Reaction Of 1a Research Articles

Simple and Efficient Synthesis of Novel 3‐Substituted 2‐Thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones and Their Reactions with Alkyl Halides and α‐Glycopyranosyl Bromides

A series of 3‐substituted 2‐thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 4a–e were synthesized from the reaction of 3‐aminonaphthalene‐2‐carboxylic acid 1 with isothiocyanate derivatives 2a–e. The alkylation of 4a–e with alkyl halides gave 3‐substituted 2‐alkylsulfanyl‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 5a–o. S‐Glycosylation was carried out via the reaction of 4a–e with glycopyranosyl bromides 7a and 7b under anhydrous alkaline conditions. The structure of the compounds was established as S‐nucleoside and not N‐nucleoside. Conformational analysis has been studied by homonuclear and heteronuclear two‐dimensional NMR methods (2D DFQ‐COSY, heteronuclear multiple quantum coherence, and heteronuclear multiple bond correlation). The S site of alkylation and glycosylation was determined from the 1H and 13C heteronuclear multiple quantum coherence experiments.

P–H Functionalized Al/P-Based Frustrated Lewis Pairs in Dipolar Activation and Hydrophosphination: Reactions with CO2 and SO2

The P–H functionalized FLPs R(H)PC(AlBis2)═C(H)-CMe3 (1a, R = Bis; 1b, R = Mes; Bis = CH(SiMe3)2) combine the typical FLP properties based on Lewis acidic Al and basic P atoms with the reactivity of a P–H bond. They allow the coordination of substrates followed by hydrophosphination with the activated P–H group. Reactions of 1a with R′–N═C═S (R′ = Ph, CMe3) or of both FLPs with Et–N═C═CPh2 afforded five-membered AlCPCS/N heterocycles (4 and 5) via coordination of C═S or C═N bonds to the FLP backbone. Isomerization by a 1,3-H shift from P to N or C (6 and 7) was only achieved in the presence of an auxiliary base (DABCO; 1–5 mol %). (Z)-1a coordinated CO2 to yield the adduct 8, which features a five-membered AlCPCO heterocycle with an exocyclic C═O bond. Addition of bases such as DABCO and DBU afforded by deprotonation of the P atom the compounds [Bis-PC(AlBis2)═C(H)–CMe3(CO2)]−[HB]+ (9a, B = DABCO; 9b, B = DBU) that displayed hydrogen bonding between the ammonium ions and the exocyclic O atom of the FLP ad...

Condensation of 4-chloro-2H-chromene-3-carbaldehydes and ethyl-3-aminocrotonates with p-TsOH: a facile approach for the synthesis of chromenyldihydropyridines

The investigated reaction of 4-chloro-2H-chromene-3-carbaldehyde 1a with ethyl 3-oxobutanoate 2a in the presence of ammonium acetate provided two compounds, 2H-chromenyldihydropyridine dicarboxylate 3a and chromenopyridine carboxylate 4a. However, the reaction of 1a with ethyl-3-aminocrotonate 5a in the presence of p-TsOH provided selectively 2H-chromenyldihydropyridine dicarboxylate 3a with very good yield. The established method was applied for the preparation of series of 2H-chromenyldihydropyridine dicarboxylates 3a–q.

Direct Functionalization of White Phosphorus to Cyclotetraphosphanes: Selective Formation of Four P-C Bonds.

Converting elemental white phosphorus directly into organophosphorus or polyphosphorus is meaningful, challenging and attractive. The ate-complexes of aluminacyclopentadienes 1a,b react with P4 to afford selectively the cyclotetraphosphanes 2a,b featuring four newly formed P-C bonds and a planar square cyclo-P4 ring. Density functional theory calculations show that the conversion of tetrahedral P4 to planar cyclo-P4 moiety undergoes through an unexpected 1,1- P-insertion/Diels-Alderreaction/isomerization cascade process. The reaction of2a with iodomethane or p-benzoquinone afforded the P-methylation product 3 and the metal-free cyclotetraphosphane 4, respectively. Interestingly, reduction of 4 generated the phospholyl anions 5 and 6 while treatment of 4 with iodomethane afforded the phospholyl cation 7.

