Diels-Alder Research Articles

Synthesis of Polyoxygenated 4,5-Diarylpyridazines with Antiproliferative and Antitubulin Activity via Inverse Electron-Demand Diels-Alder Reaction of 1,2,4,5- Tetrazine

: The synthesis of a series of multifunctionalized 4,5-diarylpyridazines via inverse electron-demand Diels-Alder reaction between highly oxygenated diarylacetylenes and unsubstituted 1,2,4,5-tetrazine was developed using polyalkoxybenzenes isolated from industrial essential oils as starting material. The reaction proceeded smoothly to afford combretastatin A-4 analogs with pyridazine linker in consistently high yield. In a phenotypic sea urchin embryo assay, diarylpyridazine with 3,4,5-trimethoxyphenyl and 3-amino-4- methoxyphenyl aryl rings was identified as a potent antimitotic microtubule-destabilizing compound.

Wave-transparent and eco-friendly flame-retardant phosphorus-based phthalonitrile/quartz composites by a synchronized self-curing strategy with cyano and alkynyl groups

The robust human–machine interaction systems of the aerospace industry necessitate the development of thermal resistant wave-transparent composites, with a pivotal focus on organic resin matrix. However, enhancing the heat resistance of such materials while preserving other critical attributes has been a formidable challenge. In this study, a novel designed strategy of a dual-curing functional phosphorus-based phthalonitrile monomer (P-ALK-PN) has been proposed. The optimized curing temperatures for intra- or intermolecular Diels-Alder reactions of alkynyl groups and polyaddition reaction of cyano groups resulted in a homogeneous and highly crosslinked N-enriched phthalonitrile system. After curing at 450 °C, the resin, namely P-ALK-PN-450 °C, demonstrated exceptional thermal stability (T5% = 644 °C), thermo-oxidative stability (T5% = 554 °C), and char yield at 800 °C (90.7 % in N2 and 67.5 % in air). Their quartz fiber reinforced composites (P-ALK-PN/QFs) were subsequently fabricated by the hot-pressing process. Upon post-curing at 420 °C, P-ALK-PN-420 °C/QF displayed elevated glass transition temperature (550 °C), flexural strength (319 MPa), and relatively low dielectric properties with a dielectric constant (Dk) of approximately 4.2 and a dissipation factor (Df) less than 0.02 across a wide temperature ranging from 25 °C to 600 °C. Especially, it exhibited excellent flame retardancy (only a 6.7 % weight loss at ambient temperatures exceeding 1300 °C for 200 s) as well, stemming from release of eco-friendly inert gases (NH3) and formation of a graphitized protective layer during pyrolysis. These promising results highlight the potential applications of P-ALK-PN resins in aerospace and high-performance engineering fields.

Three-Component Synthesis of Multiply Functionalized 5,6-Dehydroisoquinuclidines through Dearomatization of Pyridine.

A three-component synthesis of multiply functionalized 5,6-dehydroisoquinuclidines is described. After the formation of an N-alkylpyridinium salt, Grignard addition led to the formation of the corresponding 1,2-dihydropyridine bearing an alkyl, alkene, aryl, or alkynyl group. Subsequent Diels-Alder reaction with a dienophile provided functionalized dehydroisoquinuclidines in high yields (up to 93%) with endo selectivities (73:27 to >99:1). This reaction was applicable to the synthesis of an N-(4-methoxybenzyl)pyridinium salt, where the 4-methoxybenzyl group was switched to a benzyloxycarbonyl group after the formation of the dehydroisoquinuclidine.

