A challenging synthesis of new 1,3,4‐thiadiazole derivatives starting from 2‐acylamino‐3,3‐dichloroacrylonitriles

Available 2‐acylamino‐3,3‐dichloroacrylonitriles, when treated with hydrazine hydrate, provide 2‐alkyl‐ or 2‐aryl‐5‐hydrazino‐1,3‐oxazole‐4‐carbonitriles that readily add alkyl or aryl isothiocyanates and the adducts formed recyclize on heating. Finally, the synthesis results in 5‐alkyl(aryl)amino‐1,3,4‐thiadiazol‐2‐yl(acylamino)acetonitriles or the products of their further cyclization, 2‐(5‐amino‐1,3‐ oxazol‐2‐yl)‐1,3,4‐thiadiazole derivatives. The structures of the novel substituted 1,3,4‐thiadiazoles are corroborated spectroscopically as well as by X‐ray diffraction method. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:454–458, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20041     

Synthesis of some furo‐thiazolidine derivatives starting from aldimines

Alkyl and aryl substituted furothiazolidine derivatives have been synthesized by the reaction of Wittig reagent with benzylidene derivatives of 4‐thiazolidinones obtained from aldimines and thioglicolic acid.     

Stereoselective Solvent‐Free Synthesis of 4‐Hydroxy‐1,3‐thiazinane‐2‐thiones

An efficient solvent‐free one‐pot stereoselective synthesis of 4‐hydroxy‐1,3‐thiazinane‐2‐thione derivatives from the reaction of primary amines and carbon disulfide in the presence of α,β‐unsaturated aldehydes has been reported. The 4‐hydroxy‐1,3‐thiazinane‐2‐thione derivatives were easily converted to the related dehydrated or acetylated products.     

Synthesis of novel 1‐substituted [1,3]thiazolo[3,2‐a]‐[1,5]benzodiazepine derivatives from 1,5‐benzodiazepine‐2‐thiones and α‐halogen carbonyl compounds

A number of substituted 4H,5H,6H‐thiazolo[3,2‐a][1,5]benzodiazepinium salts 2a‐h, 5, 9 , which are based on the novel thiazolobenzodiazepine system, were prepared by condensation‐cyclization of 1,5‐benzodiazepine‐2‐thiones 1a‐f, h, 4 with α‐haloketones, as well as with α‐bromoacetaldehyde diethyl acetal. The structure and stereochemistry of the ring system obtained were investigated by ¹H and ¹³C nmr spectroscopy: the additional heterocyclic nucleus was found to appreciably influence the conformational mobility of the heptatomic ring. Upon treatment of salt 2d with alkali the presence of the base enamine structure in solution has been postulated.     

Diastereoselective Synthesis of Functionalized Tetrahydropyrimidin‐2‐thiones via ZnCl2 Promoted One‐pot Reactions

In the presence of zinc chloride, the in situ generated β‐enamino ester from the reaction of morpholine, piperidine and pyrrolidine with methyl propiolate reacted, with aromatic aldehydes and thiourea in ethanol resulting in the functionalized tetrahydropyrimidin‐2‐thiones in satisfactory yields and with good diastereoselectivity. When aromatic aldehydes bearing electron‐withdrawing group were used in the reaction, the 4‐hydroxytetrahydropyrimidin‐2‐thione derivatives were obtained as the main product.     

Synthesis of 2‐phosphinoxidomethyl‐ and 2‐phosphonomethyl glutaric acid derivatives

Michael addition of the corresponding anions derived from diphenylphosphine oxide, dialkylphosphites, and a cyclic phosphite to α‐methylene‐glutaric esters ( 1 ) afforded the title compounds ( 2–6 ). Double debenzylation of 2‐phosphono glutaric esters 4b and 5a by catalytic hydrogenation under the appropriate conditions gave the correspon‐ ding diacides 8 and 9 , respectively. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:562–565, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20142     

Synthesis,Crystal Structure and Anticancer Activities of Tetrahydropyrido[4,3‐d]dihydropyrimidine‐2‐thiones

