Research Article pubs.acs.org/journal/ascecg
Elementary Transformation of Glycerol to Trivalerin: Design of an Experimental Approach Kamalpreet Kaur,† Ravinder Kumar Wanchoo,† and Amrit Pal Toor*,†,‡ Dr. S. S. Bhatnagar University Institute of Chemical Engineering and Technology and ‡Energy Research Centre, Panjab University, Chandigarh 160014, India
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ABSTRACT: A novel synthesis of trivalerin was accomplished from esterification of glycerol with valeric acid over sulfated iron oxide, a green catalyst. Trivalerin is a valuable compound, extensively acknowledged for its significance as an enzymatic substrate. It is an excellent coalescing and glycogenic agent. Moreover, it acts as an appropriate building block in the production of noteworthy pharmaceutical intermediates. A recent study has reported that trivalerin reduces the extent of Salmonella enteritidis colonization in chickens. This work scrutinizes trivalerin synthesis through single-step glycerol esterification. The effect on significant reaction parameters of trivalerin formation was explored by employing a response surface methodology at two factors and three levels with one central point in the central composite design. The catalyst revealed a maximal acid conversion of 85.5% at a reaction temperature of 453.15 K and a glycerol:valeric acid molar ratio of 5:3. The highest trivalerin selectivity of 74.89% was achieved at a 1:3 molar ratio (glycerol:valeric acid) after 6 h using a catalyst loading of 13.0 g/L. Rate constants were estimated at different temperatures with an activation energy of 26.7 kJ/mol using a pseudohomogeneous model. This simple, novel, and convenient methodology resulted in greater product selectivity that can contribute to synthetic utility. KEYWORDS: Esterification, Glycerol, Sulfated iron oxide, Response surface methodology, Trivalerin
1. INTRODUCTION Glyceryl esters have attracted a great deal of attention because of their noteworthy applications. Instead of copious research of glycerol esterification by several researchers, glyceryl esters of high-chain carboxylic acids still must be elucidated because of their new potential significance. Monoacetin, diacetin, and triacetin are the glyceryl esters from acetylation of glycerol, wellknown for their use as cryogenics and fuel additives has been widely investigated by many research groups.1−7 Tributyrin is the glyceryl ester of butanoic acid, which has anticancer properties and is more potent than natural butyrate.6,7 Esterification of valeric acid with glycerol produces mono-, di-, and trivalerin that found uses in food, resin, and coating industries and also as a surfactant and plasticizer. In addition to the mentioned applications, the chief use of trivalerin is as an enzymatic substrate to check lipase activity for various materials on a large industrial scale. It has also proven to be a good glycogenic agent.8,9 Moreover, its chemical reactivity makes it an appropriate building block in the production of noteworthy pharmaceutical intermediates. Because of its superior compatibility with waterborne polymer dispersion mixtures, trivalerin assists in improving film formation properties that results in the compounds being excellent coalescing agents in paints, adhesives, and sealants.10 In a recent study, both monobutyrin and trivalerin have proven to reduce the extent of Salmonella enteritidis colonization when they are are used as feed additives for chickens.11 © 2016 American Chemical Society
Glycerol obtained from the biodiesel industry in surplus can be converted to valuable compounds through esterification, etherification, oxidation, dehydration, etc.12,13 Glycerol is a triol and has three hydroxyl groups that can be functionalized to give mono-, di-, and triacyl glycerol esters during esterification in the presence of an appropriate catalyst. Heterogeneous catalysts, especially ion exchange resins, eliminate the drawbacks offered by homogeneous biocatalysts and are widely used in organic synthesis.14−16 Sulfated metal oxides are some of the competent catalysts among other solid acid catalysts. Their high acidity, low cost, large surface area, and use of low catalyst loading to achieve the desired results in the organic reactions have proven them to be efficient. Many researchers have investigated various sulfated metal oxides, i.e., sulfated tin oxide, sulfated zinc oxide, sulfated iron oxide, sulfated copper oxide, their mixed oxides, etc., in different organic reactions.6,7,17−19 Today, a response surface methodology (RSM) has become a popular tool for optimizing experiments that have multiple factors to achieve desirable responses. Along with providing a large amount of information from minimal data, this process also elucidates the interaction between various parameters.20 RSM provides the advantage of averting the excess use of expensive chemicals, which further reduces environmental pollution along Received: September 5, 2016 Revised: November 3, 2016 Published: November 19, 2016 802
DOI: 10.1021/acssuschemeng.6b02133 ACS Sustainable Chem. Eng. 2017, 5, 802−808
Research Article
ACS Sustainable Chemistry & Engineering with overall economics. Because of the advantages of its easy handling and high efficiency, facilitating simultaneous optimization of multiple factors, RSM is broadly used to resolve analytical problems. One must be careful while selecting the initial parameters as inadequate selection of factors could result in poor convergence.21 Therefore, in this work, we have employed RSM to optimize various process parameters, i.e., temperature, molar ratio, and selectivity of formed esters, from esterification of valeric acid with glycerol. Therefore, in this study, the esterification of valeric acid with glycerol was explored using sulfated iron oxide as a catalyst. The catalyst loading and stirring speed were initially optimized for maximal acid conversion. In addition, RSM of Design Expert 9 was used to optimize the effect of the molar ratio and temperature in terms of the selectivity of mono-, di-, and trivalerin. Kinetic studies were performed using a pseudohomogeneous model to evaluate rate constants and activation energies for the system.
