Extractive Resolution of racemic mandelic acid through a bulk liquid membrane containing binary chiral carrier

Abstract

Um método empregando "bulk liquid membrane" (BLM) e o complexo ácido di(2-etilhexil) fosfórico (D2EHPA) e ácido O,O'-dibenzoil-(2R, 3R)-tartárico (L-(-)-DBTA) foi desenvolvido para a separação por extração do ácido mandélico racêmico (rac MA). Os efeitos de tempo de resolução, concentração de D2EHPA na fase orgânica, concentração de rac MA na fase doadora, velocidade de agitação e temperatura sobre a separação por extração foram estudados. Os resultados experimentais evidenciaram que o maior fator de separação (α) 2,74 e o valor do excesso enantiomérico (ee, %) 46,47% foram obtidos quando o tempo de resolução foi de aproximadamente 4 h, a razão de concentração molar de rac MA, D2EHPA e L-(-)-DBTA foi 0,05:0,2:0,3, a velocidade de agitação, 400 r min -1 e a temperatura, 35 °C. O método desenvolvido é útil para a otimização do transporte de sistemas BLM e para a produção em grande escala de enantiômero puro. A method of bulk liquid membrane (BLM) using complex of di(2-ethylhexyl) phosphoric acid (D2EHPA) and O,O'-dibenzoyl-(2R, 3R)-tartaric acid (L-(-)-DBTA) was developed forthe extractive resolution of racemic mandelic acid (rac MA). The effects of resolution time, concentration of D2EHPA in the organic phase, concentration of rac MA in the feed phase, stirring speed and temperature on extractive resolution were studied. The experimental results have shown that the greatest separation factor (α) 2.74 and the enantiomeric excess value (ee, %) 46.47% were obtained when the resolution time was about 4 h, the molar concentration ratio of rac MA, D2EHPA and L-(-)-DBTA 0.05:0.2:0.3, the stirring speed 400 r min -1 and the temperature 35 °C. The developed method is helpful for optimizing the transport of BLM systems and for large-scale production of pure enantiomer.Keywords: D2EHPA, L-(-)-DBTA, bulk liquid membrane, extraction resolution, mandelic acid IntroductionThe production of single-enantiomer drugs is one of the hot-topics in the world. 1-3 Extractive separation of liquid membrane, a new type of extractive separation technology, 4 originated in the 1960´s is widely used in chiral separation process 5,6 due to their cost effectiveness, low energy demand, set-up simplicity and the possibility to be used in continuous mode. Bulk liquid membrane (BLM) is one of the types of liquid membranes. In a BLM, a relatively thick layer of immiscible fluid is used to separate the feed and strip phases. There is no means of support for the membrane phase and it is kept apart from the external phases only by means of its immiscibility. A recent development of chiral resolution in bulk liquid membranes is the incorporation of single enantioselective carrier within the liquid membrane phase, chemically facilitating the transport of a specific compound across the membrane. [7][8][9][10][11] However, the enantioselectivity of the single carrier is somehow low, therefore the use of binary chiral carrier was introduced while looking for new unitary chiral carrier with high separation capacity and large separation scale. Binary chiral c...

Enantioseparation with liquid membranes

“…studied the synergistic extraction of salbutamol enantiomers with simultaneous stripping. The addition of the achiral co‐selector di(2‐ethylhexyl) phosphoric acid to the chiral dibenzoyl‐L‐tartaric (which normally suffers from low selectivity and extraction capacity) acid increased the selectivity to 2.0 . This is in agreement with a paper from Jiao et al ., in which an increase of the selectivity from <1.1 to >1.7 was observed .…”

“…94 This is in agreement with a paper from Jiao et al, in which an increase of the selectivity from <1.1 to >1.7 was observed. 94 Ren also studied the effect of pH on salbutamol stripping. At higher pH levels, more salbutamol is transformed into ionic forms in the stripping phase, leading to increased solubility of salbutamol.…”

Analytical Applications of Transport Through Bulk Liquid Membranes

“…BLM have shown potential applications in processes of separation and preconcentration of organic acids (Cascaval et al, 2004a-Cascaval et al, 2004bYang et al, 2009). In this case the feed phase contains beside the organic substrate a mineral acid that assures a form mainly undissociated increasing its solubility in the membrane.…”

Stereoselective Behavior of Nafion® Membranes towards (+)‐α‐Pinene and (−)‐α‐Pinene

“…Membrane techniques are promising methods for chiral separations due to their low cost, simple arrangement, low energy consumption, high capacity, and continuous operation [7,8]. A high separation efficiency accompanied by high fluxes through the membrane and a good chemical and mechanical stability are required from enantioselective membranes [9][10][11][12][13][14]. Membranes containing chiral centers are good candidates for the separation of enantiomers [7].…”