Cyclization Reaction Research Articles

Enhancement of the sensitivity of chalcone derived from vanillin as chemosensor agents for Hg(II) ions through cyclization reaction with arylhydrazine

Water pollution is currently a major problem worldwide. Given its detrimental effects on health, Hg(II) is considered an extremely hazardous heavy metal contaminant, even at low doses. Heterocyclic compounds have been thoroughly evaluated as the chemosensor agents for Hg(II) detection. However, they suffer from poor sensitivity. In this study, we prepared two fluorescence chemosensor agents from vanillin via several steps, i.e., etherification, Claisen–Schmidt, and cyclocondensation reactions to yield N-phenyl- and N-pyridine-pyrazoline compounds. Products characterization was accomplished via spectroscopic techniques. Chalcone, N-phenyl-, and N-pyridine-pyrazoline derivatives were successfully obtained at 87.04%, 90.91%, and 91.73% yields, with limits of detection of 156,840, 65.810, and 161.011 nM, respectively. These results show that the conversion of chalcone to pyrazoline structure improved the sensitivity for Hg(II) detection at the nanomolar level, which is 2384 times lower than that for chalcone. Further spectroscopic investigations through Job's plot, Fourier-transform infrared spectroscopy, and proton-nuclear magnetic resonance analyses revealed that Hg(II) ions were chelated with two nitrogen atoms of pyrazoline. Thus, this phenomenon can explain the considerable sensitivity enhancement for Hg(II) detection. N-Phenyl-pyrazoline is the more sensitive chemosensor to Hg(II) compared with N-pyridine-pyrazoline because the more nitrogen groups in the binding site, the less selective and sensitive the compound. This finding is also supported by the higher binding constant value of N-phenyl-pyrazoline (9.416 × 102 mol−1) than N-pyridine-pyrazoline (1.771 × 102 mol−1). Furthermore, N-phenyl-pyrazoline can be applied in the direct quantification of Hg(II) in tap and groundwater samples with a validity parameter in a range of 80.97%–103.54%.

Study on H3PO4-activated carbon catalytic co-pyrolysis of bamboo and LDPE to poly-generation syngas and aromatics at low temperature

Biomass-derived carbon activated by H3PO4 was adopted to catalytic co-pyrolysis of bamboo and low-density polyethylene (LDPE) to produce syngas and aromatics on a fixed bed reactor. Effects of LDPE ratio in the feedstock, catalytic co-pyrolysis temperature and ratio of catalyst to feedstock on the yields and compositions of the products were investigated. The increase of LDPE ratio in liquid first improved and then reduced the relative content of aromatics, while it showed a positive effect on the yield and the H2/CO ratio of gas. 500℃ was an optimum temperature, under which the relative content of aromatics in liquid kept higher, meanwhile, avoided the undesirable polymerization reactions of monocyclic aromatics. At the same time, the content of H2 in gas reached a maximum (59.3%), which was in favor of poly-generation. H3PO4-activated carbon catalyst (H3PO4-ACC) with abundant functional groups on surface catalyzed cracking, hydrodeoxygenation, cyclization and aromatization reactions so as to facilitate the generation of aromatics. Non-condensable gas was dry reformed on P-ACC at the expense of CO2, CH4 and CO to generate char and H2. When the reaction condition was at a LDPE ratio of 50%, a catalyst/feedstock ratio of 2:1 and at 500℃, the relative content of aromatics in liqiud was 81.65% and the proportion of syngas component in gas was 79.73%. The volume ratio of H2/CO approached to 3:1 in gas under this condition. H3PO4-ACC catalytic co-pyrolysis of bamboo and LDPE could obtain high quality gas and liquid products at a relative low reaction temperature, which provided a new research idea on high-value application of biomass and waste plastics.

