Catalyst-free Conditions Research Articles

Synthesis of Pyrrolidine-2-ylidenes from Isoxazolines and Allenes.

A diastereoselective addition and rearrangement reaction has been developed for the synthesis of pyrrolidine-2-ylidenes from NH-isoxazolines and electron-deficient allenes. This method proceeds via the rearrangement of a proposed N-alkenylisoxazoline intermediate to generate densely functionalized pyrrolidine-2-ylidenes under simple catalyst-free conditions that tolerate ketone substituents and install relative stereochemistry at positions 3 and 4 of the heterocycle. Reaction optimization and the substrate scope are described in addition to studies evaluating the reactivity of the gem-dione and enaminone groups of the products.

Activated Phenyl Ester Vitrimers.

Aromatic esters are amongst the oldest known chemical motifs that allow for thermal (re)processing of thermosetting polymers. Moreover, phenyl esters are generally known as activated esters that do not require a catalyst to undergo acyl transfer reactions. Even though dynamic aromatic esters find applications in commercialized thermoset formulations, all-aromatic esters have found limited use so far in the design of covalent adaptable networks (CAN) as a result of their high glass transition temperature (Tg)and specific curing process. Here, a strategy to include partly aromatic esters as dynamic cross-links inside low Tg (-40°C) thermosetting formulations, using aliphatic esters derived from para-hydroxybenzoic acid, which serves as a highly activated phenol or as a reactive "phenylogous anhydride" is reported. A small molecule study shows that the activated phenyl ester bonds can readily exchange with free phenol moieties at 200°C under catalyst-free conditions, while the addition of a catalyst allows for a faster exchange. Robust and hydrophobic polymer networks are conveniently prepared via rapid thiol-ene UV-curing of unsaturated phenol esters. The obtained networks show high thermal stability (350°C), fast processability, good water resistance, and low creep up to 120°C, thus showing good promise as a platform for CAN.

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

An efficient and facile synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives was developed through the isocyanide-based multicomponent reaction of isocyanides, gem-diactivated olefins, and cyclic imines such as dibenzoxazepine, dibenzothiazepine, and triazolobenzodiazepine under solvent- and catalyst-free conditions. Purposefully, this approach produced various bioactive scaffolds using environmentally friendly, mild, and simple conditions. Due to their bioactive moieties, these compounds with exclusive fluorescence properties may attract great attention in biomedical applications, clinical diagnostics, and conjugate materials.

Photochemical direct C3 cyanoalkylation of quinoxalin-2(1H)-ones with cyclobutanone oxime esters under catalyst-free conditions

A photochemical direct C3 cyanoalkylation of quinoxalin-2(1H)-ones was achieved for the first time, using cyclobutanone oxime esters as cyanoalkyl precursors, without the need for a photocatalyst. The mild and environmentally friendly conditions make this protocol a valuable alternative for synthesizing C3 cyanoalkylated quinoxalin-2(1H)-ones.

A Reactivity Study of 4-Hydroxy-2H-chromene-2-thione and 4-Hydroxy-2H-thiochromene-2-thione with tert-Butyl Nitrite and Aromatic Amines: An Environmentally Benign Synthesis of New Hydrazone Derivatives

AbstractThe synthesis of biologically active coumarin-based hydrazone derivatives is achieved through a one-pot, three-component reaction of 4-hydroxy-2H-chromene-2-thiones with aniline derivatives and tert-butyl nitrite under solvent- and catalyst-free conditions in yields of 76–86%. Similarly, the reactions of 4-hydroxydithiocoumarins with aniline derivatives and tert-butyl nitrite under identical conditions provided the corresponding hydrazone products in 79–85% yield through a four-component reaction. It is observed in both cases that the C=S group at the C2 position is converted into a C=O moiety. However, the intermediate products derived from 4-hydroxydithiocoumarin react further with another aniline molecule leading to thioesters. 4-Hydroxy-2H-chromene-2-thione and 4-hydroxydithiocoumarin exhibit distinct reactivity pathways, resulting in the formation of two different types of product. In addition, quantum chemical analysis of the mechanistic steps show that this reaction is exergonic. This protocol offers broad substrate scope and tolerates various functional groups, leading to high product yields in short reaction times.

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.

Photocatalyst-Free Transformation of C(sp3)-H Bonds to Oxime Ethers via Photoinduced Hydrogen Atom Transfer.