selectivity toward mono-, di-, and trivalerin and n-amyl isovalerate were chosen as the responses of interest. The numbers −1, 0, and +1 represent the values at low, middle, and high levels, respectively. A total of nine experiments were conducted in an arbitrary way as determined by Design Expert 9 to reduce the overall inaccuracy. The center point was used to explain the effect of an individual reaction parameter, i.e., glycerol:valeric acid molar ratio of 3:3 and temperature of 415.65 K. Response plots were assessed to predict the interaction effects among all the variables. Analysis of variance (ANOVA) was used to check the adequacy of each factor for the response. To test the fitness of the experimental model, a Fisher F test in the form of an F value was performed. Generally, the calculated F value was greater than the F value obtained from the standard distribution table, indicating that the model could not only fit the experimental data but also predict the results properly. The P value test was also employed to explain the significance of these parameters for the response. The smallest P value corresponded to the most significant effect on the response. A P value of 0.05 meant the effect is significant at the 95.0% confidence interval.
2. EXPERIMENTAL SECTION
3. RESULTS AND DISCUSSION 3.1. Optimization of Catalyst Loading and Stirring Speed. The esterification of glycerol with valeric acid is a combination of successive reactions forming mono-, di-, and trivalerin as product esters as shown in the following reactions:
2.1. Materials and Methods. Valeric acid (>99%) and glycerol (>99%) AR were supplied by Loba Chemie, Ltd. Iron(III) oxide and ammonium sulfate were purchased from Merck (Mumbai, India). Sulfated iron oxide was prepared via a procedure we described previously.6,7,18 2.2. Reaction Procedure and Analysis. The model esterification reaction is that of glycerol with valeric acid catalyzed by sulfated iron oxide. Esterification reactions were performed in a 250 mL three-neck flask that was equipped with a reflux condenser, a thermometer, and a sampling port. The catalyst and valeric acid were heated at the desired temperature. Glycerol heated at the same temperature was added and mixed constantly with the reaction mixture using a magnetic stirrer. This time was noted as the start of the reaction. The reactions were performed under the reaction conditions obtained from the RSM optimization design. Initially, the catalyst loading (7.5−15.0 g/L) and stirring speed (200−600 rpm) were optimized at the reaction temperature of 388.15 K with a glycerol:valeric acid molar ratio of 1:3. Under the optimized catalyst loading and stirring speed conditions, the temperature and molar ratio of RSM-designed reaction conditions were optimized. The glycerol:valeric acid molar ratio varied from 1:3 to 5:3 and the temperature from 378.15 to 453.15 K. The acid conversion was calculated by performing the potentiometric titration of the sample obtained from the reaction mixture with a standard solution of 0.2 N NaOH. The confirmation and quantification of esters were achieved by gas chromatography with mass spectrometry (GC−MS) [triplequadrupole MS with HP Trace 1300 GC, GC(MS)-SCION45P, TSQ 8000, Thermo Fisher Scientific] using a capillary column. 2.3. Experimental Design by RSM. From a detailed literature review, the catalyst loading, stirring speed, molar ratio, and reaction temperature were determined to be the important reaction parameters that affect both the acid conversion and selectivity of mono-, di-, and trivalerin. Under the optimized catalyst loading and stirring speed conditions, RSM in combination with a two-factor, three-level face central composite design (CCD) was employed to optimize the most influential factors, i.e., molar ratio and reaction temperature, as shown in Table 1. CCD was used to reduce the number of experiments to optimize multiple experimental conditions. Two independent variables were applied to design the experiments using Design Expert 9, i.e., molar ratio (X1) and reaction temperature (X2). Acid conversion and
glycerol + valeric acid ↔ monovalerin + water