Hydrazinolysis of aryl cinnamates and related esters: the α-effect arises from stabilization of five-membered cyclic transition state

A kinetic study is reported for nucleophilic substitution reactions of Y-substituted-phenyl cinnamates (1a–1h) with a series of primary amines including hydrazine in H2O containing 20 mol % DMSO at 25.0 °C. The Brønsted-type plot for the reaction of 2,4-dinitrophenyl cinnamate (1a) is linear with βnuc = 0.57 except hydrazine, which exhibits positive deviation from the linear correlation (i.e., the α-effect). The Brønsted-type plots for the reactions of 1a–1h with hydrazine and glycylglycine (glygly) are also linear with βlg = –0.71 and –0.87, respectively, when 1a is excluded from the linear correlation. Thus, the reactions have been concluded to proceed through a concerted mechanism on the basis of the linear Brønsted-type plots and magnitudes of the βnuc and βlg values. The α-effect shown by hydrazine is dependent on electronic nature of the substituent Y in the leaving group, e.g., it increases as the substituent Y becomes a weaker electron-withdrawing group (or as basicity of the leaving aryloxide increases), indicating that the α-effect is not due to destabilization of the ground state but mainly due to stabilization of the transition state. A five-membered cyclic TS structure, which could increase nucleofugality of the leaving aryloxide through H-bonding interaction, has been proposed to account for the leaving-group dependent α-effect found in this study. The theories suggested previously to rationalize the α-effect found for the related systems are also discussed.

Kinetic study on aminolysis of aryl X-substituted-cinnamates in acetonitrile: differential medium effect determines reactivity and reaction mechanism

A kinetic study on nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted-cinnamates (1a–1f) and Y-substituted-phenyl cinnamates (2a–2g) with a series of alicyclic secondary amines in MeCN at 25.0 ± 0.1 °C is reported. The Brønsted-type plots for the reactions of 1a–1f are linear with βnuc = 0.47∼0.50, indicating that the bond formation between the amine nucleophile and the electrophilic center is advanced slightly in the transition state. The Brønsted-type plot for the reactions of 2a–2g with piperidine is also linear with βlg = –0.66, which is a typical βlg value for reactions reported previously to proceed through a concerted mechanism. Furthermore, the Hammett plot correlated with σ– constants results in much better linearity than that correlated with σo constants, implying that expulsion of the leaving group is advanced in the rate-determining step (RDS). Thus, the reactions are concluded to proceed through a concerted mechanism. The Hammett plots for the reactions of 1a–1f consist of two intersecting straight lines, whereas the corresponding Yukawa–Tsuno plots exhibit excellent linear correlations with ρX = 0.62∼0.71 and r = 0.65∼0.68. Apparently, the nonlinear Hammett plots are not due to a change in the reaction mechanism (or the RDS) but are caused by stabilization of the substrate possessing an electron-donating group (EDG) in the cinnamoyl moiety through resonance interactions between the EDG and the C=O bond of the substrate. Medium effects on reactivity and reaction mechanism are also discussed.

Thiaborane clusters with an exoskeletal B-H group.

The thiaboranes closo-1-SB11H11 (1a) and 12-I-closo-1-SB11H10 (1b) react with 4-(dimethylamino)pyridine under inert conditions upon the formation of the nido-type thiaboranes 9-B{(4-Me2N)C5NH4}2(H)-7-SB10H11 and 9-B{(4-Me2N)C5NH4}2(H)-5-I-7-SB10H10 containing an exoskeletal B-H group. The same type of B-H moiety is also stabilised by one bipyridine molecule in a chelating fashion. These complexes are unstable in solution, and in air and hydrolyse to monodeboronated ionic compounds having [nido-7-SB10H11]- or [5-I-nido-7-SB10H10]- anions which are also products of the reactions of 1a and 1b with other N-bases such as pyridine, ammonia and DABCO. The extrusion of one boron and one sulphur atom takes place when 1a reacts with 2,6-di-tert-butylpyridine to yield decaborane.

Zwitterionic Trivalent (Alkyl)lanthanide Complexes in Ziegler-Type Butadiene Polymerization

The organolanthanide complexes Ln{C(SiHMe2)3}3 (Ln = La, 1a; Ce, 1b; Pr, 1c; Nd, 1d) react with 1 or 2 equiv of B(C6F5)3 to yield the well-defined zwitterionic species Ln{C(SiHMe2)3}2HB(C6F5)3 (Ln = La, 2a; Ce, 2b; Pr, 2c; Nd, 2d) or LnC(SiHMe2)3{HB(C6F5)3}2 (Ln = La, 3a; Ce, 3b; Pr, 3c; Nd, 3d), respectively. These complexes are shown to contain labile, bridging Si–H⇀Ln and o-F→Ln interactions based upon the observation of low one-bond silicon–hydrogen coupling constants (1JSiH) in 1H NMR spectra of 2a and 3a, the presence of one set of C6F5 signals in the 19F NMR spectra of 2a and 3a, the detection of only m-F and p-F resonances in the 19F NMR spectra of 2b–d and 3b–d, two νSiH bands in the IR spectra of 2a–d, and X-ray crystallography analyses of 2b and 3d. In addition, a hexahaptotoluene molecule is coordinated to neodymium in 3d. Reactions of 1a and (AlMe3)2 yield labile adducts. With greater than 3 equiv of AlMe3, exchange between free and bound AlMe3 groups was observed in EXSY NMR experiments. Com...

Silicon-Mediated Selective Homo- and Heterocoupling of Carbon Monoxide.

While the transformation of carbon monoxide to multicarbon compounds (fuels and organic bulk chemicals) via reductive scission of the enormously strong CO bond is dominated by transition metals, splitting and deoxygenative reductive coupling of CO under nonmatrix conditions using silicon, the second most abundant nonmetal of the earth's crust, is extremely scarce and mechanistically not well understood. Herein, we report the selective deoxygenative homocoupling of carbon monoxide by divalent silicon utilizing the (LSi:)2Xant 1a [Xant = 9,9-dimethyl-xanthene-4,5-diyl; PhC(N tBu)2] and (LSi:)2Fc 1b (Fc = 1,1'-ferrocenyl) as four-electron reduction reagents under mild reaction conditions (RT, 1 atm), affording the corresponding disilylketenes, Xant(LSi)2(μ-O)(μ-CCO) 2a and Fc(LSi)2(μ-O)(μ-CCO) 2b, respectively. However, the dibenzofuran analogue of 1b, compound 1c, was unreactive toward CO due to the longer distance between the two SiII atoms, which demonstrated the crucial role of the Si···Si distance on cooperative CO binding and activation. This is confirmed by density functional theory (DFT) calculations, and further theoretical investigations on CO homocoupling with 1a and 1b revealed that the initial step of CO binding and scission involved CO acting as a Lewis acid (four-electron acceptor), in sharp contrast to CO activation mediated by transition metals where CO serves as a Lewis base (two-electron donor). This mechanism was strongly reinforced by the reaction of 1a with isocyanide Xyl-NC (Xyl = 2,6-Me2C6H3), isoelectronic with CO. Treatment of 1a with one or two molecules of Xyl-NC furnished the unique (silyl)(imido)silene 3a and the C═C coupled bis(Xyl-NC) product 5, respectively, via the isolable doubly bridged Xant(LSi)2(μ-XylNC)2 intermediate 4. Moreover, compound 3a reacts with 1 molar equivalent of CO to give the disilylketenimine Xant(LSi)2(μ-O)(μ-CCNR) 6, representing, for the first time, a selective heterocoupling product of CO with isoelectronic isocyanide.

