Tetrathiafulvalene. XIX. Synthese und Eigenschaften elektronenleitender Poly-Dithiolenkomplexe mit Ethylentetrathiolat und Tetrathiafulvalentetrathiolat als Brückenliganden

Tetrathiafulvalenes. XIX. Synthesis and Properties of Electron Conducting Poly-Dithiolene Complexes with Ethylene Tetrathiolat and Tetrathiafulvalene Tetrathiolat as Bridge Ligands [1,3]-Dithiolo[4,5-d]-1,3-dithiol-2,5-dione 7 and 5-(5-oxo[1,3]-dithiolo[4,5–d]1,3-dithiole-2-ylidene)[1,3]-dithiolo[4,5–d]1,3–dithiol-2-one 8 were synthesised from 1,3-dithiole-2-thione-4,5-dithiolat. The ligands react with salts of iron, cobalt, nickel, palladium, platinum and copper to give the polymer complexes 22a–g and 23a–e , respectively. Irradiation of 7 in the presence of iron penta-, dicobalt octa- or nickel tetracarbonyl gives the corresponding dithiolene complexes 21a–c . The amorphous insoluble polymer complexes from types 21, 22 , and 23 have been characterised by i.r.-spectroscopy, susceptibility and conductivity measurements. The nickel complexes have the highest electrical conductivity (σ_RT ∼ 10⁻¹Ω⁻¹cm⁻¹, pellets) with a very low activation energy (0,045 eV, 100–300 K) A high electron delocalization in the direction of the polymer chain and an easy charge transfer from chain to chain is supposed.     

N-羟甲基-2,3-二丁硫基四硫富瓦烯并[6,7-c]吡咯的合成

从4,5-二丁硫基-1,3-二硫杂环戊二烯-2-酮和N-对苯磺酰基-2-硫代-1,3-二硫杂环戊二烯并[4,5-c]吡咯出发,经交叉偶联、去保护得2,3-二丁硫基四硫富瓦烯并[6,7-c]吡咯(4)。化合物4在碱存在下与甲醛水溶液(37%)反应生成N-羟甲基化的产物。用核磁共振氢谱研究了标题化合物在不同极性溶剂中的偶合行为。     

Structure-Based Design,Synthesis, and Biological Evaluation of Imidazo[4,5-b]Pyridin-2-one-Based p38 MAP Kinase Inhibitors: Part 2

We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one ( 1 ). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide ( 25 ) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors.     

Reaction of 3H, 6H-1, 2-Dithiolo[4,3-c]1,2-dithiole-3, 6-dithione with primary aliphatic amines

The reaction of 3H,6H-1,2-dithiolo[4,3-c]1,2-dithiole-3, 6-dithione ( 1 ) with primary aliphatic amines ( 8a , b ) gives 3H,6H-3,6-bisalkylimino-1,2-dithiolo[4,3-c]1,2- dithiole ( 9a , b ), 3H,3-N-alkylamino-5-N-alkylthiocarbamido-1, 2-dithiolium-4-thiolate ( 10a , b ) and 3H,3-N-alkylimino-4-alkylamino-5-N-alkylthiocarbamido-1,2-dithiole ( 11a , b ). The compounds 9-11 can be formed from one another. The compounds 10a , b react with nickel chloride to the stable complexes 14a , b . In basic medium 10 gives the salt of 3H,3N-alkylthiocarbamido-1,2-dithiole-4-thiolate 15 , which reacts with methyl iodide to 3H,3N-alkylimino-5-N-alkylthiocarbamido-4-methylthio-1,2-dithiole 16 .     

New Unsymmetrically Benzene-Fused Bis (Tetrathiafulvalene): Synthesis,Characterization, Electrochemical Properties and Electrical Conductivity of Their Materials

The synthesis of new unsymmetrically benzene-fused bis (tetrathiafulvalene) has been carried out by a cross-coupling reaction of the respective 4,5-dialkyl-1,3-dithiole- 2-selenone 6–9 with 2-(4-(p-nitrophenyl)-1,3-dithiole-2-ylidene)-1,3,5,7-tetrathia-s-indacene- 6-one 5 prepared by olefination of 4-(p-nitrophenyl)-1,3-dithiole-2-selenone 3 and 1,3,5,7-tetrathia-s-indacene-2,6-dione 4. The conversion of the nitro moiety 10a–d to amino 11a–d then dibenzylamine 12a–d groups respectively used reduction and alkylation methods. The electron donor ability of these new compounds has been measured by cyclic voltammetry (CV) technique. Charge transfer complexes with tetracyanoquino-dimethane (TCNQ) were prepared by chemical redox reactions. The complexes have been proven to give conducting materials.     

Synthesis and polymerization of novel <Emphasis Type="Italic">N</Emphasis>-substituted maleimides containing an oxazoline group

Summary A novel type of maleimide-based monomers, N-[o-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl]maleimide (DMOPMI), ()-N-[o-(4-ethyl-4,5-dihydro-1,3-oxazol-2-yl)phenyllmaleimide (()-EOPMI), and (R)-N-[o-(4-ethyl-4,5-dihydro-l,3-oxazol-2-yl)phenyllmaleimide ((R)-EOPMI), were synthesized for the first time. Their polymerization behavior was studied briefly by both radical and anionic initiating mechanisms. The results indicated that the addition polymerization takes place mainly in the vinylene group without appreciable side reactions. The polymerization in low polar media tended to increase molecular weights or optical activity of the obtained polymers.     

Thia- and selenaheterocycles by a four-component reaction using elemental sulfur and selenium

The course of the four-component reactions of (2-benzimidazolyl) acetonitrile, carbondisulfide, isothiocyanate, and sulfur and selenium, respectively, is quite different. Whereas in the case of sulfur a tetracyclic [1,3]thiazolo[4′,5′:4,5]pyrimido[1,6-a]benzimidazol-2(3H)-thione is formed, a zwitterionic 7-(benzimidazolium-2-yl)-[1,2]thiaselenolo[2,3-b][1,2,4]thiaselenazole-6-thiolate (an azaselenadithiapentalene) is the product in the case of selenium. The structures of the products have been established by X-ray crystallography, and reaction mechanisms for their formation are proposed.     

Synthesis of 1,3-Oxazines and Furo[2,3-b]pyrans by reaction of 2-amino-4,5-dihydro-3-furancarbonitriles with dibenzoyldiazomethanes

2-Amino-4,5-dihydro-3-furancarbonitriles ( 1 ) react with a slight excess of dibenzoyldiazomethane in the presence of rhodium(II) acetate to give 1,3-oxazin-4-ones ( 2 ). With three equivalents of dibenzoyldiazomethane compounds 1 react to afford furo[2,3-b]pyran-3a-carbonitriles ( 3 ). Compound 3a was also obtained by treatment of 2a with two equivalents of dibenzoyldiazomethane.     

新型dmit金属配合物的合成及其电化学性质的研究

以4,5- 二氰乙硫基-1,3- 二硫杂环戊烯-2-硫酮为原料,经醇钠消去保护基团,再与二价金属离子配位,合成了8种双(1,3-二硫杂环戊烯-2-硫酮-4,5-二硫)金属配合物,为dmit型配合物合成提出了一种新方法.研究表明这类配合物有特殊的电化学性质和很强的紫外吸收,并对其形成中性产物的主要原因和室温电导率进行了讨论.     

