Nickel-catalysed addition of dialkylzinc reagents to N-phosphinoyl- and N-sulfonylimines

A catalytic amount of a nickel complex (0.1-5.3 mol %) extraordinarily increases the reaction rate of the addition of dialkylzinc reagents to N-(diphenylphosphinoyl)- or N-(benzenesulfonyl)imines. The reaction of imines derived from both aromatic and aliphatic aldehydes with various dialkylzinc reagents in the presence of several nickel complexes gives the expected addition products in most cases in 1 h and in very good yields. In general, the formation of reduction by-products was not an important side reaction. The process represents a great improvement, with regard to the reaction rate and the yield of the addition products, in comparison with the reactions performed in the absence of the nickel catalyst, and reaction times are much shorter than the ones reported so far using other catalysts.     

Synthesis, characterization and Schlenk equilibrium studies of methylmagnesium compounds with O- and N-donor ligands - the unexpected behavior of [MgMeBr(pmdta)] (pmdta = N,N,N′,N″,N″-pentamethyldiethylenetriamine)

MgMe₂ (1) was found to react with 1,4-diazabicyclo[2.2.2]octane (dabco) in tetrahydrofuran (thf) yielding a binuclear complex [{MgMe₂(thf)}₂(μ-dabco)] (2). Furthermore, from reactions of MgMeBr with diglyme (diethylene glycol dimethyl ether), NEt₃, and tmeda (N,N,N′,N′-tetramethylethylenediamine) in etheral solvents compounds MgMeBr(L), (L = diglyme (5); NEt₃ (6); tmeda (7)) were obtained as highly air- and moisture-sensitive white powders. From a thf solution of 7 crystals of [MgMeBr(thf)(tmeda)] (8) were obtained. Reactions of MgMeBr with pmdta (N,N,N′,N″,N″-pentamethyldiethylenetriamine) in thf resulted in formation of [MgMeBr(pmdta)] (9) in nearly quantitative yield. On the other hand, the same reaction in diethyl ether gave MgMeBr(pmdta) · MgBr₂(pmdta) (10) and [{MgMe₂(pmdta)}₇{MgMeBr(pmdta)}] (11) in 24% and 2% yield, respectively, as well as [MgMe₂(pmdta)] (12) as colorless needle-like crystals in about 26% yield. The synthesized methylmagnesium compounds were characterized by microanalysis and ¹H and ¹³C NMR spectroscopy. The coordination-induced shifts of the ¹H and ¹³C nuclei of the ligands are small; the largest ones were found in the tmeda and pmdta complexes. Single-crystal X-ray diffraction analyses revealed in 2 a tetrahedral environment of the Mg atoms with a bridging dabco ligand and in 8 a trigonal-bipyramidal coordination of the Mg atom. The single-crystal X-ray diffraction analyses of [MgMe₂(pmdta)] (12) and [MgBr₂(pmdta)] (13) showed them to be monomeric with five-coordinate Mg atoms. The square-pyramidal coordination polyhedra are built up of three N and two C atoms in 12 and three N and two Br atoms in 13. The apical positions are occupied by methyl and bromo ligands, respectively. Temperature-dependent ¹H NMR spectroscopic measurements (from 27 to −80 °C) of methylmagnesium bromide complexes MgMeBr(L) (L = thf (4); diglyme (5); NEt₃ (6); tmeda (7)) in thf-d₈ solutions indicated that the deeper the temperature the more the Schlenk equilibria are shifted to the dimethylmagnesium/dibromomagnesium species. Furthermore, at −80 °C the dimethylmagnesium compounds are predominant in the solutions of Grignard compounds 4-6 whereas in the case of the tmeda complex7 the equilibrium constant was roughly estimated to be 0.25. In contrast, [MgMeBr(pmdta)] (9) in thf-d₈ revealed no dismutation into [MgMe₂(pmdta)] (12) and [MgBr₂(pmdta)] (13) even up to −100 °C. In accordance with this unexpected behavior, 1:1 mixtures of 12 and 13 were found to react in thf at room temperature yielding quantitatively the corresponding Grignard compound 9. Moreover, the structures of [MgMeBr(pmdta)] (9c), [MgMe₂(pmdta)] (12c), and [MgBr₂(pmdta)] (13c) were calculated on the DFT level of theory. The calculated structures 12c and 13c are in a good agreement with the experimentally observed structures 12 and 13. The equilibrium constant of the Schlenk equilibrium (2 9c ? 12c + 13c) was calculated to be K_gas = 2.0 × 10⁻³ (298 K) in the gas phase. Considering the solvent effects of both thf and diethyl ether using a polarized continuum model (PCM) the corresponding equilibrium constants were calculated to be K_thf = 1.2 × 10⁻³ and K_ether = 3.2 × 10⁻³ (298 K), respectively.     

