- Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
-
Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine-or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
- Bai, Feifei,Fang, Jianguo,Song, Zi-Long,Zhang, Baoxin
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p. 2214 - 2231
(2020/03/06)
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- Method for synthesizing 1,2-disulfide-3-thioketone derivative by using copper to catalyze
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The invention relates to a method for synthesizing 1,2-disulfide-3-thioketone derivative by copper-catalyzed propargylamine sulfur cyclization, and the method comprises the following steps: N, N-dimethyl-3-phenyl propyl-2-alkynyl-1-amine is taken as a substrate, cuprous chloride, cuprous bromide or cuprous iodide is added into the substrate to serve as a catalyst, potassium phosphate, sodium bicarbonate or sodium acetate is taken as an alkali, elemental sulfur is taken as a sulfur source, stirring reaction is performed in a solvent for 12 hours at the temperature of 100-120 DEG C. The elemental sulfur is used as the sulfur source, and the method has the advantages of simple and easily available raw materials, simple reaction operation, relatively mild conditions, wide substrate universality, relatively high yield and good functional group compatibility.
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Paragraph 0014; 0031-0042
(2019/06/12)
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- Copper-Catalyzed Tandem Sulfuration/Annulation of Propargylamines with Sulfur via C-N Bond Cleavage
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Copper-catalyzed aerobic oxidative sulfuration and annulation of propargylamines with elemental sulfur is described. The tandem reaction involves C-N bond cleavage and the formation of multiple C-S bonds, affording 1,2-dithiole-3-thiones in good to excellent yields with good functional group tolerance.
- Xu, Hong-Hui,Zhang, Xiao-Hong,Zhang, Xing-Guo
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p. 7894 - 7900
(2019/06/27)
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- 1,2-dithio-3-thioketone derivative synthesized by cyclizing of fluorine-sulfur removal of trifluoropropyne via copper catalyzing
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The invention discloses a 1,2-dithio-3-thioketone derivative synthesized by cyclizing of fluorine-sulfur removal of trifluoropropyne via copper catalyzing. The 1,2-dithio-3-thioketone derivative is prepared by the following steps of using a 2-chloro-3,3,3-trifluoro-1 propene compound as a primer; adding cuprous bromide as a catalyst into the primer, using cesium carbonate as alkaline, using tetramethylethylenediamine as a ligand, using elemental sulfur as a sulfur source, and stirring to react for 12 hours in a N,N-dimethyl formamide solvent at the temperature of 120 DEG C; after reaction is finished, filtering a reaction liquid, extracting a filtrate twice by a saturated sodium chloride solution, reversely extracting once, separating to obtain an organic phase, and drying with anhydrous sodium sulfate; filtering again, and removing the solvent out of the filtrate by a rotary evaporator, so as to obtain the remaining matter; performing column chromatography separating on the remainingmatter by a silicon gel column, spraying by an elution solution, and collecting an effluent solution containing the target product; combining the effluent solution, concentrating under the vacuum condition, and removing the solvent, so as to obtain the target product. The 1,2-dithio-3-thioketone derivative has the advantages that the raw materials are simple and are easy to obtain, the preparationtechnology is novel and simple, the pollution is little, the energy consumption is low, and the yield rate is high.
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-
Paragraph 0023; 0044-0058
(2018/11/03)
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- Copper-Catalyzed Defluorinative Thioannulation of Trifluoropropynes for the Synthesis of 1,2-Dithiole-3-thiones
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A simple and practical strategy for the preparation of 1,2-dithiole-3-thiones via copper-catalyzed defluorinative thioannulation of trifluoropropynes has been developed using elemental sulfur as the sole sulfur source. This reaction displays a wide substrate scope and high functional group tolerance to afford the corresponding S-heterocycles in moderate to good yields and features efficient construction of multiple C?S bonds through C?F bond cleavage of CF3 groups. (Figure presented.).
- Wei, Feng,Shen, Xiao-Qin,Zhang, Xiao-Hong,Zhang, Xing-Guo
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p. 3911 - 3915
(2018/09/21)
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- Switching Selectivity of α-Enolic Dithioesters: One Pot Access to Functionalized 1,2- and 1,3-Dithioles
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An operationally simple cascade protocol has been developed for the construction of 1,2- and 1,3-dithiole derivatives from α-enolic dithioesters. 1,2-Dithioles are achieved by the reaction of dithioesters with elemental sulfur in the presence of InCl3 under solvent-free conditions. 1,3-Dithioles have been constructed via DABCO mediated self-coupling of dithioesters in open air enabling the formation of two new C-S bonds and one ring in a single operation in contiguous fashion. The reactions proceeded smoothly affording the desired sulfur-rich heterocycles in good to excellent yields, exhibiting gram-scale ability and broad functional group tolerance utilizing easy to handle cheap and easily available reagents. The probable mechanisms for the formation of 1,2- and 1,3-dithioles from α-enolic dithioesters have been suggested.
