Membrane-Free Electrosynthesis of Epichlorohydrins Mediated by Bromine Radicals over Nanotips.

The industrial manufacture of epichlorohydrin (ECH) often suffers from excessive corrosive chlorine and multistep processes. Here, we report a one-pot membrane-free Br radical-mediated ECH electrosynthesis. Bromine radicals electro-oxidized from Br- ions initiate the reaction and then eliminate HBr from bromohydrin to give ECH and release Br- ions for reuse. A high energy barrier for *OH oxidation and isolated Br adsorption sites enables NiCo2O4 to suppress the competitive oxygen and bromine evolution reactions. The high-curvature nanotips with an increased electric field concentrate Br- and OH- ions to accelerate ECH electrosynthesis. This strategy delivers ECH with a Faradaic efficiency of 47% and a reaction rate of 1.4 mol h-1 gcat-1 at a high current density of 100 mA cm-2, exceeding the profitable target from the techno-economic analysis. Economically profitable electrosynthesis, methodological universality, and the extended synthesis of epoxide-drug blocks highlight their promising potential.

Designed Nanomaterials for Electrocatalytic Organic Hydrogenation Using Water as the Hydrogen Source.

ConspectusThe hydrogenation reaction is one of the most frequently used transformations in organic synthesis. Electrocatalytic hydrogenation by using water (H2O) as the hydrogen source offers an efficient and sustainable approach to synthesize hydrogenated products under ambient conditions. Such a technique can avoid the use of high-pressure and flammable hydrogen gas or other toxic/expensive hydrogen donors, which usually cause environmental, safety, and cost concerns. Interestingly, utilizing easily available heavy water (D2O) for deuterated syntheses is also attractive due to the widespread applications of deuterated molecules in organic synthesis and the pharmaceutical industry. Despite impressive achievements, electrode selection mainly relies on trial-and-error modes, and how electrodes dictate reaction outcomes remains elusive. Therefore, the rational design of nanostructured electrodes for driving the electrocatalytic hydrogenation of a series of organics via H2O electrolysis is developed.In this Account, we review recent advances in the electrocatalytic hydrogenation of different types of organic functional groups, including C≡C, C≡N, C═C, C═O, and C-Br/I bonds, -NO2, and N-heterocycles, with H2O over nanostructured cathodes. First, the general reaction steps (reactant/intermediate adsorption, active atomic hydrogen (H*) formation, surface hydrogenation reaction, product desorption) are analyzed, and key factors are proposed to optimize hydrogenation performance (e.g., selectivity, activity, Faradaic efficiency (FE), reaction rate, and productivity) and inhibit side reactions. Then, ex situ and in situ spectroscopic tools to study key intermediates and interpret mechanisms are introduced. Third, based on the knowledge of key reaction steps and mechanisms, we introduce catalyst design principles in detail on how to optimize the adoption of reactants and key intermediates, promote the formation of H* from water electrolysis, inhibit hydrogen evolution and side reactions, and improve the selectivity, reaction rate, FEs, and space-time productivity of products. We then introduce some typical examples. (i) P- and S-modified Pd can decrease C═C adsorption and promote H* formation, enabling semihydrogenation of alkynes with high selectivity and FEs at lower potentials. Then, creating high-curvature nanotips to concentrate the substrates further speeds up the hydrogenation process. (ii) By introducing low-coordination sites into Fe and combining low-coordination sites and surface fluorine to modify Co to optimize the adsorption of intermediates and facilitate H* formation, hydrogenation of nitriles and N-heterocycles with high activity and selectivity is obtained. (iii) By forming isolated Pd sites to induce a specific σ-alkynyl adsorption of alkynes and steering S vacancies of Co3S4-x to preferentially adsorb -NO2, hydrogenation of easily reduced group-decorated alkynes and nitroarenes with high chemoselectivity is realized. (iv) For gas reactant participated reactions, by designing hydrophobic gas diffusion layer-supported ultrasmall Cu nanoparticles to enhance mass transfer, improve H2O activation, inhibit H2 formation, and decrease ethylene adsorption, ampere-level ethylene production with a 97.7% FE is accomplished. Finally, we provide an outlook on the current challenges and promising opportunities in this area. We believe that the electrode selection principles summarized here provide a paradigm for designing highly active and selective nanomaterials to achieve electrocatalytic hydrogenation and other organic transformations with fascinating performances.

