Albrecht Mannschreck

High-pressure liquid chromatography on triacetylcellulose : Characterization of a sorbent for the separation of enantiomers☆

Abstract Microcrystalline triacetylcellulose (dp = 10–20 μm) was used for analytical liquid chromatography at pressures around 50 bar. 1,3,5-Tri-tert.-butylbenzene is proposed as a compound which is not retained on this sorbent. Thus, reliable information about porosity, linear flow-rates, u, and relative retentions become available for the first time. An attempt was made to obtain the plate height, H, dependence upon u in ethanol. For three racemates, comparable data with four eluents were obtained and discussed with a view to future separtions of enantiomers. A general increase of H values of the enantiomers with increasing k′ is found for triacetylcellulose as a sorbent.

1′,3′,3′-Trimethyl-6-nitrospiro[2H-1-benzopyran-2,2′-indoline]: its thermal enantiomerization and the equilibration with its merocyanine†

Abstract The enantiomers of the title compound, the important photochromic material (RS)-1b, have been enriched semipreparatively by liquid chromatography. As a consequence, we were able to determine the barrier of the thermal interconversion (R)-1b⇌(S)-1b via time-dependent polarimetry, amounting to ΔG≠=85.9 kJ/mol at 22.0°C in d6-DMSO ( Table 2 ). The thermal equilibration of the corresponding merocyanine 2b was monitored in d6-DMSO by time-dependent 1H NMR, resulting in ΔG1≠=102.8 and ΔG2≠=92.0 kJ/mol at 22°C ( Table 1 Table 1 . Equilibration between spiro compounds (RS)-1 and merocyanines 2 at 22°C, measured by time-dependent UV absorptions 3 for (RS)-1a⥄2a and by time-dependent 1H NMR intensities for the other compounds ). This means that, starting from (RS)-1b, the opened isomer 2b is attained by a slow reaction (ΔG1≠=102.8 kJ/mol, Fig. 4 ). Therefore, the merocyanine 2b cannot be identified with the intermediate required for the fast process of C(sp3)–O bond cleavage (ΔG≠=85.9 kJ/mol) upon the above enantiomerization of (RS)-1b. Apparently, these two thermal isomerizations ( Fig. 4 ) are independent of each other. The structure of the unknown intermediate of the interconversion (R)-1b⇌(S)-1b must therefore differ from the known one of merocyanine 2b.

Chiral recognition of allenic hydrocarbons by 1H NMR

Abstract The syntheses of the allenes (±)- 1 , (±)- 4 and (±)- 6 as well as of the enriched samples (-)- 1 , (-)- 4 and (-)- 6 are described. 1H NMR shifts and splittings induced by a mixture of the achiral salt Ag(fod) and the optically active complex (+)-Yb(hfbc)3 are given. This procedure is recommended by the magnitude of such splittings as a means of determining the enantiomeric purity of 1,3-disubstituted allenic hydrocarbons. The results for (-)- 1 and (-)- 5 represent the first application of this absolute method.

Synthesis and NMR studies of chiral 4-oxazolidinones and rhodanines

Sterically hindered N-(o-tolyl) and N-(o-chlorophenyl) substituted 2-thioxo-4-oxazolidinones 1 and-thiazolidinones (rhodanines) 2 forming enantiomers by partial rotation around the CN bond are synthesized. Their chirality is proven by the presence of diastereotopic protons (or carbon atoms) detected by 1H or 13C NMR (1c, 2c). In the presence of (S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol as an auxilliary the enantiomers showed 1H shift differences of 0.01 ppm for otherwise isochronous nuclei.

Chiroptical detection during liquid chromatography 7: The rotation angle/absorbance ratio of chiral molecules. Its possible use for on-line analysis during preparative separations of enantiomers☆

The rotation angle/absorbance ratios C+ = alpha+/A+ and C- = a-/A-, determined via detection by a polarimeter and a photometer, were checked for the first time with reference to their use for on-line analysis during preparative separations. For this purpose, (+)-, (-)- and (+/-)-carvones were investigated by liquid chromatography (LC) on microcrystalline tribenzoylcellulose. It turned out that the ratios C+ and C- depend only slightly upon concentration (Table 1). Overlapped peaks of enantiomers were successfully submitted to computer deconvolution (e.g. Fig. 2, bottom). A procedure for on-line analysis during preparative LC is proposed.

Axially chiral thioamides of acrylic acid: correlated and uncorrelated internal rotations

Abstract In acrylic thioamides ( Scheme. 1 ), two intramolecular motions are possible: thiocarbonyl–nitrogen (C–N) and alkenyl–carbonyl (C–C) rotations. Since the two mobile molecular fragments can interact by steric and by resonance effects, we intended to demonstrate the existence of correlated in addition to the above uncorrelated motions. For each of the three thioamides chosen, at least two of the four stereoisomers were enriched by crystallization and by liquid chromatography on nonracemic sorbents. Thereby axial chirality of acrylic thioamides was proven for the first time. Thermal equilibrations were monitored quantitatively by time-dependent 1H NMR spectroscopy in the presence of a nonracemic additive, a method which, to our knowledge, has not previously been described. These kinetic results were evaluated by a simulation program with reference to uncorrelated and correlated rotations ( Fig. 4 , Fig. 5 , Fig. 6 ). We have shown that all of these motions occur in thioamide 14. The enantiomers of thioamide 13 do not interconvert directly. However, indirect, two-step enantiomerizations in 13 have been proven one of the two steps consisting of correlated rotations. The latter are, therefore, possible in acrylic thioamides, a class of compounds which differ considerably from the molecules for which correlated motions were hitherto known.

