비극성 유기용매의 존재하에서 페니실린 G와 2차 아민간 추출 평형

화학공학의 이론과 응용 제8권 제1호 2002년

Theories and Applications of Chem. Eng., 2002, Vol. 8, No. 1

이상철, 안병성*

군산대학교 화학공학과, 한국과학기술연구원 환경공정부*

Extraction equilibrium between penicillin G and a secondary amine

in the presence of a nonpolar organic solvent

Sang Cheol Lee, Byoung Sung Ahn*

Department of Chemical Engineering, Kunsan National University,

Environmental & Process Technology, KIST*

Introduction

We have successfully performed the recovery of penicillin G using a secondary amine in a nonpolar organic solvent by the ELM processes in a batch reactor and a continuous extraction column [1,2], while we have not yet illuminated a detailed transport mechanism for the extraction of penicillin G in these systems for lack of the reaction equilibrium and kinetics data of penicillin G between two immiscible phases. Only a few researchers investigated the reaction equilibrium and kinetics [3,4], but their kinetics and equilibrium models do not give a satisfactory explanation for our previous ELM experimental results [1,2], nor are quite clear. On the other hand, kerosene, a highly nonpolar organic solvent, has been used as a major component of liquid membrane in the ELM processes in order to maintain emulsion more stable. In this work, we will therefore find the equilibrium expression for the reaction of penicillin G with Amberlite LA-2 as a secondary amine using kerosene as an organic solvent in a liquid-liquid extraction system, which is a primary study prior to getting reaction kinetics in the penicillin G extraction system.

Extraction equilibrium models

On the basis of the previous results [6-11] about the reaction equilibrium between an aqueous monocarboxylic acid solution and a secondary amine in a low polar organic solvent, we could suggest four reaction equilibrium models:

Model 1: If undissociated penicillin acid (HP) in the aqueous phase reacts with Amberlite LA-2 (A) dissolved in the polar organic solvent such as n-butyl acetate, only (1,1) penicillin-amine complex (AHP) is well-known to be formed. A strong interaction between the polar organic solvent and the complex gives only the (1,1) complex. On the other hand, a few researchers [5] showed that the reaction equilibrium in the liquid-liquid system with a nonpolar organic solvent could be described by the same equilibrium expression as that in the system with the polar organic solvent. Therefore, we first selected the following reaction equilibrium as one of the equilibrium models:

[eqn: {A~+~HP}~ buildrel Lrarrow { { K}_{eq } }~ {AHP }], [eqn: { K}_{eq }= { { C}_{AHP} } over { { C}_{A } { C}_{HP } }]	(1)

Model 2: Simultaneous physical and reactive extractions of salicylic acid in an aqueous solution were performed using Amberlite LA-2 in xylene [6]. According to their work, only (1,1) and (1,2) complexes appeared be formed in the organic phase by the reactive extraction. Kawano et al. [7] studied the extraction equilibria of acetic acid and propionic acid with Amberlite LA-2 in hexane. Likewise, only (1,n) complexes were obtained during the reactive extraction by the carrier. On the basis of their equilibrium description, we could thus suggest the equilibrium model including the following  reaction equilibria:

[eqn: { {A(HP)}_{i-1} ~+~HP}~ buildrel Lrarrow { { K}_{eq,i} }~ { {A(HP) }_{i } }],[eqn: { K}_{eq,i}= { { C}_{ { A(HP)}_{i} } } over { { C}_{ { A(HP)}_{i-1} } { C}_{HP } }]	(2)

Model 3: Yerger and Barrow [8] investigated the reaction between acetic acid and diethylamine in carbon tetrachloride by infrared spectroscopy. They showed that three different complexes formed were strongly dependent on initial concentrations of acetic acid in aqueous phase and diethylamine in carbon tetrachloride taken as a completely non-interacting solvent. Based on their results, we could assume three simultaneous equilibrium expressions, Eqs. (3) to (5).

[eqn: {A~+~HP}~ buildrel Lrarrow { { K}_{eq,1} }~ {AHP }],[eqn: { K}_{eq,1 }= { { C}_{AHP} } over { { C}_{A } { C}_{HP } }]	(3)

[eqn: {AHP~+~HP}~ buildrel Lrarrow { { K}_{eq,2} }~ { {A(HP) }_{2 } }],[eqn: { K}_{eq,2 }= { { C}_{ { A(HP)}_{2 } } }over { { C}_{AHP } { C}_{HP } }]	(4)

[eqn: { { A(HP)}_{2 }~+~A}~ buildrel Lrarrow { { K}_{eq,3} }~ { { A}_{2 } { (HP)}_{2 } }],[eqn: { K}_{eq,3 }= { { C}_{ { A}_{2 } { (HP)}_{2 } } } over { { C}_{ { A(HP)}_{2 } } { C}_{A } }]	(5)

Model 4: Actually, (1,1) complex seems to be difficult to exist alone in a nonpolar organic solvent because of very strong interaction between the (1,1) complexes in the environment, where there is little interaction between the complex and the nonpolar organic molecule. Therefore, we could assume that 2 moles of undissociated penicillin acid directly reacted with 2 moles of Amberlite LA-2 to form only 1 mole of (2,2) complex without formation of the first or the second complex in model 3.

