Oxime Esters Research Articles

Synthesis and antifeedant activity of 3H-indole derived oxime esters and oxime ethers against cotton bollworm

The O-acylation or O-alkylation of 3H-indole derived oximes is conveniently synthesized from indoles and the corresponding anhydrides or alcohols mediated by tert-butyl nitrite (TBN) under mild conditions. O-Acyloxime esters are obtained with yields up to 82% using anhydrides via a facile one-pot reaction. Fluorinated O-alkyloxime ethers are achieved with yields up to 38% using fluorinated alcohols through an optimized step-by-step strategy or a 2,2,6,6-tetramethylpiperidinyl-1-oxide (TEMPO)-assisted one-pot strategy. Meanwhile, the better reaction yields, up to 64%, are achieved for nonfluorinated O-alkyloxime ethers. These approaches allow access to a diversity of O-acyloxime esters and fluorinated/nonfluorinated O-alkyloxime ethers, underscoring broad substrate scopes, good functional tolerance and easily gram-scale. All the synthesized compounds were evaluated for their potential antifeedant activity and 5f shows good antifeedant activity against cotton bollworm with a negative logarithmic effective concentration for 50% feeding reduction (pEC50) at 4.217.

High Photoinitiating Efficiency of Benzothioxanthene‐Based Oxime Esters in Photopolymerization via Photocleavage and/or Single Electron Transfer under Visible Light and Sunlight

AbstractIn this work, six benzothioxanthene‐based oxime esters were employed as photoinitiators for photopolymerization under visible light (LED) and sunlight. Their abilities to behave as Type I photoinitiators by mean of a photocleavage mechanism of oxime esters but also in multicomponent photoinitiating systems with an iodonium salt (through an electron transfer mechanism) were both explored with the different structures. Due to their broad absorption spectra tailing up 600 nm, photoinitiating properties of the benzothioxanthene‐based oxime esters were systematically tested under excitation with low‐intensity LED light at wavelengths of 405 nm and 450 nm. Additionally, parallel to the polymerization tests done under artificial light, the different benzothioxanthene‐based oxime esters were also investigated as solar photoinitiators and displayed a high reactivity in France (Western Europe) even in winter conditions. For the best candidates i.e. the most reactive structures, direct laser write experiments were carried out, evidencing the interest of these structures.

High Photoinitiating Efficiency of Benzothioxanthene-Based Oxime Esters in Photopolymerization via Photocleavage and/or Single Electron Transfer under Visible Light and Sunlight.

In this work, six benzothioxanthene-based oxime esters were employed as photoinitiators for photopolymerization under visible light (LED) and sunlight. Their abilities to behave as Type I photoinitiators by mean of a photocleavage mechanism of oxime esters but also in multicomponent photoinitiating systems with an iodonium salt (through an electron transfer mechanism) were both explored with the different structures. Due to their broad absorption spectra tailing up 600 nm, photoinitiating properties of the benzothioxanthene-based oxime esters were systematically tested under excitation with low-intensity LED light at wavelengths of 405 nm and 450 nm. Additionally, parallel to the polymerization tests done under artificial light, the different benzothioxanthene-based oxime esters were also investigated as solar photoinitiators and displayed a high reactivity in France (Western Europe) even in winter conditions. For the best candidates i.e. the most reactive structures, direct laser write experiments were carried out, evidencing the interest of these structures.

A General Electron Donor‐Acceptor Photoactivation Using Oxime Esters Enabled Divergent Thioetherifications†

Comprehensive SummaryThe EDA complex‐mediated reactions involving oxime esters have been few studied. Herein, an EDA complex formed by thiophenolate anion and oxime ester is reported for photoinduced divergent synthesis of thioethers, depending on different types of oxime esters. Operational simplicity, mild reaction conditions, and flexible options of leaving group demonstrate the generality and synthetic utility of this approach. Such an approach can also enable an interesting thiol‐catalysis for the synthesis of phenanthridines.

