Synthesis of new di-(3-indolyl)arenes

1,4-Di-(3-indolyl)benzene 6 and 2,8-di-(3-indolyl)dibenzofuran 12 were synthesized from 1,4-diacetylbenzene and 2,8-diacetyldibenzofuran, respectively, via indole synthetic strategies. Investigation into the acid-catalysed formation of macrocyclic systems from these di-(3-indolyl)arenes led to the development of the 18-membered macrocycle 14 from the diindolylbenzene 6, which was capable of undergoing complexation with nickel(II) ions.     

Six-membered ring chelate complexes of Pd(II) and Pt(II) derived from di-(2-pyridyl)pyrimidin-2-ylsulfanylmethane

Cis-[MLCl₂] complexes of di-(2-pyridyl)pyrimidin-2-ylsulfanylmethane ligand (L), where M = Pd (1), and M = Pt (2) have been synthesized. Reaction of 1 with L in presence of Na[BF₄] and hot acetonitrile produced the complex [PdL₂](BF₄)₂ (3). Complexes 1-3 and ligand L have been characterized by elemental analyses, IR and NMR spectroscopy. Crystal structures of 1, 3 and L were determined by single crystal X-ray diffraction analyses, showing nonplanar structures with the pyridinic rings twisted around the bridging carbon and the ipso carbon bonds. 1 and 3 displayed a bidentate coordination of L to the palladium atom with the formation of six-membered chelate rings, where the local geometry at palladium atom was distorted square planar. In 3 the palladium atom was coordinated to two dipyridyl ligands through two of the pyridinic nitrogen atoms to form a cationic complex stabilized by two tetrafluoroborate counter-ions.     

Synthesis,antimicrobial and anticancer activities of some new N-methylsulphonyl and N-benzenesulphonyl-3-indolyl heterocycles: 1st Cancer Update

A series of 1-(N-methyl 2a–c and N-benzenesulphonyl-1H-indol-3-yl)-3-aryl-prop-2-ene-1-ones 3a–c were prepared and allowed to react with urea, thiourea or guanidine and gave the pyrimidine derivatives 4a–c to 9a–c. Base catalyzed reaction of 2a–c or 3a–c with ethyl acetoacetate gave cyclohexanone derivatives 10a–c and 11a–c, respectively. Reaction of the latter compounds with hydrazine hydrate afforded indazole derivatives 12a–c and 13a–c, respectively. On the other hand, condensation of 2c or 3c with some hydrazine derivatives namely, hydrazine hydrate, acetyl hydrazine, phenyl hydrazine and benzyl hydrazine hydrochloride gave pyrazole derivatives 14a,b-17a,b, respectively. Moreover, reaction of 2c or 3c with hydroxyl amine hydrochloride gave isoxazole derivatives 18a,b. The newly synthesized compounds were tested for their antimicrobial activity and showed that, compounds 14a, 14b, 15a and 15b were found to be the most active ones of all the tested compounds toward Salmonella typhimurium (ATCC 14,028) compared to the reference drug chloramphenicol. Eighteen new compounds namely, pyrimidin-2(1H)-ones 4a–c and 5a–c, pyrimidin-2(1H)-thiones 6a–c and 7a–c and pyrimidin-2-amines 8a–c and 9a–c were tested for their in vitro cytotoxicity against human liver carcinoma (HEPG2), human breast cancer (MCF7) and human colon cancer (HCT-116) cell lines and showed that, compounds 4c, 5c, 6c, 8c and 9c were found to be the highly active compounds compared to the reference drug doxorubicin.     

Synthesis of di- and monobromo(ferrocenylvinyl)cyclopropanes

The Wittig olefination of ferrocene-containing chalcones leads to 1,3-dienes and their cyclodimers. The reaction of 1,3-dienes with dibromocarbene yields gem-dibromo(ferrocenylvinyl)cyclopropanes. Upon reductive dehalogenation with ethylmagnesium bromide they afford the corresponding monobromo derivatives. All the obtained compounds were characterized by ¹H and ¹³C NMR, elemental analysis, and mass spectrometry. The structures of compounds 5a,b, 6g, 6h, and 7i were confirmed by X-ray diffraction analysis.     

