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Building automated platforms in chemical processes is a shared goal by many researchers. Herein, we provide essential insights into the decision-making process for choosing automation platforms, highlighting the suitability of fixed automation for standardized tasks and the strategic use of flexible automation in dynamic research settings. By addressing key factors, we aim to assist researchers in making informed decisions tailored to their specific automation needs.

Solid–liquid slurries are vital and increasingly prevalent in the pharmaceutical and chemical industries. Despite the importance of these heterogeneous systems, process control and optimization are fundamentally hindered by a lack of compatible real-time analytical techniques. We present herein an online HPLC monitoring platform enabling access to real-time compositional information on slurries. We demonstrate the system by investigating the heterogeneous synthesis reaction of tetrabenazine. Furthermore, we integrated our online HPLC platform with the orthogonal monitoring techniques of a pH probe and a microscopic imaging probe to provide additional mechanistic insight. These combined insights enable the optimization of tetrabenazine synthesis in terms of reaction time, byproduct formation, and diastereomeric purity of the final product.

Teaching laboratories are designed to educate students on basic theories and techniques through guided laboratory experiments. As advances in automation revolutionize research chemistry laboratories, teaching tools can advance to reflect these changes. In this study, we integrated several programmable instruments, including automated pumps for liquid transfer, into an augmented titration setup that can be operated remotely. Our setup empowers students to learn the conceptual, technical, and practical aspects of titration by leveraging laboratory automation tools. Our system uses Siri as a speech recognition tool and the Python programming language to develop action routines for titration uses. The application of Siri provides a smooth user-to-instrument experience, and the use of Python allows coders to effectively develop and maintain the workflow. Three chemistry professors were invited to participate in usability tests of the system using a mobile device. Their positive feedback highlights the promise of our system as a valuable addition to undergraduate chemistry teaching laboratories. This titration setup addresses accessibility challenges and distance learning requirements for chemical education. Further, our tool introduces students to the type of automated experimentation that is emerging as the modern standard in chemistry research laboratories.

Data science has revolutionized chemical research and continues to break down barriers with new interdisciplinary studies. The introduction of computational models and machine learning (ML) algorithms in combination with automation and traditional experimental techniques has enabled scientific advancement across nearly every discipline of chemistry, from materials discovery, to process optimization, to synthesis planning. However, predictive tools powered by data science are only as good as their data sets and, currently, many of the data sets used to train models suffer from several limitations, including being sparse, limited in scope and requiring human curation. Likewise, computational data faces limitations in terms of accurate modeling of nonideal systems and can suffer from low translation fidelity from simulation to real conditions. The lack of diverse data and the need to be able to test it experimentally reduces both the accuracy and scope of the predictive models derived from data science. This Account contextualizes the need for more complex and diverse experimental data and highlights how the seamless integration of robotics, machine learning, and data-rich monitoring techniques can be used to access it with minimal human labor.

The transformation of CO2to value added commodity chemicals presents an impactful strategy to obtain products that are less dependent on fossil fuels. In this study, indium tribromide (InBr3) mixed with tetrabutylammonium bromide (NBu4Br) co-catalyst has been identified as a simple, highly efficient catalyst for the synthesis of cyclic carbonates from epoxides and CO2at sub-atmospheric pressures, room temperature, and under solvent-free conditions. The InBr3/NBu4Br catalytic system is tolerant toward different functional groups with high conversions and >99% selectivity for cyclic carbonate without resorting to high pressures and temperatures. Moreover, a combination of in situIR, NMR spectroscopy, and substrate labelling experiments enabled the proof of key catalytic steps and detection of reaction intermediates to elucidate the reaction mechanism. This technology represents a potential scalable system for the utilization of waste CO2.

Automated experiments can accelerate research and development. ‘Flexible automation’ enables the cost- and time-effective design, construction and reconfiguration of automated experiments. Flexible automation is empowering researchers to deploy new science and technology faster than ever before.

Herein, we report a new one-pot sequential method for SO2F2-mediated nucleophilic acyl substitution reactions starting from carboxylic acids. A mechanistic study revealed that SO2F2-mediated acid activation proceeds via the anhydride, which is then converted to the corresponding acyl fluoride. Tetrabutylammonium chloride or bromide accelerate the formation of acyl fluoride. Optimized halide-accelerated conditions were used to synthesize acyl fluorides in 30–80% yields, and esters, amides, and thioesters in 72–96% yields without reoptimization for each nucleophile.

Advances in 3D printing technology over the past decade have led to its expansion into all subfields of science, including chemistry. This technology provides useful teaching tools that facilitate communication of difficult chemical concepts to students and researchers. Presented here is the use of 3D printing technology to create tangible models of reaction progress surfaces. Easy-to-follow step-by-step instructions are provided for the creation of these surfaces from IR, NMR, and HPLC data. More generally, this procedure enables conversion of any arrayed data set into a 3D-printable STL file. The general utility of these 3D-printed models is highlighted with three unique case studies.

