Extraction of penicillin G from aqueous solutions: Analysis of reaction equilibrium and mass transfer

Analysis of the reaction equilibrium and mass transfer in the extraction of penicillin G (Pen G) into an organic phase is an important research area to develop a cost-effective process for its separation from an aqueous fermentation media. In order to evaluate this, equilibrium experiments were first carried out to select the organic phase (composed of the carrier and solvent) that gives good values for the distribution of penicillin G between the aqueous and organic phases. An organic phase of Amberlite LA-2 in any of the solvents (Shellsol TK/butyl acetate/tributyl phosphate) gave high distribution coefficient and the stoichiometry of the reaction has been shown to follow a simple ratio of 2:2. The performance of the organic phases was evaluated in a membrane contactor and very high percentage extraction was achieved. The extraction was performed by contacting a “feed” solution containing penicillin G (flowing in the fiber side) with an “organic phase” of Amberlite LA-2 in one of the solvents (flowing on the shell side) of the contactor. The antibiotic solutes formed complex with the Amberlite LA-2 molecules which were transported across the fiber wall to the shell side and extracted in the organic phase. The extraction in once-through mode was low and the feed/organic solutions need to be recycled to increase the percentage extraction. In the recycle mode operated at flow rates of 3.6–4.4 mL/s, an extraction of 90–98% was achieved. A simple mathematical model and its semi-analytical solution presented here can be used to determine the overall mass transfer coefficient using the experimental values of the distribution coefficient, operating parameters and the dimensions of the membrane module.     

三烷基氧磷萃取对氨基苯酚的性能

以三烷基氧磷(TRPO)为反应萃取剂,研究了稀释剂种类、溶液pH值等因素对对氨基苯酚稀溶液反应萃取分配系数(D)的影响,提出了同时考虑反应萃取和物理萃取作用的分配系数的表达式.结果表明：TRPO对对氨基苯酚的萃取主要通过与其中性分子的氢键缔合和溶剂化效应实现,D值的变化与中性分子的摩尔分数有关;稀释剂的极性对对氨基苯酚的萃取影响较小;除20%TRPO/正庚烷体系外,拟合实验数据得到的表观萃取平衡常数变化较小;体系的物理萃取分配常数则随TRPO浓度的增大而增大,且符合稀释剂和TRPO的物理萃取能力的简单加和;酸性、碱性和中性的反应萃取剂都可有效地萃取对氨基苯酚,萃取能力为二(2-乙基己基)磷酸＞ TRPO ＞ 三烷基胺,相应的操作pH值为2～3、4～5和6.5～7.5,应用时可根据体系的pH值范围选用相应的萃取剂,而不必调节溶液的pH值.     

Study on new solvent extraction systems for erythromycin

New solvent systems for the extraction of erythromycin were studied in which octanol was used as the extractant instead of butyl acetate. The mechanism for these new extraction systems is not simple physical distribution but the formation of a neutral complex of erythromycin. A neutral extraction complex formed between the neutral molecules of erythromycin and extractant by hydrogen bonding, and the formed neutral extraction complex moves into the organic phase. Extraction reaction equations and mathematical models of extraction equilibrium and re‐extraction equilibrium are proposed for these new extraction systems. Experimental results show that the new extraction systems offer technological and economic advantages owing to the low solubility of the extraction solvents in the aqueous phase. The solvent consumption of the new extraction process was less than 3kg per billion active units compared with 9–10 kg per billion active units for a butyl acetate extraction system. In addition, the recovery of solvent from raffinate may be eliminated, thus reducing energy consumption. Copyright © 2005 Society of Chemical Industry     

Extraction of Caprolactam with an Alternative Benign Solvent in a Pulsed Disc and Doughnut Column

Abstract

Caprolactam is obtained by extraction using organic solvents like benzene, toluene, or chlorinated hydrocarbons. As an alternative solvent, the mixed solvent heptane‐heptanol (40 mass %) was selected in previous studies based on a relatively high distribution ratio of caprolactam, a low mutual solvent solubility, beneficial physical properties, and a low distribution ratio of impurities. Now, the hydraulic and mass transfer characteristics of the extraction of caprolactam in a pulsed disc and doughnut column (PDDC) were investigated using the benign solvent. The results were compared to those for toluene.

