Study on the antioxidant activity and quantification of thioamides based on nitrogen five-membered heterocycles by the kinetic technique

The antioxidant activity of heterocyclic thioamides based on imidazole, triazole, tetrazole, thiazole, thiazoline, and thiadiazole is estimated by spectrophotometry using the rate constant of reaction with the chromogenic radical 2,2′-diphenyl-1-picrylhydrazyl. The rate constant of direct transfer of a hydrogen atom to the radical in carbon tetrachloride is maximal for 1-methylimidazoline-2-thione. The protective antioxidant effect of the preparations in ethanol falls down abruptly from 4-phenylthiazoline-2-thione (k = 1.06 × 10⁴ M⁻¹min⁻¹) to the thioamides based on triazole and thiazoline (k ∼ 20 M⁻¹min⁻¹). In acetonitrile, thiazole derivatives show the most substantial antioxidant activity, k = n ×10⁴ M⁻¹min⁻¹, which goes down to zero if the aromaticity of the heterocycle is broken. As established, for the pseudo first order reaction between thioamides and the chromogenic radical, the reaction rate linearly depends on the concentration of thioamides. A spectrophotometry kinetic method for the quantification of heteroaromatic thioamides is elaborated.     

Mechanism of dehydration of 2-CH2R-and 2-CHR2-4-hydroxy-Δ2-thiazolines as intermediates in the Hantzsch thiazole synthesis and factors impeding the synthesis of 2-Me-, 2-Ar-, and 2-Het-substituted thiazoles and thiazolo[5,4-b]indoles

Based on the results of studies of the deuterium exchange and dehydration of 4-hydroxy-Δ²-thiazolines and 2-R-4-acetyl-8b-hydroxy-3a,8b-dihydro-4H-thiazolo[5,4-b]indoles containing the α-methylene (methine) unit at the C(2) atom, the mechanism of dehydration of these compounds generated as intermediates in the Hantzsch synthesis of thiazoles and 2-R-4-acetyl-4H-thiazolo[5,4-b]indoles was proposed. This mechanism includes an additional step of the formation of the corresponding Δ³-thiazolines. According to the results of quantum chemical calculations, this is energetically more favorable than the dehydration in terms of the commonly accepted mechanism. In some cases, an acidic medium impedes the dehydration of 4-hydroxy-Δ²-thiazolines or their cyclic analogs. The proposed mechanism provides an explanation for the empirical data on the differences in the reactivities of both thioamides and α-haloketones, which have remained unexplained in terms of the commonly accepted mechanism. The spontaneous thiazole synthesis is virtually impossible starting from thioamides of aromatic or heteroaromatic acids and α-haloketones bearing electron-withdrawing α′ substituents or cyclic bromoindoxyl-type haloketones. In the thiazole synthesis from these starting components, it is expedient to perform dehydration under basic catalysis. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1394–1402, July, 2007.     

Synthesis and anti-inflammatory activity of ethynylthiazoles

A series of acetylene derivatives of thiazole using the Sonogashira cross-coupling method was synthesized and evaluated in vivo for their anti-inflammatory activity. Four compounds exhibited good anti-inflammatory activity and two inhibited soybean lipoxygenase. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 769–774, May, 2006.     

Oximes of five-membered heterocyclic compounds with two heteroatoms. 1. Synthesis and structure (Review)

Data on the production and structure of oxazole, thiazole, and imidazole aldoximes, ketoximes, and amidoximes and their derivatives are reviewed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 483–504, April, 2007.     

Synthesis of new hetarylazoindole dyes from some 2-aminothiazole derivatives

A new series of heterocyclic disperse dyes were prepared by diazotization of some 2-aminothiazole derivatives and subsequent coupling with indole compounds. The dyes were characterized by UV-Vis, FT-IR, ¹H NMR, and mass spectra (LC-MS). Solvent effects on their visible absorption spectra were estimated. The color of the dyes is discussed with respect to the substituent therein. The effects of acids and bases on the visible absorption maxima of the dyes are also reported. Replacement of methyl group in the 4-position of the thiazole ring by phenyl group leads to red shift of the absorption maximum due to π-electron-donating properties of the phenyl group, while weak electron-withdrawing chlorine or bromine atom in the para-position of the phenyl group in the 2-amino-4-phenylthiazole fragment induce a small blue shift relative to 2-amino-4-phenylthiazole derivatives. Introduction of an electron-withdrawing 4-nitrophenylsulfonyl group into the thiazole ring produces bathochromic shift of the absorption maximum in all solvents. Published in Russian in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 4, pp. 592–599. The text was submitted by the authors in English.     

