Thione Derivatives Research Articles

An investigation of supramolecular synthons in 1,2,4-triazole-3(4H)-thione compounds. X-ray crystal structures, energetic and Hirshfeld surface analysis

A series of four closely related 1,2,4-triazole-3-thione (1-4) compounds was obtained by heterocyclization of thiosemicarbazides under basic catalytic conditions. The crystal structures of the 4-alkyl-5-(substituted-phenyl)-2H-1,2,4-triazole-3(4H)-thione derivatives [4-alkyl = 4-ethyl-5-phenyl (1), 4-hexyl-5-phenyl (2), 4-hexyl-5-p-tolyl (3), and 4-ethyl-5-(2,4,6-trimethoxyphenyl) (4)] have been determined. PIXEL lattice energy calculations revealed that dispersion components make the major contributions, with the coulombic terms also contributing significantly to the total energy. Interaction energies for the inversion dimers involving N–H⋯S=C hydrogen bonds indicate a dominant contribution to packing stabilization coming from the coulombic energy component. Hirshfeld surfaces and 2D-fingerprint plots allowed us to visualize different intermolecular contacts and their relative contributions to the total surface in each compound. The comprehensive analysis of the crystal packing and the energetic features demonstrate the key role of the R22(8) supramolecular synthon of the type (···HNCS)2 in the solid state structures of these 1,2,4-triazole-3-thiones.

Design, Synthesis and In‐Vitro Antitumor Activity of Lupeol Derivatives via Modification at C‐3 and C‐30 Positions

AbstractLupeol has been isolated from ethanol extract of stem bark of Bombax ceiba through normal phase column chromatography. Total fourteen derivatives of lupeol were synthesized and assayed for in vitro antitumor activities against MDA MB‐231, HeLa and A549 cell lines. In cell proliferation experiments, pyrimidine‐2(5H)‐thione derivative (15) was found to be most potent and significantly inhibited all three tested cancer cell lines i. e. MDA MB‐231 (IC50 27.13±2.13), HeLa (IC50 45.95±1.42) and A549 (IC50 46.27±0.9). The (2, 4‐dinitrophenyl) hydrazyl‐3‐lupeol Derivative (12) exhibited antitumor activity against MDA MB‐231 (IC50 35.88±1.9) and HeLa cells (IC50 31.91±1.6) whereas (2, 4‐dinitrophenyl)‐2H‐imidazole derivative (14) showed activity against MDA MB‐231 (IC50 38.05±1.9) and A549 (IC50 42.01±0.90) cells respectively. Structure activity relationship is also described. Our study showed that compound 15 exhibited promising activity against MDA MB‐231 and A549 cancer cell lines.

Eschenmoser‐Coupling Reaction Furnishes Diazenyl‐1,2,4‐triazole‐5(4H)‐thione Derivatives

AbstractDiazenyl 1,2,4‐triazol‐5(4H)‐thione derivatives were synthesized in good yields via Eschenmoser‐coupling reaction and nucleophilic attack between 1,4‐disubstituted thiosemicarbazides and 2,3,5,6‐tetrachloro‐1,4‐benzoquinone (p‐CHL). The structure of the synthesized compounds was confirmed by IR, NMR and mass spectral data as well as single crystal X‐ray analysis.

Synthesis and characterization of nano acid catalyst derived from rice husk silica and its application for the synthesis of 3,4-dihydropyrimidinones/thiones compounds

In the present work, the extraction of silica nanoparticles from the rice husk followed by the modification using an acidic ionic liquid containing imidazolium butyl sulfonic acid through a sol-gel method (RH@[SiPrImBuSO3H]Cl) has been investigated. The composition, morphology and structural properties of the synthesized solid acid were analyzed by fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal gravimetric analysis-derivative thermogravimetric (TGA-DTG), and nitrogen adsorption-desorption. The catalytic activity of the nanocomposite was examined through the one-pot condensation of aromatic aldehyde, β-diketone, urea or thiourea under reflux condition. Diverse 3,4-dihydropyrimidinones/thiones derivatives were produced up to excellent yields in a short period of time. This nanocatalyst could be easily recovered, and reused without considerable loss of catalytic activity. This method seems to be a promising method for synthesizing organic chemicals. In addition to the conducted experiments, the 1H and 13C chemical shift and X-ray spectra values together with the structural parameters of 3,4-dihydropyrimidinones/thiones were computed and compared to the corresponding experimental values. As a result, the calculated 1H and 13C chemical shift and X-ray spectra show a good agreement with the experimental results.

