An Efficient One‐pot Synthesis of Aryl‐substituted 1‐(Thiazol‐2‐yl)‐1H‐pyrazole‐3‐carboxylates via a Hantzsch Synthesis‐Knorr Reaction Sequence

The treatment of α‐bromoalkyl aryl ketones and 2‐(propan‐2‐ylidene)hydrazine carbothioamide afforded 4‐aryl‐2‐(2‐(propan‐2‐ylidene)hydrazinyl)thiazoles via a Hantzsch‐thiazole synthesis, which reacted with 4‐aryl‐2,4‐diketoesters via a sequential Knorr‐pyrazole reaction to deliver a variety of aryl‐substituted ethyl 1‐(thiazol‐2‐yl)‐1H‐pyrazole‐3‐carboxylates in a one‐pot fashion with moderate to high yields. The key intermediates 4‐aryl‐2,4‐diketoesters, existing as its enolic lithium salt, were synthesized in situ by a high‐yield tert‐BuOLi‐mediated Claisen condensation of alkylphenones and diethyl oxalate. This class of elegant molecule comprises aryl groups on the two different heterocyclic cores, and the configurations of two representative molecules were determined by single crystal X‐ray crystallography.     

An Efficient Synthesis of 3‐(1H‐Tetrazol‐5‐yl)coumarins (=3‐(1H‐Tetrazol‐5‐yl)‐2H‐1‐benzopyran‐2‐ones) via Domino Knoevenagel Condensation,Pinner Reaction,and 1,3‐Dipolar Cycloaddition in Water

A novel straightforward synthesis of 3‐(1H‐tetrazol‐5‐yl)coumarins (=3‐(1H‐tetrazol‐5‐yl)‐2H‐1‐benzopyran‐2‐ones) 6 via domino Knoevenagel condensation, Pinner reaction, and 1,3‐dipolar cycloaddition of substituted salicylaldehydes (=2‐hydroxybenzaldehydes), malononitrile (propanedinitrile), and sodium azide in H₂O is reported (Scheme 1 and Table 2). This general protocol provides a wide variety of 3‐(1H‐tetrazol‐5‐yl)coumarins in good yields under mild reaction conditions.     

Efficient Synthesis of 1‐Aryl‐4‐[(ethoxycarbonyl)oxy]‐1H‐pyrazole‐3‐carboxylates

Two‐step synthesis of N‐aryl 4‐[(ethoxycarbonyl) oxy]‐1H‐pyrazole‐3‐carboxylates is achieved starting from the commercially available ethyl 4‐chloroacetoacetate and aromatic amines. Azo coupling followed by cyclization with ethyl chloroformate–DMAP pair resulted in the formation of new 4‐oxy‐1H‐pyrazole derivatives in high yields.     

A Simple and Efficient Synthesis of Ethyl 1‐Aryl‐4‐formyl‐1H‐pyrazole‐3‐carboxylates

A new simple and convenient method of synthesis of ethyl 1‐aryl‐4‐formyl‐1H‐pyrazole‐3‐carboxylates from aromatic amines via diazonium salts has been developed. Hydrolysis and hydrazinolyization of these compounds has been investigated.     

One‐Pot Synthesis of 4‐(2,3‐Dihydro‐2‐hydroxy‐1,3‐dioxo‐1H‐inden‐2‐yl)‐Substituted 1‐Aryl‐1H‐pyrazole‐3‐carboxylates via a Tandem Three‐Component Reaction

The hitherto unreported, highly functionalized 1H‐pyrazole‐3‐carboxylates 3 have been synthesized in good yields via a one‐pot three‐component domino reaction of phenylhydrazines, dialkyl acetylenedicarboxylates, and ninhydrin under mild conditions for the first time. No co‐catalyst or activator is required for this multicomponent reaction, and the reaction is, from an experimental point of view, simple to perform (Scheme 1). The structures of compounds 3 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of cyclization/addition reaction is proposed (Scheme 2).     

Synthesis of 2,5,7‐Triaryl‐4,7(6,7)‐dihydropyrazolo[1,5‐a]pyrimidine‐3‐carbonitriles by Reaction of 5(3)‐Amino‐3(5)‐aryl‐1H‐pyrazole‐4‐carbonitriles with Chalcones

The reaction of 5(3)‐amino‐3(5)‐aryl‐1H‐pyrazole‐4‐carbonitriles with 1,3‐diaryl‐2‐propen‐1‐ones (chalcones) in refluxing DMF leads to 2,5,7‐triaryl‐4,7(6,7)‐dihydropyrazolo[1,5‐a]pyrimidine‐3‐carbonitriles. In DMSO solution, the latter exist in equilibrium of two tautomeric 4,7‐dihydropyrazolo[1,5‐a]pyrimidines and 6,7‐dihydropyrazolo[1,5‐a]pyrimidines in various ratios, depending on the nature of aryl substituents in chalcone building blocks.     