Chiroptical detection during liquid chromatography: III. Non-stop acquisition of circular dichroism spectra during liquid chromatography

A new type of spectrometer, built in-house, served as a circular dichroism detector for liquid chromatography. It acquired differential absorbances ΔA = f(λ) at all wavelengths, λ, between 208 and 268 nm simultaneously within a time interval of 9 s. Non-stop acquisition of circular dichroism spectra during liquid chromatography is described for the first time. The novel set-up gives automatic access to dichrograms without preparative enrichment of enantiomers, if some analytical separation on an optically active sorbent can be achieved. Like photodiode-array detection, the new technique collects ultraviolet spectra A = f(λ), but furnishes positive/negative information ΔA = f(λ) in addition. It was applied to (±)-2,2′-spirobi[2H-chromene] as a test sample and microcrystalline tribenzoylcellulose as a sorbent. Future applications of non-stop liquid chromatographic circular dichroic-ultraviolet data are discussed.

Chiroptical detection during liquid chromatography, part 5: On-line measurement of circular dichroism spectra Δε(λ) during stops of chromatographic flow

SummaryA procedure is described which serves to measure circular dichrograms Δε(λ) on line during stops of flow in liquid chromatography. Since the concentration of substrate in the spectrometer cell during the stop is not known, the differential absorption coefficients Δε are calculated from the experimental differential absorbances ΔA by means of UV absorption (i. e. photomultiplier voltage) data. Verifications of the procedure are obtained by its application to three substrates (Table 1), the Δε(λ) spectra of which were known. The present on-line technique is compared with a corresponding off-line method.The N,N-dimethylthiobenzamides1 and2 as well as the 9,10-phenanthrenequinone7 consist of interconvertible enantiomers because their planar states are destabilized by steric overcrowding of groups. The unknown dichrograms Δε(λ) of1, 2 and7 are obtained (Figs. 2 and 4) and discussed with reference to the helicities of these molecules.ZusammenfassungEin Verfahren zur on-line-Messung von Circulardichroismus-Spektren Δε(λ) während des Anhaltens des chromatographischen Flusses wird beschrieben. Die Konzentration des Substrats in der Spektrometer-Küvette während des Anhaltens ist nicht bekannt, weshalb die differentiellen Absorptionskoeffizienten Δε aus den experimentellen differentiellen Absorbanzen ΔA mit Hilfe von UV-Absorptions-Daten (d. h. Photomultiplier-Spannungen) berechnet werden. Die erfolgreiche Überprüfung des Verfahrens gelingt durch seine Anwendung auf drei Substrate (Tabelle 1), deren Δε(λ)-Spektren bekannt waren. Die vorgestellte on-line-Technik wird mit einer entsprechenden off-line-Methode verglichen.Die N,N-Dimethylthiobenzamide1 und2 sowie das 9,10-Phenanthrenchinon7 bestehen aus interkonvertierenden Enantiomeren, weil ihre ebenen Zustände durch räumliche Gruppenhäufung destabilisiert sind. Die unbekannten Dichrogramme Δε(λ) von1, 2 und7 werden ermittelt (Fig. 2 und 4) und im Hinblick auf die Helizitäten dieser Moleküle diskutiert.

Sterically hindered N-aryl pyrroles: chromatographic separation of enantiomers and barriers to racemization

The novel N-aryl-2,5-dimethylpyrrole-3-carbaldehydes (1)–(7) have been synthesized by condensation of hexane-2,5-dione with the appropriate aniline and subsequent Vilsmeier–Haack formylation of the pyrrole ring. Diastereoisomeric association complexes of these racemic pyrroles were studied by 1H n.m.r. spectroscopy chemical shifts and the splittings induced by the optically active auxiliary compound (+)-Eu(hfbc)3. Separation of the enantiomers of (6) was achieved by liquid chromatography on triacetylcellulose. The barrier to partial rotation about the C–N bond in (6) was determined and their lower limits in (2) and (4) were estimated by variable temperature 1H n.m.r. spectroscopy.

Syntheses, separation of enantiomers and barriers to racemization of some sterically hindered N-aryl-1,2,3,4-tetrahydro-3,3-dimethyl-2,4-quinolinediones and their thio analogues

SummaryThe novel N-aryl-1,2,3,4-tetrahydro-3,3-dimethyl-2,4-quinolinediones1,4 and8 were thiated with Lawesson reagent and P4S10 to yield the monothio derivatives2 and5 and the dithio compounds3, 6 and9. Their enantiomers were separated by liquid chromatography on triacetyl- or tribenzoylcellulose. Rotation barriers for1–4 and8 were determined by thermal racemization and discussed in terms of steric effects.ZusammenfassungDie neuen N-Aryl-1,2,3,4-tetrahydro-3,3-dimethyl-2,4-chinolindione1, 4 und8 wurden mit Lawesson-Reagens und P4S10 zu den Monothioderivate2 und5 und den Dithioverbindungen3, 6 und9 thioniert. Ihre Enantiomeren wurden mittels Flüssigchromatographie an Triacetyloder Tribenzoylcellulose getrennt. Die Rotationsbarrieren für1–4 und8 wurden mittels thermischer Racemisierung bestimmt und aufgrund der sterischen Gegebenheiten diskutiert.