Aldehydes 2a Research Articles

One-pot synthesis of new benzo[4,5]imidazo[1,2-a]pyrimidines and pyrazolo[1,5-a] pyrimidines as an eco-friendly and effective method catalyzed by acetic acid with prospective antimicrobial agents

A novel set chalcones 3a-d was efficiently synthesized in elevated produces across the condensing process of Claisen-Schmidt. An eco-friendly and efficient process was designed for creating a novel desired products 5a-f and 7a-f, respectively with excellent yields. This synthesis was accomplished by reacting acetophenone derivatives 1a-d, heteroaromatic aldehydes 2a,b and aminobenzoimidazole 4 or 3-aminopyrazole 6a,b, using acetic acid as both the catalyst and solvent. Solvent optimization was performed during the synthesis of the desired compounds 5a or 7a, highlighting the benefits of using acetic acid that is harmless for the environment, which offers easy procedure, rapid reaction, elevated efficiency and broad tolerance of starting materials. The preferred products were verified through compatible spectroscopic data. The antimicrobial efficacious for all compounds was successfully evaluated against various microorganisms, revealing that 3b exhibited significant antimicrobial activity across all tested microbes, with measurements of the minimum inhibitory concentrations being between 4.80 to 63.8 μM.

Exploring Border Conditions for Spontaneous Emergence of Chirality in Allylboration of 1,2,3-Triazolic Aldehydes.

A case of spontaneous chirality generation was observed during a synthetic project studying the allylboration of 1,2,3-triazolic aldehydes. Here, we present computational studies supported by experimental findings targeting the elucidation of border conditions required for the observation of spontaneous chirality generation in the reaction of 1-Ar-1H-1,2,3-triazole-4-carbaldehydes 1a,b with triallylborane. Three possible sources of symmetry breaking were found computationally. Thus, dimerization of the initial reaction products, alcoholates 4a,b, gives dimers 5a,b (homochiral) and 6a,b (heterochiral). The latter were computed to be more stable thermodynamically, which can lead to amplification of the initial stochastic imbalance of the enantiomers of 4a,b via the reservoir mechanism. Furthermore, enantiomeric excess can be increased during the transfer of the second allylic group in the reaction of optically active boronates 4a,b with 1a,b, which was computed to be enantioselective due to the strong activating and stereoregulating properties of the 1,2,3-triazole group. In addition, reactions of borinic esters 8a,b, products of the previous reaction with triallylborane, recovered in each case two molecules of 4a,b of the same handedness, which can lead to additional chirality amplification. Experimentally, reactions of optically active alcohols (+)-R-2a,b with triallylborane provided chiral alcoholates 4a,b, which were reacted with equivalent amounts of corresponding aldehydes 1a,b. Unexpectedly, in two series of 10 experiments each, preferential formation of both enantiomers of the newly formed product was observed: seven times S and three times R in the case of 1a and six times S and four times R in the case of 1b.

Synthesis of β-phosphonomalonates using a recyclable choline hydroxide catalyst

Choline hydroxide (ChOH) is an effective ionic liquid (IL) that enables the straightforward construction of β-phosphonomalonates in basic medium. A variety of compounds, including aromatic/heterocyclic and aliphatic aldehydes (1a–p) were reacted with dicyanomethane (2) and diethyl phosphonate (3) to produce the targeted products in good yields (4a–p). The constructed compounds as well as the IL were characterized using spectral 1H, 13C, and 31P NMR.

