Aliphatic and acyclic carboxylic acids

Esters have historically been the most commonly used diastereomeric derivatives for the separation of the enantiomers of optically active carboxylic acids, particularly where recovery of the individual enantiomers is required. The reactions used to form diasteromeric esters can be summarized as follows. 

The nature of the chiral derivatization reagent is critical in achieving optimum resolution of the diastereomers, and for simple carboxylic add reagents containing a phenyl or other 7t-donating group close to the chiral centre are recommended to improve the resolution. This effect was particularly well demonstrated by Kaneda [59], who showed that the S(+)-2-butanol (20) or R(—)-2-octanol (21) esters of 2-methylbutyric add were unresolved by gas chromatography but the esters with R- -methylbenzyl alcohol (19) were readily separated. (See Section 4.2.2 for the numbered structures). 

The recovery of the individual enantiomers of the acids from the diastereomeric esters has been discussed in Section 4.1. 

Diastereomeric amides are, in general, more readily separated than the corresjronding esters, particularly on normal phase silica or alumina chromatographic systems, where the amide can hydrogen bond with the stationary phase. Helmchen et al. [60] developed a series of concepts to predict the structural features of amides, which would improve separation factors, and also to construct models 

The recovery of the individual enantiomeric acids from the diastereomeric amides has not been carried out to any large extent, because of the inherent stability of the amide bond and the risk of racemization during hydrolysis. Jiang and Soderlund [62] reported the recovery of the individual enantiomers of 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid, a synthetic pyrethoid precursor, from its S( — )-(phenyl)ethylamide diastereomers by refluxing in 6 M hydrochloric acid at 

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