Facile Synthesis of Tributyrin Catalyzed by Versatile Sulfated Iron

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Facile Synthesis of Tributyrin Catalyzed by Versatile Sulfated Iron Oxide: Reaction Pathway and Kinetic Evaluation Kamalpreet Kaur, Ravinder Wanchoo, and Amrit Pal Toor Ind. Eng. Chem. Res., Just Accepted Manuscript • DOI: 10.1021/acs.iecr.5b04294 • Publication Date (Web): 11 Feb 2016 Downloaded from http://pubs.acs.org on February 26, 2016

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Industrial & Engineering Chemistry Research

Chemical Reaction Involved in Product Formation 254x190mm (96 x 96 DPI)

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Facile Synthesis of Tributyrin Catalyzed by Versatile Sulfated Iron Oxide: Reaction Pathway and Kinetic Evaluation Kamalpreet Kaur†, Ravinder Kumar Wanchoo†, Amrit Pal Toor†,‡,* †

Dr. S.S.B. University Institute of Chemical Engineering and Technology, Panjab University,

Chandigarh, 160014, India ‡

Energy Research Centre, Panjab University, Chandigarh, 160014, India

Abstract: Tributyrin, the triglyceride ester, exhibit strong properties as inhibitor of cancer cell growth in both humans and animals, which can increase the shelf life of drug. In this paper, tributyrin was synthesized by esterification reaction of butanoic acid with glycerol catalyzed by a low cost; ecofriendly green catalyst sulfated iron oxide. Effect of varying catalyst loading, stirring speed and temperature on initial reaction rate was investigated. Reaction kinetics, adsorption and thermodynamic parameters were determined by evaluating the effect of concentration of butanoic acid, glycerol and water addition on reaction rate. Eley Rideal model using activity coefficients was employed to account non-ideality of system to elucidate the experimental data. A maximal acid conversion of 91.8% was obtained at the temperature of 448.15 K. Activation energy was calculated to be 25.348 kJ/mol. The end product of reaction was characterized by means of thin layer chromatography (TLC), Fourier Transform Infrared Spectroscopy (FT-IR) and gas chromatography with mass spectrometry (GC-MS).

The

formation of mono, di and tributyrin with the selectivity of 2.12, 2.08 and 77.9% at the optimum reaction conditions was verified. Thus, a reaction mechanism on catalyst surface was revealed to describe the apparent reaction pathway to illustrate the formation of reaction products. This research work will pave ways for the improvement in the shelf life of drug in the treatment of cancer. KEYWORDS: Green chemistry, Heterogeneous catalyst, Esters, Tributyrin, Cancer protecting 1. INTRODUCTION The production of huge amount of glycerol from biodiesel industry is a subject of concern, which has also affected the economics of the process.1,2 Nonetheless, glycerol is now progressively more demanded due to its use as a low cost feedstock for synthesis of numerous significant products by miscellaneous catalytic routes. Various processes to produce glycerol value added 1 ACS Paragon Plus Environment

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derivatives involve oxidation, dehydration, esterification, etherification and many more.3 Glyceryl acyl esters are amongst the recognized compounds, which have extensive applications in emulsifier, cosmetic, pharmaceutical, food, fragrance, plasticizer, fuel and various other industries.4-6 Monobutyrin, dibutyrin and tributyrin are the esters produced by esterification of butanoic acid with glycerol. Tributyrin has strong assets as inhibitor of cancer cell growth is also more convincing in inducing cell differentiation than natural butyrate.7,

