Modeling and Optimization of Reactive Extraction of Isonicotinic Acid

Subscriber access provided by University of South Dakota

Separations

Modeling and Optimization of Reactive Extraction of iso - Nicotinic Acid using Tri-n-octylamine in Biocompatible Diluents Mixture: RSM and Regeneration of Solvents Anju Kumari, ANKUR GAUR, Kailas L. Wasewar, and Sushil Kumar Ind. Eng. Chem. Res., Just Accepted Manuscript • DOI: 10.1021/acs.iecr.8b01533 • Publication Date (Web): 27 Aug 2018 Downloaded from http://pubs.acs.org on August 28, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 36 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Industrial & Engineering Chemistry Research

Modeling and Optimization of Reactive Extraction of iso Nicotinic Acid using Tri-n-octylamine in Biocompatible Diluents Mixture: RSM and Regeneration of Solvents

Anju Kumari1, Ankur Gaur1, Kailas L. Wasewar2, Sushil Kumar1*

1

Department of Chemical Engineering, Motilal Nehru National Institute of Technology (MNNIT) Allahabad - 211004 INDIA

2

Department of Chemical Engineering, Visvesvaraya National Institute of Technology (VNIT), Nagpur - 440010 INDIA *Corresponding author: [email protected]; [email protected]

ABSTRACT The present study is aimed to recover pharmaceutically- and biochemically important compound, iso-nicotinic acid (iNA) from aqueous/fermentation broth in biocompatible extraction system using intensified approach, reactive extraction. Tri-n-octylamine (TOA) is used as extractant in non toxic diluents mixture of dodecane and n-decanol (modifier) in 1:1 v/v. However, modeling and optimization of reactive extraction using three process parameters i.e., initial iNA concentration in aqueous solution (0.0032-0.0368 kmol.m-3), TOA concentration in organic phase (0.110 – 1.259 kmol.m-3) and initial pH values of aqueous phase (1.32-4.68) is performed using response surface methodology (RSM) and rotatable central composite design (rCCD) matrix is used in experimental design. RSM model suggests that initial acid concentration is the 1

ACS Paragon Plus Environment

Industrial & Engineering Chemistry Research 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

most influential factor whereas, pH value change shows antagonistic impact on %E. At equilibrium, under constraint condition (lowest TOA concentration selected) i.e. 0.110 kmol.m-3 and iNA concentration of 0.03 kmol.m-3 and pH value of 3.76, the maximum predicted value of % E is found to be 91.13%. The corresponding experimentally determined degree of extraction is 89.4 % which is in close agreement with the value predicted by the model. Nevertheless, the back extraction of iNA is also carried out using different concentrations of aqueous solution of NaOH. It is found that 99% of iNA is recovered using 0.02 kmol.m-3 NaOH with solvent regeneration.

Keywords: Reactive extraction; Equilibria; Iso-Nicotinic acid, RSM; Rotatable central composite design (rCCD); Back-extraction

1. INTRODUCTION In recent years, iso – nicotinic acid (iNA) or pyridine-4-carboxylic acid has grown its popularity due to its various applications in chemical and biochemical industries1. It is an important pyridine derivative used in the manufacture of isoniazid, an anti- tuberculosatic drug2. Some other pharmaceutically important drugs like, terefenadine, an antihistamine and nialamide, an anti depressant are also derived from iNA. In addition, it also finds application as an anticorrosion reagent, electroplating additive, photosensitive resign stabilizer and non- ferrous metals floating agent3. iNA is an amphoteric compound with lewis acid-base character and the pKa1 and pKa2 values are 1.84 and 4.86, respectively due to –N and –COOH group4.