Green synthesis, antioxidant and antibacterial activities of 4-aryl-3,4-dihydropyrimidinones/thiones derivatives of curcumin. Theoretical calculations and mechanism study

3,4-Dihydropyrimidin-2(1H)-one/thione analogs of curcumin were synthesized in good yield by a one-pot multi-component cyclocondensation using curcumin, substituted aromatic aldehydes, and urea/thiourea in less volume of ethanol catalysed by commercial heteropolyacide Keggin type H3PMo12O40 5% mol as a recyclable and nontoxic catalyst under conventional heating and microwave irradiation. All the synthesized curcumin derivatives 4a–n were screened for antioxidant and antimicrobial activity. Biological activity data of the synthesized showed that most of the synthesized compounds exhibited greater antioxidant and antibacterial activity than curcumin. Geometries of synthesized compounds were optimized by using B3LYP method with 6-31G* basis set. Then, DFT based reactivity descriptors such as HOMO, LUMO, chemical hardness, electronegativity, chemical potential were calculated and discussed.

Synthesis and Anticancer Evaluation of Some Phenothiazine Derivatives

10H-Phenothiazine 1 reacts with 2-chloroacetonitrile to give 2-(10H-phenothiazin-10-yl)- acetonitrile 2, which upon reaction with sodium azide gives the corresponding tetrazole 3. Treatment of 2 by either hydrazine hydrate or hydroxylamine affords 2-(2-chloro-10H-phenothiazin-10-yl)acetimidohydrazide 4 and 2-(2-сhloro-10H-phenothiazin-10-yl)-N'-hydroxyacetimidamide 7, respectively. Reaction of 4 with CS2 leads to the thione derivative 5. Treatment of 7 with acetic anhydride gives 3-[(2-chloro-10H-phenothiazin-10- yl)methyl]-4,5-dihydro-1,2,4-oxadiazole 8. Alkylation of sodium salt of compounds 3, 5, 6, or 8 by 1-chloro-2- methoxyethane and/or 2-(2-chloroethoxy)ethanol leads to the corresponding acyclic derivatives 9–16. Structures of all newly synthesized compounds are confirmed by IR, NMR and mass spectroscopy. All of the synthesized compounds demonstrate high activity against breast cancer cell line (MCF7).

Efficient Synthesis and Characterization of Novel Pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidines and Their Fused [1,2,4]triazole Derivatives

Both 3‐aminothieno[2,3‐b]pyridine‐2‐carboxamide derivative 4 and bis(3‐aminothieno[2,3‐b]pyridine‐2‐carboxamide) derivative 6 are prepared, starting with pyridine‐2(1H)‐thione derivative 1 incorporating 1,3‐diarylpyrazole moiety, and were taken as starting materials for the present study. Two different synthetic routes are described for the synthesis of the target materials bis(pyridothieno[1,2,3]triazin‐4‐(3H)‐one) derivative 7 and bis(pyridothienopyrimidin‐4(3H)‐one) derivatives 10 and 13. Pyridothienopyrimidin‐4(3H)‐one derivative 14 is used as a synthetic precursor for the preparation of 4‐hydrazinylpyridothieno[3,2‐d]pyrimidine derivative 18a. Compound 18a was reacted with acetylacetone to prepare the corresponding 4‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)pyrimidine derivative 19. Compound 18a was reacted with several reagents such as carbon disulfide to synthesize the corresponding derivatives 24–27 incorporating fused [1,2,4]triazole ring. Moreover, 2,4‐dihydrazinylpyridothieno[3,2‐d]pyrimidine derivative 31 was prepared starting from 3‐aminothieno[2,3‐b]pyridine‐2‐carbonitrile derivative 28. Compound 31 was reacted with each of acetylacetone and formic acid to afford the corresponding 2,4‐bis(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)pyrimidine derivative 32 and bis([1,2,4]triazolo)[4,3‐a:4′,3′‐c]pyrimidine derivative 33, respectively. Elucidation of the structures of target molecules are achieved using elemental analyses and spectral data.

