A Facile, Mechanochemical, Solvent-, and Catalyst-Free Synthesis of Functionalized 4-Thiazolidinones

Abstract

A highly eco-friendly greener approach based on the mechanochemical method using mortar and pestle is explored for the preparation of a variety of functionalized 4-thiazolidinones. The developed methodology does not require the use of harmful or expensive reagents and organic solvents and requires very less reaction time with easy isolation. The explored greener approach for the synthesis of 4-thiazolidinones is an important in terms of their usefulness for their valuable pharmacological properties.

Key words

mechanochemistry - green chemistry - grinding - 4-thiazolidinones - solvent-free synthesis

Publikationsverlauf

Eingereicht: 01. September 2023

Angenommen nach Revision: 12. Oktober 2023

Accepted Manuscript online:
12. Oktober 2023

Artikel online veröffentlicht:
16. November 2023

• References

• 1 Manjal SK, Kaur R, Bhatia R, Kumar K, Singh V, Shankar R, Kaur R, Rawal RK. Bioorg. Chem. 2017; 75: 406
• 2 Chawla PA, Wahan SK, Negi M, Faruk A, Chawla V. Journal of Heterocyclic Chemistry 2022; 60(8): 1248
• 3 Singh SP, Parmar SS, Raman K, Stenberg VI. Chem. Rev. 1981; 81: 175
• 4 Nirwan S, Chahal V, Kakkar R. J. Heterocycl. Chem. 2019; 56: 1239
• 5 Geronikaki AA, Pitta EP, Liaras KS. Curr. Med. Chem. 2013; 20: 4460
• 6 Küçükgüzel ŞG, Oruç EE, Rollas S, Şahin F, Özbek A. Eur. J. Med. Chem. 2002; 37: 197
• 7 Rawal RK, Srivastava T, Haq W, Katti SB. J. Chem. Res. 2004; 5: 368
• 8 Behbehani H, Ibrahim HM. Molecules 2012; 17: 6362
• 9 Wang GW. Chem. Soc. Rev. 2013; 42: 7668
• 10 Egorov IN, Santra S, Kopchuk DS, Kovalev IS, Zyryanov GV, Majee A, Ranu BC, Rusinov VL. Chupakhin O. N. Green Chem. 2020; 22: 302
• 11 Margetic D, Štrukil V. Mechanochemical Organic Synthesis. Elsevier; Amsterdam: 2016
• 12 Kumar S, Sharma P, Kapoor KK, Hundal MS. Tetrahedron 2008; 64: 536
• 13 Ying P, Yu J, Su W. Adv. Synth. Catal. 2021; 363: 1246
• 14 Lu J, Zhang Q, Wang J, Saito F, Uchida M. Powder Technol. 2006; 162: 33
• 15 Rateb NM, Zohdi HF. Synth. Commun. 2009; 39: 2789
• 16 Zhang P, Liu C, Yu L, Hou H, Sun W, Ke F. Green Chem. Lett. Rev. 2021; 14: 612
• 17 Zangade S, Mokle S, Vibhute A, Vibhute Y. Chem. Sci. J. 2011; 2: 18
• 18 Kumar A, Sharma S. Green Chem. 2011; 13: 2017
• 19 Štrukil V. Synlett 2018; 29: 1281
• 20 Andersen J, Mack J. Green Chem. 2018; 20: 1435
• 21 Naikoo RA, Singh P, Kumar R, Bhargava G. J. Sulfur Chem. 2022; 43: 117
• 22 Cascioferro S, Parrino B, Carbone D, Schillaci D, Giovannetti E, Cirrincione G, Diana P. J. Med. Chem. 2020; 63: 7923
• 23 Allen S, Newhouse B, Anderson AS, Fauber B, Allen A, Chantry D, Eberhardt C, Odingo J, Burgess LE. Bioorg. Med. Chem. Lett. 2004; 14: 1619