Descriptor-Based Volcano Relations Predict Single Atoms for Hydroxylamine Electrosynthesis.

Hydroxylamine (NH2OH) is an important feedstock in fuels, pharmaceuticals, and agrochemicals. Nanostructured electrocatalysts drive green electrosynthesis of hydroxylamine from nitrogen oxide species in water. However, current electrocatalysts still suffer from low selectivity and manpower-consuming trial-and-error modes, leaving unclear selectivity/activity origins and a lack of catalyst design principles. Herein, we theoretically analyze key determinants of selectivity/activity and propose the adsorption energy of NHO (Gad(*NHO)) as a performance descriptor. A weak *NH2OH binding affinity and a favorable reaction pathway (*NHO pathway) jointly enable single-atom catalysts (SACs) with superior NH2OH selectivity. Then, an activity volcano plot of Gad(*NHO) is established to predict a series of SACs and discover Mn SACs as optimal electrocatalysts that exhibit pH-dependent activity. These theoretical prediction results are also confirmed by experimental results, rationalizing our Gad(*NHO) descriptor. Furthermore, Mn-Co geminal-atom catalysts (GACs) are predicted to optimize Gad(*NHO) and are experimentally proved to enhance NH2OH formation.

Preferential Adsorption of Ethylene Oxide on Fe and Chlorine on Ni Enabled Scalable Electrosynthesis of Ethylene Chlorohydrin.

Industrial manufacturing of ethylene chlorohydrin (ECH) critically requires excess corrosive hydrochloric acid or hypochlorous acid with dealing with massive by-products and wastes. Here we report a green and efficient electrosynthesis of ECH from ethylene oxide (EO) with NaCl over a NiFe2 O4 nanosheet anode. Theoretical results suggest that EO and Cl preferentially adsorb on Fe and Ni sites, respectively, collaboratively promoting the ECH synthesis. A Cl radical-mediated ring-opening process is proposed and confirmed, and the key Cl and carbon radical species are identified by high-resolution mass spectrometry. This strategy can enable scalable electrosynthesis of 185.1 mmol of ECH in 1 h with 92.5 % yield at a 55 mA cm-2 current density. Furthermore, a series of other chloro- and bromoethanols with good to high yields and paired synthesis of ECH and 4-amino-3,6-dichloropyridine-2-carboxylicacid via respectively loading and unloading Cl are achieved, showing the promising potential of this strategy.

σ-Alkynyl Adsorption Enables Electrocatalytic Semihydrogenation of Terminal Alkynes with Easy-Reducible/Passivated Groups over Amorphous PdSx Nanocapsules.

Highly chemo- and regioselective semihydrogenation of alkynes is significant and challenging for the synthesis of functionalized alkenes. Here, a sequential self-template method is used to synthesize amorphous palladium sulfide nanocapsules (PdSx ANCs), which enables electrocatalytic semihydrogenation of terminal alkynes in H2O with excellent tolerance to easily reducible groups (e.g., C-I/Br/Cl, C═O) and the metal center deactivating skeletons (e.g., quinolyl, carboxyl, and nitrile). Mechanistic studies demonstrate that specific σ-alkynyl adsorption via terminal carbon and negligible alkene adsorption on isolated Pd2+ sites ensure successful synthesis of various alkenes with outstanding time-irrelevant selectivity in a wide potential range. The key hydrogen and carbon radical intermediates are validated by electron paramagnetic resonance and high-resolution mass spectrometry. Gram-scale synthesis of 4-bromostyrene and expedient preparation of deuterated alkene precursors and drugs with D2O show promising applications. Impressively, PdSx ANCs can be applied to the prevailing thermocatalytic semihydrogenation of functionalized alkyne using H2.

