Photoactive building blocks for coordination complexes: Gilding 2,2′:6′,2″-terpyridine

The alkyne unit of 4′-ethynyl-2,2′:6′,2″-terpyridine has been functionalized with Ph₃PAu, (2-tolyl)₃PAu or Au(dppe)Au units to produce compounds 1-3, respectively. These derivatives have been characterized by electrospray mass spectrometry, solution ¹H and ¹³C NMR, UV-Vis and emission spectroscopies, and single crystal X-ray diffraction. In the solid state, molecules of 1 or 2 pack with separated domains of tpy and R₃PAu units; the tpy units in 2 (but not 1) exhibit face-to-face π-stacking. Compound 3 crystallizes as 2(3)^.CHCl₃, and the folded conformation of the dppe backbone results in a short (2.9470(8) Å) aurophilic interaction. Folded molecule 3 captures CHCl₃, preventing intramolecular face-to-face π-interactions between the tpy units. In CH₂Cl₂ solution, 1-3 are emissive when excited between 230 and 300 nm, but over minutes when λ_ex = 230 nm, the emission bands decay as the compounds photodegrade.     

Production of mixed halogenated congeners of the natural product heptachloro-1′-methyl-1,2′-bipyrrole (Q1) by photolysis in the presence of bromine

Halogenated 1′-methyl-1,2′-bipyrroles (MBPs) are a class of marine halogenated natural products that have been detected in biota from all over the world. However, structures and standards of many mixed chlorinated/brominated MBPs are not available. For this reason, the known 2,3,3′,4,4′,5,5′-heptachloro-1′-methyl-1,2′-bipyrrole (Q1 or MBP-79) was UV-irradiated in the presence of bromine with the goal of inducing a chlorine → bromine exchange. A few drops of bromine were added to a solution of Q1 and 10 mL of either CH₂Br₂, CH₂Cl₂, or CHCl₃. The experiments were performed both at room temperature and elevated temperature for 30 min. At least four out of five possible bromohexachloro-1′methyl-1,2′-bipyrroles (BrCl₆-MBPs), at least seven out of 13 possible Br₂Cl₅-MBPs, as well as traces of Br₃Cl₄-MBPs and Br₄Cl₃-MBPs were obtained in this way. Selective fragment ions in the GC/ECNI-MS spectra as well as electrophilic bromination of hexachloro-MBP solutions were used to verify the structures of the BrCl₆-MBP isomers. The BrCl₆-MBPs eluted from DB-5-like columns in the order of 4′-bromo-2,3,3′,4,5,5′-hexachloro-1′-methyl-1,2′-bipyrrole (Br-MBP-76), which co-eluted with 3′-bromo-2,3,4,4′,5,5′-hexachloro-1′-methyl-1,2′-bipyrrole (Br-MBP-78), followed by 2-bromo-3,3′,4,4′,5,5′-hexachloro-1′-methyl-1,2′-bipyrrole (Br-MBP-75), 3-bromo-2,3′,4,4′,5,5′-hexachloro-1′-methyl-1,2′-bipyrrole (Br-MBP-77), and 5′-bromo-2,3,3′,4,4′,5-hexachloro-1′-methyl-1,2′-bipyrrole (Br-MBP-74). These BrCl₆-MBPs were also detected in a sample of cetacean blubber from Australia, but the abundance pattern was different. While Br-MBP-76/Br-MBP-78 dominated in the cetacean, irradiation of Q1 (MBP-79) in the presence of bromine led to high proportions of Br-MBP-75. The suitability of the UV-induced Cl → Br exchange was confirmed by the Br-assisted UV-irradiation of pentachloroanisole (PCA). This experiment produced at least two bromotetrachloro- and three dibromotrichloroanisoles, the last eluting in each case being the most relevant. Thus, this method is most likely generally suited for the production of mixed-halogenated aromatic organohalogen compounds which are not readily obtainable by synthesis.     

3′-Selective modification of a 4′,5′-didehydro-5′-deoxy-2′,3′-epoxyuridine using nucleophiles

1-(2,3-Anhydro-5-deoxy-4,5-didehydro-α-l-erythro-pent-4-enofuranosyl)uracil 4 was obtained by the treatment of 5′-iodo-2′,3′-epoxyuridine 5 with LiHMDS in excellent yield. The pyrimidine nucleoside 4 possesses quite unique vinyl epoxide moiety within the molecules. The reactions of 4 with a variety of nucleophiles gave 3′-substituted pyrimidine nucleosides without the formation of the corresponding 2′-substituted isomers. In the case of NaN₃ or PhSH, the corresponding 5′-adduct was obtained as a minor product together with the expected 3′-adduct.     

