Efficient One-Pot,Four-Component Synthesis of 1,2,3-Triazole-Linked Tetrahydrobenzo[b]pyrans

A one-pot procedure has been developed for the synthesis of (1,2,3-triazolyl) methoxyphenyl tetrahydro-5-oxo-4H-chromene derivatives by concurrent reaction of aryloxy propargylated aldehydes, various azides, active methylene compounds, and 1,3-cyclohexanediones using catalytic amounts of Cu(OAc)₂ / sodium ascorbate and diammonium hydrogen phosphate in aqueous ethanol media. Excellent conversion of starting materials was achieved to the desired (1,2,3-triazolyl) methoxyphenyl tetrahydro-5-oxo-4H-chromene products.     

Synthesis Through Three‐Component Reactions Catalyzed by FeCl3 of Fused Pyridocoumarins as Inhibitors of Lipid Peroxidation

2,4‐Diphenyl substituted fused pyridocoumarins have been synthesized by one‐pot three‐component domino reactions of aminocoumarins, benzaldehyde, and phenylacetylene by using FeCl₃ (10%) as catalyst under reflux or MW irradiation. The new compounds were tested as inhibitors of lipid peroxidation. The 7,9‐diphenyl‐2H‐pyrano[2,3‐g]quinolin‐2‐one presents interesting results and could serve as lead compound.     

An Eco‐friendly Synthesis and Biological Screening of Fused Heterocyclic Compounds Containing a Thiophene Moiety via Gewald Reaction

5‐Amino‐3‐phenyl‐1‐(2,4,6‐trichlorophenyl)‐1H‐thieno[3,2‐c]pyrazole‐6‐carbonitrile ( 2 ) was designed and synthesized by one‐pot multicomponent reaction. Compound 2 was reacted with different reagents to obtain new condensed moieties with our thienopyrazole skeleton. The compounds were prepared by using environmentally benign techniques as microwave irradiation, ultrasonic irradiation, and ball‐milling. The structure of the prepared compounds was elucidated through spectroscopic methods. The new compounds were evaluated for their in vitro antibacterial and antifungal potentialities.     

Fe3O4@SiO2@D-NHCS-Tr as an efficient and reusable catalyst for the synthesis of indol-3-yl-4H-chromene via a multi-component reaction under solvent-free conditions

Fe₃O₄@SiO₂@D-NHCS-Tr was used as an efficient catalyst in the three-component reaction between indole derivatives, salicylaldehyde, and active methylene compounds under solvent-free conditions to the synthesis of indol-3-yl-4H-chromene derivatives. The features of this method include the green conditions of the reaction, easy separation, eco-friendly and cost-effectiveness of the catalyst, and high yield in short reaction times.     

A “One Pot,” Environmentally Friendly,Multicomponent Synthesis of 2‐Amino‐5‐cyano‐4‐[(2‐aryl)‐1H‐indol‐3‐yl]‐6‐hydroxypyrimidines and Their Antimicrobial Activity

A series of multifunctional 2‐amino‐5‐cyano‐4‐[(2‐aryl)‐1H‐indol‐3‐yl]‐6‐hydroxypyrimidines ( 4a , 4b , 4c , 4d , 4e , 4f ) was synthesized by multicomponent reaction of 3‐formylindole ( 1 ), cyanoethylacetate ( 2 ), and guanidine hydrochloride ( 3 ) with NaOH by using green chemical techniques, viz. microwave irradiation and grindstone technology. The same reactants when refluxed in ethanol also gave titled compounds ( 4a , 4b , 4c , 4d , 4e , 4f ). Compared with conventional procedure, the reaction can be carried out under milder conditions, requiring a shorter reaction time and giving higher yields following the green chemistry methodology. All the synthesized compounds have been characterized on the basis of elemental analyses and spectral data (IR, ¹H NMR, ¹³C NMR, and mass). All synthesized compounds were also evaluated for their antimicrobial activity against nine pathogenic bacteria, antifungal activity against Rhizopus stolonifer, Aspergillus flavus, and Fusarium oxysporum and antibacterial activity against Escherichia coli and Pseudomonas aeruginosa at different concentrations. Most of the compounds showed mild to moderate activity.     

