1‐(1,2,3‐triazol‐4‐yl)‐benzimidazolones,a new series of heterocyclic derivatives

New 1‐(1,2,3‐triazol‐4‐yl)‐benzimidazolone derivatives were obtained on pursuing research about new tricyclic derivatives of medicinal interest, bearing a 1,2,3‐triazole ring fused with another heterocyclic ring. 1‐[(5‐Carboxamido)‐1,2,3‐triazol‐4‐yl]‐benzimidazolone was prepared by four different chemical routes and it was unequivocally confirmed by spectroscopic methods. Its chemical behaviour, was evaluated by some common chemical reactions such as hydrolysis, esterification, decarboxylation, nitration and N‐methylation.     

Synthesis and spectral data of new 1,2‐bis‐(2‐hetaryl‐4‐oxothiazolidin‐3‐yl)ethanes and 1,4‐bis‐(2‐hetaryl‐4‐oxothiazolidin‐3‐yl)butanes

New αω‐bis‐(2‐hetaryl‐4‐oxothiazolidin‐3‐yl)alkanes were prepared via a common two step procedure using N,N‐bis‐hetarylidenamines condensation with α‐mercaptoacetic acid. The used bis‐aldimines were obtained from reaction between ethylenediamine or putrescine and benzaldehyde or the isomeric pyridinecarboxyaldehydes. The bis‐(2‐phenyl‐4‐oxothiazolidin‐3‐yl)alkanes were prepared by one‐pot three component reaction of diamine, aldehyde and α‐mercaptoacetic acid under very mild conditions.     

1,3‐Bis(4‐methyl­phen­yl)triazene, 1‐(4‐chloro­phen­yl)‐3‐(4‐fluoro­phen­yl)triazene and 1‐(4‐fluoro­phen­yl)‐3‐(4‐methyl­phen­yl)triazene

The title 4,4′‐disubstituted diphen­yl‐1,3‐triazines, C₁₄H₁₅N₃, (I), C₁₂H₉ClFN₃, (II), and C₁₃H₁₂FN₃, (III), each contain a triazene group (–N=N—NH–) having an extended conformation. The dihedral angles between the two benzene rings in (I), (II) and (III) are 4.3, 3.4 and 6.5°, respectively. The mol­ecules are almost entirely planar, with maximum deviations from the mean planes of 0.1087 (2), −0.1072 (7) and 0.1401 (3) Å, respectively. In each compound, the molecules are linked by N—H⋯N hydrogen bonds to form chains and pack similarly in the crystal structures.     

Synthesis and Antimicrobial Screening of Some Novel 2‐(5‐(4‐(1H‐Benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)phenols Incorporated by Triazole Moiety

A novel series of 2‐(5‐(4‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)phenols derivative has been synthesized from (E)‐3‐(4‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐1‐(2‐hydroxyphenyl)prop‐2‐en‐1‐ones in ethanol and hydrazine hydrate under reflux condition. The synthesized compounds were screened for antibacterial activity against Gram‐positive bacteria viz Staphylococcus aureus and Bacillus subtilis and Gram‐negative bacteria viz Escherichia coli and Salmonella typhi, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, ¹H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.     

An anomalous course of the reduction of 2‐(3‐oxo‐3,4‐dihydro‐quinoxalin‐2‐yl)benzene diazonium salt. Synthesis of a new quinoxalino[1,2‐c][1,2,3]benzotriazine system

By diazotization of 3‐(2‐aminophenyl)quinoxaline‐2(lH)‐one la and 3‐(2‐aminophenyl)‐6,7‐dimethylquinoxaline‐2(lH)‐one 1b followed by the reaction with sodium sulphite new quinoxalino[1,2‐c]‐[1,2,3]benzotriazins 4a and 4b were prepared, respectively.     

Synthesis of 4‐(Isothiazol‐3‐yl)morpholines and 1‐(Isothiazol‐3‐yl)piperazines,and Their Inhibitory Activity towards Acetylcholinesterase

The synthesis of novel triaryl‐substituted 4‐(isothiazol‐3‐yl)morpholines 7 and 8 , and 1‐(isothiazol‐3‐yl)piperazines 9 – 13 by reaction of the corresponding isothiazolium salts 5 and 6 with secondary amines in the presence of t‐BuOK in absolute THF is described. Some representatives of the isothiazoles were evaluated as inhibitors of acetylcholinesterase from Electrophorus electricus.     

