Chiral stationary phases carbamate derivatives

The potential for use of chiral natural materials such as cellulose for separation of enantiomers has long been recognized, but development of efficient materials occurred relatively recently. Several acylated derivatives of cellulose are effective chiral stationary phases. Benzoate esters and aryl carbamates are particularly useful. These materials are commercially available on a silica support and imder the trademark Chiralcel. Figure 2.4 shows the resolution of y-phenyl-y-butyrolactone with the use of acetylated cellulose as the adsorbent material. 

This material is enantiomerically pure, as confirmed by HPLC analysis of the 3,5-dinitrophenyl carbamate using a chiral stationary phase. The carbamate derivative of DAI B... 

Chromatographic separatum of enantiomersThe carbamate, ureido, and amide derivatives obtained without racemization from enantiomeric amines, alcohols, and carboxylic acids, respectively (equations T III), with this isocyanate are stable for months and are suitable for gas chromatographic separation using a polymeric chiral stationary phase (derived, for example, from L-valine-(S)-a-phenylethylamide). This methodology permits separation of chiral a- and /1-hydroxy acids and also N-mclhylnmino acids. 

Analytical Properties CSP (chiral stationary phase) 1 — separates some chiral binaphthyl derivatives when mixtures of hexane diethyl ether, dichloromethane, or dioxane are used as the mobile phase CSP 2 — separates compounds with carbamate or amide functions (mixtures of n-hexane and 2-propanol can be used as mobile phase) CSP 3 — separation of compounds separated by CSP 2, as well as separation of compounds with carbonyl or amide functions and some amino alcohols that have pharmaceutical relevance ((3-blockers)... 

M. Lammerhofer and W. Lindner, Quinince and quinidine derivatives as chiral selectors. Beush type chiral stationary phases for high performance liquid chromatography based on chincona carbamates and their applications as chiral anion exchanger, J. Chromatogr. 741 (1966), 33. 

These stationary phases separate enantiomers on the basis that one isomer fits in the pocket and the other does not. In this fashion, the relative speed of the isomers is different, and separation results. There are three main types of inclusion chiral stationary phases a-cyclodextrin, /Tcyclodextrin, and y-cyclodextrin. From these three native cyclodextrins, several derivations can be made to alter the selectivity of the inclusion complex, including formation of acetates, esters, and carbamates. Astec produces all three native cyclodextrin stationary phases as well as several derivatized phases (called the Cyclobond series), and as with their macrolide polypeptide phases, they are covalently bonded. 

Szasz, G., Gergely, A., Lindner, W. Liquid chromatographic enantiomer separations of novel quinazolone derivatives on quinine carbamate based chiral stationary phases using hydro-organic mobile phases, J. Chromatogr. A, 2004,1047, 59-67. 

The ester and carbamate derivatives of cellulose and amylose are among the most successful and versatile chiral stationary phases for liquid and supercritical fluid chromatography [1,4,28,107-109]. These phases are prepared by reaction of the poly(saccharide) with an acid chloride (ester derivative) or phenylisocyanate (carbamate... 

The popularity of the poly(saccharide) derivatives as chiral stationary phases is explained by the high success rate in resolving low molecular mass enantiomers. It has been estimated that more than 85% of all diversely structured enantiomers can be separated on poly(saccharide) chiral stationary phases, and of these, about 80% can be separated on just four stationary phases. These are cellulose tris(3,5-dimethylphenyl carbamate), cellulose tris(4-methylbenzoate), amylose tris(3,5-dimethylphenyl carbamate), and amylose tris(l-phenylethyl carbamate). Typically, n-hexane and propan-2-ol or ethanol mixtures are used as the mobile phase [111]. Both the type and concentration of aliphatic alcohols can affect enantioselectivity. Further mobile phase optimization is restricted to solvents compatible with the stationary phase, such as ethers and acetonitrile, as binary or ternary solvent mixtures, but generally not chloroform, dichloromethane, ethyl acetate, or tetrahydrofuran. Small volumes of acidic (e.g. tri-fluoroacetic acid) or basic (n-butylamine, diethylamine) additives may be added to the mobile phase to minimize band broadening and peak tailing [112]. These additives, however, may be difficult to remove from the column by solvent rinsing to restore it to its original condition. 

