Reaction Conditions Research Articles

Dimethyl Sulfoxide Promoted Quinazolinone Synthesis

AbstractAn efficient and one‐step synthesis of quinazolinones using 2‐aminobenzamide and benzylamine in DMSO under external catalyst‐ and base‐free conditions is reported. A broad substrate scope and environment‐benign mild reaction conditions are the major attributes of this straightforward synthesis. Moreover, the synthesized quinazolinone derivatives were used to produce pharmaceutically active rutaecarpine analogues using a two‐step reaction: N‐alkylation followed by intramolecular cyclization.

Ruthenium Complexes of Phenylbenzothiazole‐Quinoline based Ligands for Selective α‐Olefination of Methylazaarenes

This report describes synthesis of a new ligand (E)‐N‐(4‐(benzo[d]thiazol‐2‐yl)phenyl)‐1‐(quinolin‐2‐yl)methanimine (L1) and its three ruthenium(II) arene complexes with [RuCl2(p‐cymene)]2 (C1), [RuCl2(benzene)]2 (C2), and [RuCl2(hmb)]2 [hmb = hexamethylbenzene] (C3). The new ligand and complexes were characterized with the help of standard spectroscopic and analytical techniques like 1H and 13C{1H} Nuclear Magnetic Resonance (NMR), Fourier transform infrared (FTIR), High‐resolution mass spectrometry (HRMS), UV‐Visible, cyclic voltammetry, and elemental analysis. The structure of ruthenium complex (C1) and its binding mode with ligand were authenticated with the help of single crystal X‐ray diffraction. The ruthenium arene complexes (C1‐C3) were used as a catalyst for the α‐olefination of Methylazaarenes. First, methylazaarenes were reacted with alcohols under optimized reaction conditions to produce α‐olefinated products (up to 66%) selectively. Among the three ruthenium complexes, C1 demonstrated the highest yield of olefinated products with 5 mol% catalyst loading. Finally, selected olefin derivatives were tested for their inhibitory potential towards the aggregation of amyloid‐b‐40 (Aβ40) peptide relevant to Alzheimer’s disease. Overall, these complexes are promising catalysts for organic transformations, and the synthesized α‐olefinated derivatives could have potential applications for the development of therapeutic agents for Alzheimer’s disease.

Copper-Catalyzed γ-C(sp3)-H Lactamization and Iminolactonization.

Despite extensive efforts to develop γ-lactamization reactions for pyrrolidinone synthesis using either cyclometallation, C-H insertion, or radical C-H abstraction strategies, γ-lactamization reactions of aliphatic amides using practical catalysts and common protecting groups remain extremely rare. Herein we report copper-catalyzed γ-C(sp3)-H lactamization and iminolactonization of tosyl-protected aliphatic amides using inexpensive Selectfluor as the sole oxidant. A switchable selectivity of γ-Lactams or γ-iminolactones can be obtained by using two different sets of reaction conditions. Notably, structurally diverse spiro-, fused-, and bridged-lactams and iminolactones, as well as isoindolinones are accessible by this method. Further derivatization of the γ-lactam products enables the synthesis of a range of biologically important motifs, including γ-amino acids, δ-amino alcohols, and pyrrolidines.

Detection of Vibrio harveyi through RPA combined with CRISPR/Cas12a: Construction of a new method and comparative study

