Synthesis of bimodal molecular weight distribution polyethylene with α-diimine nickel(II) complexes containing unsym-substituted aryl groups in the presence of methylaluminoxane

A series of unsymmetrical complexes of 2,3-bis(2-phenylphenyl)-butanediimine nickel(II) dibromide (complex 1), 1,4-bis(2-isopropyl-6-methylphenyl)-acenaphthenediimine nickel(II) dibromide (complex 2) and meso- and rac-1,4-bis (2,4-di-tert-butyl-6-methylphenyl)-acenaphthenediimine nickel(II) dibromide (meso-3 and rac-3) were synthesized and activated by methylaluminoxane (MAO) for ethylene polymerization. By ¹³C NMR characterization, meso- and rac-stereo-isomers were detected in the condensation products resulting from the reaction of unsym-substituted anilines with diketones. It was notable that meso- and rac-isomers in ligand 1 or ligand 2 could not be separated owing to their interconversion, however, meso- and rac-isomers in ligand 3 could be isolated and identified by X-ray diffraction and NMR analysis. At low polymerization temperatures, complex 1/MAO afforded polyethylene with bimodal molecular weight distribution, while complex 2/MAO prepared polyethylene with single-modal distribution. Moreover, by raising polymerization temperature or extending time of catalyst aging, bimodal molecular weight distribution polyethylene was also produced by complex 2/MAO. The hypothesis of bimodal molecular weight distribution polyethylene synthesized by unsymmetrical α-diimine nickel(II) complexes was supported that the molecular weight of polyethylene produced by rac-3/MAO was significantly higher than that produced by meso-3/MAO under identical polymerization conditions. A unique methodology to prepare polyethylene with bimodal molecular weight distribution was demonstrated.     

Synthesis and structures of dinuclear iron, molybdenum and tungsten complexes derived from (PhCHCHPh)-coupled bis(cyclopentadiene)

Reductive coupling of phenylfulvene with amalgamated calcium metal followed by hydrolysis yields CpPhCHCHPhCp (1) in high yield. Refluxing ligand 1 and Fe(CO)₅ in xylene produces (PhCHCHPh)-coupled bis(cyclopentadienyl) tetracarbonyl diiron (PhCHCHPh)[(η⁵-C₅H₄)Fe(CO)₂]₂ (2) as a mixture of meso (2-meso) and racemic isomers (2-rac). The pure racemic isomers of the Mo and W analogues (3-rac and 4-rac) have been synthesized by lithiation of ligand 1 and addition of (MeCN)₃M(CO)₃ (M = Mo, W) followed by oxidation with 2 equiv. of ferrocenium tetrafluoroborate. All the new complexes have been fully characterized. The molecular structures of 1-meso, 2-meso, 2-rac, 3-rac, and 4-rac have been determined by X-ray diffraction analysis.     

Syntheses of rac/meso-{PhP(3-t-Bu-C5H3)2}-Zr{RN(CH2)3NR}, structural analyses of rac-{PhP(3-t-Bu-C5H3)2}Zr{RN(CH2)3NR} (where R is SiMe3 or Ph), and meso to rac isomerization

Syntheses of rac/meso-{PhP(3-t-Bu-C₅H₃)₂}Zr{Me₃SiN(CH₂)₃NSiMe₃} (rac-3/meso-3) and rac/meso-{PhP(3-t-Bu-C₅H₃)₂}Zr{PhN(CH₂)₃NPh} (rac-4/meso-4) were achieved by metallation of K₂[PhP(3-t-Bu-C₅H₃)₂] · 1.3 THF (2) with Zr{RN(CH₂)₃NR}Cl₂(THF)₂ (where R = SiMe₃ or Ph, respectively) using ethereal solvent. These isomeric pairs were characterized by ¹H, ¹³C{¹H}, and ³¹P{¹H} NMR spectroscopy; rac-3 and rac-4 were also examined via single crystal X-ray crystallography. The structures of rac-3 and rac-4 are notable in the tendency of the cyclopentadienyl rings towards η³ coordination. While isolated samples of rac-3/meso-3 and rac-4/meso-4 slowly isomerize in tetrahydrofuran-d₈ to equilibrium ratios, the isomerization rate for 3 is more than 15-fold greater than that for 4. In addition, equilibrium ratios are rapidly reached when isolated samples of rac-3/meso-3 and rac-4/meso-4 are exposed to tetrabutylammonium chloride in tetrahydrofuran-d₈ solvent. We propose that a nucleophile (either chloride or the phosphine interannular linker) brings about dissociation of one cyclopentadienyl ring, thus promoting the rac/meso isomerization mechanism.     

