Novel drug‐based Fe(III) heterochelates: synthetic,spectroscopic, thermal and in‐vitro antibacterial significance

A series of novel heterochelates of the type [Fe(Aⁿ)(L)(H₂O)₂]^?mH₂O [where H₂Aⁿ = 4,4′‐(arylmethylene)bis(3‐methyl‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐5‐ol); aryl = 4‐nitrophenyl, m = 1 (H₂A¹); 4‐chlorophenyl, m = 2 (H₂A²); phenyl, m = 2 (H₂A³); 4‐hydroxyphenyl, m = 2 (H₂A⁴); 4‐methoxyphenyl, m = 2 (H₂A⁵); 4‐hydroxy‐3‐methoxyphenyl, m = 1.5 (H₂A⁶); 2‐nitrophenyl, m = 1.5 (H₂A⁷); 3‐nitrophenyl, m = 0.5 (H₂A⁸); p‐tolyl, m = 1 (H₂A⁹) and HL = 1‐cyclopropyl‐6‐fluoro‐4‐oxo‐7‐(piperazin‐1‐yl)‐1,4‐dihydroquinoline‐3‐carboxylic acid] were investigated. They were characterized by elemental analysis (FT‐IR, ¹H‐ & ¹³C‐NMR, and electronic) spectra, magnetic measurements and thermal studies. The FAB‐mass spectrum of [Fe(A³)(L)(H₂O)₂]^?2H₂O was determined. Magnetic moment and reflectance spectral studies revealed that an octahedral geometry could be assigned to all the prepared heterochelates. Ligands (H₂Aⁿ) and their heterochelates were screened for their in‐vitro antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Serratia marcescens bacterial strains. The kinetic parameters such as order of reaction (n), the energy of activation (E_a), the pre‐exponential factor (A), the activation entropy (ΔS^#), the activation enthalpy (ΔH^#) and the free energy of activation (ΔG^#) are reported. Copyright © 2009 John Wiley & Sons, Ltd.     

Antibacterial,spectral and thermal aspects of some novel first transition metal‐based heterochelates

A new ligand, 5‐{[5‐(pyridine‐4‐yl)‐1,3,4‐oxadiazole‐2‐ylthio]methyl}quinoline‐8‐ol (K), was synthesized by base‐catalysed reaction of 5‐chloromethyl‐8‐hydroxy quinoline (CMQ) and 5‐(pyridine‐4‐yl)‐1,3,4‐oxadiazole‐2‐thiol. The obtained ligand K was characterized by ¹H NMR, ¹³C NMR and IR spectroscopic techniques and reacted with transition metal salts to afford metal‐containing heterochelates. The structures of the synthesized heterochelates were characterized using elemental analyses, infrared spectra, electronic spectra, magnetic measurements, FAB mass spectrum and thermogravimetric analyses. The kinetic parameters such as order of reaction (n) and the energy of activation (E_a) are reported using the Freeman–Carroll method. The pre‐exponential factor (A), the activation entropy (ΔS^#), the activation enthalpy (ΔH^#) and the free energy of activation (ΔG^#) were calculated. Heterochelates were also screened for their in vitro antibacterial activity against a range of Gram‐positive (Bacillus substilis, Staphylococcus aureus) and Gram‐negative (Escherichia coli, Serratiamarcescens) organisms. Copyright © 2010 John Wiley & Sons, Ltd.     

An Efficient One‐pot Three‐component Method for the Synthesis of 5‐Amino‐3‐(2‐oxo‐2H‐chromen‐3‐yl)‐7‐aryl‐7H‐thiazolo[3,2‐a]pyridine‐6,8‐dicarbonitriles

A facile, convenient, and adequate method has been developed for the synthesis of novel 5‐amino‐3‐(2‐oxo‐2H‐chromen‐3‐yl)‐7‐aryl‐7H‐thiazolo[3,2‐a]pyridine‐6,8‐dicarbonitriles ( 6 ) by employing 2‐(4‐(2‐oxo‐2H‐chromen‐3‐yl)thiazol‐2‐yl)acetonitrile ( 3 ) as an important precursor. Initially, we have synthesized the target compounds in a stepwise manner and then approached a tandem method to examine the feasibility of one‐pot method. Subsequently, one‐pot three‐component protocol has been established for the synthesis of title compounds by the reaction of 3 with benzaldehyde and malononitrile in refluxing ethanol engender a new six‐membered thiazolo[3,2‐a] pyridine as a hybrid scaffold. Reaction conditions were optimized for this reaction and a broad substrate scope with various aryl and heteroaryl aldehydes make this protocol very practical, attractive, and worthy. Mechanistic aspects for the formation of these compounds were outlined comprehensively. Characterization of these newly synthesized compounds was achieved by means of IR, ¹H NMR, ¹³C NMR, and HRMS.     

