Chemical Building Blocks Research Articles

Aromatics and Cyclic Molecules in Molecular Clouds: A New Dimension of Interstellar Organic Chemistry.

Astrochemistry lies at the nexus of astronomy, chemistry, and molecular physics. On the basis of precise laboratory data, a rich collection of more than 200 familiar and exotic molecules have been identified in the interstellar medium, the vast majority by their unique rotational fingerprint. Despite this large body of work, there is scant evidence in the radio band for the basic building blocks of chemistry on earth-five- and six-membered rings-despite long-standing and sustained efforts during the past 50 years. In contrast, a peculiar structural motif, highly unsaturated carbon in a chainlike arrangement, is instead quite common in space. The recent astronomical detection of cyanobenzene, the simplest aromatic nitrile, in the dark molecular cloud TMC-1, and soon afterward in additional prestellar and possibly protostellar sources, establishes that aromatic chemistry is likely widespread in the earliest stages of star formation. The subsequent discovery of cyanocyclopentadienes and even cyanonaphthalenes in TMC-1 provides further evidence that organic molecules of considerable complexity are readily synthesized in regions with high visual extinction but where the low temperature and pressure are remarkably low. This review focuses on laboratory efforts now underway to understand the rich transition region between linear and planar carbon structures using microwave spectroscopy. We present key features, advantages, and disadvantages of current detection methods, a discussion of the types of molecules found in space and in the laboratory, and approaches under development to identify entirely new species in complex mixtures. Studies focusing on the cyanation of hydrocarbons and the formation of benzene from acyclic precursors are highlighted, as is the role that isotopic studies might play in elucidating the chemical pathways to ring formation.

Cover Feature: Three‐Component Castagnoli‐Cushman Reaction of 3‐Arylglutaconic Acid Anhydrides, Carbonyl Compounds, and Ammonium Acetate: a Quick and Flexible Way to Assemble Polysubstituted NH‐δ‐lactams (Eur. J. Org. Chem. 11/2021)

The Cover Feature shows the synthesis of NH-δ-lactams through three-component Castagnoli–Cushman reaction of 3-arylglutaconic anhydrides with carbonyl compound and ammonium acetate. The way chemical building blocks are united to form the desired heterocyclic product is compared to the famous tile-matching Tetris game. More information can be found in the Communication by M. Krasavin et al.

The Limonene Biorefinery: From Extractive Technologies to Its Catalytic Upgrading into p-Cymene

Limonene is a renewable cyclic monoterpene that is easily obtainable from citrus peel and it is commonly used as a nutraceutical ingredient, antibacterial, biopesticide and green extraction solvent as well as additive in healthcare, fragrance and food and beverage industries for its characteristic lemon-like smell. Indeed, the lack of toxicity makes limonene a promising bio-alternative for the development of a wide range of effective products in modern biorefineries. As a consequence, industrial demand largely exceeds supply by now. Limonene can be also used as starting substrate for the preparation of building block chemicals, including p-cymene that is an important intermediate in several industrial catalytic processes. In this contribution, after reviewing recent advances in the recovery of limonene from citrus peel and residues with particular attention to benign-by-design extractive processes, we focus on the latest results in its dehydrogenation to p-cymene via heterogeneous catalysis. Indeed, the latest reports evidence that the selective production of p-cymene still remains a scientific and technological challenge since, in order to drive the isomerization and dehydrogenation of limonene, an optimal balance between the catalyst nature/content and the reaction conditions is needed.

The technical and economic comparison of ethylene production from natural gas and ethane

Abstract Ethylene is one of the most primary and widely used petrochemical products in today’s world and is considered as a chemical building block in the petrochemical industry. In this research, ethylene production from ethane and natural gas is evaluated in terms of cost and optimum conditions. Also, a comprehensive economic and technical comparison is made to achieve the optimal conditions for ethylene production concerning feed diversity. Nowadays most ethylene production units run with ethane feed. If it is possible to implement gas-ethylene processes with an inexpensive natural gas feed, it will be a significant step for technical and economic optimization. Thus, some methods are introduced and compared, and finally an economic review about best condition for ethylene production from ethane and natural gas/investment with regard to cost and economic efficiency of the methods is provided. The investment cost for Gas to Ethylene (GTE) and Ethane to Ethylene (ETE) processes is 363–701 million dollars per year, respectively. Also, rate of return (ROR) of 24 and 19% is calculated for GTE and ETE processes, respectively.

