Synthesis and characterization of diametrically substituted tetra-O-n-butylcalix[4]arene ligands and their chelated complexes of titanium,molybdenum, and palladium

The ligation properties of three new upper-rim-substituted calix[4]arene ligands, 5,17-bis(hydroxymethyl)-tetra-n-butoxycalix[4]arene ((HOCH2)2-nBu4Clx, 7), 5,17-bis((diphenylphosphinito)methoxy)-tetra-n-butoxycalix[4]arene ((PPh2OCH2)2-nBu4Clx, 8), and 5,17-bis((diphenylphosphino)methyl)-tetra-n-butoxycalix[4]arene ((PPh2CH2)2-nBu4Clx, 10) are reported herein. The newly prepared compounds differ from previously reported diametrically substituted calix[4]arene derivatives in that the lower-rim substituent was n-butyl. The presence of this lower-rim substituent did not reduce the inherent crystallinity of these complexes as purification of all materials occurred via simple crystallizations. The key precursor for the syntheses of 8 and 10 was 7, acquisition of which occurred in six steps starting from tetra-tert-butylcalix[4]arene, 1. Calix[4]arene derivatives include, tetra-n-butoxycalix[4]arene (nBu4Clx, 3), 5,11,17,23-tetrabromo-tetra-n-butoxycalix[4]arene (Br4-nBu4Clx, 4), 5,17-dibromo-tetra-n-butoxycalix[4]arene (Br2-nBu4Clx, 5), 5,17-bis(formyl)-tetra-n-butoxycalix[4]arene ((CHO)2-nBu4Clx, 6), and 5,17-bis(chloromethyl)-tetra-n-butoxycalix[4]arene ((ClCH2)2-nBu4Clx, 9), all of which were synthesized using modifications of existing procedures. Characterization of all compounds occurred, when possible, using 1H, 13C, and 31P NMR, elemental analyses, FAB-MS, ESI-MS, FT-IR, and X-ray crystallography. The solid-state structures of all calix[4]arene intermediates and ligands showed that the annulus adopted the pinched-cone conformation in which the average C(5)...C(17) intraannular separation was 4.5 +/- 0.4 A. Reaction of 7 with CpTiMe3 yielded the cis-chelate, CpTi(Me)[(OCH2)2-nBu4Clx] (11), quantitatively. Data obtained using ESI-MS (positive-ion mode) confirmed the monomer formulation showed above, and 1H NMR spectra provided sufficient information to deduce the nature of the Ti coordination sphere. Reaction of 8 with cis-Cl2Pd(NCPh)2 in refluxing benzene afforded cis-Cl2Pd[(PPh2OCH2)2-nBu4Clx] (12) in good yields. The monomeric identity of this compound was verified by both X-ray crystallography and positive-ion ESI-MS. The cis-bidentate calix[4]arene ligand did not undergo any noticeable contortion upon chelation of the PdCl2 fragment. Acid-promoted decomposition of 12 occurred in the presence of adventitious HCl and gaseous HCl, and the products of this decomposition were 9 and [mu2-ClPd(PPh2OH)(PPh2O)]2. In addition, chelates of 8 that contained Mo(CO)3L (L = NCMe (14a), NCEt (14b), and CO (14c)) showed that the mode of coordination was relatively insensitive to the identity of the metal. X-ray crystallography afforded views of the solid-state structures of 14b,c and, like 12, showed that the Mo(CO)3L fragment resided above the pinched-cone of the calix[4]arene. 1H NMR revealed that C-H/pi interactions existed between L (14a,b) and a phenyl ring of the coordinated phosphinite. Finally, the bis(diphenylphosphine)calix[4]arene ligand (10) readily coordinated the Mo(CO)3L species, but the reaction did not go to completion, as evidenced by 1H NMR, even after a 5 day reaction time. Data suggest that the product is similar to that observed for 12 and 14, but the incomplete reaction complicated attempts to obtain pure material and prohibited definitive assignment of the coordination array.     

An efficient palladium-catalyzed Negishi cross-coupling reaction with arylvinyl iodides: facile regioselective synthesis of E-stilbenes and their analogues

A general synthetic route for the Pd-catalyzed cross-coupling of an arylzinc reagent with arylvinyl iodides (Negishi cross-coupling) has been developed. The system permits efficient and selective preparation of E-stilbenes and their analogues. It also functions effectively at low levels of catalyst loading without the need for an additional ligand and tolerates a wide range of functional groups including heteroaromatic substrates. A systematic study of various parameters was performed and correlated with catalyst-substrate activity.     