A new neuroprotective candidate TJ1 targeting amyloidogenesis in 5xFAD Alzheimer’s disease mice

As one of the main pathmechanisms of Alzheimer’s disease (AD), amyloid-β (Aβ) is widely considered to be the prime target for the development of AD therapy. Recently, imidazolylacetophenone oxime ethers or esters (IOEs) have shown neuroprotective effects against neuronal cells damage, suggesting their potential use in the prevention and treatment of AD. Thirty IOEs compounds from our lab in-house library were constructed and screened for the inhibitory effects on Aβ42-induced cytotoxicity. Among them, TJ1, as a new IOEs hit, preliminarily showed the effect on inhibiting Aβ42-induced cytotoxicity. Furthermore, the inhibitory effects of TJ1 on Aβ42 aggregation were tested by ThT assays and TEM. The neuroprotective effects of TJ1 were evaluated in Aβ42-stimulated SH-SY5Y cells, LPS-stimulated BV-2 cells, and H2O2– and RSL3-stimulated PC12 cells. The cognitive improvement of TJ1 was assessed in 5xFAD (C57BL/6J) transgenic mouse. These results showed that TJ1 had strong neuroprotective effects and high blood–brain barrier (BBB) permeability without obvious cytotoxicity. TJ1 impeded the self-accumulation process of Aβ42 by acting on Aβ oligomerization and fibrilization. Besides, TJ1 reversed Aβ-, H2O2– and RSL3-induced neuronal cell damage and decreased neuroinflammation. In 5xFAD mice, TJ1 improved cognitive impairment, increased GSH level, reduced the level of Aβ42 and Aβ plaques, and attenuated the glia reactivation and inflammatory response in the brain,. Taken together, our results demonstrate that TJ1 improves cognitive impairments as a new neuroprotective candidate via targeting amyloidogenesis, which suggests the potential of TJ1 as a treatment for AD.

Metal-Free Decarboxylative Allylation of Oxime Esters under Light Irradiation.

Allylation reactions, often used as a key step for constructing complex molecules and drug candidates, typically rely on transition-metal (TM) catalysts. Even though TM-free radical allylations have been developed using allyl-stannanes, -sulfides, -silanes or -sulfones, much less procedures have been reported using simple and commercially available allyl halides, that are used for the preparation of the before-mentioned allyl derivatives. Here, we present a straightforward photocatalytic protocol for the decarboxylative allylation of oxime esters using allyl bromide derivatives under metal-free and mild conditions. This methodology yields a diverse variety of functionalized molecules including several pharmaceutically relevant molecules.

Enantioselective Aminosilylation of Alkenes by Palladium/Ming-Phos-Catalyzed Tandem Narasaka-Heck/Silylation Reaction.

A Pd-catalyzed enantioselective aminosilylation of alkenes via tandem Aza-Heck/silylation reaction under Pd/Sadphos catalysis is disclosed. A wide array of oxime esters and silicon reagents are tolerated, furnishing the chiral pyrrolines bearing one quaternary or two contiguous stereocenters in good yield with high enantioselectivity. Not only terminal alkenes but also tri-substituented internal alkenes successfully participate in the reaction, delivering vicinal stereocenters in complete diastereoselectivity and high enantioselectivity. DFT study is conducted to probe the reaction pathway and the origin of the enantioselectivity, which revealed that the stereoinduction arises from the weak interaction between the aromatic ring of the substrate fragment and naphthyl group in the ligand.

Four-Component Radical 1,2-Selenosulfonylation of Allenes.

Selenosulfones, as pivotal pharmaceutical molecule frameworks, have become a research hotspot in modern organic synthesis due to their vital need for efficient preparation. Herein, we have developed an iron-catalyzed four-component controllable radical tandem reaction of allenes involving cycloketone oxime esters, 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), and diphenyl diselenides for the synthesis of complex selenosulfones. This is the first case of achieving the 1,2-selenosulfonylation of allenes via a radical process, wherein precise control of radical rates and polarity matching enhance high regioselective conversion. The reaction conditions are ecofriendly and mild with step-efficiency by forming two new C-S bonds and one C-Se bond in one pot. Moreover, the 1,2-selenosulfonylation of allenes can be achieved by replacing cycloketone oxime esters with aryldiazonium tetrafluoroborates in this system.