Herein, a direct transformation of aliphatic C-H bonds to oxime ethers has been developed via light-promoted hydrogen atom transfer (HAT) in the absence of a photocatalyst. Singlet oxygen and chlorine radical are complementary C(sp3)-H bond cleaving agents in this reaction, enabling the extraction of hydrogen atoms from a diverse range of compounds, like cycloalkanes, ethers, amines, amides, and cyclic sulfides. This method excels in transforming common aliphatic C-H bonds into valuable oxime ethers featuring abundant chemical feedstocks, good functional group tolerance, and catalyst free conditions.

Heteroatom-Controlled Three-Component [4 + 3] or [3 + 2] Annulation of Isatin-Derived Azomethine Ylide with Azadiene: Selective Synthesis of Spirooxindole-diazepines and Density Functional Theory Studies.

A novel three-component [4 + 3] annulation reaction of isatin-derived azomethine ylides with azadienes was developed for the first time to efficiently synthesize spirooxindole-diazepines incorporating a benzothiophene moiety under catalyst-free conditions. Effects of the heteroatom of azadiene on the chemoselectivity was investigated. With the use of the azadiene bearing a benzofuran moiety as a substrate, the dominant reaction pathway was changed to an α-[3 + 2] annulation. When azadiene bearing an indenone moiety was used, a distinct γ-[3 + 2] annulation was observed. Density functional theory calculations revealed that a delicate balance between kinetic accessibility and the thermodynamic driving force controlled the competition of different annulation reactions.

Fast, Regioselective Aminolysis of Tetrasubstituted Cyclic Carbonates and Application to Recyclable Thermoplastics and Thermosets.

Herein, the long-standing challenge of the ring-opening aminolysis of CO2-derived tetrasubstituted cyclic carbonates at room temperature (r.T) is overcome under catalyst-free conditions. Molecular design of the cyclic carbonate by substitution of an alkyl group by a thioether unlocks quantitative conversion at r.T and ensures total regioselectivity toward highly substituted oxazolidone scaffolds. An in-depth rationalization of the high reactivity of these cyclic carbonate structures and of the aminolysis reaction mechanism is provided by a computational study supporting experimental observations. The high efficiency of the reaction is then translated to the deconstruction of high-performance thermoplastics containing tetrasubstituted cyclic carbonate linkages to deliver building blocks that are reused for designing recyclable thermosets bearing dynamic N,S-acetal linkages.

Domino Sequence of Ketimization and Electrophilic Amination for an Inverse Aza Intramolecular Morita-Baylis-Hillman Adduct.

Morita-Baylis-Hillman (MBH) reaction, typically catalyzed by a Lewis base, is a popular and useful method for C-C bond formation. Unfortunately, it is limited by a slow reaction rate and has sensitivity toward steric and electronic parameters. Despite tremendous efforts, the versatility of the reaction keeps the quest open for new mechanistic and catalytic pathways. Here, we have reported a Bro̷nsted acid-catalyzed, electrophilic amination (Umpolung of imine) as a method for an inverse Aza Intramolecular MBH adduct in the form of 2-acylindole. Umpolung of imine with nitrogen acting as an electrophilic center has been achieved. Interestingly, the reaction was also shown to occur under catalyst-free conditions also. The expected products of ketimine formation, 6π electrocyclization, or quinoline formation were least/not observed. A large number of examples have demonstrated the reaction strength. β-aryl-substituted acrylate and acrylamide (cinnamates and cinnamides), which are extremely sluggish in conventional MBH chemistry, are the highlights of the developed methodology. The annulated product exhibited keto-enol tautomerism, which was proven by 1H NMR integrals. As an application, another tandem reaction in the form of Michael addition on a highly complex amine was carried out to provide spiro-annulated indole.

Synthesis of novel organophosphonate Schiff bases: A potential agents for post-cancer treatment and diabetics management

Schiff bases (SBs) and organophosphonates (OPs) are recognized for their extensive pharmaceutical applications; however, examples of compounds containing both functionalities are rarely reported. This study focuses on synthesizing novel phosphonate Schiff bases (PSBs) by condensing 3-amino benzoic acid with various aldehydes, followed by phosphorylation using triethylphosphite. This synthetic strategy and oxalyl chloride modification of the carboxyl group enabled incorporation of the phosphonate moiety without the need for NH₂ blocking agents, under mild, catalyst-free conditions. Twelve PSBs were synthesized and characterized using ¹H, ¹³C NMR, and HRMS. The compounds exhibited good to excellent yields. Biological evaluations showed significant cytotoxicity and α-glucosidase inhibitory activity. Specifically, compounds P1, P6, P8, and P9 demonstrated potent inhibition with IC₅₀ values of 9.40 ± 0.27, 6.88 ± 0.15, 5.20 ± 0.13, and 10.52 ± 0.26 µM, respectively. These results suggest that PSBs could be promising candidates for treating oncological and diabetic conditions. Advance in vivo studies and clinical trials are required to further establish their pharmacotherapeutic potential.

