Selective Synthesis Research Articles

Synthesis and Properties of N,O‐Doped Aceanthrylenes

AbstractN,O‐doped aceanthrylenes have been synthesized for the first time via a selective SNAr reaction or Ullmann‐coupling of phenols, followed by an intramolecular direct arylation. The reaction has been carefully optimized and permits the selective synthesis of N,O‐doped aceanthrylenes in moderate to excellent yields and tolerate various functional groups. The aromatic behavior of the hitherto unknown heterocyclic scaffold has been further analyzed by NICS and NICS2BC calculations.

Advancements in transition metal-catalyzed 1,2,3-triazole synthesis via azide–alkyne cycloaddition

Abstract 1,2,3-triazoles have emerged as important structural motifs in chemical biology, attracting increasing focus in recent years because of their wide range of uses. These compounds can be efficiently synthesized using click reactions. Its versatility makes it valuable in drug discovery and materials science. Significant advancements have been made in recent years in the process of making 1,2,3-triazoles, reflecting the growing curiosity and investment in the area of research. The catalytic performance of transition metals Cu, Ir, Rh, Ru, Ni, Pd, Au, Ag, and Zn, which were used as ligands and salts in the azide–alkyne cycloaddition method of 1,2,3-triazole synthesis, has been covered in this review. Cu-complexes and salts were found to be more effective for selective synthesis among all transition metals. Furthermore, it is determined that some azide–alkyne reactions are entirely catalytic in nature and cannot be carried out as such by switching transition metals.

Catalytic Strategies for the Selective Synthesis of α‐ and β‐Functionalized Amines via Hydrofunctionalization of Enamides

Abstractα‐ and β‐Functionalized amines are two classes of important compounds, whose structural units are widely present in approved drugs. The hydrofunctionalization of enamides is the most direct and efficient method for constructing these two types of compounds. Regioselectivity is the focus of this conversion, and is largely influenced by the catalytic mode. Therefore, to selectively synthesize α‐ or β‐functionalized amines, the progress in the catalytic hydrofunctionalization of enamides over the past decade is reviewed, and the catalytic pathways for this process discussed in detail. This account aims to objectively evaluate the effects of various catalytic pathways on the regioselectivity of hydrofunctionalization, to provide a new perspective on the selection of catalytic methods and the design of catalytic pathways for the selective synthesis of α‐ or β‐functionalized amines.

Selective electrosynthesis of hydroxylamine from aqueous nitrate/nitrite by suppressing further reduction.

The electrocatalytic reduction of nitrogenous waste offers a sustainable approach to producing nitrogen-containing chemicals. The selective synthesis of high-value hydroxylamine (NH2OH) is challenging due to the instability of NH2OH as an intermediate. Here, we present a rational electrocatalyst design strategy for promoting NH2OH electrosynthesis by suppressing the competing pathways of further reduction. We screen zinc phthalocyanines (ZnPc) with a high energy barrier for NH2OH reduction by regulating their intrinsic activity. Additionally, we discover that carbon nanotube substrates exhibit significant NH3-producing activity, which can be effectively inhibited by the high coverage of ZnPc molecules. In-situ characterizations reveal that NH2OH and HNO are generated as intermediates in nitrate reduction to NH3, and NH2OH can be enriched in the ZnPc electrode. In the H-cell, the optimized ZnPc catalyst demonstrates a Faradaic efficiency (FE) of 53 ± 1.7% for NH2OH with a partial current density exceeding 270 mA cm-2 and a turnover frequency of 7.5 ± 0.2 s-1. It also enables the rapid electrosynthesis of cyclohexanone oxime from nitrite with a FE of 64 ± 1.0%.

Selective Access to 2‐Phenylquinazolin‐4(3H)‐Ones and 2,3‐Dihydroquinazolin‐4(1H)‐Ones from Same Precursors in Organic Salts Derived DES

AbstractA binary mixture of organic salts, also known as ionic liquids, [C12mim][Br]:[MPIM][HCOO] denoted as BmIL1 has been explored as bifunctional catalyst for the selective synthesis of 2‐phenylquinazolin‐4(3H)‐ones and 2,3‐dihydroquinazolin‐(1H)‐ones from same precursors under metal, ligand and additive free conditions. The methodology has been extended to the synthesis of 2‐phenylquinazolin‐4(3H)‐ones via another pathway from different precursors under the same catalytic system. Greener synthesis of existing drugs reestablished the multifunctionality of BmIL1. Gram scale synthesis of both the products, DFT calculations and sc‐XRD data add significance to the developed protocol. Moreover, high atom economy and eco score values justify the sustainability of the methodology.