8

Its utilization over natural

butyrate is more capable to conquer the pharmacokinetic drawbacks of butyrate by increasing the shelf life of drug. The healing of human HCT116 colon cancer cells with the emulsion of free celecoxib plus tributyrin has inhibited the cellular proliferation more efficiently than that of drug alone, proving the tributyrin emulsion as a potential celecoxib carrier to enhance its anticancer efficiency.9 Also, the supplementation of tributyrin enhances intestinal development and the immunity of IUGR piglets by stimulating the expression of GPR41.10 The intake of oral tributyrin increases the plasma butyrate level in portal vein which protects the liver from LPSassociated toxicity, extensive necrosis, cellular infiltration of hepatic lobule and hemorrhage.11 Tributyrin has also shown antitumor properties 12 and is notably used as a base for agar plates for studying lipase activity.13 It has also supplementary utilization as an intermediate in perfume, flavor, cosmetics and emulsifier industries.14 The superior aspects of heterogeneous catalysts over homogeneous have recommended their use in the organic reactions15. A large number of heterogeneous catalysts in esterification of glycerol with acetic acid such as sulfonated carbons from rice husk16, niobium supported SBA-1517, Amberlyst 15, Amberlyst 3518, H3PW12O40 oxide21, carbon based acid catalysts

22

19

, zirconia supported heteropolyacids20, graphene

, K-10 montmorillonite, HZSM-5, HUSY

silver exchanged tungstophosphoric acid

24

23

, niobic acid,

, molybdophosphoric functionalized SBA-15

25

,

yttrium containing SBA-3 26 etc. have been investigated. Although many heterogeneous catalysts has proven to be efficient towards esterification reaction, but, some of them are noticeable owing to the limitation of their high cost, reaction temperature, activation making the process economically unfeasible.27-32 Kinetic models such as Pseudohomogeneous model, Eley Rideal and Langmuir-Hinshelwood Haugan-Watson have been used to evaluate kinetic data. Although there are many studies that comprehensively assesses the esterification reaction of acetic acid with glycerol in literature, but esterification of butanoic acid with glycerol has not 2 ACS Paragon Plus Environment


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been investigated thoroughly. Weatherby in 1925

33

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studied the esterification of glycerol with

excess of butanoic acid in the absence of catalyst for 60 hours. Recently, Zhu et al., 2013

24

,

evaluated silver exchanged phosphotungstic acid catalyst in esterification of glycerol with 1butanoic acid to achieve less selectivity towards tributyrin. So, there is a need to develop a practical method to improve the selectivity of tributyrin due to its significant applications in improving human health. Our research group has recently reported the evaluation of series of sulfated iron oxide catalysts34,

35

in the esterification of butanoic acid with glycerol result an acid conversion of

82.8% with the formation of mono, di and tributyrin along with O-acetylmalic anhydride as a side product. No appropriate investigation on reaction parameters has been carried out to enhance the tributyrin formation. In the present approach, the esterification reaction of butanoic acid with glycerol catalyzed by sulfated iron oxide for tributyrin synthesis was accomplished to obtain kinetic, adsorption and thermodynamic data. The effect of process parameters such as catalyst loading, stirring speed and temperature were investigated to optimize the reaction conditions for maximum acid conversion and tributyrin selectivity. Further, the effect of variation in concentration of butanoic acid, glycerol and water on rate of reaction was evaluated. The kinetic study using the activity coefficients from UNIFAQ group contribution model to account non-ideality was described by Eley-Rideal model. The rate constants, adsorption constants, activation energy, equilibrium constants, Gibbs free energy and heat of formation of tributyrin were also determined. Gas chromatography with mass spectra (GC-MS) was used to know the selectivity of mono, di and tributyrin. 2. EXPERIMENTAL SECTION 2.1. Chemicals and preparation of catalysts. All the A.R. grade chemicals were used. Butanoic acid (purity > 99%), glycerol (purity >99%), and acetophenone (purity >99.5%), were procured from Merck. Sulfated iron oxide was synthesized as reported in our previous research work.34, 35 2.2. Apparatus and Reaction Procedure. The esterification reaction was carried out in 250 mL three necked round bottom glass flask. It is equipped with overhead stirrer having speed controller, thermometer and sampling port. Reflux condenser was connected to one neck to avoid vapor loss of volatile reactants. The temperature was sustained by using an oil bath within the accuracy of ±0.2 °C. Butanoic acid and catalyst were initially charged to reactor & heated to 3 ACS Paragon Plus Environment