The PDDC showed qualitatively comparable operational characteristics for both solvents. In the hydraulic experiments the mixed solvent showed smaller drop diameters and hold‐ups, required lower pulsation intensities for regime transitions, but the operational windows are slightly smaller. For both solvents, mass transfer resulted in increasing drop diameters and pulsation intensities required for regime transition. In the forward extraction the mixed solvent was superior, where HETS/m=0.26 to 0.37, compared to 0.42 to 0.67 for toluene, while less theoretical stages are required as well. For the back‐extraction HETS/m=0.33 to 0.40 for the mixed solvent compared to 0.30 to 0.37, but toluene requires the lower amount of theoretical stages.

The hydraulic characteristics at equilibrium and concentration profiles in both the forward and back‐extraction were described accurately using the developed models.     

磷酸三丁酯络合萃取丁酸的研究

用络合萃取法分离极性有机稀溶液 ,具有高效性和高选择性。利用磷酸三丁酯 (TBP)为络合剂 ,分别采用甲苯、异丙基甲酮、正辛醇、煤油作为稀释剂萃取丁酸稀溶液 ,系统研究了不同稀释剂对络合萃取平衡的影响 ,最终从效能、毒性、价格等综合因素考虑 ,选用正辛醇作为稀释剂 ;分析了络合剂浓度、丁酸溶液初始浓度、溶液 pH值以及温度对络合萃取相平衡分配系数的影响 ;利用红外光谱测定了负载有机相中萃合物的结构 ;并进行了有机溶剂的再生研究     

三辛胺萃取分离苹果酸的特性

为探讨有机羧酸的成键机理，以二元有机酸－苹果酸为分离溶质，实验测定了三辛胺（TOA）在正辛醇、甲基异丁基酮（MIBK）和氯仿三种稀释剂中萃取苹果酸的平衡及负载溶剂红外光谱特性，结果表明，TOA浓度，稀释剂种类对萃取平衡的影响与苹果酸的浓度有关；平衡水相酸的浓度较低时，萃取剂可提供较大的萃取能力，TOA的化学计量饱和后，存在“过载”现象，且过载量为MIBK＞正辛醇＞氯仿，TOA萃取苹果酸的萃合物主要为酸胺比为（2：1），（1：1）和（1：2）等三种形式，其中（1：2）萃合物中苹果酸与TOA之间的结合一个是离子对成盐，一个是氢键缔合，同时，以质量作用定律为基础，建立了描述萃取平衡的数学模型，求得了相应的反应萃取平衡常数K11，K12，K21。     

绿色溶剂碳酸二甲酯处理含酚废水研究

用绿色溶剂碳酸二甲酯 (DMC)对含酚废水进行了萃取处理 ,研究了时间、pH、溶剂组成、溶剂比等对萃取的影响。实验结果表明 ,DMC萃取苯酚的过程为物理溶解过程 ,因此萃取过程在几分钟之内就能达到平衡 ,而且萃取过程基本不受 pH值的影响。随着平衡水相浓度的增加 ,平衡有机相浓度增加 ,而且分配系数也增加。以 5 0 %DMC 正己烷为萃取剂 ,三级萃取 5g/L的苯酚废水 ,萃残液中的酚浓度降到了 4.82mg/L。     

Deep Eutectic Solvent as Green Solvent in Extraction of Biological Macromolecules: A Review