Selective synthesis of fluorescent metal nanoclusters over metal nanoparticles.

Metal nanoparticles and nanoclusters are pivotal in nanomaterial science, each offering unique properties for diverse applications. Nanoclusters, typically smaller than 2nm, exhibit distinct optical and electronic characteristics due to quantum confinement, resulting in fluorescence emission. In contrast, metal nanoparticles, sized between 2 and 100nm, exhibit absorption spectra. Both are synthesized by reducing metal precursors in the presence of a suitable stabilizing agent. While nanoparticles have been the historical research focus, recent attention has shifted to nanoclusters for their exceptional properties and their synthesis has evolved significantly over the past few decades. This review discusses the selective synthesis of nanoclusters over nanoparticles, emphasizing the role of various factors such as ligand concentration(metal-to-ligand ratio), reducing agents, pH,reactiontime and temperature, solvents, and assistant reagents. Higher ligand concentrations stabilize smaller nanoclusters by preventing aggregation, while lower concentrations lead to larger nanoparticles. Stronger reducing agents produce smaller, more uniform particles, whereas weaker reducingagents yield larger ones. pH affects nanocluster size and emission properties. Solvents and assistant reagents influence reaction kinetics and material properties. Temperature and reaction time also play critical roles in controlling nanocluster size and properties. These insights guide the optimized synthesis of metal nanoclusters, for their specific applications.

Inhibition of Kornblum Reaction with Lithium Salts in SN2 Reactions of Sulfonates and a Nucleophile Containing a Pyridine N-Oxide Moiety: Convergent and Selective Synthesis of an MRGPRX2 Antagonist.

A critical step in the development of a convergent synthesis of an MRGPRX2 antagonist (1) was the SN2 reaction with a highly functionalized lactamide electrophile and a unique difluoropiperidine nucleophile containing a pyridine N-oxide moiety. Initial reactions with sulfonate leaving groups exhibited superb stereoselectivity, but yields were very low due to side reactions originated from competitive Kornblum reactions of the pyridine N-oxide and the sulfonates. Markedly improved reaction profiles were achieved by including stoichiometric lithium triflate. NMR data provided insights into how the lithium cation impacted the pyridine N-oxide through coordination and attenuating its nucleophilicity, leading to the inhibition of the undesired Kornblum reactions. Our approach is highly relevant to preservation of the N-oxide, a structural motif known to several marketed products and emerging as an important class in drug discovery in nucleophilic substitutions. Application of this method enabled the production of the target (1 and its HCl salt 1a) up to multikilogram scale with high selectivity and in much improved yield.

Divergent Regioselective Synthesis of Functionalized 1,2,3-1H-Triazoles from Nitriles and Arylazides Under Metal-Free and/or Solvent-Free Conditions.

Highly selective and divergent syntheses, which are crucial in both organic synthesis and medicinal chemistry, involve significant advancements in compound accessibility. By modifying α-cyano esters into α-cyano ketones, the synthesis pathway broadens to include a diverse range of 4-CN, 5-amino, and 5-arylamino derivatives of 1,2,3-triazoles, which are achieved notably through the Dimroth rearrangement. This versatility extends further with the potential for a triple cascade reaction, leading to the production of carboximidamide compounds, which are facilitated by the Cornforth rearrangement. Advancements in compound accessibility not only expand the repertoire of synthesized molecules but also open new avenues for potential pharmacological agents. Building on these findings, we have developed an innovative and efficient method for the divergent synthesis of functionalized 1,2,3-triazoles. This method strategically utilizes α-cyanocarbonyls and arylazides by harnessing their reactivity and compatibility to orchestrate a variety of molecular transformations. By optimizing these substrates, our goal is to simplify synthetic routes, improve product yields, and accelerate the discovery and development of new chemical entities with promising biological activities.

