Action of Hydrazines on 2‐(2‐Oxindolin‐3‐ylidene)malononitrile, (E,Z)‐Ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate and Isatin‐β‐thiosemicarbazone as a Source of Spiro Indoline‐pyrazole Systems

2‐(2‐Oxindolin‐3‐ylidene)malononitrile ( 1a ) or (E,Z)‐ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate ( 1b ) or isatin‐β‐thiosemicarbazone ( 1c ) undergoes reactions with prototype hydrazine hydrate itself and some of its simple congeners to give hydrazone derivatives bearing indoline‐2‐one moiety ( 2 ). The hydrazone derivatives ( 2 ) when heated with acetyl acetone or ethyl acetoacetate in dry pyridine afforded the spiro indoline derivatives ( 3a , 3b ). Also, cinnoline derivative ( 9 ) is obtained by action of hydrazine hydrate on the N‐acetyl derivative of ( 6a ). The structures of the newly synthesized compounds were evaluated by IR, ¹H‐NMR spectroscopy, mass spectra and elemental analyses.     

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.     

Reactivity of N,N″‐1,ω‐alkanediyl‐bis‐[N′‐organylthiourea] Derivatives Towards Isatylidene Malononitrile

(Z)‐2‐(2‐Oxoindolin‐3‐ylidene)‐2‐(substituted amino)acetonitriles, 2‐thioxoimidazolidine‐1‐carbothioamides, and 2‐thioxotetrahydropyrimidine‐1(2H)‐carbothioamides were synthesized via conventional thermal or microwave‐assisted reaction of isatylidene malononitrile with N,N″‐1,ω‐alkanediyl‐bis‐[N′‐organylthiourea] derivatives. Rationale for these conversations involving the nucleophilic addition on the dicyanomethylene carbon atom and intramolecular heterocyclization of the title compounds is presented. The structure of the (Z)‐2‐(2‐oxoindolin‐3‐ylidene)‐2‐(phenylamino)acetonitrile has been confirmed by the X‐ray analysis.     

Synthesis of Some New Heteroylhydrazono‐1,3‐thiazolidin‐4‐ones

A series of (Z)‐methyl‐2‐[(Z)‐3‐substituted‐4‐oxo‐2‐(2‐picolinoyl‐/thiophene‐2‐carbonyl)‐hydrazonothiazolidin‐5‐ylidene]acetates were synthesized by condensation N‐substituted‐(2‐picolinoyl‐, thiophene‐2‐carbonyl)hydrazinecarbothioamides with dimethylacetylenedicarboxylate. The structure of thiazolidin‐4‐one derivatives has been confirmed unambiguously by single crystal X‐ray crystallography.     

The Pseudo‐Michael Reaction of 2‐Hydrazinylidene‐1‐Arylimidazolidines with Diethyl Ethoxymethylenemalonate

The pseudo‐Michael reaction of 2‐hydrazinylidene‐1‐arylimidazolidines with diethyl ethoxymethylenemalonate (DEEM) was investigated. The reaction yields the chain adduct, namely diethyl{[2‐(1‐arylimidazolidin‐2‐ylidene)hydrazinyl]methylidene}propanedioates. This is contrary to the pseudo‐Michael reaction of DEEM with 1‐aryl‐4,5‐dihydro‐1H‐imidazol‐2‐amines that does not allow isolation of chain derivatives and leads to cyclic imidazo[1,2‐a]pyrimidine derivatives while even at thermodynamic control. At first cyclization of diethyl{[2‐(1‐arylimidazolidin‐2‐ylidene)hydrazinyl]methylidene}propanedioates leads to ethyl 1‐aryl‐5(1H,8H)oxo‐2,3‐dihydro‐imidazo[2,1‐c][1,2,4]triazepine‐6‐carboxylates. 1,5‐Sigmatropic shift, following the cyclization, caused isomerization of 5(1H,8H)oxo‐2,3‐dihydro‐imidazo[2,1‐c][1,2,4]triazepine‐6‐carboxylates to ethyl 1‐aryl‐5(1H)hydroxy‐2,3‐dihydroimidazo[2,1‐c][1,2,4]triazepine‐6‐carboxylates. Presence of both isomers in the reaction product was detected in the NMR spectra. The structure of all the compounds was confirmed with spectroscopic studies (¹H NMR and MS). The structure of diethyl{[2‐(1‐phenylimidazolidin‐2‐ylidene)hydrazinyl]methylidene}propanedioate was also confirmed by X‐ray crystallography. In the addition reaction, thermodynamics and HOMO–LUMO orbitals of the reactants were studied by using quantum chemical calculations.     