Carbamates. Many examples of cellulose derivatives as chiral stationary phases (CSPs) in liquid chromatography and capillary electrophoresis have been reported in the literature [43,44]. Chankvetadze et al. [43] used cellulose chlorophenyl carbamates as liquid chromatography stationary phases to resolve enantiomers of several chiral drugs including sedatives... 

CD-bonded stationary phases are suitable for the separation of positional, geometric and optical isomers, derivatives of dansyl racemic amino acids, analogues of nicotine and nicotine analogs, arbitrates and derivatives of benzodiazepin as well as organic nitrates, imidazol derivatives, etc. Table 8.2 shows that some enantioselective stationary phases are based on modified CDs [32,33]. The first CD derivatives used as a chiral stationary phase in HPLC were hydroxypropyl, acetylated and carbamoylated /3-CD, which demonstrated better selectivity behaviors than native /3-CD. The most common commercial species of CD derivatives include water-soluble methylated CD (2,6-di-0-methyl-j8-CD) and HP-j6-CD, then acetylated CD, carboxymethylated CD, naphthyl ethyl carbamate-j8-CD,... 

The most effective cellulose and amylose based chiral stationary phases are those derivatized with the various substituted tris(3,5-dimethylphenyl carbamates). Okamoto et al. [10], carried out an extensive study on the effect of the different substituent groups on the chiral selectivity of the stationary phase to a range of protected amino acid derivatives. An example of one of their separations is given in figure 11.12. 

Xiao TL, Armstrong DW (2004) Macrocyclic antibiotics. Chapter 4. In Giibitz G, Schmid MG (eds) Chiral separations, methods and protocols. Humana Press, Totowa, NJ, pp 113-171 Lammerhofer M, Lindner W (1996) Quinine and quinidine derivatives as chiral selectors. I. Brush type chiral stationary phases for high-performance Uquid chromatography based on cinchonan carbamates and their application as chiral anion exchangers. J Chromatogr A 741 33-48... 

Lammerhofer M, Lindner W (1996) Quinine and quinidine derivatives as chiral selectors. 1. Brush type chiral stationary phases for HPLC based on dnchonan carbamates and their application as chiral anion exchangers. J Chromatogr A 741 33-48... 

New brush-type phases (donor-acceptor interactions) are appearing all the time. " Examples are stationary phases comprising quinine derivatives and trichloro-dicyanophenyl-L-a-amino acids as chiral selectors. Quinine carbamates, which are suitable for the separation of acidic molecules through an ionic interaction with the basic quinine group, are also commonly used but in general they are classified with the anion-exchange type of chiral selectors (see further) because of their interaction mechanism, even though r-donor, r-acceptor properties occur. (Some separations on Pirkle-type CSPs are shown in Table 2.)... 

By using derivatives of cellulose 3,5-dimethylphenyl carbamate (Chiracel OD) as the chiral phase Bergman measured the enantiopurity of complexes of molybdenum (2.45) and iridium (2.46) (Figure 2.67). With the same type of stationary phase, Gladysz measured the ee of rhenium complexes ReCp(NO)P(C6H5)2Br (2.13), and uranyl-salophen complexes of uranium were analysed with a Chiracel ODH column. 

In practice, it has been found that certain derivatives e.g. tris (3,5-dimethylphenyl carbamate) render the coating less culnerable to solvent dissolution. As a consequence this stationary phase can be used with buffered methanol/water or acetonitrile/water with certain care being taken. Therefore, the tris(3,5-dimethylphenyl carbamate) derivatives of both cellulose and amylose can, with caution, be used in the reversed phase mode. As example of a chiral separation using the different modes is shown in figure 8.6. 

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