A self optimizing synthetic organic reactor system using real-time in-line NMR spectroscopy

A configurable platform for synthetic chemistry incorporating an in-line benchtop NMR that is capable of monitoring and controlling organic reactions in real-time is presented. The platform is controlled via a modular LabView software control system for the hardware, NMR, data analysis and feedback optimization. Using this platform we report the real-time advanced structural characterization of reaction mixtures, including 19F, 13C, DEPT, 2D NMR spectroscopy (COSY, HSQC and 19F-COSY) for the first time. Finally, the potential of this technique is demonstrated through the optimization of a catalytic organic reaction in real-time, showing its applicability to self-optimizing systems using criteria such as stereoselectivity, multi-nuclear measurements or 2D correlations

3D-printed devices for continuous-flow organic chemistry

We present a study in which the versatility of 3D-printing is combined with the processing advantages of flow chemistry for the synthesis of organic compounds. Robust and inexpensive 3D-printed reactionware devices are easily connected using standard fittings resulting in complex, custom-made flow systems, including multiple reactors in a series with in-line, real-time analysis using an ATR-IR flow cell. As a proof of concept, we utilized two types of organic reactions, imine syntheses and imine reductions, to show how different reactor configurations and substrates give different products

Recent Developments in Process Digitalisation for Advanced Nanomaterial Syntheses

Digitalisation and industry 4.0 are set to profoundly change the way chemical and materials discovery and development work. The integration of multiple enabling technologies such as flow synthesis, automation, analytics, and real-time reaction control lead to highly efficient, productive, data-driven discovery and synthetic protocols. For instance, the development of flow chemistry enables the fine control and automation of process parameters such as flow rates, temperature, and pressure, which inherently enhances process efficiency. Flow chemistry presents a more sustainable means of manufacturing in terms of waste minimisation, as it enables the integration of synthetic processes with downstream processing. Furthermore, it allows the integration of analytical techniques to provide in situ process monitoring of large amounts of process and product data. The application of Artificial Intelligence (AI) and/or Machine Learning (ML) techniques allows rapid decision making that can optimise existing processes, and it has also been applied in the discovery of novel materials, synthetic pathways and chemicals. All this is contributing to an effective digitalisation of chemical and material synthetic processes from the laboratory to large-scale industrial deployment. This paper presents recent developments in the effective digitalisation of chemical synthetic processes which integrates continuous flow synthesis, analytics and artificial intelligence technologies. Specifically, this paper illustrates the emerging trend of process digitalisation through the advanced syntheses of materials with catalytic, optical and optoelectronic applications

Direct Air Capture and Integrated Conversion of Carbon Dioxide into Cyclic Carbonates with Basic Organic Salts

Direct air capture and integrated conversion is a very attractive strategy to reduce CO2 concentration in the atmosphere. However, the existing capturing processes are technologically challenging due to the costs of the processes and the low concentration of CO2. The efficient valorization of the CO2 captured could help overcome many techno-economic limitations. Here, we present a novel economical methodology for direct air capture and conversion that is able to efficiently convert CO2 from the air into cyclic carbonates. The new approach employs commercially available basic ionic liquids, works without the need for sophisticated and expensive co-catalysts or sorbents and under mild reaction conditions. The CO2 from atmospheric air was efficiently captured by IL solution (0.98 molCO2/molIL) and, subsequently, completely converted into cyclic carbonates using epoxides or halohydrins potentially derived from biomass as substrates. A mechanism of conversion was evaluated, which helped to identify relevant reaction intermediates based on halohydrins, and consequently, a 100% selectivity was obtained using the new methodology.Funding for open access charge: CRUE-Universitat Jaume IThis work has been partially supported by University Jaume I (UJI-B2019-40 and UJI-B2020-44) and RTI2018-098233-B-C22 y C21, PID2021-124695OB-C22 (FEDER//Ministerio de Ciencia e Innovación─Agencia Estatal de Investigación). M.Z. and V.S. thank the funding received from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Individual Fellowships (GA no. 101026335). V.S. thanks Generalitat Valenciana (CIDEGENT 2018/036) for funding. The authors are grateful to the SCIC of the Universitat Jaume I for technical support. The work has been partially supported by the project TED2021-130288B-I00 funded by MCIN/AEI/10.13039/501100011033 and by EU NextGenerationEU/PRTR

Chemistry in light-induced 3D printing

In the last few years, 3D printing has evolved from its original niche applications, such as rapid prototyping and hobbyists, towards many applications in industry, research and everyday life. This involved an evolution in terms of equipment, software and, most of all, in materials. Among the different available 3D printing technologies, the light activated ones need particular attention from a chemical point of view, since those are based on photocurable formulations and in situ rapid solidification via photopolymerization. In this article, the chemical aspects beyond the preparation of a formulation for light-induced 3D printing are analyzed and explained, aiming at giving more tools for the development of new photocurable materials that can be used for the fabrication of innovative 3D printable devices

Tuning the Reactivity of TEMPO during Electrocatalytic Alcohol Oxidations in Room-Temperature Ionic Liquids