Triphenylamine based oxime ester photoinitiator for LED-induced free radical photopolymerization and 3D printing

With the development of light-emitting diode (LED), it is increasingly important to design and prepare photoinitiators that can be used for LED excitation. We designed and synthesized four new LED oxime ester photoinitiators (TOXEs) based on the triphenylamine group. Among them, the maximum absorption wavelengths of TOXE-3 and TOXE-4 are red-shifted to 402 nm and 397 nm, and have high molar absorption coefficients (ε) of 24315 M-1cm−1 and 29915 M-1cm−1, respectively, which are higher than that of ethenone, 1-[9-ethyl-6-(2-methylbenzoyl)-9H-carbazol-3-yl] ethanone 1-(O-acetyloxime) (OXE02, 342 nm, 21836 M-1cm−1), indicating that it can be used in LED polymerization. Investigating the photopolymerization properties of the TOXEs/α, ω-diacryloyl poly(ethylene glycol) (PEGDA) system, under LED@365 nm irradiation, the double bond conversion rate (DC) of TOXE-1 and TOXE-2 were 83 % and 92 %, which were higher than OXE02 (80 %). Under LED@405 nm irradiation, the DC of TOXE-3 and TOXE-4 are 80 % and 78 % respectively, which is higher than that of OXE02 (52 %). To improve the photoinitiation ability of TOXEs, a two-component photoinitiation system using bis(4-tert-butylphenyl) iodonium (Iod) as an additive was tested. The DC of TOXEs has been improved under different light sources. Under LED@480 nm irradiation, the final DC of TOXE-4/Iod/PEGDA is 83 %. In addition, TOXE-3 and TOXE-4 can be applied to the laser cladding deposition (LCD) 3D printers. At the same time, we conduct research and verification on the polymerization mechanism of TOXEs through steady-state photolysis and electron spin resonance spin trapping experiments (ESR-ST). In addition, cytotoxicity assay and thermal stability testing showed that TOXEs exhibited excellent biocompatibility and thermal stability.

Ring-Opening of Donor-Acceptor Cyclopropane Diester for the Synthesis of Oxime Esters and 2,3-Dihydroazete Ester

AbstractA simple and efficient approach for the synthesis of privileged oxime esters by employing donor-acceptor cyclopropane diesters (DACs) as one of the potential precursors is reported. The strategy involves Lewis acid catalyzed ring-opening of DACs, resulting in an open-chain intermediate followed by the base-mediated construction of the corresponding oxime esters in a one-pot reaction. Moreover, the process also features the synthesis of diethyl 4-(4-methoxyphenyl)azete-2,2(3H)-dicarboxylate.

Carbazole-fused coumarin bis oxime esters (CCOBOEs) as efficient photoinitiators of polymerization for 3D printing with 405 nm LED

In this research, the innovative design and successful synthesis of two visible light photoinitiators, namely CCOBOE0 and CCOBOE1, have been confirmed through nuclear magnetic resonance (NMR) and mass spectrometry (MS). Both compounds exhibit strong absorption properties at 385, 405 and 450 nm, and FT-IR analyses have substantiated the ability of CCOBOE1 to initiate the polymerization of a trifunctional acrylate monomer (TMPTA) under these three light sources. The optimal conditions for maximizing the photoinitiation potential of CCOBOE1 were determined to be at a concentration of 2 × 10−5 mol.g−1 and under 405 nm LED irradiation. Photolysis experiments, theoretical calculations, detection of CO2 absorption peaks, and ESR experiments have all confirmed the generation of methyl radicals by CCOBOE1. Utilizing the identified optimal conditions, a “XYZ” pattern with a thickness of 963 μm and a 3D-object were successfully obtained via direct laser write (DLW) and digital light processing (DLP) 3D-printing upon irradiation at 405 nm. Additionally, differential scanning calorimetry (DSC) analyses demonstrated the promising performance of CCOBOE1 in initiating the thermal polymerization of acrylate monomers. In summary, the difunctional CCOBOE1 showed outstanding performance in both photo-initiation and thermal initiation of acrylate monomers. It provides a novel direction for the development of novel OXEs with dual activation modes.