An Efficient Two‐Step Synthesis of New 5‐Substituted‐1H‐tetrazoles of Biological Interest

A simple procedure for the synthesis and characterization of new 3‐alkoxy‐3‐(1H‐tetrazol‐5‐yl)propionic acids and 2‐(1H‐tetrazol‐5‐yl)tetrahydrofuran‐ and ‐(1H‐tetrazol‐5‐yl)‐2H‐pyran‐3‐carboxylic acids from the [2 + 3] cycloaddition reactions between the nitrile group of β‐cyanocarboxylic acids with sodium azide in the presence of zinc chloride is described. The tetrazolic acids were isolated in moderate to good yields and are structurally analogous to succinic acid.     

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.     

HClO4‐SiO2: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine

HClO₄‐SiO₂, efficiently catalyzed the condensation of o‐aminophenols and 2‐bromo‐1‐aryl‐ethanones to yield 3‐aryl‐2H‐benzo[1,4]oxazines in good yields.     

Design,Synthesis and Antifungal Evaluation of N‐Substituted‐1‐(3‐chloropyridin‐2‐yl)‐N‐(pyridin‐4‐yl)‐5‐(trifluoromethyl)‐1H‐pyrazole‐4‐carboxamide Derivatives

A series of 1‐(3‐chloropyridin‐2‐yl)‐5‐(trifluoromethyl)‐1H‐pyrazole‐4‐carboxamide derivatives which have di‐substituents on nitrogen were designed and synthesized. Bioassay results showed that all the synthetic compounds exhibited lower antifungal activities against Gibberella zeae, Cytospora mandshurica, and Fusarium oxysporum than T ₃ (14.7, 21.1, and 32.7 μg/mL), but some of them exhibited better activities against Botrytis cinerea, Phytophthora infestans, and Sclerotinia sclerotiorum than T ₃ (>200, >200, and >200 μg/mL); the EC₅₀ values of 7d and 7c against B. cinerea were 94.9 and 56.2 μg/mL, respectively. The EC₅₀ values of 7a , 7d , and 7c against S. sclerotiorum were 73.5, 78.7, and 68.5 μg/mL, respectively.     

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.     

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.     

Supramolecular aggregation in three 4‐aryl‐6‐(1H‐indol‐3‐yl)‐3‐methyl‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitriles

Both 6‐(1H‐indol‐3‐yl)‐3‐methyl‐4‐(4‐methylphenyl)‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile and 6‐(1H‐indol‐3‐yl)‐3‐methyl‐4‐(4‐methoxyphenyl)‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile crystallize from dimethylformamide solutions as stoichiometric 1:1 solvates, viz. C₂₉H₂₁N₅·C₃H₇NO, (I), and C₂₉H₂₁N₅O·C₃H₇NO, (II), respectively; however, 6‐(1H‐indol‐3‐yl)‐3‐methyl‐1‐phenyl‐4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile, C₃₁H₂₅N₅O₃, (III), crystallizes in the unsolvated form. The heterocyclic components of (I) are linked by C—H...π(arene) hydrogen bonds to form cyclic centrosymmetric dimers, from which the solvent molecules are pendent, linked by N—H...O hydrogen bonds. In (II), the heterocyclic components are linked by a combination of C—H...N and C—H...π(arene) hydrogen bonds into chains containing two types of centrosymmetric ring, and the pendent solvent molecules are linked to these chains by N—H...O hydrogen bonds. Molecules of (III) are linked into simple C(12) chains by an N—H...O hydrogen bond, and these chains are weakly linked into pairs by an aromatic π–π stacking interaction.     

Synthesis,Nematocidal Activity and Docking Study of Novel Chiral 1‐(3‐Chloropyridin‐2‐yl)‐3‐(difluoromethyl)‐1H‐pyrazole‐4‐carboxamide Derivatives

A novel series of pyrazole carboxamide derivatives had been designed, synthesized and some of them exhibited good nematocidal activity.     