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desired temperature of reaction. After achieving the desired temperature, preheated glycerol was charged to reactor which was considered as zero time of reaction. The reaction was preceded for a known time and samples after regular time intervals were withdrawn from reaction mixture and analyzed for the progress of reaction by potentiometric titration and gas chromatography. 2.3. Analysis. During the esterification reactions, the conversion of butanoic acid was calculated by potentiometric titration with 0.2 N standard solution of sodium hydroxide using phenolphthalein as an indicator. The samples were evaluated for progress of reaction by thin layer chromatography (TLC) using a mobile phase of ethyl acetate: hexane on precoated silica gel aluminium plates using iodine as chromogenic agent. FT-IR spectrum of product at different time intervals was recorded with a Perkin Elmer RX I FT-IR spectrometer by Nuzol method to find out the attached functional groups. The quantification of product was made by using Gas chromatography with mass spectrometry fromTrace 1300 GC, TSQ 8000, Triple Quadrupole MS HP (Thermofisher scientific, USA) (GC(MS)_SCION45P) using capillary column. Helium with flow rate of 0.7 mL/min was used as a carrier gas. 1 µL of sample was dissolved in 10 mL of acetone. The oven temperature was sustained at 60°C for the period of 3 min and then increased at 60°C/min to 120°C, which was maintained for further 3 min. After achieving this, oven temperature was increased at 80°C/min to 200°C for the time of 7 min. Before being reduced to 60°C for the injection of next sample, the oven temperature was increased to 250°C and maintained for next 2 min to restart the column. 3. RESULTS AND DISCUSSION 3.1. Effect of catalyst loading. Various heterogeneous catalysts have been evaluated for their catalytic performances in catalyzing esterification of butanoic acid with glycerol at the temperature of 368.15 K as reported in our previous research work.34 Based on that observation, sulfated iron oxide was selected as the most suitable catalyst for evaluating reaction parameters due to its high activity and adequate superacidity, high surface area and high efficiency to work at low temperatures.34-36 Catalyst loading plays an important role in conversion of acid in reaction. Preliminary experiments were done at 388.15 K to examine the effect of catalyst loading within range of 5.0 to 20.0 g/L (weight of catalyst to total volume of reaction mixture) at RPM of 500 and molar feed ratio of 3:1 (butanoic acid: glycerol). Figure 1 illustrates the effect of catalyst loading over initial rate of reaction after the reaction time of 360 min. It could be seen from figure 1 that with increase in catalyst loading from 5.0 to 12.0 g/L, the initial rate of 4 ACS Paragon Plus Environment


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reaction has also increased. This increase in catalyst loading has increased the availability of active sites in the reaction, which further increased the rate to achieve reaction equilibrium more rapidly. It was also explored that with further increase in catalyst loading from 12.0 to 15.0 g/L, the rate of reaction has reached near stationary state, tending to equilibrium conversion. However, further increase in the catalyst loading to 20.0 g/L has resulted in the decrease of reaction rate. Hence, the optimum catalyst loading for further reactions was found to be at 12.0 g/L. 0.4 0.35 0.3 0.25 -rAo (mol/L.h) 0.2 0.15 0.1 0.05 0 0

5

10 15 20 Catalyst loading (g/L)

25

Figure 1. Effect of different catalyst loadings on initial reaction rate at molar ratio of 3:1 (butanoic acid: glycerol), stirring speed of 500 RPM; temperature of 388.15 K and reaction time of 6 hours. 3.2. Effect of external mass transfer resistances. It is obligatory to evaluate the influence of external mass transfer resistances in the reaction to achieve kinetic study of reaction. So, experiments were conducted at varied stirring speeds within the range of 200 to 600 rpm. The reactions were performed with the molar ratio of 3:1 (butanoic acid: glycerol), catalyst loading of 12.0 g/L at the temperature of 388.15 K. The effect of varied stirring speeds on initial rate of reaction is presented in figure 2. It was observed that there was noteworthy increase in rate of reaction when speed was increased from 200 to 500 rpm and became constant afterwards, specifying the absence of mass transfer limitations.