Hemilability of 2-(1H-imidazol-2-yl)pyridine and 2-(oxazol-2-yl)pyridine ligands: Imidazole and oxazole ring Lewis basicity,Ni(II)/Pd(II) complex structures and spectra

Fourteen new organic molecules A1–A4, B1–B5, C1–C4 and D and a series of transition metal(II) complexes (Ni1–Ni9 and Pd1–Pd2b) were synthesized and studied in order to characterize the hemilability of 2-(1H-imidazol-2-yl)pyridine and 2-(oxazol-2-yl)pyridine ligands (A1–A4 = 2-R²-6-(4,5-diphenyl-1R¹-imidazol-2-yl)pyridines, R¹ = H or CH₃, R² = H or CH₃; B1–B5 = 1-R²-2-(pyridin-2-yl)-1R¹-phenanthro[9,10-d]imidazoles/oxazoles, R¹ = H or CH₃, R² = H or CH₃; C1–C4 = 2-(6-R²-pyridin-2-yl)-1H-imidazo/oxazo[4,5-f][1,10]phenanthrolines, R² = H or CH₃; D = 2-mesityl-1H-imidazo[4,5-f][1,10]phenanthroline). They were also used to study the substituent effects on the donor strengths as well as the coordination chemistries of the imidazole/oxazole fragments of the hemilabile ligands.All the observed protonation–deprotonation processes found within pH 1–14 media pertain to the imidazole or oxazole rings rather than the pyridyl Lewis bases. The donor characteristics of the imidazole/oxazole ring can be estimated by spectroscopic methods regardless of the presence of other strong N donor fragments. The oxazoles possessed notably lower donor strengths than the imidazoles. The electron-withdrawing influence and capacity to hinder the azole base donor strength of 4,5-azole substituents were found to be in the order phenanthrenyl (B series) > 4,5-diphenyl (A series) > phenanthrolinyl (C series). An X-ray structure of Ni5b gave evidence for solvent induced ligand reconstitution while the structure of Pd2b provided evidence for solvent induced metal–ligand bond disconnection.Interestingly, alkylation of 1H-imidazoles did not necessarily produce the anticipated push of electron density to the donor nitrogen. Furthermore, substituents on the 4,5-carbons of the azole ring were more important for tuning donor strength of the azole base. DFT calculations were employed to investigate the observed trends. It is believed that the information provided on substituent effects and trends in this family of ligands will be useful in the rational design and synthesis of desired azole-containing chelate ligands, tuning of donor properties and application of this family of ligands in inorganic architectural designs, template-directed coordination polymer preparations, mixed-ligand inorganic self-assemblies, etc.     

Synthesis and structural features of tris(5-bromo-2-methoxyphenyl)antimony dicarboxylates

Tris(5-bromo-2-methoxyphenyl)antimony bis(4-nitrophenylacetate) (I), tris(5-bromo-2-methoxyphenyl)antimony bis(2-methoxybenzoate) (II), and tris(5-bromo-2-methoxyphenyl)antimony bis(phenylpropiolate) (III) have been synthesized via the reaction between tris(5-bromo-2-methoxyphenyl) antimony and 4-nitrophenylacetic acid, 2-methoxybenzoic acid, and phenylpropiolic acid, respectively, in the presence of hydrogen peroxide (molar ratio: 1: 2: 1). According to X-ray diffraction data, the antimony atom in molecules of complexes I–III has a distorted trigonal bipyramidal coordination. The OSbO axial angles and the CSbC bond angles in the equatorial plane are 173.27(15)°, 172.96(11)°, 172.99(10)°, and 115.5(2)°–123.3(2)°, 108.81(16)°–129.32(17)°, and 110.66(17)°–127.91(17)°, respectively. The Sb-O bond lengths are 2.092(4) and 2.115(4)Å in I, 2.088(3) and 2.097(2) Å in II, and 2.096(3) and 2.120(3) Å in III. The Sb-C bonds range within 2.095(6)–2.123(6) Å in I, 2.107(4)–2.117(4) Å in II, and 2.097(4)–2.116(4) Å in III. Complexes I, II, and III are observed to have intramolecular Sb…OCH₃ contacts (3.169–3.226, 3.134–3.174, and 3.147–3.196 Å, respectively) in addition to Sb…O=C interactions (3.121, 3.139Å; 2.944, 3.038 A0; 3.111, 3.120 Å).     