Chemistry of hetero analogs of isoflavones 26. Synthesis of 2-alkyl derivatives of 3-(thiazol-2-yl)-and 3-(benzothiazol-2-yl)chromones

Treatment of substituted 2-(2,4-dihydroxyphenacyl)thiazole and 2-(2,4-dihydroxyphenacyl)benzothiazole with propionic and isobutyric anhydrides gives the substituted 2-ethyl-and 2-isopropyl-7-acyloxychromones. The use of pivaloyl chloride gives 1-pivaloyloxy-2-hetarylstyrene derivatives. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 835–840, June, 2008.     

Residue and dissipation of zinc thiazole in tobacco field ecosystem

A high-performance liquid chromatography with ultraviolet (HPLC-UV) detection method after derivatisation was developed for the first time for the novel fungicide zinc thiazole residue in tobacco samples. Field trials in two different locations were conducted to investigate the dissipation and residue of zinc thiazole in tobacco leaves and soil. The average recoveries of zinc thiazole were in the range of 82.5%–93.9% with relative standard deviations (RSDs) of 1.2%–9.1%. The zinc thiazole showed a rapid dissipation rate in fresh tobacco leaves with the half-lives of 1.1–1.6 days. The terminal residues of zinc thiazole in cured tobacco leaves and soil were 2.8–28.0 mg kg^?1and <0.05 mg kg^?1, respectively. The results could be used to establish the maximum residue limits (MRLs) and provide guidance for the scientific use of zinc thiazole in agriculture.     

Calculation of the thermondynamic values of alkylthiazoles from the Kovats retention indices on the basis of the non-linear additivity principle

Summary Retention indices and their energy equivalents were determined for ten alkylthiazoles analysed on the stationary phases Apiezon L, Triton X-305 and Carbowax 1000. It was found that the energy contributions of identical alkyl groups to the partial molar free energy of sorption of a molecule are not equivalent. Smaller energy contribututions are due to the α-position of alkyl groups with respect to the heteroatoms in the thiazole ring (α-effect). This effect was most pronounced for 2-alkylthiazoles. Higher sorption energies were found for dimethylthiazoles with two methylgroups in a vicinal position. The retention indices were predicted for ten other di- and tri-substituted methyl, ethyl and propyl thiazoles on the basis of the so-called α- and ortho-effects. The predicted values are in good agreement with the experimentally determined values. Dedicated to Prof. Dr. E. sz. Kováts (Ecole Polytechnique Fédérale de Lausanne) on the occasion of his sixtieth birthday.     

Selenonaphtheno[2,3-d]thiazole derivatives as polymethine dyes

New polymethine dyes — selenonaphtheno[2,3-d]thiazole derivatives — were synthesized. It is shown that all of the synthesized dyes which have a selenonaphtheno[2,3-d]thiazole residue are more deeply colored than the corresponding 6,7-benzobenzothiazole and thionaphtheno[2,3-d] thiazole derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 459–461, April, 1971.     

Oximes of five-membered heterocyclic compounds with two heteroatoms 2. Reactions and biological activity (Review)

Data on the reactions of oxazole, thiazole, pyrazole, and imidazole aldoximes, ketoximes, amidoximes, and their derivatives are reviewed. The synthesis of new heterocycles based on the oximes of five-membered heterocyclic compounds with two heteroatoms are considered separately. The principal results from investigation of the biological activity of the ethers of these oximes are also presented. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1123–1155, August, 2007.     