Therefore, further experiments were

conducted at the optimized stirring speed of 500 rpm to neglect the external mass transfer limitations. 5 ACS Paragon Plus Environment

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0.4 0.35 0.3 0.25 -rAo 0.2 (mol/L.h) 0.15 0.1 0.05 0 0

200 400 600 Stirring speed (RPM)

800

Figure 2. Effect of different stirring speeds) on initial reaction rate; molar ratio of 3:1 (butanoic acid: glycerol), catalyst loading: 12.0 g/L; temperature of 388.15 K and reaction time of 6 hours. 3.3. Effect of reaction temperature and time. The end product obtained from esterification of butanoic acid with glycerol at different reaction temperatures and time was characterized by means of TLC, FT-IR and GC-MS. 3.3.1. TLC of reaction product. TLC was performed on the reaction product obtained after 2 h and 6 h from the esterification reaction done at the temperature of 448.15 K. Sample obtained after the reaction time of 2 h has revealed the formation of large quantity of mono and dibutyrin along with less quantity of tributyrin as shown in figure 3 (a). But after the reaction time of 6 h, mono and dibutyrin get converted to tributyrin, so, its bulky spot was detected but mono and dibutyrin were not identified due to their very less amount as shown in figure 3(b). Retention factor Rf for tributyrin was found to be 0.9.37 Also, O-acetylmalic anhydride was not detected using TLC.

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(b)

(a)

Tributyrin

Rf= 0.9

Dibutyrin

Monobutyrin

Spot of product

Figure 3. Thin Layer Chromatography of product obtained after (a) 2 h and (b) 6 h of esterification reaction of butanoic acid with glycerol. 3.3.2. FT-IR of end product. The formation of tributyrin with reaction time for the esterification reaction of butanoic acid with glycerol has been studied by FT-IR spectroscopy. Analysis of samples at zero time (0 h) followed by 1 h, 2 h, 4 h and 6 h was done to examine the progress of tributyrin formation. FT-IR analysis shows the presence of

as indicated by

the peak at 3200 to 3550 cm-1. The C=O and -CH2- acyclic sym. stretching vibration appears in the region of 2900-3000 cm-1. The acyclic

groups appear at 2877.65 cm-1. At the

wavenumber of 1459.08 cm-1 deformation vibration appears due to –O-CH2-. Further,

R-CH3

(-CH deformation vibration) and C-O-C stretching vibration appears at 1383.64 and 1267 cm-1. The wavenumber 1095 cm-1, 1040 to 1050 cm-1, 865 to 930 cm-1, 830 to 850 cm-1, 625 to 635 cm-1 and 560 to 605 cm-1 corresponds to butyrate ester. Whereas, the O-H stretch and C-H stretch is present at 2965 cm-1 along with C=O stretch, O-H bend and C-O stretching near 1721, 1419 and 1296 respectively for butanoic acid and glycerol. With increase in reaction time, the enhancement in

group proves the increase in amount of tributyrin as shown in figure 4.

However, conducting TLC and FT-IR studies were not able to clearly detect and quantify all


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compounds present in mixture. So, reaction product was characterized by GC-MS at varying reaction temperatures and reaction time to clarify the formed products.

