevated resistance to cathodic corrosion.
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A novel electrosynthetic approach to aryl dibenzothiophenium salts, including the direct intramolecular formation of a C-S bond in a metal-free, electrochemical key step under ambient conditions, is reported. The broad applicability of this method is demonstrated with 14 examples, including nitrogen-containing heterocycles in isolated yields up to 72%. The resulting sulfonium salts can be used as precursors for fluorine labeling to give [18F]fluoroarenes as found in PET tracer ligands.
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Electrochemically generated hypervalent iodine(III) species are powerful reagents for oxidative C-N coupling reactions, providing access to valuable N-heterocycles. A new electrocatalytic hypervalent iodine(III)-mediated in-cell synthesis of 1H-N-aryl-3,4-dihydroquinolin-2-ones by dehydrogenative C-N bond formation is presented. Catalytic amounts of the redox mediator, a low supporting electrolyte concentration and recycling of the solvent used make this method a sustainable alternative to electrochemical ex-cell or conventional approaches. Furthermore, inexpensive, readily available electrode materials and a simple galvanostatic set-up are applied. The broad functional group tolerance could be demonstrated by synthesizing 23 examples in yields up to 96 %, with one reaction being performed on a 10-fold higher scale. Based on the obtained results a sound reaction mechanism could be proposed.
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Direct functionalization of C(sp3)-H bonds allows rapid access to valuable products, starting from simple petrochemicals. However, the chemical transformation of non-activated methylene groups remains challenging for organic synthesis. Here, we report a general electrochemical method for the oxidation of C(sp3)-H and C(sp2)-H bonds, in which cyclic alkanes and (cyclic) olefins are converted into cycloaliphatic ketones as well as aliphatic (di)carboxylic acids. This resource-friendly method is based on nitrate salts in a dual role as anodic mediator and supporting electrolyte, which can be recovered and recycled. Reducing molecular oxygen as a cathodic counter reaction leads to efficient convergent use of both electrode reactions. By avoiding transition metals and chemical oxidizers, this protocol represents a sustainable oxo-functionalization method, leading to a valuable contribution for the sustainable conversion of petrochemical feedstocks into synthetically usable fine chemicals and commodities.
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With LABS, an open source Python-based lab software is established that enables users to orchestrate automated synthesis setups. The software consists of a user-friendly interface for data input and system monitoring. A flexible backend architecture enables the integration of multiple lab devices. The software allows users to easily modify experimental parameters or routines and switch between different lab devices. Compared to previously published projects, we aim to provide a more widely applicable and easily customizable automation software for any experimental setup. The usefulness of this tool was demonstrated in the oxidative coupling of 2,4-dimethyl-phenol to the corresponding 2,2'-biphenol. In this context, the suitable electrolysis parameters for flow electrolysis were optimized by way of design of experiments.
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Pyrazoles are a very important structural motif widely found in pharmaceuticals and agrochemicals. An electrochemically enabled approach for the sustainable synthesis of pyrazoles via oxidative aromatization of pyrazolines is presented. Inexpensive sodium chloride is employed in a dual role as a redox mediator and supporting electrolyte in a biphasic system (aqueous/organic). The method is applicable to a broad scope and can be conducted in the simplest electrolysis set-up using carbon-based electrodes. Hence, the method allows for simple work-up strategies such as extraction and crystallization, which enables application of this green synthetic route on a technically relevant scale. This is underlined by demonstration of a multi-gram scale electrolysis without loss in yield.
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We have studied the highly selective homogeneous iridium-catalyzed hydrogen isotope exchange (HIE) with deuterium or tritium gas as an isotope source in water and buffers. With an improved water-soluble Kerr-type catalyst, we have achieved the first insight into applying HIE reactions in aqueous media with varying pH. Density functional theory (DFT) calculations gave consistent insights in the calculated energies of transition states and coordination complexes, further explaining the observed reactivity and guidance on the scope and limitations for HIE reactions in water. Finally, we successfully adapted these findings to tritium chemistry.