Synthesis and optimization of 2,5-dihydroxyterephthalic acid in a slurry reactor

doi:10.21203/rs.3.rs-4098414/v1

2,5-dihydroxyterephthalic acid (DHTA) is synthesized under 10 bar pressure and 200°C temperature. Using a slurry reactor, disodium salt of hydroquinone (DSH) is contacted by carbon dioxide gas in presence of sodium acetate as catalyst. A fractional factorial design is used to screen four parameters including reactor pressure, temperature, catalyst to DSH molar ratio, and reaction time. By performing 8 experiments in the screening phase the variables ranges are modified to 175–200°C for temperature, 1.5–2.5 for catalyst to DSH molar ratio, and 3–5 hours for reaction time. Additionally, pressure is kept fixed at 10 bar throughout the remaining experiments. An additional 14 more experiments devised by Box-Behnken design scheme are performed to determine a quadratic model for the DHTA yield against the three parameters mentioned above. A mathematical optimization of the model predicts 83.385% DHTA yield at 200°C, 2.085, and 250 minutes for temperature, catalyst to DSH molar ratio, and reaction time, respectively. These parameter values are put to the test by performing one more experiment under the suggested optimum point. This results in 83% DHTA yield which is in good agreement with the model. For all experiments, the DHTA yields and the composition of byproducts were obtained using HPLC analysis. The optimized product was analyzed using XRD and FTIR analyses and the structure of the synthesized DHTA was confirmed.

2,5-Dihydroxyterephthalic acid (DHTA), is an organic hydroxyaromatic carboxylic acid that has recently been used as a raw material in the synthesis of polymers [1, 2], polyesters [3, 4], and metal-organic frameworks [5, 6, 7, 8]. DHTA and its derivatives are also often used and give rise to a variety of chemical frameworks in which they act as linear linkers [9]. Alkali metal phenates can react with carbon dioxide through the Kolbe-Schmitt reaction to produce hydroxyaromatic carboxylic acids [10]. Also, the Kolbe-Schmitt reaction plays a crucial role in synthesizing benzoic acid. It directly routes salicylic acids through the C-H ortho carboxylation of phenoxides with carbon dioxide [10, 11, 12]. Preparation and separation of dry phenoxides from the corresponding phenols is essential to ensure the correctness of the Kolbe-Schmitt carboxylation. Furthermore, presence of water impedes the carboxylation process, necessitating the drying of starting materials [13]. In industrial processes, dry alkali metal phenolates are typically subjected to carbon dioxide under pressure, facilitating the desired carboxylation reaction [14].

Contacting the molten phase of hydroquinone with carbon dioxide gas leads to adhesion of materials to the reaction equipment and causes overheating. In addition, the lack of intense contact between the carbon dioxide gas and solid phases produces low-yield DHTA [15]. Larrosa and coworkers [16] have successfully addressed the undesired formation of H₂O, which hinders the Kolbe-Schmitt reaction. Their approach allows the reaction to proceed in a one-pot process without separation of the phenoxide precursor. They observed that the carboxylation reaction is exothermic and challenging to control. This becomes particularly severe when the reaction mixture transitions from the adhesive phase, leading to localized overheating. Ritter and Wilmington [17] reported production of DHTA through contacting a 2,5-dihaloterephthalic acid with a base to form dibasic 2,5-dihaloterephthalic acid and contacting the resultant mixture with copper source and finally with protonating acid. The existence of complex conditions, prolonged reaction time and the use of expensive raw materials make this reaction unsuitable for industrial production. A suitable approach to DHTA production could be the use of an inert solvent or suspension solution to disperse alkali metal phenates into smaller particles that carbonate more effectively [18]. It also promotes homogeneous mixing of the reaction mixture, improves its homogeneity, enhances the contact surface area between reactants, and prevents the adhesion of reaction mixture to the reaction vessel [19].