Greater awareness of environmental sustainability has driven many industries to transition from using synthetic organic solvents to greener solvents in their manufacturing. Deep eutectic solvents (DESs) have emerged as a highly promising category of green solvents with well-demonstrated and wide-ranging applications, including their use as a solvent in extraction of small-molecule bioactive compounds for food and pharmaceutical applications. The use of DES as an extraction solvent of biological macromolecules, on the other hand, has not been as extensively studied. Thereby, the feasibility of employing DES for biomacromolecule extraction has not been well elucidated. To bridge this gap, this review provides an overview of DES with an emphasis on its unique physicochemical properties that make it an attractive green solvent (e.g., non-toxicity, biodegradability, ease of preparation, renewable, tailorable properties). Recent advances in DES extraction of three classes of biomacromolecules—i.e., proteins, carbohydrates, and lipids—were discussed and future research needs were identified. The importance of DES’s properties—particularly its viscosity, polarity, molar ratio of DES components, and water addition—on the DES extraction’s performance were discussed. Not unlike the findings from DES extraction of bioactive small molecules, DES extraction of biomacromolecules was concluded to be generally superior to extraction using synthetic organic solvents.     

溶剂萃取法处理苯酚稀溶液及其废水的研究

为探索工业含酚废水处理的适宜萃取剂,选用具有物理萃取和络合萃取作用的两类萃取剂正辛醇、甲基异丁基甲酮(MIBK)和磷酸三丁酯(TBP)(以煤油为稀释剂)进行了苯酚稀溶液萃取性能的实验研究。测定了不同溶液pH值、初始苯酚浓度和TBP浓度条件下的萃取平衡数据,分析了各萃取剂萃取平衡的规律及机理。结果表明,虽然各萃取剂的萃取机理不同,但在酸性和中性范围内都可获得较大的萃取平衡分配系数,所以,这三种萃取剂的适宜pH值操作条件为酸性和中性,且在稀溶液的范围内溶剂的萃取能力为TBP > MIBK >正辛醇,而在极稀的苯酚浓度条件下(<20mgL-1),则为正辛醇> TBP > MIBK。同时,正辛醇、TBP处理工业含酚废水的错流萃取实验表明,若考虑通过单一的萃取方法使得废水中苯酚的浓度达到国家排放标准(0.5mgL-1),正辛醇为适宜的萃取剂。     

不同pH值下酚类的络合萃取

络合萃取法分离极性有机物稀溶液具有高效性和高选择性。在已有工作基础上,利用三正辛胺(TDA)、磷酸三丁酯(TBP)为络合剂,正辛醇、甲墓异丁基酮(MIBK)或煤油为稀释剂,在较宽的pH值条件下实验测定了酚类稀溶液的萃取相平衡分配系数;讨论了络合剂种类、络合剂浓度、稀释剂种类以及被萃取溶质种类对络合萃取相平衡分配系数的影响;提出了同时考虑络合萃取作用和物理萃取作用的平衡分配系数的表达式。     

An improved prediction result of entropic‐FV model for vapor–liquid equilibria of solvent–polymer systems

In this work, entropic expressions of UNIFAC‐FV and Entropic‐FV models were evaluated by using an extensive database of infinite dilution vapor–liquid equilibrium (VLE) data of athermal systems containing polypropylene, polyethylene, and polyisobutylene. For the infinite dilution athermal systems, performance of the Entropic‐FV model was better than that of the UNIFAC‐FV model. Then, finite concentration VLE data of non‐athermal systems that consisted of 16 polymers and 36 solvents containing a large variety of solvent–polymer systems ranging from nonpolar to polar substances were considered to optimized 46 pairs of group interaction parameters of the Entropic‐FV model. For systems containing polar solvents of three types of solvents studied, revised group interaction parameters gave significant improvements from 17.9 to 13.0% average absolute deviation (AAD) of solvent activities. For overall results, improvements were achieved from 15.1 to 12.4% AAD. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1145–1153, 2005     

Equilibrium studies on enantioselective extraction of oxybutynin enantiomers by hydrophilic β‐cyclodextrin derivatives

