Imine Derivatives Research Articles

Design, Synthesis, Investigation, and Biological Activity Assessments of (4-Substituted-Phenyl)-N-(3-morpholinopropyl)-3-phenylthiazol-2(3H)-imine Derivatives as Antifungal Agents.

In this study, a series of novel thiazol-2(3H)-imine (2a-2j) were designed, synthesized, and characterized by means of 1H NMR, 13C NMR, and HRMS spectral analyses. In vitro antifungal activity was performed using a modified EUCAST protocol. Two of the synthesized compounds (2d and 2e) showed activity against Candida albicans and Candida parapsilosis. Compound 2e showed activity against C. parapsilosis (MIC50 = 1.23 μg/mL) for 48 h. This value is very similar to ketoconazole. The dynamic analysis of the potential compounds 2d and 2e revealed notable stability while interacting with the 14α-demethylase enzyme substrate. The absorption, distribution, metabolism, and excretion (ADME) studies of the candidate compound showed acceptable ADME parameter data and verified their drug-likeness characteristics. According to the results of this study, compound 4-(4-fluorophenyl)-N-(3-morpholinopropyl)-3-phenylthiazol-2(3H)-imine (2e) and its derivatives as 14α-demethylase inhibitors can be used as a new antifungal for further structural improvements and additional research.

Synthesis, biochemical screening and in-silico investigations of arylsulfonamides bearing linear and cyclic tails

A small series of arylsulfonamide derivatives was designed and synthesized to study linear and cyclic inhibitors targeting human Carbonic Anhydrases (hCAs EC 4.2.1.1) as essential enzymes regulating (patho)-physiological processes. Particularly, the synthesis of these ten compounds was inspired to the well-known arylsulfonamides having flexible or constrained linkers able to maintain the two crucial moieties, anchoring zinc group and hydrophobic tail, in the optimized orientation within CA cavities of tumor-expressed isoforms hCA IX and hCA XII. The synthesized imine derivatives and related cyclic 1,3-thiazin-4-ones were screened in a stopped-flow carbon dioxide hydrase assay and proved to be effective inhibitors against hCA IX and hCA XII isoforms with Ki values ranging of 3.7–215.7 nM and 5.7–415.0 nM, respectively. Molecular docking studies of both series of arylsulfonamides were conducted to propose their binding mode within hCA IX and hCA XII active sites thus highlighting their distinct ability to occupy the two catalytic cavities. Moreover, the 4-[(3-cyanophenyl)methylidene]aminobenzene-1-sulfonamide 7 proved to reduce the cell viability of breast carcinoma (MCF-7) and colon rectal carcinoma (HCT-116) human cell lines under the fixed doses of 10 μM. These results encouraged us to continue our efforts in developing potent and efficient arylsulfonamides targeting hCA IX and hCA XII isoforms.

Synthesis, Characterization, DPPH Radical Scavenging, Urease Enzyme Inhibition, Molecular Docking Simulation, and DFT Analysis of Imine Derivatives of 4-formylpyridine with Selective Detection of Cu+2 Ions.

This study aimed to prepare three imine derivatives (1, 2, and 3) via a condensation reaction of phenyl hydrazine, 2-hydrazino pyridine, and 4-methoxy aniline with 4-formyl pyridine. Electron impact mass spectrometry (EIMS), proton nuclear magnetic resonance (1H-NMR), ultraviolet-visible (UV-Vis) and Fourier transform infrared (FTIR) spectroscopy were utilized for the characterization. The chemosensing properties of [4((2-phenyl hydrazono)methyl) pyridine] (1), [2-(2-(pyridin-4-ylmethylene)hydrazinyl) pyridine] (2), and [4-methoxy-N-yl methylene) aniline] (3) imino bases have been explored for the first time in aqueous media. The photophysical properties of chemosensors (1, 2, and 3) were examined by various cations (Na+, NH4+, Ba+2, Ni+2, Ca+2, Hg+2, Cu+2, Mg+2, Mn+2, and Pd+2). The chemosensor (1) showed very selective binding capability with copper ions at low concentrations (20 μM) without the influence of any other mentioned ions. The maximum complexation was noted with Cu+2 and 1 at pH between 7 to 7.5. The stoichiometry binding ratio between chemosensor (1) and Cu+2 was determined by Job's plot and it was found to be 1:2. The current study explored the use of these Schiff bases for the first time as heterocyclic chemosensors. DPPH radical scavenging, urease enzyme inhibition activities, molecular docking simulation, and density functional theory (DFT) analysis of compounds 1, 2, and 3 were also conducted.