Figure 4. FTIR of the product obtained at regular intervals from 0 to 6 h of esterification reaction. 3.3.3. GC-MS of end product. The effect of reaction time on both conversion and selectivity of mono, di and tributyrin was investigated in the range of 4 to 8 hours using GC-MS. The ester selectivity with reaction time is shown in figure 5 (a). With increase in time, monobutyrin get converted to dibutyrin and it further converted to tributyrin, providing its maximum selectivity of 77.9% after 6 h of the reaction time at the temperature of 448.15 K. Initially, the acid conversion has increased rapidly, but after attaining the equilibrium after the reaction time of 6 h, the conversion became constant. This may be due to the nucleophilic attack of remaining –OH groups from glycerol on acid site-butanoic acid complex which lead to consumption of entire moieties with increase in reaction time.38



The effect of reaction temperature on conversion and selectivity of mono, di and tributyrin was also studied. The conversion has increased with increase in reaction temperature along with increase in the selectivity of tributyrin. Although, a decrease in the selectivity of monobutyrin, dibutyrin and O-acetylmalic anhydride was observed with increase in temperature as shown in figure 5 (b). It can be explained since in this esterification reaction, tributyrin is formed, and get converted from monobutyrin, dibutyrin and O-acetylmalic anhydride at higher temperatures. MB TB conversion

DB OAA 92.5

80

92

70

91.5

60

91

50

90.5

40

90

30

89.5

20

89

10

88.5

0

% Conversion

90

% Selectivity

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88 4

5 6 7 Reaction time (h)

8

Figure 5(a) Percentage Conversion and Selectivity of products with reaction time at the temperature of 448.15 K, Molar ratio (Glycerol: Butanoic acid) of 2; catalyst loading of 12 g/L and RPM of 500; (MB-Monobutyrin, DB-Dibutyrin, TB-Tributyrin and OAA-O-Acetylmalic anhydride). The effect of glycerol to butanoic acid molar ratio on both conversion and selectivity of mono, di and tributyrin was also studied. Both the conversion and selectivity of tributyrin has increased with increase in molar ratio whereas the amount of O-acetylmalic anhydride was found to be decreasing as shown in figure 5 (c). The stability of excess O-acetylmalic anhydride resists the further transformation of tributyrin from mono and dibutyrin at low molar ratios. However with incorporation of additional glycerol, O-acetylmalic anhydride reacts to transform into tributyrin leading to increased selectivity of tributyrin.


MB

DB

TB

70

100 90

% Selectivity

60

80

50

70

40

60 50

30

40

20

30 20

10

10

0

0 388

408 428 Temperature (K)

448

Figure 5(b) Percentage Conversion and Selectivity of products at different reaction temperatures after the reaction time of 6 h; Molar ratio (Glycerol: Butanoic acid) of 2; catalyst loading of 12 g/L and RPM of 500; (MB-Monobutyrin, DB-Dibutyrin, TB-Tributyrin and OAA-OAcetylmalic anhydride).

MB

DB

TB

OAA

80

95

70

90

60 85

50 40

80

30

75

20

% Conversion

% Selectivity

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% Conversion

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70

10 0

65 1 1.32 1.64 2 Molar ratio (Glycerol: 3Butanoic acid)

Figure 5(c) Percentage Conversion and Selectivity of products with molar ratio at the temperature of 448.15 K, reaction time of 6 h; catalyst loading of 12 g/L and RPM of 500; (MBMonobutyrin, DB-Dibutyrin, TB-Tributyrin and OAA-O-Acetylmalic anhydride).



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3.4. Reaction Mechanism. It is found that glycerol get adsorbed on active acid sites i.e. Fe3+ which lead to the activation of glycerol. An intermediate through coordination bond of glycerol oxygen with active acid site of catalyst get formed. Similarly, the carboxylic group of acid gets activated by active sites of catalyst by forming a coordination bond as shown in figure 6 (a). The glyceryl nucleophile then attacks on carbon from carbonyl group which results into the formation of monobutyrin, water and monobutyrin intermediate on catalyst surface. The glyceryl nucleophile of intermediate further attacks on carbonyl group from acid to form dibutyrin along with water and dibutyrin intermediate on catalyst surface. The nucleophile from dibutyrin intermediate again attacks on carbonyl group from acid to form tributyrin along with water and side product i.e. O-acetylmalic anhydride as shown in figure 6 (b). In figures,

represents

carbon atom,

represents

oxygen atom and

represents hydrogen atom,

represents iron atom,

represents sulfur atom.

