Silicas aminopropyl derivatives

Despite the low reproducibility and short life time of the NP columns, they are widely used owing to their better selectivity and resolution power, which enable the separation of (3- and y-isomers easily. The most used stationary phases are silica, aminopropyl- or diol-bonded [476], A more accurate description of the column used can be found in a review about tocol-derivatives analysis by Abidi [477], Kamal-Eldin et al. [478] compare the performance of new silica-type columns, six different silica columns, three amino columns, and one diol column. The new generation column results are much more repeatable and therefore suitable for vitamers analysis. 

Starting from a collection of samples remarkably well resolved (alpha > 6) on Chiralcel OD (Cellulose tris(3,5-dimethylphenylcarbamate) coated on aminopropyl silica), a putative three-point enantiophore for binding to CSR was derived (Fig. 4-10). This enantiophore query was used to search (CFS 3D search) within a list comprising 4203 compounds tested on Chiralcel OD. From this search domain of CHIRBASE 3D, 191 structures were found to match the enantiophore. 

Fig. 1.—Preparative Separation of Amylose-derived Oligosaccharides on Aminopropyl Silica-gel L.c. Column (2 x 25 cm) Eluted with 11 9 Acetonitrile-Water at 12 mL/min. [Sample size, 500 mg pressure, 7 MPa. Refiractive index detection at I28x. Each numbered peak was collected at 86-98% purity. Numbers above peaks refer to d.p. values. See also. Ref. 8.]... 

Many types of chiral stationary phase are available. Pirkle columns contain a silica support with bonded aminopropyl groups used to bind a derivative of D-phenyl-glycine. These phases are relatively unstable and the selectivity coefficient is close to one. More recently, chiral separations have been performed on optically active resins or cyclodextrins (oligosaccharides) bonded to silica gel through a small hydrocarbon chain linker (Fig. 3.11). These cyclodextrins possess an internal cavity that is hydro-phobic while the external part is hydrophilic. These molecules allow the selective inclusion of a great variety of compounds that can form diastereoisomers at the surface of the chiral phase leading to reversible complexes. 

At present, in almost all cases, reverse phases made of chemically bonded octadecyl silica with a 5-fjtm particle size have been used for the separation of SPA. In special cases, i.e., for the effective separation of BHA isomers, y-aminopropyl packing was used, modified with A-3,5-dinitroben-zoyl derivative of D-phenylglycine (116). 

A commercially packed h.p.l.c. column (25 cm x 4.6 mm) of y-aminopropyl silanised silica [e.g. 5/mi Spherisorb (Regis Chemical Co.), or 7/im Zorbax (Dupont Co.), or 10 /im Lithosorb (Merck), or 5 m irregular (J. T. Baker Chemical Co.)] was sequentially treated, at a pumping rate of 2 ml/min, with the following solutions 2 ml of triethylamine in 40 ml of dry tetrahydrofuran, 2g of (R)-JV-(3,5-dinitrobenzoyl)phenylglycine in 40 ml of dry tetrahydrofuran, 20 ml of dry tetrahydrofuran, and finally 10 per cent propan-2-ol in hexane, until the base line stabilises. The chiral amino acid derivative (which is available from Aldrich Chemical Co.) becomes ionically bonded to the amino residues on the stationary phase. 

Several solid supports have been employed for the attachment of o-iodosobenzoic acid, including silica gel, titania and nylon [89]. Two polymer-supported o-iodoxybenzoic acid reagents have recently been reported. The first was obtained by attaching a carboxymethyloxy derivative of f-butyl o-iodo-benzoate to an aminopropylated silica gel and oxidation with oxone [90]. The second involved chloromethylated polystyrene which was coupled with methyl 5-hydroxy-2-iodobenzoate and eventually oxidized by Bu4NS05H/MeS03H [91]. Some of these polymeric reagents appear in Scheme 31. 

Aldopentoses (as l-phenyl-3- methyl-5-pyrazolone derivatives) Nucleosil silica, in-column 3-aminopropylated or Devosil NH2, 3 pm (25 mM HEPES-NaOH, pH 6.0)-acetonitrile (2 1) 345 mm x 100 pm i.d. 250 mm effective length 41 ... 

In the case of nonsymmetrical epoxides, the regioselectivity is determined by the particular reaction conditions. Thus, styrene oxide (6) undergoes methanolysis in the presence of the Lewis acid catalyst copper(II) tetrafluoroborate to give the hydroxy ether 60, derived from attack of the nucleophile at the more substituted oxiranyl carbon. Similar outcomes have been observed in the solvolysis of 6 with the assistance of aminopropyl silica gel (APSG) supported iodine in catalytic quantities <02SL1251>. This selectivity appears to be much less decisive, however, in the case of monoalkyl epoxides, as illustrated in the corresponding reaction of 1-octene oxide (61), which yields an almost 1 1-mixture of isomers under the same conditions <02OL2817>. 