New N,N-amino-diphosphonate-containing methacrylic derivatives, their syntheses and radical copolymerizations with MMA

Hydroxy-amino-diphosphonates HO-C_n-NH₂, with 2 ? n ? 11, have been successfully synthesized via the Kabachnick-Field reaction at 70 °C with high yields. These hydroxy compounds are then reacted with methacryloyl chloride to lead to novel amino-diphosphonate methacrylates MAC_nNP₂ (with 2 ? n ? 11). These highly pure methacrylate monomers were obtained with yields higher than 75%. Radical copolymerizations of MAC_nNP₂ (with 2 ? n ? 11) with MMA have been conducted and the r₁ values (related to MAC_nNP₂) are in the range of 1.1-1.3, and r₂ values (related to MMA) about 0.8; this shows that the diphosphonate groups are statistically bonded to the methacrylic backbone.     

Coordination compounds of N,N′-olefin functionalized imidazolin-2-ylidenes

N-Heterocyclic carbene ligands (NHC) were metalated with Pd(OAc)₂ or [Ni(CH₃CN)₆](BF₄)₂ by in situ deprotonation of imidazolium salts to give the N-olefin functionalized biscarbene complexes [MX₂(NHC)₂] 3-7 (3: M = Pd, X = Br, NHC = 1,3-di(3-butenyl)imidazolin-2-ylidene; 4: M = Pd, X = Br, NHC = 1,3-di(4-pentenyl)imidazolin-2-ylidene; 5: M = Pd, X = I, NHC = 1,3-diallylimidazolin-2-ylidene; 6: M = Ni, X = I, NHC = 1,3-diallylimidazolin-2-ylidene; 7: M = Ni, X = I, NHC = 1-methyl-3-allylimidazolin-2-ylidene). Molecular structure determinations for 4-7 revealed that square-planar complexes with cis (5) or trans (4, 6, 7) coordination geometry at the metal center had been obtained. Reaction of nickelocene with imidazolium bromides afforded the η⁵-cyclopentadienyl (η⁵-Cp) monocarbene nickel complexes [NiBr(η⁵-Cp)(NHC)] 8 and 9 (8: NHC = 1-methyl-3-allylimidazolin-2-ylidene; 9: NHC = 1,3-diallylimidazolin-2-ylidene). The bromine abstraction in complexes 8 and 9 with silver tetrafluoroborate gave complexes [NiBr(η⁵-Cp)(η³-NHC)] 10 and 11. The X-ray structure analysis of 10 and 11 showed a trigonal-pyramidal coordination geometry at the nickel(II) center and coordination of one N-allyl substituent.     

Syntheses and structures of zinc and tin(II) compounds with hemilabile N-silyl-tert-butylamido and N-silyl-p-tolylamido ligands that contain pendent tert-butoxy groups

Syntheses and solid-state structures of zinc and tin(II) compounds, containing the N-silyl-amide ligands (O^tBu)(NR)SiMe₂, R = ^tBu (L^tBu), or R = p-tolyl (L^pTol), are reported. The N-silyl amines were synthesized by modified published procedures from commercially available Me₂SiCl₂, ^tBuOH, and ^tBuNH₂, or p-Me-C₆H₄NH₂, respectively. Treatment of SnCl₂ with LiL^pTol furnished Sn(L^pTol)₂, which was X-ray structurally characterized and shown to contain two covalent Sn-N bonds and two asymmetrical O → Sn donor bonds. The single-crystal X-ray structure of Sn(L^tBu)₂ revealed a much more symmetrically-coordinated, pseudo-trigonal-bipyramidal tin atom. Aminolysis of diethylzinc with HL^pTol produced [EtZn(L^pTol)]₂, which crystallized as a centrosymmetric dimer, containing four-coordinate zinc atoms connected by bridging amides. Zinc dichloride, by contrast, reacted with two equivalents of LiL^tBu to produce the homoleptic, pseudo-spirocyclic Zn(L^tBu)₂.     

