Synthesis and Antimicrobial Activities of Novel Series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one Derivatives

In the present investigation, a novel series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one derivatives were synthesized by condensation of 2‐substituted‐4‐methylthiazole‐5‐carbaldehyde with 4‐(2‐substituted thiazol‐4‐yl)benzenamine followed by cyclo‐condensation with thioglycolic acid in toluene. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, and Mass) methods. The title compounds were screened for quantitative antibacterial activity (minimal inhibitory concentration). All compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h and 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h show moderate to good antimicrobial activity, whereas compounds ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h ) also show moderate antifungal activity.     

Syntheses of New Unsymmetrical 2,5‐Disubstituted‐1,3,4‐oxadiazoles and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles Bearing Thieno[2,3‐c]pyrazolo Moiety

New series of (thieno[2,3‐c]pyrazolo‐5‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles 10a , 10b , 10c and (thieno[2,3‐c]pyrazol‐5‐yl)‐1,3,4‐oxadiazol‐3(2H)‐yl)ethanones 6a , 6b , 6c has been synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by multistep reaction sequence. (5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)‐1H‐thieno[2,3‐c]pyrazoles 4a , 4b , 4c were also synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by cyclization with various aromatic carboxylic acids. The hydrazide 3 was obtained by reaction of thieno[2,3‐c]pyrazole‐5‐carboxylate 2 with hydrazine hydrate in good yield, and compound 2 was obtained by the reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde 1 and 2‐ethyl thioglycolate in presence of sodium alcoholate in good yield.     

Synthesis and Antimicrobial Studies of Novel Imidazole Containing Bisazetidinones and Bisthiazolidinone Derivatives

A simple, practical, and efficient approach to new series of imidazole containing bisazetidinones ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j and 9a , 9b , 9c , 9d , 9e , 9f , 9g , 9h , 9i , 9j ) was prepared by Staudinger [2 + 2] cycloaddition reaction, and bisthiazolidinones ( 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j and 10a , 10b , 10c , 10d , 10e , 10f , 10g , 10h , 10i , 10j ) were obtained by cyclization of bisimines with thioglycolic acid. The bisimines ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j and 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j ) were synthesized by the condensation of 3‐(1‐(3‐aminobenzyl)‐4, 5‐dihydro‐1H‐imidazol‐2‐yl) aniline ( 3 , 4 ) with a series of different substituted aromatic aldehydes. All the newly synthesized target compounds were evaluated for their in vitro antimicrobial activity against two Gram‐positive bacteria and two Gram‐negative bacteria. Additionally, these synthesized compounds were tested for their antifungal activities. Few compounds showed very good antibacterial and antifungal activity.     

Synthesis of Biologically Active[4-(4-Bromophenyl)-2-thiazolyl]hydrazones and their D-Galactose Derivatives

Benzaldehyde [4‐(4‐bromophenyl)thiazol‐2‐yl]hydrazones 5a – 5d were prepared by reacting the thiosemicarbazones 2a – 2d with 2,4′‐dibromoacetophenone ( 1 ) in absolute ethanol. Acetylation of 5a and 5b with Ac₂O/Py at room temperature gave the N‐acetyl derivatives 6a and 6b . 4‐Methyl‐2‐pentanone/cyclopentanone [4‐(4‐bromo‐phenyl)thiazol‐2‐yl]hydrazones ( 8a ) and ( 8b ) were similarly obtained from the reaction of 1 with the thiosemicarbazones 7a and 7b , respectively. Cyclization of D‐galactose thiosemicarbazone ( 9 ) and its tautomers 10 and 11 with 1 afforded an equilibrium mixture of the acyclic 2‐thiazolylhydrazone 12 , together with its respective cyclic galactosyl derivatives 13 and 14 , whose structures were studied by using ¹H and ¹³C NMR spectra. The antimicrobial activity of the synthesized thiazole derivatives was evaluated in vitro by using an agar diffusion technique, and some of these compounds showed potential activity against Candida albicans.     

