Design and Synthesis of 3‐Substituted‐thiazolyl‐2‐iminothiazolidin‐4‐ones as a New Class of Anticonvulsants

A new series of 3‐substituted‐thiazolyl‐2‐iminothiazolidin‐4‐ones were synthesized by nucleophilic substitution of p‐substituted‐thiazol‐2‐yl‐chloroacetamides with potassium thiocyanide by cyclization. The starting material p‐substituted‐thiazol‐2‐yl‐chloroacetamides were synthesized from p‐substituted‐thiazol‐2‐yl‐amines with chloroacetyl chloride, which in turn was prepared from one pot reaction of substituted aryl acetophenone and amino group of thiourea. The title compounds were investigated for their anticonvulsant activity. Among the tested compounds, compound 3‐(4‐(4‐fluorophenyl)thiazol‐2‐yl)‐2‐iminothiazolidin‐4‐one ( 16 ) emerged as the most active compound of the series, and it is moderately more potent than the reference standard diazepam.     

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.     

A New and Convenient Synthesis of Amino‐phthalimide (1H‐Isoindole‐1,3(2H)‐dione) Derivatives and Their Photoluminescent Properties

A new and convenient synthesis for amino‐phthalimide (1H‐isoindole‐1,3(2H)‐dione) derivatives has been developed starting from an α,β‐unsaturated ketone. The ketones were reacted with amines to give aromatic amine products. This is the first time that substituted amine groups have been incorporated in aromatic rings. The mechanism of the product formation is rationalized by the 1,2‐addition of amines to ketones. All aromatic compounds exhibited high fluorescence properties at the blue‐green region.     

Synthesis and Selected Transformations of 1H‐Imidazole 3‐Oxides Derived from Amino Acid Esters

A series of new optically active 1H‐imidazole 3‐oxides 5 with a substituted acetate group at N(1) as the chiral unit were prepared by the reaction of α‐(hydroxyimino) ketones, α‐amino acid methyl esters, and formaldehyde. In an analogous reaction, ethyl 2‐(hydroxyimino)‐3‐oxobutyrate and 1,3,5‐trialkylhexahydro‐1,3,5‐triazines gave 3‐oxido‐1H‐imidazole‐4‐carboxylates 14 , which easily rearranged into the 2‐oxo derivatives 15 . Selected examples of N‐oxides 5 could be transformed into the corresponding 2,3‐dihydro‐1H‐imidazole‐2‐thione derivatives 10 via a ‘sulfur‐transfer reaction’, and the reduction of the histidine derivative 5i with Raney‐Ni yielded the optically active 2,3‐bis(imidazolyl)propanoate 12 . Furthermore, reaction of the (1H‐imidazol‐1‐yl)acetates with primary amines yielded the corresponding acetamides.     

Novel Route to 4‐(Adamantan‐1‐yl)quinoline Derivatives Based on the Friedländer Condensation

2,3,4‐Trisubstituted quinolines, substituted with adamantan‐1‐yl or (adamantan‐1‐yl)methyl in the 4‐position, were prepared from the corresponding admantan‐1‐yl 2‐aminophenyl ketones or admantan‐1‐ylmethyl 2‐aminophenyl ketones and ketones with an α‐CH₂ group. These reactions were carried out under neat conditions or in toluene, and the products were obtained in moderate‐to‐excellent yields. The scope and limitations of the examined procedures are discussed. All new compounds are fully characterized by IR and NMR spectroscopy and mass spectrometry. The molecular structures of five new quinolines, obtained via single‐crystal X‐ray diffraction analyses, are discussed.     

Synthesis of N‐Substituted(Thiazol‐2‐ylidene)pyrazol‐5‐amine Derivatives via Condensation of Pyrazolylthioureas with ω‐Bromoacetophenones

1‐Substituted 3‐[3‐methyl‐1H‐pyrazol‐5‐yl]thioureas react with ω‐bromoacetophenones forming N‐substituted(thiazol‐2‐ylidene)pyrazol‐5‐amine derivatives. Rational for these conversations are presented.     

A Convenient and Facile Hantzsch Synthesis of Aryl Imidazo[1,2‐b]Isoxazolyl‐N‐aryl Thiazol Amines

The Hantzsch synthesis of novel aryl imidazo[1,2‐b]isoxazolyl‐N‐aryl thiazol amines 5 analogues were described. Reaction of 3‐aminoisoxazole 1 with substituted phenacyl bromides 2 in dry ethanol afforded the corresponding 6‐methyl‐3‐arylimidazo[1,2‐b]isoxazoles 3 in good yields. Compounds 3 on reaction with chloroacetyl chloride in 1,4‐dioxane furnished the corresponding 2‐chloro‐1‐(6‐methyl‐3‐arylimidazo[1,2‐b]isoxazol‐2‐yl)ethanones 4 . Compounds 4 on heating with N‐aryl thioureas in an oil bath underwent cyclization to afford the title compounds viz., imidazo[1,2‐b]isoxazolyl‐N‐aryl thiazol amines 5 in moderate to good yields by Hantzsch synthesis.     