Electrochemical carboxylation: Green synthesis of atrolactic acid using boron-doped diamond electrodes

Electrochemical CO2 fixation is vital for sustainability in the chemical industry, yet the selective synthesis of multi-carbon products remains challenging. Organic electrosynthesis offers promise by enabling precise control over reaction conditions and facilitating novel reactivity patterns. One such technique, electrochemical carboxylation, involves coupling CO2 with organic molecules to produce carboxylic acids. Specifically, electro-carboxylation of acetophenone yields atrolactic acid, a valuable precursor for nonsteroidal anti-inflammatory drugs, providing a greener alternative to traditional production methods. This study focuses on the synthesis and characterization of boron-doped diamond (BDD) films using the microwave plasma-assisted chemical vapor deposition (MP-CVD) method and synthesized BDD electrodes were then used for the electrolytic carboxylation of acetophenone. Various analytical techniques, including X-ray diffraction (XRD), Raman spectroscopy, and laser microscopy, etc. were employed to characterize the BDD films. Various BDD films synthesized for different durations were utilized in the electrolytic carboxylation of acetophenone, with the highest yield of atrolactic acid (25 %) achieved using a BDD film synthesized over 6 h. Also, the effect of BDD surface modification i.e. oxygen and hydrogen terminated BDD on the synthesis of atrolactic acid was studied. Additionally, different electrolytes were employed in the synthesis process of atrolactic acid. A comparative study between Pt and BDD electrodes for the electrolytic carboxylation of acetophenone was conducted, and a mechanism for the formation of atrolactic acid was proposed.

Steering the reaction kinetics of the MgO-V2O5 system toward selective synthesis of magnesium vanadates

Magnesium vanadates (MgV2O6, Mg2V2O7 and Mg3V2O8) are common redox catalysts for organic reactions and excellent energy storage materials. However, due to the diversity of magnesium vanadates and their interconvertibility, it is difficult to accurately synthesize a species of magnesium vanadate or control its stability during functioning. Herein, the reaction kinetics of MgO-V2O5 system was studied for controllable synthesis of magnesium vanadates. The MgO-V2O5 diffusion couples were prepared to explore the interface reaction characteristics of the MgO-V2O5 system at different reaction time. During reaction, the thickness of the diffusion layer and diffusion coefficient gradually increased and reached a maximal value of 29.55 μm and 6.06×10-11 cm2·s−1 at 10 h, which diffusion is faster than that of CaO-V2O5 system. Additionally, the interconvertible mechanisms of different magnesium vanadates were investigated using XRD and SEM/EDS techniques. MgV2O6 was produced during the synthesis of Mg2V2O7 in the initial 4 h, which converted into Mg2V2O7 at a longer synthesis time. Mg2V2O7 was found during the generation process of Mg3V2O8; with abundant MgO, Mg2V2O7 converted into Mg3V2O8. These findings provide important insights into the accurate control of magnesium vanadate synthesis and even the vanadium extraction process.

Selective Synthesis of Dihydro- and Dehydrogenated Spirocyclopenta[b]indoles via Acid-modulated [3+2] Cycloaddition Reaction

Selective Synthesis of Dihydro- and Dehydrogenated Spirocyclopenta[b]indoles via Acid-modulated [3+2] Cycloaddition Reaction

Iterative Catalyst-Controlled Diastereoselective Matteson Homologations Enable the Selective Synthesis of Benzestrol Isomers.

We report the development of an iterative Matteson homologation reaction with catalyst-controlled diastereoselectivity through the design of a new catalyst. This reaction was applied to the selective synthesis of each stereoisomer of benzestrol, a bioactive compound with estrogenic activity featuring three contiguous stereocenters. The different stereoisomers were assayed to determine their binding affinity for the estrogen receptor α (ERα), and the absolute configuration of the compound having uniquely high activity was determined. This research lays a framework for the catalytic synthesis and study of complete stereoisomeric sets of other bioactive molecules and chemical probes containing contiguous stereocenters.

Highly Efficient and Selective Electrocatalytic Semihydrogenation of Acetylene to Ethylene via Continuous Proton Feeding and Accelerated Transfer on Cu NP/FeNC Composite

