Carboxylic acids, resolution with brucine

Optica] resolution of these and related carboxylic acids were achieved using salt formation with alkaloids (strychnine, brucine, cinchonidine) 33,39,44 or with optically active amines [1-phenyl- or l-( 3-naphthyl)ethylamine]4o,44). The following rotations [a]D have been reported [8]paracyclophanecarboxylic acid (13) +18° (chloroform)441 [10]homologue (14) +80° (chloroform)39 and +67° (chloroform)40 its methyl-derivative (75) —28° (methanol)44 . Dioxa[10]paracyclophanecarboxylic acid (16) + 104° (ethanol)36 and bromo-dioxa[12]paracyclophanecarboxylic acid (79) —37° (acetone)33). 

Resolution of Sulfoxides. Although it can be considered as the resolution of an unique type of carboxylic acid, some racemic sulfoxides containing carboxyhc acids have been resolved via diastereomeric crystalline complexes with brucine (eq 11). ... 

Resolution of a carboxylic acid can be achieved directly by formation of diastereomeric salts with an amine. Naturally occurring bases such as brucine (34) or ephedrine (35) are often used, though it should be mentioned that choice of a suitable amine is usually a matter of trial and... 

The red crystalline product, called isamic acid, from treatment of isatin with ammonia, was proved by Cornforth to be the spiro-1,2-dihydroquinazoline-4-carboxylic acid 66 (R = H). iV-Methylisatin provided the dimethyl derivative (66 R = Me). Isamic acid has an asymmetric carbon atom and is chiral. In an attempted optical resolution, its brucine salt gave... 

Note that the resolving agent is recovered unchanged after this procedure and can be reused repeatedly. Because of the need to obtain crystalline adducts which are readily broken down to their components again, the ionic salts formed between amines and acids, either carboxylic or sulphonic, are ideal for resolution. Thus even in the last century very many amines were resolved by formation of salts with, for example, tartaric acid (16) or camphorsulphonic acid (29), while organic acids were resolved with bases such as quinine, cinchonine and the highly toxic alkaloids brucine (36) and strychnine (37). Although reliable resolution methods have now been worked out for... 

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