Self-assembled monolayers on electrode surfaces: a probe for redox kinetics

The formation and characterization of self-assembled monolayers of organosulfur compounds like alkanethiols and dialkyl (di)sulfides on metal surfaces such as gold are areas of current research interest. The presence of an aromatic ring in a thiol molecule can enhance the binding between Au and the thiol, resulting in the formation of compact and impervious self-assembled monolayers. The formation of a monolayer of 2-mercaptobenzothiazole (MBT), containing an aromatic group with a fused thiazole ring but no long alkyl chain, is achieved on a gold electrode surface. Voltammetric investigations of ferro/ferricyanide and ferrous/ferric redox systems carried out on this Au|MBT electrode are reported. Further, the possibility of using such an Au|MBT electrode to distinguish between inner and outer sphere electron transfer reactions is indicated. Received: 2 January 1998 / Accepted: 14 May 1998     

Spectral Characteristics of Sulfa Drugs: Effect of Solvents,pH and <Emphasis Type="Italic">β</Emphasis>-Cyclodextrin

The absorption and fluorescence spectra of sulfamethoxazole (SMO), sulfisoxazole (SFO), sulfathiazole (STO) and sulfanilamide (SAM) in different solvents, pH and β-cyclodextrin (β-CD) have been analyzed. The inclusion complexes of the above sulfa drugs with β-CD were investigated by UV-visible spectroscopy, fluorometry, DFT, SEM, FT-IR and ¹H NMR. The solvent study indicates that the position of the substituent (oxazole or thiazole group) in the SAM molecule (R–SO₂–NH-group) is not the key factor to change the absorption and emission behavior of these sulpha drug molecules. In aqueous solution, a single fluorescence band (340 nm) was observed whereas in solutions of β-CD dual emission (430 nm) was noticed in sulpha drug compounds. Formation of the inclusion complex in SMO, SFO and STO should result dual emission which is due to a Twisted Intramolecular Charge Transfer band (TICT). The β-CD study indicates that (i) sulpha drugs form 1:1 inclusion complexes with β-CD and (ii) the red shift and the presence of TICT in the β-CD medium confirms heterocyclic ring encapsulated in the β-CD cavity with the aniline ring present on the out side of the β-CD cavity.     

Synthesis of novel 4-(2-amino-5-thiazolyl)-pyrimidine-2-amines as potential protein kinase inhibitors

Abstract  A short and efficient sequence for the synthesis of a series of 4-(2-amino-5-thiazolyl)-pyrimidine-2-amines was developed. 1-Phenyl-2-(6-pyrimidinyl)-ethanones, obtained via Weinreb’s methodology, were used in a Hantzsch thiazole cyclization reaction, followed by introduction of the aniline moieties via nucleophilic substitution. Graphical abstract        

Polymethine dyes — Indolo[3,2-d]thiazole derivatives

New polymethine dyes with an indolo[3,2-d]thiazole residue are described, and their spectral properties are discussed. Replacement of the vinylene group in the naphtho[1,2-d]thiazole residue by an NH group leads to a considerably greater bathochromic shift of the absorption maximum of carbo- and merocyanines as compared with replacement by a sulfur atom. The basicity of the indolo[3,2-d]thiazole residue is higher than the basicity of the naphtho[1,2-d]-thiazole and thionaphtheno[3,2-d]thiazole residues.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1606–1610, December, 1972.     

Mass spectra of derivatives of imidazo[2,1-b] thiazole and thiazolo[3,2-a]benzimidazole

The mass spectra of 6-phenylimidazo[2,1-b]thiazole, thiazolo[3,2-a]benzimidazole, and a number of thiazole-ring-substituted derivatives were investigated. The fragmentation of both groups of compounds commences with cleavage of the bonds in the thiazole ring and leads to the appearance of nitrogen- and sulfur-containing fragments in the spectra. The common character of the mass spectrometric disintegration of the investigated compounds indicates that they have similar electronic structures. The mass number and position of a substituent in the thiazole ring can be determined on the basis of the mass numbers of a series of fragments.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 778–783, June, 1974.     