Synthesis and biological evaluation of several 3‐(coumarin‐4‐yl)tetrahydroisoxazole and 3‐(coumarin‐4‐yl)dihydropyrazole derivatives

A series of novel 3‐(coumarin‐4‐yl)tetrahydroisoxazoles 5a,b, 7, 9 and 3‐(coumarin‐4‐yl)dihydropyra‐zoles 13a‐d, 14,15a,b were synthesized from coumarin‐4‐carboxaldehyde 1 via the intermediate N‐methyl nitrone 3 and N‐phenyl or N‐methyl hydrazones 11a,b . These coumarin derivatives were isolated, characterized and evaluated in vitro for their ability to inhibit trypsin, β‐glucuronidase, soybean lipoxygenase and to interact with the stable radical 1,1‐diphenyl‐2‐picrylhydrazyl. The compounds were tested in vivo as anti‐inflammatory agents in the rat carrageenin paw edema assay. Compound 15a seems to be a lead molecule to be modified in order to improve the lipoxygenase inhibition. The results are discussed in terms of structural characteristics.     

Synthesis and Antimicrobial Activity of 2‐(4‐(Hydroxyalkyl)‐1H‐1,2,3‐triazol‐1‐yl)‐N‐substituted propanamides

A series of 21 2‐(4‐(hydroxyalkyl)‐1H ‐1,2,3‐triazol‐1‐yl)‐N ‐substituted propanamides (1,4‐disubstituted 1,2,3‐triazoles having amide linkage and hydroxyl group) have been synthesized from click reaction between terminal alkyne and 2‐azido‐N ‐substituted propanamide (generated in situ from reaction of 2‐bromo‐N ‐substituted propanamide and sodium azide) and characterized by FTIR, ¹H NMR, ¹³C NMR spectroscopy, and HRMS. All the newly synthesized triazoles were tested in vitro for antimicrobial activity against four bacterial cultures – Escherichia coli , Enterobacter aerogenes , Klebsiella pneumoniae , and Staphylococcus aureus – and two fungal cultures – Candida albicans and Aspergillus niger . The synthesized 1,4‐disubstituted 1,2,3‐triazoles displayed moderate to good antimicrobial potential against the tested strains.     

Ferromagnetic Interactions in a 1D Alternating Linear Chain of π‐Stacked 1,3‐Diphenyl‐7‐(thien‐2‐yl)‐1,4‐dihydro‐1,2,4‐benzotriazin‐4‐yl Radicals

X‐ray studies show that 1,3‐diphenyl‐7‐(thien‐2‐yl)‐1,4‐dihydro‐1,2,4‐benzotriazin‐4‐yl ( 6 ) adopts a distorted, slipped π‐stacked structure of centrosymmetric dimers with alternate short and long interplanar distances (3.48 and 3.52 Å). Cyclic voltammograms of 7‐(thien‐2‐yl)benzotriazin‐4‐yl 6 show two fully reversible waves that correspond to the ?1/0 and 0/+1 processes. EPR and DFT studies on radical 6 indicate that the spin density is mainly delocalized over the triazinyl fragment. Magnetic susceptibility measurements show that radical 6 obeys Curie–Weiss behavior in the 5–300 K region with C=0.378 emu K mol^?1 and θ=+4.72 K, which is consistent with ferromagnetic interactions between S=1/2 radicals. Fitting the magnetic susceptibility revealed the behavior is consistent with an alternating ferromagnetic chain (g=2.0071, J₁=+7.12 cm^?1, J₂=+1.28 cm^?1).     

Synthesis and biological evaluation of new 4‐(4‐(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)phenyl)‐2‐phenylthiazole derivatives

A novel series of 4‐(4‐(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)phenyl)‐2‐substitutedthiazole derivatives ( 8a‐l) have been synthesized by [3 + 2] cycloaddition reaction of 4‐(4‐ethynylphenyl)‐2‐substitutedthiazole with substituted benzyl azide in aqueous DMF. Starting compounds 4‐(4‐ethynylphenyl)‐2‐substitutedthiazole ( 6a‐d ) were synthesized by reaction of 4‐(2‐substitutedthiazol‐4‐yl)benzaldehyde with Ohira‐Bestmann reagent in methanol. The structures of these novel triazole‐thiazole clubbed derivatives were confirmed by the spectral analysis. The title compounds ( 8a‐l ) were tested for antimycobacterial activity against Mycobacterium tuberculosis H37Ra active and dormant (MTB, ATCC 25177) and antimicrobial activity against standard Gram‐positive bacteria, Staphylococcus aureus (NCIM 2602) and Bacillus subtilis (NCIM 2162), and Gram‐negative bacteria, Escherichia coli (NCIM 2576) and Pseudomonas flurescence (NCIM 2059). Compounds 8a , 8b , 8c , and 8h reported good activity against B subtilis, compounds 8a , 8b , and 8c showed good activity against S aureus, and compound 8b showed good activity against dormant M tuberculosis H37Rv strain. Compounds 8b and 8c found more potent against Gram positive and dormant M tuberculosis H37Rv strains. These novel triazole‐thiazole clubbed analogues found to be a capable leads for further optimization and development.     