N,N-polymethylene-bisadenine complexes with d metal ions

The reaction of N⁹,N^9′-(tri or tetramethylene)-bisadenines (Ade₂C_x; x = 3 or 4) in HCl 2 M at 50 °C with MCl₂ · 2H₂O [M = Zn(II), Cd(II)] yields outer sphere compounds like the previously described [(H-Ade)₂C₃][ZnCl₄] · H₂O (3) and [(H-Ade)₂C₃]₂[Cd₂Cl₈(H₂O)₂] · 4H₂O (4) for Ade₂C₃ and the new {[(H-Ade)₂C₄][Cd₂Cl₆(H₂O)₂] · 2H₂O}_n (5) for Ade₂C₄. On the other hand, only in case of Zn(II) complexes by changing [HCl] to 0.1 M, the inner sphere compounds [H-(Ade)₂C₃(ZnCl₃)] (6) and [H-(Ade)₂C₄(ZnCl₃)] · 1.5H₂O (7) are obtained. X-ray diffraction study of compound 6, which represents the first inner sphere complex with a N⁹,N^9′-bisadenine, shows a zwitterionic form with one adenine ring protonated at N(1) while the other ring is coordinated via N(7) to a ZnCl₃ moiety as in other alkyl-adenine derivatives. In addition, with Ade₂C₄, is also possible to obtain another inner sphere complex: [(H-Ade)₂C₄(ZnCl₃)₂] · 3H₂O (8).     

Room temperature synthesis of glycerol carbonate catalyzed by N-heterocyclic carbenes

N-Heterocyclic carbenes were used as efficient organocatalysts for the synthesis of glycerol carbonate from glycerol and dimethyl carbonate. The reaction takes place in a liquid mixture of reactants without solvent at room temperature. It provides glycerol carbonate in high yield using 2.6–4 mol % of catalyst in a reaction period of 20–30 min.     

Capillary electrophoresis-electrochemiluminescent detection of N,N-dimethyl ethanolamine and its application in impurity profiling and stability investigation of meclophenoxate

Numerous drugs are carboxylic acid derivatives containing amino group, and hydrolysis reaction of these agents often generates toxic amines. Thus, the detection of amine impurity is of great importance in drug quality control of these amino group-containing ester and amide. A capillary electrophoresis method coupled with end-column electrochemiluminescent detection based on tris(2,2′-bipyridyl)ruthenium(II) system was proposed for the analysis of N,N-dimethyl ethanolamine (DMEA, the degradation product of meclophenoxate) in the presence of its precursor. Baseline separation of DMEA and meclophenoxate can be easily achieved under the selected conditions. DMEA can be assayed within 3 min over the concentration range of 5.0 × 10⁻⁸ to 3.0 × 10⁻⁶ mol L⁻¹ with a detection limit of 2.0 × 10⁻⁸ mol L⁻¹ at the signal-to-noise ratio of 3. The relative standard deviations of the signal intensity and the migration time were less than 5.3 and 2.5% for a standard sample containing 1.0 × 10⁻⁷ mol L⁻¹ DMEA (n = 5), respectively. The presented method has been successfully applied for the profiling of DMEA resulting from the hydrolysis of meclophenoxate in commercial formulations. A primary stability investigation of meclophenoxate in aqueous solution was also carried out at different temperatures, and the results showed that the degradation of meclophenoxate accelerated at the higher temperature.     