Scalable Electrosynthesis of Formamide through C-N Coupling at the Industrially Relevant Current Density of 120†mA cm-2.

The scalable and durable electrosynthesis of high-valued organonitrogen compounds from carbon- and nitrogen-containing small molecules, especially operating at a high current density, is highly desirable. Here, a one-pot electrooxidation method to synthesize formamide (HCONH2 ) from methanol and ammonia over a commercial boron-doped diamond (BDD) catalyst is reported. The formamide selectivity from methanol and formamide Faradaic efficiency (FE HCONH 2 ${{_{{\rm HCONH}{_{2}}}}}$ ) achieve 73.2 % and 41.2 % at the current density of 120 mA cm-2 with high durability. The C-N bond originates from the nucleophilic attack of ammonia on an aldehyde-like intermediate. Impressively, an 8 L electrolyzer is employed for the pilot plant test over a 2200 cm2 BDD electrode, which exhibits 33.5 % FE HCONH 2 ${{_{{\rm HCONH}{_{2}}}}}$ at 120 mA cm-2 (current: 264 A) with a yield rate of 36.9 g h-1 , demonstrating the potential of this technique for large-scale electrosynthesis of formamide.

Integrating Hydrogen Production and Transfer Hydrogenation with Selenite Promoted Electrooxidation of α-Nitrotoluenes to E-Nitroethenes.

Developing an electrochemical carbon-added reaction with accelerated kinetics to replace the low-value and sluggish oxygen evolution reaction (OER) is markedly significant to pure hydrogen production. Regulating the critical steps to precisely design electrode materials to selectively synthesize targeted compounds is highly desirable. Here, inspired by the surfaced adsorbed SeOx 2- promoting OER, NiSe is demonstrated to be an efficient anode enabling α-nitrotoluene electrooxidation to E-nitroethene with up to 99 % E selectivity, 89 % Faradaic efficiency, and the reaction rate of 0.25 mmol cm-2 h-1 via inhibiting side reactions for energy-saving hydrogen generation. The high performance can be associated with its in situ formed NiOOH surface layer and absorbed SeOx 2- via Se leaching-oxidation during electrooxidation, and the preferential adsorption of two -NO2 groups of intermediate on NiOOH. A self-coupling of α-carbon radicals and subsequent elimination of a nitrite molecule pathway is proposed. Wide substrate scope, scale-up synthesis of E-nitroethene, and paired productions of E-nitroethene and hydrogen or N-protected aminoarenes over a bifunctional NiSe electrode highlight the promising potential. Gold also displays a similar promoting effect for α-nitrotoluene transformation like SeOx 2- , rationalizing the strategy of designing materials to suppress side reactions.

Selective Transfer Semihydrogenation of Alkynes with H2 O (D2 O) as the H (D) Source over a Pd-P Cathode.

We reported a selective semihydrogenation (deuteration) of numerous terminal and internal alkynes using H2 O (D2 O) as the H (D) source over a Pd-P alloy cathode at a lower potential. P-doping caused the enhanced specific adsorption of alkynes and the promoted intrinsic activity for producing adsorbed atomic hydrogen (H*ads ) from water electrolysis. The semihydrogenation of alkynes could be accomplished at a lower potential with up to 99 % selectivity and 78 % Faraday efficiency of alkene products, outperforming pure Pd and commercial Pd/C. This electrochemical semihydrogenation of alkynes might proceed via a H*ads addition pathway rather than a proton-coupled electron transfer process. The decreased amount of H*ads at a lower potential and the more preferential adsorption of the Pd-P to C≡C π bond than C=C moiety resulted in the excellent alkene selectivity. This method was capable of producing mono-, di-, and tri-deuterated alkenes with up to 99 % deuterium incorporation.

Electrocatalytic Deuteration of Halides with D2 O as the Deuterium Source over a Copper Nanowire Arrays Cathode.