Figure 26 Comparison of the separate of PMP derivatives of aldopentose isomers on various columns (a) a column prepared by in-column 3-aminopropylation of Nucleosil silica gel (b) a column prepared by packing a commercial sample of amino silica, Develosil NH2, in an APTMS-treated capillary (c) a column prepared by packing Develosil-NH2 in an uncoated capillary. Eluent, (25 mM HEPES-NaOH, pH 6.0)-acetonitrile (2/1, v/v) sample concentration, 50 nmol in 100 pL of eluent injection, -2 kV for 3 s (from the cathodic end) applied voltage, -20 kV detection, UV absorption at 245 nm. Peaks Ara = D-arabinose, Xyl = D-xylose, Rib = D-ribose, Lyx = D-lyxose, all as PMP derivatives. (Reprinted from Ref. 111, with permission.)...

In a broad survey of various analytes about 80 of the compounds tested could be separated on the following four CSPs amylose tris(3,5-dimethylphenyl carbamate) (commercialized as Chiralpak AD), amylose tris[(S)-a-methylbenzyl carbamate] (Chi-ralpak AS), cellulose tris(3,5-dimethylphenyl carbamate) (Chiralcel OD), and cellulose tris(4-methyIbenzoate) (Chiralcel OJ), all coated onto the surface of macroporous y-aminopropyl silica. These columns behave excellently in non-aqueous HPLC mode, but they seem to be also well suitable for SFC separations. Other less widely used, but also commercially available polysaccharide-derived CSPs, e.g. cellulose triacetate, cellulose tribenzoate, and cellulose tricinnamate, or cellulose tris(phenylcarbamate), cellulose tris(4-chlorophenylcarbamate), cellulose tris(4-methylphenylcarbamate) selectors... 

The brush-type of CSP was introduced by Pirkle who was one of the pioneers of modern enantioselective liquid chromatography [55]. The most frequently used 7i-acceptor phases are derived from the amino acids phenylglycine (DNBPG) (Fig. 6.8) or leucine (DNBLeu) covalently or ionically bonded to 3-aminopropyl silica gel [56, 57]. These CSPs are commercially available for analytical or preparative separation of enantiomers. Further CSPs based on amino acid or amine chiral selectors such as valine, phenylalanine, tyrosine [58] and l,2-tr s-diaminocyclohexane (DACH-DNB phase) [59] and 1,2-traus-diphenylethylene diamine (ULMO phase) [60] were also developed (Fig. 6.8). These CSPs have been applied for the preparative separation of the enantiomers of a few racemic compounds, but the number of reported preparative applications has remained very limited over the last 10 years. 

Having elucidated the optimum conditions for the Knoevenagel reaction in a flow reactor, a range of other reactions using different activated methylene derivatives and aldehydes (Table 14.3) was conducted. In all cases excellent product purities and yields were obtained. The reaction of benzaldehyde and ethyl cyanoacetate was also performed using 3-(dimethylamino)propyl-functionalized silica gel, 3-aminopropyl-functionalised silica gel, 3-(l,3,4,6,7,8-hexahydro-2H-pyrimidojl, 2-l]pyrimidino)propyl-functionalized silica gel and polymer-supported diazabicyclo[2.2.2]octane, whereby excellent conversions were obtained (> 99.0%) in all cases [37]. 

Other types of CSPs, known as brush type, have been constructed synthetically. A chiral structure, usually an amide, is linked to silica by a tether molecule. This approach has the potential for design of the chiral recognition elements. The ability to synthetically manipulate the structures also permits investigation of the role of specific structural elements in chiral selectivity. Several synthetic CSPs were developed by W. H. Pirkle and co-workers at the University of Illinois. An important example is the 3,5-dinitrobenzoyl (3,5-DNB) derivative of 7 -phenylglycine, which is attached to silica by aminopropyl tethers (CSP 2). The 3,5-DNB derivatives of several other amino acids (e.g., CSP 4) and diamines have also been explored. ... 

Carbodi-imide-mediated reaction with epichlorohydrin-activated agarose previously treated with glycine Reaction with a syw-trichlorotriazine-activated polystyrene anion exchanger reaction with 1,4-benzoqumone-activated aminopropyl silica reaction with an N-hydroxysuccinimide ester derivative of 3-succinimidopropyl silica Carbodi-imide- or 2,4-toluenedi-isocyanate-mediated reaction with amino-or carboxy-aerosU... 

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