The effect of novel β-lactam derivatives synthesized from substituted phenethylamines on resistance genes of MRSA isolates.

This study focuses on the activity of previously reported imine and β-lactam derivatives against methicillin-resistant Staphylococcus aureus (MRSA) isolates. The presence of mecA and blaZ genes in the isolates was determined, and the minimum inhibitory concentration (MIC) values were determined based on the antibacterial activity against these isolates. Active compounds were selected and their ability to act against resistant isolates in vitro was determined. Concurrently, biochemical (nitrocefin) and molecular (qRT-PCR) tests were used to investigate the ability of the compounds to induce resistance genes in MRSA isolates. The cytotoxicity of the compounds on human dermal fibroblasts (HDF) was investigated. The MIC values of compounds (10) and (12) against MSSA and MRSA isolates were 7.81 and 15.62 μg ml-1, respectively. The most active compounds were identified as (10) and (12), and it was observed that the isolates did not develop resistance to these compounds in vitro. These compounds were found to inhibit β-lactamase, reduce the expression of resistance genes, and exhibit reduced HDF cell toxicity in a dose-dependent manner. According to the findings of the study, it can be concluded that these compounds show promise as hits with an interesting mechanism of action for further chemical modifications to develop new MRSA inhibitors.

An In‐Depth Review on Recent Progress in Synthetic Approaches and Biological Activities of Thiazol‐2(3H)‐Imine Derivatives

AbstractThis review presents the in‐dept analysis of the synthetic approaches towards thiazol‐2(3H)‐imine and embarks at its various biological properties published during 2000 to 2023. The most important method of synthesis involves the reaction of substituted thioureas and α‐halo carbonyl compounds, and condensation and nucleophilic addition of 2‐amino‐1,3‐thiazoline with aldehydes. Additionally, isothiocyanate‐based multicomponent synthesis, and α‐nitroepoxides have been proved as benign precursors for this motif. Several eco‐friendly and solvent‐free synthesis from diazonium salts, acetylenes, tertiary enaminones and thiosemicarbazides have also been reported. This epitome is a unique combination of synthetic methods as well as biological activities like anti‐inflammatory, anti‐bacterial, anti‐cancer, anti‐leishmanial, anti‐microbial, herbicidal, anti‐HIV, and may be a valuable tool for researchers to tailor the synthetic procedures according to specific target structures and applications. Moreover, this review enlightens the applications of thiazol‐2(3H)‐imine as platelet GPIIB/IIIA receptor antagonists, alkaline phosphatase inhibitors, neurodegenerative drug Pifithrin‐α analogues, and skin whitening agents.

Synthesis of Some New Hydrazide-Hydrazone and Heterocyclic Compounds Thiophene, Imine, Coumarin and Pyrazole Derivatives