Facile syntheses, structural characterizations, and isomerization of disiloxane-1,3-diols

In the hydrolysis reaction of dichlorosilanes having an intramolecular coordinating atom, dcisiloxane-1,3-diols, [(OH){o-(CH₃)₂NCH₂-C₆H₄}RSi]₂O(R=CH₂CH (1), C₆H₅ (2), o-(CH₃)₂NCH₂C₆H₄ (3), Me (4)), were obtained in high yields. The results of the crystal structure analyses of meso-2, rac-2a, rac-2b and 3 are reported. They showed strong intramolecular hydrogen bondings between the hydroxy group and the nitrogen atom. We have also found that the diastereomeric isomerization of meso-2 to rac-2 in CDCl₃ solvent containing moisture occurred to result in the 55:45 equilibrium mixtures of the isomers and vice versa.     

Variable temperature H and Si NMR of diastereomeric 1,3-dihydroxy-1,3-bis[(2-dimethylaminomethyl)phenyl]-1,3-divinyldisiloxanes

Variable temperature NMR experiments of diastereomeric 1,3-dihydroxy-1,3-bis[(2-dimethylaminomethyl)phenyl]-1,3-divinyldisiloxanes, meso-1 and rac-1 having intramolecular hydrogen bondings were carried out. As temperature increased, the ¹H NMRs of hydroxy groups of 1 resulted in a low frequency and their ²⁹Si NMRs were very slightly shifted to a low frequency. Interestingly, the ¹H NMR of two benzylic protons was split more widely as temperature increased.     

Polymerization of ethene with zirconocene catalysts: an experimental and quantum chemical study of the influence of para-substituent in benzyl in bis{η-(1-benzyl)indenyl}zirconium dichlorides

The meso- and rac-like isomers of bis{η⁵-(1-benzyl)indenyl}zirconium dichloride (5), bis{η⁵-(1-para-methoxybenzyl)indenyl}zirconium dichloride (6), bis{η⁵-(1-para-fluoro-benzyl)indenyl}zirconium dichloride (7) and bis{η⁵-(1-phenylethyl)indenyl}zirconium dichloride (8) were synthesized and isolated. Solid-state structures of meso- and rac-like 5 were determined by X-ray structure analysis. Polymerization properties of the methylaluminoxane (MAO) activated diastereomers of complexes 5-8 were studied in ethene polymerizations under different monomer concentrations. The rac-like isomer of 1-phenylethyl-substituted 8/MAO showed significantly higher activity than the 1-benzyl substituted analogs 5-7/MAO. In addition, rac-8/MAO behaves like a single center catalyst producing polyethene with narrow molar mass distribution (1.8-1.9), while diastereomers of 5-7/MAO produce polymers with molar mass distributions varying from 2.7 up to 10.3. The rac and meso-like isomers of 5-7/MAO have different response on the monomer concentration. Quantum chemical calculations suggest a strong interaction between the benzyl substituent and the electron deficient zirconium center. The phenyl metal coordination energies depend on the electronic properties of the para-substituent. In 8/MAO, due to the ethyl spacer, the coordination does not have a significant role and therefore much higher activity and single center polymerization behavior is observed.     