Selective Extraction of Medium-Chain Carboxylic Acids by Electrodialysis and Phase Separation.

Carboxylic acids obtained via the microbial electrochemical conversion of waste gases containing carbon dioxide (i.e., microbial electrosynthesis) can be used in lieu of nonrenewable building-block chemicals in the manufacture of a variety of products. When targeting valuable medium-chain carboxylic acids such as caproic acid, electricity-driven fermentations can be limited by the accumulation of fermentation products in the culturing media, often resulting in low volumetric productivities and titers due to direct toxicity or inhibition of the biocatalyst. In this study, we tested the effectiveness of a simple electrodialysis system in upconcentrating carboxylic acids from a model solution mimicking the effluent of a microbial electrochemical system producing short- and medium-chain carboxylic acids. Under batch extraction conditions, the electrodialysis scheme enabled the recovery of 60% (mol mol–1) of the total carboxylic acids present in the model fermentation broth. The particular arrangement of conventional monopolar ion exchange membranes and hydraulic recirculation loops allowed the progressive acidification of the extraction solution, enabling phase separation of caproic acid as an immiscible oil with 76% purity.

Optimizing acido-basic profile of support in Ni supported La2O3+Al2O3 catalyst for dry reforming of methane

The increasing alarm of global warming always draws interest in reactions like dry reforming of methane (DRM) where both global warming gases (CO2 and CH4) are converted into value-added chemical building blocks, such as syngas. Nickel catalyst active sites along with support acid-base profiles play a key role in DRM. Herein, xLa2O3+(100-x) Al2O3 (x = 0, 10, 15, 20%) supports are prepared and followed by NiO dispersion over the produced support by impregnation method. It was tested for DRM reaction and characterized with TGA, XRD, TEM, IR, Surface area and porosity measurement, H2-TPR, CO2-TPD and NH3-TPD techniques. Upon increasing the basic lanthana proportion in the acidic alumina support, the crystallinity of alumina and acidity of total support decline. Up to 15% Lanthana addition in support claims a low acid and rich basic surface including super basic sites (related to unidentate carbonates) which governed optimum catalytic performance 64% CH4 conversion, 79% CO2 conversion and H2/CO ~ 1 up to 460-min in time on stream test. 20% lanthanum oxide loading led to inferior performance due to rapid loss of surface area, pore-volume, pore diameter, acidity and medium basic strength sites. Fine-tuning of acid-base lanthana-alumina support with dispersed Ni species are a means for understanding DRM.

Dehydrogenative Pd and Ni Catalysis for Total Synthesis.