Synthesis and Antimicrobial Screening of 2‐Aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole Derivatives

A new series of 2‐aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole derivatives was synthesized by condensation of 2‐(2‐substituted thiazol‐4‐yl)acetohydrazide with aryl aldehydes followed by oxidative cyclocondensation using iodobenzene diacetate. The structure of synthesized compounds was characterized by IR, NMR, and mass analysis. All the newly synthesized compounds were evaluated for their in vitro antimicrobial activity. Some of the compounds showed moderate antimicrobial activity.     

18‐Crown‐6 Catalyzed Microwave‐mediated Synthesis of Symmetric Bis‐Heterocyclic Compounds under Solvent‐free Condition

An efficient, solvent‐free and 18‐crown‐6 catalyzed method for the synthesis of N‐alkyl‐4‐(4‐(5‐(2‐(alkyl‐amino)thiazol‐4‐yl)pyridin‐3‐yl)phenyl)thiazol‐2‐amine, N‐alkyl‐4‐(5‐(2‐alkyamino)thiazol‐4‐yl)pyridine‐3‐yl)thiazol‐2‐amine, and 4,4′‐bis‐{2‐[amino]‐4‐thiazolyl}biphenyl bis‐heterocyclic derivatives via microwave accelerated cyclization is presented.     

Triethanolamine‐catalyzed expeditious and greener synthesis of 2‐amino‐4H‐chromenes

Triethanolamine (TEOA), an inexpensive and eco‐friendly base, was used to efficiently catalyze the three‐component condensation reaction of heterocyclic/aromatic aldehyde, (α/β)‐naphthol, and malononitrile in water to give the corresponding substituted 2‐amino‐4H‐chromene derivatives with excellent yields.     

Michael-Addition Reaction of Malononitrile with α,β-Unsaturated Cycloketones Catalyzed by KF／Al2O3

A series of KF/Al2O3 catalyzed Michael-addition reactions between malononitrile and α,β-unsaturated cycloketones in DMF solution were studied. At room temperature, 2-cyano-3-aryl-3-(1,2,3,4-tetrahydronaphthalen-1-one-2-yl) propionitrile derivatives were synthesized by the reaction between 2-arylmethylidene-1,2,3,4-tetra-hydronaphthalen-1-one and malononitrile. However, if the temperature was increased to 80℃, 2-amino-3-cyano-4-aryl-4H-benzo[h]chromene derivatives were obtained in high yields. When the α,β-unsaturated ketones were replaced by 2,6-biarylmethylidenecyclohexanone or 2,5-biarylmethylidenecyclopentanone, another series of 2-amino-3-cyano-4H-pyran derivatives was isolated successfully. The structures of the products were confirmed by X-ray diffraction analysis.     

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.     

Synthesis and Antibacterial Evaluation of Some New Thiazole‐Based Polyheterocyclic Ring Systems

2‐Cyanoacetamido‐thiazole ( 1 ) was employed as a key for the construction of 6‐cyano‐7‐oxo‐7H‐thiazolo[3,2‐a]pyrimidine ( 4 ) which underwent reaction with hydrazine, malononitrile, ethyl cyanoacetate, and/or various 1,3‐bi‐nuclophilic reagents furnished the corresponding tri‐heterocyclic and tetra‐heterocyclic ring systems 5 – 12 . In addition, the reactions of 1 with various types of arylidene‐malononitriles and/or ethyl 3‐aryl‐2‐cyanoacrylates yielded the corresponding 1‐thiazolyl‐pyridine derivatives 16 and 20 , respectively. Furthermore, treatment of the precursor 1 with carbon disulfide and methyl iodide afforded the ketene dithioacetal derivative 21 which cyclized upon heating with hydrazine and/or 2‐aminobenzimidazole into the corresponding derivatives of N‐(thiazol‐2‐yl)‐1H‐pyrazole‐4‐carboxamide 22 and N‐(thiazol‐2‐yl)benzimidazo[1,2‐a]‐pyrimidine‐3‐carboxamide 23 . The antibacterial properties of these thiazole‐based heterocycles were examined against panel of two bacterial strains.     

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.     

One‐Pot Four‐Component Synthesis of Thieno[2,3‐d]pyrimidin‐4‐amines via Sequential Gewald/Cyclocondensation Reactions

A one‐pot four‐component synthesis of thieno[2,3‐d]pyrimidin‐4‐amines via sequential Gewald/cyclocondensation reactions is described. 2‐Aminothiophene‐3‐carbonitriles obtained from the Gewald reaction between cyclic ketones, malononitrile, and sulfur underwent a condensation? cyclization reaction with benzonitriles under solvent‐free conditions to afford the title compounds in excellent yields.     