- Koley, Suvajit,Chanda, Tanmoy,Samai, Subhasis,Singh, Maya Shankar
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p. 11594 - 11602
(2016/12/09)
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- 3H-1,2-DITHIOCYCLOPENTENE-3-THIOKETONE COMPOUNDS AND APPLICATION THEREOF
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The present invention relates to the field of medicaments, and in particular relates to 3H-1,2-dithiocyclopentene-3-thione compounds and application thereof. 3H-1,2-dithiocyclopentene-3-thione compounds disclosed by the invention have new structures shown in formula I or formula II. Proved by experiments, 3H-1,2-dithiocyclopentene-3-thione compounds can directly protect neurons in a cellular model, and can significantly restrain excessive inflammatory responses of brain inflammatory cells; and by using 3H-1,2-dithiocyclopentene-3-thione, focal ischemic cerebral infarct volumes of mice can be remarkably reduced in an animal model. Therefore, the invention provides the application of 3H-1,2-dithiocyclopentene-3-thione compounds and pharmaceutically acceptable salts thereof in the preparation of medicaments for preventing or treating cerebral apoplexy diseases.
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-
Paragraph 0029; 0037
(2015/07/15)
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- Convenient one-pot syntheses of 1,2-dithiole-3-thiones and 3-imino-1,2-dithioles from terminal alkynes
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The reaction of acetylide anions with carbon disulfide or phenyl isothiocyanate followed by addition of sulfur in the presence of a protonating agent such as a primary amine or alcohol affords 1,2-dithiole-3-thiones or 3-imino-1,2-dithioles in good to excellent yields.
- Adams, Harry,Hughes, Amelia J.,Morris, Michael J.,Quenby, Sophia I.A.
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p. 5283 - 5285
(2015/02/02)
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- Formation of 5-phenyl-1,2-dithiole-3-thione from molybdenum dithiopropiolato complexes
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Molybdenum dithiopropiolato complexes, [(η5-C5 R4R′)Mo(CO)2(η2 -S2CC≡CPh)] (R=H, R′=Me 1a, R=R′=H 1b; R=R′=Me 1c) react with trimethylamine- N -oxide (TMNO · 2H2O) under mild the
- Mathur, Pradeep,Avasare, Vidya D.,Ghosh, Abhijit K.,Mobin, Shaikh M.
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p. 1325 - 1327
(2007/10/03)
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- Thionation with the reagent combination of phosphorus pentasulfide and hexamethyldisiloxane
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The combination of P4S10 and hexamethyldisiloxane efficiently converts esters, lactones, amides, lactams, and ketones to their corresponding thiono derivatives. In the presence of elemental sulfur, 3-oxoesters are converted to dithiolethiones by this reagent. Yields are comparable to or superior to those obtained with Lawesson's reagent. The method has the advantage that reagent-derived byproducts may be removed by a simple hydrolytic workup or by filtration through silica gel, rather than by chromatography, as required for Lawesson's reagent.
- Curphey, Thomas J.
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p. 6461 - 6473
(2007/10/03)
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- A superior procedure for the conversion of 3-oxoesters to 3H-1,2-dithiole-3-thiones
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The combination of P4S10, sulfur, and hexamethyldisiloxane converts 3-oxoesters to 3H-1,2-dithiole-3-thiones in yields generally superior to those obtained with Lawesson's reagent and without the need for chromatography to remove large amounts of phosphorous-containing byproducts. (C) 2000 Elsevier Science Ltd.
- Curphey
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p. 9963 - 9966
(2007/10/03)
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- Dianions of 3-oxodithioic acids: Preparation and conversion to 3H-1,2-dithiole-3-thiones
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Reaction of ketones with CS2 and 2 equivalents of KH in THF-N,N'-dimethylpropyleneurea solution produces the dianions of 3-oxodithioic acids. These dianions are converted in good yield to 3H-1,2-dithiole-3-thiones by the sequential action of hexamethyldisilathiane and an oxidizing agent such as hexachloroethane. (C) 2000 Elsevier Science Ltd.