Optically active 1-(benzofuran-2-yl)ethanols and ethane-1,2-diols by enantiotopic selective bioreductions

Enantiotopic selective reduction of 1-(benzofuran-2-yl)ethanones 1a–d, 1-(benzofuran-2-yl)-2-hydroxyethanones 4a–c and 2-acetoxy-1-(benzofuran-2-yl)ethanones 3a–c was performed by baker's yeast for preparation of optically active (benzofuran-2-yl)carbinols [(S)-5a–d, (S)-6a–c and (R)-6a–c, enantiomeric excess from 55 to 93% ee].     

Synthesis of Immunoactive Tris(2-hydroxyethyl)ammonium 1-R-Indol-3-ylsulfanyl(sulfonyl)acetates

Difficultly accessible 1-R-indol-3-ylsulfanyl(sulfonyl)acetic acids 1-R-IndYCH₂CO₂H (R = H, Me, Bn; Y = S, SO₂) 1a–Id were prepared. Their reaction with tris(2-hydroxyethyl)amine yielded tris(2-hydroxyethyl) ammonium 1-R-indol-3-ylsulfanyl(sulfonyl)aceetates (protatranes) 2a–2d. The immunoactive properties of 2a–2d were studied. Protatranes 2a, 2c, and 2d proved to be effective immunosuppressive agents (up to 99.5% inhibition of mice splenocyte proliferation in vitro).     

cis-Palladium(II) complexes of derivatives of di-(2-pyridyl)methane: Study of the influence of the bridge group in the coordination mode

Palladium(II) complexes containing di-(2-pyridyl)-N-methylimine (1), di-(2-pyridyl)methanol (2) and di-(2-pyridyl)methyl-N,N-diethyldithiocarbamate (4) ligands were synthesized and characterized by ¹H and ¹³C NMR in solution, IR and X-ray single crystal diffraction. Crystal structures of cis-dichloro[di-(2-pyridyl)-N-methylimine]palladium(II) (5), cis-dichloro[di-(2-pyridyl)methanol]palladium(II) (6) and cis-dichloro[di-(2-pyridyl)methyl-N,N-diethyldithiocarbamate]palladium(II) (7) showed a bidentate coordination mode of the di-(2-pyridyl)methane derivatives 1, 2 and 4. In these complexes is observed the formation of a five-membered chelate ring with the iminic ligand 1 and six-membered chelate rings with the pyridinic ligands 2 and 4. In all complexes the palladium atom displays a distorted square planar geometry.     

Copper(II) coordination chemistry of 2-methyl-2-(2-pyridyl)-1,3-propan-diol: Syntheses and structures of mono-, di-, and tricopper complexes

Six copper(II) complexes with N,O-donor ligand 2-methyl-2-(2-pyridyl)-1,3-propan-diol (H₂ppdo) were synthesized and characterized. Treatment of CuCl₂ or Cu(OTf)₂ with H₂ppdo led to the formation of bis(H₂ppdo) monomers [Cu(H₂ppdo)₂][CuCl₄] (1) and [Cu(H₂ppdo)₂](OTf)₂ (2), respectively. Both 1 and 2 are comprised of the copper atom coordinated by two ligands in an axially-compressed tetragonal geometry with the pyridyl N atoms in the axial positions and the alcohol O atoms in the equatorial plane. The treatment of 1 or 2 with Et₃N produced copper(II) complexes of varying nuclearity. Treatment of 1 with excess Et₃N generated two binuclear Cu(II) clusters [Cu₂(Hppdo)₂Cl₂] (3) and [Cu₂(Hppdo)₂Cl₂(CH₃OH)₂] (4), where only one alcohol OH group per ligand has been deprotonated, while similar treatment of 2 with excess Et₃N afforded the trimeric copper(II) species [Cu₃(Hppdo)₄](OTf)₂ (5). The structures of 3 and 4 are similar, with alkoxo-O ligand atoms bridging between two square pyramidal copper atoms, and the alcohol-O ligand atoms either coordinating in the axial position in 3, or uncoordinated in 4. Treatment of CuCl₂ with H₂ppdo and Et₃N afforded the trinuclear Cu(II) complex, [Cu₃(Hppdo)₄]Cl₂ (6). Complexes 5 and 6 are made up of one square-planar copper sandwiched between two tetragonally distorted six-coordinate Cu(Hppdo)₂ moieties, where the bridging alkoxo-O atoms link the copper atoms.     