A single‐step synthesis of 5,6‐dihydropyrrolo[2,1‐a]isoquinolines and evaluation of their anti‐leukemic activity

AbstractWhile a pharmaceutically intriguing scaffold, 5,6‐dihydropyrrolo[2,1‐a]isoquinoline (DHPIQ), has precedently been prepared from diverse tetrahydroisoquinolines (THIQs) using elaborate conditions, convenient metal‐free methods were discovered from condensation of cyanomethylene‐THIQ (1) and α‐halo‐ketones or aldehydes (1a) to afford 15 DHPIQs (2–16) in moderate yields by employing unique reactivities of the secondary amine and α‐carbon to the nitrile of 1. Preliminary biological studies with chronic myelogenous leukemia K562 and adriamycin‐resistant K562 (K562/ADM) cells exhibited some of the DHPIQs tested were active in the both cell lines. In particular, cyclohexyl‐fused DHPIQ (10) showed GI50 values of 9.79 and 13.60 μM in K562 and K562/ADM cells, respectively. Based on the flow cytometry analysis of 10, the anti‐cancer activity could be from apoptosis‐related mechanisms. Overall, this DHPIQ scaffold may be further optimized to discover clinically meaningful anti‐leukemic agents overcoming adriamycin resistance.

New biocidal hybrids bearing acridine and aminophosphonate Scaffolds against different bacterial pathogens

New hybrids containing acridine and α-amino phosphonate scaffolds 6a-h were synthesized by three one-pot reactions via Kabachnik–Fields reaction of 9-aminoacridine derivatives 3a-d, aldehydes 4a,b and triphenyl phosphite 5 in equimolar ratio under stirring at room temperature. The installation of the afforded hybrids was affirmed by different spectroscopic methods as IR, 1HNMR, 13CNMR, 31P NMR, MS and elemental analysis. The antibacterial activities of hybrids 6a-h were screened against both Gram-positive and Gram-negative bacteria of four pathogenic strains, comparable to ampicillin and chloramphenicol drugs. Most hybrids showed higher activity compared to the reference drugs. Notably, the antibacterial performance of 6c was more substantial than other analogues with best minimum inhibitory concentration (MIC) and highest zone of inhibition (ZOI) of 31, 34, 35, 38 mm, against Serratia marcescens, Streptococcus mutans, MRSA and Klebsiella pneumoniae clinical isolates respectively. In addition, Transmission Electron Microscopes (TEM) was carried out to study the mode of action of 6c with MRSA, the results confirmed that the titled hybrid caused the disruption of bacterial cell wall. Moreover, the time-dependent kill study revealed that the investigated compounds were time and dose-effective bactericidal agents and could be used as potential leads for further development and optimization of novel antibacterial agents.

A convenient approach for the synthesis of 4,4'-((substituted phenyl)methylene)bis(3-methyl-1H-pyrazol-5-ol) and their antioxidant and antimicrobial activities

A facile one-pot, three component, convenient approach for the synthesis of 4,4'-((substituted phenyl)methylene)bis(3-methyl-1H-pyrazol-5-ol) derivatives (3a–l) has been accomplished from the reaction of two moles of 5-methyl-2,4-dihydro-3H-pyrazol-3-one (1), with one mole various aromatic aldehydes (2a–l) in the presence ZnO nanoparticles as an efficient heterogeneous catalyst under microwave irradiation (MWI) and solvent-free conditions in good to excellent yields. The major advantages of the present method are, short reaction times, magnetically recyclable catalyst and high yields. The newly synthesized compounds were synthesized and characterized by melting point, IR, NMR, mass spectra. Furthermore the compounds were evaluated for their antioxidant and antimicrobial activities which showed good activities when compared to standards.

Synthesis, Characterization, Antitubercular Activity, and Molecular Docking Studies of Pyrazolylpyrazoline-Clubbed Triazole and Tetrazole Hybrids.

