Applied Chemical Engineering

Using green chemistry (deep eutectic solvents) to synthesize pyrazol-4-yl-thiazolidin-4-one derivatives and evaluate their antibacterial activity

Muna S. Aldulaimi

Forensic Evidence Department, College of Science, University of Mosul, 41002, Mosul, Iraq

Shakir M. Saied

College of Pharmacy, Al-Noor University, Mosul city, Alshallalat Road, 41003, Mosul, Iraq

Salim J. Mohammed

Department Chemistry, College of Science, University of Mosul, 41002, Mosul, Iraq

Mohanad Y. Saleh

Department of Chemistry, College of Education for Pure Science, University of Mosul, 41002, Mosul, Iraq

DOI: https://doi.org/10.59429/ace.v8i3.5708

Keywords: green chemistry; deep eutectic solvents; pyrazol-4-yl-thiazolidin-4-one derivatives; antibacterial evaluation

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Abstract

This study employed a green chemistry approach utilizing two deep eutectic solvents (DESs), namely Reline and Malonine, as environmentally friendly ionic liquids (ILs). These solvents were readily prepared from choline chloride combined with either two moles of urea or one mole of malonic acid, respectively. Acting as dual-function catalysts, they are characterized by their low melting points and suitability as attractive media for organic reactions, in addition to being cost-effective, non-toxic, bio-renewable, and biodegradable.

The two DESs were applied to improve the yields of Schiff bases, specifically 1,5-dimethyl-4-(substituted styryl)-2-phenyl-1,2-dihydro-3H-pyrazol-3-one, I(a–c). The yields increased to 95% in methods B and C, compared with 76–80% obtained using the conventional method (A). Moreover, reaction times were reduced from 120 minutes in method A to just 30 minutes in methods B and C.

Similarly, in methods E and F, solvent-free conditions combined with simplified procedures led to high yields (95%), compared with only 50–51% achieved using the conventional method (D). Reaction times were also reduced to one quarter of those in method D during the synthesis of the novel compounds II(a–c).

Both DESs (Reline and Malonine) could be efficiently recovered and reused up to seven times, after which they were reactivated by heating with choline chloride.

The antibacterial activities of the synthesized compounds II(a–c) were evaluated using standard in vitro assays against four pathogenic microorganisms: Bacillus cereus and Staphylococcus aureus (Gram-positive), as well as Escherichia coli and Pseudomonas aeruginosa (Gram-negative). Among them, Staphylococcus aureus exhibited the highest inhibition with Compound a (31 mm/mg), outperforming penicillin (16 mm/mg and 30 mm/mg, respectively). Compound b showed the strongest activity against Pseudomonas aeruginosa (40 mm/mg), significantly higher than penicillin (24 mm/mg). While penicillin demonstrated the strongest inhibition against Bacillus cereus (24 mm/mg), Compound c exhibited a comparable effect (22 mm/mg).

Overall, these findings highlight the promising antibacterial potential of Compounds b and c, with some surpassing penicillin against certain bacterial strains. Further investigations into their mechanisms of action and toxicity are recommended to assess their potential as novel antibacterial agents.

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References

[1]. Al-Jubori, H. M. S., Al-Mathkuri, T. S. F., Banoon, Z. R., & Saleh, M. Y. (2024). Synthesis of novel benzo [d] imidazole bearing α-aminophosphonate and their antimicrobial evaluation. Results in Chemistry, 8, 101586.‏ https://doi.org/10.1016/j.rechem.2024.101586

[2]. da Silva, C.M., da Silva, D.L., Modolo, L. V., Alves, R.B., de Resende, M.A., Martins, C.V.B., de Fátima, Â.: Journal of Advanced Research. 2, 1–8 (2011). https://doi.org/10.1016/j.jare.2010.05.004

[3]. Ali, R., Hussein, S.A., Znad, M.R., Al-Delfi, M.N.: Chemistry Africa. (2025). https://doi.org/10.1007/s42250-025-01216-0

[4]. Thomas, A.B., Tupe, P.N., Badhe, R.V., Nanda, R.K., Kothapalli, L.P., Paradkar, O.D., Sharma, P.A., Deshpande, A.D.: Green Chemistry Letters and Reviews. 2, 23–27 (2009). https://doi.org/10.1080/17518250902922798

[5]. Serhan, C.N., Savill, J.: Nature Immunology. 6, 1191–1197 (2005). https://doi.org/10.1038/ni1276

[6]. Sabaa, M.W., Mohamed, N.A., Mohamed, R.R., Khalil, N.M., Abd El Latif, S.M.: Carbohydrate Polymers. 79, 998–1005 (2010). https://doi.org/10.1016/j.carbpol.2009.10.024