Typ‐I‐Photoinitiator auf der Basis nachhaltiger Kohlenstoffpunkte

AbstractNachhaltige Kohlenstoffpunkte, die an der Oberfläche Oximestergruppen enthalten, welche einer homolytischen Bindungsspaltung folgen, zeigen ein Potential als Photoinitiatoren für die traditionelle freie radikalische Photopolymerisation. Die Kohlenstoffpunkte wurden nach einem solvothermalen Verfahren aus nachhaltigem Furfural, welches über Lignocellulose erhältlich ist, hergestellt. Aldehydgruppen der Oberfläche reagierten mit Hydroxylamin zu dem entsprechendem Oxim, während die Reaktion mit Benzoylchlorid zu einem bio‐basierten Typ I Photoinitiator (CD‐PI) führte, welcher nachhaltige Kohlenstoffpunkte enthält. Die Fähigkeit zur Photoinitiierung wurde unter UV‐Bestrahlung bei 365 nm mit dem traditionellen Photoinitiator (PI) Ethyl (2,4,6‐trimethyl benzoyl) phenyl phosphinat (TPO‐L) mittels Echtteit FTIR Spektroskopie verglichen. Die auf einem Gemisch von Urethandimethacrylat (UDMA) und Tripropylenglykoldiacrylat (TPGDA) basierte Photopolymerzusammensetzung führte unter Verwendung von CD‐PI oder TPO‐L zu einem ähnlichen Endumsatz von etwa 70 %. Dennoch erschien das vernetzte Material im Fall der Zusammensetzungen, die mit CD‐PI verarbeitet wurden, homogen, während jene, die mit TPO‐L hergestellt wurden, heterogen waren, was durch die beiden Glasübergangstemperaturen gezeigt wurde. Außerdem war die Migrationsgeschwindigkeit von CD‐PI in den gehärteten Proben geringer im Vergleich zu jenen Proben für die TPO‐L als PI eingesetzt wurde.

Type I Photoinitiator Based on Sustainable Carbon Dots.

Sustainable carbon dots comprising surficial oxime ester groups following homolytic bond cleavage exhibit potential as photoinitiators for traditional free radical photopolymerization. Carbon dots were made following a solvothermal procedure from sustainable furfural available from lignocellulose. Surficial aldehyde moieties reacted with hydroxylamine to the respective oxime while reaction with benzoyl chloride resulted in a biobased Type I photoinitiator comprising sustainable carbon dot (CD-PI). Photoinitiating ability was compared with the traditional photoinitiator (PI) ethyl (2,4,6-trimethyl benzoyl) phenyl phosphinate (TPO-L) by real-time FTIR with UV exposure at 365 nm. Photopolymer composition based on a mixture of urethane dimethacrylate (UDMA) and tripropylene glycol diacrylate (TPGDA) resulted in a similar final conversion of about 70 % using either CD-PI or TPO-L. Nevertheless, it appeared homogeneous in the case of compositions processed with CD-PI, while those made with TPO-L were heterogeneous as shown by two glass transition temperatures. Moreover, the migration rate of CD-PI in the cured samples was lower in comparison with those samples using TPO-L as PI.

Discovery of Novel N-Phenyltriazinone Derivatives Containing Oxime Ether or Oxime Ester Moieties as Promising Protoporphyrinogen IX Oxidase Inhibitors.