Synthesis and antibacterial evaluation of some new 4‐substituted‐3‐aryl‐1‐(2,6‐dimethylpyrimidin‐4‐yl)pyrazoles

Synthesis of a series of new 4‐substituted‐3‐aryl‐1‐(2,6‐dimethylpyrimidin‐4‐yl)pyrazoles ( 2a , 2b , 2c , 2d , 2e , 2f , 2g , 3a , 3b , 3c , 3d , 3e , 3f , 3g , and 4a , 4b , 4c , 4d , 4e , 4f , 4g ) is described. All the synthesized compounds were evaluated in vitro for their antibacterial activity against two gram‐positive and two gram‐negative bacteria, namely, Bacillus subtilis (MTCC 8509), Bacillus stearothermophilus (MTCC 8508), Escherichia coli (MTCC 51), and Pseudomonas putida (MTCC 121), and their activity was compared with two commercial antibiotics, streptomycin and chloramphenicol. Two compounds, namely, 3‐(4‐anisyl)‐1‐(2,6‐dimethylpyrimidin‐4‐yl)pyrazole‐4‐carboxaldehyde ( 2b ) and 3‐(2‐thienyl)‐1‐(2,6‐dimethyl pyrimidin‐4‐yl)pyrazole‐4‐carboxaldehyde ( 2g ) were found to be equipotent to streptomycin and chloramphenicol against gram‐negative bacteria, E. coli having minimum inhibitory concentration (MIC) value = 4 μg/mL. Compounds 4b and 4d also displayed good activity against E. coli with MIC = 8 μg/mL. J. Heterocyclic Chem., (2011).     

Synthesis and antimicrobial activity of tris phosphonates

Syntheses of novel [{(3‐dialkoxy‐phosphoryl)‐(substituted‐phenyl‐methyl)‐2‐oxo‐2‐phenyl‐2,3‐dihydro‐2λ⁵–benzo [1,3,2] diazaphosphol‐1‐yl}‐(substituted‐phenyl)‐methyl]‐phosphonic acid diethyl/dimethyl esters ( 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j ) were conveniently accomplished by cyclocondensation of [(2‐{(dimethoxy‐phosphoryl)‐phenyl‐methyl)‐amino}‐phenyl amino)‐phenyl‐methyl]phosphonic acid diethyl/dimethyl esters ( 2a , 2b , 2c , 2d , 2e , 2f , 2g , 2h , 2i , 2j ) with phenyl phosphonic dichloride in dry toluene in the presence of triethylamine at 40°C. The title compounds were characterized by physicospectral techniques. All the synthesized compounds were found to possess antimicrobial properties. J. Heterocyclic Chem., 2011.     

Synthesis of some thiazolyl and thiadiazolyl derivatives of substituted furan and pyrrole

Four series of substituted furan and pyrrole have been synthesized. The first series was prepared by cyclization of the key intermediates ethyl 5‐[(4‐substituted thiosemicarbazido)methyl]‐2‐methylfuran‐3‐carboxylates 2a‐2d and 1‐[(4‐acetyl‐5‐methyl‐1H‐pyrrol‐2‐yl)methylene]‐4‐substituted thiosemicarbazides 8a‐8d with chloroacetic acid or (ethyl bromoacetate) to afford the corresponding 4‐oxo‐3‐substituted thiazolidin‐2‐ylidene 3a‐3d or 3‐substituted thiazolidin‐4‐one 9a‐9d . On the other hand, heating of the intermediates 2a‐2d or 8a‐8d with acetic anhydride afforded the corresponding (N‐substituted acetylamino)‐2,3‐dihydro‐[1,3,4]thiadiazol‐2‐yl derivatives 4a‐4d and [1,3,4]thiadiazol‐2‐yl‐N‐substituted acetamide 10a‐10d respectively, while cyclization with p‐bromophenacyl bromide gave rise to the corresponding 3‐substituted thiazol‐2‐yl‐ylidene 5a‐5d and 11a‐11d respectively. Furthermore, 4‐oxo‐3‐substituted thioureido‐thiazolidin‐2‐yl 6a‐6d or 4‐oxo‐thiazolidin‐3‐yl‐3‐substituted thiourea 12a‐12d were obtained by reaction of the intermediates 2a‐2d or 8a‐8d with thioglycolic acid. Some of the synthesized compounds showed promising antimicrobial activities.     