The development of novel synthetic methods remains a cornerstone in simplifying complex molecule synthesis. Progress in the field of transition metal catalysis has enabled new mechanistic strategies to achieve difficult chemical transformations, increased the value of abundant chemical building blocks, and pushed the boundaries of creative and strategic route design to improve step economy in multistep synthesis. Methodologies to introduce an olefin into saturated molecules continue to be essential transformations because of the plethora of reactions available for alkene functionalization. Of particular importance are dehydrogenation reactions adjacent to electron-withdrawing groups such as carbonyls, which advantageously provide activated olefins that can be regioselectively manipulated. Palladium catalysis occupies a central role in the most widely adopted carbonyl dehydrogenation reactions, but limits to the scope of these protocols persist.In this Account, we describe our group's contributions to the area of transition-metal-catalyzed dehydrogenation using palladium catalysis and more sustainable and economical nickel catalysis. These metals are used in conjunction with allyl and aryl halides or pseudohalides that serve as oxidants to access a unique mechanistic approach for one-step α,β-dehydrogenation of various electron-withdrawing groups, including ketones, esters, nitriles, amides, carboxylic acids, and electron-deficient heteroarenes. The pivotal reaction parameters that can be modified to influence reaction efficiency are highlighted, including base and oxidant structure as well as ligand and salt additive effects. This discussion is expected to serve as a guide for troubleshooting challenging dehydrogenation reactions and provide insight for future reaction development in this area.In addition to enabling dehydrogenation reactions, our group's allyl-Pd and -Ni chemistry can be used for C-C and C-X bond-forming reactions, providing novel disconnections with practical applications for expediting multistep synthesis. These transformations include a telescoped process for ketone α,β-vicinal difunctionalization; an oxidative enone β-functionalization, including β-stannylation, β-silylation, and β-alkylation; and an oxidative cycloalkenylation between unstabilized ketone enolates and unactivated alkenes. These bond-forming methodologies broaden the range of transformations accessible from abundant ketone, enone, and alkene moieties. Both the dehydrogenation and C-C and C-X bond-forming methodologies have been implemented in our group's total synthesis campaigns to provide step-efficient synthetic routes toward diverse natural products.Through the lens of multistep synthesis, the utility and robustness of our dehydrogenation and dehydrogenative functionalization methodologies can be better appreciated, and we hope that this Account will inspire practitioners to apply our methodologies to their own synthetic challenges.

Design, synthesis and biological evaluation of Tozadenant analogues as adenosine A2A receptor ligands.

With the aim to obtain potent adenosine A2A receptor (A2AR) ligands, a series of eighteen derivatives of 4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide (SYN-115, Tozadenant) were designed and synthesized. The target compounds were obtained by a chemical building block principle that involved reaction of the appropriate aminobenzothiazole phenyl carbamates with either commercially available or readily synthesized functionalized piperidines. Their affinity and subtype selectivity with regard to human adenosine A1-and A2A receptors were determined using radioligand binding assays. Ki values for human A2AR ranged from 2.4 to 38nM, with more than 120-fold selectivity over A1 receptors for all evaluated compounds except 13k which had a Ki of 361nM and 18-fold selectivity. The most potent fluorine-containing derivatives 13e, 13g and 13l exhibited Ki values of 4.9nM, 3.6nM and 2.8nM for the human A2AR. Interestingly, the corresponding values for rat A2AR were found to be four to five times higher. Their binding to A2AR was further confirmed by radiolabeling with 18F and invitro autoradiography in rat brain slices, which showed almost exclusive striatal binding and complete displacement by the A2AR antagonist ZM 241385. We conclude that these compounds represent potential candidates for the visualization of the A2A receptor and open pathways to novel therapeutic treatments of neurodegenerative disorders or cancer.

Isobutene production in Synechocystis sp. PCC 6803 by introducing α-ketoisocaproate dioxygenase from Rattus norvegicus

Cyanobacteria can be utilized as a platform for direct phototrophic conversion of CO2 to produce several types of carbon-neutral biofuels. One promising compound to be produced photobiologically in cyanobacteria is isobutene. As a volatile compound, isobutene will quickly escape the cells without building up to toxic levels in growth medium or get caught in the membranes. Unlike liquid biofuels, gaseous isobutene may be collected from the headspace and thus avoid the costly extraction of a chemical from culture medium or from cells. Here we investigate a putative synthetic pathway for isobutene production suitable for a photoautotrophic host. First, we expressed α-ketoisocaproate dioxygenase from Rattus norvegicus (RnKICD) in Escherichia coli. We discovered isobutene formation with the purified RnKICD with the rate of 104.6 ​± ​9 ​ng (mg protein)-1 min-1 using α-ketoisocaproate as a substrate. We further demonstrate isobutene production in the cyanobacterium Synechocystis sp. PCC 6803 by introducing the RnKICD enzyme. Synechocystis strain heterologously expressing the RnKICD produced 91 ​ng ​l−1 OD750−1 ​h−1. Thus, we demonstrate a novel sustainable platform for cyanobacterial production of an important building block chemical, isobutene. These results indicate that RnKICD can be used to further optimize the synthetic isobutene pathway by protein and metabolic engineering efforts.