This study synthesizes DHTA by utilizing a slurry reaction medium to contact disodium salt of hydroquinone (DSH) with carbon dioxide in the presence of sodium acetate as catalyst. The operating parameters, such as temperature, pressure, reaction time, and catalyst-to-reactant ratio, are explored using the Box-Behnken design (BBD) [20, 21] to establish industrial production conditions. Also, High-performance liquid chromatography (HPLC) analysis is employed to determine the yield of DHTA samples as the primary test. Finally, X-ray diffraction (XRD) and Fourier Transform Infrared spectroscopy (FTIR) analyses are performed to confirm the correct synthesis of DHTA.

Materials

The disodium salt of hydroquinone was synthesized in-house through contacting hydroquinone and sodium hydroxide. Sodium acetate anhydrous (extra pure) and dried methanol (max. 0.003% of H₂O) were purchased from Merck. Carbon dioxide, with 99.95% purity, and nitrogen gas, with 99.99% purity, were obtained from Iran Dayan Gas and Kermanshah Polymer companies, respectively. Risella 907 mineral oil was acquired from Shell, and hydrochloric acid (37%) was purchased from Sigma-Aldrich. Also, Grade 4 filter paper was prepared from the Whatman brand. The hydrochloric acid (HCl) amounts used in all DHTA synthesis experiments were diluted to a concentration of 5.9%. Other materials were used without further purification.

Mineral oil acts as a neutral medium to prevent adhering the reaction mixture to the equipment and enhance the contact surface. A one-liter reactor was equipped with heating jacket and Huber thermal circulator ministat model. This thermal circulator uses a platinum pt100 temperature sensor to measure the temperature inside the reactor with 0.01°C accuracy. The pressure inside the reactor is measured using a WIKA 316L model pressure. The reactor was connected to a nitrogen line with a direct pressure of 6.5 bar and a CO₂ gas capsule with an 80 bar pressure. A regulator manufactured by Drastar Korea was utilized to precisely adjust the output pressure of the CO₂ capsule for each test. Furthermore, the reactor was equipped with a 5 cm in diameter stainless-steel propeller stirrer, facilitating efficient stirring of the mixture at 505 rpm. Figure 1 illustrates the equipment's process flow diagram (PFD) schematic.

Methods

To achieve maximum DHTA yields, optimizing the effective operating parameters in the Kolbe-Schmitt reaction is essential. A fractional factorial design was used for the first step to identify the key factors affecting the reaction yield. Type IV resolution was selected to investigate the binary interactions and the factors' main effects [22]. Four factors, including the catalyst's molar ratio (1–3), temperature (150–200°C), reaction time (2–6 hours), and pressure (1–10 bar) were investigated using the screening method. After performing fractional factorial screening, the factors with the highest impacts on the yield were identified. Then, the Box-Behnken design (BBD) was used to evaluate the yield of reaction versus the remaining parameters, consisting of molar ratio of catalyst to DSH salt, temperature, and reaction time, limited to 1.5–2.5, 175–200°C, and 3–5 hours, respectively, based on the screening phase. Overall, 23 DHTA samples were synthesized, 8 samples for fractional factorial screening, 14 for BBD optimization, and one after optimization of operating parameters. In the following, only the optimized amounts of the above-mentioned parameters are mentioned. Nonetheless, an identical procedure was used to synthesize the remaining 22 DHTA samples.

Each experiment was commenced by heating up the reactor at 140°C for 3 hours, followed by nitrogen purging. Subsequently, the reactor was cooled to 50°C and the reactants were fed to the reactor under a continuous nitrogen purge flow. The synthesized DSH (18.6055 gr, 0.1208 mol) was dehydrated and mixed with Risella 907 oil (241.8689 gr) in the reaction vessel under a nitrogen atmosphere. Sodium acetate anhydrous (19.8125 gr, 0.2415 mol) was added, and the reactor was sealed. After the temperature reached 100°C, the reaction mixture stirred, and the pressure accumulated inside the reactor evacuated three times every 5 minutes. The temperature of the reaction mixture was allowed to rise to 200°C. Then nitrogen was replaced with carbon dioxide at 10 bar and stirred at a rate of 505 rpm. The reaction of carbon dioxide and DSH was carried out for 250 minutes. Then, the mixture cooled to 80 degrees, and 138.1872 g of 5.9% hydrochloric acid solution was added and stirred for another 15–20 minutes (cf. Figure 2) until the pH range reached 5–6.