2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) is a promising, sustainable, metal-free mediator for oxidation of alcohols. In this contribution, we describe how the selectivity of TEMPO for electrocatalytic alcohol oxidations in room-temperature ionic liquids (RTILs) can be changed by design of the solvent medium. Cyclic voltammetry of TEMPO in a series of ammonium-, phosphonium-, and imidazolium-based RTILs reveals that the potential at which TEMPO is oxidized increases from 677 mV (vs. the potential of the decamethylferrocene/ decamethylferrocinium, dmFc/dmFc+, redox couple) to 788 mV as the H-bond basicity of the RTIL anions decreases. The increase in potential is accompanied by an increase in the rate constant for oxidation of benzyl alcohol from about 0.1 dm3 mol−1 s−1 to about 0.7 dm3 mol−1 s−1, demonstrating the ability to manipulate the reactivity of TEMPO by judicious choice of the RTIL anions. The rate of alcohol oxidation in a series of RTILs increases in the order 2-butanol < 1phenylethanol < octanol < benzyl alcohol, and the RTIL 1-octyl-3-methylmidazolium bis(trifluoromethanesulfonyl)imide ([NTf2]–) shows clear selectivity towards the oxidation of primary alcohols. In addition, the reaction kinetics and selectivity are better in [NTf2]–-based RTILs than in acetonitrile, often the solvent-of-choice in indirect alcohol electrooxidations. Finally, we demonstrate that electrolytic TEMPO-mediated alcohol oxidations can be performed using RTILs in a flow-electrolysis system, with excellent yields and reaction selectivity, demonstrating the opportunities offered by such systems

State-of-the-art and limitations in the life cycle assessment of ionic liquids

Even though the development and use of ionic liquids (ILs) has rapidly grown in recent years, in the literature, information addressing the environmental performance of these substances in a life cycle context is comparatively scarce. This review critiques the state-of-the-art environmental life cycle assessment (LCA) studies on ILs in the literature, identifies the existing shortcomings, which could be delaying complete employment of the LCA framework to the field of ILs, and also identifies strategies for overcoming these shortcomings. This review indicates that there are several limitations associated with the implementation of the LCA in all steps and discusses them. Since data about manufacturing at industrial scale are generally inaccessible, a set of methods and assumptions have been used in previous studies to determine the life cycle inventories (LCIs), such as simplified LCA, “tree life-cycle approach”, use of energy monitor devices, thermodynamic methods, chemical simulation process and other secondary data. However, the analysis of the data quality has not always been performed. Also, currently, there is a shortage of the characterization factors of ILs for human toxicity and ecotoxicity impact categories, which prevent its inclusion within the life cycle impact assessment (LCIA) step. Therefore, sufficient and complete life cycle inventory data for ionic liquids and precursor chemicals are essential for inventory analysis; and the LCIA needs to be clearly defined about the level of detail on the IL emissions. Current LCA studies on ILs have not covered all these aspects. To improve the present situation, it is proposed herein that for future LCA of processes involving ILs each of the LCA steps must be completed as far as scientific advances allow

An autonomous organic reaction search engine for chemical reactivity

The exploration of chemical space for new reactivity, reactions and molecules is limited by the need for separate work-up-separation steps searching for molecules rather than reactivity. Herein we present a system that can autonomously evaluate chemical reactivity within a network of 64 possible reaction combinations and aims for new reactivity, rather than a predefined set of targets. The robotic system combines chemical handling, in-line spectroscopy and real-time feedback and analysis with an algorithm that is able to distinguish and select the most reactive pathways, generating a reaction selection index (RSI) without need for separate work-up or purification steps. This allows the automatic navigation of a chemical network, leading to previously unreported molecules while needing only to do a fraction of the total possible reactions without any prior knowledge of the chemistry. We show the RSI correlates with reactivity and is able to search chemical space using the most reactive pathways

Continuous parallel ESI-MS analysis of reactions carried out in a bespoke 3D printed device

Herein, we present an approach for the rapid, straightforward and economical preparation of a tailored reactor device using three-dimensional (3D) printing, which can be directly linked to a high-resolution electrospray ionisation mass spectrometer (ESI-MS) for real-time, in-line observations. To highlight the potential of the setup, supramolecular coordination chemistry was carried out in the device, with the product of the reactions being recorded continuously and in parallel by ESI-MS. Utilising in-house-programmed computer control, the reactant flow rates and order were carefully controlled and varied, with the changes in the pump inlets being mirrored by the recorded ESI-MS spectra

Multi-step oxidative carboxylation of olefins with carbon dioxide by combining electrochemical and 3D-printed flow reactors

The selective oxidation of alkenes to form epoxides followed by the cycloaddition of CO2 is a sustainable and cost-efficient method to generate functional cyclic carbonates. The use of a continuous-flow process allows seamless integration of both reactions sequentially under tailored and optimised conditions for each of the transformations to produce the cyclic carbonates. Here, we successfully demonstrate olefin electrooxidation, followed by the cycloaddition of CO2 to produce cyclic carbonates employing 3D printed (3DP) reactors in continuous flow and without the need for intermediate purification steps. This approach is highly convenient since the electrolyte (ammonium salt) from the electrochemical reaction acts also as a catalyst in the cycloaddition reaction. Different parameters in the electrochemical oxidation were evaluated (e.g. solvent, electrode, electrolyte, concentrations and current intensity). Complete conversion and high selectivity (>80%) towards the formation of epoxide were observed. The electrolyte served as a catalyst for the cycloaddition reaction. The digital design of the 3DP reactor played a crucial role in efficient performance of the cycloaddition reaction, showing increased productivity (a space-time yield of 4.38 gprod h−1 L−1) compared to that of a coil and a packed bed reactor. Consecutive CO2 cycloaddition reactions were also evaluated and a global yield of 83% of cyclic carbonates was observed for styrene. The system exhibited stability and stable activity for at least 20 h