Salting-out extraction of carboxylic acids

Separation and Purification Technology 139 (2015) 36–42

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Salting-out extraction of carboxylic acids Hongxin Fu, Yaqin Sun, Hu Teng, Daijia Zhang, Zhilong Xiu ⇑ School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, Liaoning, People’s Republic of China

a r t i c l e

i n f o

Article history: Received 2 May 2014 Received in revised form 24 October 2014 Accepted 1 November 2014 Available online 8 November 2014 Keywords: Ethanol Ammonium sulfate Salting-out extraction Carboxylic acids Two-phase system

a b s t r a c t Developing economic and feasible technology for recovery of carboxylic acids is a challenge for their industrial production. Salting-out extraction of carboxylic acids (formic, acetic, propionic, lactic, succinic, and citric acids) was studied using a system composed of ethanol and ammonium sulfate. The system parameters influencing the extraction efficiency, such as tie line length, phase volume ratio, acid concentration, temperature, and system pH were evaluated. The results showed that partition coefficient of carboxylic acids increased or decreased linearly as tie line length increased, and strongly depended on the system pH. However, the varied phase volume ratio alone the selected tie line, acid concentration and temperature nearly had no effect on the partition coefficient of carboxylic acids in this system, although the recovery increased obviously as the phase volume ratio increased. Correlation of the hydrophobicity (ClogP) of carboxylic acids with natural logarithm of partition coefficient (ln K), indicated that the extraction efficiency was improved as hydrophobicity of carboxylic acids increased. Ó 2014 Elsevier B.V. All rights reserved.

1. Introduction The production of carboxylic acids has a long history which can date back to the 1900s. However, recovery of carboxylic acids from either fermentation broth or low titer wastewater presents a significant challenge. A great deal of effort has been made in developing feasible and economic method for recovery of carboxylic acids. For example, the precipitation with calcium hydroxide or calcium oxide, followed by filtration, acidification and crystallization, has been employed as the main recovery method, although it has great difficulty and low yield. The others acid recovery processes are available, including electrodialysis [1,2], esterification [3], chromatography [4], extractive fermentation [5,6] and solvent extraction [7,8]. Among them, liquid–liquid extraction has been considered as a promising method rather than precipitation. Efficient extractants used for recovery of carboxylic acids, such as phosphorusbonded oxygen-bearing and aliphatic amines with high molecular weight, are more effective than the conventional oxygen-bearing and hydrocarbon hydrophobic solvents, such as ketones, alcohols, ethers, and aliphatic hydrocarbons. Aqueous two-phase systems (ATPS) have been attracting more and more attention due to their advantages in the separation of biomolecules. In recent years, there are some attempts in extraction of ⇑ Corresponding author at: School of Life Science and Biotechnology, Dalian University of Technology, Linggong Road 2, Dalian 116024, Liaoning, People’s Republic of China. Tel./fax: +86 41184706369. E-mail address: [email protected] (Z. Xiu). http://dx.doi.org/10.1016/j.seppur.2014.11.001 1383-5866/Ó 2014 Elsevier B.V. All rights reserved.

organic acids using ATPS. Yankov et al. [9,10] has used polymerbased ATPS to recovery of lactic acid and studied the influence of pH and acid on the phase equilibria. The results showed that both increasing the pH and adding the acid resulted in the contraction of the two-phase region. The application of ionic liquid-based ATPS for the separation of gallic acid has also been reported [11]. The extraction efficiency of gallic acid was dependent on the pH values. Moreover, the inorganic salts (NaCl, KCl, MgCl2, and CaCl2) were used to salt-out butyric acid [11]. And it was efficient only when the acid concentration reached 200 g/L or more. However, these methods are limited to be adopted for commercialized application due to low yield and high price or toxicity [7]. Hence, it is highly desirable to develop a cost-saving, simple and environmentally friendly approach for recovery of carboxylic acids. Salting-out extraction (SOE or is referred to as aqueous twophase system) is a separation method used to extract a hydrophilic target from an aqueous solution with the aid of an organic solvent as the extractant and salt as a salting out reagent [12], and can be used as a potential alternative approach where separation, concentration, and partial purification can be achieved in a single step of extraction process [13,14]. It offers many merits such as low cost, low viscosity, easy recovery of phase-forming components, short phase separation time, easy scale up and possibility of continuous operation [15,16]. Recently, the fundamental screening and optimization of SOE systems for target products recovery have been studied and the application of SOE systems have been extended to bio-based chemicals [12,13,17–21], nature products [22–25], protein [26] and enzyme [16].