Precise deuterium incorporation with controllable deuterated sites is extremely desirable. Here, a facile and efficient electrocatalytic deuterodehalogenation of halides using D2 O as the deuteration reagent and copper nanowire arrays (Cu NWAs) electrochemically formed in situ as the cathode was demonstrated. A cross-coupling of carbon and deuterium free radicals might be involved for this ipso-selective deuteration. This method exhibited excellent chemoselectivity and high compatibility with the easily reducible functional groups (C=C, C≡C, C=O, C=N, C≡N). The C-H to C-D transformations were achieved with high yields and deuterium ratios through a one-pot halogenation-deuterodehalogenation process. Efficient deuteration of less-active bromide substrates, specific deuterium incorporation into top-selling pharmaceuticals, and oxidant-free paired anodic synthesis of high-value chemicals with low energy input highlighted the potential practicality.

Divergent Chemistry Paths for 3D and 1D Metallo-Covalent Organic Frameworks (COFs).

The marriage of dynamic covalent chemistry (DCC) and coordination chemistry is a powerful tool for assembling complex architectures from simple building units. Recently, the synthesis of woven covalent organic frameworks (COFs) with topologically fascinating structures has been achieved using this approach. However, the scope is highly limited and there is a need to discover new pathways that can assemble covalently linked organic threads into crystalline frameworks. Herein, we have identified branching pathways leading to the assembly of three-dimensional (3D) woven COFs or one-dimensional (1D) metallo-COFs (mCOFs), where the mechanism is underpinned by the absence or presence of ligand exchange.

Efficient Electrosynthesis of Syngas with Tunable CO/H2 Ratios over Znx Cd1-x S-Amine Inorganic-Organic Hybrids.

Efficient electrochemical reduction of CO2 and H2 O into industrial syngas with tunable CO/H2 ratios, especially integrated with anodic organic synthesis to replace the low-value oxygen evolution reaction (OER), is highly desirable. Here, integration of controllable partial substitution of zinc (Zn) with amine incorporation into CdS-amine inorganic-organic hybrids is used to generate highly efficient electrocatalysts for synthesizing syngas with tunable CO/H2 ratios (0-19.7), which are important feedstocks for the Fischer-Tropsch process. Diethylenetriamine could enhance the adsorption and accelerate the activation of CO2 to form the key intermediate COOH* for CO formation. Zn substitution promoted the hydrogen evolution reaction (HER), leading to tunable CO/H2 ratios. Importantly, syngas and dihydroisoquinoline can be simultaneously synthesized by pairing with anodic semi-oxidation of tetrahydroisoquinoline in a Znx Cd1-x S-Amine ∥ Ni2 P two-electrode electrolyzer.

Integrating Hydrogen Production with Aqueous Selective Semi-Dehydrogenation of Tetrahydroisoquinolines over a Ni2 P Bifunctional Electrode.

Exploring an alternative anodic reaction to produce value-added chemicals with high selectivity, especially integrated with promoted hydrogen generation, is desirable. Herein, a selective semi-dehydrogenation of tetrahydroisoquinolines (THIQs) is demonstrated to replace the oxygen evolution reaction (OER) for boosting H2 evolution reaction (HER) in water over a Ni2 P nanosheet electrode. The value-added semi-dehydrogenation products, dihydroisoquinolines (DHIQs), can be selectively obtained with high yields at the anode. The controllable semi-dehydrogenation is attributed to the in situ formed NiII /NiIII redox active species. Such a strategy can deliver a variety of DHIQs bearing electron-withdrawing/donating groups in good yields and excellent selectivities, and can be applied to gram-scale synthesis. A two-electrode Ni2 P bifunctional electrolyzer can produce both H2 and DHIQs with robust stability and high Faradaic efficiencies at a much lower cell voltage than that of overall water splitting.

Boosting Hydrogen Production by Anodic Oxidation of Primary Amines over a NiSe Nanorod Electrode.