An Eco‐friendly Synthesis of Some Novel 4‐methyl‐4‐hetaryl Chromene and Pyrano[2,3‐c]pyrazole Derivatives

Some novel chromene and pyrano[2,3‐c ]pyrazole derivatives could be achieved successfully by reacting cyclic β‐diketones with 2‐acetylfuran/2‐acetylthiophene and malononitrile in a one‐pot synthesis. Active methylene pyrazolones reacted with 2‐(1‐furan‐2‐yl‐ethylidene)‐malononitrile and 2‐(1‐thiophen‐2‐yl‐ethylidene)‐malononitrile derivatives to afford the desired pyrano[2,3‐c ]pyrazole derivatives. Structures of all new compounds were established based on analytical and spectral data as well as X‐ray crystallography. A plausible mechanism for the reaction is suggested. The solvents and catalyst used are environmentally benign, and no hazardous solvents or heavy metals were involved.     

Synthesis and Pharmacological Evaluation of a Novel Series of 2‐((2‐Aryl thiazol‐4‐yl)methyl)‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole Derivatives as Possible Antifungal Agents

In the present investigation, a novel series of 2‐[(2‐arylthiazol‐4‐yl)methyl]‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole derivatives were synthesized by cyclo‐condensation of 2‐(2‐substituted thiazol‐4‐yl)aceto hydrazide with carbon disulfide followed by S‐alkylation with alkyl halide in dry acetone. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, mass, and elemental analysis) methods. The title compounds were screened for in vitro antifungal activity and most of the synthesized compounds show moderate to good antifungal activity.     

Hantzsch reaction of 3‐(2‐bromoacetyl)‐4‐hydroxy‐chromen‐2‐one. Synthesis of 3‐(thiazol‐4‐yl)‐4‐hydroxy coumarines

3‐Acetyl‐4‐hydroxy‐chromen‐2‐one ( 1 ) was brominated with phenyltrimethylammonium tribromide to afford 3‐(2‐bromoacetyl)‐4‐hydroxy‐chromen‐2‐one ( 2 ) whose reactions with thiourea, thioacetamide and ammonium dithiocarbamate gave respectively 3‐(2‐amino‐thiazol‐4‐yl)‐4‐hydroxy‐, 4‐hydroxy‐3‐(2‐phenyl‐thiazol‐4‐yl)‐ and 4‐hydroxy‐3‐(2‐mercapto‐thiazol‐4‐yl)chromen‐2‐one. In a similar manner, com pound 2 was treated with four 1‐substituted‐2‐thioureas and thiobenzamide to give the corresponding 4‐hydroxy‐3‐(thiazol‐4‐yl)‐chromen‐2‐one derivatives.     

Synthesis and characterization of the novel diamine‐functionalized Fe3O4@SiO2 nanocatalyst and its application for one‐pot three‐component synthesis of chromenes

Fe₃O₄@SiO₂@propyltriethoxysilane@o‐phenylendiamine as an environmentally‐benign functionalized silica‐coated magnetic organometallic nanomaterial has been synthesized and characterized by Fourier transforms infrared (FT‐IR) spectroscopy, scanning electron microscopy (SEM) images and energy dispersive X‐ray (EDX) and vibrating sample magnetometer (VSM) analyses. Then, its catalytic activity was investigated for the one‐pot three‐component condensation reaction between dimedone, malononitrile and various substituted aromatic aldehydes to afford the corresponding 2‐amino‐4H‐chromene derivatives under mild reaction conditions. This nanocatalyst can be easily recovered from the reaction mixture by using a magnet and reused for at least five times without significant decrease in catalytic activity.     

Synthesis and Reactivity of 3‐oxoprop‐1‐en‐1‐olate Derivative as a Building Block for the Synthesis of Azole and Azine Derivatives

Several new heterocyclic compounds such as 7‐substituted pyrazolo[1,5‐a ]pyrimidine ( 5a–e ) derivatives have been synthesized by the reactions of the versatile unreported sodium 3‐(4‐methyl‐2‐(4‐methylphenylsulfonamido)thiazol‐5‐yl)‐3‐oxoprop‐1‐en‐1‐olate (2) with amino heterocyclic ( 3a–e ) derivatives. Reaction of (2) with hydrazonyl halide ( 7a–d ) and hydroximoyl chloride ( 11a,b ) derivatives followed by reaction with hydrazine hydrate afforded pyrazolo[3,4‐d ]pyridazine and isoxazolo[3,4‐d ]pyridazine derivatives, respectively incorporating a thiazole moiety have been described. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis.