Tandem catalysis in ionic liquids: a recyclable catalytic synthesis of benzofuran derivatives

A convenient, recyclable catalytic synthesis of benzofuran-2-acetic esters 2 by sequential Pd(0)-catalyzed deallylation—Pd(II)-catalyzed carbonylative heterocyclization of 1-(2-allyloxyphenyl)-2-yn-1-ols 1 in ionic liquids is presented. Reactions were typically carried out in BmimBF₄ as the solvent at 100 °C and under 30 atm of CO, in the presence of catalytic amounts (1 mol %) of PdI₂ in conjunction with KI (1 equiv), PPh₃ (4 mol %), MeOH (28 equiv), and H₂O (2 equiv). The solvent-catalyst system could be recycled several times without appreciable loss of catalytic activity.     

Efficient approach to allylated quinolines via palladium-catalyzed cyclization–allylation of 1-azido-2-(2-propynyl) benzenes with allyl methyl carbonate

The palladium-catalyzed cyclization–allylation reaction of ortho-azido propynylbenzenes 1 and allyl methyl carbonate 2d gives the corresponding allylated quinolines in moderate to good yields. The reaction of 1-azido-2-(2-propynyl)benzene 1a proceeds smoothly with 10 mol % Pd(PPh₃)₄ and 5 equiv K₃PO₄ or NaOAc in DMF at 100 °C to afford 3,4-diallylquinoline 3a in 69% yield in the case of R² = H and 3-allylquinoline 4 in 67% yield in the case of R² ≠ H.     

Enantioselective synthesis of β-lactams via the IndaBox-Cu(II)-catalyzed Kinugasa reaction

The enantioselective Kinugasa reaction of nitrones with terminal alkynes in the presence of 20 mol % of IndaBox-Cu(OTf)₂ and di-sec-butylamine (1.5 equiv) produced β-lactams with the highest level of enantiomeric excesses among the catalytic enantioselective Kinugasa reactions reported so far.     

One-pot synthesis of 1,4-diarylsubstituted 1,3-diynes from the sequential coupling reactions of aryl iodides and propiolic acid

1,4-Disubstituted 1,3-dialkynes were obtained from the one-pot palladium/copper-catalyzed coupling reactions of aryl iodide and propiolic acid. The optimized catalytic system consisted of 5.0 mol % Pd(PPh₃)₂Cl₂, 10 mol % dppb, 10 mol % CuI, 2.4 equiv of DBU, and 1.2 equiv of K₂CO₃. The coupling reaction was carried out at 30 °C for 6 h and subsequently at 80 °C for 3 h.     

Biomimetic sensor based on MnMn complex as manganese peroxidase mimetic for determination of rutin

A novel biomimetic sensor for rutin determination based on a dinuclear complex [Mn^IIIMn^II(Ldtb)(μ-OAc)₂]BPh₄ containing an unsymmetrical dinucleating ligand, 2-[N,N-bis(2-pyridylmethyl)-aminomethyl]-6-[N-(3,5-di-tert-butyl-2-oxidoben-zyl)-N-(2-pyridylamino)aminomethyl]-4-methylphenol (H₂Ldtb), as a manganese peroxidase mimetic was developed. Several parameters were investigated to evaluate the performance of the biomimetic sensor obtained after the incorporation of the dinuclear complex in a carbon paste. The best performance was obtained in 75:15:10% (w/w/w) of the graphite powder:Nujol:Mn^IIIMn^II complex, 0.1 mol L⁻¹ phosphate buffer solution (pH 6.0) and 4.0 × 10⁻⁵ mol L⁻¹ hydrogen peroxide. The response of the sensor towards rutin concentration was linear using square wave voltammetry in the range of 9.99 × 10⁻⁷ to 6.54 × 10⁻⁵ mol L⁻¹ (r = 0.9998) with a detection limit of 1.75 × 10⁻⁷ mol L⁻¹. The recovery study performed with pharmaceuticals ranged from 96.6% to 103.2% and the relative standard deviation was 1.85% for a solution containing 1.0 × 10⁻³ mol L⁻¹ rutin (n = 6). The lifetime of this biomimetic sensor was 200 days (at least 750 determinations). The results obtained for rutin in pharmaceuticals using the biomimetic sensor and those obtained with the official method are in agreement at the 95% confidence level.     