For electrocatalytic water splitting, the sluggish anodic oxygen evolution reaction (OER) restricts the cathodic hydrogen evolution reaction (HER). Therefore, developing an alternative anodic reaction with accelerating kinetics to produce value-added chemicals, especially coupled with HER, is of great importance. Now, a thermodynamically more favorable primary amine (-CH2 -NH2 ) electrooxidation catalyzed by NiSe nanorod arrays in water is reported to replace OER for enhancing HER. The increased H2 production can be obtained at cathode; meanwhile, a variety of aromatic and aliphatic primary amines are selectively electrooxidized to nitriles with good yields at the anode. Mechanistic investigations suggest that NiII /NiIII may serve as the redox active species for the primary amines transformation. Hydrophobic nitrile products can readily escape from aqueous electrolyte/electrode interface, avoiding the deactivation of the catalyst and thus contributing to continuous gram-scale synthesis.

Graphene-Oxide-Catalyzed Direct CH-CH-Type Cross-Coupling: The Intrinsic Catalytic Activities of Zigzag Edges.

The development of graphene oxide (GO)-based materials for C-C cross-coupling represents a significant advance in carbocatalysis. Although GO has been used widely in various catalytic reactions, the scope of reactions reported is quite narrow, and the relationships between the type of functional groups present and the specific activity of the GO are not well understood. Herein, we explore CH-CH-type cross-coupling of xanthenes with arenes using GO as real carbocatalysts, and not as stoichiometric reactants. Mechanistic studies involving molecular analogues, as well as trapped intermediates, were carried out to probe the active sites, which were traced to quinone-type functionalities as well as the zigzag edges in GO materials. GO-catalyzed cross-dehydrogenative coupling is operationally simple, shows reusability over multiple cycles, can be conducted in air, and exhibits good functional group tolerance.

Salicylideneanilines-Based Covalent Organic Frameworks as Chemoselective Molecular Sieves.

Porous materials such as covalent organic frameworks (COFs) are good candidates for molecular sieves due to the chemical diversity of their building blocks, which allows fine-tuning of their chemical and physical properties by design. Tailored synthesis of inherently functional building blocks can generate framework materials with chemoresponsivity, leading to controllable functionalities such as switchable sorption and separation. Herein, we demonstrate a chemoselective, salicylideneanilines-based COF (SA-COF), which undergoes solvent-triggered tautomeric switching. This is unique compared to solid-state salicylideneanilines' counterpart, which typically requires high energy input such as photo or thermal activation to trigger the enol-keto tautomerisim and cis-trans isomerization. Accompanying the tautomerization, the ionic properties of the COF can be tuned reversibly, thus forming the basis of size-exclusion, selective ionic binding or chemoseparation in SA-COF demonstrated in this work.

Facile Access to Fluoroaromatic Molecules by Transition-Metal-Free C-F Bond Cleavage of Polyfluoroarenes: An Efficient, Green, and Sustainable Protocol.

The creation of new bonds via C-F bond cleavage of polyfluoroarenes has proven to be an important and powerful tool in synthetic chemistry. Using such a strategy, a myriad of valuable partially fluoroaromatic molecules and building blocks can be obtained. The transition-metal-free nucleophilic aromatic substitution (SN Ar) strategy has aroused the continuing interest of researchers due to its simple, mild, economical, and environmentally benign characteristics, which have been successfully applied to C-F bond functionalizations. In this account, we present a summary of the recent investigations of polyfluoroarenes involving SN Ar reactions and discuss some of our recent endeavors in the construction of partially fluoroaromatic molecules. Through this strategy, many new bonds including C-C, C-N, C-O, C-S, and C-H bonds can be created. Additionally, brief discussions on the transformation mechanisms are also provided. Finally, we discuss the existing limitations of the SN Ar reactions of polyfluoroarenes as well as our perspective on the future development of this chemistry.

Microenvironment regulation breaks the Faradaic efficiency-current density trade-off for electrocatalytic deuteration using D2O.