Synthesis and Antimicrobial Activity of N‐[(2Z)‐3‐(4,6‐Substitutedpyrimidin‐2‐yl)‐4‐phenyl‐1,3‐thiazol‐2(3H)‐ylidene]‐3, 5‐dinitrobenzamide Analogues

In this study, we have synthesized 1‐(4,6‐disubstitutedpyrimidin‐2‐yl)‐3‐(3,5‐dinitrobenzoyl)‐thiourea derivatives ( 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h ) and N‐[(2Z)‐3‐(4,6‐disubstitutedpyrimidin‐2‐yl)‐4‐phenyl‐1,3‐thiazol‐2(3H)‐ylidene]‐3, 5‐dinitrobenzamide ( 2a‐2h ) analogues and characterized by IR spectroscopy, NMR spectroscopy, elemental analysis, and single crystal X‐ray diffraction data. The compounds ( 2a‐2h ) were screened for antimicrobial activity against Gram positive, Gram negative, and fungal species. The results of antimicrobial study indicated that compounds showed most potential and appreciable antibacterial and antifungal activities.     

Synthesis and Antimicrobial Screening of Some Novel Chromones and Pyrazoles with Incorporated Isoxazole Moieties

The title compounds 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h and 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h have been synthesized from β‐diketones and chromones, respectively, having 5‐methyl‐3‐phenylisoxazole moiety. Substituted 2‐acetylphenyl 5‐methyl‐3‐phenylisoxazole‐4‐carboxylate 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h were converted into 1‐(2‐hydroxyphenyl)‐3‐(5‐methyl‐3‐phenylisoxazole‐4‐yl)propane‐1,3‐dione 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h by Baker–Venketaraman transformation. Further, the cyclodehydration of diketone 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h with glacial acetic acid in conc. HCl at reflux gave corresponding substituted 2‐(5‐methyl‐3‐phenylisoxazole‐4‐yl)‐4H‐chromen‐4‐one 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h . The corresponding 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h react with hydrazine hydrate in presence of glacial acetic acid in ethanol at reflux to furnish 2‐(5‐5(5‐methyl‐3‐phenylisoxazole‐4‐yl)‐1H‐pyrazole‐3‐yl)phenol 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h . The structures of all newly synthesized compounds have been confirmed by IR, ¹H NMR, mass spectral data, as well as elemental analysis. The synthesized compounds have been screened for their antimicrobial activity. Some of the compounds show better antimicrobial activity as compared with the reference drugs Streptomycin, Ampicillin, Gentamycin, Cefixime, and Ketoconazole.     

Synthesis,characterization, and in vitro biological studies of some novel pyran fused pyrimidone derivatives

A variety of pyrano[2,3‐d]pyrimidine‐5‐one derivatives 5 , 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 6 , 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j have been synthesized from 6‐amino‐4‐(substituted phenyl)‐5‐cyano‐3‐methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c]pyrazole derivatives 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j via cyclization using formic acid and acetic acid. All the newly synthesized compounds have been characterized by IR, ¹H NMR, ¹³C NMR, and elemental analysis. All the synthesized compounds have been screened for antibacterial, antifungal and antitubercular activity. J. Heterocyclic Chem., (2012).     

