Cyclic Condensation Research Articles

Heterogeneous photoredox catalysis using fluorescein polymer brush functionalized glass beads

AbstractPhotocatalysis is a valuable and versatile method to perform a variety of chemical transformations under ambient temperatures and pressures using mild visible light. This work showcases an example of fluorescein‐functionalized polymers grafted to micro‐scale glass beads as heterogeneous photoredox catalysts. X‐ray photoelectron spectroscopy and thermogravimetric analysis were used to analyze the resulting functional glass beads. Model reactions that are demonstrated include a cyclic condensation and a radical dehalogenation that can both be performed to high yields. Successful recyclability of the fluorescein polymer brush beads is demonstrated with detailed characterization confirming that photocatalytic polymer brushes remain tethered to the surface. As such, this allows for purification and reuse of the heterogeneous photocatalyst beads after simple filtration.

One-Carbon Insertion and Polarity Inversion Enabled a Pyrrole Strategy to the Total Syntheses of Pyridine-Containing Lycopodium Alkaloids: Complanadine A and Lycodine.

Complanadine A and lycodine are representative members of the Lycopodium alkaloids with a characteristic pyridine-containing tetracyclic skeleton. Complanadine A has demonstrated promising neurotrophic activity and potential for persistent pain management. Herein we report a pyrrole strategy enabled by one-carbon insertion and polarity inversion for concise total syntheses of complanadine A and lycodine. The use of a pyrrole as the pyridine precursor allowed the rapid construction of their tetracyclic skeleton via a one-pot Staudinger reduction, amine-ketone condensation, and Mannich-type cyclization. The pyrrole group was then converted to the desired pyridine by the Ciamician-Dennstedt rearrangement via a one-carbon insertion process, which also simultaneously introduced a chloride at C3 for the next C-H arylation. Other key steps include a direct anti-Markovnikov hydroazidation, a Mukaiyama-Michael addition, and a Paal-Knorr pyrrole synthesis. Lycodine and complanadine A were prepared in 8 and 11 steps, respectively, from a readily available known compound.

Synthesis, spectral characterization and biological evaluations with DFT analysis on molecular geometry and NLO of 1,4,7,10-tetraazacyclotetradecane-11,14-dione

A novel 14-membered tetradentate N4 macrocyclic ligand, STETA (1,4,7,10-tetraazacyclotetradecane-11,14-dione) was synthesized by [1+1] cyclic condensation of succinic acid with triethylenetetramine through reflux method in ethanolic solvent. The synthesized macrocyclic ligand was experimentally characterized by C H N analysis, FT-IR, FT-Raman, electronic, 1H NMR, 13C NMR and ESI MS. Optimization of molecular geometry and spectral (FT-IR, FT-Raman, 1H/13C NMR) analysis of STETA were performed by employing DFT with B3LYP/6-311+G(d) basis set and computational results were correlated with experimental (NMR, IR, Raman) spectral values. Electronic absorption properties of STETA were monitored using TD-DFT approach and also theoretical UV–vis results were experimentally compared. FMO analysis, MEP plot, global reactivity descriptors, first-order hyperpolarizability and NBO analysis were rationalized on the ground of DFT computation. NLO activity of title molecule was confirmed by both molecular hyperpolarizability calculations and SHG measurements. In vitro antibacterial activity and DPPH radical scavenging effects of STETA were screened.

Assessment of Dihydro[1,3]oxazine‐Fused Isoflavone and 4‐Thionoisoflavone Hybrids as Antibacterials

AbstractA series of isoflavone functionalized 3,4‐dihydro‐1,3‐oxazine hybrids was synthesized in good to excellent yields through a Mannich‐type condensation cyclization reaction of 6‐chloro‐7‐hydroxy‐3‐(2‐methoxy‐phenyl)‐chromen‐4‐one or 6‐chloro‐7‐hydroxy‐3‐(2‐methoxy‐phenyl)‐chromene‐4‐thione with formaldehyde and primary amines. After spectroscopic characterization, these newly prepared hybrids were evaluated for their antibacterial activities against two of each Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. Among the screened compounds, dihydro[1,3]oxazine‐fused 4‐thionoisoflavones(9 band9 c) exhibited potent inhibitory activity against all the tested bacterial species. Moreover, compound 9 b possessed most promising antibacterial activity against P. aeruginosa and B. subtiliswith MIC 16 μg/mL and S. aureusand E. coliwith MIC 32 μg/mL. Further, 9 bdemonstrated better efficacy (MIC=16 μg/mL) than the standard drug ampicillin (MIC=32 μg/mL) against P. aeruginosaand it also found to be equipotent (MIC=16 μg/mL) as ampicillin against B. subtilis. Considering the disk diffusion and synergistic studies, 9 bemerged asmost active compound showing potent activity against all the tested bacterial strains. In addition, no significant hemolysis or cytotoxicity was observed towards human embryonic kidney (HEK293)cells as well as Galleria mellonellalarvae (in vivo). Hence, compound 9 bhas potential to be further explored alone and in combination with ampicillin as a next generation antibacterial agent.