A new series of tetrahydropyrido[4,3‐d]dihydropyrimidine‐2‐thiones ( 3a–3x ) were designed and synthesized. Their structures were confirmed by ¹H NMR, IR, MS and elemental analysis, and the conformation of compound 3j was confirmed by X‐ray diffraction. Preliminary bioassays indicated that most of the target compounds presented good antiproliferative activities against leukemic K562 cells, ovarian cancer HO‐8910 cells and liver cancer SMMC‐7721 cells in vitro. Among them the compounds 3i and 3m afford the best activity, the IC₅₀ of them were 3.22 and 3.65 µg/mL against leukemic K562 cells, respectively, which were lower than the anticancer drug of clinical practice 5‐FU (IC₅₀=8.56 µg/mL). Preliminary mechanism of action studies revealed that compound 3i caused DNA fragmentation and activated caspase‐3/7 in leukemic K562 cells.     

GIAO/DFT studies on 1,2,4‐triazole‐5‐thiones and their propargyl derivatives

Density functional theory (DFT)/Becke–Lee–Yang–Parr (B3LYP) and gauge‐including atomic orbital (GIAO) calculations were performed on a number of 1,2,4‐triazole derivatives, and the optimized structural parameters were employed to ascertain the nature of their predominant tautomers. ¹³C and ¹⁵N NMR chemical shifts of 3‐substituted 1,2,4‐triazole‐5‐thiones and their propargylated derivatives were calculated via GIAO/DFT approach at the B3LYP level of theory with geometry optimization using a 6‐311++G** basis set. A good agreement between theoretical and experimental ¹³C and ¹⁵N NMR chemical shifts could be found for the systems investigated. The data generated were useful in predicting ¹⁵N chemical shifts of all the nitrogen atoms of the triazole ring, some of which could not be obtained in solution state ¹⁵N HMBC/HSQC NMR measurements. The energy profile computed for the dipropargylated derivatives was found to follow the product distribution profile of regioisomers formed during propargylation of 1,2,4‐triazole thiones. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of Tetrahydrothiopyrano[2,3‐b]indole [60]Fullerene Derivatives via Hetero‐Diels–Alder Reaction of C60 and α,β‐Unsaturated Indole‐2‐thiones

Hetero‐Diels–Alder reactions of [60]fullerene with α,β‐unsaturated thio‐oxindoles ( 3a , 3b , 3c ), prepared from thio‐oxindole 1 and heteroaromatic aldehydes ( 2a , 2b , 2c ), to generate tetrahydrothiopyrano[2,3‐b ]indole [60]fullerene cycloadducts ( 5a , 5b , 5c ) under thermal or microwave irradiation were described. The yields were improved, and the reaction time was decreased by conducting the reaction under microwave irradiation.     

Synthesis,in vitro urease inhibitory activity and molecular docking of 3,5‐disubstituted thiadiazine‐2‐thiones

A series of 3,5‐disubstituted‐tetrahydro‐thiadiazine‐2‐thione ( 1 ‐ 16 ) have been synthesized, characterized by elemental analysis, infrared (IR), UV‐visible, ¹H NMR, ¹³C NMR, and MS spectroscopic techniques, and screened against jack bean urease. Among 16 compounds, compounds ( 1 ), ( 2 ), ( 3 ), ( 4 ), ( 6 ), ( 7 ), and ( 9 ) demonstrated excellent urease inhibitory activity with IC₅₀ values (9.8 ± 0.5, 11.0 ± 0.6, 16.0 ± 1.5, 17.2 ± 0.5, 15.4 ± 0.5, 19.7 ± 0.4, and 15.8 ± 0.2μM), respectively, even better than the standard thiourea (IC₅₀ = 21 ± 0.01μM). However, compound ( 8 ) shows an almost same level of inhibition (IC₅₀ = 22.9 ± 0.3μM), as like standard. In this work, we reported for the first time urease inhibitory activity of thiadiazine thiones and its molecular docking studies.     