In this study, recombinase polymerase isothermal amplification (RPA) was combined with clustered regularly interspaced short palindromic repeats/associated proteins (CRISPR/Cas) to establish a new method (RPA-CRISPR/Cas12a) for the detection of Vibrio harveyi. We used RPA to amplify the target DNA of V. harveyi and the RPA amplification product as an activator to initiate CRISPR/Cas12a cleavage of the designed ssDNA reporter probe. Then, we used fluorescence intensity as a criterion for the detection results to optimize the reaction conditions and improve the accuracy of the assay. The ToxR-specific gene sequence of V. harveyi was selected, and 3 sets of RPA primers and 2 sets of gRNA were designed for screening to optimize the ratio of LbCas12a protein, gRNA, and reporter. The specificity, sensitivity and detection of the newly developed method on simulated contaminated samples were analyzed and compared with those of the RPA method, fluorescent loop mediated isothermal amplification (LAMP), and visual LAMP methods. The results showed that the newly constructed method exhibited good specificity and no cross-reactivity with other pathogenic bacteria. Maximum fluorescence values were obtained when the molar concentration ratios of LbCas12a protein to reporter and gRNA were 1:0.8 and 1:8, respectively. The sensitivities of RPA-CRISPR/Cas12a for the detection of V. harveyi were 10−5 ng/μL, respectively, and the sensitivities for the simulated contaminated samples were 7 CFU/mL, respectively. The new RPA-CRISPR/Cas12a method provides a new strategy for the immediate detection of foodborne pathogenic microorganisms.

A Sustainable Approach for Palladium and Phosphane‐Free Sonogashira Type Cross‐Coupling of 2‐Chloroquinoline with Terminal Alkynes

AbstractAn efficient and cost‐effective Cu (I) mediated protocol for the C(sp2)–C(sp) cross‐coupling of 3‐chalcone‐2‐chloroquinoline with terminal alkynes has been disclosed by optimizing a wide range of catalysts, ligands, base, and solvents. This approach conveniently assembles various alkynylated hybrids with excellent to moderate yields. Appropriate functional group tolerance and significant mechanistic pathway with mild reaction conditions well‐justified this synthetic transformation more sustainable towards the greener exploration.

Copper‐Catalyzed γ‐C(sp3)−H Lactamization and Iminolactonization

Despite extensive efforts to develop γ‐lactamization reactions for pyrrolidinone synthesis using either cyclometallation, C−H insertion, or radical C−H abstraction strategies, γ‐lactamization reactions of aliphatic amides using practical catalysts and common protecting groups remain extremely rare. Herein we report copper‐catalyzed γ‐C(sp3)−H lactamization and iminolactonization of tosyl‐protected aliphatic amides using inexpensive Selectfluor as the sole oxidant. A switchable selectivity of γ‐Lactams or γ‐iminolactones can be obtained by using two different sets of reaction conditions. Notably, structurally diverse spiro‐, fused‐, and bridged‐lactams and iminolactones, as well as isoindolinones are accessible by this method. Further derivatization of the γ‐lactam products enables the synthesis of a range of biologically important motifs, including γ‐amino acids, δ‐amino alcohols, and pyrrolidines.

Trifluoroacetic Acid Promotes Umpolung of 2‐Methylindole to Achieve C(sp3)‐H Activation

An umpolung strategy for the C(sp3)‐H aminomethylation of 2‐methylindole has been developed using trifluoroacetic acid to induce the transformation, with aminals serving as precursors of iminium ion. Mechanistic studies have clearly shown that trifluoroacetic acid may play a pivotal role in this strategy. The utilization of readily available starting materials, mild reaction conditions, tolerance to complex functional groups, combine with yields of up to 98% and potential biological applications render this protocol applicable and useful for organic synthesis and medicinal chemistry.

A Facile and Regioselective Synthesis of 2‐Formamidothiazoles via the C−H Formamidation of Thiazole N‐oxides with Isocyanides

A facile, microwave‐promoted, regioselective C−H formamidation of thiazole N‐oxides with isocyanides in the presence of TBDPSCl was developed. Various 2‐(N‐substituted formamido)thiazoles were obtained in moderate to high yields. In the case of the C2‐substituted thiazole N‐oxides, the C‐H formamidation took place selectively at the C4 position of the thiazole ring. This transformation is also applicable to some other N‐containing heterocyclic derivatives such as pyridine, quinoline, and pyridazine N‐oxides and has advantages such as broad substrate tolerance, high regioselectivity, and mild reaction conditions.