Synthesis and Antimicrobial Activity of Novel 2‐Substituted Phenoxy‐N‐(4‐substituted Phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐yl)acetamide Derivatives

A series of 2‐substituted phenoxy‐N‐(4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazole‐2‐yl)acetamide derivatives 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n , 8o , 8p , 8q , 8r , 8s , 8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amine 5 . Their structures were confirmed by ¹H NMR, ¹³C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their antimicrobial activity against three types of plant fungi (Gibberella zeae , Phytophthora infestans , and Paralepetopsis sasakii ) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo ) and Xanthomonas axonopodis pv. citri (Xac )] showing promising results. In particular, 8b , 8f , 8g , and 8h exhibited excellent antibacterial activity against Xoo , with 50% effective concentration (EC₅₀) values of 35.2, 80.1, 62.5, and 82.1 µg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 µg/mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.     

Synthesis,Pharmacological, and Biological Screening of Novel Derivatives of Benzodiazepines

A series of novel 4‐(substituted phenyl)‐2‐(thiophen‐2‐yl)‐2,3‐dihydro‐1H‐benzo[b][1,4]diazepine have been synthesized from 3‐(substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one. 3‐(Substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one was prepared by condensing 2‐acetyl thiophene with various aromatic aldehydes in the presence of 20% NaOH as base. Different 3‐(substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one on cyclization with o‐phenylenediamine in the presence of NaOH as base resulted in 4‐(substituted phenyl)‐2‐(thiophen‐2‐yl)‐2,3‐dihydro‐1H‐benzo[b][1,4]diazepine derivatives. The structures of synthesized compounds are confirmed by IR, ¹H NMR, mass spectra, and elemental analysis. All the compounds have been screened for their antimicrobial, analgesic, and anti‐inflammatory activities.     

Studies on the Reactivity of Amino‐1‐(6‐phenyl‐pyridazin‐3‐yl)‐1H‐pyrazole‐4‐carboxylic Acid Hydrazide Towards Some Reagents for Biological Evaluation

Novel 5‐amino‐1‐(6‐phenyl‐pyridazin‐3‐yl)‐1H‐pyrazole‐4‐carboxylic acid ethyl ester ( 2 ) was formed using (6‐phenyl‐pyridazin‐3‐yl)‐hydrazine ( 1 ) and ethyl(ethoxymethylene)cyanoacetate. The β‐enaminoester derivative 2 was in turn used as precursor for the preparation of 1‐(6‐phenyl‐pyridazin‐3‐yl)‐pyrazoles ( 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 15 , 16 ), 1‐(6‐phenyl‐pyridazin‐3‐yl)‐pyrazolo[3,4‐d]pyrimidines ( 5 , 6 , 14 ) and 1‐(6‐phenyl‐pyridazin‐3‐yl)‐pyrazolo[3,4‐d][1,2,3]triazine ( 13 ). The in vitro antimicrobial activity of the synthesized compounds was evaluated by measuring the inhibition zone diameters where some of them showed potent antimicrobial activity in compared with well‐known drugs (standards).     

New Approaches for the Synthesis of Thiazoles and Their Fused Derivatives with Antimicrobial Activities

The 2‐ethoxy carbonyl methylene thiazol‐4‐one ( 3 ) reacts with acetophenone ( 4 ) to give the ethyl 2‐(4‐oxo‐4,5‐dihydro‐thiazol‐2‐yl)‐3‐phenyl‐2‐butenoate ( 5 ). The reactivity of the latter product towards aromatic aldehydes 6a‐d , cyanomethylene reagents 9a,b , aromatic aldehydes 13a‐d , phenylisothiocyanate ( 16 ), elemental sulfur and aromatic amines ( 20a‐c ) was studied to give arylidene, pyridine, thiophene and anilide derivatives. Some of the newly synthesized derivatives were used to synthesize fused derivatives. The antimicrobial activities of the newly synthesized products were tested in vitro for antimicrobial activity against two bacterial isolates, one saprophytic (Escherichia coli) and the other parasitic (Xanthomonas citri) and for antifungal activity against one saprophytic (Aspergillus fumigatus) and two phytopathogenics (Rhizoctonia solani and Fusarium oxysporum).     