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H. Fu et al. / Separation and Purification Technology 139 (2015) 36–42

Salting-out extraction system composed of dipotassium hydrogen phosphate and ethanol was selected and used to recovery of lactic acid from the model solution and real fermentation broth, and the results were optimized by orthogonal experiment and response surface methodology, respectively [13,21]. The partition coefficient and extraction yield were decreased slightly when fermentation broth was used. Moreover, a system consisting of ammonium sulfate and acetone was investigated for the extraction of succinic acid and a yield of 90% was obtained. The possibility of integration of SOE with crystallization was also proved [17]. Since nearly all of the studies mainly focus on a specific product, it is hard to compare their results due to different experiment conditions (salting-out extraction system, phase composition and operation condition) and provide a general principle to guide the experiment. To our knowledge, the factors influencing the extraction efficiency of carboxylic acids in the ethanol/ammonium sulfate SOE system have not been studied systematically, which hamper rational design of SOE process for target carboxylic acids. The objective of this study was to investigate and summarize the partition behavior of a series of carboxylic acids (formic, acetic, propionic, lactic, succinic and citric acids) in the ethanol/ammonium sulfate SOE system under different system parameters (tie line length, phase volume ratio, temperature, system pH and concentration of acids). This work was based on the phase diagram data, which is the basis of extraction experiment and was neglected by the previous researchers. Optimization the experiment with the phase diagram data in terms of tie line length and phase volume ratio, we can find the optimum process parameters and obtain useful conclusion. Undoubtedly, the method and result obtained here would be helpful in designing a suitable and economic salting-out extraction process for different target products.

in the range between 2 and 7 (8 for citric acid) due to all the acids were existed in dissociated or undissociated form within this range. The tube was shaken thoroughly in a vortex mixer for 5 min and then settled to equilibrate in a water bath setting at required temperature (0, 20, 40 and 60 °C), followed by recording the volume of the top and bottom phases and then collecting the sample for analyzing the concentration of the carboxylic acids by HPLC. All the experiments were repeated twice and the average values were given. 2.3. Analytical methods The sample withdrawn from the two phases after equilibrium were analyzed for acids concentration by HPLC (Agilent 1100) with a C18 column at 214 nm using an ultraviolet detector, 2‰ phosphoric acid and acetonitrile (96.5:3.5 v/v) as mobile phase at a flow rate of 1 ml/min. The content of ethanol was analyzed by gas chromatography (GC-2010, Shimadzu, Japan), and the ammonium sulfate concentration was determined by conductivity meter (DDS-307, Leici, China). The content of water in different phases was deduced from the mass balance. 2.4. Phase diagram The binodal curve of ethanol/ammonium sulfate salting-out system at 293.15 K was obtained by cloud point method [14]. Ammonium sulfate solution with varying concentrations was titrated dropwise with ethanol, until the solution became turbid. The over-saturated point was determined by adding the ethanol slowly with stirring at different salt concentrations until the solid phase appeared. The compositions of these mixtures were noted and determined by an analytical balance. The tie lines were determined by analyzing the composition of top and bottom phases after the phase equilibrium when selecting proper points in the liquid–liquid equilibrium region. Phases were separated with care and analyzed for ethanol and ammonium sulfate concentration. The complete phase diagram and tie line data are shown in Fig. 1 and Table 1, respectively.

2. Materials and methods 2.1. Materials All the chemicals were analytical grade and purchased from Sinopharm Chemical Reagent Co., Ltd. Deionized water was used throughout the experiment.

2.5. Tie line length (TLL)

2.2. Extraction experiments

Tie line length is one the most important parameters depicted the salting-out extraction system. It represents the length between the composition of the top and bottom phases and was calculated according to Eq. (1).

