Synthesis and spectroscopic investigation of some arylazo derivatives of thiazolidin-4-one

The reaction of 2-phenylimino- and 2-(p-tolylimino)thiazolidin-4-ones with benzene-, p-nitrobenzene, p-sulfamoylbenzene-, and p-toluenediazonium chlorides in glacial acetic acid in the presence of anhydrous sodium acetate (pH of the medium 4.5–5.0) has been studied. A spectroscopic investigation in the IR and UV regions has shown that the 5-(p-nitrophenylazo) derivatives of thiazolidin-4-one exist in the azo tautomeric form; the 5-phenylazo and p-tolylazo derivatives of thiazolidin-4-one are mixtures of the azo and hydrazone tautomers.     

An efficient synthesis of designed 4-thiazolidinone fused pyrimidine derivatives as potent antimicrobial agents

A novel series of hybrid 2-substituted ((pyrimidin-2-yl)hydrazinyl)thiazolidin-4-one derivatives were synthesized by means of aromatic nucleophilic displacement of chlorine atoms of 2,4,6-trichloro pyrimidine. Synthesis of some novel 2-(2-(6-morpholino-4-substituted(phenyl amino)pyrimidin-2-yl)hydrazinyl)thiazol-4(5H)-one derivatives have been carried out by the displacement of chlorine atoms on the basis of functionality concept on varying conditions. The synthesized hydrazinyl thiazolidin-4-one pyrimidine derivatives were evaluated for their expected antimicrobialactivity; where, the majority of these compounds showed potent antibacterial and antifungal activities against the tested strains of bacteria and fungi. Afforded title analogs were subsequently characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR, Mass spectroscopy. SAR and HOMO-LUMO studies were also carried out for confirming the structure biological activity. Thus, these studies suggested that hydrazinyl pyrimidine derivatives bearing thiazolidinone moiety are interesting scaffolds for the development of novel antimicrobial agents.     

Investigation of the mobility of methylene group hydrogen atoms in some derivatives of 2-iminothiazolidin-4-one

A study is made of the reaction of 2-arylamino- and 3-aryl-2-arylimino derivatives of thiazolidin-4-one with p-[N, N-di(2-chloroethyl)amino]benzaldehyde and p-nitroso-N, N-di(2-chloroethyl) aniline. It is shown that replacement of hydrogen at the endocyclic nitrogen atom of 2-iminothiazolidine-4-one raises mobility of hydrogen atoms in the methylene group in the order phenyl > p-tolyl > > benzyl. The results obtained are confirmed by IR spectroscopy.     

Tautomerism of some amino aza-containing heterocycles

With the aim of checking potential amino/imino tautomerism in heterocyclic series, some uv/visible spectroscopic properties of 2-N-(2,4,6-trinitrophenyl)pyridine, 2-N-(2,4,6-trinitrophenyl)pyrimidine and of 2-N-(2,4,6-trinitrophenyl)thiazoleamine are reported and discussed. In dimethyl sulphoxide the imino tautomer of the thiazole derivatives is the more populated form, while in toluene the amino aromatic form predominates. The more populated tautomer of the pyridine and pyrimidine derivatives is the amino aromatic form in both polar and apolar solvents. For the thiazole derivatives the tautomeric equilibrium in toluene is shifted toward the imino form by adding small amounts of tetrabutylammonium bromide or of dimethyl sulphoxide. The position of the tautomeric equilibrium is quantitatively evaluated and discussed.     

Synthesis of thiazolidin-4-ones via [3+2] cycloaddition of in situ generated aza-oxyallylic cations with isothiocyanates

A highly efficient one-pot synthesis of thiazolidin-4-ones via [3+2] cycloaddition of aza-oxyallylic cations with isothiocyanates is developed. The aza-oxyallyic cations were generated in situ in the present of a base. This cycloaddition reaction allows the rapid access to a variety of thiazolidin-4-one derivatives in mild conditions, good yield, and excellent functional group compatibility.     

New chiral cyclopalladated complexes based on the pinane and bornane imines

2α-Hydroxypinan-3-one imino derivatives react with lithium tetrachloropalladate to form palladacycles, while similar bornane derivative undergo cyclopalladation only when treated with palladium acetate.     