Enantioselective synthesis of axially chiral 1-(1-naphthyl)isoquinolines and 2-(1-naphthyl)pyridines through sulfoxide ligand coupling reactions

Racemic 1-(1′-isoquinolinyl)-2-naphthalenemethanol rac-12 was prepared through a ligand coupling reaction of racemic 1-(tert-butylsulfinyl)isoquinoline rac-7 with the 1-naphthyl Grignard reagent 10. Resolution of rac-12 was achieved through chromatographic separation of the Noe-lactol derivatives 14 and 15, providing (R)-(−)-12 of >99% ee and (S)-(+)-12 of 90% ee. The ligand coupling reaction of optically enriched sulfoxide (S)-(−)-7 (62% ee) with Grignard reagent 10 furnished rac-12, with the absence of stereoinduction resulting from competing rapid racemisation of the sulfoxide 7. Reaction of optically enriched (S)-(−)-7 with 2-methoxy-1-naphthylmagnesium bromide was also accompanied by racemisation of the sulfoxide 7, and furnished optically active (+)-1-(2′-methoxy-1′-naphthyl)isoquinoline (+)-3b in low enantiomeric purity (14% ee). The absolute configuration of (+)-3b was assigned as R using circular dichroism spectroscopy, correcting an earlier assignment based on the Bijvoet method, but in the absence of heavy atoms. Optically active 2-pyridyl sulfoxides were found not to undergo racemisation analogous to the 1-isoquinolinyl sulfoxide 7, with the ligand coupling reactions of (R)-(+)- and (S)-(−)-2-[(4′-methylphenyl)sulfinyl]-3-methylpyridines, (R)-(+)-17 and (S)-(−)-17, with 2-methoxy-1-naphthylmagnesium bromide providing (−)- and (+)-2-(2′-methoxy-1′-naphthyl)-3-methylpyridines, (−)-18 and (+)-18, in 53 and 60% ee, respectively. The free energy barriers to internal rotation in 3b and 18 have been determined, and the isoquinoline (R)-(−)-12 examined as a ligand in the enantioselectively catalysed addition of diethylzinc to benzaldehyde; (R)-(−)-12 was also converted to (R)-(−)-N,N-dimethyl-1-(1′-isoquinolinyl)-2-naphthalenemethanamine (R)-(−)-19, and this examined as a ligand in the enantioselective Pd-catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate.     

The first bidentate phosphanylborohydride: Synthesis, structure, and reactivity towards [CpFe(CO)2I]

Deprotonation of the phosphane-borane adduct rac/meso-(HP(BH₃)(Ph)CH₂)₂ (2) with KH provides facile access to the bidentate phosphanylborohydride rac/meso-K₂[(P(BH₃)(Ph)CH₂)₂] (3). Treatment of 3 with two equivalents of [CpFe(CO)₂I] gives the dinuclear complex rac/meso-[(CpFe(CO)₂)₂-μ-(P(BH₃)(Ph)CH₂)₂] (4). Single crystals of the pure diastereomers meso-2, meso-3(thf)₄, and rac-4 have been grown from toluene/pentane, diethyl ether/thf, and benzene/pentane, respectively. The molecular structures of all three compounds have been determined by X-ray crystallography.     

Optically active pentacyclic binuclear diorganotin compounds

Three optically active binuclear diorganotin compounds (2-4) were prepared from an optically active oxalamide: (1S,2R)-(−)-[N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N′-(2-hydroxy-phenyl)-oxalamide (1). The new compounds [1-(2′,2′-diorganyl-1′-oxa-3′-aza-2′-stanna-indan-3′-yl)-2-(2″,2″-diorganyl-4″-methyl-5″-phenyl[1,3,2]-oxazastannolidin-3″-yl)-ethane-1,2-dione {organyl = methyl (2), n-butyl (3) or phenyl (4)} were characterized by IR, elemental analysis and mass spectrometry. Compounds 3 and 4 were submitted to a detailed NMR study in order to assign their resonances (¹H and ¹³C) and specially the two different ¹¹⁹Sn signals for each compound. The X-ray diffraction analysis of compound 4 showed a planar pentacyclic framework with two penta-coordinated tin atoms with a distorted tbp geometry and 12 intramolecular hydrogen bonds.     