Total Synthesis of Nortopsentin D via a Late-Stage Pinacol-like Rearrangement.

Nortopsentin D is part of a class of bis(indole) alkaloids known for their biological activity, including inhibitory activity in tumoral cells and antifungal activity. Herein we describe the first total synthesis of nortopsentin D, in which amidine and dione undergo a pivotal condensation and subsequent cyclization via a pinacol-like rearrangement. This synthesis represents a unique strategy for the formation of 5,5-disubstituted (4H)-imidazol-4-one containing natural products, many of which have yet to succumb to total synthesis.

One-pot synthesis of Acanthus ilicifolius Linn alkaloid 2-benzoxazolinone derivatives via a tandem Ugi 4-component coupling/haloform cyclization

A one-pot, base-mediated approach to Acanthus ilicifolius Linn alkaloid 2-benzoxazolinone derivatives is developed. Starting from trichloroacetic acid, o-aminophenol, substituted benzaldehydes and alkyl isocyanides, the desired 2-benzoxazolinone derivatives are obtained in good yields via a tandem Ugi condensation and intramolecular haloform cyclization at room temperature in the presence of Et3N.

Synthesis of benzothiazoles using fluorescein as an efficient photocatalyst under visible light

This work reports a novel and efficient method for the synthesis of benzothiazoles using 2-aminothiophenol derivatives in conjunction with aromatic aldehyde as starting materials via visible-light-induced condensation cyclization. Utilizing fluorescein as the photocatalyst and blue LED lamp as the light source, the reaction proceeds in the presence of a molecular oxygen atmosphere without the need for metal catalyst or an additional oxidant. Significantly, this method exhibits good tolerance in substrates, and a variety of 2-aminothiophenol derivatives and aromatic aldehyde are amenable to producing the corresponding benzothiazoles in high to excellent yields.

Highly Selective and Sensitive Colorimetric and Fluorescent Chemosensors for Rapid Detection of Cyanide Anions in Aqueous Medium: Investigation on Supramolecular Recognition of Tweezer‑shaped Salophenes.

Three tweezer‑shaped salophenes having catechols (1), phenols (2) and anisoles (3) units in conjunction to the dipodal Schiff bases have been applied for the optical sensing of cyanide (CN¯) ions in CH3CN-H2O (7:3) as solvent of choice. Among them, compounds 1 and 2 recognized CN¯, relying on distinct color and spectral changes. They are easy-to-use probes that exhibit extremely high sensitivity (limit of detection = 1-10 nM), rapid response (5s) and excellent selectivity. Moreover, the visual detection and concentration determination of CN¯ by solution test kits of both sensors are the advantages for the practical applications. Based on the fluorescence and NMR spectroscopy, as well as the OH¯ and reversibility experiments, the explicit effect of hydroxyl groups on sensing and as well the different recognition of 1 and 2 toward CN¯ ions was proved. While probe 1 senses CN¯ via deprotonation, probe 2 recognizes it through an intramolecular aldimine condensation cyclization, leading to formation of anions of dihydroxyquinoxaline 4. This chemodosimetry is being reported for the first time in a Schiff's base. Furthermore, the similarity of fluorescence and NMR responses of 2 and 4 toward CN¯ supports the proposed process.

Efficient one-pot synthesis of oxaperylenone derivatives promoted by propylphosphonic anhydride

Propylphosphonic anhydride (T3P)-mediated condensation and intramolecular cyclization of 1-hydroxyanthraquinone with various active methylene acetates in the presence of Et3N was efficiently accomplished, affording oxaperylenone derivatives. The in situ generated propylphosphate derivatives were confirmed as reactive intermediates, which were produced by acylation from 1-hydroxyanthraquinone with T3P. The reaction mechanism was investigated theoretically using density functional theory, and a plausible reaction mechanism was proposed. This method is useful for the synthesis of the core structure of oxaperylenone derivatives. • One-pot synthesis of naptho [1,2,3- de ]chromene-2,7-dione skeleton. • Improved the synthesis method of oxaperylenone derivatives. • The mechanism relies on stabilization changes of anthraquinone-4-phosphoryl ester intermediates.

