Agent, resolving

Dissociate diastereomer to single enantiomer recover resolving agent... 

This procedure is restricted mainly to aminodicarboxyhc acids or diaminocarboxyhc acids. In the case of neutral amino acids, the amino group or carboxyl group must be protected, eg, by A/-acylation, esterification, or amidation. This protection of the racemic amino acid and deprotection of the separated enantiomers add stages to the overall process. Furthermore, this procedure requires a stoichiometric quantity of the resolving agent, which is then difficult to recover efficiendy. Practical examples of resolution by this method have been pubUshed (50,51). 

Optical resolution is another method of producing (—)-mentho1 from racemic materials. (A)-Menthol is treated with optically active resolving agents to separate the (—)-mentho1 from the (+)-menthol, which is further processed by racemization over a nickel catalyst and recycled (156). 

The six-position may be functionalized by electrophilic aromatic substitution. Either bromination (Br2/CH2Cl2/-5°) acetylation (acetyl chloride, aluminum chloride, nitrobenzene) " or chloromethylation (chloromethyl methyl ether, stannic chloride, -60°) " affords the 6,6 -disubstituted product. It should also be noted that treatment of the acetyl derivative with KOBr in THF affords the carboxylic acid in 84% yield. The brominated crown may then be metallated (n-BuLi) and treated with an electrophile to form a chain-extender. To this end, Cram has utilized both ethylene oxide " and dichlorodimethyl-silane in the conversion of bis-binaphthyl crowns into polymer-bound resolving agents. The acetylation/oxidation sequence is illustrated in Eq. (3.54). 

By far the eommonest adduetion method is via an aeid-base reaetion, in whieh an enantiomer pair eontaining an aeid funetion (e.g. a earboxylie aeid) is reaeted with a base resolving agent, or viee versa. 

It is an attractive resolving agent, because it is relatively inexpensive and commercially available on a ton scale for industrial applications. One of the remarkable properties of (-)-DAG, which other acidic resolving agents lack, is its water-insolubility. This feature permits the recovery of the resolving agent in a simple and efficient manner. 

Eor an extensive list of reagents that have been used for this purpose and of compounds resolved, see Wilen, S.H. Tables of Resolving Agents and Optical Resolutions University of Notre Dame Press Notre Dame, IN, 1972. 

The most direct method is the separation of the enantiomers by HPLC using chiral columns. It has the advantage that there is no risk of contamination from chiral resolving agents. The formation of diastereoisomers... 

Kagan and coworkers determined and studied in detail the crystal structure of a 1 1 molecular complex between (i )-methyl p-tolyl sulfoxide (10) and S)-N-(3,5-dinitrobenzoyl)-l-phenylethylamine (11). They suggested that amide 11, which had been used as a chiral solvating agent for sulfoxides, might find use as a resolving agent for these compounds. ... 

R)-(+)-a-methoxy-p-nitrobenzylamine (VIII), acid chloride form of (VII) (IX), (+)-camphor-lO-sulfony. hloride and (X), (+)-neomenthyl isothiocyanate. Where not ex.,. i.icitly stated the reagent must be in a single enantiomeric form to be of use as a resolving agent. 

Williams, B.A. and Vigh, G., Dry look at the CHARM (charged resolving agent migration) model of enantiomer separations by capillary electrophoresis,. Chromatogr. A, 777, 295, 1997. 

We have seen that the spectra of enantiomers, acquired under normal conditions, are identical. The NMR spectrometer does not differentiate between optically pure samples, and racemic ones. The wording is carefully chosen, particularly normal conditions , because it is often possible to distinguish enantiomers, by running their spectra in abnormal conditions - in the presence of a chiral resolving agent. Perhaps the best known of these is (-)2,2,2,trifluoro-l-(9-anthryl) ethanol, abbreviated understandably to TFAE. (W.H. Pirkle and D.J. Hoover, Top. Stereochem., 1982,13, 263). Structure 7.4 shows its structure. 

Optically pure mandelic acid (see Structure 7.6) can be a useful chiral resolving agent where the compound you are looking at has a basic centre, as it can form an acid-base pair with it, which is a stronger form of association. This compound is of sparing solubility in CDCI3 however and can precipitate out your compound if, as is often the case, its protonated form is of low solubility in CDCI3. 

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