The enantioselective extraction of hydrophobic oxybutynin (OBN) enantiomers by hydrophilic β‐cyclodextrin (β‐CD) derivatives was studied. The efficiency of extraction depends strongly on a number of process variables such as types of organic solvents and β‐CD derivatives, concentration of selector, pH, and temperature. The experimental data were described by a reactive extraction model with a homogeneous aqueous phase reaction of R,S‐OBN with β‐CD. Important parameters of this model were determined experimentally. The physical distribution coefficients for molecular and ionic OBN were 4.96 × 10^?3 and 9.52, respectively. The equilibrium constants of the complexation reactions were 1770 and 1340 L/mol for S‐ and R‐OBN, respectively. By modeling and experiment, an optimal extraction condition with pH of 5 and HP‐β‐CD concentration of 0.1 mol/L was obtained with enantioselectivity (α) of 1.26, which was close to the theoretical maximum of 1.32 and performance factor (pf_i) of 0.036. The model was verified experimentally with excellent results. © 2011 American Institute of Chemical Engineers AIChE J, 2011     

三烷基氧磷络合萃取邻氨基苯酚的研究

络合萃取技术对极性有机物稀溶液的分离具有高效性和高选择性,然而对同时具有Lewis酸性和Lewis碱性两种官能团化合物的络合萃取研究得相对较少。为了探讨该技术对两性有机化合物萃取规律,今以三烷基氧磷（TRPO）为萃取剂,邻氨基苯酚为萃取溶质,研究了稀释剂种类、溶液pH值以及溶质浓度等因素对邻氨基苯酚稀溶液萃取平衡分配比的影响;根据可逆络合萃取的基本理论,提出了同时考虑萃取剂络合萃取作用和稀释剂物理萃取作用的分配比的表达式。并通过参数寻优求出邻氨基苯酚的物理萃取分配常数m和表观化学反应萃取平衡常数K。结果表明,邻氨基苯酚主要通过氢键缔合与OAP的中性分子发生络合反应而萃入有机相,其在惰性稀释剂煤油中的分配比大于其在极性稀释剂正辛醇中的分配比。     

The use of environmentally sustainable bio-derived solvents in solvent extraction applications——A review

Replacement of volatile organic compounds (VOCs) by greener or more environmental y sustainable solvents is becoming increasingly important due to the increasing health and environmental concerns as wel as economic pressures associated with VOCs. Solvents that are derived from biomass, namely bio-derived solvents, are a type of green solvent that have attracted intensive investigations in recent years because of their advantages over con-ventional VOCs, such as low toxicity, biodegradability and renewability. This review aims to summarize the use of bio-derived solvents in solvent extraction applications, with special emphasis given to utilization of biodiesels and terpenes. Compared with the conventional VOCs, the overall performance of these bio-derived solvents is comparable in terms of extraction yields and selectivity for natural product extraction and no difference was found for metal extraction. To date most researchers have focused on laboratory scale thermodynamics studies. Future work is required to develop and test new bio-derived solvents and understand the kinetic performance as well as solvent extraction pilot plant studies.     

三辛胺萃取草酸的第3相特性

以三辛胺（TOA）萃取草酸时出现第3相的基本规律为研究对象,实验测定了无水溶剂及液液萃取平衡有机相中草酸的溶解度及其随TOA和正辛醇浓度的变化规律.结果显示,正辛醇对草酸及其与TOA形成的缔合物在溶剂中的溶解度影响显著;随正辛醇含量的增加,草酸及其缔合物在溶剂中的溶解度提高,因而溶剂对草酸的萃取能力随之增大;在TOA与草酸以1∶1的化学计量比饱和后,草酸溶解度出现阶跃现象,这与形成草酸二聚体的缔合物有关;相比之下,液液萃取平衡实验中有机相对草酸的溶解度大于无水溶剂的结果,溶剂中水的存在有助于缔合物溶解.同时建立了描述液液萃取平衡有机相中草酸及其缔合物溶解度的数学模型,并通过参数寻优求得了相应的模型参数.     

Comparative Study on Reactive Extraction of Nicotinic Acid with Amberlite LA‐2 and D2EHPA

Abstract

The comparative study of reactive extraction of nicotinic acid with Amberlite LA‐2 and D2EHPA in three solvents with different polarity indicated that the extractant type and solvent polarity control the extraction mechanism. Thus, the reactive extraction with Amberlite LA‐2 in low‐polar solvents occurs by means of the interfacial formation of an aminic adduct with 3 or 2 extractant molecules. If solvents with higher polarity are used, each reactant participates with one molecule to the interfacial reaction. The mechanism of reactive extraction with D2EHPA involves in all cases the formation of a salt as the product of the interfacial reaction between one molecule of each reactant.     