Microwave-Assisted Conversion of 5-Hydroxymethylfurfural into 2,5-Furandicarboxylic Acid over CuCo Oxide.

A series of CuCo bimetallic catalysts were prepared via the co-precipitation method for the catalytic transformation of biomass-derived 5-hydroxymethylfurfural (HMF) into 2,5-furandicarboxylic acid (FDCA). FDCA acts as a precursor for biodegradable biopolymer polyethylene furanoate production, thereby achieving a carbon-neutral approach. Out of all the synthesized catalysts, CuCo(1:1) showed remarkable catalytic activity and yielded 70.67% FDCA while achieving 100% HMF conversion in 5 minutes at 50 ℃ temperature in the presence of tert-butyl hydroperoxide as an oxidant. Synergistic effects of the catalyst, such as adsorbed oxygen, relative oxygen vacancy, lesser pore size, and pore volume, were key factors attributed to the catalyst's excellent activity. The synthesized catalyst showed good recyclability with a minimal decrease in FDCA yield up to 5 cycles. Pre and post-characterization of catalysts such as BET, TEM, FE-SEM, XRD, H2-TPR, CO2 TPD, ICP-OES, and XPS were done to correlate the catalyst's properties with its activity. In addition, the effect of reaction parameters such as stirring speed, temperature reaction time, catalyst weight, base, and oxidant was studied to achieve optimum reaction conditions. The reaction products were analyzed quantitatively and qualitatively using HPLC and HR-MS.

Synthesis of Diketopyrrolopyrrole Based Photoactive Materials via Photoredox C−H Activation

AbstractThe synthesis of diketopyrrolopyrrole (DPP) derivatives followed the well‐known conventional cross‐coupling methods such as Suzuki, Stille, Sonogashira, and Negishi cross‐coupling reactions. However, these methods required unfavorable reaction conditions, organometallic precursors, and high temperatures. In addition, the synthesis of conventional cross‐coupling partners including organoboranes, stannane, and acetylenes required drastic reaction conditions and strong bases. In this work, a wide variety of thiophene‐diketopyrrolopyrrole (TDPP)‐based semiconducting materials (36 compounds) were synthesized via Pd‐catalysed photoredox methodology by using N‐hydroxyphthalimide (NHP) based coupling partners, which can be readily prepared from N‐hydroxyphthalimide and carboxylic acid or aldehyde derivatives via single step C−O bond formation reactions with good yield (80–90 %). This methodology minimizes additional synthetic steps, harsh reaction conditions, and high temperature (100–150 °C). Optoelectronic studies suggest that the synthesized materials have suitable band gap, HOMO and LUMO levels for variety of optoelectronic applications. To the best of our knowledge, this is the first report on the synthesis of TDPP‐based π‐conjugated materials via the photoredox method.

Catalytic Conversion of Levulinic Acid over Sn-BTC and Sn-H3-5-SIP Heterogeneous Acid Catalysts

This work presents the synthesis and characterization of materials that contain Sn metal clusters formed by ligands of trimesic acid (Sn-BTC) or 5-sulfobenzene-1,3-dicarboxylic acid (Sn-H3-5-SIP). These catalysts were used to convert levulinic acid with ethanol to produce ethyl levulinate under mild reaction conditions. The characterization results confirmed that Sn is mainly present in the cassiterite crystalline phase with a tetragonal rutile structure in octahedral and tetrahedral coordination in the materials. The assembly of trimesic acid (a hard base) with metal species (Sn) results in the formation of acid and thermally stable metal–organic frameworks. The use of 5-sulfobenzene-1,3-dicarboxylic acid instead of trimesic acid in the synthesis incorporates sulfonic groups in the material, enhancing the total acidity of the Sn-H3-5-SIP catalyst compared to the Sn-BTC material. The Sn-H3-5-SIP catalyst exhibited the highest catalytic activity when converting levulinic acid with ethanol, resulting in a turnover frequency (TOF) of 0.0495 s−1, which is a 50% increase compared to the TOF of the Sn-BTC catalyst (0.0329 s−1). This result can be attributed to its higher concentration of acid sites (2.23 ± 0.05 mmol H+/gcat) and specific area (139 m2/g). Thus, materials containing tin metal clusters and sulfonic groups are promising materials that could be used as catalysts for synthesizing ethyl levulinate under mild reaction conditions.