Synthesis and characterization of copolymers with alternating 1,4-bis(5'-acetyl-2'-thienyl)benzene or 1,3-bis(5'-acetyl-2'-thienyl)benzene chromophore and disiloxane units

Summary Activated (Ph₃P)₃RuH₂CO (Ru) catalyzed copolymerization of 1,4-bis(5'-acetyl-2'-thienyl)benzene (I) and 1,3-divinyltetramethyldisiloxane (II) yields alt-copoly[3,3,5,5-tetramethyl-4-oxa-3,5-disila-1,7-heptanylene/2',2"-diacetyl-5',5"-(1,4-benzene)-3',3"-bis (thiophenylene)] (III). On the other hand, Ru catalyzed copolymerization of 1,3-bis(5'-acetyl-2'-thienyl)benzene (IV) and II fails. Nevertheless, Ru catalyzed reaction of IV with excess vinylpentamethyldisiloxane (V) yields 1,3-bis(4'-pentamethyldisiloxy-ethyl-5'-acetyl-2'-thienyl)benzene (VI). VI undergoes acid catalyzed siloxane equilibration polymerization to give alt-copoly[3,3,5,5-tetramethyl-4-oxa-3,5-disila-1,7-heptanylene/2',2"-diacetyl-5',5"-(1,3-benzene)-3',3"-bis(thiophenylene)] (VII) and hexamethyldisiloxane. Copolymers III and VII have been characterized. Received: 26 July 1999/Revised version: 12 October 1999/Accepted: 12 October 1999     

An efficient one-pot protocol for regioselective synthesis of 3-aryl-6,8-dialkyl-7-thioxo-7,8-dihydropyrimido[4,5-c] pyridazine-5(6H)-ones

A series of 3-aryl-6,8-dialkyl-7-thioxo-7,8-dihydropyrimido[4,5-c]pyridazine-5(6H)-one derivatives have been regioselectively synthesized via the one-pot three-component reaction of 1,3-dimethylthiobarbituric acid and 1,3-diethylthiobarbituric acid with various arylglyoxals in the presence of hydrazinium dihydrochloride in warm ethanol. These new substituted pyrimidopyridazines may be potential monoamine oxidase inhibitors.     

Tetrathiafulvalene. XXVIII. Diastereoselektive Bildung unsymmetrisch substituierter Tetrathiafulvalene

Tetrathiafulvalenes. XXVIII. Diastereoselective Formation of Unsymmetrically Substituted Tetrathiafulvalenes As a part of our work on chemistry of tetrathiafulvalenes, we make a contribution to elucidate the mechanism of forming tetrathiafulvalenes starting from 1,3-dithiole derivatives. We describe the synthesis of unsymmetrically substituted tetrathiafulvalenes ( 8a–i ) starting with the 2H-1,3-dithiolium salt ( 7a–i )/tert. amine, 2-ethylthio-1,3-dithiolium salt ( 5a–i )/triphenylphosphine or 1,3-dithiole-2-thione ( 4a–i )/triethyl phosphite. If the 1,3-dithiole derivatives are substituted by bulky groups the isolation of the cis- and trans-isomers was possible due to differences in the solubility. In these cases ( 8c–i ) the predominant formation of the cis-isomer is observed in the reaction of 2-ethylthio-1,3-dithiolium salts ( 5c–i ) with triphenylphosphine or 1,3-dithiole-2-thiones ( 4c–i ) with triethyl phosphite. This result is in agreement with the formation of an intermediate, analogously to the Wittig reaction. In the reaction of 2H-1,3-dithiolium salts ( 7a–i ) with tertiary amines the relation of isolated cis- and trans-isomers is not 1:1 and depends on the bulkiness of the tertiary amine. These observations exclude in these three reactions a carbene mechanism for the dimerization of the 1,3-dithiole units to tetrathiafulvalenes.     

Synthesis of some new 3-mercapto-5-substituted-1,2,4-triazine-s-triazoles for evaluation as antimicrobial agents

The synthesis of several S- and N-substituted derivatives of 5-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-s-triazole-3-thiol, 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)-oxymethyl]-5,6-dihydrothiazolo-[3,2-b]-s-briazole, 2-[(5,6-diphenyl-1, 2,4-triazin-3-yl)oxymethyl]-5H,6,7-dihydro-s-triazolo-[3,2-b]-1,3-thiazine, 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-5,6-dihydrothiazolo-[3,2-b]-s-triazol-5-one and 2-[(5,6-diphenyl-1,2,4-triazin-3-yl)oxymethyl]-6-phenylthiazolo-[3,2-b]-s-triazole is reported. All the novel compounds have been screened for antimicrobial activity and one of them showed noteworthy activity.     