Figure 6 (a) Formation of intermediates of glycerol and butanoic acid on catalyst surface


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Figure 6 (b) Reaction mechanism of esterification of butanoic acid with glycerol 3.5. Kinetic study. Kinetics of esterification reaction catalyzed by heterogeneous catalyst is not as easy as homogenous catalyst because of the surface conditions. Depending on the reaction mechanism and rate determining step, various kinetics models such as Pseudohomogeneous (PH) 39

, Eley-Rideal (ER)

40

and Langmuir-Hinshelwood Haugan-Watson (LHHW)

41

can be used to

represent esterification reactions. PH model does not involve the adsorption and desorption of all the components, whereas, ER is based on the postulation that reaction takes place between an adsorbed reactant molecule and a non adsorbed molecule, depending on which of the two reactants is adsorbed. LHHW model assumes the adsorption of all the components on catalyst surface. General kinetic expression used for all of the three models is as following: -

(2)

Here, ri is rate of reaction in terms of concentration of ith component, CA, CB, CE and CW represents the concentration of acid, alcohol, ester and water respectively, wcat is catalyst loading



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in g/L, k is rate constant, Ke is equilibrium reaction rate constant and KA, KB, KE and KW is adsorption constant for acid, alcohol, ester and water respectively, n is 0, 1 and 2 for PH, ER and LHHW model. Activity based kinetics models are best fitted for esterification reactions to account the liquid mixture’s non-ideal behavior. So, the widely used UNIFAC method has been used to explain its non-ideality to describe the interaction forces between different components participating in the reaction.42 Therefore, the real behavior of a liquid system has to be considered and concentration can be defined in the terms of activity to specify its departure from the ideality while estimating the rate equation. So, equation 2 is represented in the form of activity of all the components by

replacing = , where, is the activity, is the activity coefficient and is the

mole fraction, is the concentration of ith component and is the concentration of total reaction mixture. Consequently, equation 2 in the terms of activity is written as follows: " # #

-!

# # # #

(3)

Where, ! , % , & and ' is the activity of acid, alcohol, ester and water respectively and () ( * / ! % is forward reaction rate constant. Activity coefficients of all the components were calculated using the group contribution method of UNIFAC (universal functional activity coefficients) as follows: ln ln + ln / where, ln is the combinatorial part which is based on the differences of size and shape of the functional groups and ln / is known as residual part which accounts the energetic interactions between different functional groups.40, 43 In this method, the volume and surface area of the molecules are explained by their relative van der waals values of r and q (Supplementary Table 1). 3.5.1. Calculation of Adsorption and rate constant. Esterification reaction of butanoic acid with glycerol is well recognized to be endothermic in nature. In order to predict the effect of adsorption of butanoic acid, glycerol and water on kinetics of reaction, set of experiments were done with their varying concentrations at different temperatures. As, increase in temperature endorse the conversion along with the advantage of shorter reaction time, so, the effect of temperature was studied within the range of 388.15 to 448.15 K. Concentrations of reaction mixture was maintained constant using acetophenone as entrainer. As discussed earlier, 13 ACS Paragon Plus Environment

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concentration is accounted here in terms of activity to express the non-ideality of reaction mixture. The effect of activity of acid (aAo), alcohol (aBo) and water (aWo) on initial rate of reaction rAo was studied. The adsorption effect of butanoic acid on initial rate of reaction was observed to be not that significant, confirming its non considerable importance. While, with increase in activity of glycerol initial rate of reaction has increased, verifying its non-linear behavior. The effect of activity of water on initial rate of reaction was observed to be declining with increasing activity of water. This proves the inhibiting effect of addition of water deriving the equilibrium in backward reaction as it promotes ester hydrolysis.

28, 40, 42-44

(S. Figure 1-3).