Synthesis, Anti-Bacterial and Anti-biofilm Activity of New Iminothiazolidinones

Aim: Iminothiazolidinones are one of the important classes of heterocyclic compounds and they occupied unique position in medicinal chemistry due to their wide range of biological and pharmaceutical properties. In view this potential activity, it has been planned to synthesize a series of New Iminothiazolidinones on benzimidazole nucleus and to study their biological activity.
 Methodology: Iminothiazolidinones and 1,1 dioxide- Iminothiazolidinones were synthesized with a simple and efficient method of cyclic condensation of aryl thiourea containing benzimidazole and thiazole with chloroacetic acid .This method requires mild reaction conditions, simple procedure and gives good yield.
 Results: The structures of the synthesized compounds were assessed by Infrared, NMR and Mass spectroscopic methods. The synthesized compounds were screened for their antibacterial and biofilm inhibitory activities against selected multi drug resistant bacterial strains.
 Conclusion: In accordance with the results obtained, growth inhibition was found significant with compounds 5d and 5e. Methicillin resistant Staphylococcus aureus (MRSA), Vancomycin resistant Enterococcus (VRE), and extended spectrum β‑lactamase (ESBL) producing Klebsiella pneumoniae have shown varied susceptibility towards these compounds. The Biofilm inhibition Concentrations (BFIC) of compounds 5e and 5d are 3.22 ±0.56 and 6.58 ±1.5 µg/mL respectively were noted against MRSA.

Ring-opening polymerization of thiolactide by using thiol-amine combination

This is the first report about the ring-opening polymerization of thiolactide, which is the thioester analogue of lactide. The cyclic condensation of thiolactic acid gave rac-thiolactide, which underwent the ring-opening polymerization by a combination of thiol as the initiator and DBU as the catalyst. The polymerization was in equilibrium, showing that the monomer conversions were as low as 20% in solvents. The bulk polymerization at r.t. led the monomer conversions around 50%, and the molecular weights of the polymer products increased with decreasing the amount of the thiol initiator. The MALDI-TOF mass spectra revealed that the hexane-insoluble polythiolactide (Mn = 3000–3500, PDI = 1.3–1.6, 20–30%yield) had not only the linear but also the macro cyclic structures. A much weaker base, pyridine, worked as the catalyst, showing the lower activity but leading the polymerization to a more controllable fashion. DFT calculation suggested that rac-thiolactide has the smaller ring-strain than rac-lactide, which agreed with the lower polymerizability of rac-thiolactide. Polythiolactide showed the higher degradability for alkaline hydrolysis and UV photolysis than polylactide. Copolymerization of thiolactide with thioglycolide was also studied.

Novel Tandem Three Consecutive Reactions: Aza-Wittig, Imine Condensation and Electrophilic Aromatic Substitution Strategy to Indolizine Synthesis

Reaction of ethyl (Z)-3-(heteroaryl/aryl)-2-((triphenyl-λ5-phosphaneylidene) amino) acrylates intermediates with 2,3-thiophenedicarboxaldehyde was used in novel Tandem three consecutive reactions: aza-Wittig, imine condensation and electrophilic heteroaromatic cyclization to obtain a series of indolizines. A tentative mechanism of this reaction is proposed.

Self-assembly of Keggin-type U(vi)-containing tungstophosphates with a sandwich structure: an efficient catalyst for the synthesis of sulfonyl pyrazoles

Two Keggin-type U(vi)-containing tungstophosphates with sandwich structure were synthesized and characterized. Compound 1 presents excellent catalytic activity towards the condensation cyclization of sulfonyl hydrazines with 1,3-diketones to synthesize sulfonyl pyrazoles.

Synthesis of quinolines via sequential addition and I2-mediated desulfurative cyclization.

An efficient one-pot approach for the synthesis of quinolines from o-aminothiophenol and 1,3-ynone under mild conditions is disclosed. With the aid of ESI-MS analysis and parallel experiments, a three-step mechanism is proposed—a two-step Michael addition–cyclization condensation step leading to intermediate 1,5-benzothiazepine catalyzed by zirconocene amino acid complex Cp2Zr(η1-C9H10NO2)2, followed by I2-mediated desulfurative step.