Unexpected medium effect on the mechanism for aminolysis of aryl phenyl carbonates in acetonitrile and H2O: transition-state structure in the catalytic pathway

Upward curvature in the kinetic plots of pseudo first-order rate constants (kobsd) vs. [amine] for the aminolysis of aryl phenyl carbonates (5a–5j) in MeCN demonstrates that these reactions proceed via a zwitterionic tetrahedral intermediate (T±) that partitions between catalyzed and uncatalyzed routes to give the products. Yukawa–Tsuno plots for the reactions of 5a–5j with piperidine result in excellent linear correlations with ρY = 4.82 and r = 0.47 for the uncatalyzed reaction versus ρY = 2.21 and r = 0.21 for the catalyzed reaction. Brønsted plots for reactions of 4-(ethoxycarbonyl)-phenyl phenyl carbonate (5f) with a series of cyclic secondary amines exhibit excellent linear correlations with βnuc = 0.87 and 0.58 for the uncatalyzed and catalyzed reactions, respectively. The ΔH‡ and ΔS‡ values are 0.92 kcal/mol and –50.1 cal/mol K, respectively, for the catalyzed reaction of 5f with piperidine. Deuterium kinetic isotope effects found for reactions of 5f with piperidine/deuterated piperidine are 0.84 (uncatalyzed) and 1.42 (catalyzed). Multi-parameter analysis supports a concerted catalytic pathway involving a six-membered cyclic transition state rather than a traditionally accepted stepwise pathway with an anionic intermediate. The current unexpected results, where T± is the essential central intermediate in this aminolysis, contrast with previous calculation studies that deemed T± unstable in gas phase or MeCN.

Design, synthesis, DNA assessment and molecular docking study of novel 2-(pyridin-2-ylimino)thiazolidin-4-one derivatives as potent antifungal agents

A series of novel 2-imino-4-thiazolidinone derivatives 4a,b was synthesized through reaction of unsymmetrical thioureas 3a,b with chloroacetic acid. Condensation of 4a,b with aromatic aldehydes 5a-eyielded the corresponding 5-arylidene derivatives 6a-j. In addition, the reaction of 4a,b with 4-arylazo-3-hydroxybenzaldehydes 8a-c furnished the respective mono-arylazo-4-thiazolidinones10a-f. All the newly synthesized compounds were confirmed by their elemental analysis and spectral data. The antifungal activity of the newly synthesized compounds was assessed and the compounds 6d, 6e, 6i, 6j, 9a,b and 10a-frevealedhigher antifungal activity towards Alternaria solani than to the standard Ridomil gold plus. Moreover, the DNA toxicity of 4-thiazolidinone derivatives 6d, 9a, 10b, 10c and 10f on the nucleic acid of Alternaria solani (KT354939) was performed and the results showed qualitatively more than 70% cleavage. Also, compounds 6i, 6j, 9b, 10c and 10f were docked inside the active site of 1ZOYenzyme and suitable binding with the active site of amino acids, were displayed according to their bond lengths, angles and conformational energy.

Functionalization of 1,3-diphosphacyclobutadiene cobalt complexes via Si–P bond insertion