System-wide coordination and communication of lipid metabolism atlas revealed cytotoxicity of epoxy triglyceride in deep-frying oil

The epoxy triglycerides generated by oxidation, cyclization, and free radical chain reaction of unsaturated dietary oils during deep-frying are demonstrated to have cytotoxicity and can induce lipid metabolism related diseases. Metabolic diseases are usually characterized by metabolic abnormalities in different tissues, however, the relationship between changes in intratissue coordination and communication induced by epoxy triglycerides and specific pathogenic mechanisms remains largely unknown. We conducted lipid metabolomics analysis across six different tissues in C57BL/6J mice, including the medial prefrontal cortex, interscapular brown adipose tissue, epididymal white adipose tissue, liver, intestine, and heart. Normal diet intake demonstrated a high degree of association between lipid metabolites, indicative of cross-communication and cooperation among various tissues and organs, while, a global correlation that was disrupted and restructured by epoxy triglycerides intake. Examination of blood samples revealed that epoxy triglycerides enhanced bacterial translocation from the gut to the systemic circulation, consequently stimulating the TLR4/CD36/NF-κB pathway. In summary, this study found that epoxy triglyceride upsets the comprehensive coordination and information exchange of lipid metabolism, providing a fresh perspective for future research on the systemic metabolic network and identifying metabolic disease markers and associated mechanisms induced by deep-frying oil.

Pd(0)-Catalyzed Intermolecular Methylene C(sp3)-H Silylation by Using N-Heterocyclic Carbene Ligands.

The direct functionalization of methylene C(sp3)-H bonds is one of the greatest challenges in transition metal-catalyzed C-H activation. Although Pd(0)-catalyzed intramolecular cyclization reactions of methylene C(sp3)-H bonds have been reported, intermolecular functionalization remains to be discovered. Herein, we report the first example of a Pd(0)-catalyzed intermolecular methylene C(sp3)-H functionalization reaction. By use of a N-heterocyclic carbene ligand, the methylene C(sp3)-H bonds of 1-(benzyloxy)-2-iodobenzenes are activated and disilylated with hexamethyldisilane, affording disilylated products.

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline.

A new method for the synthesis of heterocyclic systems containing tetrazole and tetrahydroisoquinoline is developed via the performance of one-pot Ugi-azide and Heck cyclization reactions. The integration of the multicomponent and post-condensation reactions in one-pot maximizes the pot-, atom-, and step-economy (PASE).

Synthesis, and Spectroscopic Characterization study of some Schiff Bases N, N bis (3-methyl-1,2,4-triazole-5- thione (1,3-methylidene) benzene and N, N bis (3-methyl-1,2,4-triazole-5- thione (1,4- methylidene) benzene

Some of triazole derivatives were synthesized by cyclization reaction, of thiocarbohydrazide was synthesized by reaction of carbon disulfide and aqueous hydrazine, the basic nucleus 4-amino- 3- methyl -1, 2, 4-triazole-5-thione(L) was prepared by reaction of thiocarbohydrazide compound with glacial acetic acid under reflux condition.The compound(L) was subjected to addition reaction with different aldehydes to synthesize Schiff bases N,N bis(3-methyl-1,2,4-triazole-5- thione (1,3-methylidene )benzene (L1) and N, N bis(3-methyl-1,2,4-triazole-5- thione (1,4- methylidene )benzene (L2). The compound (L1),(L2) were confirmed by their melting point,FTIR,U.V-visible ,1HNMR spectra.

A novel method for the synthesis of macrocyclic peptides using arylsulfonyloxyacetic acids as N-terminus functional groups

We have successfully introduced arylsulfonyloxyacetic acids with long alkyl chains as lipophilic tags to the N-terminus of peptides in the final step of solid phase peptide synthesis in order to purify tagged peptides. Also, the tags allow the linear peptides to be purified by solidification after liquid–liquid extraction. Moreover, macrocyclic peptide 1 after cyclization reaction was pre-purified easily by separating the arylsulfonate produced from tags. In this report, we described the application of this methodology to the synthesis of macrocyclic peptides such as carbetocin analogues with thioether-, amino-, ether- and ester-linkage could be derived from tagged peptides.