Efficient, solventless N-Boc protection of amines carried out at room temperature using sulfamic acid as recyclable catalyst

A simple, rapid, and efficient protocol for the chemoselective N-Boc protection of amines using sulfamic acid as catalyst is described. N-Boc protection of various structurally diverse aliphatic, aromatic, alicyclic, and heterocyclic amines (1°, 2°, 3°) was carried out with (Boc)₂O using sulfamic acid as catalyst (5 mol %) at room temperature under solventless conditions. The advantages of this method are simplicity, shorter reaction times (1-15 min), a cost-effective catalyst, and excellent isolated yields (90-100%); it is also environmentally benign. Moreover, the combined use of ultrasound and sulfamic acid achieves a synergic effect that is especially marked in the N-Boc protection of deactivated (sterically hindered and electron-deficient) amines. The catalyst possesses distinct advantages: ease of handling, cleaner reactions, high activity, and excellent chemoselectivity.     

Bromamine-T/RuCl3 as an efficient system for the oxidation of tertiary amines to N-oxides

A variety of tertiary amines were efficiently and selectively oxidized to the corresponding N-oxides by bromamine-T using ruthenium trichloride as catalyst in alkaline (pH 8.4) acetonitrile/water (1:1) at 80 °C.     

Synthesis, structural and spectroscopic properties of a new Schiff base ligand N,N′-bis(trifluoromethylbenzylidene)ethylenediamine

The Schiff base compound, N,N′-bis(trifluoromethylbenzylidene)ethylenediamine (C₁₈H₁₄F₆N₂) (1), CF₃C₆H₄CHNCH₂CH₂NCHC₆H₄CF₃ has been synthesized by adding a solution of ethylenediammine (en), 0.1 mmol in chloroform to 4-(trifluoromethyl)-benzaldehyde, CF₃C₆H₄CHO (0.2 mmol) and the product was crystallized in ethanol with the mp, 109.2 °C and 75% yield. The crystal structure was investigated by a single-crystal X-ray diffraction study at 150 K. The compound crystallizes in monoclinic space group, P2₁/c with a = 9.295(3), b = 5.976(5), c = 15.204(9) Å and α = 90°, β = 96.56(5)° and γ = 90°. The crystal structure is stabilized by intermolecular CH · · · F hydrogen bonds. The asymmetric unit contains only one-half of the molecule related to the center of symmetry coinciding with C(1)-C(1′) and as a whole, the title molecule is in the staggered conformation. The phenyl rings and the CN imine bonds are co-planar. The infrared spectrum showed a sharp peak at 1640 cm⁻¹ which is typical of the conjugated CN stretching and strong peaks at 800-1400 cm⁻¹ regions are due to the C-C and C-H stretching modes. Electronic absorption spectra exhibits strong absorption in the UV region (240 nm wavelength) which have been ascribed to , and electronic transitions. The ¹H NMR spectra showed three distinct peaks at 2.5, 7.8 and 8.5 ppm which are assigned based on the splitting of resonance signals and are clearly confirmed by the X-ray molecular structure. The aromatic protons appear at about 7.8 ppm and the imine protons at 8.5 ppm. The sharp singlet at about 3.95 ppm is assigned to the CH₂-CH₂ protons. Mass spectra of the titled compound showed the molecular ion peak at m/e 372 (M⁺), and fragments at m/e 353 (M-F), 342 (M-2F), 200 (M-CF₃C₆H₄CHN), 186 (M-CF₃C₆H₄CHNCH₂).     

Aerobic oxidation of 1,3,5-triisopropylbenzene using N-hydroxyphthalimide (NHPI) as key catalyst

The first systematic study on the aerobic oxidation of 1,3,5-triisopropylbenzene was examined by the use of N-hydroxyphthalimide (NHPI) as a key catalyst. It was found that 1,3,5-triisopropylbenzene was efficiently oxidized with O₂ in the presence of a catalytic amount of NHPI and azobisisobutyronitrile (AIBN) at 75 °C. Upon treatment of the resulting products with sulfuric acid followed by acetic anhydride led to 5-acetoxy-1,3-diisopropylbenzene and 3,5-diacetoxy-1-isopropylbenzene as major products and a small amount of 1,3,5-triacetoxybenzene. When t-butylperoxypivalate (BPP) was employed as a radical initiator, the oxidation could be achieved in good yield even at 50 °C. This oxidation provides a facile method for preparing phenol derivatives bearing an isopropyl moiety, which can be used as pharmaceutical starting materials.     

