Enabling Technologies for the Future of Chemical Synthesis.

Technology is evolving at breakneck pace, changing the way we communicate, travel, find out information, and live our lives. Yet chemistry as a science has been slower to adapt to this rapidly shifting world. In this Outlook we use highlights from recent literature reports to describe how progresses in enabling technologies are altering this trend, permitting chemists to incorporate new advances into their work at all levels of the chemistry development cycle. We discuss the benefits and challenges that have arisen, impacts on academic-industry relationships, and future trends in the area of chemical synthesis.We are grateful to the Woolf Fisher Trust (D.E.F), Syngenta Crop Protection AG (C.B.) and EPSRC (S.V.L., grant codes EP/K009494/1, EP/M004120/1 and EP/K039520/1) for financial assistance.This is the final version of the article. It first appeared from the American Chemical Society via https://doi.org/10.1021/acscentsci.6b0001

Introduction of a simple experiment for the undergraduate organic chemistry laboratory demonstrating the Lewis acid and shape-selective properties of zeolite Na-Y

A simple, inexpensive, discovery-based experiment for undergraduate organic laboratories has been developed that demonstrates the Lewis acid and shape-selective properties of zeolites. Calcined zeolite Na-Y promotes the electrophilic aromatic bromination of toluene with a significantly higher para/ortho ratio than observed under conventional conditions. The experiment can be completed in one three-hour laboratory period. The zeolite can be recovered and regenerated for later reuse. A broad range of organic course topics from orientation in electrophilic aromatic substitution to photochemistry can be discussed

Social Influences on Peer Judgments about Chronic Pain and Disability

Chronic pain is a leading cause of work absenteeism and disability compensation. Previous work demonstrates that patients with chronic illness often seek advice, such as whether or not to pursue disability benefits, from peers with similar health conditions. The current study examined the extent that social factors influence patients with chronic pain (“peers”) when making disability judgments and recommendations for other patients with chronic pain. Participants (N = 71) made pain-related and disability ratings for fictional vignette patients that varied in weight (normal vs obese), fault of accident, and physical work demands. Results of repeated measures analyses of variance indicated that participants rated patients with obesity, who were not at fault, and who held a physically demanding job as experiencing more severe pain symptoms and disability and were more likely to recommend they seek disability benefits. Participants who had applied for disability benefits themselves rated patients as more disabled than participants who had not applied for disability. These data suggest that patients with chronic pain are influenced by patient and contextual factors when making pain-related and disability judgments for peers. These judgments may impact patient decision making via peer support programs and online forums

The dark side of biomass valorization: A laboratory experiment to understand humins formation, catalysis and green chemistry

This laboratory experiment introduces students to an important reaction in biomass valorization and allows them to gain a practical understanding of green chemistry. Acid-catalyzed dehydration reactions of fructose to 5-hydroxymethylfurfural and thus humins were performed both with and without aqueous solvent, along with two different catalysts (Amberlyst-15 and alumina). Students were able to compare and analyze the effects of these different conditions using thin-layer chromatography, while grasping concepts of catalysis and circular economy. By observing the formation of humins under some of the reactions tested, the students could evidence systems thinking in humin valorization

Continuous Processing and Efficient in Situ\textit{in Situ} Reaction Monitoring of a Hypervalent Iodine(III) Mediated Cyclopropanation Using Benchtop NMR Spectroscopy

Real-time NMR spectroscopy has proven to be a rapid and an effective monitoring tool to study the hypervalent iodine(III) mediated cyclopropanation. With the ever increasing number of new synthetic methods for carbon−carbon bond formation, the NMR $\textit{in situ}$ monitoring of reactions is becoming a highly desirable enabling method. In this study, we have demonstrated the versatility of benchtop NMR using inline and online real-time monitoring methods to access mutually complementary information for process understanding, and we developed new approaches for real-time monitoring addressing challenges associated with better integration into continuous processes.University of Cambridge (Daphne Jackson Fellowship), iCON through CMAC (Grant ID: RG74817), Engineering and Physical Sciences Research Council (Critical Mass grant (Grant ID: EP/K009494K/1), Core Capability grant (Grant ID: EP/K039520/1

Overcoming the Challenges to the Implementation of Green Chemistry

The Harvard-Yale-ACS GCI Green Chemistry Project is investigating the overall question of the circumstances under which firms can enact innovations that have both economic and environmental benefits, through a focused examination of the implementation of green chemistry. The research project has taken up three fundamental, interrelated questions: What factors act as barriers to the implementation of green chemistry? What actions can be taken by the government, academia, NGO’s and industry that will help alleviate these factors? What are the policy implications of these barriers and potential actions, for all of the involved stakeholders? During its initial phases, through interviews with a dozen green chemistry leaders from industry and academia, and through a multi-stakeholder workshop, the project has focused on the first two questions, and is working towards the third. Overall, we determined that there are six major classes of barriers to the implementation of green chemistry: economic, regulatory, technical, organizational, cultural and definition and metrics. From the workshop participants, six major action themes emerged to address these. They are: create incentives for the development and implementation of innovations; consider policies to shift focus to hazard reduction; facilitate linkages, networks and collaborations; act as a facilitator for multi-stakeholder initiatives; promote actions that make environmental and health impacts a larger part of the decision calculus; and support research, knowledge creation, and educational efforts to support green chemistry across a range of disciplines and problem areas

