Csp2-H functionalization of phenols: an effective access route to valuable materials via Csp2-C bond formation.

In the vast majority of top-selling pharmaceutical and industrial products, phenolic structural motifs are highly prevalent. Non-functionalized simple phenols serve as building blocks in the synthesis of value-added chemicals. It is worth mentioning that lignin, being the largest renewable biomass source of aromatic building blocks in nature, mainly consists of phenolic units, which enable the production of structurally diverse phenols. Given their remarkable applicability in the chemical value chain, many efforts have been devoted to increasing the molecular complexity of the phenolic scaffold. Among the key techniques, direct functionalization of Csp2-H is a powerful tool, enabling the construction of new Csp2-C bonds in an economical and atomic manner. Herein we present and summarize the large plethora of direct Csp2-H functionalization methods that enables scaffold diversification of simple, unprotected phenols, leading to the formation of new Csp2-C bonds. In this review article, we intend to summarize the contributions that appeared in the literature mainly in the last 5 years dealing with the functionalization of unprotected phenols, both catalytic and non-catalytic. Our goal is to highlight the key findings and the ongoing challenges in the stimulating and growing research dedicated to the development of new protocols for the valorization of phenols.

Surface-Controlled Sialoside-Based Biosensing of Viral and Bacterial Neuraminidases.

Neuraminidases (NA) are sialic acid-cleaving enzymes that are used by both bacteria and viruses. These enzymes have sialoside structure-related binding and cleaving preferences. Differentiating between these enzymes requires using a large array of hard-to-access sialosides. In this work, we used electrochemical impedimetric biosensing to differentiate among several pathogene-related NAs. We used a limited set of sialosides and tailored the surface properties. Various sialosides were grafted on two different surfaces with unique properties. Electrografting on glassy carbon electrodes provided low-density sialoside-functionalized surfaces with a hydrophobic submonolayer. A two-step assembly on gold electrodes provided a denser sialoside layer on a negatively charged submonolayer. The synthesis of each sialoside required dozens of laborious steps. Utilizing the unique protein-electrode interaction modes resulted in richer biodata without increasing the synthetic load. These principles allowed for profiling NAs and determining the efficacy of various antiviral inhibitors.

Nano-Hydroxyapatite Isolation and Characterisation of Echinometra mathaei from the Persian Gulf.

The study focuses on the preparation and characterisation (physicochemical and mechanical) of hydroxyapatite [Ca10(PO4)6(OH)2] (HA) from sea urchin, Echinometra mathaei. Therefore, nano-sized HA prepared from sea urchin shells were collected from beaches of the Persian Gulf in Iran. Sea urchin shells were found a source of calcium carbonate in the form of aragonite (calcite) that crystallised in an organic matrix. HA is one of the polymers used in coating the nanoparticles extracted from various sources. The calcined aragonite converted to nanosized hydroxyapatite powder by chemical reaction with orthophosphoric acid while maintaining stoichiometry, Ca/P = 1.667 at 80°C. To determine the purity of the nano-hydroxyapatite (nHA) numerous analytical procedures were used. Fourier transforms infrared spectroscopy (FTIR) confirmed the presence of the peak of 961 cm-1 is related to the symmetric tensile band of the P-O bond, and the peak of 1038 cm-1 and 1091 cm-1 is related to the tensile solid absorption of the PO4 as functional groups of nHA. The nanocrystalline HA can be observed from the SEM images. Thermogravimetric analysis (TGA-DTA) demonstrates the thermal stability of nHA powder. The results show successful isolation and characterisation study of this crucial nano-material shows it is valuable in biomedical applications, particularly in bone tissue engineering. Indeed, its fabrication is easy and economical.

Efficient synthesis and investigation of waste-derived adsorbent for water purification. Exploring the impact of surface functionalization on methylene blue dye removal.