水/硅胶吸附体系的热化学研究

我们用精密自动绝热量热计测定了几种不同吸附水含量的水/硅胶吸附体系在200～320 K温度范围内的热容. 结果表明, 当吸附水含量使表面复盖度(θ)大于1时, 在相应的C_p～T曲线上会出现吸附水的相变峰. 这说明吸附在硅胶表面上的水分子已经形成了聚集态; 而当θ<1时, 由于尚未形成聚集态水, 故没有相变过程出现, 其C_p～T曲线呈光滑状. 这些现象与H_2O/γ-Al_2O_3吸附体系是一致的. 又由于硅胶表面对水分子的吸附力较γ-Al_2O_3的要小, 故在同样的吸附量的C_p～T曲线上, 水/硅胶的峰要比H_2O/γ-Al_2O_3的尖锐, 且蜂温增高的速度要快. 这些都表明, 吸附在硅胶表面上的二维表相水会随吸附量的增加而以较快的趋势接近于体相水. 此外, 由不同含水量的C_p～T曲线外推, 求出了不含吸附水的硅胶在200～300 K范围内的热容.     

Elution of Cationic Species with/without Ion Pair Reagents from Polar Stationary Phases via SFC

Traditionally, the application of supercritical fluid chromatography has been limited to compounds of relatively low polarity. Thus, we report here that one secondary amine and two quaternary amine salts were successfully eluted from a Deltabond Cyano-bonded silica column with the addition of sodium alkylsulfonate to the methanol-modified, carbon dioxide-based mobile phase. A possible ion-pairing interaction between the positively charged analytes and the anionic part of the sulfonate additive has been proposed. In another set of experiments, the three amine salts readily eluted from both Ethyl-pyridine-bonded silica and Amino-bonded silica phases without the need of additive although the peak shapes were less than desirable. The addition of sulfonate salt to the mobile phase again sharpened the peaks. In the presence of a mixture of methanol and CO₂, we suggest that these stationary phases are positively charged. We describe here also for the first time the employment of a strong silica-based anion exchange (SAX) column for supercritical fluid separation of cationic species. Two elution mechanisms were proposed for the three amine salts depending upon whether the ionic additive was incorporated into the mobile phase. Separation as the ion-pair was proposed with an ionic additive in the mobile phase; whereas separation of the intact amine salt from the positively charged basic stationary phases was suggested to be operational without the ionic additive.     

Microscale sample deposition onto hydrophobic target plates for trace level detection of neuropeptides in brain tissue by MALDI-MS

A sample preparation method that combines a modified target plate with a nanoscale reversed-phase column (nanocolumn) was developed for detection of neuropeptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). A gold-coated MALDI plate was modified with an octadecanethiol (ODT) self-assembled monolayer to create a hydrophobic surface that could concentrate peptide samples into a approximately 200-500-microm diameter spot. The spot sizes generated were comparable to those obtained for a substrate patterned with 200-microm hydrophilic spots on a hydrophobic substrate. The sample spots on the ODT-coated plate were 100-fold smaller than those formed on an unmodified gold plate with a 1-microl sample and generated 10 to 50 times higher mass sensitivity for peptide standards by MALDI-TOF MS. When the sample was deposited on an ODT-modified plate from a nanocolumn, the detection limit for peptides was as low as 20 pM for 5-microl samples corresponding to 80 amol deposited. This technique was used to analyze extracts of microwave-fixed tissue from rat brain striatum. Ninety-eight putative peptides were detected including several that had masses matching neuropeptides expected in this brain region such as substance P, rimorphin, and neurotensin. Twenty-three peptides had masses that matched peaks detected by capillary liquid chromatography with electrospray ionization MS.     

Heavy metal phosphate nanophases in silica: influence of radiolysis probed via f-electron state properties

We have assessed the feasibility of carrying out time- and wavelength-resolved laser-induced fluorescence measurements of radiation damage in glassy silica. The consequences of alpha decay of Es-253 in LaPO₄ nanophases embedded in silica were probed based on excitation of 5f states of Cm³⁺, Bk³⁺, and Es³⁺ ions. The recorded emission spectra and luminescence decays showed that alpha decay of Es-253 ejected Bk-249 decay daughter ions into the surrounding silica and created radiation damage within the LaPO₄ nanophases. This conclusion is consistent with predictions of an ion transport code commonly used to model ion implantation. Luminescence from the ⁶D_7/2 state of Cm³⁺was used as an internal standard. Ion-ion energy transfer dominated the dynamics of the observed emitting 5f states and strongly influenced the intensity of observed spectra. In appropriate sample materials, laser-induced fluorescence provides a powerful method for fundamental investigation of alpha-induced radiation damage in silica.     

