Synthesis of chiral fused heterocyclic compounds containing 1,2,4‐triazole ring

A series of new chiral (S)‐3‐ary1‐6‐pyrrolidin‐2‐yl‐[1,2,4]triazolo[3,4‐b]thiadiazole (II_1‐5), (S)‐1‐(3‐aryl‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐ethylamine (II_6‐8) and (S)‐1,2‐bis(3‐aryl‐[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐ethylamine (II_9‐11) were prepared by the condensation of 3‐aryl‐4‐amino‐5‐mercapto‐1,2,4‐triazoles with different L‐amino acids in the presence of phosphorus oxychloride and evaluated for their antibacterial activity.     

Synthesis of fused triazolothienopyrimidine derivatives

Reactions of substituted 1-(thieno[2,3-d]pyrimidin-2-yl)-4-arylthiosemicarbazides with methyl iodide led to the formation of fused triazolothienopyrimidine derivatives.     

Synthesis and biological activities of new 1H‐1,2,4‐triazole alcohol derivatives containing a ferrocenyl moiety

Fourteen new 1H‐1,2,4‐triazole alcohol derivatives containing a ferrocenyl moiety were synthesized. In addition, six unexpected compounds, the hydroxyls of the title compounds, methylated by methanol, were obtained. The structures of all these new compounds were confirmed using ¹H NMR spectra, ¹³C NMR, MS and elemental analyses. Some compounds were also confirmed with IR spectra. The antifungal and plant growth regulatory activities of the title compounds are discussed. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of fused pyrimidines with N‐, S‐heterocyclic moieties by double‐annelation reaction

A variety of tri‐ and tetracyclic hetero systems were obtained by reaction of heteroaromatic ortho‐aminoesters or ortho‐aminonitriles with iminothioether, yielding double‐annelation of a thiazolo[3,2‐a]‐pyrimidine, pyrimido[2,l‐b]thiazine, imidazo[1,2‐a]pyrimidine, and pyrimido[1,2‐a]pyrimidine moieties in a one‐pot process.     

Synthesis,structures, and biological activities of new 1H‐1,2,4‐triazole derivatives containing pyridine unit

Fourteen new 1H‐1,2,4‐triazole derivatives containing pyridine moiety were synthesized by condensation of 1‐(pyridine‐3‐yl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)ethanone with aryl aldehydes, and their reaction conditions were studied. The title compounds were screened for their antibacterial and plant growth regulatory activities. The screening data revealed that most of the compounds showed some antifungal and plant growth regulatory activities. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:376–380, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20308     

Synthesis and characterization of new heterocyclic derivatives by oxidation of 1‐amino‐2‐methylindoline

1‐Amino‐2‐methylindoline is a precursor used in the synthesis of antihypertension drugs. It reacts with monochloramine to lead to the formation of 1‐amino‐2‐methylindole and azo(2‐methyl)indoline. These new products have been isolated and characterized by microanalysis, uv, gc/ms, ir, and ¹H/¹³C nmr. The reaction leads to the transient formation of an indolic aminonitrene. 1‐Amino‐2‐methylindole formation proceeds in strongly alkaline medium by rearrangement of a diaziridine intermediate. In neutral or slightly alkaline medium, one obtains a precipitate of tetrazene type (‐N‐N=N‐N‐), the azo(2‐methyl)indoline. The study of the thermochemical properties shows that tetrazene decomposes towards 150 °C to give the 1,1′‐bi(2‐methyl)indoline. The stability of the starting reagents and products was the subject of a systematic investigation. A reaction mechanism is proposed.     

