Permethylated cyclodextrins

In conclusion, the most important result is that the use of permethylated cyclodextrin as chiral solvating agent for NMR spectroscopy not only affords a simple and practical way for the determination of the stereochemical purities of trisubstituted allenes, but also allows one to simultaneously determine their absolute configuration. Indeed, TRIMEB induced only positive complexation shifts of all the allene protons, which are greater for the (S )-enantiomer than for the (R)-enantiomer, independent of the structure of the allene. This empirical correlation seems to be reliable since it has been satisfied by a large number of trisubstituted allenes. 

Barretta and coworkers63 reported a direct determination of the enantiomeric purity of chiral trisubstituted allenes by using permethylated cyclodextrin as a chiral solvating agent. They found that the heptakis ft-cyclodextrin TRIMEB discussed above can be successfully used as a chiral solvating agent (CSA) for the NMR determination of the enantiomeric purity of trisubstituted allenes llOa-f. An accurate analysis of the experimental conditions (molar ratio aliene/TRIMEB, temperature and solvent) required to optimize the enantioseparation has been carried out. The XH NMR spectra of TRIMEB, allenes llOa-f, and the mixtures TRIMEB/allene have been recorded at 300 MHz in CD3OD as solvent. 

The optical purity was determined by chiral GC, using a 20 % permethylated cyclodextrin column, after esterification of the pure product with (CF3C0)20 in dry CH2CI2 (65 °C isothermal carrier gas N2, pressure 70 kPa). T r = 26.305 min (>99%, (3R,45)-3-allyl-4-hydroxy-2-pentanone). The enantiomeric purity was estimated to be >99 % and the diastereomeric purity >99 %. 

Bicchi C, Artuffo G, D Amato A, Nano GM, Galfl A, GaUi M, Permethylated cyclodextrins in the GC separation of racemic mixtures of volatiles Part 1, J High Resolut Chromatogr 14 301-305, 1991. 

The first gas chromatographic enantiomer separation on a cyclodextrin-based stationary phase was that of the apolar, racemic hydrocarbons a- and /i-pinenc and cis- and trans-pinane on packed columns coated with native a-cyclodextrin dissolved in formamide157. Very soon, it was recognized that alkylated cyclodextrins can be employed in capillary columns for high-resolu-tion enantiomer analysis. Thus, molten permethylated /(-cyclodextrin, hcptakis(2,3,6-tri-0-methyl)-/ -cyclodextrin (Table 2), was used158- 160 at elevated temperatures. 

Jung et al. [58] obtained permethylated a-CD bridged with (nitrophenylazo)-phenol dye (Figure 21). This compound exhibits time-dependend UV-Vis and NMR spectra in aqueous solutions at room temperature in the dark. This phenomenon was interpreted in terms of self-aggregation involving intermolecular inclusion of the p-nitrophenylazophenol group with one of the two permethylated cyclodextrin residues of the original compound. 

Schurig, V., Nowotny, H.-P., and Schmalzing, D. (1989b) Gas-chromatographic enantiomer separation of unfunctionalized cycloalkanes on permethylated / -cyclodextrin, Angew. Chem. hit. Ed. 28, 736-737. 

An elaborate supramolecular sensor has been engineered by attaching a permethylated cyclodextrin to a terbium-DOTA complex. The cyclodextrin acts as a scavenger for... 

The proton spectrum of the permethylated cyclodextrin at room temperature is completely restricted to the region between 3.0 and 4.0 ppm, with the exclusion of the sharp doublet centered at 5.14 ppm. The free allene 110a shows a weU-recognizable singlet at... 

All three techniques have been unequally exemplified in the separation of heterocyclic atropisomers. GC on a 10% permethyl-(-cyclodextrin (Chirasil-Dex, Chrompack) chemically bonded to a dimethyl polysiloxane backbone (CB-(-PMCD) coupled with El—MS was employed to elucidate the structure of a hexachlorinated bipyrrole which was obtained as a byproduct during the synthesis of the achiral heptachloro-1 ( -methyl-1,2 ( -bipyrrole (02AC4287). Two baseline separated peaks were obtained in ca. 20 min confirming the chiral structure of the by-product. 

Chromatogram of Test Mixture for a y-Permethylated Cyclodextrin Stationary Phase... 

All three stationary phases are permethylated cyclodextrins and for the most part the separations obtained from each are very similar. However, it is clear that there is a reversal in the order of elution for the isomenthol isomers on the y-PM stationary phase. It is also seen, that this phase shows distinctly less selectivity for the other enantiomeric pairs. This reversal of elution is also demonstrated in figure 6.4. 

Cyclodex B (10.5% permethylated -cyclodextrin in DB-1701) Cyclosil-B (30% heptakis[2,3-di-0-methyl-6-0-f-butyldimethylsilyl]- -cyclodextrin in DB-1701) and Rt- DEXsa (heptakis[2,3-di-0-acetoxy-6-0-f-butyldime1hylsilyl]-/i-cyclodextrin in a poly(cyanopropyl-phenyldimethylsiloxane) solvent containing 14% cyanopropylphenylsiloxane monomer. 

Crystal structures of cyclodextrin and permethylated cyclodextrin complexes were determined by the X-ray method. Detailed descriptions of the structures have been described elsewhere. Experimental data are given in Table I. 

Table II shows geometrical data describing the macrocyclic conformation of cyclodextrins and permethylated cyclodextrins. The radius and side length of the 0(4) heptagon of 3-cyclodextrin, 5,0 A and 4,38-4,39 A, respectively, are similar to those (5,00-5,01 A and 4.38-4,39 A, respectively) of permethylated 3-cyclodextrin. The 0(4) hexagon of permethylated a-cyclodextrin is somewhat larger than that of a-cyclodextrin the radius of the 0(4) hexagon is 4,23 A in a-cyclodextrin and 4.30 A in permethylated a-cyclodextrin.

The effect of the permethylation on the macrocyclic conformation appears most clearly in the change of 0(2) 0(3 ) distances and tilt-angles, The average 0(2) 0(3 ) distances of permethylated cyclodextrins are about 0.6 A larger than those of parent cyclodextrins. In a- and 3-cyclodextrin, secondary hydroxyl groups form intramolecular 0(2) 0(3 ) hydrogen bonds, as indicated by the 0(2) 0(3 ) distances of 2.79-2.89 A. These intramolecular hydrogen bonds may maintain the round macrocyclic... 

Figure 7.6 Schematic of permethylated cyclodextrins used in Nucieodex a-PM, Nucieodex p-PM, and Nucieodex y-PM phases.

Schurig V, Mayer SI (2001) Separation of enantiomers by < n capillary electrochromatography on polysiloxane-bonded permethyl- -cyclodextrin. Biochem Biophys Methods 48 117-141... 

Permethylated Cyclodextrins Deprotection of methyl ethers has also been used in the selective functionaHzation of cyclodextrins. This method proved successful on a- and -cyclodextrins, and gave surprising results. 

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