Molybdenum oxide/bipyridine hybrid material {[MoO3(bipy)][MoO3(H2O)]}n as catalyst for the oxidation of secondary amines to nitrones

The inorganic-organic hybrid material {[MoO₃(bipy)][MoO₃(H₂O)]}_n (bipy = 2,2′-bipyridine) can be used as a water-tolerant catalyst for the oxidation of secondary amines under mild conditions using either urea hydrogen peroxide (UHP) or tert-butylhydroperoxide (TBHP) as the oxidant. Under optimized reaction conditions (2 mol % catalyst, 3-4 equiv TBHP, CH₂Cl₂ as the solvent, 40 °C), the corresponding nitrones were obtained with different efficiency depending on the nature of the cyclic or acyclic amine used.     

Pd(0) and Pd(II) derivatives with heteroannularly bridged chiral ferrocenyl diphosphine ligands - A stereochemical analysis

The ligands (S_c, S_p)-1-diphenylphosphino-2,1′-(1-dicyclohexylphosphinopropanediyl)ferrocene, (S_c, S_p)-PP^CyPF, and (S_c, S_p)-1-diphenylphosphino-2,1′-(1-diphenylphosphinopropanediyl)ferrocene, (S_c, S_p)-PP^PhPF, have been used in the synthesis of the new Pd(0) and Pd(II) derivatives [Pd(PP^CyPF)(DMFU)] (1) (DMFU = dimethylfumarate), [Pd(PP^CyPF)(MA)] (2) (MA = maleic anhydride), [Pd(η³-2-Me-C₃H₄)(PP)]OTf (PP = PP^CyPF, 3; PP^PhPF, 4) (OTf = triflate), [PdRR′(PP)] (R = Me, R′ = Cl, PP = PP^CyPF, 5, PP^PhPF, 6; R = R′ = Me, PP = PP^CyPF, 7, PP^PhPF, 8; R = R′ = C₆F₅, PP = PP^CyPF, 9, PP^PhPF, 10). The molecular structure of 7 has been determined by X-ray diffraction. In the cases of complexes 1-4 two isomers are formed depending on the orientation of the ancillary ligand with respect to the ferrocenyl core. The stereochemistry of these complexes has been determined. In complex 6 the two possible isomers are obtained whereas in complex 5 the derivative with the Me group trans to PPh₂ is selectively formed. Restricted rotation of the pentafluorophenyl groups with respect to the Pd-C bond has been found in 9 and 10. In all derivatives the conformation of the ferrocenyl ligand is the same as that seen by X-ray diffraction and deduced from NMR data.     

Catalytic, PMe3-mediated conversion of secondary nitroalkanes to ketones: a very mild Nef-type process

Aliphatic secondary nitro compounds are converted to ketones at room temperature, usually in 90-100% yields, by a one-pot reaction with 220-250 mol % of trimethylphosphine (PMe₃) and 50-100 mol % of ^tBuC₆H₄SSC₆H₄^tBu or PhthN-SePh, or 20 mol % of both additives. Thus, very mild catalytic variants of the reductive Nef-like reactions are disclosed.     