CuI-Zeolite Catalysis for Biaryl Synthesis via Homocoupling Reactions of Phenols or Aryl Boronic Acids

Due to the importance of biaryls as natural products, drugs, agrochemicals, dyes, or organic electronic materials, a green alternative biaryl synthesis has been developed based on easy-to-prepare and cheap copper(I)-exchanged zeolite catalysts. CuI-USY proved to efficiently catalyze the direct homocoupling of either phenols or aryl boronic acids under simple and practical conditions. The CuI-USY-catalyzed oxidative homocoupling of phenols could conveniently be performed under air either in warm methanol or water with good to high yields. In methanol, a small amount of Cs2CO3 was required, while none was necessary in water. The homocoupling of aryl boronic acids was best performed also in warm methanol, without an additive. These mild conditions showed good functional-group tolerance, leading to a variety of substituted (hetero)biaryls (28 examples). The heterogeneous CuI-USY catalyst could readily be recovered and reused. Interestingly, the homocoupling of vinyl boronic acids was successfully coupled to a Diels–Alder reaction, even in a one-pot process, allowing access to highly functionalized cyclohexenes.

Remote-Contact Catalysis for Target-Diameter Semiconducting Carbon Nanotube Arrays.

Electrostatic catalysis uses an external electric field (EEF) to rearrange the charge distribution to boost reaction rates and selectively produce certain reaction products in small-molecule reactions (e.g., Diels-Alder addition), requiring a 10 MV/cm field aligned with the reaction axis. Such a large and oriented EEF is challenging for large-scale implementation or material growth with multiple reaction axes or steps. Here, we demonstrate that the energy band at the tip of an individual single-walled carbon nanotube (SWCNT) can be spontaneously shifted in a high-permittivity growth environment, with its other end in contact with a low-work-function electrode (e.g., hafnium carbide). By adjusting the Fermi level at a point where there is a substantial disparity in the density of states (DOS) between semiconducting (s-) and metallic (m-) SWCNTs, we achieve effective electrostatic catalysis for 99.92% purity s-SWCNT growth with a narrow diameter distribution (0.95 ± 0.04 nm), targeting the requirement of advanced SWCNT-based electronics for future computing.

Computational Insights into Tunable Reversible Network Materials: Accelerated ReaxFF Kinetics of Furan-Maleimide Diels-Alder Reactions for Self-Healing and Recyclability.

In this study, ReaxFF molecular dynamics simulations were benchmarked and used to study the relative kinetics of the retro Diels-Alder reaction between furan and N-methylmaleimide. This reaction is very important for the creation of polymer networks with self-healing and recyclable properties, since they can be used as reversible linkers in the network. So far, the reversible Diels-Alder reaction has not yet been studied by using reactive molecular dynamics simulations. This work is, thus, the first step in simulating a covalent adaptable network (CAN) using Diels-Alder reactions as reversible linkers. For both endo and exo, the bond breaking in 40 product molecules was simulated using the bond boost method and the endo/exo ratio was evaluated. This ratio was benchmarked against density functional theory (DFT) and experimental results for a changing set of bond boost parameters. Given their importance to understand how the CAN performs, the effect of the addition of a polymer backbone and the effect of temperature were successfully simulated using our newly parametrized reactive force field.

Novel Recycling of Epoxy Thermosets by Blending with Reversible Diels-Alder Epoxy Resin.

The introduction of Diels-Alder (D-A) bonds into epoxy resins is a promising pathway to convert these unrecyclable materials into sustainable materials. However, D-A bonds make epoxy resins extremely brittle materials and hinder their practical usability. Nonetheless, the reversibility of D-A bonds allows the transition of the material to a de-crosslinked network formed by separated oligomers that can melt above 90-100 °C. This means that D-A epoxy resins can be reprocessed after being cured like thermoplastics. In the present work, a thermoset blend is made by adding spent epoxy particles to a D-A epoxy resin to increase its thermal and mechanical properties and to evaluate a possible reuse of conventional thermoset wastes. The application of hot-pressing to a mixture of epoxy particles and powder of cured D-A epoxy creates a material in which the interaction of the particles with the D-A resin increases the thermal resistance of the material and prevents the D-A epoxy from melting at high temperatures. In addition, the flexural strength is increased by 80% and the chemical resistance against organic solvents is also improved.

