Resolution of racemic acids

Acetophenone similarly gives an oxime, CHjCCgHjlCtNOH, of m.p. 59° owing to its lower m.p. and its greater solubility in most liquids, it is not as suitable as the phenylhydrazone for characterising the ketone. Its chief use is for the preparation of 1-phenyl-ethylamine, CHjCCgHslCHNHj, which can be readily obtained by the reduction of the oxime or by the Leuckart reaction (p. 223), and which can then be resolved by d-tartaric acid and /-malic acid into optically active forms. The optically active amine is frequently used in turn for the resolution of racemic acids. 

Resolution of Racemic Acid.—The racemic acid is dissolved in water (250 c.c.) and divided into two equal volumes. Half of the solution is carefully neutralised with caustic soda and the other half with ammonia, and the two solutions then mixed. 

Orthoformates have been used in the lipase-catalyzed esterification aimed at the kinetic resolution of racemic acids such as flurbiprofen, a nonsteroidal anti-inflammatory drug (Figure 6.18). Orthoformates trap the water as it is formed through hydrolysis, and therefore prevent the reverse reaction, and, at the same time, provide the alcohol for the esteriflcation [65]. 

Enzymes exhibit specificity as regards their behaviour towards stereo-isomerides. Pasteur s biological resolution of racemic acid with moulds depends on this fact, and such moulds may also be used for the resolution of racemic mandelic acid, for the partial digestion of racemic polypeptides according to E. Fischer s method, and in numerous other processes. 

The use of alkaloids in preparing optically active organic compounds has a venerable past. One hundred and thirty-two years ago Pasteur (1,2) used derivatives of quinine to effect the resolution of racemic acids, and even today the use of alkaloids in resolutions remains widespread (3). 

A Chiral Amines as Resolving Agents. Resolution of Racemic Acids... 

B. Campou and A. N. Klibanov, Comparison of different strategies for the lipase-catalysed preparative resolution of racemic acids and alcohols Asymmetric hydrolysis esterification and transesterification. Biotech. Bioeng., 26 1449 (1984). 

Uses. These synthetic amines are preferred to the more usual alkaloids for resolution of racemic acids because the salts can be completely cleaved by passage through a column of Amberlite IR-llO. ... 

Because of the commercial importance of fosfomycin, it is not surprising that several important and attractive synthetic methods are reported in patents. They include, for example, precursors such as dimethyl hydroxymethylphosphonate, dimethyl, dibenzyl, and diallyl formylphosphonate, trimethyl phosphite and 2-cyano-1-hydroxypropene, 9 trialkyl phosphite and 2-chloro-propionaldehyde or 2-acetoxypropionaldehydc, diethyl chloromethylphosphonate, dibenzyl phosphite, and 1-chloro-1,2-propylene oxide,2 propynylphosphonic acid, propenylphos-phonic acid,2 2-chloro-(czT-l,2-epoxypropyl)phosphonic acid, and extrusion reactions on thermolysis. The resolution of racemic acids has also been reported. In search of new effective antibiotics, a large variety of substituted epoxyethylphosphonic acids have been pre-pared.249... 

Pasteur s success in 1848 of the first enantiomer separation (optical resolution) of racemic acid as ammonium sodium ( )-tartrate tetrahydrate together with McKenzie s success in 1904 of the first asymmetric synthesis prompted many chemists to synthesize optically active compounds without recourse to the vital force of organisms, although by employing the capacity of a special species of organism, Homo sapiens, to discriminate left from right. Pasteur remarked in 1883 that The universe is dissymmetric. Since then chemists efforts have been focused on the control of asymmetry in this world of chiral and nonracemic materials. 

Alcantara AR, Dominguez de Marfa P, Fernandez M et al. (2004) Resolution of racemic acids, esters and amines by Candida rugosa lipase in slightly hydrated organic media. Food Technol Biotechnol 42(4) 343-354... 

Bacterial attack was also shown by Pasteur to be effective in the resolution of racemic acid. Penicillium glaucum allowed to grow in a dilute solution of sodium ammonium racemate destroys the d form but, apart from being a rather wasteful process, the attack is not always completely selective. 

By his discovery, he recognized that a direct relationship exists between molecular geometry and optical activity. This led him to propose that molecules that rotate plane-polarized light in equal but opposite directions are related as an object and its mirror image. However, it remained for two other chemists, Van t Hoff and Le Bel, to explain 25 years later exactly how the atoms could be assembled into such molecular structures. In the interim, Pasteur turned his attention with great success to the biological problems mentioned earlier, but it was his pioneering work on the resolution of racemic acid that led the way for other chemists to explain the relationship of chirality or handedness in molecular... 

Synthetic pathways to optically pure derivatives have made use of a variety of different methods resolution of racemic acid III (X = COOH) [22], alkylation of... 

Figures 1.38 and 1.39 illustrate selected commercially available basic and acidic resolving agents, commonly used just as examples of the many now available for the resolution of racemic acids and bases respectively.

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