In‐vitro antimicrobial,thermal and spectral studies of mixed ligand Cu(II) heterochelates of clioquinol and coumarin derivatives

The mixed‐ligand heterochelates of Cu(II) with 5‐chloro‐7‐iodo‐8‐hydroxyquinoline (clioquinol) and various uninegative bidentate ligands were prepared. The structure of mixed‐ligand heterochelates was investigated using spectral, physicochemical, elemental analysis and thermal studies. The FAB‐mass spectrum of [Cu(A²)(CQ)(H₂O)₂].2H₂O has been carried out. Magnetic moment and reflectance spectral studies reveal that an octahedral geometry has been assigned to all the prepared heterochelates. The kinetic parameters such as order of reaction (n), the energy of activation (E_a), the pre‐exponential factor (A), the activation entropy (ΔS^#), the activation enthalpy (ΔH^#) and the free energy of activation (ΔG^#) have been reported. The ligands, metal salts, heterochelates, control and standard drug were tested for their in‐vitro antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Bacillus substilis. The metal complexes exhibit good activity against bacterial strains compared with parental compounds, and moderate compared with the standard drug (clioquinol). Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis of N1‐substituted coumarino[4,3‐c] pyrazoles

3‐Acyl‐4‐hydroxy‐2‐oxo‐2H‐chromen derivatives 1a‐d were condensed with (7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl)‐acetic acid hydrazide 2 , (4‐methyl‐2‐oxo‐2H‐chromen‐7‐yloxy)‐acetic acid hydrazide 3 , and (7‐hydrazinocarbonylmethoxy‐2‐oxo‐2H‐chromen‐4‐yl)‐acetic acid hydrazide 4 , to give corresponding 3‐alkyl‐1‐[2‐(7‐hydroxy‐2‐oxo‐2H‐chromeno‐4‐yl)‐acetyl]‐1H‐chromeno[4,3‐c]pyrazole‐4‐one 5a‐d , 3‐alkyl‐1‐[2‐(4‐methyl‐2‐oxo‐2H‐chromeno‐7‐yloxy)‐acetyl]‐1H‐chromeno[4,3‐c]pyrazole‐4‐one 6a‐d , and 1‐{4‐[(3‐alkyl‐1H‐chromeno[4,3‐c]pyrazole‐4‐one‐1‐yl)‐carbonylmethyl]‐2‐oxo‐2H‐chromen‐7‐yloxy‐acetyl}‐3‐alkyl‐1H‐chromeno[4,3‐c]pyrazole‐4‐one 7a‐d.     

Synthesis,spectroscopic, thermal and biological aspects of drug‐based copper(II) complexes

A series of novel complexes of the type Cu(II)(L_n)₂(H₂O)₂]^•xH₂O [where L_n = L _1–4 , these ligands being described as: L ₁ , 2‐({4‐[6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐ylsulfonyl]phenylimino}methyl)phenol, x = 1; L ₂ , 2‐({4‐[6,7‐dihydrothieno[3,2‐c] pyridin‐5(4H)‐ylsulfonyl]phenylimino}methyl)‐5‐(methoxy)phenol, x = 2; L ₃ , 5‐chloro‐2‐({4‐[6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐ylsulfonyl]phenylimino}methyl)phenol, x = 2; and L ₄ , 5‐bromo‐4‐chloro‐2‐({4‐[6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐ylsulfonyl]phenylimino} methyl)phenol, x = 1] was investigated. They were characterized by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR and electronic spectra, magnetic measurements and thermal studies. The FAB‐mass spectrum of [Cu(II)( L ₁ )₂(H₂O)₂]^•H₂O was determined. A magnetic moment and reflectance spectral study revealed that an octahedral geometry could be assigned to all the prepared complexes. Ligands (L_n) and their metal complexes were screened for their in vitro antibacterial activity against Bacillus subtillis, Pseudomonas aeruginosa, Escherichia coli and Serratia marcescens bacterial strains. Kinetic parameters such as order of reaction (n), the energy of activation (E_a), the pre‐exponential factor (A), the activation entropy (ΔS^≠), the activation enthalpy (ΔH^≠) and the free energy of activation (ΔG^≠) are reported. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis of new 3‐(4‐oxo‐4H‐chromen‐3‐yl)‐3a,6a‐dihydropyrrolo[3,4‐d]isoxazole‐4,6‐dione derivatives by 1,3‐dipolar cycloaddition reaction

