Application of Classical Resolution for Separation of DL‐Serine

Abstract

For resolution of chiral compound-forming substances diastereomeric salt formation is the most important classical separation technique. Diastereomeric salts possess different physical and chemical properties, e.g., solubilities, which facilitate the effective separation via crystallization. A maximum recovery of both diastereomeric salts is usually unachievable when there is a lack of quantitative information regarding solubility and metastable zone width. The present work provides experimental results for the formation of diastereomeric salts of DL-serine. As basic thermodynamic data binary melting and ternary solubility phase diagrams are shown and discussed. A plan for a series of crystallization processes is suggested for the recovery of both salts in pure form with a maximum possible yield. Copyright © 1999-2010 John Wiley & Sons, Inc. All Rights Reserved. [accessed May 7, 2010

Diastereomeric salt crystallization of chiral moleculesvia sequential coupled‐Batch operation

“…The limitations associated with this classical type of resolution include poor enantiomeric purity due to increased levels of the undesired enantiomer and is typically limited to simple eutectic systems . The resolution of DL‐serine·2,3‐dibenzoyl‐D‐tartaric acid experimentally demonstrated by Sistla et al is an example of a simple eutectic system resolved in a conventional batch crystallization.…”

Analysis and Comparison of Commonly Used Acidic Resolving Agents in Diastereomeric Salt Resolution – Examples for dl-Serine

“…The synthesis of all diastereomeric salts was initiated according to the procedure proposed by V.S. Sistla et al 12 In the final synthesis step D-/L-serine benzyl ester was converted with the different resolving agents in methanol. The final reactions are shown in Scheme 3, referring to the complete structures given in Scheme 2.…”

“…These 3 commonly used resolving agents were chosen as representatives to come to a realistic assessment. Each diastereomeric salt pair was synthesized separately and subsequently investigated in detail. , As d / l -Serine has both acidic and basic functional groups (carboxylic and amino groups, respectively) in its chemical structure, the carboxylic group was derivatized to exclude side effects, forming d -/ l -serine benzyl ester . For differentiation of the salt pairs an additional simplified nomenclature was used.…”

“…11,12 As D/L-Serine has both acidic and basic functional groups (carboxylic and amino groups, respectively) in its chemical structure, the carboxylic group was derivatized to exclude side effects, forming D-/L-serine benzyl ester. 12 For differentiation of the salt pairs an additional simplified nomenclature was used. The pair of salts of 2,3-dibenzoyl-Ltartrate salt of D-/L-serine benzyl ester are called D-L and L-L salts; the L-(þ)-tartrate salts are called D-LT and L-LT salts and finally the pair of the L-(þ)-mandelate salts are called D-LM and L-LM.…”

Crystallization-Based Resolution Process for the 2,3-Dibenzoyl-d/l-tartrate Salts of d-/l-Serine Benzyl Ester

“…The separation of enantiomers can be efficiently carried out after forming diastereomeric salts using a suitable enantiopure resolving agent (RA). Frequently maximum possible yields are not reached via this classical resolution due to the unavailability of basic thermodynamic data of the salts in binary (melting points) and in ternary (solubilities) systems. − Measurement of such data is laborious but very important, because these salts might show diverse behavior in their binary and ternary systems. Diastereomeric salts are characterized by three types of behavior: (1) simple eutectic; (2) formation of mixed crystals (solid solutions); (3) formation of double salts.…”