Sulfuryl fluoride, SO2F2, has been known and used as a fumigant for over 50 years but it has only recently gained widespread interest as a reagent for organic synthesis. Herein we report a novel application of sulfuryl fluoride gas in a new 1,1-dihydrofluoroalkylation reaction, which simply involves bubbling SO2F2through a solution of amine, 1,1-dihydrofluoroalcohol, and diisopropylethylamine. The reaction is successful for a wide range of primary and secondary amines, as well as several 1,1-dihydrofluoroalcohols, to afford the 1,1-dihydrofluoroalkylated amines in 42% to 80% isolated yields. The reaction also displays excellent functional group tolerance. The ease of the one-pot activation and alkylation, combined with the wide substrate scope make this new procedure an attractive alternative to existing 1,1-dihydrofluoroalkylation methodologies.

Detailed kinetic analysis for the Cu(I)-catalyzed Kinugasa reaction forming β-lactams has revealed an anomalous overall zero-order reaction profile, due to opposing positive and negative orders in nitrone and alkyne, respectively. Furthermore, the reaction displays a second-order dependence on the catalyst, confirming the critical involvement of a postulated bis-Cu complex. Finally, reaction progress analysis of multiple byproducts has allowed a new mechanism, involving a common ketene intermediate to be delineated. Our results demonstrate that β-lactam synthesis through the Kinugasa reaction proceeds via a cascade involving (3 + 2) cycloaddition, (3 + 2) cycloreversion, and finally (2 + 2) cycloaddition. Our new mechanistic understanding has resulted in optimized reaction conditions to dramatically improve the yield of the target β-lactams and provides the first consistent mechanistic model to account for the formation of all common byproducts of the Kinugasa reaction.

Monitoring the reaction progress of biphasic reaction mixtures has long presented a significant challenge to modern analytical techniques. While a multitude of widely utilized chemical transformations have been performed under such conditions, in-line separation and analysis of each phase have not been possible, inhibiting detailed kinetic and mechanistic studies of these important processes. Herein, we disclose a novel sampling technology capable of accurately monitoring reaction progress in biphasic mixtures using online high-performance liquid chromatography (HPLC) and multinuclear flow nuclear magnetic resonance (NMR) spectroscopy. A biphasic sampling platform was developed to circulate a single phase of a biphasic reaction mixture for analysis using these techniques. The utility of this methodology was demonstrated through analysis of boronic acid distribution and speciation under basic conditions as well as for monitoring the reaction progress of a biphasic Suzuki-Miyaura cross-coupling.

Online HPLC reaction progress monitoring provides detailed data-rich profiles; however, extracting kinetic information requires ultraviolet–visible response factors to determine concentrations from peak areas. If the reaction’s overall mass balance is known and some analytical trend for all relevant species can be recorded, it is possible to estimate the absolute response factors of all species using a system of linear equations. We delineate a method using the Microsoft Solver plug-in to convert time course profiles to reagent concentrations without analytical standards.

An accessible machine-learning tool has been developed that can accelerate the optimization of a wide range of synthetic reactions — and reveals how cognitive bias might have undermined optimization by humans.

A new class of supported oxazolidinone chiral auxiliary has beensynthesized from l-phenylalanine. The useof a perfluorooctyl chain as a support facilitates enolate reactionsunder standard solution conditions, with reaction products rapidlyisolated by solid-phase extraction on fluorous silica. Reactionsemploying a syn-oxazolidinone affordedyields and stereoselectivities in titanium-mediated aldol reactionsthat were comparable to those reported in the literature using thestandard Evans-type auxiliaries under similar conditions. Theseresults are the first demonstration of asymmetric enolate chemistryusing fluorous compounds.

The mechanisms for the three- and four-component variants of the Castagnoli–Cushman reaction (CCR) have been investigated. A series of crossover experiments were conducted to probe the structure and reactivity of known amide-acid intermediates for the three- and four-component variants of the CCR (3CR and 4CR, respectively). Control experiments paired with in situreaction monitoring with infrared spectroscopy for the 4CR align with a mechanism in which amide-acids derived from maleic anhydride can reversibly form free amine and cyclic anhydride. Although this equilibrium is unfavorable, the aldehyde present can trap the primary amine through imine formation and react with the enol form of the anhydride through a Mannich-like mechanism. This detailed mechanistic investigation coupled with additional crossover experiments supports an analogous mechanism for the 3CR and has led to the elucidation of new 3CR conditions with homophthalic anhydride, amines, and aldehydes for the formation of dihydroisoquinolones in good yields and excellent diastereoselectivity. This work represents the culmination of more than a decade of mechanistic speculation for the 3- and 4CR, enabling the design of new multicomponent reactions that exploit this novel mechanism.

Treatment of triazines of type (I) with catalytic amounts of Cu(I) salts allows new access to 7‐aza‐5‐deazapurine derivatives.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

For Abstract see ChemInform Abstract in Full Text.