Cross coupling of 3-bromopyridine and sulfonamides (RNHSO2R·R = H, Me, alkyl; R = alkyl and aryl) catalyzed by CuI/1,3-di(pyridin-2-yl)propane-1,3-dione

N-(3-Pyridinyl)-substituted secondary and tertiary sulfonamides have been synthesized in good to excellent yields by the reaction of 3-bromopyridine with primary and secondary alkyl and aryl sulfonamides (MeSO₂NH₂, MeSO₂NHMe, TolSO₂NH₂, TolSO₂NHMe, 1,3-propanesultam, and 1,4-butanesultam), catalyzed by CuI (20 mol %) and 1,3-di(pyridin-2-yl)propane-1,3-dione (20 mol %) with K₂CO₃ (200 mol %) in DMF (0.17 M for ArBr) at 110-120 °C over 36-40 h. 2-Bromopyridine, 4-bromopyridine, and a wide variety of substituted phenyl bromides can also be successfully coupled with sulfonamides under these reaction conditions.     

Some phosphinite complexes of Rh and Ir, their intramolecular reactivity and DFT calculations about their application in biphenyl metathesis

Biphen(OPR₂) (with R: Ph, iPr, Cy) is reacted with [Rh(COE)₂Cl]₂. The corresponding μ-chloro-bridged dimers are received. An X-ray analysis of [Biphen(OPCy₂)RhCl]₂ is included. This compound shows a dynamic behaviour in solution, ascribed to a monomer/dimer equilibrium. The difference of the Biphen ligands to Milsteins PCP pincer-type ligand is shown. A catalytic cycle for biphenyl metathesis containing the coupling of oxidative addition and reductive elimination of the bridging C-C single bond in the biphenyl fragment using Rh^I/III complexes and the concept of chelating assistance was calculated using DFT (B3PW91/LANL2DZ). According to the calculations the activation energy of the oxidative addition is about 30 kcal/mol and for the reductive elimination about 19 kcal/mol. The fac-Rh^III complex is by far the most stable compound, but the formation of it is kinetically strongly disfavoured. Pre-catalysts (COD)M(Ph-O-PR₂) (M: Rh, Ir) were synthesized by pre-coordinating the phosphinite to the metal (X-ray structures of four such compounds included) followed by treatment with 2 equiv. of sec. BuLi (X-ray structures of two such compounds included). In case of Ir this synthesis is complicated by C-H activation (X-ray structure of (COD)Ir(H)(Cl)(2-Br-phenyl-O-(diisopropylphosphinite)) included) and fast oxidative addition of the Ph-C-Halide bond. For (COD)Ir(H)(Cl)(2-phenyl-O-(diisopropylphosphinite)) the C-H activation is reversible and thermodynamic parameters for the ring closure reaction were determined by VT-NMR measurement (ΔH = −21.1 ± 0.5 kJ/mol, ΔS = −62.8 ± 1.7 J/(mol K)). The pre-catalysts were reacted with Biphen(OPR₂) to enter the calculated catalytic cycle. With Rh as center metal this reaction works out cleanly to give new complexes with the three P-atoms coordinated to one Rh center. No hemi-labile character was found for these P-donors even at 105 °C in toluene. If (COD)Rh(2-phenyl-O-(diisopropylphosphinite)) is reacted with 2 equiv. of 2-iodo-phenyl-O-(diisopropylphosphinite) oxidative addition of one C-Iodo bond is observed and the corresponding mer-Rh^III complex is received. Upon treatment with 2 equiv. of sec. BuLi the resulting product is(Biphen(OPiPr₂))Rh^I(2-phenyl-O-(diisopropylphosphinite)) rather than mer-Rh^III(2-phenyl-O-(diisopropylphosphinite))₃. Reaction of [Rh(COD)Cl]₂ with 3 equiv. of 2-bromo-phenyl-O-(diphenylphosphinite) shows a fast scrambling of the chlorine into all possible ortho positions of the phenolate rings in the final Rh^III reaction product.     

