A general and convenient synthesis of N-aryl piperazines

A general and convenient synthesis of N-aryl piperazines from bis(2-chloroethyl)amine hydrochloride and a broad range of anilines in diethylene glycol monomethyl ether is described.     

Cover Picture

The cover picture shows a model of the "progenitor-TADDOLs" in front of a panorama of the Fünffingersstocks and the Wenden Glacier in the Titlisgebiet (Switzerland). The model is flanked by a stylized view of the general mechanistic model for the preferred stereochemical pathway of the Ti-TADDOLate-catalyzed reaction of chelating substrates (left) and a blackboard (right) showing formulae of compounds that can be prepared with high enantioselectivity by nucleophilic addition in the presence of titanium TADDOLates. From TADDOL, introduced in 1982, a genuine auxiliary system for the "introduction of chirality" (not only by reaction) has been developed, which, in the final sprint against the competition has a good chance of securing a place on the winning podium. The photograph of the mountain landscape was taken by Dr. J. Frackenpohl, the cover picture was generated by one of the authors (A.H.) of the comprehensive review of TADDOLs in this issue (p. 92 ff.) with the help of the program Povray. Supporting information for this article is available on the WWW under http://www.angewandte.com or from the author.     

Cyclopeptid-Antibiotika aus Aspergillus-Arten. Struktur der Echinocandine C und D

Cyclopeptide antibiotics from Aspergillus species. Structure of echinocandins C and D The echinocandins B, C and D are antifungal antibiotics produced by a strain of Aspergillus rugulosus. All three metabolites are closely related representing cyclic oligopeptides composed of six amino acids and a linolic acid residue in an amide linkage. The complete structure of echinocandin B ( 1 ) has recently been established by X-ray analysis. Structural assignments to the new minor metabolites C and D have now been made by hydrolytic and oxidative cleavage reactions, formation of N-acyl-α-aminoethers as well as by chemical correlations and extensive NMR. examinations. Echinocandin C ( 2 ), C₅₂H₈₁N₇O₁₅, contains 3-hydroxyhomotyrosine in the place of 3, 4-dihydroxyhomotyrosine present in 1 . Echinocandin D ( 3 ), C₅₂H₈₁N₇O₁₃, differs in two amino acids: 3, 4-dihyroxyhomotyrosine and 4, 5-dihydroxyornithine, unusual units of 1 being replaced by 3-hydroxyhomotyrosine and ornithine.     

Comparison of mono- and polyatomic primary ions for the characterization of organic dye overlayers with static secondary ion mass spectrometry

Organic carbocyanine dye coatings have been analyzed by time-of-flight static secondary ion mass spectrometry (TOF-S-SIMS) using three types of primary ions: Ga(+) operating at 25 keV, and Xe(+) and SF(5) (+) both operating at 9 keV. Secondary ion yields obtained with these three primary ions have been compared for coatings with different layer thickness, varying from (sub)-monolayer to multilayers, on different substrates (Si, Ag and AgBr cubic microcrystals). For (sub)-monolayers deposited on Ag, Xe(+) and SF(5) (+) primary ions generate similar precursor ion intensities, but with Ga(+) slightly lower precursor ion intensities were obtained. Thick coatings on Ag as well as mono- and multilayers on Si produce the highest precursor and fragment ion intensities with the polyatomic primary ion. The yield difference between SF(5) (+) and Xe(+) can reach a factor of 6. In comparison with Ga(+), yield enhancements by up to a factor of 180 are observed with SF(5) (+). For the mass spectrometric analysis of dye layers on AgBr microcrystals, SF(5) (+) again proves to be the primary ion of choice.     

Ab initio study of AmCl(+): f-f spectroscopy and chemical binding

A valence full configuration interaction study with a polarized double-zeta quality basis set has been carried out for the lowest 49 electronic states of AmCl(+). The calculations use a pseudopotential treatment for the core electrons and incorporate a one-electron spin-orbit interaction operator. Electrons in the valence s, p, d, and f subshells were included in the active space. The resulting electronic potential energy curves are largely repulsive. The chemical bonding is ionic in character with negligible participation of 5f electrons. The molecular f-f spectroscopy of AmCl(+) arises essentially from an in situ Am(2+) core with states slightly redshifted by the presence of chloride ion. Am(+)+Cl asymptotes which give rise to the few attractive potential energy curves can be predicted by analysis of the f-f spectroscopy of isolated Am(+) and Am(2+). The attractive curves have substantial binding energies, on the order of 75-80 kcal/mol, and are noticeably lower than recent indirect measurements on the isovalent EuCl(+). An independent empirical correlation supports the predicted reduction in AmCl(+) binding energy. The energies of the repulsive curves are strongly dependent on the selection of the underlying atomic orbitals while the energies of the attractive curves do not display this sensitivity. The calculations were carried out using our recently developed parallel spin-orbit configuration interaction software.     