An Expeditious Synthesis of Near-Infrared-Absorbing Imide-Based Graphene Nanoribbons and Their Photothermal Properties.

Graphene nanoribbons (GNRs) with low band gap and strong near-infrared (NIR) absorption are potential candidates for optoelectronic and biomedical applications. In this context, imide-based GNRs are promising, but there are no rational design principles that yield these robust GNRs with strong NIR absorption. Here, we demonstrate a rational synthesis route to achieve NIR-absorbing imide-based robust GNRs by exploring the bay region of polyperylene (PP). Using the oxidative Diels-Alder reaction, we have successfully introduced mono and diimide functional groups on PP. After cyclodehydrogenation, the resultant GNRs, benzoperylene imide GNR (BPI-GNR) and coronene diimide GNR (CDI-GNR), show oscillatory edge geometry with strong NIR absorption (up to 1000 nm) and optical band gap of ~1.3 eV. Computational studies also indicate that imide substituents play an important role in fine-tuning the optoelectronic properties of GNRs. Moreover, these GNRs are solution-processable and can be made into thin films via spray coating. Owing to the strong NIR absorption and imide substitutions, BPI and CDI-GNRs show good photothermal conversion with excellent cyclic stability.

Fullerene-Hybridized Fused-Ring Electron Acceptor with High Dielectric Constant and Isotropic Charge Transport for Organic Solar Cells.

A novel isotropic fullerene-hybridized fused-ring electron acceptor, designated C60-Y, has been synthesized via a mild [4+2] Diels-Alder cycloaddition reaction with fullerene C60 to enhance the performance of organic solar cells (OSCs). Comparative analysis shows that C60-Y significantly outperforms the control acceptor Me-Y, with a notable increase in the relative dielectric constant from 2.79 to 3.95. This improvement enhances exciton dissociation and reduces non-radiative energy losses. Additionally, the isotropic molecular packing of C60-Y, similar to fullerene, facilitates efficient interface formation with donor polymers and improves charge mobility. As a result, incorporating C60-Y as an electron acceptor increases the power conversion efficiency (PCE) of binary OSCs to 15.02 %, surpassing the 13.31 % achieved with Me-Y. Moreover, when integrated into a ternary blend system, an impressive PCE of 19.22 % is achieved, top-performing among reported ternary OSCs utilizing fullerene derivatives as the third component. These results suggest that fullerene-hybridized acceptors like C60-Y hold great potential for advancing high-efficiency OSCs by enhancing exciton dissociation, reducing energy losses, and improving charge mobility.

Construction of Naphtho[2,1-d]oxazoles and 1,4-Epoxyisoquinolines via Regioselectivity-Switchable Diels-Alder Reaction of 4-Alkenyloxazoles with Arynes.

A Regioselectivity-switchable Diels-Alder reaction of arynes and 4-alkenyloxazoles was explored. By regulating the reaction temperature and the polarity of the solvent, the reaction activity of aryne was controlled to selectively react with different favorable reaction sites of 4-alkenyloxazoles, providing naphtho[2,1-d]oxazoles and 1,4-epoxyisoquinolines. Density functional theory (DFT) calculations demonstrated that the Diels-Alder reaction on acyclic dienes site needs more energy than the reaction on cyclic dienes to overcome the potential reaction barrier.

Using Near-Infrared Irradiation for Heating Mechanochemical Reactions in Organic-Dye-Doped Epoxy Milling Jars.

Albeit mechanochemistry is a novel promising technology that give access to reactivity under solvent-free conditions, heating such reactions is sometimes compulsory to obtain satisfactory results in terms of conversion, selectivity and/or yield. In this work, we developed a novel approach using a dye that absorbs NIR photons and release the energy as heat. Hence, de novo milling jars in epoxy resin doped with the dye were thus produced to obtain reactors that would produce heat upon irradiation at 850 nm. Temperature profiles were recorded, depending on the irradiance, dye charge in the resin, and milling frequency, showing an excellent control of the temperature. The usefulness of the heating jar was then demonstrated in mechanochemical reactions that are known to require heat to yield the desired product, namely Diels-Alder reactions with high activation energies and the newly developed rearrangement of a sydnone into corresponding 1,3,4-oxadiazolin-2-one.