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is one of the most important targets for the discovery of green herbicides. In order to find novel PPO inhibitors with a higher herbicidal activity, a series of novel N-phenyltriazinone derivatives containing oxime ether and oxime ester groups were designed and synthesized based on the strategy of pharmacophore and scaffold hopping. Bioassay results revealed that some compounds showed herbicidal activities; especially, compound B16 exhibited broad-spectrum and excellent 100% herbicidal effects to Echinochloa crusgalli, Digitaria sanguinalis, Setaria faberii, Abutilon juncea, Amaranthus retroflexus, and Portulaca oleracea at a concentration of 37.5 g a.i./ha, which were comparable to trifludimoxazin. Nicotiana tabacum PPO (NtPPO) enzyme inhibitory assay indicated that B16 showed an excellent enzyme inhibitory activity with a value of 32.14 nM, which was similar to that of trifludimoxazin (31.33 nM). Meanwhile, compound B16 revealed more safety for crops (rice, maize, wheat, peanut, soybean, and cotton) than trifludimoxazin at a dose of 150 g a.i./ha. Moreover, molecular docking and molecular dynamics simulation further showed that B16 has a very strong and stable binding to NtPPO. It indicated that B16 can be used as a potential PPO inhibitor and herbicide candidate for application in the field.

Efficient and safe coumarin-carbazole-based oxime esters for one/two-photon polymerization of LEDs/NIR light

Photocuring has developed rapidly in recent years owing to its unique “5E” characteristics, especially in the industrial and manufacturing fields, where photoinitiators (PIs) are essential components of the polymerization system. However, most PIs have limited applications in fields that directly contact the human body, such as food packaging or biomedicine, due to migration stability and toxicity. Here, four oxime esters were designed as PIs by using coumarin-carbazole as the conjugate structure, and their properties were optimized by multisite modification of the molecular structure. First, substituents with different electronic properties were introduced at the 4-position of coumarin. The introduction of electron-withdrawing trifluoromethyl redshifted the molecule and better matched the light-emitting diode (LED) emission spectra (i.e., 365–450 nm). In addition, the introduction of long and branched alkyl chains on carbazole increased the solubility of the four PIs. The initiation efficiency of the PIs was improved by inserting long or cyclized alkyl chains at the α-position of C = N double bond. The experimental results demonstrated that these four PIs are superior to the commercial oxime ester OXE 02 in terms of light absorption and initiation ability under LED irradiation. The migration stability and cytocompatibility of these PIs were validated, ensuring a green and safe application in photocuring applications. Furthermore, these PIs exhibited a considerable writing speed and remarkable nanopatterning capabilities under 780 nm laser in two-photon polymerization. These outstanding properties indicated their great potential for applications in diverse areas of photocuring, especially in food packaging, bio-3D printing, tissue engineering, and nano-additive manufacturing.

Novel 2,4-Dichloro-5-sulfamoylbenzoic Acid Oxime Esters: First Studies as Potential Human Carbonic Anhydrase Inhibitors.

In this study, a focused library of oxime ester derivatives of 2,4-dichloro-5-sulfamoylbenzoic acid (lasamide) containing Schiff bases was synthesized and tested in vitro for their ability to inhibit the cytosolic human carbonic anhydrases (hCAs) I and II, as well as the transmembrane and tumor-associated IX and XII isoforms. As a result, we obtained a first line of knowledge on lasamide derivatives potentially useful for development as CA inhibitors (CAIs). In particular, we focused our attention on the derivative 11, which was selective toward hCAs IX and XII over the cytosolic isoenzymes. An in silico study was conducted to assess the binding mode of 11 within hCAs IX and XII. Also, antiproliferative assays highlighted promising derivatives. The data obtained in this study are currently in use for the development of better-performing compounds on the tumor-associated isoforms.

The role of the Terminal Benzene Derivatives in Triphenylamine‐Based Oxime Esters for Free Radical Photopolymerization

AbstractIn this study, we investigate the effect of terminal benzene derivatives in triphenylamine‐based oxime esters on their photoreactivity. Five novel oxime esters (Miko series) that containing different benzene derivatives as terminal groups, were synthesized. The electronic properties of the substituents on the benzene ring range from electron‐donating to electron‐withdrawing. Specifically, a methoxy benzene for Miko‐MOB, tert‐butyl benezene for Miko‐t‐Bu, chloro benzene for Miko‐CB, trifluoromethyl benzene for Miko‐TFM, and nitro benzene for Miko‐NB. Additionally, a compound with benzene only as the terminal substituent (TP‐1) was selected for comparision. All the new compounds exhibited higher molar extinction coefficients than TP‐1. Additionally, the steady‐state photolysis and electron spin resonance (ESR) properties would decrease from the electron‐donating substitutes to electron‐withdrawing substitutes. Finally, these oxime esters are utilized in Type I photoinitiating systems for the free radical polymerization of trimethylolpropane triacrylate (TMPTA) under UV or LED@405 nm light irradiation conditions. Among all formulations, Miko‐MOB demonstrated the highest double bond conversion efficiency under both UV and LED@405 nm light irradiation. Thus, terminal benzene derivatives in oxime esters play an important role in tuning the optical and photochemical reaction performance, offering significant value for the design strategy of such photoinitiators.