New active ruthenium(II) complexes based N3,N3′-bis(diphenylphosphino)-2,2′-bipyridine-3,3′-diamine and P,P′-diphenylphosphinous acid-P,P′-[2,2′-bipyridine]-3,3′-diyl ester ligands for transfer hydrogenation of aromatic ketones by propan-2-ol

The dimeric starting material [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂ reacts with N3,N3′-bis(diphenylphosphino)-2,2′-bipyridine-3,3′-diamine, 1 and P,P′-diphenylphosphinous acid-P,P′-[2,2′-bipyridine]-3,3′-diyl ester, 2 ligands to afford bridged dinuclear complexes [C₁₀H₆N₂{NHPPh₂-Ru(η⁶-p-cymene)Cl₂}₂], 3 and [C₁₀H₆N₂{OPPh₂-Ru(η⁶-p-cymene)Cl₂}₂], 4 in quantitative yields. These bis(aminophosphine) and bis(phosphinite) based Ru(II) complexes serve as active catalyst precursors for the transfer hydrogenation of acetophenone derivatives in 2-propanol and especially 4 acts as a good catalyst, giving the corresponding alcohols in 99% yield in 20 min (TOF ? 280 h⁻¹).     

Effect of conformational adaptation of 4,4′-(hexafluoro-isopropylidene) diphthalic anhydride (6FDA) on the structural features of a perylene-containing copolyimide

A series of perylene-containing random copolyimides with different ratios of diaminododecyl perylene tetracarboxylic dianhydride (PPI-12) and 4,4′-(hexafluoro-isopropylidene) diphthalic anhydride (6FDA) have been studied. Copolymerization improves the solubility and the copolyimide with a low percentage (less than 20% of total dianhydrides) of perylene becomes highly soluble in conventional solvents, such as, CHCl₃, CH₂Cl₂, or THF etc. The positions of the absorption maxima in the UV-visible spectra do not change with 6FDA concentration, but the relative intensities do. Although the homopolymer PPI-12 does not show a distinct glass transition, its T_g was derived by extrapolation of the DSC results with the copolymers. The copolymers are semi-crystalline up to a concentration of 60% (mol) 6FDA. It is of interest that the spacings of X-ray reflections also do not change with the addition of 6FDA. This is rationalized on the basis that the conformation of the 6FDA segment does not cause any significant difference in the preferred conformational shapes of the homopolymer of PPI-12. Due to this “conformational isomorphism” 6FDA is not a significant chain “kinker” in this case.     

5′-Noraristeromycin possessing a C-1′ cyclopentyl double bond: a new carbanucleoside structural prototype

Prior to this work only two examples of carbanucleosides possessing a C-1′/C-6′ double bond had been reported and they were minor derivatized side products arising during other targeted syntheses. To develop this structural feature into a new class of potential antiviral agents, the 5′-nor derivative of aristeromycin with such an olefinic structure (6) represents the first example. In this regard, treatment of (1′S,2′S,3′S,4′R,5′S)-6-chloro-9-(2′,3′-isopropylidenedioxy-6′-oxabicyclo[3.1.0]hex-4′-yl)purine (7) with sodium methoxide yielded 6 via an E′₂-like elimination pathway. A convenient way to the C-4′ epimer of 6 (that is, 17) also arose during these studies and is described. Antiviral analysis of 6 and 17 failed to produce any significant activity.     

Concise and efficient synthesis of 3′-O-triphosphates of 2′-deoxyadenosine and 2′-deoxycytidine

We describe concise and efficient synthesis of 2′-deoxyadenosine-3′-O-triphosphate (2′-d-3′-ATP) and 2′-deoxycytidine-3′-O-triphosphate (2′-d-3′-CTP) which are well known for their various biological applications. One-pot synthetic methodology was used to convert N⁶-Benzoyl-5′-O-levulinoyl-2′-deoxyadenosine into N⁶-Benzoyl-5′-O-levulinoyl-2′-deoxyadenosine-3′-O-triphosphate in 72% yield. One-step concurrent deprotection of N⁶-Benzoyl and 5′-O-levulinoyl groups using concentrated aqueous ammonia resulted in 2′-d-3′-ATP in 75% yield. The same synthetic strategy was successfully employed to convert N⁴-Benzoyl-5′-O-levulinoyl-2′-deoxycytidine into 2′-d-3′-CTP in 66% yield.     

