Investigation of the Chemo- and Stereoselectivity of the Ketene-Claisen Rearrangement

A novel type of ketene-Claisen rearrangement in which the precursor of the rearrangement is generated in situ by reaction of optically active allyl thioethers with dichloroketene is described. A characteristic feature of this rearrangement is the excellent chemoselectivity in favor of allyl thioethers vs. allyl ethers, i.e., exclusive chirality transfer of the allylic sulfur moiety is observed with 12, 13 , and 25--27 . The cyclic, optically active allyl thioethers (+)-(R)- 4 and (?)-(S)- 4 and the open-chain allyl thioethers 11--13 rearrange with in situ generated dichloroketene to the optically active thioesters (?)-(S)- 28 , (+)-(R)- 28 , and 31-33 , respectively. A chirality-transfer of > 99% in the cyclic cases (+)-(R)- 4 and (?)-(S)- 4 , and 96--98 % in the open-chain cases 11--13 is observed. Furthermore, the dichloroketene-Claisen rearrangement is characterized by a high asymmetric 1,2-induction. The chiral allylic sulfides 25--27 give the optically active thioesters 36--38 with a 1,2-induction > 99% as determined by NMR-shift experiments.     

Atropisomerism of phosphorus-containing N-aryl carbamates. Experimental and computational data

Studies by ¹H NMR spectroscopy and X-ray diffraction analysis revealed hindered rotation of the aromatic substituent about the C_Ar—N bond in ortho-substituted (except for o-fluorine-substituted) phosphorus-containing carbamates. The energy barriers to rotation (G _c ) and coalescence temperatures (T _c) determined by the coalescence method increase with increasing volume of the ortho substituent. Conformations resulting from rotation of the ortho-substituted aryl group about the C_Ar—N bond were analyzed by quantum-chemical methods, potential curves were constructed, and differences between the conformational energies and the heights of rotation barriers were estimated. The theoretical rotation barriers change in parallel with the experimental values of G _c ; however, the theoretical values are much smaller in magnitude.     

On-line coupling of packed capillary electrochromatography with coordination ion spray-mass spectrometry for the separation of enantiomers

Pressure-supported packed capillary electrochromatography (CEC) and packed capillary high-performance liquid chromatography (pHPLC) have been coupled on-line to electrospray ionization-mass spectrometry (ESI-MS) and coordination ion spray-mass spectrometry (CIS-MS). Separation of enantiomers of barbiturates and chlorinated alkyl phenoxypropanoates were performed on a permethylated beta-cyclodextrin stationary phase by pressure-supported CEC. For on-line detection with ESI- and CIS-MS, a modified sheath-liquid interface was used. CIS-MS is a universal, novel ionization technique which improves the selectivity as well as the sensitivity. Charged complexes were formed through the addition of central complexing ions such as silver(I), cobalt(II), copper(II), and lithium(I) to the sheath flow. Advantages of CIS-MS detection compared to the ESI-MS mode are discussed. In the CIS-MS mode, increased sensitivity and high selectivity was attained through different possibilities of complexation. The superiority of pressure-supported CEC compared to pHPLC in the hyphenation with CIS-MS is demonstrated.     

Splitless on-line coupling of capillary high-performance liquid chromatography,capillary electrochromatography and pressurized capillary electrochromatography with nuclear magnetic resonance spectroscopy

A mixture of unsaturated fatty acid methyl esters was separated with a new splitless capillary set-up. With the employed apparatus configuration different capillary separation techniques such as capillary high-performance liquid chromatography (cHPLC), capillary electrochromatography (CEC) and pressurized capillary electrochromatography (pCEC) could be applied. The detection and identification of the sample compounds were accomplished by hyphenating these capillary separation techniques with nuclear magnetic resonance (NMR) spectroscopy using a novel configuration of the detection capillary set-up. Using modified electrokinetically driven separation techniques, the electric field was applied solely across the separation column. With this improved interface for capillary liquid chromatography-NMR on-line coupling, the stereochemical assignment of the cis and trans configuration of unsaturated fatty acids could be easily accomplished. Finally, the results of cHPLC-NMR, CEC-NMR and pCEC-NMR coupling experiments were compared.Dedicated to Professor Günter Häfelinger on the occasion of his 65th birthday     

C→N Migrations of the ethoxycarbonyl group in reactions of ortho-substituted aryl isocyanates with the 1,3-zwitterion derived from triisopropylphosphine and ethyl 2-cyanoacrylate

The reactions of meta—para-substituted aryl isocyanates with phosphorus-containing 1,3-zwitterions, which proceed with the CN migration of the CO₂Et group to form the corresponding carbamates, were extended to ortho-substituted aryl isocyanates. The influence of the steric and electronic effects of the ortho substituents in the aromatic rings of aryl isocyanates on the ease of this rearrangement is qualitatively considered.     

Multi-residue determination of seven quinolones antibiotics in gilthead seabream using liquid chromatography-tandem mass spectrometry

A sensitive and selective confirmatory analytical method for the multi-residue determination of seven quinolones (ciprofloxacin, enrofloxacin, sarafloxacin, danofloxacin, oxolinic acid, nalidixic acid and flumequine) in gilthead seabream (Sparus aurata) was developed. The sample pre-treatment involves extraction with 0.1M NaOH and purification by solid-phase extraction (SPE) on Waters Oasis HLB cartridges followed by the determination of all compounds in a single LC-electrospray ionization MS/MS run. Separation was achieved on a Perfectsil ODS-2, 5mum, 250mmx4mm, analytical column (MZ Analysentechnik) by gradient elution using a mixture of 0.2% (v/v) formic acid, methanol and acetonitrile within 30min. Multiple reaction monitoring (MRM) was used for selective detection of each quinolone. Accuracy was evaluated through recovery studies at three different fortification levels. The mean recoveries are between 90 and 132% for the selected levels with RSD values lower than 20%. The method presents satisfactory results for linearity, precision and limits of quantification. The latter are much lower than the maximum residue limits (MRLs) established by the European Union for quinolones in fish tissues (6-8mug/kg).