Synthesis and antitumor evaluation of some new derivatives and fused heterocyclic compounds derived from thieno[2,3‐b]pyridine

On the basis of the proven activity of thieno[2,3‐b]pyridines as anticancer, we have designed to synthesize a novel several heterocyclic compounds utilizing thieno[2,3‐b]pyridine as a skeleton through various chemical reactions. The synthesized compounds bear rings that are either directly attached to the thieno[2,3‐b]pyridine as in compounds 4 to 6 and 9 or connected through an amide bridge as compounds 2 , 3a ‐ b , 7 , and 8 . As well as, compounds 10 , 12 to 28 , 30 , 31 , and 33 to 36 bear fused rings to the thieno[2,3‐b]pyridine backbone. The newly synthesized compounds were screened for their antiproliferative activity in vitro against hepatocellular carcinoma (HepG‐2) and breast cancer (MCF‐7) compared with the standard drug (doxorubicin). Compounds 3b , 4 , 6 , 22 , and 28 exhibited promising growth inhibitory effect toward both HepG‐2 and MCF‐7 cell lines with IC₅₀ values ranging from 5.88 to 11.70 μg/mL and 9.64 to 15.10 μg/mL, respectively.     

Synthesis of trifluoromethyl‐1,2,4‐triazine‐ and trifluoromethylpyrimidine‐fused uracils

A variety of trifluoromethyl‐1,2,4‐triazine‐ and trifluoromethylpyrimidine‐fused uracils ( 9 ), ( 12 ), ( 15 ) and ( 18 ) were synthesized from trifluoroacetaldehyde ethyl hemiacetal or trifluoroacetic anhydride and corresponding uracil derivatives.     

Synthesis of novel pyrazolo[3,4‐d]pyrimidines peri‐fused with 1,4‐diazepine, 1,4‐thiazepine,and 1,2,4‐triazepine rings

A simple and efficient synthesis of novel ortho‐ and peri‐annulated heterocyclic systems—2,6,7,9‐tetrahydro‐8H‐pyrazolo[5,4,3‐de]pyrimido[4,5‐e][1,4]diazepine, 2,6,7,9‐tetrahydro‐8H‐pyrazolo[5,4,3‐de]pyrimido [5,4‐f][1,4]thiazepine, and 6,9‐dihydro‐2H‐pyrazolo[3,4,5‐ef]pyrimido[5,4‐f][1,2,4]triazepine is described. J. Heterocyclic Chem.,, (2012).     

Synthesis of new bis‐3,5‐diphenylpyrazolines derivatives linked with alkyl chains

New bis‐3,5‐diphenylpyrazoline derivatives have been synthesized according to Elway [1] (1999) and Sangwan's[2] (1992) methodology. Most of them were obtained in good yields, from the reaction between an alkyl linked bis‐chalcones and hydrazine in acetic acid. The activity of some bis‐pyrazolines was evaluated against Helicobacter pylori.     

Ring-cleavage of isoxazoles with heterocyclic amines. Synthesis of fused pyrimidines

The reaction between 2-substituted ethyl 2,5-dihydro-5-oxoisoxazole-4-carboxylates ( 2a,b ) and heterocyclic amines 1, 4 , and 6 , having the amino group in position 2 with respect to the nuclear nitrogen afforded fused pyrimidines 3, 5 , and 7 .     

Synthesis and antimicrobial and pharmacological properties of new thiosemicarbazide and 1,2,4‐triazole derivatives

Reaction of 4‐phenyl‐4H‐1,2,4‐triazole‐3‐thione with ethyl bromoacetate has led to the formation of ethyl [(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)sulfanyl]acetate 1 , the structure of which was confirmed by X‐ray analysis. In the next reaction with 80% hydrazide hydrate, appropriate hydrazide 2 was obtained, which in reaction with isothiocyanates was converted to new acyl derivatives of thiosemicarbazides 2 , 3 , 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h . The cyclization of these compounds in alkaline media has led to formation of new derivatives of 5‐{[(4‐phenyl‐4H‐1,2,4‐triazole‐3‐yl)sulfanyl]methyl}‐4H‐1,2,4‐triazole‐3(2H)‐thiones 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4j . The structure of the compounds was confirmed by elementary analysis and IR, ¹H‐NMR, ¹³C‐NMR, and MS spectra. Compounds 2 , 3 , 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h and 4a , 4b , 4c , 4d , 4e , 4f , 4g were screened for their antimicrobial activities, and the influence of the compounds 4a , 4b , and 4e , 4f , 4g on the central nervous system of mice in behavioral tests was examined. J. Heterocyclic Chem., (2011).     