An evidence of contact ion pair in β-(acyloxy)alkyl radical heterolysis during copper(I)-mediated synthesis of trisubstituted alkenes

The first evidence for a unified mechanism of heterolysis in β-(acyloxy)alkyl radical involving contact ion pair (CIP) is presented for both fragmentation and rearrangement of the acyloxy group in the reaction of 1-alkoxy-2,2,2-trichloroethyl acetate with 2 mol equiv each of CuCl and bpy in refluxing DCE under a N₂ atmosphere and availed this reaction for the synthesis of Z-stereoselective trisubstituted alkenes. The stereochemistry of the trisubstituted alkenes was assigned by the uniform pattern of the chemical shift values of some relevant signals in ¹H and ¹³C NMR spectra. This assignment was further supported by the X-ray diffraction spectroscopy of Z-1-chloro-2-(4-nitrobenzyloxy)vinyl acetates.     

Copper-catalyzed cross-coupling of aryl iodides and aryl acetylenes using microwave heating

An efficient copper-catalyzed cross-coupling of aryl iodides with aryl acetylenes under microwave irradiation is described. The reaction proceeds under microwave heating with 10 mol % CuI and 2 equiv Cs₂CO₃ in 43-87% yields.     

Catalytic imino Diels-Alder reaction by triflic imide and its application to one-pot synthesis from three components

An imino Diels-Alder reaction of 2-siloxydienes with aldimines catalyzed by triflic imide (Tf₂NH; 0.1∼10 mol % amount) has been developed leading to substituted piperidin-4-ones. Tf₂NH catalyst is compatible with basic functions, such as pyridine and indole rings in the imino Diels-Alder reaction. Furthermore, X-ray crystallographic analysis indicates that trans-2,6-diphenyl-4-piperidinone 4a obtained by this reaction has a unique conformation in the solid state.     

Voltammetry determination of trace manganese with pretreatment glassy carbon electrode by linear sweep voltammetry

This paper described the determination of trace manganese using linear sweep voltammetry at a pretreatment glassy carbon electrode. The glassy carbon electrode pretreated by electrochemical method in the 0.1 mol l⁻¹ NaOH solution greatly improved the electrode responsibility in the determination of manganese(II). The barrier to the detection of low manganese concentration was overcome by means of autocatalytic effect of manganese oxide deposited on the electrode in advance. Under the optimum experiments condition (0.04 mol l⁻¹ NH₃-NH₄Cl buffer solution, pH 9.0), the linear range was 4×10⁻⁸ to 1×l0⁻⁶ mol l⁻¹ Mn(II) for linear sweep voltammetry and 1×10⁻⁹ to 4×10⁻⁸ mol l⁻¹ Mn(II) for convolution voltammetry. The relative standard deviation for 2×10⁻⁸ mol l⁻¹ Mn(II) is 3.4%. The proposed method is simple, rapid, sensitive and selective. It had been applied to the determination of trace manganese in samples with satisfactory results.     

Extraction of arsenic compounds from lichens

Different extraction procedures were applied to improve the extraction efficiency of arsenic compounds from lichens. Two lichen species were chosen from an arsenic-contaminated environment: epiphytic Hypogymnia physodes (L.) Nyl. and terricolous Cladonia rei Schaer. Samples were extracted with water at temperatures of 20, 60 and 90 °C, using mixtures of methanol/water (9:1, 1:1 and 1:9), Tris buffer and acetone and the extracts speciated. Water and Tris buffer showed the best extraction efficiency of all extractants used; however, the extraction efficiency was still less than 23%. Since a major fraction of arsenic appeared to be associated with trapped soil particles, a sequential extraction procedure originally designed for soils (extraction steps: (1) 0.05 mol l⁻¹ (NH₄)₂SO₄; (2) 0.05 mol l⁻¹ (NH)₄H₂PO₄; (3) 0.2 mol l⁻¹ NH₄-oxalate buffer, pH 3.25; (4) mixture of 0.2 mol l⁻¹ NH₄-oxalate buffer and 0.1 mol l⁻¹ ascorbic acid, pH 3.25; (5) 0.5 mol l⁻¹ KOH) was applied and found to remove 45% of the total arsenic from H. physodes and 83% from C. rei. The lipid-soluble fraction of arsenic was estimated by k₀-INAA analysis of diethylether extracts and was found to be negligible. An HPLC-UV-HGAFS system was used to determine the arsenic compounds extracted. In both lichen species, arsenous acid, arsenic acid, monomethylarsonic acid, dimethylarsinic acid, arsenobetaine, trimethylarsine oxide and glycerol-ribose were detected. In addition, phosphate-ribose was found in H. physodes.     