Diels–Alder Adducts of <i>N</i>-Substituted 2-Pyridones with Maleinimides. Synthesis and Antiviral Activity

Adducts of N-substituted 2-pyridones [pyridine-2(1H)-ones] and N-substituted maleic acid imides were synthesized under thermal conditions of the Diels–Alder reaction with yields from 68 to 97%. Cytotoxicity and antiviral activity of the obtained compounds were studied using a model of adenovirus infection [human adenovirus type 5 (AdV5)] in MA-104 cell culture. It was shown that the synthesized adducts have low toxicity and medium antiviral activity. Only 9-hexyl-2-phenyl-3a,4,7,7a-tetrahydro-1H-4,7-(epiminomethano)isoindole-1,3,8-trione has the most pronounced viral inhibitory properties with a selectivity index of 7.

Revisiting the Enhanced Chemical Reactivity in Water Microdroplets: The Case of a Diels-Alder Reaction.

Often, chemical reactions are markedly accelerated in microdroplets compared with the corresponding bulk phase. While identifying the precise causative factors remains challenging, the interfacial electric field (IEF) and partial solvation are the two widely proposed factors, accounting for the acceleration or turning on of many reactions in microdroplets. In sharp contrast, this combined computational and experimental study demonstrates that these two critical factors have a negligible effect on promoting a model Diels-Alder (DA) reaction between cyclopentadiene and acrylonitrile in water microdroplets. Instead, the acceleration of the DA reaction appears to be driven by the effect of confinement and the concentration increase caused by evaporation. Quantum chemical calculations and ab initio molecular dynamics simulations coupled with enhanced sampling techniques predict that the air-water interface exhibits a higher free-energy barrier of this reaction than the bulk, while external electric fields marginally reduce the barrier. Remarkably, the catalytic capability of the IEF at the water microdroplet surface is largely hampered by its fluctuating character. Mass spectrometric assessment of the microdroplet reaction corroborates these findings, suggesting that the DA reaction is not facilitated by the IEF as increasing the spray potential suppresses the DA products by promoting substrate oxidation. While the DA reaction exhibits a surface preference in water microdroplets, the same reaction tends to occur mainly within the core of the acetonitrile microdroplet, suggesting that the partial solvation is not necessarily a critical factor for accelerating this reaction in microdroplets. Moreover, experiments indicate that the rapid evaporation of microdroplets and subsequent reagent enrichment within the accessible confined volume of microdroplets caused the observed acceleration of the DA reaction in water microdroplets.

Concise Synthesis of Tetrasubstituted 1,6-Dihydropyridazine and Pyridazine Derivatives

AbstractA novel one-pot three-steps process has been developed, including phosphine-catalyzed Rauhut–Currier reaction of γ-alkyl allenoates, Diels–Alder reaction with di-tert-butyl azodicarboxylate, followed by deprotection of Boc group to prepare tetra-substituted 1,6-dihydropyridazines in good yields. The 1,6-dihydropyridazines were easily converted to pyridazine derivatives via oxidative aromatization by DDQ.

Cycloaddition of Butadiene with Perfluoroethylene: Prediction of a Periselectivity Switch under Pressure.

Defying the common Diels-Alder reactivity, the thermal cycloaddition between butadiene and tetrafluoroethylene (TFE) yields exclusively a [2 + 2] cycloadduct via a stepwise diradical mechanism. Here, we study the possibility of reverting to the normal [4 + 2] reactivity in this reaction under high pressure. DFT calculations using the eXtreme Pressure Polarizable Continuum Model (XP-PCM) suggest a more negative activation volume for the concerted [4 + 2] mechanism than the stepwise [2 + 2] mechanism and predict a switch in periselectivity at 1.4 gigapascal (GPa).