Palladium-catalyzed asymmetric synthesis of allylic alcohols from unsymmetrical and symmetrical racemic allylic carbonates featuring C-O-bond formation and dynamic kinetic resolution

Described is the asymmetric synthesis of the allylic alcohols 11 (85% ee), 15 (99% ee), 17 (93% ee), 19 (61% ee), and 21 (69% ee) through a Pd-catalyzed reaction of the unsymmetrical carbonates rac-10, rac-12, rac-14, rac-16, rac-18, and rac-20, respectively, with KHCO₃ and H₂O in the presence of bisphosphane 6. Similarly the allylic alcohols 23 (99% ee) and 25 (97% ee) have been obtained from the symmetrical carbonates rac-22 and rac-24, respectively. Reaction of the meso-biscarbonate 26 with H₂O and Pd(0)/6 afforded alcohol 27 (96% ee), which was converted to the PG building block 32. The unsaturated bisphosphane 33 showed in the synthesis of alcohols 36, 37, and 39 a similar high selectivity as 6. The formation of alcohols 11, 15, and 17 involves an efficient dynamic kinetic resolution.     

Synthesis, crystal structure analysis, and pharmacological characterization of desmethoxy-sila-venlafaxine, a derivative of the serotonin/noradrenaline reuptake inhibitor sila-venlafaxine

rac-Desmethoxy-sila-venlafaxine (rac-3) is a derivative of the noradrenaline-selective serotonin/noradrenaline reuptake inhibitor rac-sila-venlafaxine (rac-1b), a silicon analogue of the serotonin-selective serotonin/noradrenaline reuptake inhibitor rac-venlafaxine (rac-1a) (rac-1a, rac-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol; rac-1b, rac-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]-1-silacyclohexan-1-ol). The synthesis and crystal structure analyses of rac-3 and rac-3 · HCl are reported, and the pharmacological properties of rac-1a, rac-1b, rac-2 (a sila-venlafaxine derivative with a silacyclopentanol skeleton instead of a silacyclohexanol framework), and rac-3 are compared (comparison of the pharmacological selectivity profiles with respect to serotonin, noradrenaline, and dopamine reuptake inhibition).     

Molecular recognition of biotin, barbital and tolbutamide with new synthetic receptors

We have measured, by means of NMR titrations, the binding constants for the complexes between hosts N,N′-bis(6-methylpyridin-2-yl)-1,3-benzenedicarboxamide (7) and 4-chloro-N,N′-bis(6-methylpyridin-2-yl)-2,6-pyridinedicarboxamide (8, hydrated) with biotin methyl ester (1), N,N′-dimethylurea (2), 2-imidazolidone (3), N,N′-trimethylenurea (4), barbital (5) and tolbutamide (6) as guests. Molecular Mechanics calculations (Monte Carlo Conformational Search, AMBER and OPLS force fields, MacroModel v.8.1) on the complexes formed between the foregoing guests and hosts 7 and 8, comparatively with 4-oxo-N,N′-bis(6-methylpyridin-2-yl)-1,4-dihydro-2,6-pyridinedicarboxamide (9a) have been carried out in order to determine the correlation between experimental and theoretical results and to understand the behaviour of the designed new hosts. Finally we have performed single point DFT [B3LYP/6-31G(d,p)] calculations on the optimised Molecular Mechanics geometries for the complexes between hosts 7-9 and water.     

Structural characterization of a copper(II) complex containing oxidative cyclization of N-2-(4-picolyl)-N′-(4-methoxyphenyl)thiourea,new ligands of 4-picolylthiourea derivatives and the precursor molecular structure of oxidative cyclization of N-(2-pyridyl)-N′-(4-methoxyphenyl)thiourea

Three new compounds of aryl thiourea derivatives, namely N-2-(4-picolyl)-N′-(4-methoxyphenyl)thiourea (L1), N-2-(6-picolyl)-N′-(4-methoxyphenyl)thiourea (L2) and N-2-(4-picolyl)-N′-(4-nitrophenyl)thiourea (L3), and the new copper(II) complex [Cu(4PicTz4OMePh)(OAC)(EtOH)] (C1), as a result of oxidative cyclization of the ligand (L1), were synthesized. In addition, pure precursor (P1), as the product of the oxidative cyclization of N-(2-pyridyl)-N′-(4-methoxyphenyl)thiourea (L4), was isolated and characterized. Ligands (L1) and (L2) were characterized by ¹H and ¹³C NMR and single crystal X-ray analysis. ¹H NMR spectroscopy showed strong hydrogen bonding interactions between N′H-functionalities and the pyridine nitrogen atoms as well as weak intermolecular hydrogen bonding between the thione sulfur and the NH hydrogen. Structural studies of complex (C1) showed that the copper ion is five-coordinated with a square-pyramidal environment. The oxidative cyclization of ligand (L1) results in an anionic bidentate ligand in complex (C1). Both ligand (L1) and precursor (P1) crystallize as centrosymmetric dimers.     