تم تشييد سلسلة من المشتقات الجديدة الثايوفين ، الايمين ، الكومارين و البيرازول X4-X16 باستخدام N – (1- (4- (بنزيل سلفونيل) فينيل) ايثيليدين)-2- سيانو اسيتو هيدرازيد X3 بوصفه مادة اساسية أولية عن طريق مفاعلتها مع كواشف مختلفة مثل (التترالون ، سايكلو بنتانون ، سايكلو هبتانون ، 2-هيدروكسي بنزالديهايد ، 2-هيدروكسي-1- نفثالديهايد ، كبريتيد ثنائي كاربون و فنيل ايزوثايو سيانيد). تم تحضير المركب X3 من تصعيد 4-(بنزايل سلفونيل) اسيتوفينون مع 2- سيانو اسيتوهيدرازايد في الايثانول. تم تشخيص تراكيب المركبات المحضرة الجديدة من خلال القياسات الفيزيائية و الطيفية (الأشعة تحت الحمراء والتحليل الطيفي البروتون والكاربون 13 النووي المغناطيسي).

Synthesis and molecular structure exploration of novel piperidin-4-one imine derivatives combined with DFT and X-ray: A new class of antioxidant and anti-inflammatory agents

Inflammation is one of the pertinent responses of the body, depending mainly on the process and factors involved in combating the oxidative species produced either by any infection or failure of the antioxidant pathways. In search of new compounds to exhibit antioxidant and anti-inflammatory activity here, we have successfully reported the synthesis of three novel compounds of Piperidin-4-one skeleton by adopting simple and convenient methods. Compound 1, (3, 3-dimethyl-2, 6-bis(3,4,5-trimethoxyphenyl) piperidin-4-one) was synthesized by one-pot Mannich condensation reaction having good yield (88 %). Furthermore in the next step highly functionalized imine derivatives, Compound 2 (3,3-dimethyl-2,6-bis (3,4,5-trimethoxyphenyl) piperidine-4-one) hydrazine carbothioamide) and Compound 3 (3,3-dimethyl-2,6-bis(3,4,5-trimethoxyphenyl) piperidin-4-one oxime) were prepared by the condensation reaction with thiosemicarbazide and hydroxylamine hydrochloride with compound 1, respectively. The structure of the compounds has been deduced by the combined use of modern spectroscopic and single crystal x-ray diffraction (XRD) techniques. in-silico ADMET studies predict pharmacokinetic properties and showed that compounds are non toxic on vital organs. The optimized geometry and reactivity parameters of compounds were further calculated based on the B3LYP/6-31G (d, p) density functional theory (DFT). The negative values of chemical potential follow the trend as 2 (−0.2101) >3 (−0.2198) >1(-0.2233) signifies that all compounds are reactive in nature as evident from in-vitro antioxidant and anti-inflammatory response were determined by using the DDPH assay and protein denaturation methods respectively. Compounds possess good radical scavenging activity having IC 50 values 30.392 μM (2), 37.802 (1) μM, and 72.285 (3) μM, and anti-inflammatory response in same manner indicating that 2 (71.3 %) is more active than compound 1 (43.5 %) and 3 (39.3 %) marking them as a potential antioxidant and anti-inflammatory agents.

Direct synthesis of partially ethoxylated branched polyethylenimine from ethanolamine

We report here a method to make a branched and partially ethoxylated polyethyleneimine derivative directly from ethanolamine. The polymerization reaction is catalysed by a pincer complex of Earth-abundant metal, manganese, and produces water as the only byproduct. Industrial processes to produce polyethyleneimines involve the transformation of ethanolamine to a highly toxic chemical, aziridine, by an energy-intensive/waste-generating process followed by the ring-opening polymerization of aziridine. The reported method bypasses the need to produce a highly toxic intermediate and presents advantages over the current state-of-the-art. We propose that the polymerization process follows a hydrogen borrowing pathway that involves (a) dehydrogenation of ethanolamine to form 2-aminoacetaldehyde, (b) dehydrative coupling of 2-aminoacetaldehyde with ethanolamine to form an imine derivative, and (c) subsequent hydrogenation of imine derivative to form alkylated amines.