PbS nanoparticles stabilized on HPG-modified FeNi3 as catalyst for synthesis of 2-amino-4H-chromene under mild conditions

FeNi₃\SiO₂\HPG\PbS magnetic nanoparticles (MNPs) catalyst was readily prepared from inexpensive starting materials in aqueous media which catalyzed the synthesis 2-amino-4H-chromene via intermittent microwave irradiation. X-ray diffraction, transmission electron micrographs, and scanning electron micrographs were employed to characterize the properties of the synthesized FeNi₃\SiO₂\HPG\PbS MNPs. High catalytic activity and ease of recovery from the reaction mixture using external magnet and several reuse times without significant losses in performance are additional eco-friendly attributes of this catalytic system.     

Synthesis,In Vitro Biological Screening,and In Silico Computational Studies of Some Novel Imidazole‐2‐thiol Derivatives

Substituted imidazole analogues 2‐((5‐acetyl‐4‐methyl‐1‐phenyl‐1H‐imidazole‐2‐yl)thio)‐N‐phenylacetamides ( 3a – 3m ) have been synthesized from 1‐[1‐(phenyl)‐2‐mercapto‐4‐methyl‐1H‐imidazol‐5‐yl]‐ethanone ( 1a – 1e ) and 2‐chloro‐N‐phenylacetamide ( 2a – 2i ) in the presence of potassium carbonate as a catalyst in dimethylformamide under microwave irradiation as well as conventional method. Structures of the obtained compounds have been confirmed by advance spectroscopic techniques such as IR, ¹H NMR, ¹³C NMR, and mass spectrometry. All the synthesized compounds were tested for their in vitro antimicrobial and antituberculosis activities. Good antibacterial molecules were further screened for the bacterial resisted cell line, from which compound 3b shows maximum inhibition. In silico molecular docking study was carried out to discover the binding affinity of synthesized compounds with active site of transferase (PDB ID: 1HNJ) and antibiotic resistance (PDB ID: 1W3R) protein. Moreover, molecular dynamics study of the 3b ‐1W3R complex has also been performed, as 3b has a good antibacterial activity as compared with other.     

Microwave‐Assisted Synthesis and Antituberculosis Screening of Some 4‐((3‐(Trifluoromethyl)‐5,6‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrazin‐7(8H)‐l)methyl)benzenamine Hybrids

In the present investigation, a series of 4‐((3‐(trifluoromethyl)‐5,6‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrazin‐7(8H)‐yl)methyl)benzenamine analogs 6a–o were synthesized and characterized by IR, NMR (¹H and ¹³C), and mass spectra. All newly synthesized compounds 6a–o were prepared under conventional and microwave irradiation methods. These compounds obtained in higher yields and in shorter reaction times in the microwave irradiation method when compared with the conventional method. Synthesized compounds 6a–o were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis H₃₇Ra using an established XTT reduction menadione assay. Among the screened compounds, 6i (IC₅₀: 1.82 μg/mL), 6j (IC₅₀: 1.02 μg/mL), and 6k (IC₅₀: 1.59 μg/mL) showed excellent activity. Furthermore, compound 6i showed MIC₉₀ value of 16.02 μg/mL. In summary, the results indicate the identification of some novel, selective, and specific inhibitors against M. tuberculosis that can be explored further for the potential antitubercular drug.     

Design and Synthesis of Antimicrobial Active (E)‐(3‐(Substituted‐styryl)‐7H‐furo[2,3‐f]chromen‐2‐yl)(phenyl)methanone Derivatives and Their In Silico Molecular Docking Studies