Enhancing Sustainable Production of Biodiesel from Xanthoceras sorbifolia Bunge Oil Using Bio-Based Heterogeneous Catalyst

The swift exhaustion of natural oil reserves and worsening environmental issues have prompted the quest for an economical method to produce biofuels. The superiority of heterogeneous catalysis promotes the development of bio-based catalysts. Carbon materials prepared from agricultural and forestry biomass waste have good application prospects in catalysis. In the present study, Xanthoceras sorbifolia shell waste was used as the raw material, Xanthoceras sorbifolia Bunge Carbon (XC) was used as the catalyst carrier, and K2CO3 was used as the activator to prepare a heterogeneous catalyst (KXC). The heterogeneous catalyst was characterized by scanning electron microscopy-energy dispersion X-ray spectroscopy (SEM-EDS), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and Brunauer–Emmett–Teller (BET) and X-ray photoelectron spectroscopy (XPS) analysis techniques to evaluate its chemical composition, structure, and physical morphology. EDS and XPS revealed the presence of K metal, which provided an alkaline site for the transesterification reaction to produce biodiesel. The biodiesel yield was observed by gas chromatography−mass spectrometry (GCMS). Under the reaction conditions of a methanol-to-oil molar ratio of 12:1, a reaction time of 90 min, a temperature of 65 °C, and a catalyst loading of 4 wt.% using 25KXC-600-4, the yield of biodiesel can reach 95.13 ± 0.82%. After being repeated five times, the yield was still 58.11 ± 3.80%. The catalyst has no waste generation, and has the characteristics of simple preparation and environmental friendliness, which make it a green heterogeneous catalyst for biodiesel production.

Applications of Diels-Alder Chemistry in Biomaterials and Drug Delivery.

Recent studies, leveraging click chemistry reactions, have significantly advanced the fields of biomaterials and drug delivery. Of these click reactions, the Diels-Alder cycloaddition is exceptionally valuable for synthetic organic chemistry and biomaterial design, as it occurs under mild reaction conditions and can undergo a retrograde reaction, under physiologically relevant conditions, to yield the initial reactants. In this review, potential applications of the Diels-Alder reaction are explored within the nexus of biomaterials and drug delivery. This includes an emphasis on key platforms such as polymers, nanoparticles, and hydrogels which utilize Diels-Alder for drug delivery, functionalized surfaces, bioconjugation, and other diverse applications. Specifically, this review will focus on the use of Diels-Alder biomaterials in applications of tissue engineering and cancer therapies, while providing a discussion of the advantages, platforms, and applications of Diels-Alder click chemistry.

Nitration of Benzene to Nitrobenzene Using NO2 as Nitro Source Under Mild and Solvent‐Free Conditions

AbstractIn this work, a green and efficient method has been developed to catalyze the nitration of benzene to nitrobenzene in NO2‐O2 system by using acidic ion exchange resin as catalyst under mild (0 °C and atmospheric pressure) and solvent‐free conditions. Based on experimental screening, commercial acid ion exchange resin Amberlite FPC3500 was identified as the optimal catalyst. Under the optimized reaction conditions, 99.9 % conversion of benzene was obtained with 99.1 % selectivity of nitrobenzene. Furthermore, the catalyst is easily reusable. The results demonstrate a greener route for the production of nitrobenzene.