A novel fluorescence enhancement Al(III) sensor based on C1 symmetric Binol imine derivative: Recognition, binding mechanism and Bio-imaging application

A novel C1 symmetric Binol imine Schiff base fluorescence sensor (Sa,R)-6 was designed and synthesized by using (S)-Binol-3-aldehyde as initial material. The probe showed great fluorescence enhancement at λ = 552 nm and visual light yellow fluorescence under 365 nm UV lamp irradiation with presence of Al3+. Quantitative test was feasible from 10 μM to the detection limit which reaches nanomole level. Job’s plot, HRMS spectroscopic and NMR titration indicated the formation of Al[(Sa,R)-6]2+. DFT calculations suggested the coordination reaction lead to a CHEF effect and the “turn-on” fluorescence response. Moreover, (Sa,R)-6 was well tolerable to human normal astrocyte cell line HA-1800 in cell viability test so that it could be utilized for detecting trace Al3+ in vitro in a concentration-dependent manner via confocal imaging which proved its potential of diagnosis and treatment of Aluminum related diseases.

Developing a novel imine derivative as a corrosion inhibitor for Q235 carbon steel in 1 M HCl solution: Experiments and theoretical calculations

During oil and gas extraction, metals are inevitably exposed to acidic environments on a regular basis. Acid solutions, particularly hydrochloric acid, are employed in a multitude of industrial processes, including oil well acidising, steel pickling, ferroalloy pickling and acid cleaning. These applications frequently result in severe metal corrosion. To cope with corrosion, the superlative simple and effective method is to prevent corrosion inhibitors. Naphthyridinimides are not as effective as rust inhibitors, but their corrosion inhibition is significantly improved by the addition of Br ions. This thesis focuses on the synthesis of naphthylimine-type novel organic corrosion inhibitors and the corrosion inhibition mechanism, with the main content of 3,3′-(1,3,6,8-tetraoxo-1,3 6,8-tetrahydrobenzo[lmn] [3,8] phenanthroline-2,7-diyl) bis (N-ethyl -N, N-Dimethyl-1-propylamine) bromide (NDI-N-Br) on Q235 carbon steel in an acidic environment (1 M hydrochloric acid solution). The corrosion inhibition efficiencies of NDI-N-Br reached 93.53 % at 300 ppm at an ambient temperature of 298 K. The corrosion inhibitor NDI-N-Br forms a protective film on the metal surface and organizes the interaction between the metal matrix and the corrosive medium, providing a rust inhibiting effect. This thesis shows that this class of compounds can be well applied to acidic environments and provide ideas for the subsequent development of naphthylimide-based organic corrosion inhibitors.

Subtle structural variation of antipyrine derivatives for ESIPT based fluorescence recognition of Al3+ and Zn2+ ions

Three imine derivatives containing antipyrine moiety viz. A1, A2 and A3 have been synthesized and characterized by SC-XRD analysis. The molecules are weakly fluorescent due to ESIPT process. The A1 and A2 have high affinity as well as selectivity for Al3+ that allow its nano-molar level detection. On the other hand, A3 interacts with both Al3+ and Zn2+ as reflected from the change of emission profiles at two different wavelengths. Such distinctive photo-physical interaction of A3 over A1 and A2 may be elucidated through hard-soft interaction concept. Various spectroscopic techniques have been used to explain the sensing mechanism. DFT studies have been performed to explain and justify experimental findings. The interaction of A3 towards Al3+ and Zn2+ has been utilized to construct a logic gate. Moreover, real water analysis has also been performed.

Synthesis of ionizable lipopolymers using split-Ugi reaction for pulmonary delivery of various size RNAs and gene editing.