AbstractWe report the synthesis of functionalized 1,3-bis(diphosphacyclobutadiene) complexes via the insertion of carbon-oxygen bonds of ethers, esters, aldehydes and amides into the P–Si bond of silylated complexes. Reactions of [K(tol)2][Co(η4-P2C2R2)2] [[K(tol)2][1a]:R=tBu,[K(tol)2][1b]:R=tPent (=tert-pentyl)] with Me3SiCl afford the trimethylsilyl-substituted derivatives [Co(η4-P2C2R2SiMe3)(η4-P2C2R2)] (2a,b, R=tBu,tPent). The Me3Si group is connected to a phosphorus atom of one of the 1,3-diphosphacyclobutadiene ligands.2a,breadily react with organic substrates containing C–O single and C=O double bonds at ambient temperature. [Co(η4-P2C2R2(CH2)4OSiMe3)(η4-P2C2R2)] (3a,b) are formed by reaction of2a,bwith traces of THF. They can also be isolated by reacting the THF solvates [K(thf)2{Co(P2C2tBu2)2}] ([K(thf)2][1a]) and [K(thf)3{Co(P2C2tPent2)2}] ([K(thf)3][1b]) with Me3SiCl in toluene or THF. The adamantyl-substituted complex [Co(η4-P2C2Ad2(CH2)4OSiMe3)(η4-P2C2Ad2)] (3c) was prepared analogously from [K(thf)4{Co(P2C2Ad2)2}] and Me3SiCl.[K(thf)2][1a]reacts cleanly with Ph3SnCl affording [Co(η4-P2C2tBu2SnPh3)(η4-P2C2tBu2)] (4) in high yield. Reaction of2awith styrene oxide affords [Co(η4-P2C2tBu2PhC2H3OSiMe3)(η4-P2C2tBu2)] (5) as a single regioisomer. By contrast, multinuclear NMR spectroscopic studies indicate mixtures of two isomeric insertion products6/6′ and7/7′, respectively, which result from the insertion of 1,2-epoxy-2-methylpropane and 1,2-epoxyoctane. Moreover, these monitoring studies show that reactions of2awith acyclic ethers afford alkyl substituted complexes such as [Co(η4-P2C2tBu2Et)(η4-P2C2tBu2)] (8) and alkylsilyl ethers. Reaction of2awithγ-butyrolactone gives [Co(η4-P2C2tBu2(CH2)3C(O)OSiMe3)(η4-P2C2tBu2)] (9) via cleavage of the endocyclic C–O single bond of the lactone. Benzaldehyde and acetone cleanly react with2ato [Co(η4-P2C2tBu2CH(Ph)OSiMe3)(η4-P2C2tBu2)] (10) and [Co(η4-P2C2tBu2CMe2OSiMe3)(η4-P2C2tBu2)] (11), while the sterically more demanding ketones 3-pentanone and acetophenone selectively yield the known hydride complex [Co(η4-P2C2tBu2)2H] (A). Phenyl isocyanate reacts with2aat elevated temperature to form [Co(η3-P2C2tBu2CON(Ph)SiMe3)(η4-P2C2tBu2)] (12) with a functionalizedη3-coordinated ligand.[K(tol)2][1a],[K(tol)2][1b],2a,2b,3a–c,4,5, and9–12were isolated and characterized by multinuclear NMR spectroscopy, UV/Vis spectroscopy and elemental analysis.[K(tol)2][1b],2a,2b,3c,4,5, and9–12were additionally characterized by X-ray crystallography.

Highly β( Z)-Selective Hydrosilylation of Terminal Alkynes Catalyzed by Thiolate-Bridged Dirhodium Complexes.

A series of novel monothiolate-bridged dirhodium complexes, [Cp*Rh(μ-SR)(μ-Cl)2RhCp*][BF4] {Cp* = η5-C5Me5, R = tertiary butyl ( tBu), 1a; R = ferrocenyl (Fc), 1b; R = adamantyl (Ad), 1c} were designed and successfully synthesized, which can smoothly facilitate highly regioselective and stereoselective hydrosilylation of terminal alkynes to afford β( Z) vinylsilanes with good functional group compatibility. Furthermore, the hydride bridged dirhodium complex [Cp*Rh(μ-S tBu)(μ-Cl)(μ-H)RhCp*][BF4] (5) as a potential intermediate was obtained by the reaction of 1a with excess HSiEt3.