Synthesis of Novel 3‐(3‐(5‐Methylisoxazol‐3‐yl)‐7H‐[1,2,4]Triazolo [3,4‐b][1,3,4]Thiadiazin‐6‐yl)‐2H‐Chromen‐2‐Ones

A novel series of coumarin substituted triazolo‐thiadiazine derivatives were designed and synthesized by using 5‐methyl isoxazole‐3‐carboxylic acid ( 1 ), thiocarbohydrazide ( 2 ), and various substituted 3‐(2‐bromo acetyl) coumarins ( 4a , 4b , 4c , 4e , 4d , 4f , 4g , 4h , 4i , 4j ). Fusion of 5‐methyl isoxazole‐3‐carboxylic acid with thiocarbohydrazide resulted in the formation of the intermediate 4‐amino‐5‐(5‐methylisoxazol‐3‐yl)‐4H‐1,2,4‐triazole‐3‐thiol ( 3 ). This intermediate on further reaction with substituted 3‐(2‐bromo acetyl) coumarins under simple reaction conditions formed the title products 3‐(3‐(5‐methylisoxazol‐3‐yl)‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl‐2H‐chromen‐2‐ones ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j ) in good to excellent yields. All the synthesized compounds were well characterized by physical, analytical, and spectroscopic techniques.     

Synthesis of Some New Benzimidazole–Thiazole Derivatives as Anticancer Agents

4‐(1H‐benzo[d]imidazol‐2‐yl)thiazol‐2‐amine and its 1‐methyl derivative ( 1 ) were reacted with different reagents such as acid anhydrides, malononitrile, chloroacetyl chloride, and aromatic aldehydes to produce the corresponding benzimidazole products 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , respectively. Also, 2‐chloro‐N‐(4‐(1‐methyl‐1H‐benzo[d]imidazol‐2‐yl)thiazol‐2‐yl) acetamide ( 6 ) was reacted with diaminoethane, ortho‐substituted aniline, thioglycolic acid, thiosemicarbazide derivatives, secondary amines, and potassium isothiocyanate to afford the corresponding derivatives 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , respectively. The cytotoxic activity of some newly synthesized derivatives was studied against two different cell lines HepG2 and PC12. Compounds 9 and 15b showed promising anticancer activity against both types of the tested cancerous cell lines.     

Synthesis and In Vitro Study of Hybrid Heterocyclic's as Potential Nematicidal Agents

A series of novel 5‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐3‐(4‐fluorophenyl)‐6‐phenyl‐3,3a,5,6‐tetrahydroisoxazolo[3,4‐d]thiazoles 10a–g were synthesized by the reaction of chalcone derivatives of 2‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐3‐phenylthiazolidin‐4‐one 9 with hydroxylamine hydrochloride. The chemical structures of newly synthesized compounds were elucidated by IR, NMR, MS, and elemental analysis. The compounds 10 a–g were evaluated for their nematicidal activity against Dietylenchus myceliophagus and Caenorhabditis elegans ; compound 10e and 10f showed appreciable nematicidal activity. Further, the compounds 10a – g were screened for their antifungal activity against Candida albicans (ATCC 10231), Aspergillus fumigates (HIC 6094), Trichophyton rubrum (IFO 9185), and Trichopyton mentagrophytes (IFO 40996). The compounds 10b and 10f displayed notable antifungal activity against all the microorganisms employed. The activity of these compounds is almost equal to the standard. It is also interesting to note that the compounds 10b and 10f and 10g showed activity towards C. albicans at the concentration of 3.75 μM, which is less than the concentration of the standard Amphotericin B.     