A series of new 3‐(4‐oxo‐4H‐chromen‐3‐yl)‐3a,6a‐dihydropyrrolo[3,4‐d]isoxazole‐4,6‐dione have been synthesized by the reaction of N‐arylmaleimides with nitrile oxide, prepared from α‐chloro‐4‐oxo‐4H‐chromen‐carbaldehyde oximes in situ through 1,3‐dipolar cycloaddition reaction. The structures of all new compounds were confirmed by elemental analysis, ir,¹H nmr and mass spectral data.     

Preparation of Furo[3,2‐c]coumarins from 3‐Cinnamoyl‐4‐hydroxy‐2H‐chromen‐2‐ones and Acyl Chlorides: A Bu3P‐Mediated C‐Acylation/Cyclization Sequence

A Bu₃P‐mediated cyclization reaction of 3‐cinnamoyl‐4‐hydroxy‐2H‐chromen‐2‐ones though electrophilic addition of acyl chlorides towards the synthesis of highly functionalized furo[3,2‐c]coumarins bearing a phosphorus ylide moiety is described. These unprecedented cyclization reaction proceeds under mild reaction conditions within short reaction times (1 min to 1 h), and can be further applied in the synthesis of alkenyl‐substituted furo[3,2‐c]coumarins by the treatment with carbonyl electrophiles under basic conditions.     

Synthesis of Some New Nitrogen Bridge‐head Triazolopyridines,Pyridotriazines, and Pyridotriazepines Incorporating 6‐Methylchromone Moiety

Some new triazolo[1,5‐a]pyridines, pyrido[1,2‐b][1,2,4]triazines, and pyrido[1,2‐b][1,2,4]triazepines incorporating 6‐methylchromone moiety were prepared from the reaction of 1,6‐diamino‐4‐(6‐methyl‐4‐oxo‐4H‐chromen‐3‐yl)‐2‐oxo‐1,2‐dihydropyridine‐3,5‐dicarbonitrile ( 4 ) with some electrophilic reagents.     

Synthesis of [2‐aryl‐6‐oxo‐6H‐chromeno[6,7‐d]oxazol‐8‐yl]‐acetic acid ethyl esters

A number of coumarino[6,7‐d]oxazoles (nitrogen analogs of psoralens) have been synthesized from (7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl) acetic acid ethyl ester 1 . The synthetic route began with the nitration of 1 with nitric acid in acetic acid to give (6‐nitro‐7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl) acetic acid ethyl ester 2 ; (3,6‐dinitro‐7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl) acetic acid ethyl ester 3 and (3,6,8‐trinitro‐7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl) acetic acid ethyl ester 4 . The reduction of 2 was accomplished with tin(II) chloride, tin, and concentrated hydrochloric acid in ethanol giving (6‐amino‐7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl) acetic acid ethyl ester 5 . After the condensation of aminocoumarin 5 with aromatic aldehyde in glacial acetic acid medium, followed the dehydrocyclization to coumarino[6,7‐d]oxazoles 7a‐k . The intermediate Schiff's bases 6a‐k have been obtained from 5 with aromatic aldehyde in ethanol. Antibacterial and antifungal activities of the compounds have been evaluated.     

Polycyclic N‐Heterocyclic Compounds. Part 84: Reaction of N‐(pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4‐yl)amidines or N‐(pyrido[2′,3′:4,5]furo[3,2‐d]pyrimidin‐4‐yl)amidines with Hydroxylamine Hydrochloride

The reactions of nine N‐(pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4‐yl)amidines ( 3 ) with hydroxylamine hydrochloride produced new cyclization products. These were formed via ring cleavage of the pyrimidine component followed by a 1,2,4‐oxadiazole‐forming ring closure to give N‐[2‐([1,2,4]oxadiazol‐5‐yl)thieno[2,3‐b]pyridin‐3‐yl]formamide oximes ( 11 ). Reaction of six N‐(pyrido[2′,3′:4,5]furo[3,2‐d]pyrimidin‐4‐yl)amidines ( 12 ) with hydroxylamine hydrochloride gave similar results. Effects of the newly synthesized compounds on pentosidine formation were also evaluated.     