We present an efficient approach for synthesizing cationic poly(ethylene imine) derivatives using the multicomponent split-Ugi reaction to rapidly create a library of complex functional ionizable lipopolymers. We synthesized a diverse library of 155 polymers, formulated them into polyplexes to establish structure-activity relationships crucial for endosomal escape and efficient transfection. After discovering a lead structure, lipopolymer-lipid hybrid nanoparticles are introduced to preferentially deliver to and elicit effective mRNA transfection in lung endothelium and immune cells, including T cells with low in vivo toxicity. The lipopolymer-lipid hybrid nanoparticles showed 300-fold improvement in systemic mRNA delivery to the lung compared to in vivo -JetPEI ® . Lipopolymer-lipid hybrid nanoparticles demonstrated efficient delivery of mRNA-based therapeutics for treatment of two different disease models. Lewis Lung cancer progression was significantly delayed after treatment with loaded IL-12 mRNA in U155@lipids after repeated i.v. administration. Systemic delivery of human CFTR (hCFTR) mRNA resulted in production of functional form of CFTR protein in the lungs. The functionality of hCFTR protein was confirmed by restoration of CFTR- mediated chloride secretion in conductive airway epithelia in CFTR knockout mice after nasal instillation of hCFTR mRNA loaded U155@lipids. We further showed that, U155@lipids nanoparticles can deliver complex CRISPR-Cas9 based RNA cargo to the lung, achieving 5.6 ± 2.4 % gene editing in lung tissue. Moreover, we demonstrated successful PD-1 gene knockout of T cells in vivo . Our results highlight a versatile delivery platform for systemic delivering of mRNA of various sizes for gene therapy for a variety of therapeutics.

Design and synthesis of broadband absorption covalent organic framework for efficient artificial photocatalytic amine coupling

Developing highly active materials that efficiently utilize solar spectra is crucial for photocatalysis, but still remains a challenge. Here, we report a new donor-acceptor (D-A) covalent organic framework (COF) with a wide absorption range from 200 nm to 900 nm (ultraviolet-visible-near infrared light). We find that the thiophene functional group is accurately introduced into the electron acceptor units of TpDPP-Py (TpDPP: 5,5’-(2,5-bis(2-ethylhexyl)−3,6-dioxo-2,3,5,6-tetrahydropyrrolo [3,4-c]pyrrole-1,4-diyl)bis(thiophene-2-carbaldehyde), Py: 1,3,6,8-tetrakis(4-aminophenyl)pyrene) COFs not only significantly extends its spectral absorption capacity but also endows them with two-photon and three-photon absorption effects, greatly enhancing the utilization rate of sunlight. The selective coupling of benzylamine as the target reactant is used to assess the photocatalytic activity of TpDPP-Py COFs, showing high photocatalytic conversion of 99% and selectivity of 98% in 20 min. Additionally, the TpDPP-Py COFs also exhibit the universality of photocatalytic selective coupling of other imine derivatives with ~100% conversion efficiency. Overall, this work brings a significant strategy for developing COFs with a wide absorption range to enhance photocatalytic activity.

Synthesis and Evaluation of Promising Antibacterial, Antifungal, and Antioxidant Activities for New Imidazo[1,2‐A]Pyridine‐Derived Imines

AbstractThis study presents the synthesis of a novel series of imine derivatives derived from imidazo[1,2‐a]pyridine as potential therapeutic agents. The imines were obtained by condensing 2‐(4‐bromophenyl)‐6‐chloroimidazo[1,2‐a]pyridine‐3‐carbaldehyde with primary amines, leading to high‐purity products that were characterized using various spectroscopic techniques. The compounds demonstrated promising in vitro antimicrobial activity against various bacteria, including Staphylococcus aureus and Escherichia coli, as well as fungi, such as Candida albicans, Saccharomyces cerevisiae, and Aspergillus brasiliensis. Furthermore, the antioxidant properties of the imine derivatives were evaluated using DPPH and ABTS techniques, and the IC50 values measured revealed their ability to scavenge free radicals. Overall, this study provides a valuable contribution to the field of pharmacology by synthesizing a new series of imine derivatives with significant potential as new therapeutic agents, exhibiting both antimicrobial and antioxidant properties.