The high Faradaic efficiency (FE) of the electrocatalytic deuteration of organics with D2O at a large current density is significant for deuterated electrosynthesis. However, the FE and current density are the two ends of a seesaw because of the severe D2 evolution side reaction at nearly industrial current densities. Herein, we report a combined scenario of a nanotip-enhanced electric field and surfactant-modified interface microenvironment to enable the electrocatalytic deuteration of arylacetonitrile in D2O with an 80% FE at -100 mA cm-2. The increased concentration with low activation energy of arylacetonitrile due to the large electric field along the tips and the accelerated arylacetonitrile transfer and suppressed D2 evolution by the surfactant-created deuterophobic microenvironment contribute to breaking the trade-off between a high FE and large current density. Furthermore, the application of our strategy in other deuteration reactions with improved Faradaic efficiencies at -100 mA cm-2 rationalizes the design concept.

Electrochemical hydrogenation and oxidation of organic species involving water.

Fossil fuel-driven thermochemical hydrogenation and oxidation using high-pressure H2 and O2 are still popular but energy-intensive CO2-emitting processes. At present, developing renewable energy-powered electrochemical technologies, especially those using clean, safe and easy-to-handle reducing agents and oxidants for organic hydrogenation and oxidation reactions, is urgently needed. Water is an ideal carrier of hydrogen and oxygen. Electrochemistry provides a powerful route to drive water splitting under ambient conditions. Thus, electrochemical hydrogenation and oxidation transformations involving water as the hydrogen source and oxidant, respectively, have been developed to be mild and efficient tools to synthesize organic hydrogenated and oxidized products. In this Review, we highlight the advances in water-participating electrochemical hydrogenation and oxidation reactions of representative organic molecules. Typical electrode materials, performance metrics and key characterization techniques are firstly introduced. General electrocatalyst design principles and controlling the microenvironment for promoting hydrogenation and oxygenation reactions involving water are summarized. Furthermore, paired hydrogenation and oxidation reactions are briefly introduced before finally discussing the challenges and future opportunities of this research field.

Alkynes Electrooxidation to α,α-Dichloroketones in Seawater with Natural Chlorine Participation via Competitive Reaction Inhibition and Tip-Enhanced Reagent Concentration.

The traditional synthesis of α,α-dichloroketones usually requires corrosive chlorine, harsh reaction conditions, or excessive electrolytes. Here, we report an electrooxidation strategy of ethynylbenzenes to α,α-dichloroketones by directly utilizing seawater as the chlorine source and electrolyte solution without an additional supporting electrolyte. High-curvature NiCo2O4 nanocones are designed to inhibit competitive O2 and Cl2 evolution reactions and concentrate Cl- and OH- ions, accelerating α,α-dichloroketone electrosynthesis. NiCo2O4 nanocones produce 81% yield, 61% Faradaic efficiency, and 44.2 mmol gcat.-1 h-1 yield rate of α,α-dichloroketones, outperforming NiCo2O4 nanosheets. A Cl• radical triggered Cl• and OH• radical addition mechanism is revealed by a variety of radical-trapping and control experiments. The feasibility of a solar-powered electrosynthesis system, methodological universality, and extended synthesis of α,α-dichloroketone-drug blocks confirm its practical potential. This work may provide a sustainable solution to the electrocatalytic synthesis of α,α-dichloroketones via the utilization of seawater resources.

Aqueous pulsed electrochemistry promotes C-N bond formation via a one-pot cascade approach.

Electrocatalytic C - N bond formation from inorganic nitrogen wastes is an emerging sustainable method for synthesizing organic amines but is limited in reaction scope. Integrating heterogeneous and homogeneous catalysis for one-pot reactions to construct C - N bonds is highly desirable. Herein, we report an aqueous pulsed electrochemistry-mediated transformation of nitrite and arylboronic acids to arylamines with high yields. The overall process involves nitrite electroreduction to ammonia over a Cu nanocoral cathode and subsequent coupling of NH3 with arylboronic acids catalyzed by in situ dissolved Cu(II) under a switched anodic potential. This pulsed protocol also promotes the migration of nucleophilic ArB(OH)3- and causes the consumption of OH- near the cathode surface, accelerating C - N formation and suppressing phenol byproducts. Cu(II) can be recycled via facile electroplating. The wide substrate scope, ready synthesis of 15N-labelled arylamines, and methodological expansion to cycloaddition and Click reactions highlight the great promise.