-Oxo anilides in Heterocyclic Synthesis: Novel Synthesis of Pyridazinones, Pyrazolopyridazines, and Cinnolines

Compound 1 coupled smoothly with aromatic diazonium salts to yield the corresponding arylhydrazones 2a-d. Compounds 2a-d condensed with DMF-DMA in refluxing xylene to yield the pyridazinones 3a-d. Compounds 3a-d were also established based on its further reaction with some active methylene reagents and some nucleophilic reagents. So, reactions of 3a, b with malononitrile in refluxing ethanolic piperidine afforded arylidinemalononitrile 4a,b. The pyridazinone derivatives 3a, b reacted with hydrazine hydrate to afford the hydrazine derivatives 5a, b. When 3a,b were fused with hydrazine hydrate without solvent, the pyrazolo[4,3-c]-pyridazines 6a,b were obtained. Compounds 6a, b were also obtained when compounds 5a, b melt over melting point for short time. Condensation of 2a, b with ethyl cyanoacetate yield 7a, b. Similarly, reactions of 2a,b with 1 mole of malononitrile afforded the pyridazine derivatives 8a,b. While, when 2 moles of malononitrile reacted with 2a, b in the same experimental conditions to yield the cinnoline derivative (9a, b). Reactions of pyridazine 8a,b with 1 mole of malononitrile afforded 9. Compound 2b was reacted with a mixture of arylidinemalononitrile and acrylonitrile to yield product formulated as triazole moieties 12a, b. Similarly, compound 2b was reacted with a mixture of maleic anhydride and acrylonitrile in the same above experimental conditions to give 13. Also, reactions of 2b with hydroxylamine hydrochloride yield 14.

Synthesis, characterization, and antitumor activity of some novel S-functionalized benzo[d]thiazole-2-thiol derivatives; regioselective coupling to the –SH group

Abstract Several 2-substituted sulfanyl benzo[d]thiazoles were regioselectively synthesized by the reaction of benzo[d]thiazole-2-thiol (1a) with a variety of reagents under different basic conditions. Some 2-(2,3-disubstituted propyl sulfanyl)benzo[d]thiazoles were obtained from 2-(allylthio)benzo[d]thiazole, which was prepared by the allylation of 1a with allyl bromide in the presence of sodium hydride in dry N,N-dimethylformamide. Reaction of 1a with various pyrazolyl-quinoxaline derivatives was also investigated. Better yields and shorter reaction time were achieved for the synthesis of some derivatives by using ultrasound irradiation. The structural elucidation of all compounds was based on both analytical and spectroscopic data. The newly synthesized compounds were tested in vitro for their antitumor activity against Ehrlich ascites carcinoma (EAC) cells grown in albino mice. Doxorubicin was used as a standard antitumor antibiotic, and some compounds showed half maximal inhibitory concentration (IC50) in the range 40–68 μg mL−1.

Synthesis of New Potential Hydrophobic Agents Composed of Three-Module Type Molecules

A new synthetic route was developed to three-module type potential hydrophobic agents, with the molecule consisting of an N-[3-(triethoxysilyl)propyl]amide anchor part (I), a connecting unit formed upon 1,3-propansultone ring cleavage (II), and a polyfluoroheptyloxy functional hydrophobic spacer (III). Proceeding from commercially available polyfluorinated heptanols 1a and 1b and 1,3-propanesultone 3, potassium sulfonates 4a and 4b were prepared. The reaction of 4a and 4b with phosphorus oxychloride resulted in the first synthesis of fluorine-containing sulfonyl chlorides 5a and 5b, which were reacted with 3-aminopropyltriethoxysilane 6 to give the target N-[3-(triethoxysilyl)propyl]-3-(polyfluoroheptyloxy)propane-1-sulfonamides 7a and 7b. The structures of the compounds were proved by NMR spectroscopy, mass spectrometry, and elemental analysis. The studies of their hydrophobizing properties are in progress.