Axially chiral α-boryl-homoallenyl boronic esters as versatile toolbox for accessing centrally and axially chiral molecules

Axially chiral allenes bearing organoboron groups are highly sought-after building blocks in organic synthesis due to their potential for generating a wide range of axially and centrally chiral molecules. However, the existing methods for preparing axially chiral allenes containing boron group are primarily limited to the synthesis of allenyl boronic esters, and strategies for accessing axially chiral homoallenyl boronic esters are still scarce. Here, we report the general method for synthesizing axially chiral α-boryl-homoallenyl boronic esters through a highly regio- and stereoselective copper-mediated SN2’-addition of newly prepared (diborylalkyl)copper species to chiral propargyl electrophiles. The reaction conditions were optimized to achieve high yields and excellent stereospecificity. The obtained products were successfully transformed into various axially chiral allenes and other chiral molecules by transforming diboron units. The potential for axial-to-central chirality transfer of axially chiral α-boryl-homoallenyl boronic esters is also demonstrated through the stereospecific addition to aldehydes and N-H aldimines, yielding enantioenriched 1,2-oxaborinin-3,5-dienes and 2-aminomethyl-1,3-dienes.

Facile and Metal‐Free Synthesis of Isoflavones Using α‐Aryl‐β,β‐Ditosyloxy Ketones

AbstractConsidering the drawbacks associated with available synthetic methodologies of isoflavones, herein we have reported a metal‐free and eco‐friendly approach to these natural products. In the present study, we have carried out the synthesis of eight isoflavone derivatives 7a–7h using α‐aryl‐β,β‐ditosyloxy ketone protocol. Initially, we have protected the 2’‐hydroxy group of respective chalcone moiety in order to remove its interference under reaction conditions. The protected chalcones were then subjected to 1,2‐aryl migration by being treated with hydroxy(tosyloxy)iodobenzene (HTIB) reagent in a non‐nucleophilic solvent (CH2Cl2). This migration furnished the formation of α‐aryl‐β,β‐ditosyloxy ketones via C−C bond formation from their corresponding chalcones in moderate to good yields (55–82 %). The ambiguity regarding the exact molecular structure of the α‐aryl‐β,β‐ditosyloxy ketones was examined through the single crystal X‐ray diffraction data. At last, the synthesis of isoflavones was carried out in moderate to good yields (50–80 %) by performing the reaction of α‐aryl‐β,β‐ditosyloxy ketones with sodium hydroxide in aqueous methanol.

In situ decorated pd NPs on Triazin-encapsulated Fe3O4/SiO2-NH2 as magnetic catalyst for the synthesis of diaryl ethers and oxidation of sulfides

This article is devoted to the synthesis of a new magnetic palladium catalyst that has been immobilized on A-TT-Pd coated-magnetic Fe3O4 nanoparticles. Such surface functionalization of magnetic particles is a promising method to bridge the gap between heterogeneous and homogeneous catalysis approaches. The structure, morphology, and physicochemical properties of the particles were characterized through different analytical techniques, including TEM, FT-IR, XRD, SEM, EDS, TGA-DTG, ICP, and VSM techniques. The obtained Fe3O4@SiO2@A-TT-Pd performance can show excellent catalytic activity for the synthesis of diaryl ethers and oxidation of sulfides, and the corresponding products were obtained with high yields. The advantages of this catalyst include a simple test method, green reaction conditions, no use of dangerous solvents, short reaction time, low catalyst loading, and reusability. Also, the nanocatalyst was easily separated from the reaction mixture with the help of a bar magnet and recovered and reused several times without loss of stability and activity.