The Reactivity of Dimethyl Acetylenedicarboxylate and Heterocyclization of Hydrazinecarbothioamides to 1,3‐Thiazolidin‐4‐ones

2‐Substituted hydrazinecarbothioamides and N,2‐disubstituted hydrazinecarbothioamides react, in high yields with dimethyl acetylenedicarboxylate to give 4‐oxo‐Z‐(thiazolidin‐5‐ylidene)acetate derivatives. Several mechanistic options involving interaction are presented. The structures of thiazolidin‐4‐ones have been unambiguously confirmed by single crystal X‐ray crystallography.     

4‐(9,10‐Dihydroacridin‐9‐ylidene)thiosemicarbazide and its five‐membered thiazole and six‐membered thiazine derivatives

Two methyl derivatives, five‐membered methyl 2‐{2‐[2‐(9,10‐dihydroacridin‐9‐ylidene)‐1‐methylhydrazinyl]‐4‐oxo‐4,5‐dihydro‐1,3‐thiazol‐5‐ylidene}acetate, C₂₀H₁₆N₄O₃S, (I), and six‐membered 2‐[2‐(9,10‐dihydroacridin‐9‐ylidene)‐1‐methylhydrazinyl]‐4H‐1,3‐thiazin‐4‐one, C₁₈H₁₄N₄OS, (II), were prepared by the reaction of the N‐methyl derivative of 4‐(9,10‐dihydroacridin‐9‐ylidene)thiosemicarbazide, C₁₄H₁₂N₄S, (III), with dimethyl acetylenedicarboxylate and methyl propiolate, respectively. The crystal structures of (I), (II) and (III) are molecular and can be considered in two parts: (i) the nearly planar acridine moiety and (ii) the singular heterocyclic ring portion [thiazolidine for (I) and thiazine for (II)] including the linking amine and imine N atoms and the methyl C atom, or the full side chain in the case of (III). The structures of (I) and (II) are stabilized by N—H...O hydrogen bonds and different π–π interactions between acridine moieties and thiazolidine and thiazine rings, respectively.     

Reactivity study on morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide

Regioselective reactions of morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide ( 1 ) with electrophiles and nucleophiles were studied. The compound ( 1 ) reacts with alkyl halides in basic medium to afford S‐substituted isothiourea derivatives, with amines to give 1,1‐disubstituted‐3‐(2‐phenyl‐3H‐quinazolin‐4‐ylidene) thioureas and l‐substituted‐3‐(2‐phenyl‐quinazolin‐4‐yl) thioureas via transami‐nation reaction. The reaction of ( 1 ) with amines in the presence of H₂O₂ provided N⁴‐disubstituted‐N'⁴‐(2‐phenylquinazolin‐4‐yl)morpholin‐4‐carboximidamide via oxidative desulfurization. Estimation of reactivity sites on ( 1 ) was supported using the ab initio (HF/6‐31G**) quantum chemistry calculations. The ir, ¹H nmr, ¹³C nmr, mass spectroscopy and x‐ray identified the isolated products.     

Synthesis of novel palladium N‐heterocyclic‐carbene complexes as catalysts for Heck and Suzuki cross‐coupling reactions

Novel palladium‐1,3‐dialkylperhydrobenzimidazolin‐2‐ylidene (2a–c) and palladium‐1,3‐dialkylimidazolin‐2‐ylidene complexes (4a,b) have been prepared and characterized by C, H, N analysis, ¹H‐NMR and ¹³C‐NMR. Styrene or phenylboronic acid reacts with aryl halide derivatives in the presence of catalytic amounts of the new palladium‐carbene complexes, PdCl₂(1,3‐dialkylperhydrobenzimidazolin‐2‐ylidene) or PdCl₂(1,3‐dialkylimidazolin‐2‐ylidene) to give the corresponding C? C coupling products in good yields. Copyright © 2006 John Wiley & Sons, Ltd.     