• 24 Zhou H, Wu S, Zhai S, Liu A, Sun Y, Li R, Zhang Y, Ekins S, Swaan PW, Fang B, Zhang B. J. Med. Chem. 2008; 51: 1242
• 25 Bhat M, Poojary B, Kalal BS, Gurubasavaraja Swamy PM, Kabilan S, Kumar V, Shruthi N, Alias Anand SA, Pai VR. Future Med. Chem. 2018; 10: 1017
• 26 Khan SA, Asiri AM, Sharma K. Med. Chem. Res. 2013; 22: 1998
• 27 Geronikaki A, Eleftheriou P, Vicini P, Alam I, Dixit A, Saxena AK. J. Med. Chem. 2008; 51: 5221
• 28 Patil RD, Adimurthy S. Asian J. Org. Chem. 2013; 2: 726
• 29 General Procedure for the Synthesis of 2,3-Diphenyl-Substituted Thiazolidin-4-one Derivatives 1a–k The reaction involved the preparation of series of imines 4a–k by stirring the mixture of various aliphatic and aromatic amines 2 (1 equiv) and various substituted benzaldehydes 3a–k (1.1 equiv) in dichloromethane as solvent at room temperature in the presence of sodium sulfate (2 equiv) as dehydrating agent. After isolation, the mixture of prepared series of imines 4a–k were mixed and grinded using mortar and pestle with thioglycolic acid 5 (1.5 equiv) and Na₂SO₄ (2 equiv) for 9–12 min till the completion of reaction. The reaction was monitored by using TLC. After the reaction was found to be completed, the workup of the reaction was done by using ethyl acetate (2 × 20 mL). the crude product obtained was dried using magnesium sulfate, filtered, and dried to collect the crude product. The impure product was purified by adding the mixture of diethyl ether and hexane in the ratio of 3:1 dropwise with stirring. After keeping the reaction mixture aside for some time, solid precipitates were found at the bottom of the beaker. Mother liquor was decanted off, and the product obtained was dried to obtain pure solid compounds of 2,3-diphenyl-substituted thiazolidin-4-one derivatives. The same process was repeated 2–3 times to obtain the product without any impurities.
• 30 2,3-Diphenylthiazolidin-4-one (1a) Yield: 4.93 g (90%); yellow solid; mp 127–129 °C. IR(KBr): ν = 1655 (C = O) cm^–1. ¹H NMR (500 MHz, DMSO): δ = 3.98 (dd, 2 H, CH₂), 5.84 (s, 1 H, CH), 7.31 (dd, 1 H, CH), 7.5 (dd, 1 H, CH), 7.8 (dd, 2 H, CH), 7.9 (d, 2 H, CH), 8.0 (dd, 2 H, CH) ppm.
• 31 2-(2-Nitrophenyl)-3-phenylthiazolidin-4-one (1b) Yield: 6.12 g (95%); pale yellow solid; mp 136 °C. IR(KBr): ν = 1654 (C=O), 1595–1313 (NO₂) cm^–1. ¹H NMR (500 MHz, DMSO): δ = 3.90–4.00 (dd, 2 H, CH₂), 6.44 (s, 1 H, CH), 7.99 (d, 1 H, CH), 7.57 (dd, 1 H, CH), 7.72 (dd, 1 H, CH), 7.54 (d, 1 H, CH), 7.31 (d, 2 H, CH), 7.27 (dd, 2 H, CH), 7.13 (dd, 1 H, CH) ppm.

For complete data of known 4-thiazolidinone please, see:
• 32a Kumar D, Sonawane M, Pujala B, Jain VK, Bhagat S, Chakraborti AK. Green Chem. 2013; 15: 2872
• 32b Luo J, Zhong Z, Ji H, Chen J, Zhao J, Zhang F. J. Sulfur Chem. 2016; 37: 438
• 32c Lingampalle D, Jawale D, Waghmare R, Mane R. Synth. Commun. 2010; 40: 2397