[eqn: { 2A~+~2HP}~ buildrel Lrarrow { { K}_{eq} }~ { { A}_{2 } { (HP)}_{2 } }],[eqn: { K}_{eq }= { { C}_{ { A}_{2 } { (HP)}_{2 } } } over { { C}`_{A } ^{2 } { C}`_{HP } ^{2 } }]	(6)

The nth-order equations for CHP and/or CA are derived using the overall material balances of penicillin G and amine for each model. The equations were solved by the FORTRAN subroutine ZPORC or NEQNF available from IMSL MATH/LIBRARY (Problem-solving Software Systems) in order to get CHP satisfying the constraint 0 < (1+10pH-pKa)CHP < CPG.

Experimental

The organic solution was prepared by dissolving 20∼160mM Amberlite LA-2 in kerosene. 0.408M citrate buffer solution was prepared at pH 4.5∼5.8, and 5∼220mM penicillin G potassium salt was dissolved in the buffer solutions. Equal volumes (30cm3) of the prepared organic and aqueous solutions in a flask were vigorously mixed by a shaker maintained at 25℃ for about one hour, and the penicillin G concentration in the aqueous phase was measured by UV spectrophotometer (UV2-100, ATI Unicam) at 258nm after separation of two phases. Also, IR spectra for penicillin G in a solid state, and unreacted Amberlite LA-2 and penicillin-Amberlite LA-2 complex in kerosene were recorded at room temperature with a Thermo Nicolet Model MAGNA-IR 560 double beam FTIR spectrophotometer with a KBr window.

Results and discussion

The experimental data of 96 runs were obtained through the equilibrium experiments, and an objective function  was introduced so as to optimize reaction equilibrium constants of each equilibrium model as follows:

[eqn: f~=~ SUM from { {i }=1} to N SQRT { { (1- { E}_{exp,i }/ { E}_{cal,i} )}^{2 } }]	(7)

where  and  are experimental data and calculated results for degree of extraction, respectively. Fig. 1 shows the effect of overall penicillin G concentration on degree of extraction of penicillin G at several overall amine concentrations. The results calculated from models 3 and 4 agreed with the experimental data much better than those from models 1 and 2. Accordingly, we could consider that model 3 or 4 was more probable than models 1 or 2 as an equilibrium model. To investigate whether model 3 is appropriate as extraction equilibrium model and thus existence of the three complexes in an organic solution depends on overall penicillin G and Amberlite LA-2 concentrations, infrared spectroscopic studies were therefore performed on organic solutions obtained by five extraction equilibrium experiments with different overall penicillin G and Amberlite LA-2 concentrations.

According to the work of Tamada about carboxylic acid-amine complex [9], it has been known that an equilibrium between carboxylate and carbonyl forms of a (1,1) complex exists in organic solution. For strong acids the equilibrium is shifted towards the carboxylate form (1600cm-1). For weak acids in inert diluents, the equilibrium is shifted toward the carbonyl form (1720 cm-1) in structure I of Fig. 2. However, we could not find a carbonyl peak near the band in IR spectra for organic solutions obtained in Runs 1 to 5 while a small carbonyl peak (1718 cm-1) exits in IR spectra for penicillin G in a solid state. Nonexistence of  the carbonyl peak for the runs means that formation of the (1,1) complex is difficult in such a nonpolar solvent. The fact supports that only (2,2) complex exists in the organic phase.  Accordingly, model 4 including the sole complex is likely to be more appropriate than model 3 as an equilibrium model of penicillin G extraction.

Conclusions

Extraction equilibrium experiments for penicillin G were performed using kerosene and Amberlite LA-2. Four probable equilibrium models were suggested and the calculated results from models 3 and 4 fit the experimental data better than those from models 1 and 2. In order to find the most reasonable model, the infrared absorption spectra of five organic solutions of Runs 1 to 5 have been recorded. From the facts that no bands attributable to C=O stretching of carboxylic group near 1718 cm-1 are detectable and there is not any shifting in main peaks with the increase in degree of extraction, model 4 including the sole complex, A2(HP)2, appears to be the most suitable as an equilibrium model of penicillin G extraction.

화학공학의 이론과 응용 제8권 제1호 2002년

References

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8. Yerger, E.A.; Barrow, G.M. Acid-base reactions in non-dissociating solvents. Acetic acid and diethylamine in carbon tetrachloride and chloroform. Am. Chem. Soc. 1955, 77, 4474-4481.

9. Tarmada, J.A. Extraction of carboxylic acids by amine extractants, Ph.D. Dissertation, University of California at Berkeley, 1989.