In pursuit of sustainable water management, the preparation of adsorbent materials via waste upcycling for water purification practices plays a decisive role. The sulphonated biochar, PiNe-SO3H, employed to target the methylene blue dye adsorption, was successfully synthesized via a mild, step-economical chemical carbonization-functionalization reaction. The presence of SO3H groups on the PiNe-SO3H surface played a critical role in significantly enhancing the adsorption capacity. The observed MB dye uptake was predominantly attributed to chemisorption processes as evidenced by the results from kinetics, thermodynamics, and isotherms. To further confirm the role of -SO3H in the adsorption mechanism, a comparison was made with other PiNe materials lacking sulphonic groups, highlighting the superior adsorption capacity of PiNe-SO3H. Additionally, a fast and efficient regeneration process was proposed to develop a truly waste minimized protocol, enabling the recovery of up to 94 % of the ethanolic mixture used during this step.

A General Enantioselective C-H Arylation Using an Immobilized Recoverable Palladium Catalyst.

We herein report a general and efficient enantioselective C-H arylation of aryl bromides based on the use of BozPhos as the bisphosphine ligand and SP-NHC-PdII as recoverable heterogeneous catalyst. By exploiting the "release and catch" mechanism of action of the catalytic system, we used BozPhos as a broadly applicable chiral ligand, furnishing high enantioselectivities across all types of examined substrates containing methyl, cyclopropyl and aryl C-H bonds. For each reaction, the reaction scope was investigated, giving rise to 30 enantioenriched products, obtained with high yields and enantioselectivities, and minimal palladium leaching. The developed catalytic system provides a more sustainable solution compared to homogeneous systems for the synthesis of high added-value chiral products through recycling of the precious metal.

POLITAG-M-F as Heterogeneous Organocatalyst for the Waste-Minimized Synthesis of ß-Azido Carbonyl Compounds in Batch and under Flow Conditions.

We herein report a waste minimization protocol for the ß-azidation of α,ß-unsaturated carbonyl compounds using TMSN3. The selection of the appropriate catalyst (POLITAG-M-F), in combination with the reaction medium, resulted in enhanced catalytic efficiency and a low environmental footprint. The thermal and mechanical stability of the polymeric support allowed us to recover the POLITAG-M-F catalyst for up to 10 consecutive runs. The CH3CN:H2O azeotrope has a 2-fold positive effect on the process, increasing the efficiency of the protocol and minimizing waste generation. Indeed, the azeotropic mixture, used as a reaction medium and for the workup procedure, was recovered by distillation, leading to an easy and environmentally friendly procedure for product isolation in high yield and with a low E-factor. A comprehensive evaluation of the environmental profile was performed by the calculation of different green metrics (AE, RME, MRP, 1/SF) and a comparison with other literature available protocols. A flow protocol was defined to scale-up the process, and up to 65 mmol of substrates were efficiently converted with a productivity of 0.3 mmol/min.

Pd-Catalyzed direct C-H arylation of pyrrolo[1,2-a]quinoxalines.

An efficient Pd-catalyzed direct C-H arylation of pyrrolo[1,2-a]quinoxalines with aryl iodides is described, providing a selective route toward a series of 1-arylated and 1,3-diarylated pyrrolo[1,2-a]quinoxalines in good yields. This method features a broad substrate scope, good functional group tolerance and gram-scale synthesis. Furthermore, the C3-thiocyanation of the arylated product is also achieved. We believe that these novel aryl-substituted pyrrolo [1,2-a]quinoxalines will have a variety of applications in organic synthesis and medicinal chemistry.

C(sp3 )-H Arylation Promoted by a Heterogeneous Palladium-N-Heterocyclic Carbene Complex in Batch and Continuous Flow.

A heterogeneous reusable palladium(II)-bis(N-heterocyclic carbene) catalyst was prepared and shown to catalyze the intramolecular C(sp3 )-H activation/cyclization of N-alkyl-2-bromoanilines furnishing indolines. This new catalytic system was based on a bis-imidazolium ligand immobilized on a spaced cross-linked polystyrene support. The iodide ligands on the catalyst played a central role in the efficiency of the process occurring through a "release and catch" mechanism. The heterogeneous nature of the catalyst was further exploited in the design of a continuous-flow protocol that allowed a more efficient recovery and reuse of the catalyst, as well as a very fast and safe procedure.

Sulfation Pattern Dependent Iron(III) Mediated Interleukin-8 Glycan Binding.