Novel trifluoromethyl ketone derivatives as oral cPLA2/COX-2 dual inhibitors for resolution of inflammation in rheumatoid arthritis

Thirty-five trifluoromethyl hydrazones and seventeen trifluoromethyl oxime esters were designed and synthesized via molecular hybridization. All the target compounds were initially screened for in vitro anti-inflammatory activity by assessing their inhibitory effect on NO release in LPS-stimulated RAW264.7 cells, and the optimal compound was finally identified as 2-(3-Methoxyphenyl)-N'-((6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-ylidene)acetohydrazide (F26, IC50 = 4.55 ± 0.92 μM) with no cytotoxicity. Moreover, F26 potently reduced the production of PGE2 in LPS-stimulated RAW264.7 cells compared to indomethacin. The interaction of F26 with COX-2 and cPLA2 was directly verified by the CETSA technique. F26 was found to modulate the phosphorylation levels of p38 MAPK and NF-κB p65, as well as the protein expression of IκB, cPLA2, COX-2, and iNOS in LPS-stimulated rat peritoneal macrophages. Additionally, F26 was observed to prevent the nuclear translocation of NF-κB p65 in LPS-stimulated rat peritoneal macrophages by immunofluorescence localization. Therefore, the aforementioned in vitro experiments demonstrated that F26 blocked the p38 MAPK and NF-κB pathways by binding to COX-2 and cPLA2. In the adjuvant-induced arthritis model, F26 demonstrated a significant effect in preventing arthritis symptoms and inflammatory status in rats, exerting an immunomodulatory role by regulating the homeostasis between Th17 and Treg through inhibition of the p38 MAPK/cPLA2/COX-2/PGE2 and NF-κB pathways. Encouragingly, F26 caused less acute ulcerogenicity in rats at a dose of 50 mg/kg compared to indomethacin. Overall, F26 is a promising candidate worthy of further investigation for treating inflammation and associated pain with lesser gastrointestinal irritation, as well as other symptoms in which cPLA2 and COX-2 are implicated in the pathophysiology.

Photocatalyzed Formation of gem‐Difluoroalkenes Using Oxime Esters

AbstractIn this manuscript a general photocatalytic approach for the synthesis of alkyl‐substituted gem‐difluoroalkenes using readily available oxime esters and 1‐bromo‐1,1‐difluoroprop‐2‐ene (BDFP) has been established. This strategy involving a radical bromo elimination provides access to a large variety of value‐added fluorinated molecules. The mild reaction conditions are compatible with many functional groups including complex natural products or drug molecules. Experimental and theoretical mechanistic investigations indicate that the efficiency of the process relies on the crucial role of imine radical, which is formed after photoexcitation via energy transfert (EnT) and decarboxylation of the oxime ester. Indeed, the imine radical would either behave as a bromine radical scavenger or an XAT promoter in this reaction.

Photoinduced Palladium-Catalyzed Radical Heck-Type Coupling of Cyclobutanone Oxime Esters with Vinyl Arenes.

A palladium-catalyzed radical Heck-type coupling reaction of cyclobutanone oxime esters with olefins under visible-light irradiation has been developed. The cyanoalkyl/Pd(I) hybrid species generated by selected ring-opening C-C bond cleavage of imino/Pd(I) species reacted smoothly with vinyl arenes, delivering the cyanoalkylation olefins under mild conditions. This elegant strategy has a broad scope and functional group tolerance. Subsequently, late-stage functionalization of bioactive molecules and synthetic transformations of the product further confirm the practicality.