Ratiometric fluorescent strategy for malononitrile determination in organic and aqueous medium and biological imaging

Malononitrile is a versatile dinitrile compound with high reactivity, which has wide prospect in application for multisynthetic organic medical chemistry and industrial manufacture. Considering of the transformation to HCN in animal tissue metabolism, malononitrile has potential environmental pollution and health risks. Here, a ratiometric fluorescent probe 4-(benzothiazol-2-yl)-2-hydroxy benzaldehyde (HBTA) for detection of malononitrile in organic and aqueous phase is developed on the basis of reaction-triggered fluorophore for the first time. The ratiometric assay with malononitrile-responsive fluorescence signal was contributed by Knoevenagel condensation and intramolecular cyclization, which was confirmed by HR-MS analysis and NMR titration spectra. In addition, this ratiometric probe provided a fancy strategy for detection of malononitrile with fast response, high sensitivity and selectivity, declaring excellent imaging performance in vivo capable of semi-quantification for malononitrile level.

Condensation–cyclization reaction for one-pot synthesis of 1,3-thiazolidin-4-one derivatives by poly(p-phenylenediamine) grafted on LDHs as a catalyst with green tool

The three-component reaction between amine, carbonyl compound and thioglycolic acid is now considered as a major strategy for synthesis of 1,3-thiazolidin-4-ones, which consists of the following steps: (i) condensation of aldehyde and amine which results the formation of an imine; (ii) the reaction between thioglycolic acid and the imine which is followed by an intramolecular cyclization reaction, which leads to the formation of the final product. In this way, if no suitable catalyst is employed, the completion of the reaction will not be achieved. Hence, it is of great importance to select an appropriate catalyst so that these compounds can be successfully synthesized. Herein, we employed LDHs@PpPDA as a versatile catalyst for the fabrication of novel derivatives of 1,3-thiazolidin-4-one.

Iodine‐Mediated Condensation–Cyclization of α‐Azido Ketones with p‐Toluenesulfonyl Hydrazide for Synthesis of 4‐Aryl‐NH‐1,2,3‐Triazoles

A molecular iodine mediated condensation–cyclization reaction for the synthesis of 4‐aryl‐NH‐1,2,3‐triazoles has been developed from readily available α‐azido acetophenones and p‐toluenesulfonyl hydrazide. This reaction provides a metal‐free strategy for the sequential formation of C–N and N–N bonds in mild condition.

Microwave-Assisted Three-Component Domino Synthesis of Polysubstituted 4H-Pyran Derivatives and Their Anticancer Activity

An efficient microwave-assisted one-pot procedure has been proposed for the synthesis of new 4-aryl-6-(methylamino)-5-nitro-2-(1H-pyrrol-2-yl)-4H-pyran-3-carbonitriles by condensation of 3-oxo-3-(1H-pyrrol-2-yl)propanenitrile with (E)-N-methyl-1-(methylsulfanyl)-2-nitroethenamine and substituted benzaldehydes in the presence of a catalytic amount of piperidine using ethanol as a solvent. The transformation occurs via successive Knoevenagel condensation, Michael addition, and intramolecular cyclization. The proposed procedure is advantageous due to its one-pot mode, short reaction time, simple purification by recrystallization, and excellent yields. The product structure was confirmed using various spectroscopic techniques, including IR,1H and 13C NMR, LC/MS, elemental analysis, and single crystal X-ray diffraction study. The synthesized compounds were evaluated for their anticancer activity against 60 different human cancer cell lines in nine cancer panels, and two compounds were found to be potent against different cell lines.

An efficient synthesis of 9‐anthrone lactone derivatives via the Knoevenagel condensation and intramolecular cyclization

AbstractOne‐step synthesis of 9‐anthrone lactone derivatives from 1‐acetyloxyanthraquinone with a variety of dicarbonyl substrates in the presence of K2CO3 by Knovenagel condensation and intramolecular cyclization is developed. Possible reaction mechanisms have been investigated using the density functional theory (DFT), which has been widely used in the study of reaction mechanism. The strategy could be useful for the synthesis of the core structure of marine natural product aspergiolide.

An Efficient Synthesis, Anti inflammatory activity and Molecular Docking Studies of new Triazinanes and Iminothiazolidinones

A series of new triazinane-2-thiones and imino thiazolidinone-4-ones were synthesized from 2-acetyl benzimidazole (1). Treatment of compound 1 with urea in the presence of I2 furnishes compound (2), which on reaction with Aryl isothiocyanateaffords the compound (3), which undergoes Cyclic condensation of classical Mannich amino methylation of compound 3with formaldehyde and methyl amine produces corresponding triazinane -2-thiones (4), whereas cyclic condensation of compound 3 with cholroacetic acid to furnish the corresponding iminothiazolidinones-4-ones(5).the chemical structures of the newly synthesized compounds have been characterized on the basis of spectral (IR, 1HNMR and Mass) and analytical data. The title compounds were evaluated for their anti-inflammatory activity and molecular docking studies. The docking studies are supporting anti-inflammatory activity exhibiting high inhibition constant and binding energy.