Design, Synthesis and In-vivo Anti-inflammatory Activity of New Celecoxib Analogues as NSAID.

A new series of Celecoxib analogues were easily synthesized via reactions of 4-(2-(1-chloro-2-oxopropylidene)hydrazinyl)benzene sulfonamide (1) with active methylene compounds and dialkyl malonate. In addition, compound 1 was reacted also with thiourea derivatives and thiosemicarbazone derivatives to afford thiazole derivatives 9 and 11, respectively. Furthermore, triazolo pyrimidine derivatives 13 were prepared via reaction of compound 1 with pyrimidine thione derivatives. The structures of the new synthesized compounds were assigned by elemental analysis and spectroscopic data. The new analogues were screened for their in vivo anti-inflammatory activity using carrageenan-induced paw edema method. They showed moderate to good in vivo anti-inflammatory effects. Compounds 1, 6 and 11b were the most active compounds that reduced the paw edema induced by carrageenan by 12.25 %, 12.96 % and 12.97% respectively, as compared to the Indomethacin that inhibited the oedema volume by 7.47 %.

Heterocyclization of Isoniazid: Synthesis and Antimicrobial Activity of Some new Pyrimidine 1, 3-Thiazole, 1, 2, 4-Thiadiazole, and 1, 2, 4-Triazole, Derivatives Derived from Isoniazid

The reaction of isonicotinic hydrazide (1) (isoniazid) with cinnamoyl isothiocyanate (2) afforded cinnamoyl thiosemicarbazide derivative 3. Treatment of 3 with lead acetate in acetic acid, sodium ethoxide, sulphuric acid, chloroacetylchloride and sodium hypochlorite and sodium hydroxide gave the corresponding dihydropyrimidine 4, triazolethiazine 5, 1,3,4-thiadiazole 6, 1,3-thiazole 7 and 1,2,4-thiadiazole 8, respectively. The reactivity of isoniazid 1 towards ammonium thiocyanate, cyclohexanone and acetophenone to give 1,2,4-triazole thione 10, hydrazones 9 and 12 was studied. Treatment of hydrazones 9 and 12 with carbon disulfide and aryl isothiocyanates gave 1,3,4-thiadiazolidine 11 and 1,2,4-triazole thione derivatives 13a, b. The antimicrobial activity of these new compounds has been evaluated against 6 microbial strains. Some of the newly synthesized compounds showed a moderate activity.

New series of 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine thione (THTT) derivatives: Synthesis and potent antileishmanial activity

Four series of heterocyclic compounds, namely, tetrahydro-2H-1,3,5-thiadiazine thione derivatives were synthesized in good to excellent yields and were screened for their in vitro antileishmanial activities against Leishmania major (promastigotes). Most of the compounds showed significant antileishmanial activity within the range of IC50 = 15.48–39.36 μM when compared with standard pentamidine (IC50 = 14.95 μM). The structure-activity relationship showed that N-3 and N-5 substituents have a key role against leishmanicidal activity. The ester analogues (series B) were found to have a 1.5 to 5-fold reduced activity compared to their acidic counterparts. Cytotoxicity against mammalian mouse fibroblast 3 T3 cells was also evaluated and compared between the acid and its ester analogue. The reduction of antileishmanial activity and loss of toxicity in the newly developed THTT ester derivative indicates that these compounds can be used as a template study for the production of effective antileishmanial ester prodrugs.

Iodine-Catalyzed Chemoselective C-N Bond-Forming Reactions Using Benzylic or Cinnamyl Alcohols with Heterocyclic Thiols and Thiones.

A chemoselective formation of C-N bond catalyzed by iodine has been developed using heterocyclic thiols and thiones. The reaction occurs at the nitrogen center over the sulfur, leading to the amination against the traditional sulfenylation. A wide variety of allylic and benzylic alcohols serve as coupling partners. This method showed a good tolerance toward 1 H-tetrazole-5-thiol, 5-methyl-1,3,4-thiadiazole-2-thiol, benzo[ d]thiazole-2(3 H)-thione, and benzo[ d]oxazole-2(3 H)-thione derivatives.