To increase the antitubercular potency, we synthesized a series of novel pyrazolylpyrazoline derivatives (9a-p) using the one-pot multicomponent reaction of the substituted heteroaryl aldehyde (3a,b), 2-acetyl pyrrole/thiazole (4a,b), and substituted hydrazine hydrates (5-8) in the presence of base NaOH as a catalyst in ethanol as the solvent at room temperature. Substituted heteroaryl aldehyde (3a,b) was synthesized from 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-methyl-carbaldehyde on protection with ethylene glycol followed by treatment with 4-amino triazole/5-amino tetrazole and then deprotection using acid. The salient features of the green protocol are the one-pot reaction, shorter reaction time, and straightforward workup procedure. All of the compounds were tested against Mycobacterium tuberculosis H37Rv, wherein compounds 9i, 9k, 9l, 9o, and 9p were found to be most effective. The structures of newly synthesized compounds were determined using spectral methods. Furthermore, molecular docking investigations into the active site of mycobacterial InhA yielded well-clustered solutions for these compounds' binding modalities producing a binding affinity in the range from -8.884 to -7.113. Theoretical results were in good accord with the observed experimental values. The docking score of the most active compound 9o was found to be -8.884, and the Glide energy was -61.144 kcal/mol. and it was found to accommodate well into the active site of InhA, engaging in a network of bonded and nonbonded interactions.

A New Strategy for the Synthesis of Porphyrin and Expanded Porphyrin Derivatives from Di‐ and Tripyrromethanes: Antioxidant, Cytotoxic Activity, and Molecular Docking Evaluation

AbstractWe present a novel and effective process for producing porphyrins in the absence of a solvent condition, in contrast to earlier procedures. An aldehyde and pyrrole were condensed by grinding in the presence of an acidic catalyst during the synthetic process. By adjusting reactant molar ratios and concentrations, dipyrromethane 3 and tripyrromethane 4 derivatives, the synthesis was improved at room temperature in 5–10 minutes with excellent yields. In this work, we successfully synthesized a number of novel porphyrin derivatives, 6 b–j. Here, we describe a method for reacting dipyrromethane 3a with various aryl aldehydes 5 b–j while using DMF as a capping agent. Moreover, expanding porphyrin derivatives 7 a, and 7 b were synthesized from the reaction of 4a with aldehydes 5a and 5b at 0 °C. Porphyrin derivatives 6 g and 6 h displayed good antioxidant potential. The cytotoxic activity of compounds 6 h, 6 b, and 6c against the human cell lines HePG‐2 and MCF‐7 were studied. The binding modes of the synthesized compounds were analyzed by docking studies that showed good binding scores against the diverse amino acids of the selected proteins (Bcl‐2). The conducted docking studies were found to be consistent with cytotoxic results.

Green Route Synthesis and Molecular Docking of Azines Using Cellulose Sulfuric Acid under Microwave Irradiation

A novel catalytic approach for the synthesis of symmetric and asymmetric azines has been developed. The environmentally benign protocol was achieved via condensation of 1-[(2-thienyl)ethylidene]hydrazine (1) with different aromatic aldehydes 2a–h and acetyl heterocyclic compounds (4, 6, 8, 10, and 12) in the presence of cellulose sulfuric acid (CSA) as the green catalyst. These procedures offer an interesting method for the large-scale industrial manufacture of azines due to their high percentage yield, mild reaction conditions, broad substrate range, and utilization of an economical and environmentally acceptable catalyst. Additionally, the molecular docking of the products to the monoamine oxidase (MAO-A) target protein was achieved to highlight the possible binding interaction with the amino acid residues Arg51, Glu43, Gly22, Gly49, Gly443, Ala272, Ile335, and Tyr407 at the point of binding. The binding interaction energy was discovered to be (− 6.48 kcal/mol) for the protein MAO-A (PDB ID: 2Z5X). The most effective azine derivatives 7 and 13 revealed some major conserved interactions between the MAO-A protein’s binding site amino acid residues and the PDB co-crystal ligand 2Z5X. Moreover, azine derivatives 3a and 3f showed the lowest binding activity with the target MAO-A.

