Daicel stationary phases

Table 4. Systematic method development protocol for Daicel stationary phases.

Basic compounds, such as primary and secondary amines, and acidic compounds, such as acids or phenols, have a tendency to show a tailing of peaks. This tailing can be efficiently suppressed by adding a basic (DEA, TEA) or acidic (TEA, acetic acid) additive (0.1-0.5%) to the eluent. Daicel stationary phases are available as 5, 10, and 20 im materials. The 20 im particle size is most often used for preparative separations (see Section 2.6.6). 

All aldehydes used in the experiment were freshly distilled or washed with aqueous NaHC03 solution to minimize the amount of free acid. Chiral HPLC was performed using a chiral OJ-H column (0.46 cm x 25 cm, Daicel industries) with a water 717 auto sampler and a UV-vis detector (254 nm). The eluting solvent used was different ratios of hexane and 2-propanol. Chiral gas chromatography analysis was performed in a Shimadzu auto sampler with cyclodextrins columns as chiral stationary phase (fused-silica capillary column, 30 m X 0.25 mm x 0.25 gm thickness, /3-Dex-120 and /3-Dex-325 from Supelco, USA) using He as a carrier gas (detector temperature 230 °C and injection temperature 220 °C). 

The enantiomeric purity is determined by chiral stationary phase, supercritical fluid chromatographic (CSP-SFC) analysis (Berger Instruments, Daicel Co. CHIRALCEL OD column 4% methanol, 180 psi, 3.0 mUmin flow rate detection at 220 nm). Racemic 1-phenylpropanol exhibited base-line separation of peaks of equal intensity arising from the R-isomer (tp, 2.74 min) and the S-isomer (tp, 3.10 min) whereas the synthetic alcohol showed these peaks in the ratio 97.7 / 2.3. This chromatographic method allowed for identification of the trace contaminants propiophenone (tp, 1.63 min) and benzyl alcohol (tp 3.40 min). 

The ratio of the enantiomeric benzyl amide products was determined by analyzing a diluted aliquot of the quenched reaction mixture by HPLC using a chiral stationary phase column (Chiralcel OD, Daicel Chemical Co.). Since racemization is a pseudo-first-order kinetic process, these data (along with the time zero value) are sufficient for determination of the intrinsic rate of racemization kR. The half-life for racemization lRU2 can be directly calculated from the l/d ratio (or % enantiomeric excess, %ee) where t was the time of benzylamine addition (the delay time) ... 

The mixture was extracted with diethyl ether (three times). The combined organic layers were washed with brine and dried over sodium sulfate. After concentration in vacuo, the residue was purified by silica gel flash column chromatography (hexane/ethyl acetate = 20/1-3/1) to give (5)-l (426.3 mg, 74%, 98% ee) as a colourless solid. The enantiomeric excess of (5)-l was determined by chiral stationary-phase HPLC analysis DAICEL CHIRALCEL OD-H, j-PrOH/hexane 1/4, flow rate l.OmLmin tR 14.0 min [(R)-isomer)] and 21.3 min [(5)-isomer), detection at 254 nm]. ... 

S)-l-Phenylethylamine was purchased from Aldrich Chemical Co., Inc. and used as received. The enantiomeric purity of (S)-l-phenylethylamine was determined as the dinitrobenzoyl derivative to be 95% ee using a chiral stationary phase HPLC column and a chiral stationary phase SEC column (see (Note 21)). The submitters used reverse phase CSP HPLC analysis for this purpose (Daicel CROWNPAK CR, aq. HCIO4 (pH 1.5), 0.8 mL/min, 25°C, 210 nm). 

For situations in which the impurity is an enantiomer, the choice of stationary phase will be limited to chiral stationary phases. For a typical screen, the four common Daicel phases (Chiralcel OD, OJ, and Chiralpak AD, AS) are tried first. The initial screen for these columns is done with... 

The first exemplary problem is the separation of a racemic mixture EMD53986 (R S-enantiomers = 1 1) on the chiral stationary phase Chiralpak AD from Daicel (20 pm particle diameter) (Tab. 7.1). 

Enantiomeric purity of binaphthol is determined using chiral stationary phase HPLC Pirkle Type 1-A column (Regis Chemical Company) eluted with 20 1 hexane/2-propanol 1 or poly(triphenylmethyl)methacrylate on silica gel (Chiralpak OT, Daicel Chemical Industries, LTD) eluted with methanol. To determine enantiomeric purities >99% ee an HPLC trace of the unknown is compared to the HPLC trace of unknown containing 0.2% deliberately-added racemic material. 

Chiral polymers can be obtained in two different ways. The use of a chiral catalyst during polymerization can lead to helical structures, as observed in polysaccharides. The other synthesis path uses chiral monomers, which are polymerized to give a chiral polymer capable of folding to a supramolecular stmcture [20]. For application in HPLC, all of these polymers must be coated onto silica, since they are imable to withstand the high pressures encountered in HPLC. Currently, chiral stationary phases based on polyacrylates or polymethacrylates play only a minor role. Chirasphere (Merck) is derived from a silica material coated with poly(N-acryloyl-(S)-phenylalanine ethyl ester) and can be used for the separation of P-blockers in the normal-phase mode. The chiral polymethacrylates Chiralpak OP and Chiralpak OT (Daicel) are able to separate aromatic compounds into their enantiomers. 

More immobilized cellulose and amylose phases are currently tmder development at Daicel. Daicel is promoting the concept of a CSP library of more than 100 stationary phases that are not currently commercially available, which can be screened for enantiomer separations. Astec has recently presented an improved linking of antibiotic phases (Chirobiotic). As yet, no chiral monolithic stationary phases are commercially available, although one can assume that various companies are currently endeavoring to change the surface of monolithic material with chiral modifiers. 

The resolution of racemate, the key prerequisite for the above study, was carried out by HPLC on a chiral stationary phase (Daicel Chiralpak AD). In this context, the resolution of racemates of some meta substituted caUx[4]arenes on the 40-50 mg scale was reported. The corresponding circular dichroism (CD) spectra were obtained in all cases to confirm the separation [5]. 

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