Synthesis of N,N-dialkylaminobenzonitriles and halo-(N,N-dialkyl)benzamidines by reaction of halobenzonitriles with lithium amides

3- and 4-N,N-Dialkylaminobenzonitriles and 4-chloro-(N,N-dialkyl)benzamidines were isolated by reacting 4-chlorobenzonitrile with hindered lithium amides under thermodynamic (0 °C) and kinetic control conditions (−78 °C), respectively. As previously reported, a benzyne mechanism seems to be confirmed since N,N-dialkylaminobenzonitriles are formed. Only benzamidines were isolated in fair to high yields at both 0 °C and −78 °C with non-hindered lithium amides. Exploitation and mechanistic rationale of the reaction of different halobenzonitriles are also reported.     

A macromolecular N,N-dichlorosulfonamide as oxidant for residual sulfides

A redox copolymer, a macroporous poly(S/DVB) resin bearing N,N-dichlorosulfonamide groups, was used to remove residual sulfides from aqueous solutions by its oxidation to non-toxic products. The resin contains 8.2 meq active chlorine/g and shows strong oxidizing properties. It was employed in static and flow processes for treatment of sulfide solutions containing 32, 100 or 320 mg S²⁻/dm³. The effects of various parameters on the reaction course have been studied (molar ratio of the reagents, alkalinity of the reaction media, flow rate in column processes). The data showed that the reactive copolymer easily oxidizes sulfides--it was possible to reduce the concentration below 10 μg S²⁻/dm³. During oxidation processes the formation of two end products was confirmed--these were sulfates (in majority) and sulfur which causes the turbidity of the effluents. The reaction conditions to eliminate sulfur formation were sought. To utilize the polymer-bonded active chlorine with good efficiency, it was necessary to maintain a suitable level of alkalinity of the influx. The exhausted copolymer contained unsubstituted sulfonamide groups. It could be regenerated with a slightly acidified sodium chlorate(I) and reused for further processes.     

N-Demethyl-sauroxine,a novel Lycodine Group alkaloid from Huperzia saururus

The present study describes the isolation and identification of N-demethyl-sauroxine, a novel Lycopodium alkaloid obtained from Huperzia saururus (Lam.) Trevis. (Lycopodiaceae). Its structure and relative stereochemistry were elucidated on the basis of its spectral data and chemical correlations. Additionally, acetylcholinesterase inhibitory activity was evaluated (IC₅₀ = 209.6 ± 1.1 μM). The structure of the already identified alkaloid sauroxine was also re-validated through two dimensional NMR data.     

Two-stage formation of chloro (N-o-chlorobenzamido-meso-tetraphenylporphyrinato) zinc(II) methylene chloride solvate: Zn(N-NHCO(o-Cl)C6H4-tpp)Cl · CH2Cl2

The coordinating properties of N-o-chlorobenzamido-meso-tetraphenylporphyrin (N-NHCO(o-Cl)C₆H₄-Htpp; 11) have been investigated for the Zn²⁺ ion. Insertion of Zn results in the formation of the zinc complex Zn(N-NCO(o-Cl)C₆H₄-tpp)(MeOH) · MeOH (12 · MeOH). The diamagnetic 12 · MeOH can be transformed into the diamagnetic Zn(N-NHCO(o-Cl)C₆H₄-tpp)Cl · CH₂Cl₂ (13 · CH₂Cl₂) in a reaction with aqueous hydrogen chloride (2%). X-ray structures for 12 · MeOH and 13 · CH₂Cl₂ have been determined. The coordination sphere around the Zn²⁺ ion in 12 · MeOH is a distorted trigonal bipyramid with N(2), N(4) and O(2) lying in the equatorial plane, whereas for the Zn²⁺ ion in 13 · CH₂Cl₂, it is a square-based pyramid in which the apical site is occupied by the Cl(1) atom.     