Cover: Journal of the Chinese Chemical Society 7/2018

Novel coumarinyl–1,3–thiazin–2–thione derivatives were efficiently synthesized via multi–component reaction of 3 –chloro–3–(2–oxo–2H–chromen–3–yl)acrylaldehyde,carbon disulfide and amines. All the derivatives were screened for their anti‐proliferative activity against several cancer cell lines. The molecular docking study and ADME profile were also performed to explore the binding interaction of these coumarinyl–1,3–thiazin–2–thione analogues with Hsp100 proteins. More details will be discussed by Dr. Santhosh Penta and his co‐workers on page 811–821 in this issue. image

Facile synthesis and characterization of novel pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one and pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine incorporating 1,3-diarylpyrazole moiety

4-(3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-6-phenyl-2-thioxo-1,2-di hydro-pyridine-3-carbonitrile (1) reacted with ethyl chloroacetate (2) in ethanolic sodium acetate solution to yield the corresponding ethyl (3-cyanopyridin-2-ylsulphanyl)acetate derivative 3. Intramolecular cyclization of compound 3 was achieved by its heating in DMF containing potassium carbonate to afford the corresponding ethyl 3-aminothieno[2,3-b]pyridine-2-carboxylate derivative 4 which reacted with hydrazine hydrate in refluxing pyridine to yield the starting material 3-aminothieno[2,3-b]pyridine-2-carbohydrazide derivative 7. Compound 7 reacted with different reagents such as triethylorthoformate, formic acid, acetic acid and acetic anhydride to afford the target molecules pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives 8–10, 12 and 13 in good to excellent yields. On the other hand, pyridine-2(1H)-thione derivative 1 reacted with hydrazine hydrate in refluxing pyridine to give the other starting material 3-amino-1H-pyrazolo[3,4-b]pyridine derivative 20 which reacted with acetylacetone under reflux to afford the target molecule pyrido[2′,3′:3,4]pyrazolo[1,5-a]-pyrimidine derivative 21 in a good yield. The structures of target molecules were elucidated using elemental analyses and spectral data.

Facile synthesis and characterization of novel bis(2-S-alkylpyridines) and bis(3-aminothieno[2,3-b]pyridines) incorporating 1,3-diarylpyrazole moiety

ABSTRACT3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (1) is condensed with acetophenone to afford the corresponding unsaturated carbonyl compound 4 whose potassium salt is reacted with 1,4-dibromobutane to afford the bis-unsaturated carbonyl compound 3. Both carbonyl compounds 3 and 4 are reacted with 2-cyanoethanethioamide, through Michael addition reaction followed by cyclocondensation, to prepare the starting materials bis(pyridine-2(1H)-thione) derivative 5 and pyridine-2(1H)-thione derivative 8. Two synthetic routes to synthesize the target materials 7 and 14 are described to get the most efficient method for preparation and maximum yield%. The first route came from the direct alkylation of the bis(pyridine-2(1H)-thione) derivative 5 using iodomethane (6a) and benzyl chloride (6b) to afford the corresponding bis(2-S-alkylpyridine) derivatives 7a,b. The reaction of 5 with halo-containing compounds 10a–d to synthesize the target materials bis(3-aminothieno[2,3-b]pyridine) derivatives 14a–d failed under various reaction conditions. The second route involves the reaction of pyridine-2(1H)-thione derivative 8 with 6a,b and 10a–d to afford the corresponding 2-S-alkylpyridine derivatives 9a,b and 3-aminothieno[2,3-b]pyridine derivatives 13a–d, through the formation of 2-S-alkylpyridine derivatives 12a–d followed by a Thrope-Ziegler reaction, whose potassium salts reacted with 1,4-dibromobutane to afford the corresponding target materials 7a,b and 14a–d, respectively. The structures of target molecules were elucidated using elemental analyses and spectral data.