β-萘酚稀溶液萃取动力学研究

选用磷酸三丁酯 甲苯混合溶剂对β 萘酚稀溶液进行萃取动力学研究,考察了搅拌强度、二相界面积、水相β 萘酚质量浓度、水相pH值、有机相内萃取剂体积分数和温度对萃取速率的影响。实验结果表明,磷酸三丁酯萃取β 萘酚的动力学模式为化学反应控制模式,且为水相内反应控制类型。根据实验结果建立了磷酸三丁酯萃取β 萘酚的动力学模型。     

Prediction of partition coefficients using COSMO-RS: Solvent screening for maximum conversion in biocatalytic two-phase reaction systems

Many biocatalytic reaction systems are biphasic with a reactive and an immiscible non-reactive phase. The reactive, mostly aqueous phase provides a natural enzyme environment and the non-reactive phase serves for delivery of dissolved substrates at high concentrations and for extraction of products. The proper choice of the non-reactive phase will have manifold influence on the catalytic parameters, such as activity, selectivity, and stability, but also on the maximum obtainable conversion or yield.

Conversion or yield constitutes a concise target of practical relevance for rational solvent screening which requires thermodynamic information on coupled reaction and phase equilibria as input information. As long as the reactive phase is kept constant, only the partition equilibrium of each solute in any solvent combination has to be determined. The experimental determination of these data requires a considerable laboratory effort. Therefore, an in-silico screening of solvents for maximal conversion of alcohol dehydrogenase-catalysed oxidoreductions of prochiral ketones was evaluated. COSMO-RS was used for the prediction of solute partitioning between organic solvents and aqueous reaction medium.

Although significant absolute deviations were found, COSMO-RS still predicted the correct trends for the partition coefficients of solutes in different solvents. The calculated overall reaction equilibrium using these partition coefficients again resulted in the prediction of the correct best solvent regarding conversion.     

Separation of Ionic Liquid Dispersions in Centrifugal Solvent Extraction Contactors

Abstract

Separations of dispersions formed by mixing immiscible organic room‐temperature ionic liquids (IL)/hydrocarbon/and aqueous systems using a centrifugal solvent‐extraction contactor have been successfully demonstrated in proof‐of‐concept testing. This accomplishment is significant in that physical property factors that are typical of ionic liquid systems (e.g., similar densities of the bulk phases, low interfacial tensions, and high viscosities) are typically unfavorable for dispersion separation, particularly in continuous processes. Efficient separation of dispersions containing ionic liquid solvents is essential for utilization of these compounds in liquid‐liquid extraction applications to maximize both solute transfer efficiency and solvent recovery. Efficient solvent recovery is of particular concern in IL applications because of the high cost of most IL solvents.

This paper presents the results of initial experiments with three hydrophobic ionic liquids to determine how their physical properties affect phase mixing and phase disengagement in contact with an aqueous solution using a centrifugal contactor. While the results of the reported work are promising, additional work is needed to optimize existing mathematical models of contactor hydraulics to address special considerations involved in IL‐based processes and to optimize the equipment itself for IL applications.     

溶剂脱毒汽爆玉米秸秆对酶解以及发酵的影响

以脱毒对酶解及发酵的影响为研究对象,以酶解还原糖得率及发酵乙醇质量浓度为指标,采用溶剂萃取的方法对无催化汽爆玉米秸秆进行萃取脱毒。结果表明,酶解还原糖得率随着萃取剂及萃取方式介于34.85%和89.7%,酶解还原糖得率和发酵乙醇质量浓度与脱毒有机溶剂的沸点高度负相关,表明有机溶剂的残留是导致酶失活的主要原因。而对于所考察的溶剂,乙醇产率为0.47～0.49 g乙醇/g还原糖,表明有机溶剂残留对乙醇发酵并无显著影响。采用乙醚和丙酮的组合萃取,乙醇最高产率可以达到理论值的96.1%。