Microwave in glycosylation reaction: design, and synthesis of highly substituted nicotinonitrile nucleosides

An efficient and rapid regiospecific approach for the synthesis of cyclic and acyclic nucleosides of 2-oxonicotinonitriles was performed. Whereas, glycosylation of 2-oxonicotinonitriles 1a, b with peracetylated sugars (namely, peracetylated glucose, galactose and ribose) under MWI tolerated exclusively the desired N-nucleosides 2a, b, 4a, b and 6a, b in significant yields (75–86%) and in short reaction time (5–7 min.). The same products were obtained under the conventional conditions, using halo-sugar with low yields in hard conditions. Similarly, the acyclic nucleosides 8a, b and 9a, b were obtained under MWI and conventional conditions via reaction of 1a, b with 4-bromo butyl acetate and 2-acetoxyethoxymethyl bromide. Finally, deprotection of the latter blocked N-nucleosides was performed via treatment with aqueous methanolic solution containing a catalytic amount of triethyl amine to give the desired free nucleosides 3a, b, 5a, b, 7a, b, 10a, b and 11a, b, respectively. The free nucleosides (3a, b, 5a, b, 7a, b and 11a, b) were evaluated against Gram (+ ve) bacteria, Gram (–ve) bacteria and one pathogenic Fungi namely, Aspergillus flavus. Good results were obtained for compounds 7a, b and 11a, b compared with the used standard drugs (Cefotaxime and Dermatin).

Synthesis of New Benzothiazole Acylhydrazones as Anticancer Agents.

During the last five decades, a large number of BT (Benzothiazole) derivatives formed one of the eligible structures in medicinal chemistry as anticancer agents. Most of the studies reveal that various substitutions at specific positions on BT scaffold modulate the antitumor property. The potential of BTs encouraged us to synthesize a number of new 2-((5-substitutedbenzothiazol-2-yl)thio)-N’-(2-(4-(substitutedphenyl)ethylidene)acetohydrazide derivatives and investigate their probable anticancer activity. 4-Substitued benzaldehyde derivatives (1a–1e) were afforded by the reaction of appropriate secondary amine and 4-fluorobenzaldehyde in DMF. Equimolar quantitates of 5-substitutedbenzothiazole-2-thiol, ethyl chloroacetate and K2CO3 were refluxed in acetone to obtain 2-((5-substitutedbenzothiazol-2-yl)thio)acetate derivatives (2a,2b), which reacted with excess of hydrazine hydrate to get 2-((5-substitutebenzothiazol-2-yl)thio)acetohydrazides (3a,3b). In the last step, 2-((5-substitutedbenzothiazol-2-yl)thio)-N’-(4-substitutedbenzylidene)acetohydrazide derivatives (4a–4j) were synthesized by the reaction of 1a–1e and 3a–3b in EtOH. The anticancer activity of target compounds was evaluated in three steps. First, an MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed to observe cytotoxic activity of the compounds against carcinogenic C6 (Rat brain glioma cell line), A549 (Human lung adenocarcinoma epithelial cell line), MCF-7 (Human breast adenocarcinoma cell line), and HT-29 (Human colorectal adenocarcinoma cell line) cancer cell lines. Healthy NIH3T3 (Mouse embryo fibroblast cell line) cells were also subjected to MTT assay to determine selectivity of the compounds towards carcinogenic cell lines. Secondly, inhibitory effects of selected compounds 4d, 4e, and 4h on DNA synthesis of C6 cells were investigated. Finally, flow cytometric analysis were performed to identify the death pathway of the carcinogenic cells.

Synthesis, Structures, and Reactivity of Single and Double Cyclometalated Complexes Formed by Reactions of [Cp*MCl2]2 (M = Ir and Rh) with Dinaphthyl Phosphines.