Synthesis and Antimicrobial Evaluation of Some New Spiroindolinone Derivatives

In an attempt to find a new class of antimicrobial agents, a series of spiroindolinone compounds containing pyridine, pyrimidine, benzopyrans, pyrido, naphtodiazepines, pyrazole, and isoxazole ring systems were prepared via the reaction of 3‐(2‐oxo‐2‐(3‐oxo‐3H‐benzo[f]chromen‐2‐yl)ethylidene)indolin‐2‐one ( 4 ) with an appropriate nucleophilic reagent. Newly synthesized compounds were characterized by elemental analysis and spectral data (IR, ¹H‐NMR, ¹³C‐NMR, and mass spectra). Representative compounds were tested and evaluated as antimicrobial agents.     

Synthetic,spectroscopic and thermal aspects of some heterochelates

The present article describes the synthesis, structural features and thermal studies of heterochelates of the type [M(SB)(benen)(H₂O)]·nH₂O [where H₂SB=(Z)-2-(2,2,2-trifluoro-1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)ethylideneamino)benzoic acid, benen=bis(benzylidene)ethylenediamine and M=Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and VO(IV)]. The Schiff base (H₂SB) have been characterized on the basis of elemental analysis, IR, ¹H and ¹³C NMR. The heterochelates have been characterized on the basis of elemental analyses, magnetic measurements, solid state conductivity measurements, IR, reflectance spectra, and thermal studies. The FAB mass spectrum of [Co(SB)(benen)(H₂O)] has been carried out. The kinetic parameters such as order of reaction (n) and the energy of activation (E _a) have been reported using Freeman-Carroll method. The pre-exponential factor (A), the activation entropy (ΔS ^#), the activation enthalpy (ΔH ^#) and the free energy of activation (ΔG ^#) have been calculated.     

A Facile Synthesis of Aryl‐Substituted Hydrazono‐Pyrazolyl[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin Derivatives

Some inimitable and therapeutic coumarin‐substituted fused[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadizole derivatives were synthesized by the cyclocondensation reaction of 2‐oxo‐2H‐chromene‐3‐carboxylic acid ( 1 ) and 4‐amino‐5‐hydrazinyl‐4H‐[1,2,4]‐triazole‐3‐thiol ( 2 ) by using phosphorous oxychloride as a cyclizing agent. This cyclized intermediate 3‐(3‐hydrazino‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐chromen‐2‐one ( 3 ) later condensation with various ethyl 2‐(2‐arylhydrazono)‐3‐oxobutanoates ( 4 ) in NaOAc/MeOH under reflux conditions afforded the corresponding new series of aryl‐substituted hydrazono‐pyrazolyl‐[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin derivatives ( 5 ) in good to excellent yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR and mass spectroscopic studies.     

Sulfamic Acid–Catalyzed One‐Pot Synthesis of 3‐(4,6‐Dimethyl‐oxazolo[4,5‐c]quinolin‐2‐yl)‐chromen‐2‐ones using the Conventional Method and Microwave Irradiation

A rapid and efficient method for the preparation of 3‐(4,6‐dimethyl‐oxazolo[4,5‐c]quinolin‐2‐yl)‐chromen‐2‐ones by the reaction between 3‐amino‐2,8‐dimethyl‐quinolin‐4‐ol and 2‐oxo‐2H‐chromen‐3‐carboxylic acid using sulfamic acid as a acid catalyst and dimethyl formamide as a solvent using the conventional method and microwave irradiation is reported.     

