Enantiomers industrial applications

For most chemical transformations, especially for industrial applications, the yield of 50% cannot be accepted. Since each enantiomer constitutes only 50% of the racemic mixture, the best way to increase the yield of the desired enantiomer is racemization of the unwanted one (Scheme 5.7). This reaction mustproceed simultaneously with the enzymatic kinetic resolution. In order to indicate the dynamic character of such processes, the term dynamic kinetic resolution has been introduced. 

The R,S-family 33, and of course its enantiomer, provide high enantioselectiv-ities and activities for the reductions of itaconic and dehydroamino acid derivatives as well as imines [141], The JosiPhos ligands have found industrial applications for reductions of the carbon-carbon unsaturation within a,/ -unsaturated carbonyl substrates [125, 127, 131, 143-149]. In contrast, the R,R-diastereoisomerof30 does not provide high stereoselection in enantioselective hydrogenations [125, 141]. 

As already mentioned, the most important industrial application of homogeneous hydrogenation catalysts is for the enantioselective synthesis of chiral compounds. Today, not only pharmaceuticals and vitamins [3], agrochemicals [4], flavors and fragrances [5] but also functional materials [6, 7] are increasingly produced as enantiomerically pure compounds. The reason for this development is the often superior performance of the pure enantiomers and/or that regulations demand the evaluation of both enantiomers of a biologically active compound before its approval. This trend has made the economical enantioselective synthesis of chiral performance chemicals a very important topic. 

A third class of compounds that can be hydrogenated are ketones or aldehydes containing another polar group. The pressures used are high (50-100 bar H2) but the enantioselectivities are excellent. The general reaction (R can be varied extensively) is shown in Figure 4.16. Since these B-substituted ketones are easy to make, this method is extremely powerful for the synthesis of enantiomers. Furthermore, the catalyst is also very selective in the formation of diastereomers. An industrial application is shown below [19],... 

Several important industrial applications of the Heck reactions are known. The world s largest producer of Naproxen is Albemarle and they make Naproxen using two homogeneously catalysed steps, a Heck reaction and a palladium catalysed hydroxycarbonylation. The last step is carried out using palladium without chiral ligand and the enantiomers obtained are separated, see Figure 13.18. 

Since Pasteur s time, stereochemistry has experienced an enormous intellectual growth and has also found widespread industrial application. In recent years, a spate of articles, reviews, books, and international conferences and symposia have dealt with the role of chirality in chemistry, and three new journals have been specifically devoted to this topic Chirality, by Wiley-Liss in 1989, Tetrahedron Asymmetry, by Pergamon Press in 1990, and Enantiomer, by Gordon and Breach in 1996. Much of the research reported in these media, though motivated to some degree by market forces—notably by the demand of pharmaceutical industry for enantiopure drugs4—serves as a reminder that molecular chirality remains the centerpiece of stereochemistry and allied branches of science. 

For industrial application we can conclude that the best and simple way to obtain a pure enantiomer from its racemic mixture by preferential crystallization would be to use washed seed crystals. 

Large scale industrial applications of enzymes have been largely confined to the use of simple hydrolases which do not require cofactors such as ATP or NAD(P)H, and are in general, kinetic resolutions, i.e. where one enantiomer of a racemic mixture in hydrolysed much faster than the other. The process then simply requires the removal of the desired enantiomer and recycling (via racemisation) of the other enantiomer for economic and environmental reasons. 

In the field of pharmaceuticals and pesticides, the desired big activity of the molecule is in a pure enantiomer (chiral molecule). This has been made possible by using either enzymes or chiral metal complexes (asymmetric catalysts). These chiral metal complexes, though expensive, are important for industrial application (i.e., have a high turnover frequency). A typical example is the synthesis of (S)-me olachlor, a herbicide. It is prepared by asymmetric... 

As can be seen from the example above, the enantiomer obtained again depends on the geometry of die starting alkene as well as the handedness of the catalyst. TTie mechanism is not fundamentally different from that of hydrogenation, except that the hydrogen is derived this time from the substrate rather than from hydrogen gas. For a remarkable industrial application of this asymmetric 1,3-hydrogen shift, see section 7.4.3. 

Thin layer chromatography. 2. Enantiomers—Separation. 3. Chirality—Industrial applications. I. Kowalska, Teresa. II. Sherma, Joseph. III. Title. IV. Series. 

Enantiomeric separations have become increasingly important, especially in the pharmaceutical and agricultural industries as optical isomers often possess different biological properties. The analysis and preparation of a pure enantiomer usually involves its resolution from the antipode. Among all the chiral separation techniques, HPLC has proven to be the most convenient, reproducible and widely applicable method. Most of the HPLC methods employ a chiral selector as the chiral stationary phase (CSP). 

In general, high selectivities can be obtained in liquid membrane systems. However, one disadvantage of this technique is that the enantiomer ratio in the permeate decreases rapidly when the feed stream is depleted in one enantiomer. Racemization of the feed would be an approach to tackle this problem or, alternatively, using a system containing the two opposite selectors, so that the feed stream remains virtually racemic [21]. Another potential drawback of supported enantioselective liquid membranes is the application on an industrial scale. Often a complex multistage process is required in order to achieve the desired purity of the product. This leads to a relatively complicated flow scheme and expensive process equipment for large-scale separations. 

The original applications of NIR were in the food and agricultural industries where the routine determination of the moisture content of foodstuffs, the protein content of grain and the fat content of edible oils and meats at the 1% level and above are typical examples. The range of industries now using the technique is much wider and includes pharmaceutical, polymer, adhesives and textile companies. The first in particular are employing NIR spectrometry for the quality control of raw materials and intermediates and to check on actives and excipients in formulated products. Figure 9.26(b) demonstrates that even subtle differences between the NIR spectra of enantiomers can be detected. 

---