Cellulose 4-methylbenzoate

Fig. 20 Methods for determination of enantiomeric excess reported in Journal of The American Chemical Society in 2010 (a) and 2012 (b). Left circle Methods for e.e. determination. Middle circle CSPs for HPLC and SFC. Right circle Polysaccharide-based CSPs. OD cellulose 3,5-dimethtylphenylcarbamate, AD amylase 3,5-dimethylphenylcarbamate, OJ cellulose 4-methylbenzoate, AS amylase (S)-l-phenylethylcarbamate, lA immobilized AD, IB immobilized OD, IC immobilized cellulose 3,5-dichlorophenylcarbamate...

Chiralcel OJ Cellulose tris(4-methylbenzoate) coated on silica gel [19] Daicel... 

A precursor in the synthesis of a promising calcium sensitizing agent from E. Merck [33], a chiral thiadiazin-2-one EMD 53986, 3,6-Dihydro-5-[l,2,3,4-tetrahy-dro-6-quinolyl]-6-methyl-2H-l,3,4-thiadiazin-2-one [26]. The study was performed using Celluspher , a CSP prepared from cellulose tri(p-methylbenzoate) according to a patent from Ciba-Geigy [34]. The spherical particles had a mean particle diameter of 20 3 pm and the mobile phase was pure methanol. 

These polysaccharide-based stationary phases appear to be the most useful in organic, bio-organic and pharmaceutical analysis. Of the above-mentioned derivatives three of them, namely cellulose tris-(3,5-dimethylphenylcarbamate), amylose tris-(3,5-dimethylphenylcarbamate) and cellulose tris-(4-methylbenzoate), have very complementary properties and numerous publications have demonstrated that they have been able to achieve the chiral resolution of more than 80% of the drugs currently available on the market. " These CSPs are known under the commercial names, Chiralcel OD-H , Chiralpak AD and Chiralcel OJ , respectively (Figure 4). Their very broad enantiorecognition range is also the... 

Figure 3.1 Chemical structures of the current most successfully employed derivatised polysaccharide CSPs. (a) CHIRALPAK AD Amylose tris (3,5-dimethylphenylcarbamate) coated onto a silica support, (b) CHIRALPAK AS Amylose tris [(S)-a-methylbenzylcarbamate] coated onto a silica support, (c) CHIRALCEL OD Cellulose tris (3,5-dimethylphenylcarbamate) coated onto a silica support, (d) CHIRALCEL OJ Cellulose tris (4-methylbenzoate) coated onto a silica support.

Cellulose triacetate Cellulose tribenzoate Cellulose mew-methylbcnzoate Cellulose para-methylbenzoate Cellulose phenylcarbamate... 

Chiralcel CMB Cellulose tris(3-methylbenzoate) Aryl esters and arylalkoxy esters ... 

From the polymeric cellulose tris(4-methylbenzoate) derivative, Francotte et al. [158,159] prepared also spherical beads for preparative separations, as they provided higher loadability than the coated CSPs and which have better mechanical properties and efficiencies than the pure microcrystalline cellulose derivatives. 

CHROMATOGRAPHIC DATA OBTAINED WITH THERMALLY INITIATED RADICALLY CROSS-LINKED CELLULOSE TRIS(4-METHYLBENZOATE) (REPRINTED FROM REF. 11641)... 

Cellulose tris(4-methylbenzoate) Chiralcel OJ Daicel, Chiral Technologies... 

Column 150 X 2.1 Tolycellulose EXP BlOl (tris(4-methylbenzoate)cellulose covalently bonded to 10 pm aminopropylsilica)... 

Column 150 x 4.6 10 jim EXP BlOl tris(4-methylbenzoate) cellulose on silica (Bio-Rad)... 

Figure 9. Enantioseparation of the precursor of Ca-sensitizing drug EMD 53998 on cellulose tris(p-methylbenzoate) beads (a) poly(N-acryloyl-aminoacid ester) silica (b) allulose tris(p-methylbenzoate) silica (Chiralal OJ) (c) and anylose tris(3,5-dimethylphenylcarbamate) silica (Chiralpak AD) (d) [153].

SMB parameters Cellulose tris(p-methyl- benzoate) beads Poly(N-acryloyl-amino acid ester) silica CSP Cellulose tris(p-methylbenzoate) coated on silica (Chiralcel OJ) Amylose tris(3,5-dimethylphenyl-carbamate) coated on silica (Chiralpak AD)... 

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. 

The Daicel polysaccharide CSPs that became available in 1985 have been largely used in the field of atropisomeric heterocycles both at the analytical or semipreparative scale. Cellulose tris (p-methylbenzoate), cellulose tris(3,5-dimethylphenylcarbamate), amylose tris(3,5-dimethylphe-nyl-carbamate), and amylose tris[(S)alpha-phenethyl]carbamate) were... 

The enantiomers of pyriproxyfen were studied in a similar fashion (hexane with added alcohol mobile phase modifiers) on a methylbenzoate modified cellulose support (A = 254 nm). In this study, the capacity factor (k ) and separation (a) were monitored at 95/5 hexane/alcohol (methanol or ethanol) or 90/10 hexane/alcohol ( -propyl alcohol, IPA, 1- and 2-butanol, iso- and /-butyl alcohol, 1-, 2-, and 3-pentanol, and 1- and 2-hexanol). Similar increases in retention were recorded as the modifier was changed fiom methanol to 1-pentanol [637]. In this study, however, IPA gave lower retention times than n-propyl alcohol. It is also interesting to note that the elution order for the S versus the R enantiomer was S then R for methanol,... 

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