A concise synthesis of 3′-α-fluoro-2′,3′-dideoxyguanosine (FddG) via 3′-α-selective fluorination of 8,2′-thioanhydronucleoside

The antiviral nucleoside 3′-α-fluoro-2′,3′-dideoxyguanosine (FddG) was synthesized via 3′-α-selective fluorination of 8,2′-thioanhydronucleoside as the key step. Desulfurization of 3′-α-fluoro-3′-deoxy-8,2′-thioanhydronucleoside could be achieved by the treatment with Raney Ni in toluene. This method provides a concise route to 3′-α-fluoro-2′,3′-dideoxynucleosides that avoids the use of explosive and expensive SF₄-related fluorinating reagents.     

Proton NMR study on two structures of 3′-O-(acetylimino)3′-de(phosphinico)-thymidylyl-(3,5′)-deoxythymidine in aqueous solution

The solution structure of one of dithymidine monophosphate (TpT) analogues, containing an (N-acetyl)imino backbone linkage (NCOCH₃) of 3′-O-(acetylimino)3′-de(phosphinico)-thymidylyl-(3,5′)-deoxythymidine (T_NT), has been determined by proton NMR. Two structures, designated as major and minor forms, in a ratio of about 3:2 coexist when the solution temperature is <25°C. Both forms adopt anti conformation with respect to the glycosidic bond, S-type deoxyribofuranose pucker, and have no base stacking. The backbone torsion angles ε′, φ_ON, φ_NC, and γ′ are trans, gauche⁺, gauche⁺, and gauche⁺ for the major form; and gauche⁻, gauche⁻, gauche⁻, and gauche⁺ for the minor form. Only major form is found at >25°C.     

Studies on photocrosslinkable copolymers of 4-methacryloyloxyphenyl-3′,4′-dimethoxystyryl ketone and methyl methacrylate

Copolymers with various contents of 4-methacryloyloxyphenyl-3′,4′-dimethoxystyryl ketone (MPDSK) and methyl methacrylate (MMA) were prepared in methyl ethyl ketone solution using benzoyl peroxide as a free radical initiator at 70 °C. Characterization of the resulting polymers was done by UV, FT-IR, ¹H NMR and ¹³C NMR spectroscopic techniques. The copolymer compositions were determined by ¹H NMR analysis. The monomer reactivity ratios were calculated using linearisation methods such as Finemann-Ross (r₁ = 0.4283 and r₂ = 0.3050), Kelen-Tudos (r₁ = 0.4264 and r₂ = 0.2606), and extended Kelen-Tudos (r₁ = 0.4022 and r₂ = 0.2704) methods as well as by a non-linear error-in-variables model (EVM) method using the computer program RREVM (r₁ = 0.4066 and r₂ = 0.2802). The molecular weights ( and ) and the polydispersity index of the copolymers were determined by gel permeation chromatography. The thermal stability of the copolymers increases with increase in concentration of MPDSK. Glass transition temperatures were determined by differential scanning calorimeter under nitrogen atmosphere. The photoreactivity of the copolymers having pendant chalcone moieties was studied in chloroform solution.     

A new series of potentially hexadentate ligands derived from 2,2′-bipyridine

Reaction of 2,2′-bipyridine-6-carboxaldehyde with the appropriate aliphatic diamine in MeOH and subsequent reduction with NaBH₄ gives the new, potentially hexadentate, ligands N,N′-bis(2,2′-bipyridin-6-ylmethyl)ethane-1,2-diamine (bmet), N,N′-bis(2,2′-bipyridin-6-ylmethyl)propane-1,3-diamine (bmpp) and N,N′-bis(2,2′-bipyridin-6-ylmethyl)hexane-1,6-diamine (bmhx). The syntheses and characterisation of these ligands are reported; the ligands are isolated as the hydrochloride salts, with purification effected by either recrystallisation or cation exchange chromatography. [Co(bmet)](ClO₄)₃ · H₂O is obtained on reaction of bmet · 4.25HCl · 2.5H₂O with Na₃[Co(O₂CO)₃] · 3H₂O, and X-ray structural analysis shows this to have a pair of very short Co–N bonds. The synthesis and characterisation of the first coordination complex containing 6-(aminomethyl)-2,2′-bipyridine (amb) is also described.     