The aqueous phase was isolated from the two-phase mixture as shown in Fig. 3, and 93.0095 grams of methanol was added. After filtering the resultant impurities, the reaction mixture was dried at 80 degrees for 6 hours to form a yellow-greenish powder.

Analysis of the DHTA powder

High-performance liquid chromatography (HPLC) analysis was employed to quantify the synthesized DHTA with a focus on time resolution [23, 24]. Additionally, the FT-IR and XRD analyses were used to identify the correctness of the synthesized DHTA [25]. An Agilent 1220 Infinity Isocratic LC was employed for the high-performance liquid chromatography (HPLC) analysis. This analysis was carried out in C18-type chromatography column, a mobile phase containing acetonitrile, water, and phosphoric acid in volume ratios of 29.9, 70, and 0.1, and a UV detector. X-ray diffraction (XRD) analysis was conducted at room temperature using a monochromatized Cu-Kα₁ STOE STADIP MODEL apparatus using a copper source (λ = 1.54056 Å). The spectra of the analyzed samples were measured in the range of 15 to 60 degrees (2θ) with a step length of 0.02. Fourier Transform Infrared Spectrometer (FT-IR) analysis was performed using the Bruker Universal Alpha FT-IR Spectrometer in the wavelength range of 400 to 4000 cm^-1. The pellets were made by using KBr as carrier.

Figure 4 shows the concentration of synthesized DHTA in all samples versus the elution time. This figure is produced by converting material percentages to the signal intensity. Elution of DHTA takes place at 6.1–6.3 minutes and is highlighted by a symmetrical peak, which is indicative of a good chromatographic performance. Furthermore, 2, 5 dihydroxy benzoic acid (DHBA) and hydroquinone (HQ) are by-products with elution times of around 7.3 and 9.2 minutes, respectively. Clearly, mass conservation implies that samples with higher amounts of DHTA should contain lower amounts of by-products.

Using a fractional factorial screening, it was observed that, within the range of experiments, CO₂ pressure only slightly increases DHTA yield. Therefore, to achieve the maximum yield, pressure was kept at the maximum, i.e. 10 bar, throughout the rest of the experiments. As mentioned earlier, 14 more experiments were performed based on a Box-Behnken desing taking molar ratio of catalyst to DSH salt (parameter A), temperature (parameter B), and reaction time (parameter C) within the modified ranges as mentioned earlier. The yields of various components synthesized during these experiments along with the other experiments are shown in Fig. 4. Using a response surface regression, a quadratic model achieves the highest adjusted and predicted R-squared values of 0.9791 and 0.9135, respectively. An analysis of variance, performed on the quadratic model as shown in Table 1, reveals the model is significant and that temperature has the importance among the three variables studied.

Table 1

ANOVA table for 2,5-dihydroxyterephthalic acid.
Source	Sum of scores	df	Mean Score	F-value	p-value
Model	4563.86	9	507.10	68.52	0.0005	Significant
A- Molar ratio	107.86	1	107.86	14.57	0.0188
B- Temperature	3570.09	1	3570.09	482.39	0.0001>
C- Time of Reaction	462.31	1	462.31	62.46	0.0091
AB	416.501	1	416.501	56.283	0.0082
AC	315.	0	20.07	2.71	0.1749
BC	0.7877	1	0.7877	0.1064	0.7606
A²	238.78	1	238.78	32.26	0.0047
B²	13.61	1	13.61	1.84	0.2466
C²	38.58	1	38.58	5.21	0.0845
Residuals	29.60	4	7.40
Cor Total	4593.46	13