A simple and highly efficient catalyst-free for the synthesis of dihydro pyrido[1, 2-a]quinoxaline derivatives by four component reactions and evaluation of their antibacterial activity

In the current work, a new series of methyl-10-amino-9-cyano-6-oxo-8-aryl-6,8-dihydro-5H-pyrido[1,2-a]quinoxaline-7-carboxylate derivatives were efficiently designed and prepared using a convenient route in excellent yields by four-component reactions among benzene-1,2-diamine, dimethyl acetylenedicarboxylate, various aromatic aldehydes and malononitrile. These reactions were carried out in acetonitrile at ambient temperature under catalyst-free conditions for 7 h. The structures of the new obtained compounds were confirmed by NMR, IR, EI-MS and elemental analysis. The antibacterial activity of the synthesized products was studied using bacterial strains: Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The results showed that all the synthesized compounds are effective against Staphylococcus aureus, Bacillus subtilis and Escherichia coli bacteria.

Catalyst-Free [4+1] Annulation of α-Imidoyl Sulfoxonium Ylides and Diazo Compounds Enabling the Modular Synthesis of 2-Indanones and 3(2H)-Furanones.

A novel substrate-regulated [4+1] annulation of α-imidoyl sulfoxonium ylides with diazoketones under catalyst-free conditions is described. The reaction proceeds through a coupling of sulfoxonium ylides and in situ-generated ketenes to form the key reactive zwitterionic intermediates, followed by selective formation of C-C or C-O bonds to achieve five-membered ring systems. The cascade reaction permits the direct synthesis of synthetically useful 2-indanones and 3(2H)-furanones, which expands the reaction pattern of sulfoxonium ylides in annulation transformation.

One-pot sequential synthesis of fused and non-fused poly-substituted dihydropyridine derivatives under catalyst-free conditions

A one-pot, sequential, three-component procedure is reported for the synthesis of poly-substituted dihydropyridines via the condensation reaction of diamines or aminophenoles, 1,1-bismethylmethio-2-nitroethylene and α,β-unsaturated aromatic ketones in acetonitrile under reflux conditions. A range of fused and non-fused poly-substituted dihydropyridines were prepared in good to high yields with short reaction times.

Furan-containing polymer-coated magnetic nanoparticles using the ‘graft-to’ approach

Coating of magnetic nanoparticles with functional polymers increases the applicability of these nanomaterials. A modular approach to functionalizing these polymer coatings can be achieved using click chemistry. This work reports the synthesis of magnetic nanoparticles coated with a dopamine anchoring group containing polymer with furan groups as side chain residues. Using the ‘graft-to’ approach, polymers are coated onto magnetic nanoparticles using a simple place exchange reaction. Various analytical techniques were used to characterize the polymer-coated nanoparticles for their size and surface composition. Utilization of poly(ethylene glycol) (PEG)-based polymer renders the magnetic nanoparticles water dispersible. The presence of the furan ring on the polymer brushes enables their facile functionalization using a maleimide group-bearing molecule under catalyst-free conditions. A hydrophobic fluorescent dye, used as a model drug, is conjugated onto the nanoparticles using the Diels-Alder reaction. One can anticipate that the facile fabrication and functionalization of these clickable polymer-coated magnetic nanoparticles will be attractive for various biomedical applications.

Versatile Light-Mediated Synthesis of Degradable Bottlebrush Polymers Using α-Lipoic Acid.

Bottlebrush polymers have a variety of useful properties including a high entanglement molecular weight, low Young's modulus, and rapid kinetics for self-assembly. However, the translation of bottlebrushes to real-world applications is limited by complex, multi-step synthetic pathways and polymerization reactions that rely on air-sensitive catalysts. Additionally, most bottlebrushes are non-degradable. Herein, we report an inexpensive, versatile, and simple approach to synthesize degradable bottlebrush polymers under mild reaction conditions. Our approach relies on the "grafting-through" polymerization of α-lipoic acid (LA)-functionalized macromonomers. These macromonomers can be polymerized under mild, catalyst-free conditions, and due to reversibility of the disulfide bond in LA, the resulting bottlebrush polymers can be depolymerized by cleaving disulfide backbone bonds. Bottlebrushes with various side-chain chemistries can be prepared through the atom transfer radical polymerization (ATRP) of LA-functionalized macromonomers, and the backbone length is governed by the macromonomer molecular weight and solvent polarity. We also demonstrate that LA-functionalized macromonomers can be copolymerized with acrylates to form degradable bottlebrush networks. This work demonstrates the preparation of degradable bottlebrush polymers with a variety of side-chain chemistries and provides insight into the light-mediated grafting-through polymerization of dithiolane-functionalized macromonomers.