Nine new (E)‐(3‐(substituted‐styryl)‐7H‐furo[2,3‐f]chromen‐2‐yl)(phenyl)methanone derivatives, 7 ( a – i ), with an efficient microwave‐assisted synthetic method was achieved by reacting with (E)‐3‐(aryl)‐1‐(5‐hydroxy‐2H‐chromen‐6‐yl)prop‐2‐en‐1‐ones and 2‐bromo‐1‐(4‐bromophenyl)ethanone. The microwave irradiation method was found to be best with high yields and with shorter reaction times compared with the conventional method. All the new products structural assignments were confirmed by spectral data like FTIR, ¹H NMR, ¹³C NMR, ESI MS, and analytical data. Moreover, these newly synthesized compounds were tested in vitro for their antimicrobial activity against various bacterial and fungal strains. Some of these new chromen derivatives like 7b , 7c , and 7d exhibits good antibacterial and antifungal activities. Furthermore, these biological evolution results were a good correlation with molecular docking studies performed based on their computational DFT minimized structures exhibited high binding energies.     

Synthesis,antioxidant, and antimicrobial activity of 3-(1H-indole-3-carbonyl)-2H-chromen-2-ones

A simple and convenient method for the one-pot synthesis of 3-(1H-indole-3-carbonyl)-2H-chromen-2-one derivatives from the reaction of 3-cyanoacetyl indole and salicylaldehyde in the presence of Na₂CO₃ in water: methanol (1:1) is described. Wider substrate scope, high yields, operational simplicity, and simple purification process make the protocol highly applicable in the synthesis of 3-(1H-indole-3-carbonyl)-2H-chromen-2-ones. For the first time, in vitro antioxidant and antimicrobial activity was studied. Compounds 5e , 7a , and 7b exhibits good radical scavenging ability against DPPH free radical. Compounds 7b , 5f , and 5g possess lower EC₅₀ values than the Standards AA and BHA and thus proving their high reducing power. Compounds 5d and 5f show good antibacterial activity against gram-positive bacteria (MRSA) while compounds 5c , 7a , and 7b exhibits good antibacterial activity against Bacillus sp. Compounds 5b and 5e show good antibacterial activity against gram negative bacterial strains (Escherichia coli, Klebsiella pneumoniae) and compounds 5g and 5h exhibits good antifungal activity against Candida albicans.     

A series of (E)‐5‐(arylideneamino)‐1‐tert‐butyl‐1H‐pyrrole‐3‐carbonitriles and their reduction products to secondary amines: syntheses and X‐ray structural studies

An efficent access to a series of N‐(pyrrol‐2‐yl)amines, namely (E)‐1‐tert‐butyl‐5‐[(4‐chlorobenzylidene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₆ClN₃, (7a), (E)‐1‐tert‐butyl‐5‐[(2,4‐dichlorobenzylidene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₅Cl₂N₃, (7b), (E)‐1‐tert‐butyl‐5‐[(pyridin‐4‐ylmethylene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₅H₁₆N₄, (7c), 1‐tert‐butyl‐5‐[(4‐chlorobenzyl)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₈ClN₃, (8a), and 1‐tert‐butyl‐5‐[(2,4‐dichlorobenzyl)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₇Cl₂N₃, (8b), by a two‐step synthesis sequence (solvent‐free condensation and reduction) starting from 5‐amino‐1‐tert‐butyl‐1H‐pyrrole‐3‐carbonitrile is described. The syntheses proceed via isolated N‐(pyrrol‐2‐yl)imines, which are also key synthetic intermediates of other valuable compounds. The crystal structures of the reduced compounds showed a reduction in the symmetry compared with the corresponding precursors, viz. Pbcm to P from compound (7a) to (8a) and P2₁/c to P from compound (7b) to (8b), probably due to a severe change in the molecular conformations, resulting in the loss of planarity observed in the nonreduced compounds. In all of the crystals, the supramolecular assembly is controlled mainly by strong (N,C)—H…N hydrogen bonds. However, in the case of (7a)–(7c), C—H…Cl interactions are strong enough to help in the three‐dimensional architecture, as observed in Hirshfeld surface maps.     