Synthesis, structural characterization and antitrypanosomal activity of ferrocenyl-based imines with (2 or 4)-nitrophenyl-2-furan group

Two new metallocene complexes with formulation [Fe(η5-C5H5){(η5-C5H4)-NCH-2-C4H2O-(5-C6H4-2-NO2)}] (3) and [Fe(η5-C5H5){(η5-C5H4)-NCH-2-C4H2O-(5-C6H4-4-NO2)}] (4) have been synthesized and their antitrypanosomal activity has been evaluated. Complexes 3 and 4 were obtained by condensation reaction of ferrocenylamine (1) with respective 5-(2-nitrophenyl)-2-furancarboxaldehyde (2a) or 5-(4-nitrophenyl)-2-furancarboxaldehyde (2b). The complexes were fully characterized by spectroscopic techniques (FT-IR, 1H and 13C{1H} NMR, and HRMS), which confirm their correct obtainment. The crystal structures of 3 and 4 were also determined by single crystal X-ray diffraction. Furthermore, UV–visible studies revealed that compounds 3 and 4 exhibited suitable stability in DMSO:HEPES buffer solution (80:20) throughout 24 h. The in vitro antiparasitic activities of ferrocenyl imine derivatives 3 and 4 were assessed against two species of parasites, Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei). The obtained results revealed that compound 3 (EC50 = 0.44 μM) exhibited nearly a 40-fold greater efficacy as an anti-T. brucei agent compared to derivative 4 (EC50 = 16.0 μM). Moreover, compound 3 demonstrated superior potency when compared with its organometallic analogs (EC50 = 2.42–13.3 μM), which were previously reported by our research group. Interestingly, the EC50 value of 3 was found to be 8 times greater than that of nifurtimox (EC50 = 3.56 μM). The cytotoxicity of the ferrocenyl imines was also evaluated on the L6 rat skeletal myoblast cell line.

Novel Yellow Aromatic Imine Derivative Incorporating Oxazolone Moiety for Color Resist Applications

A novel aromatic imine derivative, 2′-(1,4-phenylene)bis[4-[(4-methoxyphenyl)methylene]-5(4H)-oxazolone] (PBMBO), was designed and synthesized as a yellow colorant additive for green color filters used in image sensors. The optical and thermal properties of the newly developed material were evaluated both in solution and within color filter film conditions. PBMBO demonstrated a molar extinction coefficient of 2.24 × 104 L/mol·cm in solution, surpassing that of the commercially employed yellow colorant MBIQO by a factor of 1.82. Color resist (CR) films incorporating PBMBO exhibited outstanding optical characteristics, displaying 0.03% transmittance at 435 nm, 99.3% transmittance at 530 nm, and a sharp slope within the 400 to 550 nm range. The decomposition temperature of PBMBO was 303 °C, indicating relatively superior thermal stability compared to MBIQO. Consequently, PBMBO emerges as a highly promising candidate for a yellow colorant additive in imaging sensor color filters, owing to its exceptional optical and thermal stability. Its potential applications are anticipated to extend across various fields of organic semiconductors.

Effect of hydroxy groups on structural, electronic, and biological properties of methyl carbazate containing hydroxy benzaldehyde-based imines. A combined experimental and theoretical investigation

Interactions present in differently substituted hydroxy based imine derivatives were characterised and identified by the utilisation of spectroscopic techniques in conjunction with X-ray crystallography and theoretical computations. All the target compounds ‘a-c’ crystallises in monoclinic crystal system with P21/c and C2/c space groups. CH…Pi and Pi…Pi interaction are the characteristic interactions present in the target compounds ‘a-c’ The most significant contributions to the crystal packing were found using Hirshfeld surface analysis, and potential contact points were identified. H…H, O…H and C…H contacts and π stacking interactions are the dominant contacts observed in all the crystals these results showed that hydrogen bonding and hydrophobic interactions were significantly present. Furthermore, investigations related to calculations of the molecular electrostatic potential and frontier molecular orbital (highest occupied–lowest unoccupied) were carried out for the optimised structure. The HOMO-LUMO energy gap made it possible to determine the molecule's chemical hardness, chemical inertness, electronegativity, and electrophilicity index, which showed its possible kinetic stability and reactivity. The target compounds' predicted activity spectra (PASS) showed that these compounds exhibit significant Testosterone 17beta-dehydrogenase (NADP+) inhibition activity, with Pa 7.18–7.95. Finally, Testosterone 17beta-dehydrogenase (NADP+) (PDB-ID 3KLP) was used to conduct molecular docking investigations of compounds ‘a-c’. Due to their tiny size and lack of rigidity, which enable them to bind well at any position, a and b exhibit higher binding free energies of -7.08 and -7.00 kcal/mol and inhibition constants of 0.1 and 1.2 µM than compound c.