AbstractElectrocatalytic hydrogenation of acetylene to ethylene in aqueous electrolytes under ambient conditions faces efficiency and selectivity limitation due to the competitive formation of 1,3‐butadiene and hydrogen. In this study, the development of a copper nanoparticle/FeNC composite catalyst is reported through a simple mechanical grinding approach that demonstrates remarkable performance, achieving a highest ethylene Faradaic efficiency of 97.7% at 180 mA cm−2 and selectivity of 92.6% at 200 mA cm−2. Experimental investigations reveal that Cu atoms serve as the active sites, and the integration of FeNC improves the specific surface area through its 2D nanosheet morphology. Further analysis utilizing in situ Raman measurements coupled with theoretical calculations confirms that FeNC accelerates water dissociation to provide abundant protons and improving their transfer, thereby suppressing 1,3‐butadiene formation and elevating acetylene selectivity. Notably, the integration of FeNC also transforms the desorption of *C2H4 into an exothermic process, further facilitating ethylene production. Overall, this study introduces a simple and innovative preparation approach of composite catalysts for selective ethylene synthesis, expanding the application scope of Cu‐based FeNC materials in various electrocatalytic hydrogenation reactions.

Highly Efficient and Selective Synthesis of Renewable Isoprene Over Mo-Fe-O and MgO/Mg(OH)2 Composite Catalysts.

Synthesis of renewable isoprene continues to attract significant interest, yet catalysts still need improvement for industrial applications. We report herein an efficient and novel Prins tandem approach for highly selective production of isoprene from bio-based methanol and isobutene over Mo-Fe-O and MgO/Mg(OH)2 acid-base bifunctional catalysts. Hydration decreases the number of strong basic sites O2- ions and increases OH groups over MgO, thus improving the isoprene selectivity. Basic OH on Mg(OH)2 promotes the Prins condensation of formaldehyde and isobutene, while acidic OH promotes dehydration of isoprenol to isoprene. Suitable contents and proportions of basic and acidic OH groups over Mg(OH)2 increase isoprene selectivity and methanol conversion to 90 and 92 % on the Mo-Fe-O+Mg(OH)2 composite catalysts, respectively. It exhibits good recycling stability, with isoprene selectivity remaining 90 % after five successive regenerations. DFT calculations reveal OH groups formed after hydration reduce the energy barrier of the H transfer step, thereby promoting the overall reaction.

Alkylsulfonic acid functionalized aluminoborate: A highly efficient and regioselective solid acid catalyst for ring-opening addition of epoxide under solvent-free condition

Functionalized solid acid material has more accessible active surface and therefore is usually considered as an important substitute for conventional liquid mineral acid. In this work, a novel alkylsulfonic acid functionalized porous aluminoborate molecular sieve (PKU-1) has been prepared through 3-step post-synthetic method, and the high-density acidic sites were tailored and comprehensively characterized by various measurements. These acidity-controllable active sites exhibit high activity and specific regioselectivity towards alcoholysis reaction for the solvent-free production of methoxyl alcohol, and turnover frequency reaches ∼1000 h–1, which is much superior to previous reports. Comprehensive characterizations indicate catalytic centers exclusively come from –SO3H acid sites, rather than other type of Brönsted or Lewis acid sites. A plausible reaction mechanism was proposed to interpret the key role of –SO3H active sites on alcoholysis reaction based on the related experimental results. This work offers a promising solution to generate the controllable acidity and provides an available candidate in the environmentally benign catalysis for selective synthesis of some value-added compounds.

The Reaction of Fenchone and Camphor Hydrazones with 5-Acyl-4-Pyrones as a Method for the Synthesis of New Polycarbonyl Conjugates: Tautomeric Equilibrium and Antiviral Activity.

Selective synthesis of polycarbonyl conjugates of (+)-fenchone and (+)-camphor was carried out (44-91 % yields) via the ring-opening transformation of 5-acyl-4-pyrones with hydrazones of the corresponding monoterpenoids. A strong influence of the hydrazone fragment on the observed tautomeric equilibrium of the tricarbonyl system was shown. Although the major tautomer of the conjugates is the acyclic polycarbonyl form, the camphor-based conjugates undergo new type of ring-chain tautomerism, diketoenaminone-dihydropyridone equilibrium, and predominantly exist in the cyclic dihydropyridone form in DMSO-d6. The polyketones can undergo intramolecular cyclization to form N-amino-4-pyridones in high selectivity. In vitro screening for activity against the influenza virus H1 N1 and vaccinia virus was estimated for the obtained conjugates. The (+)-fenchone derivatives demonstrated the higher activity against vaccinia virus than camphor derivatives. The conjugate, which was prepared from diethyl isochelidonate and hydrazone (+)-fenchone, showed the highest activity against vaccinia virus (SI=17).