Reactions of two dinaphthyl phosphines with [Cp*IrCl2]2 have been carried out. In the case of di(α-naphthyl)phenylphosphine (1a), a simple P-coordinated neutral adduct 2a is obtained. However, tert-butyldi(α-naphthyl)phenylphosphine (1b) is cyclometalated to form [Cp*IrCl(P^C)] (3b). Complexes 2a and 3a undergo further cyclometalation to give the corresponding double cyclometalated complexes [Cp*Ir(C^P^C)] (4a,b) upon heating. In the presence of sodium acetate, reactions of 1a,b with [Cp*IrCl2]2 directly afford the final double cyclometalated complexes (4a,b). In the absence of acetate, [Cp*RhCl2]2 shows no reaction with 1a,b, whereas with acetate the reactions form the corresponding single cyclometalated complexes [Cp*RhCl(P^C)] (5a,b), which react with tBuOK to form the corresponding rhodium hydride complexes (6a,b). Treatment of 4a with CuCl2 or I2 leads to opening of two Ir–C σ bonds to yield the corresponding P-coordinated iridium dihalide (7 or 8) by means of an intramolecular C–C coupling reaction. A new chiral phosphine (11) is formed by the ligand-exchange reaction of 8 with PMe3. Reactions of the single cycloiridated complex 3b with terminal aromatic alkynes result in the corresponding five- and six-membered doubly cycloiridated complex 12 and/or η2-alkene coordinated complexes 13–15; the latter discloses that the electronic effect of terminal alkynes affects the regioselectivity. While the single cyclorhodated complex 5b reacts with terminal aromatic alkynes to form the corresponding six-membered cyclometalated complexes 16a–c by vinylidene rearrangement/1,1-insertion. Plausible pathways for formation of insertion products 13–16 were proposed. Molecular structures of twelve new complexes were determined by X-ray diffraction.

Reductive O2 Binding at a Dihydride Complex Leading to Redox Interconvertible μ-1,2-Peroxo and μ-1,2-Superoxo Dinickel(II) Intermediates.

Dioxygen activation at nickel complexes is much less studied than for the biologically more relevant iron or copper systems but promises new reactivity patterns because of the distinct coordination chemistry of nickel. Here we report that a pyrazolate-based dinickel(II) dihydride complex [KL(Ni-H)2] (1a) smoothly reacts with O2 via reductive H2 elimination to give the μ-1,2-peroxo dinickel(II) complex [KLNi2(O2)] (2a) and, after treatment with dibenzo[18]-crown-6, the separated ion pair [K(DB18C6)][LNi2(O2)] (2b); these are the first μ-1,2-peroxo dinickel intermediates to be characterized by X-ray diffraction. In 2a, the K+ is found side-on associated with the peroxo unit, revealing a pronounced weaking of the O-O bond: d(O-O) = 1.482(2) Å in 2a versus 1.465(2) in 2b; ν̃(O-O) = 720 cm-1 in 2a versus 755 cm-1 in 2b. Reaction of 1a (or 2a/2b) with an excess of O2 cleanly leads to [LNi2(O2)] (3), which was shown by X-ray crystallography ( d(O-O) = 1.326(2) Å), electron paramagnetic resonance and Raman spectroscopy (ν̃(O-O) = 1007 cm-1), magnetic measurements, and density functional theory calculations to feature two low-spin d8 nickel(II) ions and a genuine μ-1,2-superoxo ligand with the unpaired electron in the out-of-plane π*O-O orbital. These μ-1,2-superoxo and μ-1,2-peroxo species, all containing the O2-derived unit within the cleft of the dinickel(II) core, can be reversibly interconverted chemically and also electrochemically at very low potential ( E1/2 = -1.22 V vs Fc/Fc+). Initial reactivity studies indicate that protonation of 2a, or reaction of 3 with TEMPO-H, ultimately gives the μ-hydroxo dinickel(II) complex [LNi2(μ-OH)] (4). This work provides an entire new series of closely related and unusually rugged Ni2/O2 intermediates, avoiding the use of unstable nickel(I) precursors but storing the redox equivalents for reductive O2-binding in nickel(II) hydride bonds.