Quantum-chemical study of the protonation of pyrrolo[2,1-b]thiazole and its selenium and tellurium analogs

The possibility of proton attack on various centers in pyrrolo[2,1-b]thiazole (1) has been evaluated. The results of semiempirical (MNDO, AM1, and PM3) andab initio (6-31G^*) calculations were compared. The MNDO and 6-31G^* methods give “chemically proper” and qualitatively coincident results. Analysis of the intramolecular (geometric and electronic) reorganization of molecule1, depending on the protonation center, has been carried out. The most probable attack centers, depending on the mechanism of electrophilic reaction, have been recognized. The energy parameters of intramolecular prototropic rearrangements in cation1 and the “blocking” factor value of methyl groups reducting the corresponding complex stability have been evaluated. It has been established that the relative stability of the protonated forms does not change on going to pyrrolo[2,1-b]selenium- and telluriumazoles, but the range of variations is considerably narrowed in the series S>Se>Te. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1707–1711, October, 2000.     

Bromination of 4-(2-thienyl)thiazoles and 2-(2-thienyl)quinoline

Depending on the substituent, the bromination of 4-(2-thienyl)thiazoles and 2-(2-thienyl)quinoline takes place in the 5 position of the thiophene or thiazole ring. When an amino group is present in the 2 position of the thiazole ring, bromination takes place in the 5 position of the thiazole ring. When excess brominating agent is present, a second bromine atom enters the 5 position of the free ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 35–38, January, 1982.     

Nitration of 2- and 4-[2-(2-furyl)vinyl]thiazole derivatives

Nitration of 4-methyl-2-[2-(nitro-2-furyl)vinyl]thiazole with a mixture of concentrated nitric and sulfuric acids leads to 4-methyl-5-nitro-2-[2-(3,5-dinitro-2-furyl)vinyl]thiazole. Under the same conditions 2-methyl- and 2-acetamido-4-[1-R-2-(5-nitro-2-furyl)vinyl]thiazoles (R=CH₃, Cl) are nitrated in the 3 position of the furan ring, 2-amino-4-[1-chloro-2-(5-nitro-2-furyl)vinyl]thiazole is nitrated in the 5 position of the thiazole ring and 2-acetamido-5-nitro-4-[2-(2-furyl)vinyl]thiazole undergoes profound changes. Under the influence of a mixture of of nitric acid and acetic anhydride the latter compound is converted quantitatively to the 5-nitro derivative (with respect to the furan ring), whereas 4-[2-(5-nitro-2-furyl)vinyl]thiazole derivatives do not undergo reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 314–317, March, 1977.     

Diels–Alder reaction of 2,7‐dichloroquinoline‐5,8‐dione with a thiazole o‐quinodimethane. Assignment of the regiochemistry by 1H–13C HMBC correlations

The Diels–Alder reaction between a thiazole o‐quinodimethane and 4,6‐dichloroquinoline‐5,8‐dione gave 6‐chloro‐9‐azaanthra[2,3‐b]thiazole‐5,10‐dione as a single regioisomer. Its structure was assigned by 2D ¹H–¹³C HMBC short‐ and long‐range correlations. Measuring the spectra in CF₃CO₂D indicated that both nitrogen atoms of pyridine and thiazole rings are deuterated. Copyright © 2001 John Wiley & Sons, Ltd.     

Features of the reaction of unsymmetrical 2-mercapto-imidazoles with aromatic and aliphatic ketones

The cyclization of unsymmetrical 2-mercaptoimidazoles with aliphatic and aromatic ketones has been studied. Using ¹H NMR and X-ray analysis it has been shown that 4-R¹-1H-2-mercaptoimidazoles undergo selective oxidative cyclization to the corresponding 3-R³-2-R²-6-R¹-imidazo[2,1-b][1,3]thiazoles while 6-R⁴-1H-2-mercaptobenzo[d]imidazoles give a mixture of 6-R⁴-3-R²-2-R³-benzo[4,5]imidazo[2,1-b][1,3]thiazole and 7-R⁴-3-R²-2-R₃-benzo[4,5]imidazo[2,1-b][1,3]thiazole in the ratio 1: 1. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 115–122, January, 2007.