Photochemistry of 1,3-cyclopentanediones. Oxetane formation involving both energy transfer and electron transfer processes

Photolysis of 2,2-dimethyl-1,3-cyclopentanedione in acetone resulted in oxetane formation in a two photon process involving energy transfer from triplet excited acetone and electron transfer from singlet excited acetone.     

pH sensitivity of Si--C linked organic monolayers on crystalline silicon surfaces.

The electrochemical behavior of Si--C linked organic monolayers is studied in electrolyte-insulator-Si devices, under conditions normally encountered in potentiometric biosensors, to gain fundamental knowledge on the behavior of such Si electrodes under practical conditions. This is done via titration experiments, Mott-Schottky data analysis, and data fitting using a site-binding model. The results are compared with those of native SiO(2) layers and native SiO(2) layers modified with hexamethyldisilazane. All samples display pH sensitivity. The number of Si--OH groups on the alkylated samples is calculated to be less than 0.7 % of that of a pure SiO(2) insulator, which still causes a pH sensitivity of approximately 25 mV per pH unit in the pH range: 4-7. The alkylated samples hardly suffer from response changes during up- and down-going titrations, which indicates that very little oxide is additionally formed during the measurements. The pK(a) values of all samples with monolayers (4.0-4.4) are lower than that of native SiO(2) (6.0). The long-term drift (of approximately 1 mV h(-1)) is moderate. The results indicate that biosensors composed of alkylated Si substrates are feasible if a cross-sensitivity towards pH in the sensor signal is taken into account.     

Sequence-Specific Spin Labeling of Oligothymidylates by Phosphotriester Chemistry

Oligothymidylates (oligo(dT)'s) with the sequence-specifically-incorporated one-atom-tethered C(5)-nitio-xide-labeled nucleoside 1 were synthesized by the phosphotriester method. Some modifications of the protocol were required to account for the chemical reactivity of the nitroxide, the stability of which was monitored during the synthesis by electron paramagnetic resonance (EPR) spectroscopy. The EPR specific activity (A_EPR) of the FPLC-purified nitroxide-labeled oligomers was determined and found to be in agreement with enzymatically prepared spin-labeled nucleic acids. Annealing the nitroxide-labeled oligo(dT)'s to (dA)_n or oligo(dA) resulted in different EPR-lineshape changes suggesting a strong coupling of the short-tethered nitroxide to global macro-molecular motion.     

Quantitative reaction cascades of ninhydrin in the solid state

Crystalline ninhydrin (1) undergoes waste-free solid-state cascade reactions with dimedone, L-proline, three o-phenylenediamines, o-mercaptoaniline, two ureas, three thioureas, and methyl 3-aminocrotonate. The yields are quantitative and give pure crystalline products without workup just by milling stoichiometric mixtures of the crystalline reagents. The structures of the new and the previously obtained products with lower yields from solutions are established or confirmed by spectroscopic data and density functional calculations at the B3LYP/6-31G* level. The success of 3- and 4-cascade reactions in the crystal without melting is unusual and of unmatched atom economy. They are mechanistically investigated with atomic force microscopy techniques (AFM) on six different faces of 1 when o-phenylenediamine was the reagent (substitution, elimination, cyclization, elimination) and interpreted on the basis of known crystal structure data. Strict correlations to the crystal packings are observed. The characteristic surface features grow to microm heights in some cases at distances of 0.5 mm from the contact edge of the reacting crystals. The waste-free and easy syntheses of highly functionalized (C=O; O-H; C=N) heterocycles or of a tetraketone are also of interest for synthetic use.     

Quantitation in capillary electrophoresis-mass spectrometry

CE-MS has evolved into a strong alternative to LC-MS. Most of CE-MS applications deal with characterization and identification. However, quantitative aspects have gained importance in, e.g., pharmaceutical and biotechnological applications. Here we summarize and evaluate various methodological aspects in order to achieve sensitive and reproducible results. Similar to LC-MS, aspects of matrix influence on the electrospray process need to be carefully addressed when quantitative results are intended by CE-MS. Due to a more complicated coupling special emphasis needs to be put on the CE-MS interface. Generally linearity over more than three orders of magnitude can be achieved by CE-ESI-MS. Furthermore, a literature survey has been performed in order to give an overview over quantitative measurements performed by CE-MS. The precision can be doubled when changing from a structural related to an isotopically labeled internal standard. Thus a level of precision better than 5% RSD can be achieved.