5‐Fluoro­indoline‐2,3‐dione

In the title compound (5‐fluoro­isatin), C₈H₄FNO₂, the N atom of one mol­ecule is linked to the amido‐O atom of an adjacent mol­ecule across a center of symmetry by a cyclic hydrogen bond [N?O = 2.888 (4) Å].     

Synthesis of novel 2‐amino‐6,8‐dithioxopurine derivatives

The synthesis of novel 2‐amino‐9‐alkoxyalkylpurine derivatives with both identical and different sulfur containing substituents at positions 6 and 8 of the purine cycle has been accomplished. The thionation and alkylation of the key intermediate ‐ 2‐[2‐(acetylamino)‐6,8‐dichloro‐9H‐purin‐9‐yl]methoxyethyl acetate or its reactions with thiolates were used. The structures of compounds obtained were confirmed by spectroscopic data and X‐ray diffraction analysis.     

Synthesis of some 3‐aryl‐1H‐isochromene‐1‐thiones

A rapid microwave‐accelerated thionation of some 3‐substitued isocoumarins to corresponding 1‐thio‐isocoumarins was achieved employing Lawesson's reagent under solventless conditions.     

Synthesis of 1,2,4‐triazolo[1,5‐d]‐1,2,4‐triazine‐5‐thiones

In an attempt to discover bicyclic compounds containing the 1,2,4‐triazine moiety, 1,2,4‐triazolo[1,5‐d]‐1,2,4‐triazine‐5‐thiones from one pot reaction of arylnitriles with 4‐amino‐1,2,4‐triazine‐3‐thione‐5‐one in the presence of potassium tert‐butoxide were synthesized.     

Synthesis of N-alkyl derivatives of 4-(2′-aminoethyl)indole

N-Substituted 4-(2′-aminoethyl)indoles are attainable in good yields from indole-4-acetic acid ( 2 ). Several methods of preparation for 2 were tried or considered. A new sequence involving Arndt-Eistert homologation of indole-4-carboxylic acid has been devised, which is no more laborious than a literature homologation sequence involving indole-4-acetonitrile, and which provides somewhat better overall yields than the literature method.     

Synthesis of glycosyl esters from phosphoroates derivatives of 2‐bromosugars

This work presents the synthesis of glycosyl esters of 2‐bromo‐2‐deoxy‐D ‐hexopyranose, having the α‐D ‐manno ( 10a–cα ), β‐D ‐gluco ( 11a–dβ ) and α‐D ‐gluco ( 11a,bα ) configuration, by a stereoselective reaction between phosphoroates 3–8 and carboxylic acids 9a–d. Derivatives of 10a–c and 11a–d are formed in an overall quantitative yield, in an aprotic solvent in the presence of silver salts as a leaving group activator. The phosphoroselenoate of 3 was obtained by the condensation reaction of the triethylammonium salt of phosphoroseleno acid 2 with α‐1,2‐D ‐manno‐pyranosyl dibromide 1 with high stereoselectivity. The structures of the compounds 3,10a–c and 11a–d were established by ¹H and ¹³C NMR spectra and by elemental analyses. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:292–298, 2000     

New Pyrimidine‐2‐thiones from Reactions of Amidrazonethiols with 2‐Amino‐1,1,2‐ethenetricarbonitrile and Investigation of Their Antitumor Activity

Reactions of thiosemicarbazones with 2‐amino‐1,1,2‐ethenetricarbonitrile were reported. The reaction occurred in the amidrazonyl site, and new pyrimidine‐2‐thiones were obtained. The reaction mechanism was discussed. The structure of products was elucidated by MS, IR, and NMR spectra together with elemental analyses. The antitumor activity was evaluated against one tumor cell line. Using a standard MTT assay, the effect of the samples on the growth of HepG2 cells was investigated. Half of these compounds showed no cytotoxic effect on HepG2 cells, while the others result in decreasing in the HepG2 cell viability.