Novel magnesium and zinc porphyrazines containing galactose moieties: Synthesis via click reaction and characterization

In this study, galactose conjugated new magnesium and zinc porphyrazines were synthesized by the cyclotetramerization reaction of 2,3-bis[1-(2,2,7,7-tetramethyltetra-hydro-bis[1,3]dioxolo[4,5-b;4′,5′-d]pyran-5,methyl)-1H-[1,2,3]triazol-4-yl methylsulfanyl]-but 2-enedinitrile. This substituted dicyano compound was prepared via two different routes. One started from cis-1,2-dicyano-1,2-ethylenedithiolate disodium, [1-(2, 2, 7,7-tetramethyltetrahydrobis[1,3]dioxolo[4,5-b;4′,5′-d]pyran-5-yl-methyl)-1H-[1,2,3]triazo-l-4-yl]methanol and ended in a multi-step reaction sequence via Click procedures. The other reaction was between 5-azidomethyl-2,2,7,7-tetramethyltetrahydro-bis[1,3]dioxolo[4,5-b;4′,5′-d]pyran and (2Z)-2,3-bis(prop-2-yl-1-yl-thio)but-2-enedinitrile. A very soluble galactose linked magnesium porphyrazine derivative in common polar solvents and water was achieved by the deprotected isopropylidene groups in TFA and water media. It is first time, zinc porphyrazine complex has been achieved at one-step reaction by using Zn(BuO)₂ as template agent. The new compounds have been characterized by a combination of elemental analysis, ¹H, ¹³C NMR, IR, UV–vis and MS spectral data.     

A Novel Class of N-Sulfonyl and N-Sulfamoyl Noscapine Derivatives that Promote Mitotic Arrest in Cancer Cells

Noscapine displays weak anticancer efficacy and numerous research efforts have attempted to generate more potent noscapine analogues. These modifications included the replacement of the N-methyl group in the 6′-position with a range of substituents, where N-ethylcarbamoyl substitution was observed to possess enhanced anticancer activity. Herein, we describe advances in this area, namely the synthesis and pharmacological evaluation of a series of N-sulfonyl and N-sulfamoyl noscapine derivatives. A number of these sulfonyl-containing noscapinoids demonstrated improved activities compared to noscapine. ((R)-5-((S)-4,5-Dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-((1-methyl-1H-imidazol-4-yl)sulfonyl)-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinoline) ( 14 q ) displayed sub-micromolar activities of 560, 980, 271 and 443 nM against MCF-7, PANC-1, MDA-MB-435 and SK-MEL-5 cells, respectively. This antiproliferative effect was also maintained against drug-resistant NCI/Adr^RES cells despite high expression of the multidrug efflux pump, P-glycoprotein.     

Synthesis of trans-4,5-epoxy-(E)-2-decenal and its deuterated analog used for the development of a sensitive and selective quantification method based on isotope dilution assay with negative chemical ionization

The volatile compound trans-4,5-epoxy-(E)-2-decenal (1) was synthesized in two steps with good overall yields. The newly developed method is based on trans-epoxidation of (F)-2-octenal with alkaline hydrogen peroxide followed by a Wittig-type chain elongation with the ylide formylmethylene triphenylphosphorane. For the synthesis of [4,5-²H₂]-trans-4,5-epoxy-(E)-2-decenal (d-1), [2,3-²H₂]-(E)-2-octenal was prepared by reduction of 2-octyn-1-ol with lithium aluminum deuteride and subsequent oxidation of [2,3-²H₂]-(E)-2-octen-1-ol with manganese oxide. Compound d-1 was used as internal standard for the quantification of 1 by isotope dilution assay. Among various mass spectrometry (MS) ionization techniques tested, negative chemical ionization with ammonia as reagent gas gave best results with respect to both sensitivity and selectivity. The detection limit was found to be at about 1 pg of the analyte introduced into the gas chromatography-MS system.     