The intramolecular asymmetric Pauson-Khand cyclization as a novel and general stereoselective route to benzindene prostacyclins: synthesis of UT-15 (treprostinil)

A general and novel solution to the synthesis of biologically important stable analogues of prostacyclin PGI(2), namely benzindene prostacyclins, has been achieved via the stereoselective intramolecular Pauson-Khand cyclization (PKC). This work illustrates for the first time the synthetic utility and reliability of the asymmetric PKC route for synthesis and subsequent manufacture of a complex drug substance on a multikilogram scale. The synthetic route surmounts issues of individual step stereoselectivity and scalability. The key step in the synthesis involves efficient stereoselection effected in the PKC of a benzoenyne under the agency of the benzylic OTBDMS group, which serves as a temporary stereodirecting group that is conveniently removed via benzylic hydrogenolysis concomitantly with the catalytic hydrogenation of the enone PKC product. Thus the benzylic chiral center dictates the subsequent stereochemistry of the stereogenic centers at three carbon atoms (C(3a), C(9a), and C(1)).     

Solvent effects on infrared spectra of methyl 4-hydroxybenzoate in pure organic solvents and in ethanol/CCl4 binary solvents

Infrared spectroscopy studies of methyl 4-hydroxybenzoate (MHB) in 17 different organic solvents and in ethanol/CCl4 binary solvent were undertaken to investigate the solvent-solute interactions. The frequencies of carbonyl stretching vibration nu(C=O) of MHB in single solvents were correlated with the solvent acceptor number (AN) and the linear solvation energy relationships (LSER). The assignments of the two bands of nu(C=O) of MHB in alcohols and the single one of that in non-alcoholic solvents were discussed. The shifts of nu(C=O) of MHB in ethanol/CCl4 binary solvents showed that several kinds of solute-solvent hydrogen bonding interactions coexisted in the mixture solvents, with a change in the mole fraction of ethanol in the binary solvents.     

Diastereoselective formation of glycoluril dimers: isomerization mechanism and implications for cucurbit[n]uril synthesis

Cucurbit[6]uril (CB[6]) is a macrocyclic compound, prepared in one pot from glycoluril and formaldehyde, whose molecular recognition properties have made it the object of intense study. Studies of the mechanism of CB[n] formation, which might provide insights that allow the tailor-made synthesis of CB[n] homologues and derivatives, have been hampered by the complex structure of CB[n]. By reducing the complexity of the reaction to the formation of S-shaped (12S-18S) and C-shaped (12C-18C) methylene bridged glycoluril dimers, we have been able to probe the fundamental steps of the mechanism of CB[n] synthesis to a level that has not been possible previously. For example, we present strong evidence that the mechanism of CB[n] synthesis proceeds via the intermediacy of both S-shaped and C-shaped dimers. The first experimental determination of the relative free energies of the S-shaped and C-shaped dimers indicates a thermodynamic preference (1.55-3.25 kcal mol(-)(1)) for the C-shaped diastereomer. This thermodynamic preference is not because of self-association, solvation, or template effects. Furthermore, labeling experiments have allowed us to elucidate the mechanism of this acid-catalyzed equilibrium between the S-shaped and C-shaped diastereomers. The equilibration is an intramolecular process that proceeds with high diastereoselectivity and retention of configuration. On the basis of the broad implications of these results for CB[n] synthesis, we suggest new synthetic strategies that may allow for the improved preparation of CB[n] (n > 8) and CB[n] derivatives from functionalized glycolurils.     

Synthesis and Crystal Structure of Two One—dimensional Chain Copper Complexes [Cu（TTA）2（4,4‘’—azpy）] and [Cu（TTA）2（3,3‘’—azpy）

Two copper complexes [Cu(TTA)₂(4,4′‐azpy)] (1) and [Cu‐(TTA)₂(3,3′‐azpy)] (2) (HTTA = 1,1,1‐trifluoro‐3‐(2‐thenoyl)‐acetone, 4,4′‐azpy = 4,4′‐azobispyridine, 3,3′‐azpy = 3,3′‐azobispyridine) were synthesized and characterized. The crystal structures were determined by X‐ray diffraction analysis. The crystal 1 belongs to triclinic with space group P1 , a = 0.8515(2) nm, b = 0.9259(2) nm, c = 0.9468(2) nm, a = 66.126(9)°, β = 79.667(9)°, γ = 90.13(1)°, Z = 1, V = 0.6692(2) nm³, D_c = 3.425 g/cm³, γ = 2.113 mm^?1, F(000) = 694, R₁ = 0.0594, wR₂ = 0.1499. The crystal 2 belongs to monoclinic with space group P2₁/c, a = 1.0661(2) nm, b = 1.4296(3) ran, c = 1.0041(3) nm, β = 114.50(3)°, V = 1.3926(5) nm³, Z = 2, D_c = 1.646 g/ cm³, μ = 1.015 mm^?1, F(000) = 694, R₁, = 0.0535, wR₂ = 0.1113. In the crystals of complexes 1 and 2, the copper atoms have distorted octahedral symmetry. The two compounds possess very similar one‐dimensional linear chains linked through the rodlike 4,4′‐azpy ligands or 3,3′‐azpy ligands.