Chiral Polar Bifunctional Polyimide Enantiomers for Asymmetric Photo‐ and Piezo‐Catalysis

AbstractChiral catalysts for asymmetric catalysis represent a crucial research focus in chemistry and materials science. However, a few cases about chiral‐dependent photocatalysts primarily focus on plasmonic noble metals. Particularly, developing chiral nano‐catalysts that can be driven by mechanical energy remains in the blank stage. Herein, organic polymer‐based enantiomers, chiral polar polyimide (PI) microspheric nano‐assembly are synthesized as novel bifunctional catalysts for asymmetric photocatalysis and piezocatalysis. The PI catalyst enantiomers present enantioselectivity towards left‐ and right‐circularly polarized light, demonstrating chiral‐dependent H2O2 photoproduction. Interestingly, enantioselectivity of the catalyst reverses under irradiation of different bands, presenting tunability in the interaction between chiral catalysts and circularly polarized light. For the first time, enantioselective piezocatalytic behavior is demonstrated by the chiral polar PI catalysts. They show remarkable chiral preference for asymmetric Diels–Alder reaction and enantioselective conversion of tyrosine substrates under ultrasonic vibration. The findings provide a new perspective into exploring metal‐free chiral catalysts and their asymmetric catalysis applications across multiple energy forms.

Chiral Polar Bifunctional Polyimide Enantiomers for Asymmetric Photo- and Piezo-Catalysis.

Chiral catalysts for asymmetric catalysis represent a crucial research focus in chemistry and materials science. However, a few cases about chiral-dependent photocatalysts primarily focus on plasmonic noble metals. Particularly, developing chiral nano-catalysts that can be driven by mechanical energy remains in the blank stage. Herein, organic polymer-based enantiomers, chiral polar polyimide (PI) microspheric nano-assembly are synthesized as novel bifunctional catalysts for asymmetric photocatalysis and piezocatalysis. The PI catalyst enantiomers present enantioselectivity towards left- and right-circularly polarized light, demonstrating chiral-dependent H2O2 photoproduction. Interestingly, enantioselectivity of the catalyst reverses under irradiation of different bands, presenting tunability in the interaction between chiral catalysts and circularly polarized light. For the first time, enantioselective piezocatalytic behavior is demonstrated by the chiral polar PI catalysts. They show remarkable chiral preference for asymmetric Diels-Alder reaction and enantioselective conversion of tyrosine substrates under ultrasonic vibration. The findings provide a new perspective into exploring metal-free chiral catalysts and their asymmetric catalysis applications across multiple energy forms.

Stereochemical Shape Morphing in Diels-Alder Polymer Networks.

The intrinsic reversibility of dynamic covalent bonding, such as the furan-maleimide Diels-Alder (DA) cycloaddition reactions, enables reprocessable, self-healing polymer materials that can be reconfigured via the mechanism of solid-state plasticity. In this work, the temperature-dependent exchange rates of stereochemically distinct endo and exo DA bonds are leveraged to achieve tunable, temperature- and stress-activated shape morphing in Diels-Alder polymer (DAP) networks. Through thermal annealing, ≈35% of endo DA isomers are converted in neat DAP networks to the thermodynamically favored exo form, achieving ≈97% exo after complete annealing at 60°C. This conversion results in a ≈1.7 fold increase in elastic modulus, from 1.7 to 3.0MPa, and significantly alters the stress relaxation and shape recovery behavior. Spatially resolved annealing, is further showcased enabling the precise control of spatial distributions of endo and exo DA bonds across planar geometries. The locally distinct concentrations of endo/exo isomers, achieved by temperature-induced conversion of endo DA isomers to the thermodynamically stable exo DA isomers, gave rise to the spatial distributions of stress relaxation rates and elastic strain recovery mismatch to enable controlled stereochemical shape morphing. This approach provides a simplified, thermally driven method for shape morphing, with potential applications in soft robotics and flexible electronics.