monovalerin + valeric acid ↔ divalerin + water divalerin + valeric acid ↔ trivalerin + water
Different catalysts were compared to explore sulfated iron oxide as a preeminent catalyst among all the other catalysts, which was also explored in our previous work.6,7,18 Therefore, sulfated iron oxide was used in further esterification reactions. An appropriate measure of catalyst accelerates a reaction and helps in rapidly achieving equilibrium for reversible organic reactions. Therefore, to study the effect of catalyst loading of sulfated iron oxide in the esterification reaction, we performed experiments in the catalyst loading range of 7.5−15.0 g/L. It can be seen from Figure 1 that an increase in catalyst loading from 7.5 to 13.0 g/L resulted in an enhancement in acid conversion from 42.42 to 58.42% at 388.15 K. This is due to the increase in the total number of existing active sites, which might effectively drive the esterification reaction to completion. However, with a further
Table 1. Levels of Selected Factors for the Experimental Design of Esterification of Valeric Acid with Glycerol Using Sulfated Iron Oxide factor
level −1
level 0
level +1
glycerol:valeric acid molar ratio temperature (K)
1:3 378.15
3:3 415.65
5:3 453.15
Figure 1. Fractional conversion vs catalyst loading at a reaction temperature of 388.15 K, a glycerol:valeric acid molar ratio of 1:3, and 500 rpm after a reaction time of 6 h. 803
DOI: 10.1021/acssuschemeng.6b02133 ACS Sustainable Chem. Eng. 2017, 5, 802−808
Research Article
ACS Sustainable Chemistry & Engineering Table 2. Experimental Results and Response Values for Esterification Reactions after a Reaction Time of 6 h run
glycerol:valeric acid molar ratio
temperature (K)
fractional conversion
selectivity of monovalerin (%)
selectivity of divalerin (%)
selectivity of trivalerin (%)
selectivity of n-amyl isovalerate (%)
1 2 3 4 5 6 7 8 9
1 (1:3) 5 (5:3) 1 (1:3) 5 (5:3) 3 (3:3) 3 (3:3) 3 (3:3) 1 (1:3) 5 (5:3)
378.15 415.65 453.15 453.15 453.15 378.15 415.65 415.65 378.15
0.560 0.731 0.695 0.855 0.756 0.601 0.673 0.625 0.642
3.80 8.25 0.60 0.73 0.70 9.27 6.50 1.40 15.9
2.89 1.06 1.56 1.05 1.40 1.63 1.57 2.10 1.07
61.47 57.77 74.89 66.32 69.51 58.99 62.60 71.92 48.00
31.84 32.92 23.00 31.90 27.39 33.11 29.33 24.58 35.03
acid and process variables can be represented by the following quadratic equation (eq 1):
increase in catalyst loading to 15.0 g/L, no significant increase in conversion was observed. Therefore, optimized catalyst loading of 13.0 g/L has been used in subsequent reactions. Furthermore, external mass transfer also plays a crucial role in restricting the reaction rate in heterogeneously catalyzed systems. In an attempt to explore the effect of stirring speed, esterification reactions were performed in the range of 200−600 rpm. Conversion increased from 42.0 to 58.4% with an increase in stirring speed from 200 to 500 rpm at a catalyst loading of 13.0 g/L with a reaction time of 6 h. This may be due to the proper mixing of the reaction mixture, which enhances the exchange of functional groups for product formation. No comprehensible difference in the estimation of conversion using a stirrer speed of >500 rpm was found, which was selected as optimal for further experimentation without limitation of mass transfer. 3.2. RSM Design. With the stirring speed and catalyst loading fixed at values at which no external mass transfer limitations were witnessed, a series of kinetic runs were generated and completed using response surface model (RSM) design. To verify the obtained model from RSM, nine runs were performed and the responses listed in Table 2 were recorded. The regression coefficient (R2) gives the consistency between actual and predicted data, which is found to be 0.986. This confirms that the applied model is adequate to cover the variations of around 98%, whereas 2% of variations do not fit the model as shown in Figure 2. The relationship between the fractional conversion of
FC = 0.68 + 0.058A + 0.084B + 0.020AB
(1)
where A is the glycerol:valeric acid molar ratio and B is the reaction temperature. Values from ANOVA were also considered to evaluate the accuracy of the model. An F value of 222.37 and a P value of
