Resolution of Enantiomers by Non-Conventional Methods

Abstract

Despite unprecedented advances in enantioselective synthesis and separation techniques, large scale production of enantiopure substances, such as required by the pharmaceutical and pesticide industries, is still heavily dependent upon the separation of diastereomers obtained from the enantiomers and an optically active resolving agent. Economy of the process can be much enhanced when only a half-equivalent of the resolving agent is used. Substitution of the other half-equivalent by some achiral compound, as well as separation of the unreacted portion of the substrate from the diastereomer by various physical methods, is discussed. Methods for selecting optimal conditions of resolution and for the purification of partially resolved mixtures are also discussed.

Synthesis and characterization of fluorous (S)- and (R)-1-phenylethylamines that effect heat facilitated resolution of (±)-2-(8-carboxy-1-naphthylsulfinyl)benzoic acid via diastereomeric salt formation and study of their circular dichroism

“…The scope and limitations of this novel non-conventional resolution method are being investigated and further results will be published later [17].…”

“…Only the bis(perfluoroalkylalkyl)-and bis(perfluoroalkoxyalkyl)-derivatives among the HCl salts tested were found to be soluble in benzotrifluoride (Table 1, entries 7 and 12). Methanol and chloroform displayed good solvation power in all cases (Table 1, entries [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

“…Unlike to this heat facilitated optical resolution procedure the general practice applies cooling instead of heating to effect diastereomeric salt crystallizations [8,17].…”

Solvent dependency though not solvate formation in the derivative–derivative resolution of N-formylphenylalanine

“…1). In several previous communications, 6 we dealt with the applicability of structurally related resolving agents and auxiliary reagents in the resolution of FPhA. Separation methods of FPhA enantiomers were worked out for several benzylamine-derivative resolving 0957 Herein we report on the structural similarity using the secondary amine type benzylamine-derivative: 2-benzylaminobutanol (BAB) as a resolving agent.…”

Strategies in optical resolution: a practical guide

“…5 Further rich sources of information about resolution can be found in books by Jacques, Wilen and Collet, 6 Sheldon, 7 Eliel, Wilen and Mander, 8 Kozma, 9 Faigl and Kozma, 10 recently by Faigl et al, 11 as well as in two reviews. 12,13 It is thus apparent that a wealth of practical experience and general knowledge has been made public and therefore it has become timely to systematize and update the strategies of resolution.…”