Synthesis of some polycyclic 1,2,4‐triazines disposing of acidic N‐H group

7‐(6‐Azauracil‐5‐yl)‐isatin 1 was converted through its thiosemicarbazone 2 to 6‐(6‐azauracil‐5‐yl)‐2,3‐dihydro‐5H‐1,2,4‐triazino[5,6‐b]indol‐3‐thione 3 and through the thiosemicarbazone of appropriate isatinic acid to 2‐(2‐thio‐6‐azauracil‐5‐yl)‐6‐(6‐azauracil‐5‐yl)‐aniline 4. The course of the cyclocondensation of this compound was studied and the reaction was found to proceed in both possible ways, resulting in a mixture of compound 3 and regioisomer 6‐(2‐thio‐6‐azauracil‐5‐yl)‐2,3‐dihydro‐5H‐1,2,4‐triazino[5,6‐b]‐indol‐3‐one 5. Substituted aniline 4 was oxidized to 2,6‐bis‐(6‐azauracil‐5‐yl)‐aniline 7 , which served for the preparation of hydrazone 8 , cyclization of which led to 1‐[2,6‐bis‐(6‐azauracil‐5‐yl)‐phenyl]‐6‐azauracil‐5‐carbonitrile 9. This is the first tricyclic 6‐azauracil with vicinal arrangement of 6‐azauracil rings.     

Synthesis of some isomeric quinoxaline derivatives with 6‐azauracil cycle

By diazotization of 3‐(2‐aminophenyl)‐1,2‐dihydroquinoxaline 1c, its 3‐(4‐aminophenyl)‐isomer 2c , 3‐(2‐aminobenzyl)‐1,2‐dihydroquinoxaline‐2‐one 3c and its 3‐(4‐aminobenzyl)‐isomer 4c and by azo coupling of formed diazonium salts with ethyl cyanoacetylcarbamate, corresponding hydrazones ld‐4d were prepared. Cyclization of these compounds afforded compounds containing two heterocyclic rings with acidic N‐H groups in their molecules: 3‐[2‐(5‐cyano‐6‐azauracil‐1‐yl)‐phenyl]‐1,2‐dihydroquinoxaline‐2‐one 1e , its 4‐isomer 2e , 3‐[2‐(5‐cyano‐6‐azauracil‐1‐yl)‐benzyl]‐1,2‐dihydroquinoxaline‐2‐one 3e and its 4‐isomer 4e . The aminoderivative 1c was prepared by the reaction of N‐acetylisatine with o‐phenylenediamine and by hydrolysis of prepared N‐acetylderivative 1a . The aminoderivative 2c was prepared by the condensation of 4‐acetylaminophenylglyoxylic acid with o‐phenylenediamine and by hydrolysis of prepared N‐acetylderivative 2a . The aminoderivative 3c was prepared by the condensation of 2‐nitrophenylpyruvic acid with o‐phenylenediamine and by the reduction of the formed nitroderivative 3b and finally starting aminoderivative 4c was obtained by the condensation of o‐phenylenediamine with 4‐aminophenylpyruvic acid.     

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.     

Design and Synthesis of Novel 6‐(5‐Methyl‐1H‐1,2,3‐triazol‐4‐yl)‐5‐[(2‐(thiazol‐2‐yl)hydrazono)methyl]imidazo[2,1‐b]thiazoles as Antimicrobial Agents

Novel 6‐(1,2,3‐triazol‐4‐yl)‐5‐[(2‐(thiazol‐2‐yl)hydrazono)methyl]imidazo[2,1‐b ]thiazoles 7 , 9a , 9b , 9c , 9d , and 11 were prepared by reaction of thiosemicarbazone 5a , 5b with either hydrazonoyl chloride 6 , phenacylbromides 8 or 2‐bromo‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)ethanone 10 respectively. The new products were tested for their antimicrobial activities using 96‐well micro‐plate assay, and compound 7 showed excellent antibacterial activities compared with Vancomycine (reference drugs), while compounds 5b and 9c exhibited good results against yeast. The minimum inhibitory concentration (MIC) was determined, and compound 7 showed the lowest MIC against Gram positive bacteria while compound 5b showed the lowest MIC against yeast.     