Since activity of alcohol and water has shown the non-linear behavior to initial rate of reaction, so, they both have attributed to preferential adsorption effect. The adsorption of ester and entrainer (acetophenone) was reported to be negligible. This favors the Eley-Rideal model approach and its reaction rate expression neglecting the adsorption of butanoic acid and tributyrin (ester) is written as follows: −!

" # #

(4)

# #

where () is rate constant of forward reaction in L2/(g. mol. h), 12# is catalyst loading in g/L and 34 is equilibrium constant. After rearranging the above and plotting between slope of

"

and intersection of

"

# ,5 # ,5 6 ,5

and %,7 gives a straight line with the

for four different temperatures. 28, 40, 42-44 It is also

important to investigate the hydrophobic or hydrophilic nature of solid acid catalyst surface, which may affect the rate of reaction. It was determined by the following equation, as no ester in starting of reaction: # ,5 # ,5

−!,7 "

(5)

# ,5 #,5

A plot between slope of

"

# ,5 # ,5 6 ,5

and ',7 at constant acid activity !,7 and alcohol activity %,7 gives the

and intersection of

# ,5 "

(S. Figure 4, 5).

28, 40, 42-44

The values of kf, KB and

KW were calculated from the slopes and intercepts obtained from the above equation for four different temperatures using ‘The Method of Averages’ are summarized in Table 1.



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As calculated by Eley Rideal model, adsorption of glycerol and water was observed to decrease with increase in temperature, whereas, forward rate constant was found to increase. Table 1. Values of kf, KB and KW at different temperatures Temp (K)

kf (L2g-1mol-1h-1)

KB (mol-1L)

KW (mol-1L)

388.15

0.080

1.45

4.09

408.15

0.120

1.39

3.95

428.15

0.189

1.34

3.70

448.15

0.220

1.30

3.41

3.5.2. Calculation of Activation energy. The effect of temperature on reaction rate constant was evaluated by using an Arrhenius temperature dependency: &

k = ( 8 exp (

/9

)

(6)

Where k is forward reaction rate, EA is activation energy and ( 8 is frequency factor. The linear regression fitting results were good giving the coefficient of determination R2=0.976. The activation energy was calculated to be 25.348 kJ/mol and pre-exponential factor ()8 is 2.122 x 102 L2 g−1 mol−1 h−1 from figure 7 (a). The activation energy is reported to be 21.54 kJ/mol for the esterification of acetic acid with glycerol in literature

26

, which is found to be in good

agreement with our results. The enthalpy of adsorption was observed to be negative i.e. -2636.53 and -4382.72 J/mol for glycerol and water as shown in figure 7 (b). 1/T 0 0.0022 -0.5

0.0023

0.0024

0.0025

-1

(a) ln kf -1.5 -2 -2.5 -3


0.0026

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2 1.5

(b) ln K

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1

Kb Kw

0.5 0 0.0021

0.0023

0.0025

0.0027

1/T

Figure 7. Plot of kf, KB and KW between 1/T at the catalyst loading of 12.0 g/L, RPM of 500. The equations for kf, KB and KW to correlate with temperature are written as follows: k ; exp 5.3585 − 3% exp

CI.* /9

3' exp

(7)

− 0.4469

(8)

N*I.N /9

C8DE.F GH

− 0.0647

(9)

3.5.3. Calculation of Equilibrium constant, enthalpy and entropy. In order to investigate the effect of backward reaction, it is necessary to calculate the equilibrium constant Keq by following equation: Keq = P

Q P CRP

(10)

where S!4 is fractional conversion at equilibrium and M =C 5 . 5

The temperature dependency of equilibrium constant was also determined by following equation: ln Keq =

∆U6 /9

+

∆V

(11)

/

Where, ∆Hr is enthalpy of reaction and ∆S is entropy. Plot of ln Keq and inverse of temperature is shown in figure 8. It is observed that equilibrium constants have increased with increase in temperature because of endothermic nature of reaction.