A convenient synthesis of 1′-H-spiro-(indoline-3,4′-piperidine) and its derivatives

A simple synthetic route has been developed to prepare 1′-H-spiro(indoline-3,4′-piperidine) (1d). Dialkylation of 2-fluorophenylacetonitrile with N-(tert-butyloxycarbonyl)-bis(2-chloroethyl)amine (5) gave 6. Deprotection of Boc followed by cyclization resulted 1d in 67% overall yield. Selective Boc or Cbz protection of 1′-N gave 1a or 1b with 90 and 85% yield, respectively. Thus, in a five-step procedure, 1a and 1b were synthesized from commercially available reagents in over 50% overall yield. All 3 compounds (1a, 1b and 1d) can be utilized as templates to synthesize compounds for GPCR targets.     

An approach to the synthesis of chemically modified bisazocalix[4]arenes and their extraction properties

Bisazocalix[4]arenes [N,N′-bis(5-azo-25,26,27-tribenzoyloxy-28-hydroxycalix[4]arene)benzene (1), N,N′-bis(5-azo-25,26,27-tribenzoyloxy-28-hydroxycalix[4]arene)biphenyl (2) and N,N′-bis(5-azo-25,26,27-tribenzoyloxy-28-hydroxycalix[4]arene)-2,2′-dinitro biphenyl (3)] have been synthesized from 25,26,27-tribenzoyloxy-28-hydroxycalix[4]arene by diazocoupling with the corresponding aromatic diamines (p-phenylenediamine, 4,4′-diamino biphenyl and 4,4′-diamino-2,2′-dinitrobiphenyl). Extraction studies of bisazocalix[4]arenes 1, 2, and 3 show no difference in their extraction behavior and selectivity, whereas azocalix[4]arenes are a poor extractant for heavy metal cations. The absorption spectra of the prepared bisazocalix[4]arenes are discussed, both the effect of varying pH and solvent upon the absorption ability of bisazocalix[4]arenes.     

Thermal decomposition of the tert-butyl perester of thymidine-5′-carboxylic acid. Formation and fate of the pseudo-C4′ radical

Thermal decomposition of the tert-butyl perester of thymidine-5′-carboxylic acid 1 carried out at 85 °C in different solvents affords the tert-butylacetal 4a, deriving from in cage decomposition, and pseudo C4′ radicals 2. Radicals 2 can be reduced to 5 by hydrogen atom abstraction from thiol (thiophenol or glutathione) or THF, or can be oxidized to cations 8 by dioxygen or perester 1 itself. Cations 8 are stereoselectively trapped by the nucleophilic solvent (tert-butanol, methanol, water) to give acetals 4a-c.     

Reactions of bis(tetrazole)phenylenes. Surprising formation of vinyl compounds from alkyl halides

The reactions of 1,2-bis(tetrazol-5-yl)benzene (1), 1,3-bis(tetrazol-5-yl)benzene (2), 1,4-bis(tetrazol-5-yl)benzene (3), 1,2-(Bu₃SnN₄C)₂C₆H₄ (4), 1,3-(Bu₃SnN₄C)₂C₆H₄ (5) and 1,4-(Bu₃SnN₄C)₂C₆H₄ (6) with 1,2-dibromoethane were carried out by two different methods in order to synthesise pendant alkyl halide derivatives of the parent bis-tetrazoles. This lead to the formation of several alkyl halide derivatives, substituted at either N1 or N2 on the tetrazole ring, as well as the surprising formation of several vinyl derivatives. The crystal structures of both 1,2-[(2-vinyl)tetrazol-5-yl)]benzene (1-N,2-N′) (1b) and 1,3-bis[(2-bromoethyl)tetrazol-5-yl]benzene (2-N,2-N′) (5d) are discussed.     