On the Reactivity of (7‐Oxabicyclo[2.2.1]hept‐5‐en‐2‐ylidene)amines. Different Reaction Paths Leading to the Same Final Products

The reaction of amines, N‐substituted by a 7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐ylidene moiety, either with PhSCl or mCPBA (meta‐chloroperbenzoic acid) unexpectedly afforded the same type of furan derivatives by two different reaction paths. The results confirm the intervention of a homoconjugative, electron‐releasing effect of the oxabicycloalkenylideneamine moieties, as predicted theoretically.     

The Behavior of (cyclic‐alkylidene)hydrazinecarbothioamides in Cyclization with Dimethyl acetylenedicarboxylate

A series of (Z )‐methyl 2(Z )‐3‐substituted‐2‐(cycloalkylidenehydrazono)‐4‐oxothiazolidin‐5‐ylidene)‐acetate derivatives were synthesized via condensation alkylidene‐N‐substituted hydrazinecarbothioamides with dimethyl acetylenedicarboxylate. The synthesized compounds were characterized by using different spectroscopic methods and confirmed by single crystal X‐ray analysis. The behavior of (cyclic‐alkylidene) hydrazinecarbothioamides in cyclization was presented. The mechanism of transformation of (Z )‐methyl 2‐((Z )‐3‐(cyclopentylideneamino)‐4‐oxo‐2‐(phenylimino)thiazolidin‐5‐ylidene)acetate ( 14) into the more stable (Z )‐Methyl 2‐[(Z )‐2‐(cyclopentylidenehydrazono)‐4‐oxo‐3‐phenylthiazolidin‐5‐ylidene]acetate ( 5a) was discussed and confirmed.     

Zur Hydrolyse von 2,3‐Dihydro‐1,3‐di‐tert‐butyl‐4,5‐dimethylimidazol‐2‐yliden. Die Kristallstruktur von 1,3‐Di‐tert‐butyl‐4,5‐dimethylimidazoliumhydrogencarbonat

On the Hydrolysis of 2,3‐Dihydro‐1,3‐di‐tert‐butyl‐4,5‐dimethylimidazol‐2‐ylidene. The Crystal Structure of 1,3‐Di‐tert‐butyl‐4,5‐dimethylimidazolium Bicarbonate 1,3‐Di‐tert‐butyl‐4,5‐dimethylimidazolium bicarbonate ( 7 ), formed on the exposure of 2,3‐dihydro‐1,3‐di‐tert‐butyl‐4,5‐dimethylimidazol‐2‐ylidene ( 6 ) towards air, is prepared on the reaction of 6 with ammonium bicarbonate; its crystal structure analysis reveals the presence of dimeric bicarbonate anions linked to each other and to the imidazolium ions with hydrogen bonds.     

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.     

An Approach to the Synthesis of Spiro[indene‐pyridoisoquinoline] Derivatives via 1,4‐Dipolar Cycloaddition of Isoquinoline and Acetylene Esters,and (1,3‐Dihydro‐1,3‐dioxo‐2H‐inden‐2‐ylidene)malononitrile

A concise and efficient approach to the spiro‐tetrahydroisoquinoline derivatives has been developed by 1,4‐dipolar cycloaddition of zwitterions resulting from isoquinoline and acetylene esters and (1,3‐dihydro‐1,3‐dioxo‐2H‐inden‐2‐ylidene)malononitrile in MeCN at room temperature. The significance of this method lies in good yields and ease of product purification, and no inert atmosphere is required. The structures of the products were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme).     

