Resolving agents, chiral amines

Addition of borane to a-pinene produces a useful chiral, reducing agent. 10-Camphorsulfonic acid is a useful resolving agent for amines. 

Derivatization of the optically active aldehydes to imines has been used for determination of their enantiomeric excess. Chi et al.3 have examined a series of chiral primary amines as a derivatizing agent in determination of the enantiomeric purity of the a-substituted 8-keto-aldehydes obtained from catalysed Michael additions. The imine proton signals were well resolved even if the reaction was not completed. The best results were obtained when chiral amines with —OMe or —COOMe groups were used [2], The differences in chemical shifts of diastereo-meric imine proton were ca. 0.02-0.08 ppm depending on amine. This method has been also used for identification of isomers of self-aldol condensation of hydrocinnamaldehyde. 

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

Other resolving agents are readily prepared from inexpensive chiral starting materials such as glucose, aspartic acid, or glutamic acid. A literature example is the use of /V-methylglucamine 6, obtained by reductive amination of D-glucose, in the resolution of naproxen (Chapter 6).13... 

Phenylethylamine (6), one of simple chiral amines, has been widely used as a resolving agent in the resolution of various kinds of racemic acids. There is a chiral carbon at the a-position, and a large phenyl group, a middle methyl group, and a small hydrogen atom are bonded to the carbon atom. One of... 

Both enantiomers of A -acetyl alanine have a free carboxy group that can react with an amine in an acid-base reaction. If a chiral amine is used, such as (/ )-a-methyibenzyiamine, the two salts formed are diastereomers, not enantiomers. Diastereomers can be physically separated from each other, so the compound that converts enantiomers into diastereomers is called a resolving agent. Either enantiomer of the resolving agent can be used. 

The above-mentioned antiarrhythmic agent tocainide has also been resolved with (R)-(-)-0-methylmandeIic acid chloride, [10], using normal-phase LC in a study of the stereoselective disposition of the drug (58). In the assay, CDA [10] was dissolved in the organic solvent used for the extraction of tocainide from urine (58). The S form of this CDA was used by Helmchen and Strubert in early studies on indirect resolutions of chiral amines using LC (59). Both enantiomers of the parent acid of [10] are commercially available. 

Other alkaloids such as brucine were used as resolving agents but their expense and extreme toxicity has made them unpopular and the availability of a range of amines (chapter 22), often made from the chiral pool, has made them unnecessary. 

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