Quantum chemical studies on some potentially tautomeric oxazolidin-4-one derivatives and their thio and azo anologs

The basicities and nucleophilicities along with prototautomerism of biologically active oxazolidin-4-one and its thio and azo analogs were investigated by semi-empirical methods. The oxo and thion protonation were found to be easier than that of azo protonation for 4-oxo and 4-thion derivatives whereas amino protonation was found to be easier than imino and azo protonation in 4-imino derivative. The preferred tautomeric form for 4-oxo and 4-thion derivatives were found to be the keto and thion forms, respectively, whereas the amino form was found to be preferred in 4-imino derivatives. An acceptable correlation between gas phase proton affinities and aqueous phase acidity constants as well as the correlation between nucleophilicity and acidity constants was observed.     

Design,Synthesis of New 1,2,4-Triazole/1,3,4-Thiadiazole with Spiroindoline,Imidazo[4,5-b]quinoxaline and Thieno[2,3-d]pyrimidine from Isatin Derivatives as Anticancer Agents

The current work aims to design and synthesis a new series of isatin derivatives and greatly enhances their cytotoxic activity. The derivatives 3-((bromophenyl) imino)-1-(morpholino (pyridine) methyl) indolin-2-one, 2-((oxoindoline) amino) benzoic acid, 3-(thiazolo-imino) indolinone, ethyl-2-((oxoindolin-3-ylidene)amino)-benzothiophene-3-carboxylate, 1-(oxoindoline)-benzo[4,5] thieno [2,3-d]pyrimidin-4(1H)-one, ethyl-2-(2-oxoindoline) hydrazine-1-carboxylate, N-(mercapto-oxo-pyrimidine)-2-(oxoindoline) hydrazine-1-carboxamide, N-(oxo-thiazolo[3,2-a] pyrimidine)-2-(oxoindolin-ylidene) hydrazine-carboxamide, 3-((amino-phenyl) amino)-3-hydroxy- indolinone, 3-((amino-phenyl) imino)-indolinone, 2-(2-((oxoindoline) amino) phenyl) isoindolinone, 2-(oxoindoline) hydrazine-carbothioamide, 5′-thioxospiro[indoline-3,3′-[1,2,4]triazolidin]-one, 5′-amino-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one and 3-((2-thioxo-imidazo[4,5-b]quinoxaline) imino) indolinone were synthesized from the starting material 1-(morpholino (pyridine) methyl) indoline-2,3-dione and evaluated for their in vitro cytotoxic activity against carcinogenic cells. The new chemical structures were evidenced using spectroscopy (IR, NMR and MS) and elemental analysis. The results show that compounds imidazo[4,5-b]quinoxaline-indolinone, thiazolopyrimidine-oxoindoline, pyrimidine-oxoindoline-hydrazine-carboxamide, spiro[indoline-3,2′-[1,3,4] thiadiazol]-one and spiro[indoline-3,3′-[1,2,4]triazolidin]-one have excellent anti-proliferative activities against different human cancer cell lines such as gastric carcinoma cells (MGC-803), breast adenocarcinoma cells (MCF-7), nasopharyngeal carcinoma cells (CNE2) and oral carcinoma cells (KB).     

Structure and temperature controlled synthesis of novel thiazolidin-4-one derivatives bearing an azasugar

Novel thiazolidin-4-one linked pseudo-aza-disaccharides and thiazolidin-4-ones containing C-pseudo-aza-nucleosides were synthesized via a one-pot three component reaction. The former was synthesized stereoselectively by the tandem Staudinger/aza-Wittig/cyclization reaction of azasugar aldehyde 1, an azidosugar, and mercaptoacetic acid. The reaction was structure and temperature controlled, and could be performed stereospecifically under 40 °C. It was the first report of a stereospecific synthesis of thiazolidin-4-one linked derivatives. However, these derivatives were synthesized with low stereoselectivity by involving the condensation reaction of azasugar aldehyde 1, aniline, and mercaptoacetic acid.     

Application of infrared spectrometry to the study of tautomerism and conformational and configurational isomerism in medical and biochemical agents: N,N'-disubstituted amidines.

Infrared investigations on the v(NH) and v(C = N) vibrations of N,N'-disubstituted formamidines, acetamidines and benzamidines, containing the same or different groups at the amino and imino nitrogen atoms, and of some model compounds (N-monosubstituted amides, imidazoles and 2-aminopyridines), carried out in CCl4 at various temperatures and concentrations, and in other solvents, show that all the amidines studied have the E configuration on the C = N double bond and display conformational isomerism on the C-N single bond. Formamidines exist predominantly in the form of a conformer with a hydrogen atom synperiplanar to the imino nitrogen atom, and can form a cyclic dimer. In acetamidines and benzamidines the other conformer, with a hydrogen antiperiplanar to the imino nitrogen, prevails, and hence they can form mainly linear dimers. Different positions of the v(NH) and v(C = N) bands observed for N,N'-diaryl and N,N'-dialkyl derivatives permit determination of the composition of tautomeric mixtures in N-alkyl-N'-arylamidines.     