- Curphey,Libby
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p. 6977 - 6980
(2007/10/03)
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- A facile and convenient synthesis of 3-alkylamino-5-arylthiophenes with a variety of substituents at C-2 and studies of reaction mechanisms
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Thioaroylketene S,N-acetals were treated with active methylene compounds including β-keto ester, nitromethane, cyanoacetic acid, p- toluenesulfonylacetone, 4-nitrophenylacetic acid, and diethyl (2- oxopropyl)phosphonate in the presence of mercury(II) acetate in CH2Cl2 at room temperature. These reactions gave 3-alkylamino-5-arylthiophenes containing various substituents, which comprised, respectively, alkoxycarbonyl, nitro, cyano, p-toluenesulfonyl, 4-nitrophenyl, and diethylphosphono groups at C-2 in good yields. The reaction of 3-methylamino- 3-methylthio-1-phenylthioxopropene with malonic acid or Meldrum's acid under the same conditions gave 3-methylamino-5-phenylthiophene. Similarly, treatment of 3-methylamino-3-methylthio-1-phenylthioxopropene with various enolizable cyclic ketones such as 4-hydroxy-6-methyl-2-pyrone, homophthalic anhydride, 2-hydroxy1,4-benzoquinone, and 1,3-diethyl-2-thiobarbituric acid gave thieno[3,2-b]pyridin-4-one, thieno[3,2c]isoquinolin-5-one, thieno[3,2- c]benzazepine-1,6-dione, and thieno[3,2-d]pyrimidine-2,4-dione, respectively.
- Kim, Bo Sung,Kim, Kyongtae
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p. 3690 - 3699
(2007/10/03)
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- Sulfur-Containing Heterocycles Derived by Reaction of ω-Keto Amides with Lawesson's Reagent
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The reaction of ω-keto amides with Lawesson's reagent (LR: 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide) is described. Treatment of 3-keto amides (2-acylacetamides) 1 with LR gave the corresponding 3-keto thioamides 2, along with 1,2-dithiole-3-thiones 3. Treatment of 4-keto amides, 3-acyl propionamides 5, with LR yielded five-membered heterocycles, pyrroles 6 and/or 2-aminothiophenes 7. 5-Keto amides, 3-benzoyl butyramides 8, reacted with LR to give dihydrothiopyran-2-thione 9 as the sole product, but in low yield. 2-Acylbenzamides 10 also reacted with LR to afford 3-mercaptoisoindolin-2-ones 11 or dihydroisobenzothiophene-1-thiones 12.
- Nishio, Takehiko
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p. 1207 - 1214
(2007/10/03)
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- N2S2 tetradentate ligands for soft cationic species: preparation of new ligands of potential interest in nuclear medicine
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The synthesis of N2S2 tetradentate ligands of the bis-(enaminothioester) type was carried out starting from 3-(methylthio)-3H-1,2-dithiolylium iodides and diamines.The title compounds, which are potential ligands for soft cationic species, can be obtained from 1,3-diaminopropan-2-ol and subsequently modified into the dissymmetrical succinic acid ester of the ligand and N-hydroxysuccinimide.The appendage of such a linking group on the chelating structure should allow further grafting to monoclonal antibodies in view of potential applications in nuclear medicine. 3H-1,2-dithiole-3-thione / 1,3-diaminopropan-2-ol / bis-(enaminothioester) / N2S2 tetradentate ligand / N-hydroxysuccinimidyl ester
- Charbonnel-Jobic, Gaelle,Guemas, Jean-Pierre,Adelaere, Bruno,Parrain, Jean-Luc,Quintard, Jean-Paul
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p. 624 - 636
(2007/10/02)
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- ZUR UMSETZUNG VON ARYLMETHYLKETONEN MIT SCHWEFEL, SEKUNDAEREN AMINEN UND SCHWEFELDIOXID
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The acetophenones 2 react with different sulfurdioxide-secondary amine adducts 1 and sulfur to yield the red-coloured zwitterionic 2-imino-dithioacetates 3.Enamines can be proved to be intermediates in this reaction.Thus enamines 5 and other derivatives such as acetophenone anil, acetophenone diethyl acetal and diphenacyl sulfide also give 3.In the absence of 1, 3a react with hydrogen sulfide to form the thioamide of phenylacetic acid 8. Key words: 2-Iminio-dithioacetates; iminium salts; zwitterionic; SO2-secondary amin adducts; Willgerodt-Kindler-reaction; enamines; heptathiocanes.