Synthese und reaktionen von di(benzthiazol-2-yl)- und di(benzoxazol-2-yl)methylgerman

Reaction of benzthiazol-2-yl and benzoxazol-2-yl-trimethylstannane with methyltrichlorogermane leads to the mono-, bis- and tris-heterocyclic substituted germanes RGe(Me)Cl₂, R₂Ge(Me)Cl, R₃GeMe (2, 3, 4: R = benzthiazol-2-yl; 6, 7, 8: R = benzoxazol-2-yl), which exist in a mobile equilibrium. From the chlorogermanes 2, 3 and 6, 7 the corresponding germanes 9, 10 and 11, 12 can be obtained by reaction with trimethylstannane. From the germane 10 the mono- and bis-N-methylated salts 15 and 17 can be synthesized. The compounds 10, 12 and 15 easily decompose by α-elimination reactions. The salt 17 can be regarded as a suitable model substance for the synthesis of a germacyanine dye.     

New hydrogen-bonded dimeric and polymeric gold(I) complexes of the heterodifunctional ligand Ph2PNHP(O)Ph2

The preparation of several new gold(I) complexes by chloride metathesis of [AuCl(HL)] [HL=Ph₂PNHP(O)Ph₂] with either HL or K[Ph₂P(E)NP(E)Ph₂] (E=S or Se) is described. All compounds were characterised by a combination of ³¹P{¹H}, ¹H and IR spectroscopy, microanalysis and X-ray crystallography. X-ray structural studies reveal that [Au(HL)₂]Cl [monoclinic, space group P2₁/c, a=9.0726(3) Å, b=21.0847(6) Å, c=12.0131(3) Å, β=105.1090(10)°, V=2219 ų, Z=2, final R=3.97] forms a one dimensional polymeric structure in which alternating [Au(HL)₂]⁺ and Cl⁻ ions are linked through intermolecular N–H⋯Cl hydrogen-bonding. In contrast the three-co-ordinate compound [Au{Ph₂P(Se)NP(Se)Ph₂-Se,Se′}(HL)] [monoclinic, space group P2₁/a, a=21.6752(5) Å, b=9.1200(10) Å, c=24.0742(7) Å, β=106.080(2)°, V=4573 ų, Z=4, final R=8.94] forms hydrogen-bonded dimer pairs analogous to that previously observed in non-complexed HL. The X-ray crystal structure of the gold(I) precursor [AuCl(HL)] has also been determined: monoclinic, space group P2₁/c, a=10.217(8) Å, b=23.256(5) Å, c=20.086(5) Å, β=101.15(4)°, V=4683 ų, Z=8, final R=5.2. The X-ray crystal structure reveals intermolecular N–H⋯OP hydrogen-bonding between adjacent [AuCl(HL)] molecules forming infinite chains.     

Carbene—23: Phosphene: [2+2]-und [4 + 2]-cycloaddition von (diphenylmethylen) phenylphosphan-oxid mit α,β-ungesättigten ketonen

The photolysis of 1 produces the carbene 2, which is transformed into the short lived phosphene 4 by phenyl migration. With the α, β-unsaturated ketones 6a–d in a [2+2] cycloaddition 4 yields the 1,2λ⁵-oxaphos-phetanes 7a–d The heterocycles partially undergo a photofragmentation, which produces the olefines 9a–d and the heterocumulene 8. If 4 is generated from 1 under thermal conditions in the presence of 6a–c, formation of four membered rings and fragmentation is observed too; in addition 4 undergoes a [4+2] cycloaddition with the hetero-1, 3-dienes 6a–c, leading to 15a-c. This behaviour corresponds to that of the carbonylanalogue diphenyl-ketene with 6a (formation of CO₂ and 9a via the β-lactone 16 such as of 17).     