Copper-Catalyzed Ligand-Controlled Selective Borocarbonylation of α-Substituted Styrenes Toward β-Boryl Aldehydes and Cyclopropyl Boronate Esters

Copper-Catalyzed Ligand-Controlled Selective Borocarbonylation of α-Substituted Styrenes Toward β-Boryl Aldehydes and Cyclopropyl Boronate Esters

Green synthesis and antimicrobial activity of substituted diethyl (((5-(ethylthio)-1,3,4-thiadiazol-2-yl)amino)(phenyl)methyl)phosphonates

The one-pot, three-component, and facile synthesis of substituted diethyl (((5-(ethylthio)-1,3,4-thiadiazol-2-yl)amino)(phenyl)methyl)phosphonates (4a–j) has been achieved from the reaction of 2-amino-5-ethylthio-1,3,4-thiadiazole (1), various aromatic aldehydes (2a–j) and diethylphosphite (3) using Kabachnik–Fields reaction in the presence SnO2 nanoparticles as an efficient heterogeneous catalyst under solvent-free MWI condition. Furthermore, these series of new compounds were characterized by melting point, IR, NMR, and mass spectra. The newly synthesized compounds were evaluated for their antimicrobial activity which showed good activity compared to standard.

Fruit juice mediated multicomponent reaction for the synthesis of substituted isoxazoles and their in vitro bio-evaluation

A simple, efficient and eco-friendly procedure for the synthesis of isoxazole derivatives (4a–4h) using one-pot three-component reaction between substituted aldehydes (1a), methyl acetoacetate (2a) and hydroxylamine hydrochloride (3a) has been achieved in presence of Cocos nucifera L. juice, Solanum lycopersicum L. juice and Citrus limetta juice respectively. The homogeneity of synthesized compounds was confirmed by melting point and thin layer chromatography. The synthesized compounds were characterized by using 1H NMR, FTIR and CHN analyses and evaluated for in vitro herbicidal activity against Raphanus sativus L. (Radish seeds). The compounds (4a–4h) were also screened for their fungicidal activity against Rhizoctonia solani and Colletotrichum gloeosporioides. Antibacterial activity was also tested against Erwinia carotovora and Xanthomonas citri. From bio-evaluation data, it was found that compound 4b was most active against Raphanus sativus L. (root) and Raphanus sativus L. (shoot) respectively. Compound 4b was also found most active against both the fungus viz. R. solani and C. gloeosporioides showing maximum percentage growth inhibition i.e. 90.00 against R. solani and 82.45 against C. gloeosporioides at 2000 µg/mL concentration. Compound 4 h has shown maximum inhibition zone i.e. 3.00–9.60 mm against Erwinia carotovora at 2000 µg/mL concentration. Maximum Xanthomonas citri growth was also inhibited by compound 4 h showing inhibition zone 1.00–5.00 mm at highest concentration.

Synthesis, Anticancer Evaluation, Computer-Aided Docking Studies, and ADMET Prediction of 1,2,3-Triazolyl-Pyridine Hybrids as Human Aurora B Kinase Inhibitors.

A novel series of 1,2,3-triazolyl-pyridine hybrids were prepared through the reaction of the triazole derivative (1) with the appropriate aldehyde (2a–g) and malononitrile or ethyl cyanoacetate in the presence of ammonium acetate in refluxed acetic acid. The chemical composition of the products was established on the basis of spectral and elemental analyses. Aurora B kinase is a protein with diverse biological actions in controlling tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, making it an emerging target for diseases such as hepatocellular carcinoma (HCC). Alteration in the target protein expression causes unequal distribution of genetic information, causing HCC. The new compounds were tested for their antihepatic cancer activity, and some of them had strong efficacy against human hepatoblastoma (HepG2) cell lines.

Nucleophilic Acylation with Aromatic Aldehydes to 2 Bromoacetonitrile: An Umpolung Strategy for the Synthesis of Active Methylene Compounds.