Figure 5 shows the binary interactions of factors affecting DHTA yield. As noted above, temperature has the most profound impact which is stressed in Figs. 5a and 5c. An arc shaped behavior observed in Figs. 5a and 5c and further highlighted in Fig. 5b indicates the presence of an optimum value in the midranges for both catalyst molar ratio and reaction time factors for which DHTA yield is the maximum. Moving to the extremes of the above variables’ ranges, DHTA yield decreases rather sharply and slightly for catalyst molar ratio and reaction time, respectively. Increasing the molar ratio of catalyst to 3 reduces the DHTA yield down to 38.344%. Additionally, increasing the reaction time to more than 250 minutes leads to the formation of by-products and a 2–4% reduction in DHTA yield. On the other hand, further increases in reaction temperature seem to improve DHTA yield. However, this could not be maintained using the experimental setup employed in this study. Therefore, the optimal conditions for DHTA synthesis were mathematically taken as 200°C for temperature, 2.085 for the catalyst molar ratio, and 250 minutes for reaction time. Using these parameter values in the quadratic model extracted from Table 1 and formulated in Eq. 1 gives 83.385% for the maximum DHTA yield. Performing one more experiment under these optimum conditions revealed a product with 83% DHTA yield which is indeed the maximum obtained in this study.

\(Yield \left(\%\right)=28.4782+166.86A-3.79B+29.52C-0.138AB+4.48AC-0.035BC-37.87{A}^{2}+0.015{B}^{2}-3.804{C}^{2}\)(1)

The product obtained from the last experiment which was performed under the optimal conditions, was also tested using XRD and FTIR analyses to further characterize the product. Figure 6 successfully compares the XRD patterns of the sample produced in this study with those of DUSJUX CCDC. It has to be noted that obtain 2,5-dihydroxyterephthalic acid dihydrate is obtained after 3.5 hours drying. Further drying at 80°C for 6 hours removes the dehydrate molecules in the material's molecular structure to obtain anhydrous DHTA. The prominent peaks of DHTA are observed at 19, 22, and 28 degrees. In the dihydrate sample, it is observed that the first two peaks are shifted to positions 17 and 20, and the third peak appears at 26 degrees (2θ).

Figure 7 demonstrates the infra-red spectrum obtained from FTIR analysis of the final optimized product in this study. All the functional groups needed to form DHTA are seen in this spectrum. Hydroxyl groups (-OH) are detected by observing a broad peak within the 3200–3600 cm^− 1 range (stretching) and a sharp peak around 1500 cm^− 1 (bending). Carboxylic acid (COOH) groups show characteristic peaks. The stretching vibration of the carbonyl group (C = O) occurs around 1700–1750 cm^− 1. The O-H stretching vibration of the carboxylic acid group appears as a broad peak in the 2500–3300 cm^− 1 range. The benzene ring in DHTA is identified at the 1515, 1557, and 1641 cm^− 1 peaks. C-H aromatic stretching vibrations usually appear as moderate to strong peaks in the 3000–3100 cm^− 1 range. The peaks at 1416 and 1363 cm^− 1 are related to C-O-H bending, and the peaks at 1196 and 1095 cm^− 1 indicate the existence of a C = O bending bond. Therefore, based on what FTIR analysis reveals, it is concluded that the DHTA has been successfully synthesized.

2,5 Dihydroxyterephthalic acid was produced on experimental scale from disodium salt of hydroquinone at rather mild conditions. Using mineral oil as a reaction medium prevented the reaction mixture adhesion to the reaction vessel and improved homogeneous mixing. Four parameters including CO₂ pressure, reaction temperature, catalyst to DSH molar ratio, and reaction time were first screened by performing 8 fractional factorial designed experiments to explore their meaningful range and impact on DHTA yield. Due to its relatively low impact within the studied range, CO₂ pressure was excluded from the next phase of design of experiments. Using a BBD scheme, 13 more experiments were performed and a quadratic model fitted the experiments results. Through optimization of the quadratic model, 200℃ for temperature, 2.085 for the catalyst molar ratio, and 250 minutes for reaction time were deemed the optimum reaction conditions. The above optimized conditions were put into test and the actual measures DHTA yield, i.e. 83%, compared well with the model prediction, i.e., 83.385%. HPLC was used to analyze all experiments products and hence measure and identify the reaction main product and byproducts. The product of the last experiment, performed under the optimized conditions, was tested by XRD and FTIR analyses to confirm the correctness of the produced DHTA.

Acknowledgments

The financial and equipment support from Kermanshah Polymer Company is greatly appreciated.