Selective spectrofluorimetric determination of glutathione in clinical and biological samples using 1,3,5,7-tetramethyl-8-phenyl-(2-maleimide)-difluoroboradiaza-s-indacene

This work reports the development of a selective, sensitive and rapid spectrofluorimetric method for the determination of reduced glutathione (GSH) in the presence of relatively high levels of cysteine (Cys) in clinical and biological samples using 1,3,5,7-tetramethyl-8-phenyl-(2-maleimide)-difluoroboradiaza-s-indacene (TMPAB-o-M). The fluorescence from TMPAB-o-M is strongly quenched by its maleimide moiety, but after reaction with thiol, the fluorescence is restored with a 350-fold intensity increase (fluorescence quantum yield from 0.002 to 0.73). In H₃Cit-Na₂HPO₄ buffer (pH 7.40), the derivatization is completed in just 5 min under 37 °C. The linear range is 0.005-0.2 μmol L⁻¹, with detection limit of 1.1 × 10⁻¹⁰ mol L⁻¹ (signal-to-noise ratio = 3). Almost all amino acids, including Cys, impose no interference even if present at relatively high concentrations (amino acids:GSH = 100:1, Cys:GSH = 1:1, molar ratio, C_GSH = 3 × 10⁻⁷ mol L⁻¹). The sample can be used directly without further treatment after the protein is removed. The developed method is precise with a relative standard deviation (R.S.D.) lower than 5.0% (n = 6) and has been applied to the determination of GSH in human blood and pig’s liver with recoveries between 94.4 and 105.6%.     

Synthesis of α-aminonitriles under mild catalytic,metal-free conditions

α-Aminonitriles have been synthesized by a Strecker synthesis from aldehydes and ketones under mild catalytic, metal-free conditions. Aromatic aldehydes (1 equiv) were reacted with aromatic and 1° or 2° aliphatic amines (1 equiv) in EtOH containing 3 mol % of NH₄Cl to give high yields of α-aminonitriles. An alternative to adding NH₄Cl as a catalyst involved the use of excess TMSCN (1 equiv) and to promote the process. The reaction was also successful under microwave conditions using excess TMSCN with no solvent. Ketones similarly reacted with aromatic amines and excess TMSCN under conventional and microwave heating, but 30 mol % of added NH₄Cl was required for optimum conversion.     

Rosmarinic acid determination using biomimetic sensor based on purple acid phosphatase mimetic

A new heterodinuclear Fe(III)Zn(II) complex which mimics the active site of the hydrolytic enzyme red kidney bean purple acid phosphatase was synthesized and characterized by IR, CHN and X-ray crystallographic analyses. This complex, [Fe^IIIZn^II(μ-OH)bpbpmp-CH₃](ClO₄)₂, containing the ligand (H₂bpbpmp-CH₃ = {2-[bis(2-pyridylmethyl)aminomethyl]-6-[(2-hydroxy-5-methylbenzyl) (2-pyridyl-methyl) aminomethyl]-4-methyl-phenol}) was employed in the construction of a biomimetic sensor and used in the determination of rosmarinic acid in plant extract samples. The response parameters and optimization of the biomimetic sensor design were evaluated. The best performance of this sensor was obtained for 75:15:10% (w/w/w) of the graphite powder:nujol:Fe(III)Zn(II) complex, 0.1 mol L⁻¹ phosphate buffer solution (pH 7.5), 1.19 × 10⁻⁴ mol L⁻¹ hydrogen peroxide with frequency, pulse amplitude, and scan increment at 30 Hz, 100 mV, and 0.6 mV, respectively. The rosmarinic acid concentration was linear in the range of 2.98 × 10⁻⁵ to 3.83 × 10⁻⁴ mol L⁻¹ (r = 0.9991) with a detection limit of 2.30 × 10⁻⁶ mol L⁻¹. This biomimetic sensor demonstrated long-term stability (300 days; 900 determinations) and reproducibility, with a relative standard deviation of 12.0%. The recovery study of rosmarinic acid in plant extract samples gave values from 90.3 to 98.3% and the concentrations determined showed agreement when compared with those obtained using capillary electrophoresis at the 95% confidence level.     