Regio‐ and Site Selectivity in the Reactions of Hydrazonoyl Chlorides with 3‐substituted Indolin‐2‐one Derivatives

The reaction of 3‐(3‐amino‐5‐oxo‐1,5‐dihydropyrazol‐4‐ylidene)‐1,3‐dihydroindol‐2‐one with N‐aryl‐2‐oxopropane hydrazonoyl chlorides in dioxane in the presence of triethylamine proceeded regio‐ and site selectively to give 3‐(2‐arylazo‐3‐methyl‐6‐oxo‐imidazo[1,2‐b ]pyrazol‐7‐ylidene‐indol‐2‐ones rather than the isomeric form 3‐(3‐arylazo‐2‐methyl‐6‐oxo‐imidazo[1,2‐b ]pyrazol‐7‐ylidene‐indol‐2‐ones. On the other hand, the reaction of N ’‐(2‐oxoindoline‐3‐ylidene)hydrazinecarbothiohydrazide with hydrazonoyl chlorides in refluxing ethanol and in the presence of triethylamine proceeded regio‐ and site selectively to give the respective 3‐(substituted‐1,3,4‐thiadiazol‐2‐ylidenehydrazono)indolin‐2‐ones. The mechanism of formation of the new products was also discussed. The structure assigned for the products was established by elemental and spectral data (¹H‐NMR, IR, and Mass) and NOE experiment. Moreover, the biological activity of the products was evaluated against some fungi and bacteria, and the results obtained revealed the high potency of some of them compared with the used standard references.     

Synthesis of New Gluco‐, Galacto‐, and Mannopyranosylthiazoles,Thiazolidinones, and Pyranosylthiazlidin‐4‐ones from Sugar Thiosemicarbazone Derivatives

A new series of potentially biological active derivatives, namely alkyl‐2‐((4‐oxo‐2‐(phenylimino)‐3‐(β‐d ‐pyranosyl‐2‐ylamino)thiazolidine‐5‐ylidene)acetate ( 5a–f ), 4‐(4‐bromophenyl)thiazol‐2(3H)‐ylidene)hydrazinyl)‐β‐d ‐pyranosyl ( 4a–c ), and 5‐(4‐bromophenyl)‐2‐(phenylimino)‐3‐(β‐d ‐pyranosyl‐2‐ylamino)thiazolidine‐4‐one ( 6 ) were synthesized via a reaction of the sugar thiosemicarbazone derivatives with 2,4′‐dibromoacetophenone, dialkylacetylenedicarboxylate, and ethylbromoacetate, respectively. The structures of the synthesized compounds were established by spectroscopic methods (FT‐IR, ¹H NMR, ¹³C NMR, and 2D NMR) and elemental analyses. Furthermore, the effect of various solvents at reflux and also ambient temperature on the reactions of the sugar thiosemicarbazone with 2,4′dibromoacetophenone, diethyl acetylenedicarboxylate, and dimethyl acetylenedicarboxylate was investigated. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:200–207, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21083     

Tailored‐design Synthesis of Sulfapyrimidine Derivatives

In this paper, we report an efficient and convenient approach for the synthesis of tailored‐design target sulfapyrimidine derivatives expected to show remarkable antimicrobial activities. The approach is based on reacting arylsulfonyl guanidine with α,β‐unsaturated carbonyl compounds to afford N‐(4,6‐diarylpyrimidin‐2‐yl)arylsulfonamide or with ylidene derivatives to afford N‐(6‐aryl‐5‐cyanopyrimidin‐2‐yl)arylsulfonamide, N‐(4‐amino‐5‐cyano‐6‐(methylthio)‐pyrimidin‐2‐yl)‐arylsulfonamide, and N‐(5‐cyanopyrimidin‐2‐yl)arylsulfonamide compounds through Michael addition reaction. The structure of the newly synthesized compounds was confirmed from spectral data and elemental analysis.     

Synthesis,cytotoxicity and antibacterial studies of symmetrically and non‐symmetrically benzyl‐ or p‐cyanobenzyl‐substituted N‐Heterocyclic carbene–silver complexes