Synthesis of 5,5′-diarylated 2,2′-bithiophenes via palladium-catalyzed arylation reactions

2,2′-Bithiophene and 3,3′-dicyano-2,2′-bithiophenes are diarylated directly with aryl bromides at the 5- and 5′-positions accompanied by C-H bond cleavage in the presence of Pd(OAc)₂ and a bulky phosphine ligand using Cs₂CO₃ as base. In the reaction using (2,2′-bithiophen-5-yl)diphenylmethanol as the substrate, monoarylation at the 5-position via C-C bond cleavage occurs selectively to give 5-aryl-2,2′-bithiophenes and the subsequent arylation with a different aryl bromide affords the corresponding unsymmetrically 5,5′-diarylated products.     

A regioselective three-component reaction for synthesis of novel 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione derivatives

A ring opening and regioselective three-component reaction of isatoic anhydride, isatins, and aromatic or aliphatic primary amines in the presence of catalytic amount of KAl(SO₄)₂·12H₂O (alum) to yield a novel series of 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione is described.     

Synthesis of 2′,3′-dideoxy-6′,6′-difluoro-3′-azanucleosides

The straightforward synthesis of four novel 2′,3′-dideoxy-6′,6′-difluoro-3′-azanucleosides 1a-d is described. Efficient construction of the fluorine-containing pyrrolidine ring through two different ways and installation of pyrimidine rings using the amino groups in the intermediates 12, 26 were the key steps of our synthesis.     

Nucleophilic substitution approach to 4′-substituted thymidines by employing 4′-benzenesulfonyl leaving group

Synthesis of 4′-substituted thymidines was investigated based on nucleophilic substitution using organosilicon and organoaluminum reagents. Two substrates having a benzenesulfonyl leaving group at the 4′-position were prepared for this purpose: 1-[4-benzenesulfonyl-3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-α-l-threo-pentofuranosyl]thymine (8α) and the 4′-(benzenesulfonyl)thymidine derivative (8β). The reaction of 8α with organosilicon reagents (Me₃SiCH₂CHCH₂ and Me₃SiN₃) in combination with SnCl₄ gave preferentially the 4′-substituted β-d-isomer: the 4′-allyl (12β) and 4′-azido (15β) derivatives, respectively. The reaction of 8α with AlMe₃, however, gave the 4′-methyl-α-l-isomer (16α) as the major product, presumably through an ion pair mechanism. By employing the substrate 8β in this reaction, the 4′-methylthymidine derivative (16β) was obtained exclusively in high yield. The 4′-ethyl (20β) and 4′-cyano (24β) derivatives were also synthesized by reacting 8β with the respective organoaluminum reagent.     

Synthesis of a series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides

A series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides 1a-d, analogues of 3TC that has high biological activities against HIV and HBV, have been synthesized from the gem-difluorohomoallyl amine 7 in a straightforward fashion. Our synthesis featured the construction of thiofuranose skeleton through ring closure of key intermediates and installation of pyrimidine ring with amino group in compounds 13a,b.     

Synthesis and anti-HIV activities of bis-(cycloSaligenyl) pronucleotides derivatives of 3′-fluoro-3′-deoxythymidine and 3′-azido-3′-deoxythymidine

Anti-HIV nucleoside monophosphates have limited cellular uptake due to the presence of negatively-charged phosphate group. Bis-(cycloSaligenyl) derivatives containing two anti-HIV nucleosides, 3′-fluoro-3′-deoxythymidine (FLT) and 3′-azido-3′-deoxythymidine (AZT) were synthesized to increase intracellular delivery of nucleoside monophosphates. 2,5-Bis(hydroxymethylene)benzene-1,4-diol was selected as a monocyclic bidentate scaffold and synthesized by three different methods from bis(hydroxymethylene)cyclohexan-1,4-diene-1,4-diol, or diethyl 2,5-dihydroxyterephthalate. The reaction of the tetraol with diisopropylphosphoramidous dichloride in the presence of 2,6-lutidine, followed by conjugation reactions with nucleosides (i.e., FLT and AZT) and oxidation afforded symmetrical and unsymmetrical bis-(cycloSaligenyl) diphosphate triester products, AZT-AZT, FLT-FLT, and FLT-AZT conjugates, in 63-74% overall yields and modest anti-HIV activities (IC₅₀ = 2.8-69.6 μM).     