Synthesis and anticancer activity of novel quinazolinone and benzamide derivatives

In trying to develop new anticancer agents, a series of quinazolinone and benzamide derivatives were synthesized via reaction of 6-iodo-2-phenyl-4H-benzoxazin-4-one with nitrogen nucleophiles, namely, formamide, ammonium acetate, hydrazine hydrate, hydroxylamine hydrochloride, substituted aromatic amines, benzyl amine, and/or thiocarbonohydrazide. All compounds were fully characterized by means of IR, MS, and 1H-NMR spectra. Some of the synthesized compounds were evaluated in vitro for their anti-proliferative activity against HePG-2 and MCF-7 cell lines. 2-(Benzoylamino)-N-(4-hydroxyphenyl)-5-iodobenzamide and tetrazino[1,6-c]quinazoline-3(4H)-thione derivative were the most potent against the two cancer cells comparable to that of doxorubicin. Most of the synthesized compounds also exhibited good cytotoxic activity.

One-Pot Synthesis of 3,4-Dihydropyrimidine-2(1H)-thione Derivatives Using DBU as Green and Recyclable Catalyst

One-Pot Synthesis of 3,4-Dihydropyrimidine-2(1H)-thione Derivatives Using DBU as Green and Recyclable Catalyst

Synthesis of 4-Arylisoquinoline-1(2H)-thione Derivatives by Sodium Hydride-Mediated Cyclizations of 2-(1-Arylethenyl)benzothioamides

Synthesis of 4-Arylisoquinoline-1(2H)-thione Derivatives by Sodium Hydride-Mediated Cyclizations of 2-(1-Arylethenyl)benzothioamides

Base-mediated one-pot synthesis of 3,4,5,6-tetrahydro-4-substituted benzo[h]quinazoline-2(1H)-thione derivatives and evaluation of their antioxidant activity

ABSTRACTOne-pot three-component Beginelli-like reactions of a ketone 1, an aryl aldehyde 2, and thiourea 3 in the presence of sodium hydroxide are described. In this reaction, 3,4,5,6-tertrahydro-4-substituted quinazoline-2(1H)-thione derivatives 4a–h were obtained in good yields (73–85%). The compound 4a has been characterized by single crystal X-ray analysis. All the synthesized compounds 4a–h and 5a–b were screened for their in vitro antioxidant activity. Compounds 4c, 4e, and 4h have exhibited an excellent than the standard ascorbic acid. Compounds 4d, 4f, and 4g have also shown good activity. Remaining compounds show moderate antioxidant activity.

Fe+3-montmorillonite K10: As an effective and reusable catalyst for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones and –thiones

In this study, a novel, clean, convenient, appropriate and environmentally benign route to dihydropyrimidinone and thione derivatives has been developed using the reaction between various benzaldehydes, urea or thiourea, and ethyl acetoacetate in the presence of Fe +3 -montmorillonite K10 under grind condition. The present methodology has several advantages such as simple work-up, solvent-free conditions, environmental friendliness and shorter reaction time along with high yields. Several aromatic aldehydes carrying either electron-releasing or electron-withdrawing substituents in the ortho and para positions were tested in this reaction. Another important feature of this procedure is the survival of a variety of functional groups under the reaction conditions. All of synthesized compounds were characterized by IR, 1 HNMR, 13 CNMR and elemental analyses. KEY WORDS : Grinding, K10, Urea, Thiourea, Ethyl acetoacetate, Biginelli reaction Bull. Chem. Soc. Ethiop. 2017 , 31(2), 313-321. DOI: http://dx.doi.org/10.4314/bcse.v31i2.12

Graph Theoretical Analysis, Insilico Modeling, Design and Synthesis of Biologically Active Pyrimidines and Quinazolines as Antimicrobial and Antitubercular Agent

Backround: Twenty four 4-(4-substituted phenyl)-6-(furan-2-yl)-3,4-dihydro pyrimidin- 2(1H)-one,4-(4-substituted phenyl)-6-(furan-2-yl)-3,4-dihydro pyrimidin-2(1H)-thione and 4-substituted phenyl-3,4,5,6,7,8-hexa hydro quinazolin-2(1H)-one, 4-substituted phenyl-3,4,5,6,7,8-hexa hydro quinazoline-2(1H)-thione derivatives were constitute attractive targets for the development of active antimicrobial as well as antimycobacterial agent. Keywords: AntiTB, graph theoretical analysis, microbial pathogenic strains, pyrimidines, quinazolines.