Dissociable diastereomers

Dissociate diastereomer to single enantiomer recover resolving agent... 

The use of dissociable diastereomers for enantiomer resolution may be illustrated by the case where racemic mandelic acid is resolved using en-antiomerically pure a-methylbenzylamine. The n and p salts of a-methylbenzyl-amine mandelate have aqueous solubilities of 49.1 and 180 g/L, respectively, at 25°C [153], A more recent example, which focuses on the crystallographic origin of the solubility differences, is provided by the resolution of ( )-mandelic acid with (-)-ephedrine in water or methanol solution [154], In general, the relative solubilities of the n and p salt pairs are strongly influenced by the choice of solvent medium and temperature, which provide considerable flexiblity in optimizing the crystallization conditions and the efficiency of resolution. This process may be facilitated by the development of a full solubility phase diagram. 

Enantiomerically pure mandelic acid has also been prepared by resolution of the racemic substance through the formation of a dissociable diastereomer with ephedrine [5]. In a typical preparation, 12 g of (L)-ephedrine and 12 g of racemic mandelic acid are heated together in 40 mL of 90% ethanol. The diastereomer salt is obtained upon cooling of the solution, and may be purified by recrystallization from a small volume of alcohol. )-... 

The preceding example demonstrates the general view that the procedure most likely to alter the crystallization thermod)mamics of true race-mate systems will entail the formation of dissociable diastereomer species [50-54]. In most instances, these diastereomers are simple salts formed between proton donors and proton acceptors, or electron-pair donors and electron-pair acceptors. For example, the first resolving agents introduced for acidic enantiomers were alkaloid compounds, and hydroxyl acids were used for the resolution of basic enantiomers. This t) e of resolution procedure has been known since the time of Pasteur, and extensive tables of resolving agents and procedures are available [48,55,66]. 

The current volume contains profiles on Buclizine, Chitin, Ezetimibe, Gemfloxacin, Glimepiride, Lomoxicam, Magnesium Silicate, and Tadalafil. The volume also contains a chapter reviewing the direct crystallization of enantiomers and dissociable diastereomers and a review of the literature published during 2009 that pertains to cocrystal systems having pharmaceutical interest. 

The procedure most commonly used to alter the crystallization thermodynamics of true racemate systems involves the formation of dissociable diastereomer species [44]. These are most often simple salts... 

---