Unveiling the Oxazolidine Character of Pseudoproline Derivatives by Automated Flow Peptide Chemistry.

Pseudoproline derivatives such as Thr(ΨPro)-OH are commonly used in peptide synthesis to reduce the likelihood of peptide aggregation and to prevent aspartimide (Asi) formation during the synthesis process. In this study, we investigate notable by-products such as aspartimide formation and an imine derivative of the Thr(ΨPro) moiety observed in flow peptide chemistry synthesis. To gain insight into the formation of these unexpected by-products, we design a series of experiments. Furthermore, we demonstrate the oxazolidine character of the pseudoproline moiety and provide plausible mechanisms for the two-way ring opening of oxazolidine leading to these by-products. In addition, we present evidence that Asi formation appears to be catalyzed by the presence of the pseudoproline moiety. These observed side reactions are attributed to elevated temperature and pressure; therefore, caution is advised when using ΨPro derivatives under such harsh conditions. In addition, we propose a solution whereby thermodynamically controlled Asi formation can be kinetically prevented.

Studies of the Functionalized α-Hydroxy-p-Quinone Imine Derivatives Stabilized by Intramolecular Hydrogen Bond.

In this work, reactions between 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-diones with different benzohydrazides were studied. Nucleophilic substitution at C(6) was followed by isomerization and led to α-hydroxy-p-quinone imine derivatives. Synthesized compounds represent a combination of several structural motifs: a benzimidazole core fused with α-hydroxy-p-quinone imine, which contains a benzamide fragment. X-ray crystallography analysis revealed the formation of dimers linked through OH···O interactions and stabilization of the imine form by strong intramolecular NH···N hydrogen bonds. The protonation/deprotonation processes were investigated in a solution using UV-Vis spectroscopy and a 1H NMR titration experiment. Additionally, the electrochemical properties of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its α-hydroxy-p-quinone imine derivative as cathode materials were investigated in acidic and neutral environments using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as a potentially effective active electrode in aqueous electrolyte batteries; however, further optimization is required.

Umpolung reactivity of strained C–C σ-bonds without transition-metal catalysis

Umpolung is an old and important concept in organic chemistry, which significantly expands the chemical space and provides unique structures. While, previous research focused on carbonyls or imine derivatives, the umpolung reactivity of polarized C–C σ-bonds still needs to explore. Herein, we report an umpolung reaction of bicyclo[1.1.0]butanes (BCBs) with electron-deficient alkenes to construct the C(sp3)-C(sp3) bond at the electrophilic position of C–C σ-bonds in BCBs without any transition-metal catalysis. Specifically, this transformation relies on the strain-release driven bridging σ-bonds in bicyclo[1.1.0]butanes (BCBs), which are emerged as ene components, providing an efficient and straightforward synthesis route of various functionalized cyclobutenes and conjugated dienes, respectively. The synthetic utilities of this protocol are performed by several transformations. Preliminary mechanistic studies including density functional theory (DFT) calculation support the concerted Alder-ene type process of C–C σ-bond cleavage with hydrogen transfer. This work extends the umpolung reaction to C–C σ-bonds and provides high-value structural motifs.