Hydrazine electrooxidation performance of cyano-substituted indole derivatives as organic anode catalyst

Here we present the new EWG-substituted indole derivatives, namely 2-((5-(1-methyl-2-phenyl-1 H-indol-3-yl)thiophen-2-yl)methylene) malonitrile (IPTM), 2-((5-(1-methyl-2-phenyl-1 H-indol-3-yl)furan-2yl)methyl)malonitrile(IPFM) and 2-((4-(1-methyl-2-phenyl-1 H-indol-3-yl)benzylidene) malonitrile (IPPM) was synthesized by using Sonogashira coupling, electrophilic cyclization, Suzuki-Miyaura coupling and condensation reactions. The isolated yields were obtained as 86 %, 71 %, and 69 % yields, respectively. Cyclic voltammetry(CV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS) were used for the electrochemical measurements to observe the electrocatalytic behavior of IPTM, IPFM and IPPM. The results exhibited that the highest-performance organic-based catalyst was 2.601 mA/cm2 (0.073 mA/mg) for IPPM which could be a good candidate as a metal-free electrocatalyst for hydrazine electrooxidation.

Nucleophilic Selenocyclization Reaction of Benzodiynes Promoted by Sodium Selenide: Synthesis of Isoselenochromenes.

We describe here the synthesis of isoselenochromenes via a nucleophilic selenocyclization reaction of benzodiynes with sodium selenide. The central parameters that affect this cyclization reaction were studied, and the best reaction conditions were applied to different substrates to determine the scope of the method. The results indicated that isoselenochromenes were obtained in higher yields when the reactions were performed by the addition of NaBH4 (3 equiv), at room temperature, under nitrogen atmosphere, to a solution of elemental selenium (2 equiv) in dimethylformamide (2 mL). After 1 h, a benzodiynes (0.25 mmol) solution in EtOH (3 mL) was added at room temperature. The reaction was stirred at 75 °C until the starting material was consumed. The best conditions were applied to benzodiynes having electron-rich, electron poor aromatic rings, and alkyl groups directly bonded to the alkynes. The same reaction condition was extended to isothiochromene derivatives but failed to prepare isotelurochromenes. The isoselenochromenes were easily transformed into three new classes of organoselenium compounds using classical methods available in the literature. We also conducted several control experiments to propose a reaction mechanism.

Controlling associative transcarbamoylation reactions by light in dynamic polyurethane networks using reversible spiropyran photoswitches

Polyurethanes represent a versatile class of polymers and are one of the most employed in the thermoset market. However, due to their thermodynamically stable carbamate bond, they suffer from a lack of reprocessability, recyclability, and degradability, and are therefore usually discarded after use. Recently, transcarbamoylation in polyurethane thermosets has been demonstrated via associative exchange in the presence of a strong organic acid. Intending to introduce spatiotemporal control in the processability of polyurethane materials, in this work we investigate dynamic transcarbamoylation by the addition of a latent acidic catalyst into an aromatic and an aliphatic polyurethane network. We introduce three photoswitches based on merocyanine/spiropyran compounds which, upon exposure to visible light, undergo a reversible cyclization reaction, resulting in the formation of strong acids. The use of such photoswitches prevents the presence of a permanent acidic species in the network, which would eventually lead to its degradation over time. Importantly, due to the reversible nature of the cyclization reaction, the release of the acidic catalyst is not permanent, as evidenced by stress relaxation measurements. Overall, the evidence of the light-induced, acid-catalyzed transcarbamoylation is supported by stress relaxation, optical microscopy, and self-healing measurements.

3+3] Annulation of Diazoenals and α-Mercapto Ketones via Protic Sulfonium Ylides: Direct Synthesis of 2H-Thiopyrans, Innovative Progenitors for Unstudied 2H-Thiopyran-2-ones and 4H-Thiopyran-4-ones.

Herein, we report a new Rh(II)/Sc(III)-catalyzed [3+3] annulation between diazoenals and α-mercapto ketones for the direct synthesis of 4-formyl-2H-thiopyrans. The reaction proceeds via protic sulfonium ylides derived from highly electrophilic Rh-enalcarbenoids, followed by regioselective intramolecular aldol condensation. Further studies revealed that 4-formyl-2H-thiopyrans are novel precursors for unstudied 2H-thiopyran-2-ones and 4H-thiopyran-4-ones. The 4H-thiopyran-4-ones were obtained via a novel O2/Et3N-mediated oxidative deformylation. This methodology was applied to the short synthesis of structurally complex pyrimidine-fused 2H-thiopyran via cascade Schmidt, Ritter, and intramolecular cyclization reactions.

