Fractional distillation, optical resolution

Although fractional crystallization has always been the most common method for the separation of diastereomers. When it can be used, binary-phase diagrams for the diastereomeric salts have been used to calculate the efficiency of optical resolution. However, its tediousness and the fact that it is limited to solids prompted a search for other methods. Fractional distillation has given only limited separation, but gas chromatography and preparative liquid chromatography have proved more useful and, in many cases, have supplanted fraetional crystallization, especially where the quantities to be resolved are small. 

The design of host compounds for optical resolution has received much attention. Toda [23,24] has reviewed the subject, and has used a number of novel techniques to effect efficient optical separation. He has demonstrated the possibility of resolving a racemic oil by stirring in a water suspension of a chiral host [25], and has applied fractional distillation techniques at different temperatures to separate a variety of racemic guests in the presence of chiral hosts [26]. An overview of the industrial applications and production of optically active materials is given in the book Chirality in Industry [27],... 

Optical Resolution by Inclusion Crystallization in Suspension Media and by Fractional Distillation... 

It was found that efficient inclusion crystallization can be accomplished simply by mixing powdered crystalline host and a hydrophobic guest compound in hexane or water. By using the inclusion crystallization in suspension media, very efficient optical resolution method was established. Furthermore, when inclusion complexation between chiral host and rac-guest in the solid state is combined with a distillation procedure, optical resolution can easily be accomplished by the fractional distillation procedure. 

Although some kinds of optically active compounds can be prepared by an asymmetric synthesis using a chiral catalyst, this method is not applicable for preparation of all kinds of compounds. Furthermore, optical yields of the product are not always very high. On the contrary, optical resolution method by inclusion complexation with a chiral host is applicable to various kinds of guest compounds as described in this chapter. When optically pure product cannot be obtained by one resolution procedure, perfect resolution can be accomplished by repeating the process, although asymmetric synthetic process cannot be repeated. Especially, optical resolutions by inclusion complexation with a chiral host in a water suspension medium and by fractional distillation in the presence of a chiral host are valuable as green and sustainable processes. 

Toda, F., and Tohi, Y. (1993) Novel Optical Resolution Methods by Inclusion Crystallisation in Suspension Media and by Fractional Distillation, J. Chem. Soc., Chem. Commun., 1238-1240. 

Cramer, F., and Dietsche, W. 378 (1959) Occlusion compounds. XV. Resolution of racemates with cyclodextrins, Chem. Ber. 92 b) Toda, F., and Tohi, Y. (1993) Novel optical resolution methods by inclusion crystallization in suspension media and by fractional distillation,/. Chem. Soc., Chem. Commun., 1238-1240 c) Toda, F., and Tanaka, K. (1988) A new chiral host compound... 

The identity of most physical properties of enantiomers has one consequence of great practical significance. They cannot be separated by ordinary methods not by fractional distillation, because their boiling points are identical not by fractional crystallization, because their solubilities in a given solvent are identical (unless the solvent is optically active) not by chromatography, because they are held equally strongly on a given adsorbent (unless it is optically active). The separation of a racemic modification into enantiomers—the resolution of a racemic modification—is therefore a special kind of job, and requires a special kind of approach (Sec. 7.9). 

From amongst the numerous applications of adsorption column chromatography, an interesting example is provided by the separation of a mixture of two enantiomers into its constituents whose separation cannot be carried out by the other usual physical methods like fractional crystallization or fractional distillation. A well-known illustration of the separation of enantiomers without their having to be converted into diastereoisomers by chemical reaction with optically active acids is the resolution of Troger s base, effected by V. Prelog and P. Wieland in 1944,... 

A mixture of the (+) and (-) enantiomers in equal proportions is called a racemic modification (racemate) and is optically inactive. The optical inactivity results from the rotation caused by one enantiomer canceling out that produced by its complementary enantiomer. The racemic modification is designated as ( ) e.g. ( ) lactic acid). As the enantiomers of a substance have identical physical properties, they cannot be easily resolved employing the usual separation techniques such as fractional distillation. As a result, the isolation of optical isomers often pose difficult separation problems and it is usually necessary to resort to some very special techniques to achieve a satisfactory resolution hence the raison d etre for this book. 

A mixture of (+) and (—) isomers in equal proportion is known as a racemic mixture. A racemic mixture is optically inactive, as expected. Sometimes, a racemic mixture exhibits different physical and chemical properties than any other isomer. The separation of a racemic mixture into its enantiomeric components ((+) and (—) forms) is called resolution. Since the (+) and (—) forms have the same physical and chemical properties, they cannot be separated by ordinary methods such as fractional crystallization and fractional distillation. The use of enzymes and chromatography has enabled the separation of some isomers. 

Given a mixture of all four stereoisomeric 2,3-dichloropentanes, we could separate it, by distillation, for example, into two fractions but no further. One fraction would be the racemic modification of I plus II the other fraction would be the racemic modification of III plus IV. Further separation would require resolution of the racemic modifications by use of optically active reagents (Sec. 7.9). 

The structure of conhydrine, i.e., l-(a-piperidyl)-propan-l-ol, has been deduced from a study of the Hofmann degradation of the base (33). It has now been fully confirmed by synthesis of the optically active base. a-Pyridylethyl ketone in hydrochloric acid solution is hydrogenated catalyticaUy in the presence of platinum and gives rise to a product which, after distillation in vaevx), consists of a mixture of both racemates of a-piperidylethylcarbinol, m.p. 87-90°. Fractional crystallization in ether yields the high-melting racemate, m.p. 100°. The two optically active enantiomorphs of this racemate are obtained by resolution with d- and Z-dinitrodiphenic acid. The dextrorotatory form, m.p. 121°, [oJ -flO.O in absolute ethanol, is identical with conhydrine (34). 

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