All the experiments were conducted in 10 ml graduated tubes (0.2 ml). In order to study the effect of tie line length and phase volume ratio, predetermined and weighed amounts of ethanol, ammonium sulfate and carboxylic acids solution (25 g/L) were added to the tube (Tables 1 and 2) in order to fall on the different tie lines or construct various phase volume ratio along the selected tie line, making the total system 100% (w/w). The 27.3% (w/w) salt-rich carboxylic acid solutions with various concentrations and pH values were mixing with half volume of absolute ethanol in order to maintain the phase volume ratio approximately to 1. Acid concentration studied here were 100, 50 and 25 g/L except for succinic acid (50, 25 and 12.5 g/L) due to its relative low solubility. The pH of the solution was adjusted by adding sulphuric acid or sodium hydroxide, and the value was

TLL ¼

qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi 2 2 DEthanol þ DSalt 100%

ð1Þ

where D represent the mass fraction differences of ethanol and ammonium sulfate between the top and bottom phases. 2.6. Phase volume ratio (Vr) The phase volume ratio was calculated according to Eq. (2).

V r ¼ V t =V b

ð2Þ

Table 1 Experimental data for studying the effect of the tie line length in the system of ethanol (1) + ammonium sulfate (2) + water (3) at temperature of 293.15 K. Tie line

1 2 3

Top phase composition (w/w)

Bottom phase composition (w/w)

102 w1

System composition (w/w) 102 w2

102 w3

102 w1

102 w2

102 w1

102 w2

25.10 25.94 26.78

18.87 19.65 20.43

56.03 54.41 52.79

44.47 50.81 52.77

5.26 3.86 3.14

5.00 8.24 7.09

29.48 32.65 35.10

Phase volume ratio

1.02 1.00 0.98

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H. Fu et al. / Separation and Purification Technology 139 (2015) 36–42 Table 2 Experimental data for studying the effect of phase volume ratio in the system of ethanol (1) + ammonium sulfate (2) + water (3) at temperature of 293.15 K. Lu/Lla

System composition (w/w) 2

3 2 1 1/2 1/3 a

Phase volume ratio 2

2

10 w1

10 w2

10 w3

18.27 21.18 27.00 32.82 35.74

23.42 21.40 17.37 13.33 11.31

58.31 57.42 55.63 53.85 52.95

0.37 0.62 1.26 2.70 3.90

Lu/Ll is the ratio of upper and lower portion on the first tie line.

partition coefficients of all the carboxylic acids except for citric acid were found to increase with increasing TLL from 42.5 to 56.6 when the phase volume ratio was fixed (midpoint of the tie lines). An increase in TLL resulted in an increasing divergence of system composition between the two phases, which allowed carboxylic acids selectively partition between the phases. This might be explained based on the enhanced salting-out effect as the TLL increased. However, the trend for citric acid was adverse. This was attributed to its high hydrophilicity, making it apt to stay in the aqueous phase. On the other hand, the high concentration of ethanol and ammonium sulfate (at longer TLL) in the separated phases is beneficial for their subsequent recovery processes, which can be achieved by distillation and dilution crystallization, respectively.

3.2. Effect of phase volume ratio Fig. 1. Phase diagram for salting-out extraction system of ethanol (1) + ammonium sulfate (2) + water (3) at 293.15 K.

The influence of TLL on partition coefficient of carboxylic acids was studied at three different tie line lengths (42.5, 51.4, and 56.6) for ethanol/ammonium sulfate SOE system. As shown in Fig. 2, the

The first tie line (42.5) was divided into two parts (the ratios between the upper and lower portion were 3, 2, 1, 1/2 and 1/3, resulting in an increase in the Vr) on the basis of lever rule and used to investigated its effect on the partition coefficient and recovery. The recovery of all the acids was found to increase with an increase in Vr as shown in Fig. 3. It should be stressed that in the ethanol/ ammonium sulfate SOE system, the partition coefficient for all the carboxylic acids studied was almost a constant on the same tie line when the other variables remained unchanged. Hence, the increased recovery with the Vr was due to the enlarged volume of the top phase because recovery is the function of partition coefficient and Vr. Although the recovery of the carboxylic acids can be improved by increasing the Vr on the selected tie line, the cost for

Fig. 2. Effect of tie line length (TLL) on nature logarithm of partition coefficient (ln K) of carboxylic acids for salting-out extraction system of ethanol/ammonium sulfate at 293.15 K.