Recycling bread waste into chemical building blocks using a circular biorefining approach.

Food waste is a global problem, causing significant environmental harm and resulting in substantial economic losses globally. Bread is the commonly wasted food item in the developed world and presents a severe problem for the majority of European nations. It is the second most wasted food item in the UK after potatoes, with an equivalent of 20 million slices of bread thrown away daily. Bread is a starchy material and a rich and clean source of easily extractable fermentable sugars – this is in direct contrast to lignocellulosic feedstocks where harsh physical, chemical and/or enzymatic pretreatment processes are required for release of fermentable sugars. Furthermore, these necessary lignocellulosic pretreatment methods often produce sugars contaminated with fermentation inhibitors. Therefore, bread waste presents a clear opportunity as a potential carbon source for novel commercial processes and, to this end, several alternative routes have been developed to utilize bread waste. Possibilities for direct recycling of bread waste within the food industry are limited due to the relatively short material lifetime, stringent process and hygiene requirements. Anaerobic digestion (AD) and incineration are commonly employed methods for the valorisation of bread waste, generating limited amounts of green energy but with little other environmental or economic benefits. Most food wastes and by-products in the UK including bakery waste are treated through AD processes that fail to harness the full potential of the these wastes. This short communication reviews the challenges of handling bread waste, with a focus on a specific UK scenario. The review will consider how bread waste is generated across the supply chain, current practices to deal with the waste and logistics challenges in waste collection. The presence of clean and high-quality fermentable sugars, proteins and other nutrients in bread make it an ideal substrate for generating chemicals, fuels, bioplastics, pharmaceuticals and other renewable products through microbial fermentations. We suggest potential applications for recycling bread waste into its chemical building blocks through a fermentative route where a circular biorefining approach could maximize resource recovery and environmental savings and eliminate waste to as close to zero as possible.

Conversion of Carbon Monoxide to Chemicals Using Microbial Consortia.

Syngas, a gaseous mixture of CO, H2 and CO2, can be produced by gasification of carbon-containing materials, including organic waste materials or lignocellulosic biomass. The conversion of bio-based syngas to chemicals is foreseen as an important process in circular bioeconomy. Carbon monoxide is also produced as a waste gas in many industrial sectors (e.g., chemical, energy, steel). Often, the purity level of bio-based syngas and waste gases is low and/or the ratios of syngas components are not adequate for chemical conversion (e.g., by Fischer-Tropsch). Microbes are robust catalysts to transform impure syngas into a broad spectrum of products. Fermentation of CO-rich waste gases to ethanol has reached commercial scale (by axenic cultures of Clostridium species), but production of other chemical building blocks is underexplored. Currently, genetic engineering of carboxydotrophic acetogens is applied to increase the portfolio of products from syngas/CO, but the limited energy metabolism of these microbes limits product yields and applications (for example, only products requiring low levels of ATP for synthesis can be produced). An alternative approach is to explore microbial consortia, including open mixed cultures and synthetic co-cultures, to create a metabolic network based on CO conversion that can yield products such as medium-chain carboxylic acids, higher alcohols and other added-value chemicals.

A Short Review of Recent Advances in Direct CO2 Hydrogenation to Alcohols

The continuous increase in anthropogenic carbon dioxide (CO2) emission resulting in global climate change has been of great concern in the past decades. With the renewable hydrogen resource being more realistic, the transformation of CO2 with hydrogen into value-added chemicals becomes a promising route to address the environment and climate issues. The chemical synthesis of alcohols which serve as chemical building blocks and the hydrogen energy carrier through direct CO2 hydrogenation has attracted more attention and been studied extensively nowadays. There remain major challenges in developing catalysts with high activity, selectivity and stability. In this review, we summarize the state of the art advances and perspectives in direct CO2 hydrogenation to methanol and other higher alcohols. We focus on the catalyst design, mechanistic investigation and the structure-performance relations of two categories of catalysts, noble metal and non-noble metal. Then, we propose an outlook for further catalyst design and study in this area.