Synthesis of some oxazolyl ‐ pyrazolyl; 1,4‐Dihydropyridinyl‐pyrazolyl and 1,2,3,4‐tetrahydro pyrimidinyl‐pyrazolyl coumarins

Various 3‐[1‐phenyl‐4‐(2‐substituted‐5‐oxo‐oxazol‐4‐ylidenemethyl) pyrazol‐3‐yl] coumarins 4a‐f ; 3‐[1‐phenyl‐4‐(2,6‐dimethyl‐3,5‐disubstituted‐1,4‐dihydropyridin‐4‐yl) pyrazol‐3‐yl] coumarins 5a‐f and 3‐[1‐phenyl‐4‐(6‐methyl‐5‐substituted‐2‐oxo‐1,2,3,4‐tetrahydropyrimidin‐4‐yl) pyrazol‐3‐yl] coumarins 6a‐f have been synthesized utilizing Erlenmyer‐Plochl reaction, Hantzsch reaction and Biginelli reaction respectively using 3‐(1‐phenyl‐4‐formyl‐pyrazol‐3‐yl) coumarins 3a‐c as a starting material.     

Novel Bis(2‐(5‐((5‐phenyl‐1H‐tetrazol‐1‐yl)methyl)‐4H‐1,2,4‐triazol‐3‐yl)phenoxy)Alkanes: Synthesis and Characterization

In this study, 10 different substituted aromatic bis‐benzaldehydes were synthesized by treating hydroxy benzaldehydes with various dihaloalkanes. Bis aldehydes 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j were treated with 2‐(5‐phenyl‐1H‐tetrazole‐1‐yl)acetohydrazide ( 3 ) in acidic medium and in the presence of ammonium acetate to yield a series of new isomeric bis(2‐(5‐((5‐phenyl‐1H‐tetrazol‐1‐yl)methyl)‐4H‐1,2,4‐triazol‐3‐yl)phenoxy)alkanes ( 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j ) in excellent to good yield. The newly synthesized compounds were characterized by the available spectroscopic analysis.     

Synthesis and cytotoxicity studies of achiral azaindole‐substituted titanocenes

From the reaction of 1‐methyl‐1 H‐pyr‐rolo[2,3‐b]pyridine ( 1a ),1‐(methoxymethyl)‐1 H‐pyrrolo[2,3‐b]pyridine ( 1b ), 1‐isopropyl‐1 H‐pyrrolo[2,3‐b]pyridine (1c ), and 1‐(4‐methoxybenzyl)‐1 H‐pyrrolo[2,3‐b]pyridine ( 1d ) under Vilsmeier–Haak conditions, the corresponding aldehydes in position 3 ( 2a–2d ) were synthesized. These aldehydes were transformed in the corresponding fulvenes ( 3a–3d ) by the Knoevenagel condensation and treated with Li[BEt₃H] to obtain the corresponding lithiated cyclopentadienide intermediates ( 3′a–3′d ). These intermediates were, finally transmetallated to titanium with TiCl₄ to yield the 7‐azaindol‐3‐yl‐substituted titanocenes bis {[(1‐methyl‐1‐H‐pyrrolo[2,3‐b]pyridin‐3‐yl)methyl] cyclopentadienyl} titanium(IV) dichloride ( 4a ), bis{[(1‐methoxymethyl‐1‐H‐pyrrolo[2,3‐b]pyridin‐3‐yl)methyl]cyclopentadienyl} titanium(IV)dichloride ( 4b ), bis{[(1‐Isopropyl‐1‐H‐pyrrolo[2,3‐b]pyridin‐3‐yl)methyl]cyclopentadienyl} titanium(IV) dichloride ( 4c ), and bis{[(4‐methoxybenzyl‐1‐H‐pyrrolo[2,3‐b]pyridin‐3‐yl)methyl]cyclopentadienyl} titanium(IV) dichloride ( 4d ). All the titanocenes had their cytotoxicity investigated through MTT‐based preliminary in vitro testing on the Caki‐1 cell lines to determinate their IC₅₀ values. Titanocenes 4a–4c were found to have IC₅₀ values of 120 ± 10, 83 ± 13, and 54 ± 12, µM respectively, whereas 4d showed no cytotoxic activity. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:148–157, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20668