Experimental and Theoretical Study of the Synthesis of a Deep Eutectic Solvent Based on Protonated Caffeine, Ethylene Glycol, and ZnCl2
Abstract
:1. Introduction
2. Results and Discussion
2.1. Activation of Caffeine’s Imidazole Ring
2.2. Synthesis of Protonated Caffeine-Based DES
2.3. Sigma Profile
2.4. Radial Distribution Functions
3. Materials and Methods
3.1. Activation of Caffeine’s Imidazole Ring
3.1.1. Chemical Reagents
3.1.2. Reaction Setup and Procedure
- First stage, production of anhydrous hydrogen chloride: Anhydrous hydrogen chloride was generated by the reaction between sodium chloride and sulfuric acid, as shown in Figure 9. The system consisted of a round-bottomed flask containing sodium chloride, with sulfuric acid added dropwise, while the mixture was maintained at a constant temperature of C using a heating mantle, as reported by Groover [45]. An excess of hydrogen chloride (5 molar equivalents) was bubbled into the ethanol solution containing caffeine to drive the equilibrium of the protonation reaction toward product formation, ensuring complete protonation of the caffeine.
- Second stage, protonation reaction: The protonation reaction was carried out at C (Figure 10) with caffeine dissolved in anhydrous ethanol. A total of 110 mL of anhydrous ethanol was used to fully dissolve the caffeine at this temperature. The gaseous hydrogen chloride produced in the first stage was continuously bubbled into the ethanol solution, leading to the protonation of caffeine, which was indicated by the precipitation of a white solid after 1 h of reaction.
- Purification of caffeine hydrochloride: The solid product, caffeine hydrochloride (CafCl), was purified through rotary evaporation at C and 200 mbar to eliminate excess ethanol. The resulting solid was subsequently dried in a vacuum oven at C for 24 h to ensure complete removal of residual solvents. The final product yield was 88.4%.
3.1.3. Characterization of Protonated Caffeine (CafCl)
3.2. Synthesis of Protonated Caffeine-Based DES
3.2.1. Chemical Reagents
3.2.2. Characterization of the Synthetized DES
3.3. Computational Detail
3.3.1. COSMO-RS Calculation
3.3.2. Ab Initio Molecular Dynamics (AIMD)
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Proton | Theoretical Caffeine | Literature Caffeine | Experimental CafCl | Literature CafCl | Experimental Peak Integration |
---|---|---|---|---|---|
8 | 7.5 | 7.58 | 7.27 | 7.99 | 1.0 |
11 | 3.48 | 3.37 | 3.27 | 3.13 | 3.10 |
13 | 3.51 | 3.55 | 3.71 | 3.33 | 3.10 |
14 | 4.0 | 4.01 | 4.13 | 3.82 | 3.04 |
15 | 8.5 | 11.27 | 0.99 |
HBD | HBA | Molar Ratio | Observations About CafCl Incorporation |
---|---|---|---|
Ethylene glycol (ETG) | Choline chloride (ChCl) | 2:1 | Partial incorporation with high viscosity |
Benzoic acid | Choline chloride | 1:1 | Crystal formation, partial incorporation with high viscosity |
Benzamide | Choline chloride | 2:1 | Partial incorporation with high viscosity |
Ethylene glicol | Tetraethylammonium bromide | 2:1 | Complete incorporation with medium viscosity |
Ethylene glicol | Hydrated iron chloride | 3:1 | Partial incorporation with high viscosity |
Ethylene glicol | Zinc chloride | 2:1 | Complete incorporation with manageable viscosity |
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Benavides-Maya, L.S.; Torres-Perdomo, M.F.; Ocampo-Carmona, L.M.; Echeverry-Vargas, L. Experimental and Theoretical Study of the Synthesis of a Deep Eutectic Solvent Based on Protonated Caffeine, Ethylene Glycol, and ZnCl2. Molecules 2025, 30, 1557. https://doi.org/10.3390/molecules30071557
Benavides-Maya LS, Torres-Perdomo MF, Ocampo-Carmona LM, Echeverry-Vargas L. Experimental and Theoretical Study of the Synthesis of a Deep Eutectic Solvent Based on Protonated Caffeine, Ethylene Glycol, and ZnCl2. Molecules. 2025; 30(7):1557. https://doi.org/10.3390/molecules30071557
Chicago/Turabian StyleBenavides-Maya, Laura Sofía, Manuel Felipe Torres-Perdomo, Luz M. Ocampo-Carmona, and Luver Echeverry-Vargas. 2025. "Experimental and Theoretical Study of the Synthesis of a Deep Eutectic Solvent Based on Protonated Caffeine, Ethylene Glycol, and ZnCl2" Molecules 30, no. 7: 1557. https://doi.org/10.3390/molecules30071557
APA StyleBenavides-Maya, L. S., Torres-Perdomo, M. F., Ocampo-Carmona, L. M., & Echeverry-Vargas, L. (2025). Experimental and Theoretical Study of the Synthesis of a Deep Eutectic Solvent Based on Protonated Caffeine, Ethylene Glycol, and ZnCl2. Molecules, 30(7), 1557. https://doi.org/10.3390/molecules30071557