Structural and spectral investigations on some new Ni(II) complexes of di-2-pyridyl ketone N(4)-phenylthiosemicarbazone

Ni(II) complexes (1–5) of di-2-pyridyl ketone N(4)-phenylthiosemicarbazone (HL) have been synthesized and spectrochemically characterized. Elemental analyses revealed a NiL₂ · 2H₂O stoichiometry for compound 1. However, the single crystals isolated revealed a composition NiL₂ · 0.5(H₂O)0.5(DMF). The compound crystallizes into a monoclinic lattice with the space group P2₁/n. Complexes 2, 3 and 4 are observed to show a 1:1:1 ratio of metal:thiosemicarbazone:gegenion, with the general formula NiLX · yH₂O [X = NCS, y = 2 for 2; X = Cl, y = 3 for 3 and X = N₃, y = 4.5 for 4]. Compound 5 is a dimer with a metal:thiosemicarbazone:gegenion ratio of 2:2:1, with the formula [Ni₂L₂(SO₄)] · 4H₂O.     

Alkaline cleavage of some (1-phenylsulfonyl-2-pyrazolin-5-yl)-methyl ketones and related compounds

The (1-phenylsulfonyl-2-pyrazolin-5-yl)-methyl ketones 1a–c and the ethylene hemithioketal of 1b are converted by ethanolic sodium hydroxide into a variety of heterocyclic products such as pyridines, pyrazoles (2a, 2c, and the ethylene hemithioketal of 2f, respectively) and pyridazines (7a, b). The formation of part of these products involves a novel variant of the van Alphen rearrangement and a novel 3H-pyrazole → pyridazine ring enlargement reaction. The oximes of the ketones 1a–c as well as the oxime ether 14 are converted under elimination of their side chains and/or the benzenesulfonyl group into aromatic pyrazole derivatives and ring transformation products, viz. derivatives of 2-isoxazoline and pyridine, respectively. The cleavage reactions of the oxime derivatives are compared with those of their parent ketones.     

Preparation of various enantiomerically pure (benzotriazol-1-yl)- and (benzotriazol-2-yl)-alkan-2-ols

(S)-(−)-(Benzotriazol-1-yl)- and (S)-(−)-(benzotriazol-2-yl)-alkan-2-ols 7a–9a, 7b–9b and their (R)-(+)-acetates 10a–12a and 10b–12b were prepared in high enantiomeric excess via lipase from Pseudomonas fluorescens (Amano AK) catalyzed enantioselective acetylation of racemic alcohols 4a–6a and 4b–6b with vinyl acetate in tert-butyl methyl ether or toluene at 23 °C. The enantioselectivity of this transformation was dependent on the length of the alkyl chain with E-values ranging from 30 to 57. Several benzotriazole substituted ketones 1a–3a and 1b–3b were synthesized from 1H-benzotriazole and corresponding haloketones. These compounds were stereoselectively reduced with Baker’s yeast in water or in organic solvent containing 5% v/v of water at 30 °C to give the (S)-(−)-alcohol. Better stereoselectivity was observed in the kinetic resolution of racemic alcohols 4a–6a and 4b–6b (ee = 69–92% at 44–52% conversion) compared to reduction of corresponding prochiral ketones 1a–3a and 1b–3b with Baker’s yeast (ee = 40–67% at 39–89% conversion). Enhanced enantioselectivities were observed at lower temperatures.     

Diastereoselective Diels–Alder cycloaddition of [(1R)-10-(N,N-diethylsulfamoyl)isobornyl] 2H-azirine to nucleophilic 1,4-disubstituted 1,3-dienes

Chiral [(1R)-10-(N,N-diethylsulfamoyl)isobornyl] 2H-azirine 1 [Timén, A. S.; Somfai, P. J. Org. Chem. 2003, 9958–9963; Timén, A. S.; Fisher, A.; Somfai, P. Chem. Commun. 2003, 1150–1151]. was combined to a number of 1,4-disubstituted-2-aza-1,3-dienes 2a–g [Alves, M. J.; Durães, M. M.; Gil Fortes, A. Tetrahedron 2004, 6541–6553] to give cycloadducts 8a–g as major isomers. High to good diastereofacial differentiation of the two faces of the azirine is observed when R¹,R² = Ar 2a–e; diastereoselectivity drops drastically when R¹ = Me or H 2f,g. Cycloaddition of the azirine 1 to E,E-1,4-diacetoxy-1,3-butadiene shows complete diastereoselectivity giving cycloadduct 11a.     