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3 2.5 2 ln Keq 1.5 1 0.5 0 0.0021 0.0022 0.0023 0.0024 0.0025 0.0026 0.0027 1/T

Figure 8. Plot between equilibrium constants versus inverse of temperatures The relationship between lnKeq and 1/T obtained from above figure is shown by following equation: ln Keq =

CFDD 9

+ 11.311

(12)

The results reflect the thermodynamic character of reaction in which Gibbs free energy for formation of tributyrin was calculated at varying temperature. The values of ∆Hr and ∆Sr are found to be 32.790 kJ/mol and 0.0940 kJ/mol. The values of ∆Gr at different temperatures were calculated and are presented in table 2. Table 2. Values of Gibbs free energy ∆Gr for esterification reaction Temperature (K)

∆Gr (kJ/mol)

388.15

-3.6961

408.15

-5.5761

428.15

-7.4561

448.15

-9.3361

∆Hr (kJ/mol)

∆Sr (kJ/mol)

32.790

0.0940

The negative value of ∆G explains the reason for spontaneity and the higher selectivity towards the tributyrin and is in good agreement with the literature.26 3.5.4. Determination of Heat of formation of Tributyrin. The heat of formation of tributyrin can be calculated from standard heat of formation using following equation: ∆X6 ∑Z67[\2 ] ∆X) − ∑64#2

#^ ] ∆X)


(13)

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The standard heat of formation of all the components is listed in Table 3. Table 3. Standard heat of formation of components Component

Butanoic acid

Glycerol

Water

kJ/mol

-533.92

-669.6

-242.00

The heat of this reaction is found as ∆X6 = 32.790 kJ/mol. The standard heat of formation of tributyrin was determined to be -928.73 kJ/mol from the available data.

4. CONCLUSIONS The potential use of sulfated iron oxide to enhance the selectivity of tributyrin with anti-cancer properties in esterification of butanoic acid with glycerol was established. The results showed the optimum stirring speed and catalyst loading was 500 RPM and 12.0 g/L for maximum acid conversion of 91.8% using molar ratio of glycerol to butanoic acid of 2, at the temperature of 448.15 K for the reaction time of 6 hours. The formation of mono, di and tributyrin was verified by conducting TLC, FT-IR and GC-MS. It can be concluded that TLC and FT-IR were not able to detect all the products in obscure mixture. So, GC-MS was used to confirm the maximum tributyrin selectivity of 77.9% at the reaction temperature of 448.15 K in the reaction time of 6 h. Tributyrin selectivity was observed to be increased with increase in temperature but no large change was observed after the reaction time of 6 h. A reaction mechanism for elaborating the pathway of formation of products was proposed. The non-ideality of reaction mixture was represented in terms of activity to explain the kinetics using rate expressions from Eley Rideal model. A decrease in adsorption constants of glycerol (KB) and water (KW) was observed with increase in temperature. However, rate constant (kf) has increased with increase in reaction temperature. Activation energy was calculated to be 25.348 kJ/mol. The negative value of ∆G explains the reason for spontaneity and the higher selectivity towards the tributyrin. This study will provide the conduit in formation of significant products using highly substituted species.

AUTHOR INFORMATION Corresponding Author

* Amrit Pal Toor, E-mail: [email protected]

ACKNOWLEDGEMENTS 18 ACS Paragon Plus Environment


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Ms. Kamalpreet Kaur acknowledges UGC-MANF (Government of India) for providing scholarship for her research work and Energy Research Centre (ERC) for providing the facilities for carrying out the research work. We also acknowledge DST-PURSE and TEQIP-II grant for providing chemicals and analysis.

SUPPLIMENTARY INFORMATION Figures regarding adsorption of butanoic acid, glycerol and water are shown in supplementary information. This material is available free of charge via the Internet at http://pubs.acs.org.

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Facile Synthesis of Tributyrin Catalyzed by Versatile Sulfated Iron

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