Synthesis, reactions and antimicrobial activities of 8-ethoxycoumarin derivatives

Condensation of 3-acetyl-8-ethoxycoumarin (3) with thiosemicarbazide gave ethylidenehydrazinecarbothioamide 5, which was transformed into the thiazolidin-4-one derivatives 6,7. Interaction of 3 with DMF/POCl(3) gave b-chloroacroline derivative 8. Treatment of 3 with malononitrile gave benzo[c]chromone and 2-aminobenzonitrile derivatives 9 and 10, respectively with respect to the reaction conditions. Condensation of 3-(2-bromoacetyl)-8-ethoxycoumarin (4) with o-phenylenediamine gave 3-(quioxaline-2-yl)-8-ethoxycoumarin hydrobromide (11), while 4 reacted with 2-aminopyridine to give chromenopyridopyrimidine derivative 12. Condensation of 4 with potassium thio-cyanate/methanol gave an unexpected derivative, 2H-chromeno-3-carboxy(methyl-carbonimidic)thioanhydride 16, which upon treatment with (NH(2))(2)·H(2)O gave 3-ethoxy-2-hydroxybenzaldehyde azine 19. Interaction of 4 with thiourea derivatives gave thiazole derivatives 20a-c. The structures of the newly synthesized compounds were confirmed by their spectra data. The newly synthesized compounds were also screened for their antimicrobial activity.     

Synthesis and transformations of 3-azido-5-amino-1,2,4-triazines

The reaction of the tetrazolediazonium ion with malonic acid dinitrile and nitroacetonitrile leads to the formation of 3-azido-5-amino-1,2,4-triazine derivatives. According to the mass-spectrometric data and the results of X-ray diffraction analysis, the crystalline compounds exist in the amino form. The facile hydrolysis of the amino and azido groups to azauracils is an argument in favor of the existence of the imino form in solution.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 557–561, April, 1984.     

Tautomerism of acridin-9-amines substituted at the exocyclic nitrogen atom: spectroscopic investigations and theoretical studies

In the ground electronic state, the first two (1 and 2) of the compounds investigated--9-(methoxyamino)acridine (1), 9-hydrazinoacridine (2), N-(2-chloroethyl)acridin-9-amine (3) and N-(5-methylpyridin-2-yl)acridin-9-amine (4)--exist principally in the imino tautomeric form, while the other two (3 and 4) can coexist as amino and imino tautomers in solvents of various polarities and abilities to enter into specific interactions. These features of the molecules are reflected in the experimental absorption spectra and the predicted thermodynamic and spectral data. The predicted thermodynamic characteristics suggest that in the S1 state, the imino tautomers of 1, 2 and 4 and the amino tautomer of 3 are more stable than their tautomeric counterparts. However, the predicted rates of intersystem crossing suggest that the imino tautomers of 1-3 and the amino tautomer of 4 lose excitation energy very rapidly, so that only their counterpart tautomers in fact emit radiation. This explains why 1 and 2 do not fluoresce and why the amino form of 3 and the imino form of 4 are the emitters. 3 and 4 thus represent acridin-9-amines whose imino forms are preferred in the ground state, but whose respective amino and imino forms are preferred in the excited state. Because 3 and 4 are capable of tautomeric transformations in the ground and excited states, and also enter into specific interactions with solvents, these compounds could be potent spectral indicators or probes of environmental properties.     

Synthesis of 5-benzylidene-3-(3-fluoro-4-yl-morpholin-4-yl-phenylimino)-thiazolidin-4-one derivatives catalyzed by [BmIm] OH and their anti-microbial activity

A series of novel 5-benzylidene-3-(3-fluoro-4-yl-morpholin-4-yl-phenylimino)thiazolidin-4-one derivatives were synthesized using[bmIm]OH as a catalyst and were tested for their antibacterial and antifungal activities.These compounds showed moderate in vitro activities against the microorganisms tested.     

Synthesis of Heterocycles from Arylation Products of Unsaturated Compounds: XIII. 5-R<Superscript>1</Superscript>-Benzyl-2-(R<Superscript>2</Superscript>-2-pyridylimino)thiazolidin-4-ones

Meerwein reactions of arenediazonium bromides with methyl and ethyl acrylates gave 3-aryl-2-bromopropionic acid esters which were subjected to cyclocondensation with N-(2-pyridyl)- and N-(6-methyl-2-pyridyl) thioureas to obtain 5-R¹-benzyl-2-(R²-2-pyridylimino)thiazolidin-4-ones. The latter were shown to exist in solution as E isomers of the imino form.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1071–1075.Original Russian Text Copyright © 2005 by Matiichuk, Obushak, Tsyalkovskii.     