Fig. 3. Effect of phase volume ratio on partition coefficient (K) and recovery (Y) of carboxylic acids for salting-out extraction system of ethanol/ammonium sulfate at 293.15 K.

where Vt and Vb are the volumes of the top and bottom phases, respectively.

3. Results and discussion 3.1. Effect of tie line length


solvent recovery is increased at the same time, which should be taken into account.

3.3. Effect of carboxylic acids concentration As shown in Fig. 4, six (seven for citric acid) constant-pH lines were obtained by varying the carboxylic acids concentration. The carboxylic acid extracted into the top phase was proportional to that in the bottom phase, which meaned that the acids concentration nearly had no effect (except for propionic acid due to its high hydrophobicity) on the partition coefficient, implying this method was efficient even when the concentration of acid was low. Moreover, the slopes of the constant-pH lines were found to increase with a decrease in pH, especially close to their dissociation constant (pKa, Table 3) values. This result indicated that extraction efficiency was improved as the system pH decreased and greatly depended on the form of acid existing in the system.

3.4. Effect of system pH In order to investigate the influence of pH on carboxylic acid partition in the ethanol/ammonium sulfate SOE system, experiment was performed at pH values from 2 to 7 (8 for citric acid), and the results are shown in Fig. 5. In general, the partition coefficient was found to increase with a decrease in pH except at extremely low or high pHs where partition coefficient nearly had no change, indicating that the extraction efficiency strongly depended on the system pH. The change in partition coefficient was caused by the transformation of existence form of carboxylic acid in the aqueous solution. This phenomenon was similar to the results when using the Alamine 336 (a tertiary amine) [8] and ionic liquid-based ATPS [11]. From Fig. 5, we also noticed that the shape of the curve correlated partition coefficient with system pH was similar to the dissociation curve of the corresponding acid, implying that the undissociated acid was apt to extract into the top

39

phase. Therefore, the pH value of the solution is a dominant parameter which can control the partition behavior of carboxylic acids. However, if only the undissociated acid could be extracted by the top phase, there should be no carboxylic acid appeared in the top phase at high pH value (pH = 7 or 8). This is true for most of the extraction processes. Hence, this pH effect in ethanol/ ammonium sulfate SOE system on carboxylic acids extraction cannot be explained by the dissociation of acid alone and should consider the composition of this extraction system. Since salting-out extraction system is composed of organic solution, salt and water, the top phase contains a certain amount of water and salt determined by the phase diagram. Therefore, both dissociated (distributes along with the water) and undissociated forms of the carboxylic acid exist in the top phase, which can be demonstrated by the equilibrium acids concentration in the top and bottom phases (Fig. 4). 3.5. Effect of temperature The effect of temperature on partition coefficient of some carboxylic acids using amine extractants has been reported [27–29]. The partition coefficient decreased with different level depending on the type and concentration of carboxylic acids as the temperature increased, which allowed the back-extraction of carboxylic acids with water and recovery of extractants at higher temperature. However, the effect of temperature in the ethanol/ammonium sulfate SOE system was not obvious for most of the acids. As shown in Fig. 6, extraction efficiency increased with different extent depending on the hydrophobicity of carboxylic acids with increasing temperature form 0 to 60 °C. This might be attributed to the change of the solubility of salt into water and intermolecular force of hydrogen bond in the system. Compared the partition behavior of propionic acid with other acids at different temperature, we can concluded that the noticeable increase in partition coefficient for propionic acid was mainly due to the decreased intermolecular force between water and propionic acid.