Aryloxy tetrazoles with axial chirality: Synthesis and partial resolution of 5‐(1‐(2‐methoxynaphthalen‐1‐yl)naphthalen‐2‐yloxy)‐1H‐tetrazole

5‐(1‐(2‐Methoxynaphthalen‐1‐yl)naph‐ thalen‐2‐yloxy)‐1H‐tetrazole as the first aryloxy tetrazole with axial chirality was synthesized. Partial resolution was achieved using (S)‐proline and methylbenzylamine as the resolving agents. Best results were obtained using methylbenzylamine with 75–85% ee. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:416–419, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20241     

Ni‐Catalyzed Synthesis of Fluoroarenes via [2+2+2] Cycloaddition Involving α‐Fluorine Elimination

A method for direct synthesis of tetrasubstituted fluoroarenes via nickel‐catalyzed [2+2+2] cycloaddition is presented. The reaction combines one molecule of 1,1‐difluoroethylene with two molecules of alkynes and involves sequential cleavage of the C?F and C?H bonds in difluoroethylene. The catalytic cycle is established by reduction of the intermediary Ni^II fluoride with a triethylborane‐based borate.     

An Innovative Protocol for the Synthesis of 3‐(Pyridin‐2‐yl)‐5‐sec‐aminobiphenyl‐4‐carbonitriles and 9,10‐Dihydro‐3‐(pyridine‐2‐yl)‐1‐sec‐aminophenanthrene‐2‐carbonitriles

Herein, we present an innovative, novel, and highly convenient protocol for the synthesis of 3‐(pyridin‐2‐yl)‐5‐sec‐aminobiphenyl‐4‐carbonitriles ( 6a , 6b , 6c , 6d , 6e , 6f , 6g ) and 9,10‐dihydro‐3‐(pyridine‐2‐yl)‐1‐sec‐aminophenanthrene‐2‐carbonitriles ( 10a , 10b , 10c , 10d , 10e ), which have been delineated from the reaction of 4‐sec‐amino‐2‐oxo‐6‐aryl‐2H‐pyran‐3‐carbonitrile ( 4a , 4b , 4c , 4d , 4e , 4f , 4g ) and 4‐sec‐amino‐2‐oxo‐5,6‐dihydro‐2H‐benzo[h]chromene‐3‐carbonitriles ( 9a , 9b , 9c , 9d , 9e ) with 2‐acetylpyridine ( 5 ) through the ring transformation reaction by using KOH/DMF system at RT. The salient feature of this procedure is to provide a transition metal‐free route for the synthesis of asymmetrical 1,3‐teraryls like 3‐(pyridin‐2‐yl)‐5‐sec‐aminobiphenyl‐4‐carbonitriles ( 6a , 6b , 6c , 6d , 6e , 6f , 6g ) and 9,10‐dihydro‐3‐(pyridine‐2‐yl)‐1‐sec‐aminophenanthrene‐2‐carbonitriles ( 10a , 10b , 10c , 10d , 10e ). The novelty of the reaction lies in the creation of an aromatic ring from 2H‐pyran‐2‐ones and 2H‐benzo[h]chromene‐3‐carbonitriles via two‐carbon insertion from 2‐acetylpyridine ( 5 ) used as a source of carbanion.     

Synthesis of Novel Fluorescent 2‐{4‐[1‐(Pyridine‐2‐yl)‐1H‐pyrazol‐3‐yl] phenyl}‐2H‐naphtho [1,2‐d] [1,2,3] triazolyl Derivatives and Evaluation of Their Thermal and Photophysical Properties

Novel 2‐{4‐[1‐(pyridine‐2‐yl)‐1H‐pyrazol‐3‐yl] phenyl}‐2H‐naphtho [1,2‐d] [1,2,3] triazolyl fluorescent derivatives were synthesized from p‐nitrophenylacetic acid and 2‐hydrazino pyridine through Vilsmeier–Haack and diazotization reactions. Photophysical properties were evaluated, and results show that compounds have good fluorescence quantum yields. Thermal analysis showed that they are reasonably stable. The structures of the compounds were confirmed by FT‐IR, ¹H NMR, ¹³C NMR, and mass spectral and elemental analysis.     

Synthesis of Some 3‐(4‐Aryl‐benzofuro[3,2‐b]pyridin‐2‐yl)coumarins and Their Antimicrobial Screening

The synthesis of some 3‐(4‐aryl‐benzofuro[3,2‐b]pyridin‐2‐yl)coumarins 3a–r has been carried out by the reaction of 3‐coumarinoyl methyl pyridinium salts 1a–c with 2‐arylidene aurones 2a–f in the presence of ammonium acetate and acetic acid under Kröhnke's reaction conditions. All the synthesized compounds were characterized by analytical and spectral data. They have been screened for their antibacterial activity against Escherichia coli (ATCC 25922) as Gram‐negative bacteria, Bacillus subtillis (ATCC 1633) as Gram‐positive bacteria and antifungal activity against Aspergillus niger (ATCC 9029).