Nanofiber cellulose di- and tri-acetate using ferric chloride as a catalyst promoting highly efficient synthesis under microwave irradiation

An efficient method for the generation of cellulose di- and tri-acetate nano-structures is obtained through testing ferric chloride hydrate (FeCl₃·6H₂O) as a valuable Lewis acid catalyst with acetic anhydride under microwave irradiation. Our target was to evaluate the effects of the reaction conditions on the products' properties such as surface area and particle size distribution. It was found that changes in the degree of substitution (DS), the surface area, the degree of polymerization and the particle size distribution of the products correlated with reaction conditions. Cellulose tri-acetate nanofibers with DS of 2.94 with 98.03% yield was prepared using 200 mg of FeCl₃·6H₂O, 25 ml of Ac₂O and 4 minutes of microwave irradiation. Also, cellulose di-acetate nanofibers were prepared with DS values ranged between 2.37 and 2.72 with yield ranged between 78.92 and 90.58%. The percentage of acetyl groups (Ac%) as well as the BET specific surface area, total pore volume, mean pore diameter, mono layer volume and the mean particle size of the products were determined. The maximum specific surface area obtained for the acetylated cellulose was about ten times larger than that measured for the commercial cotton cellulose and about six times larger than that of the commercial cellulose acetate. The lowest mean particle size (34.90 nm) was about eleven times smaller than the mean particle size of the commercial cellulose acetate (394 nm). The present work has proved that FeCl₃·6H₂O was a highly active catalyst for the esterification of cellulose with unexpected yields and for the formation of nanofibers with low molecular weight.     

Microwave-assisted synthesis and antimicrobial activity of novel spiro 1,3,4-thiadiazolines from isatin derivatives

This work describes the synthesis of spiro 1,3,4-thiadiazolines from isatin-β-thiosemicarbazone acetylation, using microwave irradiation as a source of heating the reaction medium. N-substituted isatin derivatives were used as substrates to obtain thiosemicarbazones by adding thiosemicarbazide to the isatin ketone carbonyl. The final synthetic step was the reaction of thiosemicarbazones with acetic anhydride under microwave irradiation to get the spiro compounds. Reaction times ranged from 6 to 18 minutes resulting in yields of up to 90%. Biological assays have shown promising antibacterial and antifungal activity, especially spiro thiadiazolines derived from allylated isatins. All the proposed molecules proved to be potential drug candidates based on the results of the in silico investigation, with satisfactory drug-likeness and drug-score, respecting Lipinski's rule. The use of the microwave reactor was efficient for the synthesis of thiosemicarbazones and spiro compounds, resulting in a significant reduction in reaction times with conventional heating. Taking into account the threat of antimicrobial resistance, this work presents a series of bioactive molecules that are easily obtained via microwave reaction.     

Synthesis and Antimicrobial Activity Evaluation of Novel Oxadiazino/Thiadiazino‐Indole and Oxadiazole/Thiadiazole Derivatives of 2‐Oxo‐2H‐benzopyran

A series of novel oxadiazino/thiadiazino‐indole and oxadiazole/thiadiazole derivatives of 2‐oxo‐2H‐benzopyran were synthesized and evaluated for their antimicrobial activities against the bacteria Staphylococcus aureus, Salmonella typhi, and Escherichia coli and two fungal species Candida albicans and Aspergillus niger. The antibacterial activities were expressed as minimum inhibitory concentration (MIC₅₀) in microgram per milliliter. The title compounds 4b and 10b revealed promising antibacterial activity whereas 6d , 7d , 9d , and 10b exhibited significantly impressive antifungal activity.     

A CONVENIENT SYNTHESIS OF 2-AMINO-5,6,7,8,-TETRAHYDRO-5-OXO-4-ARYL-7,7-DIMETHYL-4H-BENZO-[b]-PYRAN-3-ETHYLCARBOXYLATES UNDER MICROWAVE IRRADIATION

A series of 2-amino-5,6,7,8-tetrahydro-5-oxo-4-aryl-7,7-dimethyl-4H-benzo-[b]-pyran-3-ethylcarboxylates were synthesized by reaction of β-cyano-β-carbothoxy styrene and 5,5-dimethyl-1,3-cyclo-hexanedione under microwave irradiation without catalyst and solvent.     