Regio-, Site- and Stereo-Selective Aziridination of Conjugated Dienes Enabled by Palladium/Copper/Iodide/Oxygen Cooperation.

Vinylaziridines are important building blocks in organic chemistry, especially in the synthesis of nitrogen-containing heterocycles. The direct and efficient transfer of an appropriate nitrogen source to readily accessible conjugated dienes is a notable methodology. The Pd-catalyzed oxidative 1,2-difunctionalization of conjugated dienes through a π-allyl-palladium species should be an ideal method for the selective synthesis of vinylaziridines. However, this method faces the challenge of regioselectivity, often resulting in 1,4-difunctionalization instead. In this study, we developed a Pd-catalyzed aerobic 1,2-difunctionalization of conjugated dienes via a π-allyl-palladium species to achieve regio-, site- and stereo-selective aziridination under the synergistic effects of Pd(II), Cu(I), I-, and O2. The π-allyl palladium species formed in the system undergoes an unusual iodination process, leading to the formation of an allyl iodide intermediate. Subsequently, the vinylaziridine is obtained through intramolecular SN2' substitution of the allyl iodide.

Design and Preparation of Heterostructured Cu2O/TiO2 Materials for Photocatalytic Applications.

The extensive use of fossil fuels has sped up the global development of the world economy and is accompanied by significant problems, such as energy shortages and environmental pollution. Solar energy, an inexhaustible and clean energy resource, has emerged as a promising sustainable alternative. Light irradiation can be transformed into electrical/chemical energy, which can be used to remove pollutants or transform contaminants into high-value-added chemicals through photocatalytic reactions. Therefore, photocatalysis is a promising strategy to overcome the increasing energy and environmental problems. As is well-known, photocatalysts are key components of photocatalytic systems. Among the widely investigated photocatalysts, titanium dioxide (TiO2) has attracted great attention owing to its excellent light-driven redox capability and photochemical stability. However, its poor solar light response and rapid recombination of electron-hole pairs limit its photocatalytic applications. Therefore, strategies to enhance the photocatalytic activity of TiO2 by narrowing its bandgap and inhibiting the recombination of charges have been widely accepted. Constructing heterojunctions with other components, including cuprous oxide (Cu2O), has especially narrowed the bandgap, providing a promising means of solving the present challenges. This paper reviews the advances in research on heterostructured Cu2O/TiO2 photocatalysts, such as their synthesis methods, mechanisms for the enhancement of photocatalytic performance, and their applications in hydrogen production, CO2 reduction, selective synthesis, and the degradation of pollutants. The mechanism of charge separation and transfer through the Cu2O/TiO2 heterojunctions and the inherent factors that lead to the enhancement of photocatalytic performance are extensively discussed. Additionally, the current challenges in and future perspectives on the use of heterostructured Cu2O/TiO2 photocatalysts are also highlighted.

Stereodivergent atom transfer radical addition of α-functionalized alkyl iodides to alkynes: a strategy for selective synthesis of both E- and Z-iodoalkenes.

The geometrical control of atom transfer radical addition (ATRA) reactions to alkynes poses significant challenges. Herein, we present a uniform solution by developing a stereodivergent synthetic method for both isomers of the resulting alkene products, starting from the same materials. The synthesis of the thermodynamically more stable isomer utilizes the strategy of uphill catalysis while the accumulation of the less stable isomer is facilitated by a manganese-catalyzed iodo-abstraction/radical rebound process, taking advantage of its reversibility. Various substituted alkyl iodides can be used to provide easy access to both isomers of iodoalkene products with valuable functional groups such as CF3, CF2H, CN, ester, or amide at the allylic position.

Ethylene Glycol Mediated, Catalyst-Free Synthesis of Bis(pyrazolo) pyridines and Their Photophysical Studies

AbstractA new hetero-annulation procedure for the selective synthesis of bis(pyrazolo)-fused pyridines using pyrazole-5-amines and aryl glyoxal monohydrate is described. This distinct hetero-annulation, carried out under catalyst-free conditions with ethylene glycol as the medium, illustrates a domino reaction that involves the formation of two C–C bonds and one C–N bond. The photophysical properties of the synthesized derivatives were briefly analyzed. The emission spectra of the derivatives exhibited distinct charge transfer peaks, which depends on the structure of the derivatives. The green metrics calculation for the protocol to quantify the waste, reaction efficiency, and sustainability was evaluated.