A one‐dimensional lead(II) coordination polymer with terminal and bridging 5‐carboxy‐2‐(pyridin‐3‐yl)‐1H‐imidazole‐4‐carboxylate ligands

In the coordination polymer catena‐poly[[[diaqua[5‐carboxy‐2‐(pyridin‐3‐yl)‐1H‐imidazole‐4‐carboxylato‐κ²N³,O⁴]lead(II)]‐μ‐5‐carboxy‐2‐(pyridin‐3‐yl)‐1H‐imidazole‐4‐carboxylato‐κ³N³,O⁴:N²] dihydrate], {[Pb(C₁₀H₆N₃O₄)(H₂O)₂]·2H₂O}_n, the two 5‐carboxy‐2‐(pyridin‐3‐yl)‐1H‐imidazole‐4‐carboxylate ligands have different coordination modes, one being terminal and the other bridging. The bridging ligand links Pb^II cations into one‐dimensional coordination polymer chains. The structure is also stabilized by intra‐ and interchain π–π stacking interactions between the pyridine rings, resulting in the formation of a two‐dimensional network. Extensive hydrogen‐bonding interactions lead to the formation of a three‐dimensional supramolecular network.     

Synthesis and Antibacterial Activity of Novel (4‐Fluorophenyl)(4‐(naphthalen‐2‐yl)‐6‐aryl‐2‐thioxo‐2,3‐dihydropyrimidin‐1(6H)‐yl)methanone Derivatives

A novel series of (4‐fluorophenyl)(4‐(naphthalen‐2‐yl)‐6‐aryl‐2‐thioxo‐2,3‐dihydropyrimidin‐1(6H)‐yl)methanone derivatives were synthesized from reaction of 6‐(naphthalen‐2‐yl)‐4‐aryl‐3,4‐dihydropyrimidine‐2(1H)‐thiones with 4‐fluorobenzoylchloride in dichloromethane in the presence of triethylamine. The synthesized compounds were screened for antibacterial activity against Gram positive bacteria, namely, Staphylococcus aureus ATCC25923 and Listeria monocytogenes MTCC657, and Gram negative bacteria, namely, Escherichia coli ATCC25922 and Klebsiella pneumoniae ATCC700603, respectively. Some of the tested compounds showed significant antimicrobial activity.     

Syntheses of Some 3—[1′（1′H）—Substituent—pyrazol—5′—yl] benzo [5,6] coumarins

3-[1′(1′H)-Substituent-pyrazol-5′-yl]benzo[5,6]coumarins and 3-(1′,2′-oxazol-5′-yl)benzo[5,6]coumarin were prepared via condensation of 3-(2′-formyl-1′-chlorovinyl)benzo[5,6] coumarin with hydrazine derivatives or hydroxylamine.Reaction of 3-[1′(1′H)-pyrazol-5′-yl]benzo[5,6]coumarin with alkyl halides,olefinic compunds or acid chlorides are described.     

Facile Synthesis of N‐(Benzyl‐1H‐1,2,3‐Triazol‐5‐yl) Methyl)‐4‐(6‐Methoxybenzo [d] Thiazol‐2‐yl)‐2‐Nitrobenzamides via Click Chemistry

A series of novel N‐((l‐benzyl‐lH‐l,2,3‐triazol‐5‐yl) methyl)‐4‐(6‐methoxy benzo[d ]thiazol‐2‐yl)‐2‐nitrobenzamide derivatives were prepared from 4‐(6‐methoxybenzo[d ]thiazol‐2‐yl)‐2‐nitro‐N‐(prop‐2‐ynyl) benzamide with benzyl azides by using click reaction (copper‐catalyzed Huisgen 1,3‐dipolar cycloaddition reaction) in the presence of CuSO₄.5H₂O and sodium ascaorbate. All the newly synthesized compounds were evaluated further in vitro antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtillis ), Gram‐negative bacteria (Echerichia coli and Pseudomonas aeuroginosa ), and fungi (Aspergillus niger and Aspergillusfumigatus ) strains. The new compounds were characterized based on spectroscopic evidence. Among them compounds 10a , 10h , and 10i were showed promising activity when compared with standard drugs Ciprofloxacin and Miconazole.     

A Facile Synthesis of Novel (Z)‐ethyl‐3‐(5‐substituted‐1‐alkyl/aryl‐1H‐indol‐3‐yl)‐2‐(1H‐tetrazol‐5‐yl)acrylate

A novel route was developed for synthesis of high potential 1H‐tetrazoles by using conventional method. Tetrazole scaffold is a promising pharmacophore fragment, frequently used in the development of various novel drugs. Here, the novel (Z)‐3‐(N‐alkyl‐indol‐3‐yl)‐2‐(1H‐tetrazole‐5‐yl)acrylates 5 ( a – i ) have been synthesized from (Z)‐ethyl‐3‐(1H‐indol‐3‐yl)2‐(1H‐tetrazol‐5‐yl)acrylates 4 ( a – c ) by using various alkylating agents such as Dimethyl Sulphate (DMS), Diethyl Sulphate (DES), and benzyl chloride; 4 ( a – c ) were synthesized from sodium azide in the presence of copper sulfate in dimethylformamide; 3 ( a – c ) have been prepared by Knoevenagel condensation of indole‐3‐carbaldehyde 1 ( a – c ) and ethylcyanoacetate 2 in the presence of L‐Proline as a catalyst at room temperature in ethanol for an hour. This is an efficient and clean click chemistry method that has various advantages such as easy workup, higher yields, shorter reaction times, and more economical.     