Synthesis of novel multidentate carbohydrate-triazole ligands

Cu(I)-catalyzed 1,3-dipolar cycloaddition (click reaction) of 1 mol equiv of N,N′-di-prop-2-ynyl-phthalamide (1a), N,N′-di-prop-2-ynyl-isophthalamide (1b), and pyridine-2,6-dicarboxylic acid bis-prop-2-ynylamide (1c), respectively with 2 mol equiv of 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl azide (2a), 2-azidoethyl 2,3,4,6-tetra-O-acetyl-β-d-glucopyranoside (2b), and 2-azidoethyl 2,3,4,6-tetra-O-acetyl-α-d-mannopyranoside (2c), respectively, afforded the corresponding bis-cycloadducts 3-5, containing two 1,2,3-triazole moieties each, in 38-76% yield. Reaction of 1 mol equiv of 2c with 1 mol equiv of 1c under otherwise identical conditions gave the mono-cycloadduct 6, containing one 1,2,3-triazole and one 2-propynylamide moiety, in 77% yield. Reaction of 6 with 2a afforded 7, containing two different sugar moieties, in 67% yield.     

Application of sequential injection-square wave voltammetry (SI-SWV) to study the adsorption of atrazine onto a tropical soil sample

Square wave voltammetry automated by sequential injection analysis was applied to determine the Freundlich adsorption coefficients for the adsorption of atrazine onto a clay rich soil. The detection limit in soil extracts was between 0.18 and 0.48 μmol L⁻¹, depending on the medium used to prepare the extracts (0.010 mol L⁻¹ KCl, CaCl₂ or HNO₃ and 0.0050 mol L⁻¹ H₂SO₄), all of them conditioned in 40 mmol L⁻¹ Britton-Robinson buffer at pH 2.0 in presence of 0.25 mol L⁻¹ NaNO₃. Also in soil extracts the linear dynamic range was between 1.16 and 18.5 μmol L⁻¹ (0.25-4.0 μg mL⁻¹), with a sampling frequency of 190 h⁻¹. The K_f Freundlich adsorption coefficient was 3.8 ± 0.2 μmol^1−1/n Lⁿ kg⁻¹ in medium of 0.010 mol L⁻¹ KCl or CaCl₂, but increased to 7.7 ± 0.1 and 9.0 ± 0.3 μmol^1−1/n Lⁿ kg⁻¹ in 0.010 mol L⁻¹ HNO₃ and 0.0050 mol L⁻¹ H₂SO₄, respectively. The increase of K_f was related to the decrease of pH from 6.4-6.7 in KCl and CaCl₂ to 3.7-4.0 in presence of HNO₃ or H₂SO₄, which favors protonation of atrazine, facilitating electrostatic attractions with negative charges of the clay components of the soil. The 1/n parameters were between 0.76 and 0.86, indicating that the isotherms are not linear, suggesting the occurrence of chemisorption at specific adsorption sites. No statistically significant differences were observed in comparison to the adsorption coefficients obtained by HPLC. The advantage of the proposed SI-SWV method is the great saving of reagent because it does not use organic solvent as in the case of HPLC (50% (v/v) acetonitrile in the mobile phase). Additionally the start up of SI-SWV is immediate (no column conditioning necessary) and the analysis time is only 19 s.