- Matschiner, Hermann,Maschmeier, Claus-Peter,Maier, Nadja,Hansen, Jens
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p. 223 - 230
(2007/10/02)
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- A New Synthesis of 3H-1,2-Dithiole-3-thiones
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Exposure of 3-oxo dithioic acids to a solution of polysulfanes in liquid hydrogen sulfide gives 3H-1,2-dithiole-3-thiones in yields varying from poor to excellent.The method tolerates the presence of functional groups which are problematical for other met
- Curphey, Thomas J.,Joyner, H. Howard
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p. 3703 - 3706
(2007/10/02)
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- Synthesis of 3H-1,2-dithiole-3-thiones by a novel oxidative cyclization
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Reaction of 3-oxo dithioic acids with a combination of hexamethyldisilathiane and N-chlorosuccinimide in the presence of a catalytic amount of imidazole brings about oxidative ring closure to 3H-1,2-dithiole-3-thiones. Yields vary from poor to good.
- Curphey, Thomas J.,Joyner, H. Howard
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p. 7231 - 7234
(2007/10/02)
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- Use of carbon-sulfur cathodes in electro-organic chemistry - Part 2 - Reactions with activated alkenes; evidence for a vicarious substitution specific of this type of electrode.
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The sulfur-carbon electrode, used as a cathode, appears to be an excellent source of nucleophiles which are good sulfuration reagents towards alkenes not substituted by leaving groups.However, the electrochemical reactions are often complex.It should be w
- Guillanton, G. Le,Do, Q. T.,Simonet, J.
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p. 427 - 439
(2007/10/02)
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- Studies of Heterocyclic Compounds. Part 28. Condensation of 3-Substituted 5-Phenyl-1,2-dithiolylium Salts with 2-Amino-N-heterocycles
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3-Chloro-5-phenyl-1,2-dithiolylium chloride condenses in ethanol with 2-amino-N-heterocycles at the amino-group to yield yellow compounds; in many instances reaction occurs also at the ring nitrogen atom yielding orange compounds. 2-Amino-Δ2-thiazoline, 2-aminothiazole, 2-aminopyridine and its monomethyl derivatives, 2-amino-4,6-dimethylpyridine ,2-aminopyrimidine, and 2-aminobenzimidazole all underwent reaction at the amino-group to give the corresponding yellow 2-(5-phenyl-1,2-dithiol-3-ylidenamino)-N-heterocycles. 2-Amino-Δ2-thiazoline, 2-aminothiazole, 2-aminopyridine, 2-amino-3-methylpyridine, 2-amino-4-methylpyridine,and 2-amino-5-methylpyridine also underwent reaction at the ring nitrogen atom to give in low yield 4,5-dihydro-3-thiobenzoylmethylene-3H -thiazolothiadiazole, 3-thiobenzoylmethylene-3H-thiazolothiadiazole, and 3-thiobenzoylmethylene-3H-pyridothiadiazole and its 7-,6-,and 5-methyl derivatives, respectively,as polar orange compounds.The condensations of 3-methoxy-5-phenyl-1,2-dithiolylium fluorosulphonate with 2-amino-Δ2-thiazoline, 2-aminothiazole, and 2-amino-4-methylpyridine were studied.Condensation of 4-methyl-2-tricloromethylthioaminopyridine with benzoylacetic acid in dimethylformamide in the presence of triethylamine gave 6-methyl-3H-pyridothiadiazol-3-one (main prduct) and 6-methyl-3-benzoylmethylene-3H-pyridothiadiazole.Thionation of the latter with tetraphosphorous decasulphide in pyridine gave 6-methyl-3-thiobenzoylmethylene-3H-pyridothiadiazole.The results of 1H n.m.r. spectral studies, and of X-ray crystallographic studies by other workers, are discussed in relation to the structure of the yellow and the orange series of condesation products.It is proposed that the 3-thiobenzoylmethylene-3H-thiazolothiadiazoles and the 3-thiobenzoylmethylene-3H-pyridothiadiazoles, whose formation involves an S-S -> S-N bond switch, are formed via 3H-6,6aλ4-dithia-1,3-diazapentalenes which are higer energy intermediates or transition states. 3-Chloro-5-phenyl-1,2-dithiolylium chloride condensed with 2,6-diaminopyrimidine in a 2:1 ratio to give an orange and a polar red product for which structures are proposed.
- Mitchell, James A.,Reid, David H.