Synthesis of some new 1‐acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazole

Some new compounds (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 5a–e were prepared by 1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐ethanone and various aromatic aldehydes. Then one pot reaction was happened by compounds 5a–e with hydrazine hydrate in acetic acid or propionic acid, respectively, to give the title compounds 1acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazoles 6a–i . All structures were established by MS, IR, CHN, ¹H‐NMR and ¹³C‐NMR spectral data. J. Heterocyclic Chem., (2012).     

Microwave‐assisted Synthesis of 6‐{(5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)methyl}‐6H‐indolo[2,3‐b]quinoxalines

An efficient and convenient synthesis of a new series of 2‐{(6H‐indolo[2,3‐b]quinoxalin‐6‐yl)methyl}‐5‐aryl‐1,3,4‐oxadiazoles from readily available 1,2‐diaminobenzene and isatins under microwave irradiation conditions was disclosed. The 6‐{(5‐aryl‐1,3,4‐oxadiazol‐2‐yl)methyl}‐6H‐indolo[2,3‐b]quinoxalines were also prepared by the thermal cyclo‐condensation reaction of 2‐(6H‐indolo[2,3‐b]quinoxalin‐6‐yl)acetohydrazides with carboxylic acids in refluxing POCl₃. The microwave‐assisted synthesis was rapid and resulted in higher yield of the products at lower operating temperature with reduced waste generation in comparison with the thermal reaction protocol.     

Four (E,Z,E)‐1‐(4‐alkoxy­phen­yl)‐6‐(4‐nitro­phen­yl)hexa‐1,3,5‐trienes

The crystal structures of the four E,Z,E isomers of 1‐(4‐alk­oxy­phen­yl)‐6‐(4‐nitro­phen­yl)hexa‐1,3,5‐triene, namely (E,Z,E)‐1‐(4‐methoxy­phen­yl)‐6‐(4‐nitro­phen­yl)hexa‐1,3,5‐triene, C₁₉H₁₇NO₃, (E,Z,E)‐1‐(4‐ethoxy­phen­yl)‐6‐(4‐nitro­phen­yl)hexa‐1,3,5‐triene, C₂₀H₁₉NO₃, (E,Z,E)‐1‐(4‐nitro­phen­yl)‐6‐(4‐n‐propoxyphen­yl)hexa‐1,3,5‐triene, C₂₁H₂₁NO₃, and (E,Z,E)‐1‐(4‐n‐butoxy­phen­yl)‐6‐(4‐nitro­phen­yl)hexa‐1,3,5‐triene, C₂₂H₂₃NO₃, have been determined. Inter­molecular N⋯O dipole inter­actions between the nitro groups are observed for the meth­oxy derivative, while for the eth­oxy derivative, two adjacent mol­ecules are linked at both ends through N⋯O dipole–dipole inter­actions between the N atom of the nitro group and the O atom of the eth­oxy group to form a supra­molecular ring‐like structure. In the crystal structures of the n‐prop­oxy and n‐but­oxy derivatives, the shortest inter­molecular distances are those between the two O atoms of the alk­oxy groups. Thus, the nearest two mol­ecules form an S‐shaped supra­molecular dimer in these crystal structures.     

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).     

An Efficient and Facile Synthesis of 5‐(Thiophene‐2‐carbonyl)‐6‐(trifluoromethyl)‐tetrahydro‐pyrimidin‐2(1H)‐one and 6‐(Thiophen‐2‐yl)‐4,5‐dihydropyrimidin‐2(1H)‐one from Same Substrates Under Different Conditions

A series of 5‐(thiophene‐2‐carbonyl)‐6‐(trifluoromethyl)‐tetrahydropyrimidin‐2(1H)‐one and 6‐(thiophen‐2‐yl)‐4,5‐dihydropyrimidin‐2(1H)‐one derivatives have been synthesized from the reactions of aromatic aldehydes, 4,4,4‐trifluoro‐1‐(thien‐2‐yl)butane‐1,3‐dione and urea under the different conditions with high yields. In this research, it was found that the p‐toluenesulfonic acid was an efficient catalyst for obtaining 5‐(thiophene‐2‐carbonyl)‐6‐(trifluoromethyl)‐tetrahydropyrimidin‐2(1H)‐one derivative. At the same time, solvent‐free and NaOH were the preferred conditions for the synthesis of 6‐(thiophen‐2‐yl)‐4,5‐dihydropyrimidin‐2(1H)‐one derivative. Moreover, because of short reaction time, excellent yields, simple setup, this research offered an efficient process for preparing these kind compounds.     