Copper-Catalyzed [4+1] and [4+2] Reactions through Tandem ­Remote Propargylation/Cyclization/Isomerization with an Amine or a Hydrazine

AbstractTwo novel copper-catalyzed cyclization reactions involving a remote propargylic substitution/cyclization/isomerization cascade are disclosed. Derivatives of the seldomly studied heterocycles thieno[2,3-c]pyrrole and thieno[2,3-d]pyridazine are conveniently synthesized in moderate to good yields from primary amines or arylhydrazines through [4+1] and [4+2] reactions, respectively. Preliminary mechanistic experiments corroborated the occurrence of the designed cascade reactions.

Facile synthesis of dihydroisobenzofuran derivatives via a one-pot sequential Passerini-azide/Ag(I)-catalyzed cyclization process

A facile one-pot synthesis of dihydroisobenzofuran derivatives by Passerini-azide/Ag(I)-catalyzed cyclization sequence has been developed. The Passerini-azide reactions of 2-(alkynyl)benzaldehydes, trimethylsilyl azide, and isocyanides gave tetrazole intermediates, which were transformed to the dihydroisobenzofurans in moderate to good yields via Ag(I)-catalyzed 5-exo-dig cyclization reaction.

Iodine(III)-Catalyzed Oxidative Cyclization of Aryl Amines to Construct N-Alkylbenzimidazoles.

An I(III)-catalyzed oxidative cyclization reaction using selectfluor as the oxidant was developed that converts ortho-substituted anilines to benzimidazoles. The mild reaction requires as little as 0.5 mol % of iodobenzene, and its scope is broad: electron-withdrawing or electron-releasing groups on the aniline portion are tolerated, and cyclic or acyclic N-alkylamines are permitted as ortho-substituents. Preliminary mechanistic investigations suggest that benzimidazole formation occurs via cationic reactive intermediates, and an intramolecular kinetic isotope effect of 1.98 ± 0.05 was measured.

One-Pot Three-Component Reaction for the Synthesis of 3,4-Dihydroquinazolines and Quinazolin-4(3H)-ones.

A highly efficient and straightforward one-pot synthesis of diversely substituted 3,4-dihydroquinazolines and quinazolin-4(3H)-ones has been achieved through a domino three-component assembly reaction of arenediazonium salts, nitriles, and bifunctional aniline derivatives. This new protocol involves three C-N bond formations through the initial formation of N-arylnitrilium intermediates from arenediazonium salts and nitriles, followed by the sequential nucleophilic addition and cyclization reactions with bifunctional anilines, leading to such N-heterocyclic compounds of biological and pharmacological importance. This method offers a simple, expedient, and robust approach with the use of amenable and easily accessible reactants/reagents under metal-free mild conditions, good functional group tolerance, and high efficiency. The synthetic applications were also demonstrated by derivatization of the products obtained from these processes and syntheses of a diverse range of valuable polycyclic N-heterocycles.

Palladium(II)-Catalyzed Tandem γ-C(sp2)-H Arylation and Cyclization for the Construction of Natural Product-Like Polycyclic Fused ortho-Quinone Scaffolds.

Here, we report a novel strategy for the direct construction of polycyclic fused ortho-quinone scaffolds through palladium(II)-catalyzed tandem γ-C(sp2)-H arylation and cyclization of arylglyoxals with aryl iodides. This transformation features unique tandem transient directing of γ-C(sp2)-H arylation and cyclization reaction mode, broad substrate scope, especially for the aromatic substrates containing oxygen and sulfur atoms, and avoiding the common issue of aromatization due to the construction of the hexatomic ring.

Photocatalytic alkenes to ring-fused quinazolin-4(3H)-ones via proton-transfer shuttle using TFA

Herein, a novel metal-free photocatalytic system is reported that enables intramolecular hydroarylation of unactivated alkenes via a proton transfer shuttle using TFA, providing a concise access to the formation of pyrroloquinazolinone and pyridyquinazolinone products in moderate to good yields. Mechanistic studies revealed that the protonated quinazolinone is the key radical precursor mediating the intramolecular cyclization reaction.