2


Page 2 of 36

Page 3 of 36 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Currently, 4- Picolin is the starting material for the chemical synthesis of iso-nicotinic acid (iNA). This oxidation process,under very high temperature and pressure process results in high cost and low productivity of the desired product

5, 6

. However, the enzyme-catalyzed reactions

work under moderate environment conditions and are specific towards the production of certain bioproduct, like nitrilase, a low cost and readily available enzyme specific towards synthesis of iNA as dilute fermentation broth7. However, the production is at lower rate and concentration in the broth is very low. Generally, the downstream processing of bio-products costs about 60% of total production cost5, 8. Hence, for large scale production, it is not preferred over the chemical synthesis route. Thus, an alternate efficient method is required for its recovery from dilute fermentation broth via bio synthetic method due to increasing demand of pure iso- nicotinic acid9. Reactive extraction is one of the efficient alternate to remove valuable organic acids/ bio compounds from an aqueous medium, using a suitable organic extractant/diluent system10-13. It represents a reaction between the solute such as organic acid and the extractant molecules such as high molecular weight aliphatic amine and organophosphoric derivative, at the interface of aqueous and organic phase where transfer of solute molecules takes place by diffusion and solubilzation mechanism14-16.

For the recovery of valuable bio products from fermentation/aq. streams, there is need to optimize suitable parameters for maximum recovery. Response surface methodology (RSM) is an assemblage of mathematical and statistical technique to build empirical model and to optimize processes17. The main target is to optimize the response (output variable), which is influenced by number of independent factors (input variables) and their interactions. It was first described by Box and Wilson18. It is mainly composed of three main steps: 1.Experimental design 2.Response 3



Page 4 of 36

surface modelling 3.Process optimization. However, RSM generally uses an experimental design such as central composite design (CCD), Box- Behnken design (BBD), three level factorial design and Doehlert design19, 20. Rotatable central composite design (rCCD) is the most suitable second order model in the optimization process, as rotatability allows the equality of the variance at a particular location from centre point 21. CCD also allows studying the effect of independent variables and their interactions by performing minimum number of experimental run. The response can be shown graphically either in the form of 3D – surface graph and/or as contour plots 22. Earlier, response surface methodology has been used for the optimization of recovery of different organic compounds like carboxylic acids, esters, phenols etc

23-26

. However, very less

study on iNA has been done till date and no recent literature on optimization of iso -nicotinic acid by reactive extraction method with the help of RSM modeling has been reported. Optimization studies were performed on phenolic extraction of fruit and vegetable such as apple peels, jack fruit and potato peel using CCD, BBD and CCD respectively27-29. Nevertheless, RSM was used in the optimization of recovery process of glycolic acid by applying central composite orthogonal design30. However, lactic acid extraction was performed by using box behnken experimental design by emulsion liquid membrane

31

. A five level 2 factor central composite

rotatable design (CCRD) was used to optimize the reactive extraction of gallic acid by extractant/diluents system32. Similarly, tartaric acid recovery from winery lees and citric acid production from candida lypolytica Y- 1095 was also carried out by using CCD method by varying different parameters33. Very recently in 2017, optimization of α- toluic acid removal by CaO2 nanoparticle was also performed by CCD method34.

4


Page 5 of 36 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Most organic solvents are toxic to microorganisms to some extent. Increased toxicity is associated with increased polarity of the organic solvent. Blending of a slightly toxic solvent (polar) with a non toxic one (inactive higher hydrocarbon) may yield a biocompatible mixture35, 36

. This study aims to optimize the recovery of iso-nicotinic acid from fermentation broth with

tri-n-octylamine (TOA) as extractant37,

38

in less toxic and bio compatible diluent mixture of

dodecane (log Pa = 6.6) and n-decanol as modifier (log Pa = 4.0) in 1:1 v/v. However, the combined use of diluents with polar modifier, positively affect the extraction yield. Nevertheless, with increase in number of carbon chain, toxicity of alcohol and alkane decreases. Hence, the combination of dodecane and n-decanol as diluent system will create a less toxic environment friendly organic phase. In this study, the effect of acid concentration (factor1), TOA concentration (factor 2) and initial pH of aqueous solution (factor 3) on degree of extraction (response) is performed and finally modeling and optimization is performed by RSM. The back extraction or regeneration is also performed from the loaded organic phase of iNA using NaOH solution (stripping agent). Since, little attention has been devoted for the production of isonicotinic acid through fermentation by nitrilases due to higher downstream cost. Hence, research work is going on to find an efficient recovery method to make fermentation route economical viable. Our study may be pointer in this direction.

2. EXPERIMENTAL AND THEORY

2.1.