Catalyst-free gallic acid-based epoxy vitrimers with reprocessability and high glass transition temperature

General approaches for preparing epoxy vitrimers required lots of catalysts to accelerate transesterification to form the cross-linked network and the residual catalyst not only resulted in toxicity but also poor compatibility with other components. Herein, a green and facile strategy for preparing gallic acid epoxy resin (GA-EP) was developed under catalyst-free condition using renewable gallic acid, xylitol and hexahydro 4-methylphthalic anhydride (MHHPA) as feedstocks. The results indicated that the bio-based epoxy vitrimer had higher glass transition temperature (122 °C), satisfactory mechanical, thermal and degradation properties compared to neat Bisphenol A-based epoxy vitrimer. Furthermore, recycled GA-EP was ground into powder and added to the fresh resin to investigate its reusability. Compared to the original, the recycled epoxy vitrimer system demonstrated comparable performance, except for minor reductions in glass transition temperature (Tg) and modulus, likely stemming from the inherent inhomogeneity of the reprocessed material. This work provides a new approach to the production of high Tg bio-based epoxy vitrimers without adding any catalyst.

Synthesis and Thermo-Selective Recycling of Diels-Alder Cyclopentadiene Thermoplastics.

Catalyst-free and reversible step-growth Diels-Alder (DA) polymerization has a wide range of applications in polymer synthesis and is a promising method for fabricating recyclable thermoplastics. The effectiveness of polymerization and depolymerization relies on the chemical building blocks, often utilizing furan as the diene and maleimide as the dienophile. Compared to the traditional diene-dienophile or two-component approach that requires precise stoichiometry, cyclopentadiene (Cp) can serve dual roles via self-dimerization. This internally balanced platform offers a route to access high-molecular-weight polymers and a dynamic handle for polymer recycling, which has yet to be explored. Herein, through a reactivity investigation of different telechelic Cp derivatives, the uncontrolled cross-linking of Cp was addressed, revealing the first successful DA homopolymerization. To demonstrate the generality of our methodology, we synthesized and characterized six Cp homopolymers with backbones derived from common thermoplastics, such as poly(dimethylsiloxane), hydrogenated polybutadiene, and ethylene phthalate. Among these materials, the hydrogenated polybutadiene-Cp analog can be thermally depolymerized (Mn = 68 to 23 kDa) and repolymerized to the parent polymer (Mn = 68 kDa) under solvent- and catalyst-free conditions. This process was repeated over three cycles without intermediate purification, confirming the efficient thermo-selective recyclability. The varied degradable properties of the other four Cp-incorporated thermoplastics were also examined. Overall, this work provides a general methodology for accessing a new class of reversible homopolymers, potentially expanding the design and construction of sustainable thermoplastics.

Catalyst-free selective oxidation of C(sp3)-H bonds in toluene on water

The anisotropic water interfaces provide an environment to drive various chemical reactions not seen in bulk solutions. However, catalytic reactions by the aqueous interfaces are still in their infancy, with the emphasis being on the reaction rate acceleration on water. Here, we report that the oil-water interface activates and oxidizes C(sp3)-H bonds in toluene, yielding benzaldehyde with high selectivity (>99%) and conversion (>99%) under mild, catalyst-free conditions. Collision at the interface between oil-dissolved toluene and hydroxyl radicals spontaneously generated near the water-side interfaces is responsible for the unexpectedly high selectivity. Protrusion of free OH groups from interfacial water destabilizes the transition state of the OH-addition by forming π-hydrogen bonds with toluene, while the H-abstraction remains unchanged to effectively activate C(sp3)-H bonds. Moreover, the exposed free OH groups form hydrogen bonds with the produced benzaldehyde, suppressing it from being overoxidized. Our investigation shows that the oil-water interface has considerable promise for chemoselective redox reactions on water without any catalysts.

Electrochemically Direct Fluorination Functionalization of Styrenes with Different Fluorine Source: Access to Fluoroalkyl Derivatives.

A mild protocol for electrochemically oxidative fluorodifunctionalization of styrenes has been demonstrated. The reaction proceeds under metal, external oxidant, and catalyst free conditions, allowing tunable access to a wide variety of synthetically useful fluoroalkyl derivatives, such as β-fluorosulfone/fluoromethyl, fluorothiocyanation, and vinylsulfonyl derivatives. Moreover, CsF was shown to be the proper fluorine source for this electrochemical fluorodifunctionalization transformation.