Stereospecific synthesis and absolute configuration of the (2S,3S,4S)-isomer of 2-methyl-2-(carboxycyclopropyl)glycine (MCCG)

The conformationally restricted metabotropic glutamate receptor antagonist (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)glycine 1 (MCCG) has been synthesized in a stereoselective manner (>99% ee) with the (2S,3S,4S) absolute configuration of this molecule being confirmed by X-ray crystallographic analysis. Subsequent physico–chemical studies were undertaken and the data are at odds with those of the commercially available product.     

Triosmium clusters containing bridging dppm and EPh (E = S,Te) ligands: X-ray structures of [(μ-H)Os3(CO)7(μ-SPh){μ3-η4-Ph2PCHP(Ph)C6H4}], [Os3(CO)8(μ-SPh)2(μ-dppm)] and [Os3(CO)8(μ-TePh)2(μ-dppm)]

Heating [Os₃(CO)₁₀(μ-dppm)] (1) with two equivalents of PhSSPh in toluene under reflux provided three new triosmium compounds [(μ-H)Os₃(CO)₇(μ-SPh){μ₃-η⁴-Ph₂PCHP(Ph)C₆H₄}] (2), [Os₃(CO)₈(μ-SPh)₂(μ-dppm)] (3) and [(μ-H)Os₃(CO)₇(μ-η²-SC₆H₄)(μ-SPh)(μ-dppm)] (4) in 20%, 21% and 26% yields, respectively. In contrast, a similar reaction of 1 with two equivalents of PhTeTePh in refluxing toluene gave the binuclear compound [Os₂(CO)₄(μ-TePh)₂(μ-dppm)] (6) in 15% yield, and two 50 electron isomeric compounds 5 and 7 with the formula [Os₃(CO)₈(μ-TePh)₂(μ-dppm)] in 20% and 23% yields, respectively. Thermolysis of 3 at 110 °C afforded 4 in 53% yield which on further thermolysis in refluxing octane at 128 °C gave 2 in 45% yield. Thermolysis of 3 in refluxing octane also gave 2 in 50% yield. The new compounds, 2–7, were all spectroscopically characterized, and the X-ray structures of 2, 3 and 7 have been determined. Compound 2 contains a bridging SPh ligand and a μ₃,η⁴-Ph₂PCHP(Ph)C₆H₄ ligand, formed by two kinds of C–H activation, including orthometallation of a phenyl group as well as an unusual activation of the methylene group of the dppm ligand. The molecular structure of 3 reveals that two SPh groups span the open Os–Os edge of the Os₃ triangle, while the dppm ligand bridges one of the closed Os–Os edges. In compound 7, one TePh group spans the open Os–Os edge, while the other spans one of the two closed Os–Os edges and the dppm ligand bridges the third Os–Os vector.     

Correlation between molecular structure and optical properties for the bis(2-(2-hydroxyphenyl)benzothiazolate) complexes

A series of methyl-substituted bis(2-(hydroxyphenyl)benzothiazolate)zinc derivatives [Zn(n-MeBTZ)₂, n = 3 (1a), 4 (1b), 5 (1c)] were synthesized to investigate the correlation between molecular structures and optical properties. The results indicate that the blue-emitting (λ_max = 470 nm) complex 1b is monomer with a higher PL quantum efficiency than complexes 1, 1a, 1c. Two green-emitting (λ_max = 507 nm and 499 nm) complexes 1a and 1c have special bi-molecular structures. The molecular structure for Zn(BTZ)₂ (complex 1) is dimer. Bilayer organic light-emitting devices were fabricated by using these complexes as emitting layer. The maximum emission wavelengths of the devices are in the range of 501–553 nm. The devices show turn-on voltages at 9.2, 12.7, 2.3 and 10.7 V for complex 1, 1a, 1b, and 1c, respectively. In particular, the device with complex 1b shows a higher brightness than the other complexes under the same conditions.