Materials

Iso- nicotinic acid, Tri-n-octylamine, n- Decanol and Dodecane were used without any further purification. All the aqueous phases were prepared by using Millipore water (Milli -Q Advance 5



Page 6 of 36

A 10 TOC, Flix, Bangalore). pH values (1.32-4.68) of the aqueous solutions were adjusted using reagent grade dilute hydrochloric acid (1N) and sodium hydroxide (1N) solution. The physiochemical properties of the chemicals are shown in Table 1.

Table 1. The physiochemical properties of chemicals used. Reagents

IUPAC

supplier

name iso-

Pyridine-4-

Spectroch

Nicotinic

carboxylic

em,

acid

acid

Mumbai,

Purity

Mol. wt.

Density

Viscosity

(% w)

(kg.kmol-1)

(kg.m-3)

(mPa.s)

99

123.11

1.3

-

95

353.67

809

8.32

(India) Tri-n-

N,N, dioctyl

Spectroch

octylamine

octan-1-

em,

amine

Mumbai,

(296 K)

(India) n- decanol

1-decanol

Spectroch

98

158.28

829.7

em,

12.048 (298 K)

Mumbai, (India) ndodecane

dodecane

Spectroch

99

170.34

em, Mumbai,

6


750

1.40 (293 K)

Page 7 of 36 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(India)

2.2.

Method

The aqueous stock solution of iNA (0.04 kmol.m-3) was prepared by adding weighed isonicotinic acid in Millipore water. Aqueous solution of different concentrations (0.0032-0.0368 kmol.m-3) was prepared by diluting the stock solution. The relative uncertainty in the concentration measurement was found to be within ± 5%. The organic phase was prepared by dissolving different concentrations (0.0458- 1.373 kmol.m-3) of tri-n-octylamine (TOA) in mixture (1:1 v/v) of n-decanol plus dodecane. All extraction experiments were carried out on a constant temperature water bath shaker (Daihan Labtech co.,Ltd) for 6 h at 120 ± 5 rpm. All experiments were performed in 100 ml Erlenmeyer flasks with screw cap by taking equal volumes (20ml) of aqueous and organic phases at temperature 298 ± 1K and pressure 101.325 ± 1kPa for equilibrium. After attaining equilibrium, the mixture of aqueous and organic phase was allowed to settle in a 60 ml separating funnel maintained at that temperature in an incubator, for 120 min to achieve complete separation. The concentration of iso -nicotinic acid (iNA) in aqueous phase was determined using a UV-Vis spectrophotometer, (Agilent Technology) at 261 nm. The concentration in the organic phase was determined by mass balance. pH of the aqueous solution was measured using a pH meter (Eutect Instrument) with the accuracy of 0.01. All experiments were performed twice and their mean value was taken with the accuracy of ± 5%.

Response of extraction i.e. Degree of extraction (%E) for all batch experiments were conducted and calculated by Eq. 1.

7



%E =

Page 8 of 36

C iNA x100 C 0 iNA

(1)

Where, CiNA is the acid concentration in organic phase at equilibrium and C 0 iN A is the initial iNA concentration in aqueous solution. Z=

CiNA [T0 ]in

(2)

Where, [T0 ]in is the initial TOA concentration.

2.3.

Process Variables and Experimental Design

On the basis of their importance in design of extraction process for the recovery of iNA, initial concentration of iNA (C0), extractant (TOA) concentration in the organic phase (T0) and initial pH of the aqueous phase (pH) were identified as set of three independent variables to study their effect on the response variable, recovery of iNA in terms of degree of extraction. A five point, rotatable central composite design (rCCD) was applied for modeling and optimization of the process variables. After determining the upper and lower limits of the process variables, the quantitative values were transformed to their respected coded values in terms of ±1, 0 and ± α as given by Eq. 3

xi =

Xi − X0 ∆X

(3)

8


Page 9 of 36 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


where xi is the (dimensionless) coded value of Xi (uncoded value) , X0 is the value of Xi at the center point, and ∆X is the step change value39. The selected process variables with their limits, units and notations are given in Table 2.