Conflict of interests

On behalf of all authors, the corresponding author states that there is no conflict of interest.

W.-T. Chen, M.-J. Tsai and J.-Y. Wu, "A Thermally Stable Undulated Coordination Layer Showing a Sequentially Interweaving 2D → 3D Net as a Turn-On Sensor for Luminescence Detection of Al3+ in Water," Crystal Growth & Design, vol. 22, no. 1, pp. 228-236, 2022.
T.-H. Lee, M. Forrester, T.-p. Wang, L. Shen, H. Liu, D. Dileep, B. Kuehl, W. Li, G. Kraus and E. Cochran, "Dihydroxyterephthalate—A Trojan Horse PET Counit for Facile Chemical Recycling," Advanced Materials, vol. 35, no. 21, p. 2210154, 2023.
G. N. Short, H. T. H. Nguyen, P. I. Scheurle and S. A. Miller, "Aromatic polyesters from biosuccinic acid," Polymer Chemistry, vol. 9, no. 30, pp. 4113-4119, 2018.
D. J. Sikkema, "Chapter 4: Rigid-chain polymers: Aromatic polyamides, heterocyclic rigid rod polymers, and polyesters," Advanced Industrial and Engineering Polymer Research, vol. 5, no. 2, pp. 80-89, 2022.
J. Beamish-Cook, K. Shankland, C. A. Murray and P. Vaqueiro, "Insights into the Mechanochemical Synthesis of MOF-74," Crystal Growth & Design, vol. 21, no. 5, pp. 3047-3055, 2021.
H. Liu, W. Liu, G. Xue, T. Tan, C. Yang, P. An, W. Chen, W. Zhao, T. Fan, C. Cui, Z. Tang and G. Li, "Modulating Charges of Dual Sites in Multivariate Metal–Organic Frameworks for Boosting Selective Aerobic Epoxidation of Alkenes," Journal of the American Chemical Society, vol. 145, no. 20, pp. 11085-11096, 2023.
P. A. Julien, K. Užarević, A. D. Katsenis, S. A. J. Kimber, T. Wang, O. K. Farha, Y. Zhang, J. Casaban, L. S. Germann, M. Etter, R. E. Dinnebier, S. L. James, I. Halasz and T. Friščić, "In Situ Monitoring and Mechanism of the Mechanochemical Formation of a Microporous MOF-74 Framework," Journal of the American Chemical Society, vol. 138, no. 9, pp. 2929-2932, 2016.
Z. Gao, L. Liang, X. Zhang, P. Xu and J. Sun, "Facile One-Pot Synthesis of Zn/Mg-MOF-74 with Unsaturated Coordination Metal Centers for Efficient CO2 Adsorption and Conversion to Cyclic Carbonates," ACS Applied Materials & Interfaces, vol. 13, no. 51, pp. 61334-61345, 2021.
S. Kitagawa, R. Kitaura and S.-i. Noro, "Functional Porous Coordination Polymers," Angewandte Chemie International Edition, vol. 43, no. 18, pp. 2334-2375, 2004.
A. S. Lindsey and H. Jeskey, "The Kolbe-Schmitt Reaction," Chemical Reviews, vol. 57, no. 4, pp. 583-620, 1957.
H. K. Lee, C. S. Koh, W.-S. Lo, Y. Liu, I. Y. Phang, H. Y. Sim, Y. H. Lee, G. C. Phan-Quang, X. Han, C.-K. Tsung and X. Y. Ling, "Applying a Nanoparticle@MOF Interface To Activate an Unconventional Regioselectivity of an Inert Reaction at Ambient Conditions," Journal of the American Chemical Society, vol. 142, no. 26, pp. 11521-11527.
J. Luo and I. Larrosa, "C−H Carboxylation of Aromatic Compounds through CO2 Fixation," ChemSusChem, vol. 10, no. 17, pp. 3317-3332.
F. Wessely, K. Benedikt, H. Benger, G. Friedrich and F. Prillinger, "Zur Kenntnis der Carboxylierung von Phenolen," Monatshefte für Chemie und verwandte Teile anderer Wissenschaften, vol. 81, no. 7, pp. 1071-1091, 1950.
P. H. Pandey and H. S. Pawar, "Cu dispersed ZrO2 catalyst mediated Kolbe- Schmitt carboxylation reaction to 4-hydroxybenzoic acid," Molecular Catalysis, vol. 530, p. 112595, 2022.
