Carboxylic acids Camphor-10-sulfonic acid

Racemic piperazine-2-carboxylic acid (4-azapipecolic acid, 22) is obtained by hydrogenation of pyrazine carboxylic acid salts/236 For its enantiomeric resolution several methods have been described, e.g. fractional crystallization of its S-camphor-10-sulfonic add salt/236,237 fractional crystallization of l,4-dibenzylpiperazine-2-carboxylic add menthyl ester/238 or selective digestion of racemic piperazine-2-carboxylic add amide by leucine aminopeptidase/239 ... 

Dimethylbiphenyl-2,2 -dicarboxylic acid, l,l -binaphthyl-2,2 -diyl hydrogen phosphate, camphor-10-sulfonic acid, acenocoumarol, proglumide, Af-succinyl-1-phenylethylamine, 3,4-dihydro-4-(2-naphthyl)-1,3,6-trimethyl pyrimidine-2(lH)-one-5-carboxylic acid... 

Other methods to form carboxylic acids Cyanotrimethylsilane, 87 a-Substituted carboxylic acids (see also Amino acids, Halo carbonyl compounds, Hydroxy acids) Camphor-10-sulfonic acid, 62 Chiral compounds Alcohols... 

Camphor-10-sulfonic acid (1) is available in large quantities in both enantiomeric forms. In only 3 steps the cyclic sulfonamide 2 (sultam) can be synthesized, which can be acylated with acid chlorides after deprotonation with sodium hydride (Scheme 1) [1, 2]. The resulting amides 3 are considerable more reactive towards nucleophiles than the corresponding carboxylic esters and the a,/ -unsaturated derivatives undergo, with excellent selectivities, Diels-Alder reactions or Michael additions under mild conditions. Al-... 

Many organosulfur compounds can be resolved into optically active forms (enantiomers) owing to the presence of a chiral (asymmetric) sulfur atom 5 important examples include sulfoxides and sulfonium salts. Chiral sulfoxides containing amino or carboxylic acid groups have been resolved by formation of the diastereoisomeric salts with d-camphor-10-sulfonic acid or d-brucine. The salts can then be separated by fractional crystallisation and the free optically isomeric sulfoxides liberated by acid hydrolysis. However, a more convenient synthetic procedure for the preparation of chiral sulfoxides of high optical purity is Andersen s method (see p. 30). 

ASYMMETRIC HALOGENATION OF CARBOXYLIC ACIDS DERIVATIVES PREPARED FROM CAMPHOR-IO-SULFONIC ACID... 

Direct introduction of a solubilizing function can be achieved by carboxylation and by sulfonation. The historical example of carboxylation is the Kolbe synthesis of salicylic acid. Sulfonation was employed to solubilize guaiacol, camphor and 7-chloro-8-hydroxyquinoline (Fig. 36.1). 

Several syntheses of chiral camphor derivatives make use of the CH acidity of the methylene group attached in a-position to the carbonyl function (C-3). Thus, isoamyl nitrite converts camphor to 3-isonitrosocamphor which readily undergoes hydrolysis to the yellow camphorquinone. Bromination leads to 3-bromocamphor which is sulfonated to 3-bromocamphor-3-sulfonic acid with concentrated sulfuric acid. 3-Lithiated camphor obtained with phenyllithium is carboxylated to endo- and exo-isomers of camphor carboxylic acid. The Claisen condensation of camphor with esters of carboxylic acids provides enolized chiral 1,3-diketones, converting metal cations to chiral metal chelates. 

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