Table 2. Independent variables and their values used for central composite rotatable design. Factors

Code

Levels -1.682

-1

0

1

1.682

Initial iNA conc (kmol.m-3)

XCo

0.003

0.010

0.020

0.030

0.036

Extractant conc. (kmol.m-3)

XTo

0.110

0.343

0.687

1.030

1.259

pH of aqueous solution

XpH

1.32

2

3

4

4.68

For a design of three independent variables (n =3), the total number of experiments (N) was calculated as N= (2n + 2n+ nc) = 23+2*3+ 6 = 20, where n is the number of factor; nc is the centre point of repeat runs. Here, for three variables, α (1.682) could be calculated as Eq. 4.

α = 2(k − p)/4

(4)

Where, k is number of repeatable runs and n is number of factors40.

All the experiments conducted according to the rCCD matrix at random, to avoid the possibility of any systematic errors in measurement are shown in Table 3. Design expert, version 10(stat ease) software is used to analyse all the experimental data. 9



Page 10 of 36

Table 3. Experimental design matrix for rCCD in terms of coded and uncoded values of independent variables along with their responses, degree of extraction (%E)

Run XCo / Initial

XTo /

XpH / pH of

iNA conc

TOA conc

aqueous

(kmol.m-3)

(kmol.m-3)

solution)

%E (degree of extraction)

Predicted

Experimental

1

0(0.02)

0(0.687)

0(3)

87.94

86.28

2

0(0.02)

0(0.687)

0(3)

87.94

84.11

3

0(0.02)

0(0.687)

0(3)

87.94

91.46

4

0(0.02)

0(0.687)

0(3)

87.94

90.36

5

0(0.02

0(0.687)

0(3)

87.94

88.55

6

0(0.02)

0(0.687)

0(3)

87.94

86.92

7

0(0.02)

0(0.687)

1.68179(4.68)

64.28

64.79

8

0(0.02)

-1.68179(0.110)

0(3)

78.82

79.06

9

0(0.02)

1.68179(1.259)

0(3)

83.43

82.94

10

1.68179(0.037)

0(0.687)

0(3)

87.19

88.84

11

0(0.02)

0(0.687)

1.68179(1.32)

88.52

87.76

12

1.68179(0.003)

0(0.687)

0(3)

51.91

50.01

13

1(0.03)

-1(0.343)

1(4)

90.20

87.01

14

-1(0.01)

1(1.030)

-1(2)

86.38

89.75

10


Page 11 of 36 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


15

-1(0.01)

-1(0.343)

1(4)

51.21

53.73

16

1(0.03)

-1(0.343)

-1(2)

83.95

85.51

17

-1(0.01)

1(1.030)

1(4)

51.30

49.91

18

1(0.03)

1(1.030)

1(4)

78.25

79.59

19

-1(0.01)

-1(0.343)

-1(2)

68.95

67.79

20

1(0.03)

1(1.030)

-1(2)

89.35

87

2.4.

RSM Modeling

After the experimental design is completed, the experimental runs are performed according to the design matrix. Data obtained from rCCD were regressed and fitted to following quadratic polynomial equation as shown in Eq. 5.

n

Y = β0 +

∑ i =1

n

n −1

β i X i + ∑ β i i X i2 + ∑ i =1

i =1

n

∑β

ij

XiX j + e

(5)

i =1

Where, Y represents the response function. β 0 is an intercept function, β i is linear coefficients,

βii is quadratic coefficient and β ij is interactive coefficient. Accordingly X i , X j are the coded independent variable and e is the residual error. The response variable, Y (Degree of extraction) of iNA recovery from aqueous solution can be expressed in terms of second order quadratic polynomial equation as shown in Eq. 6.

11



%E = β 0

+

β1 Xc

0

+

β 2 Xc 2 + β 3 XT 0 + β 4 XT 02 + β 5 XpH + β 6 XpH 2 + β 7 Xc XpH + β 8 XT 0 XpH 0

0

Page 12 of 36

+

β 9 XpH Xc

0

(6)

Where, XCo, XTo & XpH are the coded values of process variables (initial iNA in aqueous phase, extractant concentration in organic phase and initial pH of the aqueous solution respectively). The adequacy of the model and statistical analysis were done using ANOVA and t- test statistics. It helps to determine the significance of the model and the process variables. The actual and the predicted values were used to calculate the correlation coefficient (R2), root mean square error in prediction (RMSEP) and relative standard error in prediction (RSEP) as given by Eq. 7 and 8 respectively, were used to the determine the predictability of the model itself.