Synthesis of 6- or 8-Carboxamido Derivatives of Imidazo[1,2-a]pyridines via a Heterogeneous Catalytic Aminocarbonylation Reaction

Imidazo[1,2-a]pyridines and especially their amide derivatives exhibit a wide range of favourable pharmacological properties. In this work, Pd-catalysed carbonylation was used for the first time for the introduction of the carboxamide moiety into positions 6 or 8. A recyclable Pd catalyst, with palladium immobilised on a supported ionic liquid phase decorated with pyridinium ions, was used efficiently for the conversion of 6- or 8-iodo derivatives to the products. In the case of 6-iodo derivatives, a competing mono- and double carbonylation could be observed in the reactions of aliphatic amines as nucleophiles, but under the proper choice of reaction conditions, good-to-excellent selectivities could be achieved towards either the corresponding amides or α-ketomides. The heterogeneous catalyst showed excellent recyclability and low Pd-leaching.

NiII, PdII and PtII pincer complexes of 2-(diphenylphosphanyl)-N-(2-(diphenyl-phosphanyl)benzyl)benzamide: synthesis, reactivity and catalytic studies.

In this article, the synthesis of bis(phosphine), o-Ph2PC6H4C(O)N(H)CH2C6H4PPh2-o (1) (hereafter referred to as "PCNHCP" and its anionic form as "PCNCP") and its group 10 metal chemistry and catalytic studies are described. PCNHCP (1) on reaction with NiCl2(DME) and PdCl2(COD) afforded pincer complexes, [MCl{(PCNCP)κ3-P,N,P}] (M = Ni, 2; Pd, 3). A similar reaction of 1 with PtCl2(COD) yielded a chelate complex, [PtCl2{(PCNHCP)κ2-P,P}] (4), which on further treatment with LiHMDS produced the 1,2-azaphospholene-phosphine complex, [PtCl(Ph){(o-P(Ph)C6H4CONCH2C6H4PPh2-o)κ2-P,P}] (5) via P-C/P-N bond metathesis. Passing dry HCl gas through the solution of 5 resulted in benzene elimination to form [PtCl2{(o-P(Ph)C6H4CONCH2C6H4PPh2-o)κ2-P,P}] (6). Treatment of 1 with PtCl2(COD) and Pt(Cl)(Me)(COD) in the presence of a base resulted in pincer complexes [PtX{(PCNCP)κ3-P,N,P}] (X = Cl, 7; Me, 8). Nickel complex 2 catalyzed the Suzuki-Miyaura cross coupling reaction between bromobenzene and phenyl boronic acid to give the corresponding biphenyls in good yield. The platinum complex 5 showed good catalytic activity towards regio- and stereoselective hydroboration of terminal alkynes. Both the catalytic reactions were performed under mild reaction conditions with a very low catalyst loading.

Atomically Asymmetrical Ir-O-Co Sites Enable Efficient Chloride-mediated Ethylene Electrooxidation in Neutral Seawater.

The chloride-mediated ethylene oxidation reaction (EOR) of ethylene chlorohydrin (ECH) via electrocatalysis is practically attractive because of its sustainability and mild reaction conditions. However, the chlorine oxidation reaction (COR), which is essential for the above process, is commonly catalyzed by dimensionally stable anodes (DSAs) with high contents of precious Ru and/or Ir. The development of highly efficient COR electrocatalysts composed of nonprecious metals or decreased amounts of precious metals is highly desirable. Herein, we report a modified Co3O4 with a single-atom Ir substitution (Ir1/Co3O4) as a highly efficient COR electrocatalyst for chloride-mediated EOR to ECH in neutral seawater. Ir1/Co3O4 achieves a Faradaic efficiency (FE) of up to 94.8% for ECH generation and remarkable stability. Combining experimental results and density functional theory (DFT) calculations, the unique atomically asymmetrical Ir-O-Co configuration with a strong electron coupling effect in Ir1/Co3O4 can accelerate electron transfer to increase the reaction kinetics and maintain the structural stability of Co3O4 during COR. Moreover, a coupling reaction system integrating the anodic chloride-mediated and cathodic H2O2-mediated EOR show a total FE of ~170% for paired electrosynthesis of ECH and ethylene glycol (EG) using ethylene as the raw material. The technoeconomic analysis highlights the promising application prospects of this system.