Recyclable Thermoplastic Elastomer from Furan Functionalized Hairy Nanoparticles with Polystyrene Core and Polydimethylsiloxane Hairs.

Polymers synthesized with end-of-life consideration allow for recovery and reprocessing. "Living-anionic polymerization (LAP)" and hydrosilylation reaction were utilized to synthesize hair-end furan functionalized hairy nanoparticles (HNPs) with a hard polystyrene (PS) core and soft polydimethylsiloxane (PDMS) hairs via a one-pot approach. The synthesis was carried out by first preparing the living core through crosslinking styrene with divinylbenzene using sec-butyl lithium, followed by the addition of the hexamethylcyclotrisiloxane (D3) monomer to the living core. The living polymer was terminated by dimethylchlorosilane to obtain the HNPs with Si-H functional end groups. The furan functionalization was carried out by the hydrosilylation reaction between the Si-H of the functionalized HNP and 2-vinyl furan. Additionally, furan functionalized polystyrene (PS) and polydimethylsiloxane (PDMS) were also synthesized by LAP. 1H NMR and ATR-IR spectra confirmed the successful synthesis of the target polymers. Differential scanning calorimetry showed two glass transition temperatures indicative of a polydimethylsiloxane soft phase and a polystyrene hard phase, suggesting that the HNPs are microphase separated. The furan functionalized HNPs form thermo-reversible networks upon crosslinking with bismaleimide (BMI) via a Diels-Alder coupling reaction. The kinetics of the forward Diels-Alder reaction between the functionalized polymer and BMI were studied at three different temperatures: 50 °C, 60 °C, and 70 °C by UV-Vis spectroscopy. The activation energy for the furan functionalized HNPs reaction with the bismaleimide was lower compared to the furan functionalized polystyrene and polydimethylsiloxane linear polymers. The crosslinked polymer network formed from the Diels-Alder forward reaction dissociates at around 140-154 °C, and the HNPs are recovered. The recovered HNPs can be re-crosslinked at 50 °C. The results suggest that furan functionalized HNPs are promising building blocks for preparing thermo-reversible elastomeric networks.

All-In-One Epoxy/MXene Nanocomposites with Bead-Type Polymeric Imidazole Latent Curing Agent for Enhancing Storage Stability and Flame Retardancy.

Developing a single-component epoxy system is challenging but crucial for advanced thermoset applications. Unfortunately, conventional latent curing agents using chemical or physical passivation do not provide satisfactory storage stability and the necessary property requirements. Here, it is demonstrated that all-in-one epoxy/MXene nanocomposite system, comprising epoxy resin, polymeric imidazole latent curing agent beads (PILCAB), and Ti3C2Tx MXene, exhibits excellent storage stability, improved flame retardancy, and enhanced mechanical strength. PILCABs, prepared through a Diels-Alder (DA) crosslinking reaction between furan groups of poly(imidazolyl methacrylate)-random poly (furfuryl methacrylate) (PIm-r-PFu) copolymer and bismaleimide (BMI), exhibit excellent storage stability, as stable as under 60 °C storage due to the imidazole reactivity being suppressed synergistically by both physical and chemical passivation mechanisms. Ti3C2Tx MXene flakes, surface-functionalized with alkylated 3,4-dihydroxyl-L-phenylalanine, exhibit excellent compatibility with the epoxy matrix. Consequently, the enhanced storage stability, flame retardancy, and mechanical strength of the all-in-one epoxy/MXene nanocomposite are attributed to the strong DA bond formation in latent curing agent, efficient charring capability of MXene and BMI, and the catalytic effect of the MXene. This study opens new avenues for designing and developing single-component epoxy systems that satisfy demanding requirements, including storage stability, mechanical strength, and flame retardancy, which are essential for practical applications.