∑

RMSEP =

(Ypred ,i - Ymeas ,i ) 2 N

N

RSEP =

N i =1

∑

(Y -Y )2 pred , i meas, i X100 N 2 ∑i=1(Ymeas, i )

(7)

i =1

(8)

where, Ypred,i and Ymeas,i represent the model predicted and measured values of the dependent variable (initial iNA concentration, TOA concentration and pH of aqueous solution) and N represents the number of experimental observations.

3. RESULTS AND DISCUSSION

12


Page 13 of 36 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


As mentioned earlier, the selectivity of the solvents for iso-nicotinic acid is also an important parameter in the simultaneous extraction. The efforts have been made to find the optimum conditions for the extraction of iso-nicotinic acid using TOA in biocompatible mixture of 1decanol and n-dodecane (1:1 v/v). Since TOA concentration plays an important role in the extraction efficiency along with the fermentation conditions (pH and aq. phase concentration), these three parameters have been chosen in optimization with significant impact on response, %E. However, RSM modeling is performed by rotatable central composite design (rCCD) based on preliminary experimentation followed by statistical analysis, model fitting, and optimization. Finally solvent regeneration is performed as discussed below.

3.1.

The effect of initial concentration of iNA on degree of extraction (%E)

Different iNA concentrations (0.002, 0.015, 0.02, 0.03 and 0.04 kmol.m-3) are used to investigate the effect of acid concentration on degree of extraction when other two variables are set as follows: TOA conc 0.228 kmol.m-3 and pH value of 3.32 (due to its own iNA concentration). Figure 1 shows that initial extraction of iNA increases with increase in acid concentration upto 0.02 kmol.m-3 and thereafter degree of extraction decreases gradually. Hence, TOA concentration may be the limiting factor at higher concentration of iNA.

13



100 95 Degree of extraction

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

90 85 80 75 70 0.00

0.01

0.02

0.03

0.04

iNA conc (kmol.m-3 )

Figure 1. Effect of initial iNA concentration on degree of extraction.

3.2.

The effect of extractant concentration (TOA) on degree of extraction (% E)

The degree of extraction (% E) is also affected by different TOA concentration (0.046, 0.114, 0.687, 1.053 and 1.373 kmol.m-3), when other two parameters are kept constant i.e. iNA concentration 0.02 kmol.m-3 and pH value of 3.32 as seen in Figure 2. Degree of extraction increases significantly from 62 to 84% when TOA concentration increases from 0.046 to1.373 kmol.m-3. It suggests that 0.687 kmol.m-3 of TOA provides sufficient number of moles for iNA extraction through complex formation. Maximum degree of extraction is obtained at 0.687 kmol.m-3 of TOA concentration and thereafter not much increase in extraction efficiency is observed. However, some decrease in degree of extraction is found to be with increasing TOA concentration beyond 1.373 kmol.m-3. At very high concentration of TOA (60%), an increase in viscosity and density of the solution may leads to less interaction between TOA and acid

14


Page 14 of 36

Page 15 of 36

molecules. Hence, 0.687 kmol.m-3 of TOA concentration is considered to be limiting to obtain maximum degree of extraction.

100

D egree of extraction

90

80

70

60

50 0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

TOA conc (kmol.m-3)

Figure 2. Effect of TOA concentration on degree of extraction.

3.3.

The effect of pH change on degree of extraction (%E)

Different pH value of aqueous solution are used (1, 2.5, 4, 6 and 9) to determine their effect on degree of extraction by keeping iNA concentration fixed at 0.02 kmol.m-3 and TOA concentration at 0.228 kmol.m-3. Figure 3 indicates that degree of extraction is maximum at 2.5 pH and thereafter, extraction of iNA decreases with increase in pH of aqueous solution.

100 90 Degree of extractio n

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


80 70 60 50 40 0

1

2

3

4

5

6

7

8

9

pH

15


10


Figure 3. Effect of initial pH of aqueous solution on degree of extraction.

Based on pKa1and pKa2 value, the cationic form of iNA exists at lower pH (pH< pKa1) while the anionic form appears at higher pH (pH>pKa2) and neutral iNA dominates at an intermediate pH (pKa1

Modeling and Optimization of Reactive Extraction of Isonicotinic Acid

Recommend Documents