Palladium mediated synthesis of isoindolinones and isoquinolinones

The palladium-catalyzed reactions of 2-iodo-N-substituted benzamides 5-10 with acrylic esters 11-14 led to N-substituted-3-alkylisoindolinone esters 15-22 in good yields. The esters of isoindolinones 15-22 underwent hydrolysis reactions yielding the N-aryl-1,2,3,4-tetrahydro-1-oxoisoquinoline-3-carboxylic acid 26-31 in good yields.     

Synthesis and X-ray structures of new chiral Ag(I) complexes with biaryl-based N4-donor ligands

Condensation of (R)-2,2′-diamino-1,1′-binaphthyl or (R)-6,6′-dimethylbiphenyl-2,2′-diamine with 2 equiv of 2-pyridine carboxaldehyde in toluene in the presence of molecular sieves at 70 °C gives (R)-N,N′-bis(pyridin-2-ylmethylene)-1,1′-binaphthyl-2,2′-diimine (1), and (R)-N,N′-bis(pyridin-2-ylmethylene)-6,6′-dimethylbiphenyl-2,2′-diimine (3), respectively, in good yields. Reduction of 1 with an excess of NaBH₄ in a solvent mixture of MeOH and toluene (1:1) at 50 °C gives (R)-N,N′-bis(pyridin-2-ylmethyl)-1,1′-binaphthyl-2,2′-diamine (2) in 95% yield. Rigidity plays an important role in the formation of helicate silver(I) complexes. Treatment of 1, or 3 with 1 equiv of AgNO₃ in mixed solvents of MeOH and CH₂Cl₂ (1:4) gives the chiral, dinuclear double helicate Ag(I) complexes [Ag₂(1)₂][NO₃]₂ (4) and [Ag₂(3)₂][NO₃]₂ · 2H₂O (6), respectively, in good yields. While under the similar reaction conditions, reaction of 2 with 1 equiv of AgNO₃ affords the chiral, mononuclear single helicate Ag(I) complex [Ag(2)][NO₃] (5) in 90% yield. [Ag₂(1)₂][NO₃]₂ (4) can further react with excess AgNO₃ to give [Ag₂(1)₂]₃[NO₃]₂[Ag(CH₃OH)(NO₃)₃]₂ · 2CH₃OH (7) in 75% yield. All compounds have been fully characterized by various spectroscopic techniques and elemental analyses. Compounds 1 and 5-7 have been further subjected to single-crystal X-ray diffraction analyses.     

New silatranes possessing urea functionality: Synthesis, characterization and their structural aspects

The present work aims at the synthesis of various novel silatranes bearing substituted urea functionality. Nucleophilic addition of various amines (morpholine, aniline, ethylenediamine and 3-aminopropyltriethoxysilane) to 3-isocyanatopropyltriethoxysilane resulted in the four triethoxysilanes; N-[3-(triethoxysilyl)propyl]morpholine-4-carboxylic acid amide (1), 1-[3-(triethoxysilyl)propyl]-3-phenylurea (2), 1,2-bis{N′-[3-(triethoxysilyl)propyl]ureido}-ethane (3) and N-[3-(triethoxysilyl)propyl]-N′-[3-(triethoxysilyl)propyl]urea (4), respectively. In the presence of a base the resulting silanes undergo transesterification reaction with triethanolamine, thus forming the corresponding silatranes, N-(3-silatranylpropyl)morpholine-4-carboxylic acid amide (5), 1-(3-silatranylpropyl)-3-phenylurea (6), 1,2-Bis[N′-(3-silatranylpropyl)ureido]-ethane (7) and N-(3-silatranylpropyl)-N′-(3-silatranylpropyl)urea (8), respectively. Among these are four novel compounds (5-8), which were characterized by elemental analysis, IR, multinuclear (¹H, ¹³C and ²⁹Si) NMR and mass spectroscopy. Structures of compounds 5 and 6 were deduced by X-ray crystallography. Single crystal X-ray studies revealed distorted trigonal bipyramidal coordination about Si in 5 and 6 with Si-N bond distance of 2.121(1) Å and 2.189(2) Å, respectively.