Synthesis, structural characterization, and reactivity of organolanthanides derived from a new chiral ligand (S)-2-(pyrrol-2-ylmethyleneamino)-2′-hydroxy-1,1′-binaphthyl

Condensation of (S)-2-amino-2′-hydroxy-1,1′-binaphthyl with 1 equiv. of pyrrole-2-carboxaldehyde in toluene in the presence of molecular sieves at 70 °C gives (S)-2-(pyrrol-2-ylmethyleneamino)-2′-hydroxy-1,1′-binaphthyl (1H₂) in 90% yield. Deprotonation of 1H₂ with NaH in THF, followed by reaction with LnCl₃ in THF gives, after recrystallization from a toluene or benzene solution, dinuclear complexes (1)₃Y₂(thf)₂ · 3C₇H₈ (3 · 3C₇H₈) and (1)₃Yb₂(thf)₂ · 3C₆H₆ (4 · 3C₆H₆), respectively, in good yields. Treatment of 1H₂ with Ln[N(SiMe₃)₂]₃ in toluene under reflux, followed by recrystallization from a benzene solution gives the dimeric amido complexes {1-LnN(SiMe₃)₂}₂ · 2C₆H₆ (Ln = Y (5 · 2C₆H₆), Yb (6 · 2C₆H₆)) in good yields. All compounds have been characterized by various spectroscopic techniques, elemental analyses and X-ray diffraction analyses. Complexes 5 and 6 are active catalysts for the polymerization of methyl methacrylate (MMA) in toluene, affording syn-rich poly-(MMA)s.     

Synthesis and characterization of novel fluorinated polyimides derived from 1,1′-bis(4-aminophenyl)-1-(3-trifluoromethylphenyl)-2,2,2-trifluoroethane and aromatic dianhydrides

A novel fluorinated aromatic diamine 1,1′-bis(4-aminophenyl)-1-(3-trifluoromethylphenyl)-2,2,2-trifluoroethane (6FDAM) was synthesized in a simple procedure, which was then employed to prepare a series of fluorinated polyimides with commercial aromatic dianhydrides, such as pyromellitic dianhydride (PMDA), 2,2-bis(3,4-dicarboxyphenyl)hexafluoropropane (6FDA), 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (BTDA) and 4,4′-oxydiphthalic anhydride (ODPA). The polyimides exhibited good solubility in strong dipolar solvents such as NMP, DMAc, DMF and m-cresol as well as some of low boiling point organic solvents of THF and CHCl₃, etc. Experimental results indicated the polyimides possessed low moisture adsorptions of 0.42-0.95%, low dielectric constant of 2.71-2.95 at 1 MHz, high dielectric strength of 92.0-122.6 kV/mm and good optical transparency with cutoff wavelengths of UV-vis at 330-375 nm. The polyimides also exhibited good mechanical properties as well as excellent thermal and thermo-oxidative stability. The fluorinated polyimides possessed better solubility, lower dielectric constant and water adsorption as well as higher optical transparency than the representative non-fluorinated polyimide derived from PMDA and 4,4′-oxydianiline (ODA).     

Synthesis and structural investigation of 1′,3′,3′-trimethyl-6-hydroxy-spiro(2H-1-benzopyran-2,2′-indoline), 1′,3′,3′-trimethyl-6-methacryloyloxy-spiro(2H-1-benzopyran-2,2′-indoline) and a copolymer with methyl methacrylate by 1D and 2D NMR spectroscopy

Photo-responsive spiropyran-based compounds, such as, 1′,3′,3′-trimethyl-6-hydroxy-spiro(2H-1-benzopyran-2,2′-indoline) [OHSP], its monomer, such as 1′,3′,3′-trimethyl-6-methacryloyloxy-spiro(2H-1-benzopyran-2,2′-indoline) [MOSP] and its copolymers with methyl methacrylate [MMA] were synthesised using conventional synthetic routes. The copolymerisation was carried out either in tetrahydrofuran [THF] or in toluene using 2,2′-azobisisobutyronitrile [AIBN] as an initiator. The structures of these materials were investigated using ¹H and ¹³C NMR spectroscopy. DEPT-135, HCCOSW and COSY45 NMR experiments were used to assign and interpret the complex structure of spiropyran based materials.