The Synthesis of 2‐(Chromon‐2/3‐yl)‐3‐(5‐thione‐4‐hydro‐1,3,4‐thiadiazol‐2‐yl)‐4‐oxo‐thiazolidine

2‐Formylchromones and 3‐formylchromones as the first materials singly reacted with 2‐amino‐5‐mercapto‐1,3,4‐thiadiazole to give the corresponding Schiff bases, which on cyclocondensation with mercapto‐acetic acid in 1,4‐dioxane yielded target compounds named 4‐oxo‐thiazolidines. The structures of all the synthetic compounds were confirmed by elemental analysis and IR, ¹H NMR, LC‐MS (ESI) spectral data.     

Synthesis and tautomerization of 6,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines

The condensation of 5‐amino‐4‐phenyl‐1,2,3‐triazole ( 1 ) with chalcones 2a‐e or 3‐dimethylamino‐propiophenone ( 4f ) leads to the 6,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines 3a‐f. The equilibrium of 3 and the tautomeric 4,7‐dihydro‐(1,2,3)‐triazolo[1,5‐a]pyrimidines 3′ is described.     

A Facile and Efficient Synthesis of 2‐(5‐(4‐Substitutedphenyl)‐4, 5‐dihydro‐3‐phenylpyrazol‐1‐yl)‐6‐Substitutedbenzothiazoles and Their Biological Studies

A series of new 1‐substituted 3, 5‐diarylpyrazolines ( 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ) were synthesized in good yield by both conventional and microwave‐assisted synthesis from α, β‐ unsaturated ketones ( 6 , 7 , 8 , 9 ) in n‐butanol and benzothiazole hydrazines ( 2 , 3 , 4 , 5 ). All the new compounds were characterized by IR, NMR, and mass spectral data. The synthesized compounds ( 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ) were evaluated for antibacterial and anthelmintic activities. The compounds showed potent anthelmintic activity against earthworm species (Eudrilus eugeniae) and moderate antibacterial activity against bacterial strains such as Gram positive bacteria, Enterococcus faecalis, Staphylococcus aureus, and Bacillus subtilis, and Gram negative bacteria, Escherichia coli and Proteus mirabilis.     

Synthesis and antibacterial activity of novel series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline

A new series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline were synthesized from oxidative cyclization of N′‐((2‐(p‐tolyloxy)quinoline‐3‐yl)methylene)isonicotinohydrazide in DMSO/I₂ at reflux condition for 3–4 h. The structures of the new compounds were confirmed by elemental analyses as well as IR, ¹H‐NMR, and mass spectral data. All the synthesized compounds were screened for their antibacterial activities against various bacterial strains. Several of these compounds showed potential antibacterial activity. J. Heterocyclic Chem., (2011).     

An efficient synthesis of 5‐aryl‐4,5‐dihydro‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐(4‐phenylthiazol‐2‐yl)pyrazoles

Some new target products 5‐aryl‐4,5‐dihydro‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐(4‐phenylthiazol‐2‐yl)pyrazoles 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j have been synthesized by reaction of 2‐bromo‐1‐phenylethanone and compounds 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j which were prepared from the combination of thiosemicarbazide and (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j . All the structures were established by MS, IR, CHN, and ¹H NMR spectra data. Synthesis of structure diversity is applied. J. Heterocyclic Chem., (2011).     