[7]. Rostom, S.A.F.: Bioorganic & Medicinal Chemistry. 18, 2767–2776 (2010). https://doi.org/10.1016/j.bmc.2010.02.006

[8]. Hamdoon, A., Saleh, M., Saied, S.: Egyptian Journal of Chemistry. 65, 305–312 (2022). https://doi.org/10.21608/ejchem.2022.120818.5418

[9]. Murtaza, S., Akhtar, M.S., Kanwal, F., Abbas, A., Ashiq, S., Shamim, S.: Journal of Saudi Chemical Society. 21, S359–S372 (2017). https://doi.org/10.1016/j.jscs.2014.04.003

[10]. Kerru, N., Gummidi, L., Bhaskaruni, S.V.H.S., Maddila, S.N., Jonnalagadda, S.B.: Monatshefte für Chemie - Chemical Monthly. 151, 981–990 (2020). https://doi.org/10.1007/s00706-020-02625-2

[11]. Ali, R., Han, J., Kazemi, M., Javahershenas, R.: ChemistryOpen. (2025). https://doi.org/10.1002/open.202500041

[12]. Patel, A.B., Chikhalia, K.H., Kumari, P.: Journal of Saudi Chemical Society. 18, 646–656 (2014). https://doi.org/10.1016/j.jscs.2014.02.002

[13]. Mashrai, A., Mahmood Dar, A.: Medicinal chemistry. 06, (2016). https://doi.org/10.4172/2161-0444.1000358

[14]. Saini, N., Sharma, A., Thakur, V.K., Makatsoris, C., Dandia, A., Bhagat, M., Tonk, R.K., Sharma, P.C.: Current Research in Green and Sustainable Chemistry. 3, 100021 (2020). https://doi.org/10.1016/j.crgsc.2020.100021

[15]. Hamdoon, A., Saleh, M., Saied, S.: Egyptian Journal of Chemistry. 65, 305–312 (2022). https://doi.org/10.21608/ejchem.2022.120818.5418

[16]. Marchel, M., Cieśliński, H., Boczkaj, G.: Industrial & Engineering Chemistry Research. 61, 11288–11300 (2022). https://doi.org/10.1021/acs.iecr.2c01898

[17]. SARAH H. ABDUL-KHUDHUR, R.J.N.: International Journal of Pharmaceutical Research. 12, (2020). https://doi.org/10.31838/ijpr/2020.SP1.256

[18]. Saleh, A., Saleh, M., Chemistry, C.: Egyptian Journal of Chemistry. 65, 783–792 (2022). https://doi.org/10.21608/ejchem.2022.133946.5904

[19]. Hoàn, D.Q.: Hue University Journal of Science: Natural Science. 127, 5 (2018). https://doi.org/10.26459/hueuni-jns.v127i1A.4516

[20]. Di Carmine, G., Abbott, A.P., D’Agostino, C.: Reaction Chemistry & Engineering. 6, 582–598 (2021). https://doi.org/10.1039/D0RE00458H

[21]. Abbott, A.P., Capper, G., Davies, D.L., Rasheed, R.K., Tambyrajah, V.: Chemical Communications. 70–71 (2003). https://doi.org/10.1039/b210714g

[22]. Mnguni, M.J., Lemmerer, A.: Acta Crystallographica Section C Structural Chemistry. 71, 103–109 (2015). https://doi.org/10.1107/S2053229614027247

[23]. Ali, A.H., Saleh, M.Y., Owaid, K.A.: Iranian Journal of Catalysis. 13, 73–83 (2023). https://doi.org/10.30495/IJC.2023.1973500.1977

[24]. Salih, M.M., Saleh, A.M., Hamad, A.S., Al-Janabi, A.S.: Journal of Molecular Structure. 1264, 133252 (2022). https://doi.org/10.1016/j.molstruc.2022.133252

[25]. Nguyen, D., Van Huynh, T., Nguyen, V.S., Doan Cao, P.-L., Nguyen, H.T., Wei, T.-C., Tran, P.H., Nguyen, P.T.: RSC Advances. 11, 21560–21566 (2021). https://doi.org/10.1039/D1RA03273A

[26]. Th. Sadeek, G., Faiyq Saeed, Z., Yakdhan Saleh, M.: Research Journal of Pharmacy and Technology. 975–982 (2023). https://doi.org/10.52711/0974-360X.2023.00163

[27]. Truong Nguyen, H., Nguyen Chau, D.-K., Tran, P.H.: New J. Chem. 41, 12481–12489 (2017). https://doi.org/10.1039/C7NJ02396K