A novel one-pot N-heterocyclic carbene (NHC)-catalysed acylation of 2- bromoacetonitrile with aromatic aldehydes is reported. The protocol involves carbonyl umpolung reactivity of aldehydes in which the carbonyl carbon attacks nucleophilically (as d1 nucleophile) on the electrophilic terminal of 2-bromoacetonitrile to afford 3-aryl-3-oxopropanenitrile. The salient features of this procedure are short reaction time, operational simplicity, ambient temperature, no by-product formation and high yields. A flame-dried round bottom flask was charged with Imidazolium salts (3a) (0.20 mmol). Aldehyde 1a (1.0 mmol), 2-bromoacetonitrile 2 (1.0 mmol), and THF / t-BuOH 5 mL; 10:1) were added at positive nitrogen pressure followed by the addition of DBU (0.15 mmol) through stirring. The resulting yellow- orange solution was stirred at room temperature for 5-6 h. After completion of the reaction (TLC monitored), the reaction mixture was concentrated under reduced pressure. The product was purified using hexane / EtOAc (10:1) as an eluent to provide analytically pure compound 4a. Physical data of representative compounds and the NMR spectroscopic data are in agreement with the literature value. The salient features of this procedure are short reaction time, operational simplicity, ambient temperature, no by-product formation and high yields. To sum up, we have developed a convenient, efficient and one-pot route for 3-oxo-3- phenylpropanenitrile synthesis from NHC promoted direct nucleophilic acylation of aromatic aldehydes using 2- bromoacetonitrile. This method provided a wide range of products and good yields. To best of our knowledge, this is the new report for the synthesis of 3-oxo-3-phenylpropanenitrile through NHC promoted nucleophilic acylation of aromatic aldehyde.

An efficient approach for the synthesis of novel methyl sulfones in acetic acid medium and evaluation of antimicrobial activity.

A series of nine methyl sulphones ( 3a –3 i ) starting from the aldehydes ( 1a–1i ) were synthesized in two consecutive steps. In the first step, preparation of allyl alcohols ( 2a–2i ) from their corresponding aldehydes by the reaction of sodium borohydride in methanol at room temperature is reported. Finally, methyl sulphones are synthesized by condensing sodium methyl sulfinates with allyl alcohols in the presence of BF 3 .Et 2 O in acetic acid medium at room temperature for about 2–3 h. The reaction conditions are simple, yields are high (85%–95%), and the products were obtained with good purity. All the synthesized compounds were characterized by their 1 H, 13 C NMR, and mass spectral analysis. All the title compounds were screened for antimicrobial activity. Among the compounds tested, the compound 3f has inhibited both Gram positive and Gram negative bacteria effectively and compound 3i has shown potent antifungal activity. These promising components may help to develop more potent drugs in the near future for the treatment of bacterial and fungal infections.

Fluorine Effects for Tunable C–C and C–S Bond Cleavage in Fluoro-Julia–Kocienski Intermediates

Classical Julia–Kocienski fluoroolefination represents an indispensable platform for the construction of monofluoroalkenes. Nevertheless, its complex multistep mechanistic manifold along with the u...

Synthesis of novel benzimidazoles at room temperature, under solvent-free condition and their biological studies

An efficient and facile synthesis of substituted novel benzimidazoles (3a–3h) mediated by fruit juices viz. Cocos nucifera L. juice, Citrus limetta juice and Citrus sinensis L. juice, via condensation of substituted aldehydes (1a–1h) and o-phenylenediammine (2a) under solvent-free condition at room temperature is presented in this paper. The purity of compounds was confirmed by melting point and thin layer chromatography. All synthesized compounds (3a–3h) were fully characterized via NMR and FTIR spectral data and evaluated for in vitro herbicidal activity against Raphanus sativus L. (Radish) seeds. The compounds (3a–3h) were also evaluated for their antibacterial activity against Erwinia cartovora and Xanthomonas citri by inhibition zone method. Antifungal activity was also determined against Rhizoctonia solani and Colletotrichum gloeosporioides by poisoned food techniques method. From activity data, it was found that compounds 3d and 3e were most active against R. sativus L. (root) and R. sativus L. (shoot), respectively. Compound 3g has shown maximum inhibition zone i.e. 8.00 mm against E. cartovora at 2000 µg/mL concentration. Maximum X. citrii growth was inhibited by compounds 3a showing inhibition zone 5.20 mm at highest concentration. Compound 3f was found most active against R. solani and C. gloeosporioides fungus at 2000 µg/mL concentration. In comparison with the conventional methods, the present method complies with several key requirements of green chemistry principles such as the utilization of renewable feedstock, auxiliary aqueous conditions and reduces waste with the use of nature-derived catalyst. Therefore, the present method offers an attractive option because of its ecological safety, environmental acceptance, cost effective and easy workup process.

