2- Aminoalcohols separation

A rich family of 2-alkoxycarbonyl-l,3,2-oxazaphospholidine-2-oxides 179-181 was prepared from the reaction of camphor derived aminoalcohols 177 and 178 with either methoxycarbonyl phosphonic dichloride or ethyl dichlorophosphite followed by the reaction with methyl bromoacetate. The reaction with aminoalcohol 177a afforded the phosphorus epimers 179 and 180, in ratios from 1/1 to 12/1 depending on the iV-substituent which could be separated easily by column chromatography. The reaction with aminoalcohols 178a-c, however, gave a single epimer 181a-c in each case (Scheme 50) [81]. 

A different approach involving cyanohydrin formation from the 3-keto sugar was also explored in the D-Fru series (Scheme 17). A mixture of epimeric cyanohydrins was quantitatively formed by reaction with sodium cyanide in methanol, albeit without stereoselectivity. Chromatographic separation of (R)- and (A)-isomers was straightforward and the former epimer was selected to exemplify the two-step transformation into an OZT. Reduction of this nitrile by lithium aluminum hydride led to the corresponding aminoalcohol, which was further condensed with thiophosgene to afford the (3i )-spiro-OZT in ca. 30% overall yield. Despite its shorter pathway, the cyanohydrin route to the OZT was not exploited further, mainly because of the disappointing yields in the last two steps. 

In recent work we have developed a modified autoclave which solves these difficulties by allowing the starting components, aminoalcohol and aqueous NaOH containing the catalyst, to be preheated separately to reaction temperature before mixing (10). Here we have made use of this modified reactor to determine rate constants for a range of alcohols with different structures. 

A syn displacement of the bromine by benzylamine in the presence of triethylamine led, by a Sn2 reaction, to the a and p amino compounds which were separated into 326 (18%) and 327 (81%) respectively. The dichloroacetamide 328 derived from the latter, when subjected to the action of tri-n-butyltinhydride (2eq) and 2,2 -azobisisobutyronitrile underwent a 5-ero ring closure to furnish via the radical 329, the hydrooxindole 330 (51%) and significant amount of the rearrangement product 331 (30%). The latter is believed to be formed by fragmentation of the cyclohexadienyl radical 332 generated from the cyclohexyl radical 329. On diborane reduction, 330 provided the cis hydroindole 333, which on 0,N-debenzylation afforded ( )-c -fused bicyclic aminoalcohol 334, a compound that had been previously cyclised with formaldehyde to ( )-elwesine (320) by Stevens et al [85]. 

W. Steuer, M. Schindler, G. Schill, and F. Erni, Supercritical fluid chromatography with ion-pairing modifiers separation of enantiomeric 1,2-aminoalcohols as diastereomeric ion pairs, J. Chromatogr., 447 287 (1988). 

Dehydrative cyclization of A-(4-methoxyphcnyl) protected 7-aminoalcohols 157 by the Staab reagent (1,1 -carbonyldiimidazole, CDI) led to the formation of iV-(4-methoxyphenyl)azetidines 158 (Equation 37) <2004SL2751>. The reactions were carried out in a Kugelrohr apparatus. The imidazole formed in the reaction was separated by filtration through silica gel. 

In separate experiments, the catalytic reaction was found to be first order in enantiomerically pure (i-aminoalcohol catalyst precursor, zero-order in di-ethylzinc and zero-order in aldehyde above 0.3 M. When racemic catalyst was employed, however, the overall turnover rate was six times slower, and there was a dependency of rate on the concentrations of all three species. This was elaborated further in a quantitative analysis of positive non-linearity, which is one of the classic examples of this effect. 

Aminoalcohols such as 2-aminoethanol(ethanolamine, Heta) and 2-amino-1-pro-panol(propanolamine, Hpra) have been known to combine as a neutral bidentate or as a deprotonated aminoalcoholate In 1973, Ogino et al. communicated CD spectral studies of [Co(en)2(Heta)p and [Co(en)2(L-Hpra)fthe complexes were prepared from frans-[Co8r2(en)2] and the Ugands via [Co8r(en)2(Ham)] (Ham = Heta or L-Hpra) according to 8uckingham et al. Each complex was separated into two diastereoisomers by Sephadex chromatography. 

An advantage of this method is the good volatility and hence ready separation of medium sized poly-aminoalcohols by gas chromatography. A mixture of small peptides, obtained by enzymatic or chemical partial hydrolysis of a polypeptide, can be reduced and separated in this way before each fraction is submitted to... 

Pettersson, C. SchiU, G. Chiral separation of aminoalcohols hy ion-pair chromatography. CUiromatographia 1982,16,192. 

Unfortunately, the position of the equilibrium does not favor synthesis, which requires to push the reaction by employing either an excess of the donor glycine (which is difficult to separate from the product) or the acceptor aldehyde (which at high concentrations may deactive the enzyme). A recently developed protocol relies on pulling of the equilibrium by (irreversible) decarboxylation of the formed a-amino-p-hydroxycarboxylic acid catalyzed by a decarboxylase to yield the corresponding aminoalcohols as final products [1452]. 

Because the lanthanide and actinide metal ions are readily hydrolyzed (and precipitated) in alkaline solutions, these studies require the presence of water-soluble com-plexants. Both solvating and chelating extractants have been used in these studies. Primary and quaternary amines, alkylpyrocatechols, /J-diketones, pyrazolones, and N-alkyl derivatives of aminoalcohols are the extractants indicated as useful for alkaline extraction processes. A variety of diluents have been used, but their nature seems to have little effect on the extraction efficiency or separation factors. 

Geasshof [8] quotes similar thin-layer chromatographic behaviour on magnesium silicate (Firm 153), using chloroform-methanol (50 + 50) or n-propanol-water-chloroform (66 + 22 -f 11) for amines or the analogous aminoalcohols, respectively. On the other hand, the TLC-separation of aminoalcohols on neutral alumina (Firm 153) and of amines on sihca gel (Firm 153) and on neutral alumina, using the same solvents, has proved unsatisfactory. 

RP-modified silica gel. The advantages of the concentrating zone can also be utilized by combination with RP layers. The most important application of an RP-18 layer with a concentrating zone is the separation of polycyclic aromatic hydrocarbons, which is important in environmental analyses (253-255). Further applications are the separations of aminoalcohols (256), analgesics (257), and lipids (258). 

---