S. Cadot, L. Veyre, D. Luneau, D. Farrusseng and E. Alessandra Quadrelli, "A water-based and high space-time yield synthetic route to MOF Ni2(dhtp) and its linker 2,5-dihydroxyterephthalic acid," Journal of Materials Chemistry A, vol. 2, no. 42, pp. 17757-17763, 2014.
J. Luo, S. Preciado, P. Xie and I. Larrosa, "Carboxylation of Phenols with CO2 at Atmospheric Pressure," Chemistry – A European Journal, vol. 22, no. 10, pp. 6798-6802, 2016.
J. Ritter and D. Wilmington, "Process for the synthesis of 2,5-dihydroxyterephthalic acid". United State of America Patent US7345195B1, 18 March 2008.
K. M. a. t. M. C. C. S. L. M. a. c. o. D. Lloyd B. Barkley, "Method of Carboxylating Phenols". United State of America Patent US2824892, 1958.
I. Stanescu and L. E. K. Achenie, "A theoretical study of solvent effects on Kolbe–Schmitt reaction kinetics," Chemical Engineering Science, vol. 61, no. 18, pp. 6199-6212, 2006.
S. L. C. Ferreira, R. E. Bruns, H. S. Ferreira, G. D. Matos, J. M. David, G. C. Brandão, E. G. P. da Silva, L. A. Portugal, P. S. dos Reis, A. S. Souza and W. N. L. dos Santos, "Box-Behnken design: An alternative for the optimization of analytical methods," Analytica Chimica Acta, vol. 597, no. 2, pp. 179-186.
A. Czyrski and J. Sznura, "The application of Box-Behnken-Design in the optimization of HPLC separation of fluoroquinolones," Scientific Reports, vol. 9, no. 1, p. 19458, 2019.
M. J. &. W. P. Anderson, RSM Simplified: Optimizing Processes Using Response Surface Methods for Design of Experiments, Second ed., Productivity Press., 2016.
M. Kunert, E. Dinjus, M. Nauck and J. Sieler, "Structure and Reactivity of Sodium Phenoxide - Following the Course of the Kolbe-Schmitt Reaction," Chemische Berichte, vol. 130, no. 10, pp. 1461-1465, 1997.
Y. Fan, J. Feng, M. Yang, X. Tan, H. Fan, M. Guo, B. Wang and S. Xue, "CO2(aq) concentration–dependent CO2 fixation via carboxylation by decarboxylase," Green Chemistry, vol. 23, no. 12, pp. 4403-4409, 2021.
M. Przybyłek, D. Ziółkowska, M. Kobierski, K. Mroczyńska and P. Cysewski, "Utilization of oriented crystal growth for screening of aromatic carboxylic acids cocrystallization with urea," Journal of Crystal Growth, vol. 443, pp. 128-138, 2016.
M. Hasheminasab, M. J. Kermani, S. S. Nourazar and M. H. Khodsiani, "A novel experimental based statistical study for water management in proton exchange membrane fuel cells," Applied Energy, vol. 264, p. 114713, 2020.
M. Shamsuzzaman, A. Shamsuzzoha, A. Maged, S. Haridy, H. Bashir and A. Karim, "Effective monitoring of carbon emissions from industrial sector using statistical process control," Applied Energy, vol. 300, p. 117352, 2021.
P.-W. Cheng, C.-F. Cheng, Y. Chun-Ting and C.-H. Lin, "2,5-Dihydroxyterephthalic acid dihydrate," Acta Crystallographica Section E, vol. 66, no. 8, p. o1928, 2010.

Synthesis and optimization of 2,5-dihydroxyterephthalic acid in a slurry reactor

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Version 1

Abstract

Figures

Introduction

Materials and Methods

Results and Discussions

Conclusions

Declarations

References

Status:

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