A cascade formation of N-pyridylacrylamides from pyrido[1,2-a]pyrimidine diones and chromene aldehydes

Various N-(pyridin-2-yl)acrylamides bearing 4H-chromene fragment were synthesized via the condensation of 4H-chromene-3-carbaldehydes and their fused analogues with 2H-pyrido[1,2-a]pyrimidine-2,4(3H)-diones employing NH₄OAc/AcOH system. Possible mechanism of this hetero- domino reaction involves the consecutive Knoevenagel condensation, oxa-6v-electrocyclization, aza-6v-electrocyclic ring-opening, nucleophilic addition, retro-Alder-ene reaction and oxa-6v-electrocyclic ring-disclosure.     

Synthesis of Functionalized H‐[1]Benzopyrano[2,3‐b]pyridines by the Friedländer Approach: Antimycobacterial and Antimicrobial Profile

A series of functionalized H‐[1]benzopyrano[2,3‐b]pyridine derivatives were synthesized by the Friedländer reaction of 2‐amino‐4‐oxo‐4H‐chromene‐3‐carbonitriles 1 with malononitrile, ethyl cyanoacetate, or acetophenone (Scheme). The synthesized compounds 2 – 4 were screened for their in vitro activity against antitubercular, antibacterial, and antifungal species (Fig., Table). Among the synthesized compounds, 3c and 4f were the most active with 99% inhibition against Mycobacterium tuberculosis H₃₇Rv, while compounds 2f, 3f , and 4d exhibited 69%, 63%, and 61% inhibition, respectively. The 4‐amino‐7,9‐dibromo‐1,5‐dihydro‐2,5‐dioxo‐2H‐chromeno[2,3‐b]pyridine‐3‐carbonitrile ( 3b ) showed the most potent antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. Several chromeno[2,3‐b]pyridine derivatives showed equal or more potency against Staphylococcus aureus and Candida albicans.     

One-pot synthesis of bis (phenylimino dihydro thiazolyl-2H-chromene) derivatives

A novel series of bis (phenylimino dihydro thiazolyl-2H-chromene) derivatives have been synthesized through an efficient one-pot multicomponent approach involving different substituted of 3-(2-bromoacetyl)-2H-chromen-2-ones, phenyl isothiocyanates and para-phenylenediamine in presence of dimethylformamide solvent. The target compounds were obtained in a shorter reaction time through simple reaction work up with good yields. All the synthesized products were characterized by their spectral and analytical data like IR, ¹H NMR, ¹³C NMR, Roesy, and mass spectral data.     

CAN-catalyzed microwave promoted reaction of indole with Betti bases under solvent-free condition and evaluation of antibacterial activity of the products

CAN-catalyzed reaction of Betti bases with indoles under microwave irradiation gives 3-(α,α-diarylmethyl)indoles. Better yield of the products, especially when one of the aryl ring is phenol were achieved. The reaction is performed in solvent-free condition. The antibacterial studies of the synthesized compounds were performed and some of the compounds showed good activity against Methicillin-resistant Staphylococcus aureus bacteria.     

(5RS)‐6H‐Spiro[pyrazolo[1,5‐c]quinazoline‐5,4′‐thiochroman]: efficient synthesis under mild conditions,molecular structure and supramolecular assembly

Pyrazolo[1,5‐c]quinazolines are fused‐quinazoline derivatives which have been reported as potential agents against neurological disorders. The normal synthesis routes to these compounds require harsh reaction conditions, long reaction times or multistep sequences. The title compound, C₁₈H₁₅N₃S, has been prepared under very mild conditions by condensation of thiochroman‐4‐one with 5‐(2‐aminophenyl)‐1H‐pyrazole, which had itself been prepared by the reaction of hydrazine hydrate with 4‐hydroxyquinoline mediated by a brief period of microwave heating. Within the molecule in the crystal structure, the reduced pyrimidine ring adopts an envelope conformation, whereas the thiane ring adopts a half‐chair conformation. Molecules are linked into sheets by a combination of one N—H...S hydrogen bond and two independent C—H...π(arene) hydrogen bonds, which utilize the same aryl ring as the acceptor, with one C—H bond donating to each face of the ring. Comparisons are made with some related compounds.