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).     

Synthesis and conversion of 2‐(pyrazol‐1‐yl)quinoxaline 4‐oxides

The reaction of 6‐chloro‐2‐hydrazinoquinoxaline 4‐oxide 1b with acetylacetone or benzoylacetone gave 6‐chloro‐2‐(3,5‐dimethylpyrazol‐i‐yl)quinoxaline 4‐oxide 5a or 6‐chloro‐2‐(3‐methyl‐5‐phenylpyrazol‐1‐yl)quinoxaline 4‐oxide 5b , respXectively. Compound 5a or 5b was converted into the pyrrolo[1,5‐a]quinoxaline 6a or 6b , triazolo[4,3‐a]quinoxaline 9a or 9b , and tetrazolo[1,5‐a]quinoxaline 10.     

Synthesis and Fungicidal Activity of (1Z, 3Z)‐4,4‐Dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one O‐[2,4‐dimethylthiazole(or 4‐methyl‐1,2,3‐thiadiazole)]‐5‐carbonyl Oximes

A series of novel (Z)‐1‐tert‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐ethanone O‐[2,4‐dimethylthiazole (or 4‐methyl‐1,2,3‐thiadiazole) ?5‐carbonyl] oximes 5a – 5c and (1Z, 3Z)‐4,4‐dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one O‐[2,4‐dimethylthiazole (or 4‐methyl‐1,2,3‐thiadiazole)‐5‐carbonyl] oximes 6a – 6e were synthesized by the condensations of (Z)‐1‐tert‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐ethanone oximes 3 or (1Z, 3Z)‐4,4‐dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one oximes 4 with 2,4‐dimethylthiazole‐5‐carbonyl chloride or 4‐methyl‐1,2,3‐thiadiazole‐5‐carbonyl chloride in the basic condition. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays showed the title compounds 5 and 6 exhibited moderate to good fungicidal activities. For example, compound 6c possessed 86.4% inhibition against Fusarium oxysporum, and compound 6b exhibited 86.4 and 100% inhibition against Fusarium oxysporum and Cercospora arachidicola Hori at the concentration of 50 mg/L, 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 of Novel Bis[(5‐cyanopyridin‐6‐yl)sulfanyl]butanes,Bis(2‐S‐alkylpyridines), and Bis(3‐aminothieno[2,3‐b]pyridines) Incorporating 2,6‐Dibromophenoxy Moiety

The synthetic precursors pyridine‐2(1H)‐thiones 2a , b and bis(pyridine‐2(1H)‐thione) derivative 4 , using aldehydes 1a , b incorporating 2,6‐dibromophenoxy moiety, were prepared and used to synthesize the novel target materials bis[(5‐cyanopyridin‐6‐yl)sulfanyl]butanes 5a , b , bis(2‐S‐alkylpyridines) 8a , b , and bis(3‐aminothieno[2,3‐b]pyridines) 13a–c through facile procedures. Characterization of the newly prepared compounds via elemental analyses and spectral data is established.     

Quinolone Analogs 14: Synthesis of Antimalarial 1‐Aryl‐3‐(4‐quinolon‐2‐yl)ureas and Related Compounds

The 4‐quinolone‐2‐carbohydrazide 6a was converted into 1‐aryl‐3‐(4‐quinolon‐2‐yl)ureas 5a , 5b , 5c , 5d , 5e , 1‐aryl‐3‐(4‐quinolon‐2‐yl)imidazolidine‐2,4‐diones 9a , 9b , and N‐(4‐quinolon‐2‐yl)carbamates 10a , 10b via 4‐quinolone‐2‐carbonylazide 7a . The 4‐methoxyquinoline‐2‐carbohydrazide 6b was also transformed into 1‐aryl‐3‐(4‐methoxyquinolin‐2‐yl)ureas 11a , 11b , 11c , 11d , 1‐aryl‐3‐(4‐methoxyquinolin‐2‐yl)imidazolidine‐2,4‐diones 12a , 12b , and N‐(4‐methoxyquinolin‐2‐yl)carbamates 13a , 13b via 4‐methoxyquinoline‐2‐carbonylazide 7b . Some of the 1‐aryl‐3‐(4‐quinolon‐2‐yl)ureas 5a , 5b , 5c , 5d , 5e showed the in vitro antimalarial activity to chloroquine‐resistant Plasmodium falciparum, wherein IC₅₀ was 0.93 to 4.00 μM.