An Efficient Synthesis of Fused Polycyclic Triazolo[4,5-a]acridine Derivatives under Catalyst-Free Conditions with High Regioselectivity

An efficient synthesis of fused polycyclic 11-aryl-7,8,9,11-tetrahydro-1H-[1,2,3] triazolo[4,5-a]acridin-10(6H)-one derivatives is described in EtOH with high regioselectivity. This new procedure includes a three-component reaction of benzaldehyde, 1H-benzo[d] [1,2,3]triazol-5-amine and cyclohexane-1,3-dione under catalyst-free conditions, and has the advantages of one-pot reaction, milder reaction conditions, high yields and high regioselectivity.     

Synthesis of new fluorine containing ring-opened polynorbornene dicarboximides using ruthenium alkylidene catalysts

Summary  The synthesis of new N-4-trifluoromethylphenyl-exo-endo-norbornene-5,6-dicarboximide (TFmNDI, 2a) and N-3,5-difluorophenyl-exo-endo-norbornene-5,6-dicarboximide (DFNDI, 2b) was carried out. Polynorbornene dicarboximides, 3a and 3b, were obtained via ring opening metathesis polymerization (ROMP) using bis(tricyclohexylphosphine) benzylidene ruthenium(IV) dichloride (I) and tricyclohexylphosphine [1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][benzylidene] ruthenium dichloride (II), respectively. T_g’s for polymers 3a and 3b were observed at 155 C and 142 C, respectively. Compared to polymer 3b, polymer 3a with the bulky trifluoromethyl group showed the highest glass transition temperature and improved mechanical properties.     

New Insight into Dearomatization and Decarbonylation of Antitubercular 4H-Benzo[e][1,3]thiazinones: Stable 5H- and 7H-Benzo[e][1,3]thiazines

8-Nitro-4H-benzo[e][1,3]thiazinones (BTZs) are potent in vitro antimycobacterial agents. New chemical transformations, viz. dearomatization and decarbonylation, of two BTZs and their influence on the compounds’ antimycobacterial properties are described. Reactions of 8-nitro-2-(piperidin-1-yl)-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-4-one and the clinical drug candidate BTZ043 with the Grignard reagent CH₃MgBr afford the corresponding dearomatized stable 4,5-dimethyl-5H- and 4,7-dimethyl-7H-benzo[e][1,3]thiazines. These methine compounds are structurally characterized by X-ray crystallography for the first time. Reduction of the BTZ carbonyl group, leading to the corresponding markedly non-planar 4H-benzo[e][1,3]thiazine systems, is achieved using the reducing agent (CH₃)₂S ⋅ BH₃. Double methylation with dearomatization and decarbonylation renders the two BTZs studied inactive against Mycobacterium tuberculosis and Mycobacterium smegmatis, as proven by in vitro growth inhibition assays.     

A convenient access to 1,2-diferrocenyl-substituted ethylenes via [3 + 2]-cycloelimination of 2-silylated 4,4,5,5-tetrasubstituted 1,3-dithiolanes

Ferrocenyl thioketones bearing a hetaryl, phenyl or alkyl group as the second substituent react with (trimethylsilyl)diazomethane at ca. ?30°C in THF solution without formation of a stable [3?+?2]-cycloadduct. After the spontaneous evolution of N₂, the corresponding sterically crowded 4,4,5,5-tetrasubstituted 2-silylated 1,3-dithiolanes are formed as products of the second [3?+?2]-cycloaddition of the intermediate thiocarbonyl S-methanide with the starting thioketone. After desilylation by treatment with TBAF, they are converted into the corresponding carbanions, which display different stability depending on the type of substituent. The presence of hetaryl and phenyl groups results in the exclusive formation of 1,2-diferrocenyl ethylenes. In contrast, the presence of methyl groups significantly enhances the stability of the carbanion, which by protonation yields trans-4,5-diferrocenyl-4,5-dimethyl-1,3-dithiolane.