Reactions of 1,2,5‐thiadiazole 1,1‐dioxide derivatives with nitrogen nucleophiles. Part IV. Addition of α‐diamines

α‐diamines, such as ethylendiamine and o‐phenylendiamine, add to 3,4‐aryl‐disubstituted 1,2,5‐thiadiazole 1,1‐dioxides to give dihydropyrazines or quinoxalines, respectively and sulfamide. The new compound acenaphtho [5,6‐b]‐2,3‐dihydropyrazine was synthesized and characterized. The addition of ethylendiamine to 3,4‐diphenyl‐ 1,2,5‐thiadiazoline 1,1‐dioxide gives 3,4‐disubstituted thiadiazolidine 1,1‐dioxide, dihydropyrazines, or pyrazines, depending on the reaction condition used. The reactions were followed by cyclic voltammetry and NMR spectroscopy which, in some cases, allowed the detection of the thiadiazolidine intermediate. Copyright © 2008 John Wiley & Sons, Ltd.     

5-Phenyl-2-(pyrazol-4-yl)-1,3,4-thiadiazoles

By recyclization of 2-R-6-ethyl-7-hydroxy(methoxy)-3-(5-phenyl-1,3,4-thiadiazol-2-yl)chromones when treated with hydrazine hydrate and phenylhydrazine, we synthesized 5-phenyl-2-(3-R-5-R1-1H-pyrazol-4-yl)-1H-1,3,4-thiadiazoles and 2-(3-R-5-R1-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1H-1,3,4-thiadiazoles. We confirmed the structure of the latter from ¹H NMR spectra.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 781–787, May, 2005.     

Multinuclear magnetic resonance studies of 2‐aryl‐1,3,4‐thiadiazoles

The ¹H, ¹³C and ¹⁵N spectra of aryl‐substituted 1,3,4‐thiadiazoles were recorded. The results obtained were correlated with Hammett coefficients. The experimental results were compared with DFT‐calculated chemical shifts. The results obtained were compared with those for 1,3,4‐oxadiazoles and 1,3,4‐selenadiazoles. Copyright © 2012 John Wiley & Sons, Ltd.     

Microwave‐Promoted Efficient Synthesis of 3‐(5‐Arylfuran‐2‐yl)‐6‐aryl/aryloxymethylene‐1,2,4‐s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles

A simple, rapid, and efficient method for the synthesis of substituted 1,2,4‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles under microwave irradiation conditions is reported, and a series of 3‐(5′‐aryl‐2′‐furyl)‐6‐aryl/aryloxymethylene‐1,2,4‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles was synthesized via this method.     

Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells

A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ_25-35-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ_25-35-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ_25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ_25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.     

Different patterns of supramolecular assembly in constitutionally similar 6‐arylimidazo[2,1‐b][1,3,4]thiadiazoles

Four imidazo[2,1‐b][1,3,4]thiadiazoles containing a simply‐substituted 6‐aryl group have been synthesized by reaction of 2‐amino‐1,3,4‐thiadiazoles with bromoacetylarenes using microwave irradiation and brief reaction times. 6‐(2‐Chlorophenyl)imidazo[2,1‐b][1,3,4]thiadiazole, C₁₀H₆ClN₃S, (I), 6‐(2‐chlorophenyl)‐2‐methylimidazo[2,1‐b][1,3,4]thiadiazole, C₁₁H₈ClN₃S, (II), 6‐(3,4‐dichlorophenyl)imidazo[2,1‐b][1,3,4]thiadiazole, C₁₀H₅Cl₂N₃S, (III), and 6‐(4‐fluoro‐3‐methoxyphenyl)‐2‐methylimidazo[2,1‐b][1,3,4]thiadiazole, C₁₂H₁₀FN₃OS, (IV), crystallize with Z′ values of 2, 1, 1 and 2 respectively. The molecular skeletons are all nearly planar and the dihedral angles between the imidazole and aryl rings are 1.51 (8) and 7.28 (8)° in (I), 9.65 (7)° in (II), 10.44 (8)° in (III), and 1.05 (8) and 7.21 (8)° in (IV). The molecules in (I) are linked by three independent C—H...N hydrogen bonds to form ribbons containing alternating R₂²(8) and R₄⁴(18) rings, and these ribbons are linked into a three‐dimensional array by three independent π‐stacking interactions. Both (II) and (III) contain centrosymmetric dimers formed by π‐stacking interactions but hydrogen bonds are absent, and the molecules of (IV) are linked into centrosymmetric R₂²(8) dimers by C—H...N hydrogen bonds. Comparisons are made with a number of related compounds.     

A Simple and Convenient Method for the Synthesis of 3,5‐disubstituted 1,2,4‐thiadiazoles via Oxidative Dimerization of Primary Thioamides

A simple and efficient protocol has been developed for the preparation of 3,5‐diaryl‐1,2,4‐thiadiazoles in high yields through the oxidative dimerization of primary thioamides in aqueous medium at room temperature.     

Radical anions containing the dioxidated 1,2,5‐thiadiazole heterocycle

Radical anions of 3,4‐aryl disubstituted 1,2,5‐thiadiazole 1,1‐dioxide were obtained by chemical and electrochemical reduction of their substrates, and characterized by ESR spectroscopy and cyclic voltammetry. The radical anion of the phenanthro[9,10‐c]‐1,2,5‐thiadiazole 1,1‐dioxide was found to be very stable in an aprotic solvent solution and did not react readily when water was added to the aprotic solvent, or the solution was saturated with oxygen gas. The radical formation chemical reaction competed with nucleophilic addition to the C?N bond of the thiadiazoles. A possible reaction mechanism, and a common reaction intermediate, supported by density functional theory calculations, is presented for the most stable radical. Copyright © 2009 John Wiley & Sons, Ltd.     

均三唑并噻二唑衍生物的微波合成

在无溶剂无催化剂微波辐射下,羧酸与1,3-二氨基硫脲快速反应高产率得到了3-取代基-4-氨基-5-巯基-1,2,4-三唑,该化合物与苯甲酰氯在无溶剂无催化剂微波促进下可以方便地制备化合物3-取代基-6-苯基-1,2,4-三唑[3,4-b][1,3,4]噻二唑。该方法具有反应时间短、环境友好、易于纯化及高产率的优点。产物结构经IR和1HNMR谱进行了表征。     

新型含噻二唑环的二茂铁衍生物的合成与电化学性质研究

Three novel thiadiazolo-ferrocence derivatives containing long chain alkyl group were synthesized and characterized. The voltammetric behaviour of these thiadaizolo-ferrocene derivatives was studied on gold electrode (diameter 1 mm) in CH2Cl2/0.2 mol/L tetra-n-butylammonium hexafluorophosphate. The influence of β-cyclodextrinon the voltammetric behaviour of the compounds was also studied.