Cytokines such as interleukin-8 activate the immune system during infection and interact with sulfated glycosaminoglycans with specific sulfation patterns. In some cases, these interactions are mediated by metal ion binding which can be used to tune surface-based glycan-protein interactions. We evaluated the effect of both hyaluronan sulfation degree and Fe3+ on interleukin-8 binding by electrochemical impedance spectroscopy and surface characterizations. Our results show that sulfation degree and metal ion interactions have a synergistic effect in tuning the electrochemical response of the glycated surfaces to the cytokine.

A Waste-Minimized Approach to Cassar-Heck Reaction Based on POLITAG-Pd0 Heterogeneous Catalyst and Recoverable Acetonitrile Azeotrope.

Three different Pd0 -based heterogeneous catalysts were developed and tested in the Cassar-Heck reaction (i. e., copper-free Sonogashira reaction) aiming at the definition of a waste minimized protocol. The cross-linked polymeric supports used in this investigation were designed to be adequate for different reaction media and were decorated with different pincer-type ionic ligands having the role of stabilizing the formation and dimension of palladium nanoparticles. Among the ionic tags tested, bis-imidazolium showed the best performances in terms of efficiency and durability of the metal catalytic system. Eventually, aqueous acetonitrile azeotrope was selected as the reaction medium as it allowed the best catalytic efficiency combined with easy recovery and reuse. Finally, the synergy between the selected catalyst and reaction medium allowed to obtain highly satisfactory isolated yields of a variety of substrates while using a low amount of metal catalyst. The high performance of the designed POLymeric Ionic TAG (POLITAG)-Pd0 , along with its good selectivity achieved in a copper-free process, also led to a simplified purification procedure allowing the minimization of the waste generated as also proven by the very low E-factor values (1.4-5) associated.

Metal Nanoparticles as Sustainable Tools for C-N Bond Formation via C-H Activation.

The design of highly active metal nanoparticles to be employed as efficient heterogeneous catalysts is a key tool for the construction of complex organic molecules and the minimization of their environmental costs. The formation of novel C-N bonds via C-H activation is an effective atom-economical strategy to access high value materials in pharmaceuticals, polymers, and natural product production. In this contribution, the literature of the last ten years on the use of metal nanoparticles in the processes involving direct C-N bond formation will be discussed. Where possible, a discussion on the role and influence of the support used for the immobilization and/or the metal chosen is reported. Particular attention was given to the description of the experiments performed to elucidate the active mechanism.

Azeotropes as Powerful Tool for Waste Minimization in Industry and Chemical Processes.

Aiming for more sustainable chemical production requires an urgent shift towards synthetic approaches designed for waste minimization. In this context the use of azeotropes can be an effective tool for "recycling" and minimizing the large volumes of solvents, especially in aqueous mixtures, used. This review discusses the implementation of different kinds of azeotropic mixtures in relation to the environmental and economic benefits linked to their recovery and re-use. Examples of the use of azeotropes playing a role in the process performance and in the purification steps maximizing yields while minimizing waste. Where possible, the advantages reported have been highlighted by using E-factor calculations. Lastly azeotrope potentiality in waste valorization to afford value-added materials is given.

Sulfenylation of Arenes with Ethyl Arylsulfinates in Water.

A tetrabutylammonium iodide-mediated direct sulfenylation of arenes with ethyl arylsulfinates in water was developed. Various electron-rich arenes and ethyl arylsulfinates were investigated in the reaction, and a series of aryl sulfides were obtained in excellent yields. The advantages of this green protocol were simple reaction conditions (metal-free, water as the solvent, and under air), odorless and easily available sulfur reagent, broad substrate scope, and gram-scale synthesis. Moreover, the potential application of aryl sulfides was exemplified by further transformations.

I2/DMSO-Catalyzed Transformation of N-tosylhydrazones to 1,2,3-thiadiazoles.

An iodine/DMSO catalyzed selective cyclization of N-tosylhydrazones with sulfur without adding external oxidant was developed for the synthesis of 4-aryl-1,2,3-thiadiazoles. In this reaction, oxidation of HI by using DMSO as dual oxidant and solvent is the key, which allowed the regeneration of I2, ensuring thus the success of the synthesis. This protocol features by simple operation, high step-economy (one-pot fashion), broad substrate scope as well as scale-up ability.