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p. 499 - 507
(2007/10/02)
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- UNSATURATED THIOLATES AND THEIR ANALOGS IN CYCLOADDITION REACTIONS VII. ALKALI-METAL SALTS OF 2-ARYLETHYNETELLUROL
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Salts of 2-arylethynetellurols were obtained by the reaction of alkali-metal arylacetylides with tellurium in dimethyl sulfoxide.Treatment of the products with an ether solution of hydrogen chloride led to 2,4-di (p-R-benzylidene)-1,3-ditelluranes, and treatment with water (or oxidation with iodine) led to di (2-arylethynyl)tellurides.Sodium 2-phenylethynetellurolate enters into a cyclization reaction with carbon bisulfide and dimethyl acetylenedicarboxylate.In the latter case nucleophilic addition products are formed.The initial product in the reaction of sodium 2-phenylethynetellurolate with dithylamine is the unstable N,N-diethylphenylthioacetamide.
- Laishev, V. Z.,Petrov, M. L.,Petrov, A. A.
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p. 1842 - 1847
(2007/10/02)
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- 1,1',2,2'-Tetrathiafulvalenes, II. - Thienothiophenes from 1,2-Dithiole Compounds; 3H-1,2-Dithiol-3-ylidenes (1,2-Dithiole-3-carbenes) as Supposed Intermediates
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3,3'-Bi(3H-1,2-dithiolylidenes) (1,1',2,2'-Tetrathiafulvalenes) 5 are not obtainable with the following reactions which, however, have proved to be a good approach to the corresponding 1,3-isomers 3: 1) Deprotonation of 1,2-dithiolylium cations 4, 2) pyrolysis of alkali derivatives from 1,2-dithiol-2-one tosylhydrazones 26 (Bamford-Stevens reaction), or 3) partial desulfuration of 1,2-dithiole-3-thiones 6 by means of trivalent phosphorus compounds.These reactions with the 1,2-isomers always yield thienothiophenes 8 accompanied by the related 1,2-dithiole-3-thiones 6 (1,2-trithiones) and in the case of 26 also by azines 27.Partial desulfuration of 1,2-trithiones 6 by copper bronze again yields the corresponding thienothiophenes 8 instead of 5.Thermal decomposition of the 1,2-dithiolylium iodide 34 or 34' yields the thienothiophene 8a together with the 1,2-trithione 6a.Surprisingly, the P4S10-sulfuration of "desaurines" 37 gives thienothiophenes again and also 1,2-dithiole-3-thiones 6. - 1-Morpholinocyclohexene (18) reacts with the 1,2-dithiolylium cation 4a (X = ClO4) to give a formal 1:1 adduct from the carbene 9a and the enamine for which the structure 19 is proposed.
- Behringer, Hans,Meinetsberger, Eike
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p. 1729 - 1750
(2007/10/02)
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- 1,1'2,2'-Tetrathiafulvalenes, III. - Syhthesis, Properties, and Reactions of 3,3'-Bi(3H-1,2-dithiolylidenes)(1,1',2,2'-Tetrathiafulvalenes)
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1,1',2,2'-tetrathiafulvalenes 1 can be prepared by different methods from the cations of 1,2-dithiolylium salts 4 which are either unsubstituted or appropriate substituted in 3-position (instead of 3-Cl also H or SCH3).The structure of 1 is substantiated by chemical arguments.IR and 13C-NMR spectra support the absence of thioxo groups. - Like the 1,1',3,3'-isomers 2 the 1,1',2,2'-tetrathiafulvalenes are disposed to stepwise donation of electrons with formation of the radical cation and dication salts 25 or 11, respectively, as well as to the formation of charge transfer complexes with tetracyanoethylene, tetracyanoquinodimethane, and 2,3-dichloro-5,6-dicyanobenzoquinone.Tris(triphenylphosphine)rhodium(I) chloride and tetrakis(triphenylphosphine)platinum(O) yield complexes with 1a. - Thermolysis of 1 produces thienothiophenes 6.Partial desulfuration of 1a, for example, is also feasible with oxidizing agents like lead(IV) acetate.Selenium dioxide, however, gives the corresponding thienofuran 41.The reaction with trialkyl phosphites yields a disulfide - probably the 2,2'-bi(2H-thietylidene) 38 - the thermolysis of which gives the thienothiophene 6a. - Compounds 1a and 1c do not react with dimethyl acetylenedicarboxylate, isothiocyanate, several 1,3-dipoles (azides), and also not with elementary sulfur, however, 1e forms with sulfur the 3H-1,2-dithiol-3-thione 5e (X = S).
- Behringer, Hans,Meinetsberger, Eike
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p. 1928 - 1959
(2007/10/02)
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- Method of preparing alkali metal complex compounds
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The invention includes novel alkali metal complex compounds (and processes for their preparation) which are useful, inter alia for the hydrogenation of alkali metals at room temperature or below room temperature to form hydrides or nitrides.
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