Microbiology challenges and opportunities in the circular economy.

Our knowledge and understanding of micro-organisms have led to the development of safe food, clean water, novel foods, antibiotics, vaccines, healthier plants, animals and soils, and more, which feeds into the United Nations Sustainable Development Goals (UN SDGs). The circular economy can contribute to the UN SDGs and micro-organisms are central to circular nutrient cycles. The circular economy as described by the Ellen MacArthur foundation has two halves, i.e. technical and biological. On the technical side, non-biological resources enter manufacturing paths where resource efficiency, renewable energy and design extend the life of materials so that they are more easily reused and recycled. Biological resources exist on the other half of the circular economy. These are used to manufacture products such as bioplastics and paper. The conservation of nature’s stocks, resource efficiency and recycling of materials are key facets of the biological half of the circular economy. Microbes play a critical role in both the biological and technical parts of the circular economy. Microbes are key to a functioning circular economy, where natural resources, including biological wastes, are converted by microbes into products of value and use for society, e.g. biogas, bioethanol, bioplastics, building block chemicals and compost for healthy soils. In more recent times, microbes have also been seen as part of the tool kit in the technical side of the circular economy, where microbial enzymes can degrade plastics and microbes can convert those monomers to value-added products.

Phytocat – a bio-derived Ni catalyst for rapid de-polymerization of polystyrene using a synergistic approach

A bio-derived Ni catalyst (phytocat) was developed using microwave assistedin-situbiosynthesis. The efficient use of naturally bound nickel in phytocat was successful in synergistic valorization of polystyrene to yield valuable chemical building blocks.

Fabrication and characterisation of a silicon-borosilicate glass microfluidic device for synchrotron-based hard X-ray spectroscopy studies.

Some of the most fundamental chemical building blocks of life on Earth are the metal elements. X-ray absorption spectroscopy (XAS) is an element-specific technique that can analyse the local atomic and electronic structure of, for example, the active sites in catalysts and energy materials and allow the metal sites in biological samples to be identified and understood. A microfluidic device capable of withstanding the intense hard X-ray beams of a 4th generation synchrotron and harsh chemical sample conditions is presented in this work. The device is evaluated at the K-edges of iron and bromine and the L3-edge of lead, in both transmission and fluorescence mode detection and in a wide range of sample concentrations, as low as 0.001 M. The device is fabricated in silicon and glass with plasma etched microchannels defined in the silicon wafer before anodic bonding of the glass wafer into a complete device. The device is supported with a well-designed printed chip holder that made the microfluidic device portable and easy to handle. The chip holder plays a pivotal role in mounting the delicate microfluidic device on the beamline stage. Testing validated that the device was sufficiently robust to contain and flow through harsh acids and toxic samples. There was also no significant radiation damage to the device observed, despite focusing with intense X-ray beams for multiple hours. The quality of X-ray spectra collected is comparable to that from standard methods; hence we present a robust microfluidic device to analyse liquid samples using synchrotron XAS.

Crystal engineering of porous coordination networks for C3 hydrocarbon separation

AbstractC3 hydrocarbons (HCs), especially propylene and propane, are high‐volume products of the chemical industry as they are utilized for the production of fuels, polymers, and chemical commodities. Demand for C3 HCs as chemical building blocks is increasing but obtaining them in sufficient purity (>99.95%) for polymer and chemical processes requires economically and energetically costly methods such as cryogenic distillation. Adsorptive separations using porous coordination networks (PCNs) could offer an energy‐efficient alternative to current technologies for C3 HC purification because of the lower energy footprint of sorbent separations for recycling versus alternatives such as distillation, solvent extraction, and chemical transformation. In this review, we address how the structural modularity of porous PCNs makes them amenable to crystal engineering that in turn enables control over pore size, shape, and chemistry. We detail how control over pore structure has enabled PCN sorbents to offer benchmark performance for C3 separations thanks to several distinct mechanisms, each of which is highlighted. We also discuss the major challenges and opportunities that remain to be addressed before the commercial development of PCNs as advanced sorbents for C3 separation becomes viable.