Synthesis of some new substituted ethanone hydrazones containing 1H‐1,2,4‐triazole and thiazole

Three new thiosemicarbazones have been synthesized by condensation reaction of 2‐bromo‐1‐arylethanones with thiosemicarbazide, which reacted with various 2‐bromo‐1‐arylethanones in ethanol under refluxing to give a series of substituted ethanone hydrazone derivatives. Their structures were confirmed by elemental analysis, IR, ¹H NMR, and MS spectra.     

Synthesis of heterocyclic nitrogen derivatives from aryl‐1,4‐benzoquinones

Treatment of 2‐aryl‐3,6‐bis(arylamino)‐1,4‐benzoquinones 2a‐h with different acid chlorides, namely acetyl, phenylacetyl and chloroacetyl chloride yields 3a,7a‐dihydropyrrolo[2,3‐f]indole‐2,6‐dione 3, 5‐(N‐phenylacetylarylamino)‐3‐phenylindole‐2,6‐dione 4 and 3‐chloro‐5‐(N‐chloroacetylarylamino)indole‐2,6‐dione 5 respectively. Stirring 2‐aryl‐1,4‐benzoquinones ( 1 ) with ethylenediamine and/or o‐phenyl‐enediamine in methylene chloride gives pyrazino[2,3‐g]quinoxalines derivative 6 and/or tetrapentacene derivative 7 respectively. The products 5‐aryl‐ and 6‐aryl‐1/H‐indazole‐4,7‐diones 8 and 9 were obtained in the 1,3‐dipolar cycloaddition of diazomethane to ( 1 ).     

Synthesis of sulfur‐containing hyperbranched polymers by the bisthiolation polymerization of diethynyl disulfide derivatives

The reaction of phenyl propynyl ether and diphenyl disulfide in the presence of 1 mol % tetrakis(triphenylphosphine)palladium as a model reaction of the polymerization of bis(4‐prop‐2‐ynyloxyphenyl) disulfide ( 1a ) gave a Z‐substituted dithioalkene. No E‐substituted dithioalkene was formed in this reaction. The palladium‐catalyzed bisthiolation polymerization of a diethynyl disulfide derivative, 1a , in benzene, was carried out to give a hyperbranched polymer ( 5a ) containing a Z‐substituted dithioalkene unit after reaction for 4 h at 70 °C. From the gel permeation chromatography analysis (chloroform, PSt standards), the number‐average and weight‐average molecular weights of 5a were found to be 8,100 and 57,000, respectively. The structure of 5a was confirmed by ¹H and ¹³C NMR spectra. The obtained polymer was soluble in common organic solvents such as benzene, acetone, and CHCl₃. Polymerization for more than 5 h gave insoluble products. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3580–3587, 2007     

Synthesis and pharmacological properties of N‐substituted‐N′‐(4,6‐dimethylpyrimidin‐2‐yl)‐thiourea derivatives and related fused heterocyclic compounds

A series of new N‐Substituted‐N′‐(4,6‐dimethylpyrimidin‐2‐yl)‐thiourea derivatives ( 3a , 3b , 3c , 3d ) and related fused heterocyclic compounds ( 4a , 4b , 4c , 4d ) were synthesized using tetrabutylammonium bromide as phase transfer catalyst (PTC). N‐[(2E)‐5,7‐dimethyl‐2H‐[1,2,4] thiadiazolo [2,3‐a] pyrimidin‐2‐ylidene] derivatives ( 4a , 4b , 4c , 4d ) were prepared by oxidative cyclization of 3a , 3b , 3c , 3d . The structures of these novel compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectrometry, and the elemental analysis. The crystal structures were determined from single crystal X‐ray diffraction data. The results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms and showed higher activity against fungi than bacteria. Compounds 3d and 3a exhibited the greatest antimicrobial activity. J. Heterocyclic Chem., 2011.