C2-H Arylation of Indoles Catalyzed by Palladium-Containing Metal-Organic-Framework in γ-Valerolactone.

An efficient and selective procedure was developed for the direct C2-H arylation of indoles using a Pd-loaded metal-organic framework (MOF) as a heterogeneous catalyst and the nontoxic biomass-derived solvent γ-valerolactone (GVL) as a reaction medium. The developed method allows for excellent yields and C-2 selectivity to be achieved and tolerates various substituents on the indole scaffold. The established conditions ensure the stability of the catalyst as well as recoverability, reusability, and low metal leaching into the solution.

Polarclean/Water as a Safe and Recoverable Medium for Selective C2-Arylation of Indoles Catalyzed by Pd/C.

Herein, we report the use of nontoxic, water-miscible Polarclean as a safe dipolar aprotic solvent for the metal-catalyzed direct C2-H arylation of indoles using Pd/C as a catalyst. The developed method allows reaching excellent yields and regioselectivities, and it tolerates various substituents on both indole and diaryliodonium salt scaffolds. Polarclean is fully recoverable and reusable; it shows a very low leaching of the metal catalyst, allowing its complete recovery and reuse for at least six representative reaction runs.

Polymer-Anchored Bifunctional Pincer Catalysts for Chemoselective Transfer Hydrogenation and Related Reactions.

A series of polymer-supported cooperative PC(sp3 )P pincer catalysts was synthesized and characterized. Their catalytic activity in the acceptorless dehydrogenative coupling of alcohols and the transfer hydrogenation of aldehydes with formic acid as a hydrogen source was investigated. This comparative study, examining homogeneous and polymer-tethered species, proved that carefully designing a link between the support and the catalytic moiety, which takes into consideration the mechanism underlying the target transformation, might lead to superior heterogeneous catalysis.

Reusable Pd@PEG Catalyst for Aerobic Dehydrogenative C-H/C-H Arylations of 1,2,3-Triazoles.

Dehydrogenative C-H arylations of 1,2,3-triazoles were accomplished with the aid of a reusable palladium catalyst in PEG. The widely applicable oxidative palladium catalysis enabled the synthesis of fully decorated 1,2,3-triazoles with a broad functional-group tolerance and ample substrate scope. The sustainability of the aerobic C-H arylation was reflected by the use of PEG as green reaction medium and demonstrated by recycling studies of the catalyst and the reaction medium.

C-H functionalization reactions under flow conditions.

C-H functionalization technologies have progressed enormously in the last decade as testified by the great number of publications that have appeared in the literature, which are receiving great attention from researchers from different areas of expertise. While most of the protocols reported realize the C-H functionalization processes under batch conditions, there is a growing interest in the development of continuous-flow procedures aiming at increasing the performances of established methodologies or the definition of otherwise unfeasible transformations. This review summarizes the application of flow technologies for the realization of C-H functionalization reactions. According to the type of flow reactors necessary, two main general approaches are possible for the application of flow techniques, namely the use of homogeneous or heterogeneous conditions. Each example is discussed and accompanied by the description of the main features and benefits of the use of flow compared to batch conditions.

Sustainable Protocol for the Reduction of Nitroarenes by Heterogeneous Au@SBA-15 with NaBH4 under Flow Conditions.

A gold-incorporated SBA-15 catalyst was prepared by a solvent-free ball-milling approach. The catalyst showed high reactivity and selectivity in the reduction of a variety of nitroarenes to anilines operating in absolute EtOH with NaBH4 as reducing agent. The catalyst was reused in batch conditions over five consecutive runs without any losses of activity or selectivity. Considering the high chemical stability and reusability of the catalytic system, a continuous-flow protocol was also investigated and defined to minimize the generation of waste and optimize the continuous reuse of the catalyst. Benefits of flow conditions were proven by turnover numbers that increased from 47.5 to 1902 and also by the minimization of both leaching (9.5 vs. 1 ppm) and E-factor values (8 vs. 23 in batch).