Syntheses of 4‐(5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones and 4‐(4‐arylamino‐5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones from Sydnone Derivatives and Their Fragments

4‐(5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones 11 and 4‐(4‐arylamino‐5‐oxo‐1,2,4‐triazol‐3‐yl)‐sydnones 13 have been obtained from a‐chloroformylarylhydrazine hydrochloride 2 . Moreover, the intermediates, including 3, 4 , 9 and 10 , in this study are synthetically informative and valuable. It is also noteworthy that three reactants, 1, 2 and sydnonecarbaldehydes, were prepared from sydnone derivatives and their fragments. The oxidative cyclizations of sydnonecarbaldehyde semicarbazones 9 and carbazones 10 with two different oxidizing agents (Cu(ClO₄)₂ and Fe(ClO₄)₃) have been extensively examined. The reaction time and the yields of cyclizations were affected by the substituents of semicarbazones 9 and carbazones 10.     

An Efficient Synthesis of 3‐(3‐benzyl‐2‐(phenylimino)‐2,3‐dihydrothiazol‐4‐yl)‐6‐methyl‐4‐(2‐oxo‐2‐phenylethoxy)‐3,4‐dihydro‐2H‐pyran‐2‐one Derivatives via Multi‐Component Approach

An easy, highly efficient and a new convenient one‐pot, two‐step approach to the synthesis of 3‐(3‐benzyl‐2‐(phenylimino)‐2,3‐dihydrothiazol‐4‐yl)‐6‐methyl‐4‐(2‐oxo‐2‐phenylethoxy)‐3,4‐dihydro‐2H‐pyran‐2‐one is described. These compounds were synthesized from 3‐(3‐benzyl‐2‐(phenylimino)‐2,3‐dihydrothiazol‐4‐yl)‐4‐hydroxy‐6‐methyl‐3,4‐dihydro‐2H‐pyran‐2‐one and α‐bromoketones in good yields. The compounds 4 were synthesized by a multi‐component reaction between 1 , 2 , and 3 and the prominent features of this protocol are mild reaction conditions, operation simplicity, and good to high yields of products.     

4‐(4‐Fluoro‐3‐phenoxy­phen­yl)‐6‐(4‐fluoro­phen­yl)‐2‐oxo‐1,2‐dihydro­pyridine‐3‐carbonitrile and the 6‐(4‐methyl­phen­yl)‐ analogue

The crystal structures of the title compounds, viz. C₂₄H₁₄F₂N₂O₂, (I), and C₂₅H₁₇FN₂O₂, (II), respectively, have been determined in order to unravel the role of an ordered F atom in generating stable supra­molecular assemblies. On changing the substitution from fluorine to a methyl group, C—H⋯F inter­actions are replaced by C—H⋯π inter­actions, revealing the importance of such weak inter­actions when present alongside N—H⋯O and C—H⋯O hydrogen bonds. The dihedral angle between the planes of the 4‐fluoro­phenyl ring and the pyridine ring is 26.8 (1)° in (I), while that between the planes of the 4‐methyl­phenyl and pyridine rings is 29.5 (1)° in (II).     

1‐(Thiophen‐3‐yl)ethanone

The structure of the title compound, C₆H₆OS, exhibits a flip‐type disorder of the thiophene ring [occupancy ratio = 0.848 (3):0.152 (3)], which is typical for many thiophene derivatives. The puckered thiophene ring is essentially coplanar with the plane formed by the non‐H atoms of the acetyl substituent, similar to its simple analogues, i.e. 3‐acetyl‐2‐carboxythiophene, 4‐acetyl‐3‐carboxythiophene and 3,5‐diacetyl‐2‐ethylamino‐4‐methylthiophene. In the crystal structure, molecules are connected by C—H...π hydrogen bonds, forming a sheet parallel to the (001) plane. Moreover, an inspection of the crystal lattice reveals that there are short S...O contacts connecting the molecules of adjacent sheets. Comparison of the title crystal structure with its simple 3‐methoxythiophene analogue shows a close similarity in the herringbone arrangement of molecules and in the presence of C—H...π interactions and S...O contacts.     

Synthesis and Antimicrobial Activity of N‐Aryl‐4‐(cyano/alkoxycarbonyl)‐5‐(pyridin‐3‐yl)‐1H/3H‐1,2,3‐triazole Derivatives

A convenient synthesis of a new series of N‐aryl‐5‐(pyridin‐3‐yl)‐1H/3H‐1,2,3‐triazole‐4‐carbonitriles and alkyl N‐aryl‐5‐(pyridin‐3‐yl)‐1H/3H‐1,2,3‐triazole‐4‐carboxylic acid esters is reported. The newly synthesized 5‐(pyridin‐3‐yl)‐1,2,3‐triazole derivatives are evaluated for their antibacterial and antifungal activity. Some of these triazole derivatives have exhibited moderate antimicrobial activity.