Fig. 4. Effect of carboxylic acids concentration on partition coefficient (K) of carboxylic acids for salting-out extraction system of ethanol/ammonium sulfate at 293.15 K: equilibrium acids concentration in top phase versus that in bottom phase. (A: formic acid B: acetic acid C: propionic acid D: lactic acid E: citric acid F: succinic acid).

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Table 3 Dissociation constant (pKa) and the calculated 1-octanol/water partition coefficient (CLogP) of carboxylic acids. Carboxylic acids

Molecular formulas

pKa

CLogPa

Formic acid Acetic acid Propionic acid Lactic acid Succinic acid Citric acid

HCOOH CH3–COOH CH3–CH2–COOH

3.77 4.79 4.85

1.316 0.194 0.335

CH3–CHOH–COOH HOOC–CH2–CH2–COOH HOOC–CH2–(C(OH)COOH)– CH2–COOH

3.86 4.20, 5.64 3.13, 4.76, 6.40

0.7338 0.5256 1.9978

a The hydrophobicity of organic molecules is an important characteristic and can be described in terms of calculated 1-octanol/water partition coefficient (ClogP) with high accuracy [30] and obtained automatically from software of ChemBioDraw. The larger the ClogP value is, the stronger the hydrophobicity, and the weaker the hydrophilicity of the compound.

3.6. Effect of the hydrophobicity of carboxylic acids

Fig. 6. Effect of temperature on partition coefficient (K) of carboxylic acids for salting-out extraction system of ethanol/ammonium sulfate.

As indicated in Fig. 7, plot of natural logarithm of partition coefficient (ln K) versus the calculated 1-octanol/water partition coefficient (ClogP) [30] of all the studied acids on the three tie lines yielded good straight lines (Table 3), demonstrating the partition coefficient was strongly dependent on the hydrophobicity of the carboxylic acids. The extraction efficiency of carboxylic acids with ethanol/ ammonium sulfate SOE system was in the order propionic acid > acetic acid > succinic acid > lactic acid > formic acid > citric acid. It was obviously that the ln K value for aliphatic carboxylic acids increased with an increase in the number of carbon atoms. On the other hand, the carboxylic acids with more than one hydrophilic group such as hydroxyl group and/or carboxylic group, that was lactic, succinic, and citric acids, made themselves more difficult than the acids with same carbon atoms to extract into

the top phase. For example, the partition coefficient of propionic acid was much larger than that of lactic acid. This was attributed to the increased hydrophilicity and thus it could not be salted out efficiently by the ammonium sulfate. It should be noted that the equations obtained here (Table 4) can be used to predict the partition coefficient of other carboxylic acids whose hydrophobicity located within the studied hydrophobic range in the ethanol/ammonium sulfate SOE system. Moreover, the critical ClogP value, the minimum ClogP value which allows it to distribute into the top phase (K > 1), can be obtained through these equations and is shown in Table 4. On the other hand, since a SOE system has certain extraction ability for a kind of products due to the similar critical ClogP values (especially at the longer

Fig. 5. Effect of system pH on partition coefficient (K) of carboxylic acids for salting-out extraction system of ethanol/ammonium sulfate at 293.15 K. (A: formic acid B: acetic acid C: propionic acid D: lactic acid E: citric acid F: succinic acid).


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Acknowledgment This work was financially supported by ‘‘863’’ projects (2012AA021202-3) of the Ministry of Science & Technology of the People’s Republic of China.

References

Fig. 7. Natural logarithm of partition coefficient (ln K) vs. the calculated 1-octanol/ water partition coefficient (ClogP) of carboxylic acids for salting-out extraction system of ethanol/ammonium sulfate at 293.15 K.

Table 4 Linear relationship between natural logarithm of partition coefficient (ln K) versus the calculated 1-octanol/water partition coefficient (ClogP) for all the studied acids and the critical ClogP values for the three tie lines. TLL

Equation

R2

Critical ClogP valuea

1 2 3

ln K = 0.839ClogP + 1.346 ln K = 0.999ClogP + 1.575 ln K = 1.123ClogP + 1.767

0.959 0.966 0.974

1.604 1.577 1.573

a The minimum ClogP value which allows it to distribute into the top phase (K > 1).

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