From the reaction of 1H‐imidazole ( 1a ), 4,5‐dichloro‐1H‐imidazole ( 1b ) and 1H‐benzimidazole ( 1c ) with p‐cyanobenzyl bromide ( 2 ), symmetrically substituted N‐heterocyclic carbene (NHC) [( 3a–c )] precursors, 1‐methylimidazole ( 5a ), 4,5‐dichloro‐1‐methylimidazole ( 5b ) and 1‐methylbenzimidazole ( 5c ) with benzyl bromide ( 6 ), non‐symmetrically substituted N‐heterocyclic carbene (NHC) [( 7a–c )] precursors were synthesized. These NHC? precursors were then reacted with silver(I) acetate to yield the NHC‐silver complexes [1,3‐bis(4‐cyanobenzyl)imidazole‐2‐ylidene] silver(I) acetate ( 4a ), [4,5‐dichloro‐1,3‐bis(4‐cyanobenzyl)imidazole‐2‐ylidene] silver(I) acetate ( 4b ), [1,3‐bis(4‐cyanobenzyl)benzimidazole‐2‐ylidene] silver(I) acetate ( 4c ), (1‐methyl‐3‐benzylimidazole‐2‐ylidene) silver(I) acetate ( 8a ), (4,5‐dichloro‐1‐methyl‐3‐benzylimidazole‐2‐ylidene) silver(I) acetate ( 8b ) and (1‐methyl‐3‐benzylbenzimidazole‐2‐ylidene) silver(I) acetate ( 8c ) respectively. The four NHC‐precursors 3a–c, 7c and four NHC–silver complexes 4a–c and 8c were characterized by single crystal X‐ray diffraction. The preliminary antibacterial activity of all the compounds was studied against Gram‐negative bacteria Escherichia coli, and Gram‐positive bacteria Staphylococcus aureus using the qualitative Kirby‐Bauer disc‐diffusion method. All NHC–silver complexes exhibited medium to high antibacterial activity with areas of clearance ranging from 4 to 12 mm at the highest amount used, while the NHC‐precursors showed significantly lower activity. In addition, all NHC–silver complexes underwent preliminary cytotoxicity tests on the human renal‐cancer cell line Caki‐1 and showed medium to high cytotoxicity with IC₅₀ values ranging from 53 ( ± 8) to 3.2 ( ± 0.6) µM. Copyright © 2010 John Wiley & Sons, Ltd.     

Hydrogen‐bonding patterns in enaminones: (2Z)‐1‐(4‐bromophenyl)‐2‐(pyrrolidin‐2‐ylidene)ethanone and its piperidin‐2‐ylidene and azepan‐2‐ylidene analogues

The title compounds, namely (2Z)‐1‐(4‐bromophenyl)‐2‐(pyrrolidin‐2‐ylidene)ethanone, C₁₂H₁₂BrNO, (I), (2Z)‐1‐(4‐bromophenyl)‐2‐(piperidin‐2‐ylidene)ethanone, C₁₃H₁₄BrNO, (II), and (2Z)‐2‐(azepan‐2‐ylidene)‐1‐(4‐bromophenyl)ethanone, C₁₄H₁₆BrNO, (III), are characterized by bifurcated intra‐ and intermolecular hydrogen bonding between the secondary amine and carbonyl groups. The former establishes a six‐membered hydrogen‐bonded ring, while the latter leads to the formation of centrosymmetric dimers. Weak C—H...Br interactions link the individual molecules into chains that run along the [011], [101] and [101] directions in (I)–(III), respectively. Additional weak Br...O, C—H...π and C—H...O interactions further stabilize the crystal structures.     

Three‐Component Reaction for Construction of Spiro[indoline‐3,7′‐thiazolo[3,2‐a]pyridines] and Spiro[benzo[4,5]thiazolo[3,2‐a]pyridine‐3,3′‐indolines]

The three‐component reaction of thiazole (benzothiazole), dialkyl but‐2‐ynedioate, and isatinylidene malononitriles in toluene at 110–120°C in a sealed tube afforded a mixture of cis/trans‐isomers of functionalized diastereoisomeric spiro[indoline‐3,7′‐thiazolo[3,2‐a]pyridines] and spiro[benzo[4,5]thiazolo[3,2‐a]pyridine‐3,3′‐indolines] in good yields. Both cis‐isomers and trans‐isomers were successfully separated out and fully characterized with spectroscopy and single crystal determination. Under similar conditions, the three‐component reaction containing 2‐(1,3‐dioxo‐1H‐inden‐2(3H)‐ylidene)malononitrile resulted in spiro[indene‐2,7′‐thiazolo[3,2‐a]pyridine] derivatives.