Effective synthesis of circRNA via a thermostable T7 RNA polymerase variant as the catalyst.

Circular RNAs (circRNAs) are endogenous noncoding RNAs (ncRNAs) with transcriptional lengths ranging from hundreds to thousands. circRNAs have attracted attention owing to their stable structure and ability to treat complicated diseases. Our objective was to create a one-step reaction for circRNA synthesis using wild-type T7 RNA polymerase as the catalyst. However, T7 RNA polymerase is thermally unstable, and we streamlined circRNA synthesis via consensus and folding free energy calculations for hotspot selection. Because of the thermal instability, the permuted intron and exon (PIE) method for circRNA synthesis is conducted via tandem catalysis with a transcription reaction at a low temperature and linear RNA precursor cyclization at a high temperature. To streamline the process, a multisite mutant T7 RNA polymerase (S430P, N433T, S633P, F849I, F880Y, and G788A) with significantly improved thermostability was constructed, and G788A was used. The resulting mutant exhibited stable activity at 45°C for over an hour, enabling the implementation of a one-pot transcription and cyclization reaction. The simplified circRNA production process demonstrated an efficiency comparable to that of the conventional two-step reaction, with a cyclization rate exceeding 95% and reduced production of immunostimulatory dsRNA byproducts.

Discovery of a new class of potent pyrrolo[3,4-c]quinoline-1,3-diones based inhibitors of human dihydroorotate dehydrogenase: Synthesis, pharmacological and toxicological evaluation

Twenty N-substituted pyrrolo[3,4-c]quinoline-1,3-diones 3a-t were synthesized by a cyclization reaction of Pfitzinger's quinoline ester precursor with the selected aromatic, heteroaromatic and aliphatic amines. The structures of all derivatives were confirmed by IR, 1H NMR, 13C NMR and HRMS spectra, while their purity was determined using HPLC techniques. Almost all compounds were identified as a new class ofpotent inhibitors against hDHODH among which 3a and 3t were the most active ones with the same IC50 values of 0.11 μM, about seven times better than reference drug leflunomide. These two derivatives also exhibited very low cytotoxic effects toward healthy HaCaT cells and the optimal lipophilic properties with logP value of 1.12 and 2.07 respectively, obtained experimentally at physiological pH. We further evaluated the comparative differences in toxicological impact of the three most active compounds 3a, 3n and 3t and reference drug leflunomide. The rats were divided into five groups and were treated intraperitoneally, control group (group I) with a single dose of leflunomide (20 mg/kg) group II and the other three groups, III, IV and V were treated with 3a, 3n and 3t (20 mg/kg bw) separately. The investigation was performed in liver, kidney and blood by examining serum biochemical parameters and parameters of oxidative stress.

Synthesis and performance of a nanosensing platform for homocysteine detection: A series of iridium(III) complexes containing aldehyde group as probe and MOF as supporting substrate

The low cost and simple detection method for Hcy (homocysteine) is highly desired in analytical and biological fields since Hcy has been regarded as a bio-marker for multiple diseases. In this work, five Ir(C^N)2(N^N)+ compounds having –CHO group in their C^N or N^N ligand were synthesized and tried for Hcy sensing. Electron-donating groups such as –NH2 and –CH3 were incorporated into the C^N or N^N ligand. Their geometric structure, electronic structure, and optical parameters (with or without Hcy) were analyzed and compared carefully to explore their Hcy sensing potential. The sensing mechanism was revealed by NMR titration and theoretical simulation as a cyclization reaction between the –CHO group and Hcy. The optimal compounds, which showed increased emission quantum yield (2.5-fold) and emission blue-shift (by ∼ 100 nm) upon Hcy, were then covalently grafted into a porous host bio-MOF-1. Linear working plots were fitted, with good selectivity, LOD of 0.15 μM, and response time of 33 s. The novelty of this work was the eye-sensitive emission color change of this nanosensing platform from red (without Hcy) to green (with Hcy).