Efficient “on water” green route heterocyclization of thiosemicarbazones with DMAD

A simple, efficient, and eco-friendly procedure for the synthesis of thiazolidin-4-one derivatives in water from cyclocondensation reaction of thiosemicarbazone derivatives and dimethylacetylene dicarboxylate (DMAD) in good yield is reported. The regiochemistry of the cyclized products is established by elemental analysis, IR, NMR, and mass spectral data. A single crystal X-ray diffraction study of a representative compound, 3f, is reported.     

Synthesis of new 2-pyridinone and thiazole derivatives containing coumarin moiety

Coumarin has shown considerable therapeutic potency because of its versatile biological prosperities. Also, pyridines have been adopted in medicinal chemistry as potent ring. Moreover, several investigations reported the potency of thiazole-containing compounds. So, during this research, new functionalized 2-pyridinone and thiazole derivatives bearing coumarin moiety were aimed to synthesize. Many trials to obtain the 6-amino-2-oxo-pyridine-3,5-dicarbonitriles through the condensation of cyanoacetohydrazone of 3-acetyl coumarin with 2-(arylidene)malononitriles were carried out using different reaction conditions. In all cases, the reaction gave none of the corresponding 2-pyridinone derivatives except the reaction with 2-(benzylidene)-malononitrile afforded product in few yield. Moreover, the reaction of another cyanoacetanilide with the 2-(arylidene)-malononitrile afforded the unexpected arylidene derivatives rather than the expected pyridin-2-one derivatives. Finally, new thiazoles bearing coumarin moiety were synthesized using 3-acetylcoumarin N-(2,4-dimethoxyphenyl)-thiosemicarbazone. Cyclization of thiosemicarbazone derivative with ethyl 2-chloroacetate, chloroacetone or phenacyl bromide afforded in high yields the corresponding derivatives of thiazolidin-4-one, 4-methylthiazole or 4-phenylthiazole, respectively.     

Acylation of 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine and tautomerism of the reaction products

The acylation of 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine with the chlorides and anhydrides of saturated carboxylic and sulfonic acids leads to N-monoacyl derivatives of dithiazine in 85–96% yields. It was established by IR and UV spectroscopy that 2H,6H-2,6-dimethyl-4-acylamino-1,3,5-dithiazines with donor substituents exist primarily in the amino form and that the equilibrium is shifted to favor the imino form for compounds with acceptor substituents to a greater degree in solutions than in the crystalline state.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 622–626, May, 1982.     

Reaction of 2- and 3-furylmethanephosphonates with esters

2- and 3-furylmethanephosphonates are acylated with ethyl formate, diethyl oxalate, and ethyl trifluoroacetate in toluene in the presence of sodium foil to afford five phosphorylated derivatives of furylacetic aldehyde, furylpyruvic acid, and 1,1,1-trifluoro-1-(2-furyl)propan-2-one. In a chloroform solution these compounds exist in the equilibrium with their enolic forms. When treated with sodium ethylate they form sodium salts which were isolated and characterized by ¹H, ¹³C, and ³¹P NMR spectroscopy. It was shown that in DMSO solutions sodium salts of formyl and oxalyl derivatives of 2-furylmethanephosphonate exist as mixtures of the carbanion and enolate forms. In the first case the carbanion form is predominant, while in the second one the enolate forms prevail. Sodium salt of formylated 3-furylmetanephosphonate exists only in the carbanion form, while the salt of 3-furylpyruvate is enolate. The alkylation of these salts with iodomethane proceeds at the carbon atom as well as at the oxygen one. First reaction pathway is often preferred.     

Synthesis and spectroscopic study of arylazo derivatives of benzimidazolo[2′, 1′:2, 3]thiazolidin-4-one

The coupling of benzimidazolo[2, 1:2, 3]thiazolidin-4-one with benzenediazonium chlorides in acetic acid in the presence of sodium acetate at pH 4.5–4.0 has yielded 5-arylazo derivatives of the thiazolidone. By a study of the IR and UV spectra of the aryl derivatives of benzimidazolo[2, 1:2, 3]thiazolidin-4-one synthesized, it has been shown that the latter has the azo structure.