Facile Synthesis of Novel 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one Derivatives as Potential Anticancer Agents

A series of 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 6a – l ) derivatives has been efficiently synthesized by straightforward sequential reactions. Tandem Vilsmeier Hack reaction/cyclization/bromination/Suzuki cross‐coupling reactions were successfully applied to the preparation of title compounds in good‐to‐high yields. In the synthetic sequences, 3‐chloro‐3‐(2‐oxo‐2H‐chromen‐3‐yl)acrylaldehydes ( 2 ) were found to react with ammonium thiocyanate to yield the corresponding 3‐(isothiazol‐5‐yl)‐2H‐chromen‐2‐ones ( 3 ). These derivatives were brominated with N‐bromo succinamide to yield the corresponding regioselective 3‐(4‐bromoisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 4 ). Finally, compound 4 was treated with various phenyl/pyrazole/7H –pyrrolo[2,3‐d]pyrimidinyl boronic acids 5a – l in the presence of K₂CO₃ and Pd catalyst in dimethylformamide to yield the corresponding title derivatives 6a – l . All the synthesized compounds were characterized by analytical and spectral studies. All the final compounds were screened against different cancer cell lines (A549, PC3, SKOV3, and B16F10), and among these compounds, 6b , 6g , 6h , and 6l displayed moderate cytotoxic activity against the tested cell lines.     

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 of Some Novel 3‐Substituted Indole Derivatives Using Polyamine Functionalized Heterogeneous Catalyst

In present work, we have described the use of polyamine solid supported GN3 as catalyst in organic transformations using 1H‐indole‐3‐carbaldehyde. To the best of our knowledge, reports for the synthesis of chromen substituted at 3C position of indole are extremely rare in the literature. The polyamine functionalized immobilized silica (GN3) was found to be an excellent catalyst for synthesis of novel 2‐amino‐4‐(1H‐indol‐3‐yl)‐5‐oxo‐4,5‐dihydropyrano[3,2‐c]chromene‐3‐carbonitrile derivatives and Knoevenagel condensation. Catalyst GN3 was able to furnish excellent yield for a wide range of products. Moreover, the catalyst was reusable and reused for several times without loss of its catalytic activity.     

A convenient one‐pot synthesis of new 3‐(4‐aryl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2‐yl)‐2H‐chromen‐2‐ones

Anhydrous zinc bromide catalysed reactions of arylidine‐3‐acetyl coumarins ( 1a‐c ) and 5,6‐benzoanalogs of arylidine 3‐acetyl coumarins ( 4a,4b ) with 1,3‐cyclohexanedione gives ‐(4‐aryl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2yl)‐2H‐chromen‐2‐ones ( 3a, 3c ) and 5,6‐benzoanalogs of 3‐(4‐aryl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2yl)‐2H‐chromen‐2‐one ( 5a,5b ). Under similar conditions arylidine‐3‐acetylcoumarins ( 1a, 1b,1d, 1e, 1f ) and 5,6‐benzoanalog of arylidine 3‐acetyl coumarin ( 4b ) react with 5,5‐dimethyl‐1,3‐cyclohexanedione (dimedone) yielding 3‐(4‐aryl‐7,7‐dimethyl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2‐yl)‐2H‐chromen‐2‐ones ( 3d‐3h ) and the 5,6‐benzoanalog of 3.(4‐aryl‐7,7‐dimethyl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2‐yl)‐2H‐chromen‐2‐one ( 5c ).     

Facile and simple synthesis of some new polyfunctionally heterocyclic derivatives incorporating 2‐imino‐2H‐chromene moiety

1,2‐Dihydro‐2‐imino‐6‐(2‐imino‐2H‐chromen‐3‐yl)‐1,4‐diphenyl‐pyridine‐3‐carbonitrile 4 has been synthesized and reacted with ethyl cyanoacetate to yield the new 5‐amino‐1,7‐dihydro‐2‐(2‐imino‐2H‐chromen‐3‐yl)‐7‐oxo‐1,4‐diphenyl‐1,8‐naphthyridine‐6‐carbonitrile 6 , which consider a good and available starting intermediate for synthesis of series of functionalized chromenes. So, the compound 6 was utilized as a key for the synthesis of some new pyrimido[5,4‐c][1,8]naphthyridinones, pyrido[2,3‐c][1,6]naphthyridinones, triazolo[3′,4′:1,6]triazino][5,4‐c][1,8]naphthyridinones, triazolo[2′,3′:1,6]pyrimido[4,5‐c][1,8]naphthyridinones, triazepino[6,5‐c][1,8]naphthyridinone, and triazino[5,4‐c][1,8]naphthyridinones. The structures of these compounds were established by elemental analysis, IR, MS, and NMR spectral analysis. J. Heterocyclic Chem., (2012).