Dioxomolybdenum(VI) complexes containing N-heterocyclic carbenes

Compound MoO₂Cl₂(THF)₂ reacts with two equivalents of 1,3-dialkyl substituted 4,5-dimethylimidazol-2-ylidenes to give the dioxomolybdenum(VI) complexes MoO₂Cl₂(L^R)₂ [R = Me (1), i-Pr (2)]. Treatment of MoO₂Cl₂(THF)₂ with one equivalent of the N-heterocyclic carbenes L^Me, L^i-Pr and ^C1L^n-Bu (L^Me = 1,3,4,5-tetramethylimidazol-2-ylidene, L^i-Pr = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene, and ^C1L^n-Bu = 1,3-dibutyl-4,5-dichloroimidazol-2-ylidene) affords the monocarbene adducts MoO₂Cl₂(L^R) [R = Me (3), i-Pr (4)] and MoO₂Cl₂(^C1L^n-Bu) (5), respectively. Decomposition of complexes 1-5 affords a molybdenum oxychloride anion [Mo₂O₅Cl₄]²⁻ as an imidazolium salt.     

Enantioselective cyanosilylation of ketones catalyzed by double-activation catalysts with N-oxides

Enantioselective addition of trimethylsilyl cyanide to ketones by a catalytic double-activation method is described. By combinatorially using 2.0 mol% of a chiral salen-titanium complex and 1.0 mol% of an achiral tertiary amine N-oxide, aromatic, aliphatic and α,β-unsaturated ketones are converted into corresponding cyanohydrin trimethylsilyl ethers with 50-93% yield and 59-86% ee. The effects of ligand structure, catalyst loading and substrate concentration, solvents, the nature of Lewis base, counter ion and other additives, temperature, and substrate structure on the enantioselectivity are discussed. Three possible paths to achieve the asymmetric version of double-activation catalysis and two independent examples of it are proposed.     

Structure of N,C,N-chelated organotin(IV) fluorides

The set of starting tri-, di- and monoorganotin(IV) halides containing N,C,N-chelating ligand (L^NCN = {1,3-[(CH₃)₂NCH₂]₂C₆H₃}⁻) has been prepared (1-5) and two compounds structurally characterized ([L^NCNPh₂Sn]⁺I₃⁻ (1c), L^NCNSnBr₃ (5)) in the solid state. These compounds were reacted with KF with 18-crown-6, NH₄F or L^CNnBu₂SnF to give derivatives containing fluorine atom(s). Triorganotin(IV) fluorides L^NCNMe₂SnF (2a) and L^NCNnBu₂SnF (3a) revealed monomeric structural arrangement with covalent Sn-F bond both in the coordinating and non-coordinating solvents, except the behaviour of 3a that was ionized in the methanol solution at low temperature. The products of fluorination of L^NCNSnPhCl₂ (4) and 5 were described by NMR in solution as the ionic hypervalent fluorostannates or the oligomeric species reacting with chloroform, methanol or moisture to zwitterionic monomeric stannate L^NCN(H)⁺SnF₄⁻ (5c), which was confirmed by XRD analysis in the solid state.     

Novel coated-graphite membrane sensor based on N,N′-dimethylcyanodiaza-18-crown-6 for the determination of ultra-trace amounts of lead

A novel selective membrane electrode for determination of ultra-trace amount of lead was prepared. The PVC membrane containing N,N′-dimethylcyanodiaza-18-cown-6 (DMCDA18C6) directly coated on a graphite electrode, exhibits a Nernstian response for Pb²⁺ ions over a very wide concentration range (from 1.0×10⁻² to 1.0×10⁻⁷ M) with a limit of detection of 7.0×10⁻⁸ M (∼14.5 ppb). It has a fast response time of ∼10 s and can be used for at least 2 months without any major deviation in potential. The electrode revealed very good selectivity with respect to all common alkali, alkaline earth, transition and heavy metal ions. The proposed sensor was used as an indicator electrode in potentiometric titration of lead ions and in determination of lead in edible oil, human hair and water samples. The proposed sensor was found to be superior to the best Pb²⁺-selective electrodes reported in terms of detection limit and selectivity coefficient.