Synthesis of Semiochemicals via Olefin Metathesis

Semiochemicals are substances or mixtures that carry messages and are used for communication between individuals of the same or different species. Semiochemicals that are used in pest control are called biopesticides. Conventional pesticides, which are generally synthetically derived and unnatural, inactivate or kill the pests, whereas biopesticides are naturally occurring compounds that attract insects to a trap or interfere with their reproduction. There are several advantages to biopesticides. Compared with conventional pesticides, biochemical-based pesticides are often less toxic and therefore have a significantly lower impact on human health and the environment. Moreover, biopesticides are pest-selective and as such do not negatively impact other organisms such as insects, mammals, or birds. Other advantages of biopesticides include high potency, meaning that smaller amounts of biopesticide are required, less resistance by target organisms, and the ability to biodegrade more quickly than conventional pesticides. Although biochemical-based pesticides are very promising materials, their production is often cumbersome, and their application is often limited. To date, most biopesticides have been synthesized by multistep, classical organic reactions that are not economical and have high environmental impact. However, in recent decades many efforts have been made to implement cost-effective and safer chemical procedures for the widespread application of biochemical-based pesticides. The purpose of this Perspective is to draw the attention of the green chemistry community to the applicability of olefin metathesis reactions in environmentally benign and cost-effective biopesticide synthesis. We review seminal work on the total synthesis of biopesticides using olefin metathesis as a key reaction step, and in doing so, we hope to inspire new ideas for forthcoming olefin-metathesis-based biopesticide development

Scope and Mechanistic Study of the Coupling Reaction of α,β-Unsaturated Carbonyl Compounds with Alkenes: Uncovering Electronic Effects on Alkene Insertion vs Oxidative Coupling Pathways

The cationic ruthenium-hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4– (1) was found to be a highly effective catalyst for the intermolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds to give (Z)-selective tetrasubstituted olefin products. The analogous coupling reaction of cinnamides with electron-deficient olefins led to the oxidative coupling of two olefinic C–H bonds in forming (E)-selective diene products. The intramolecular version of the coupling reaction efficiently produced indene and bicyclic fulvene derivatives. The empirical rate law for the coupling reaction of ethyl cinnamate with propene was determined as follows: rate = k[1]1[propene]0[cinnamate]−1. A negligible deuterium kinetic isotope effect (kH/kD = 1.1 ± 0.1) was measured from both (E)-C6H5CH═C(CH3)CONHCH3 and (E)-C6H5CD═C(CH3)CONHCH3 with styrene. In contrast, a significant normal isotope effect (kH/kD = 1.7 ± 0.1) was observed from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene and styrene-d8. A pronounced carbon isotope effect was measured from the coupling reaction of (E)-C6H5CH═CHCO2Et with propene (13C(recovered)/13C(virgin) at Cβ = 1.019(6)), while a negligible carbon isotope effect (13C(recovered)/13C(virgin) at Cβ = 0.999(4)) was obtained from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene. Hammett plots from the correlation of para-substituted p-X-C6H4CH═CHCO2Et (X = OCH3, CH3, H, F, Cl, CO2Me, CF3) with propene and from the treatment of (E)-C6H5CH═CHCO2Et with a series of para-substituted styrenes p-Y-C6H4CH═CH2 (Y = OCH3, CH3, H, F, Cl, CF3) gave the positive slopes for both cases (ρ = +1.1 ± 0.1 and +1.5 ± 0.1, respectively). Eyring analysis of the coupling reaction led to the thermodynamic parameters, ΔH⧧ = 20 ± 2 kcal mol–1 and ΔS⧧ = −42 ± 5 eu. Two separate mechanistic pathways for the coupling reaction have been proposed on the basis of these kinetic and spectroscopic studies

Patient race and opioid misuse history influence provider risk perceptions for future opioid-related problems

In response to the dual public health crises of chronic pain and opioid use, providers have become more vigilant about assessing patients for risk of opioid-related problems. Little is known about how providers are making these risk assessments. Given previous studies indicating that Black patients are at increased risk for suboptimal pain care, which may be related to stereotypes about drug abuse, the current study examined how patient race and previous opioid misuse behaviors impact providers' risk assessments for future prescription opioid-related problems. Physician residents and fellows (N = 135) viewed videos and read vignettes about 8 virtual patients with chronic pain who varied by race (Black/White) and history of prescription opioid misuse (absent/present). Providers rated patients' risk for future prescription opioid-related adverse events, misuse/abuse, addiction, and diversion, and also completed measures of implicit racial attitudes and explicit beliefs about race differences in pain. Two significant interactions emerged indicating that Black patients were perceived to be at greater risk for future adverse events (when previous misuse was absent) and diversion (when previous misuse was present). Significant main effects indicated that Black patients and patients with previous misuse were perceived to be at greater risk for future misuse/abuse of prescription opioids, and that patients with previous misuse were perceived to be at greater risk of addiction. These findings suggest that racial minorities and patients with a history of prescription opioid misuse are particularly vulnerable to any unintended consequences of efforts to stem the dual public health crises of chronic pain and opioid use