Correction to: 1H-imidazol-3-ium tricyanomethanide {[HIM]C(CN)3} as a nanostructured molten salt catalyst: application to the synthesis of pyrano[4,3‐b]pyrans

In this work, we have synthesized a novel nanostructured molten salt, 1H-imidazol-3-ium tricyanomethanide {[HIMI]C(CN)3} (1), as an efficient and green protocol-compatible catalyst. This new molten salt has been fully characterized by different analytical techniques, such as FT-IR, 1HNMR, 13CNMR, thermal gravimetric analysis, derivative thermal gravimetric analysis, differential thermal analysis, X-ray diffraction, scanning electron microscopy, and high-resolution transmission electron microscopy. Additionally, the catalytic activity of {[HIMI]C(CN)3} (1, 2 mol%) has been tested in a three-component domino Knoevenagel condensation reaction. A range of structurally diverse aromatic aldehydes (2a–p), malononitrile (3), and 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one (4) are tolerated for the synthesis of 2-amino-7-methyl-5-oxo-4-aryl-4,5-dihydropyrano[4,3-b]pyran-3-carbonitrile derivatives (5a–p) under neat conditions at 50 °C. The obtained results have demonstrated that catalyst 1 shows interesting catalytic properties, such as clean reaction profile, cost-effectiveness, and green conditions. Importantly, the aforementioned catalyst is thermally stable with a 171 °C melting point not showing any significant loss in catalytic activity after 7 reaction cycles.

Preparation and Mechanistic Studies of 2‐Substituted Bisthiazolidines by Imine Exchange

Bisthiazolidines (BTZ) are bicyclic compounds considered penicillin analogs that inhibit the full range of Metallo-β-Lactamases (MBLs) and potentiate β-lactam activity against resistant bacteria. Herein we present a new methodology to prepare 2-substituted bisthiazolidines by aldehyde exchange. Thirteen new bisthiazolidines were prepared using this methodology, with yields ranged from 31 to 75%. The reaction is based on in situ imines formation, which are able to exchange side chains. The reaction intermediates were studied based on NMR experiments and a key imine 1b-II could be detected in the reaction mixture. Furthermore, a DFT computational analysis was performed to gain insights into the reaction mechanism, allowing us to unveil the different pathways and their activation barriers within the synthetic route. The results suggest that the most favorable route involve the formation of the thiazolidine 1b-III by i) a N-assisted N-C bond cleavage, and ii) a thiol-mediated 5 endo-trig cyclization followed by a C-N bond cleavage. In contrast with previously reported evidence, the imine metathesis was discarded as a plausible pathway. Finally, the reaction of 1b-III with aldehyde 2a leads to bicycle 4a via the iminium ion 1b-V.

Synthesis of Novel Biologically Important 5-Amino-2-Oxo-7-Aryl-3,7-Dihydro-2H-Pyrano[2,3-d]Thiazole-6-Carbonitriles in Trifluoroethanol (TFE) under Ultrasound Irradiation Condition and Their Antimicrobial Activity

A series of novel 5-amino-2-oxo-7-aryl-3,7-dihydro-2H-pyrano[2,3-d]thiazole-6-carbonitriles 5a–j have been synthesized by adopting a facile and simple methodology. The reaction of monochloroacetic acid (1), thiourea (2), aryl and aliphatic aldehydes 3a–j and malononitrile (4) in trifluoroethanol (TFE) under ultrasound irradiation condition afforded 2 H-pyrano[2,3-d]thiazole-6-carbonitriles (5a–j). The remarkable advantages of this method are the simple procedure; high yields, short rection time and environmentally benign method are the advantages of this protocol.