Biosourced All-Acrylic ABA Block Copolymers with Lactic Acid-Based Soft Phase.

Lactic acid is one of the key biobased chemical building blocks, given its readily availability from sugars through fermentation and facile conversion into a range of important chemical intermediates and polymers. Herein, well-defined rubbery polymers derived from butyl lactate solvent were successfully prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization of the corresponding monomeric acrylic derivative. Good control over molecular weight and molecular weight distribution was achieved in bulk using either monofunctional or bifunctional trithiocarbonate-type chain transfer agents. Subsequently, poly(butyl lactate acrylate), with a relative low Tg (−20 °C), good thermal stability (5% wt. loss at 340 °C) and low toxicity was evaluated as a sustainable middle block in all-acrylic ABA copolymers using isosorbide and vanillin-derived glassy polyacrylates as representative end blocks. Thermal, morphological and mechanical properties of copolymers containing hard segment contents of <20 wt% were evaluated to demonstrate the suitability of rubbery poly(alkyl lactate) building blocks for developing functional sustainable materials. Noteworthy, 180° peel adhesion measurements showed that the synthesized biosourced all-acrylic ABA copolymers possess competitive performance when compared with commercial pressure-sensitive tapes.

Biocatalysis in the Swiss Manufacturing Environment

Biocatalysis has undergone a remarkable transition in the last two decades, from being considered a niche technology to playing a much more relevant role in organic synthesis today. Advances in molecular biology and bioinformatics, and the decreasing costs for gene synthesis and sequencing contribute to the growing success of engineered biocatalysts in industrial applications. However, the incorporation of biocatalytic process steps in new or established manufacturing routes is not always straightforward. To realize the full synthetic potential of biocatalysis for the sustainable manufacture of chemical building blocks, it is therefore important to regularly analyze the success factors and existing hurdles for the implementation of enzymes in large scale small molecule synthesis. Building on our previous analysis of biocatalysis in the Swiss manufacturing environment, we present a follow-up study on how the industrial biocatalysis situation in Switzerland has evolved in the last four years. Considering the current industrial landscape, we record recent advances in biocatalysis in Switzerland as well as give suggestions where enzymatic transformations may be valuably employed to address some of the societal challenges we face today, particularly in the context of the current Coronavirus disease 2019 (COVID-19) pandemic.

Two-in-One Catalyst Turns Carbon Dioxide in Base Chemicals

Cascading chemical reactions can be realized when the local structure and composition of two catalytically active phases are fine-tuned and combined in one material. In this issue of Chem, Fan et al. report an innovative approach for the conversion of carbon dioxide into light olefins with a metal oxide-zeolite tandem catalyst.

Sonification of a 3-D Spider Web and Reconstitution for Musical Composition Using Granular Synthesis

AbstractThree-dimensional spider webs feature highly intricate fiber architectures, which can be represented via 3-D scanning and modeling. To allow novel interpretations of the key features of a 3-D Cyrtophora citricola spider web, we translate complex 3-D data from the original web model into music, using data sonification. We map the spider web data to audio parameters such as pitch, amplitude, and envelope. Paired with a visual representation, the resulting audio allows a unique and holistic immersion into the web that can describe features of the 3-D architecture (fiber distance, lengths, connectivity, and overall porosity of the structure) as a function of spatial location in the web. Using granular synthesis, we further develop a method to extract musical building blocks from the sonified web, transforming the original representation of the web data into new musical compositions. We build a new virtual, interactive musical instrument in which the physical 3-D web data are used to generate new variations in sound through exploration of different spatial locations and grain-processing parameters. The transformation of sound from grains to musical arrangements (variations of melody, rhythm, harmony, chords, etc.) is analogous to the natural bottom–up processing of proteins, resembling the design of sequence and higher-level hierarchical protein material organization from elementary chemical building blocks. The tools documented here open possibilities for creating virtual instruments based on spider webs for live performances and art installations, suggesting new possibilities for immersion into spider web data, and for exploring similarities between protein folding, on the one hand, and assembly and musical expression, on the other.