A Rapid, Greener, and Sustainable Synthesis of N-Acylhydrazones of Isoniazid in a Deep-Eutectic Solvent

Abstract

This study introduces an efficient, environmentally friendly, and sustainable method for synthesizing N-acylhydrazone analogues by engaging isoniazid in a condensation reaction with variously substituted benzaldehydes. The deep-eutectic solvent (ZnCl₂/urea) employed in this study acted not only as a solvent but also as a catalyst to facilitate the synthesis of the target compounds within two to six minutes without the requirement of any lengthy purification techniques. The synthetic protocol is operationally simple and offers other remarkable advantages such as a short reaction time, good to excellent yields, a scalable protocol, and a recyclable and reusable catalyst. Additionally, green metrics calculations suggest the present method to be environmentally benign. Finally, the frontier molecular orbitals and the global reactivity parameters of the synthesized compounds were predicted by using density functional theory calculations.

Key words

deep-eutectic solvents - acylhydrazones - isoniazid - green chemistry - DFT

Publication History

Received: 09 August 2024

Accepted after revision: 17 September 2024

Accepted Manuscript online:
17 September 2024

Article published online:
09 October 2024

• References and Notes

• 1 Sheldon RA. Green Chem. 2005; 7: 267
• 2 Kumar G, Bhargava G, Kumar S, Rajput JK, Singh B, Singh P, Kumar R. Inorg. Chim. Acta 2024; 563: 121935
• 3 Kumar G, Bhargava G, Kumar Y, Kumar R. J. Chem. Sci. 2022; 134: 44
• 4 Clarke CJ, Tu W.-C, Levers O, Brohl A, Hallett JP. Chem. Rev. 2018; 118: 747
• 5 Kumar G, Singh P, Bhargava G, Gill BS, Rajput JK, Kumar R. J. Sulfur Chem. 2023; 44: 751
• 6 Hessel V, Tran NN, Asrami MR, Tran QD, Long NV. D, Escribà-Gelonch M, Tejada JO, Linke S, Sundmacher K. Green Chem. 2022; 24: 410
• 7 Kumar G, Seboletswe P, Manhas N, Singh P, Bhargava G, Rajput JK, Kumar R. J. Heterocycl. Chem. 2024; 61: 347
• 8 Płotka-Wasylka J, de la Guardia M, Andruch V, Vilková M. Microchem. J. 2020; 159: 105539
• 9 Krishnan A, Gopinath KP, Vo D.-VN, Malolan R, Nagarajan VM, Arun J. Environ. Chem. Lett. 2020; 18: 2031
• 10 Wang A, Zheng X, Zhao Z, Li C, Zheng X. Huaxue Jinzhan 2014; 26: 784
• 11 Smith EL, Abbott AP, Ryder KS. Chem. Rev. 2014; 114: 11060
• 12 Nazar M, Hussain SM. S, Kamal MS. Energy Fuels 2024; 38: 10653
• 13 Prabhune A, Dey R. J. Mol. Liq. 2023; 379: 121676
• 14 Socea L.-I, Barbuceanu S.-F, Pahontu EM, Dumitru A.-C, Nitulescu GM, Sfetea RC, Apostol T.-V. Molecules 2022; 27: 8719
• 15 Dias Viegas FP, de Freitas Silva M, Divino da Rocha M, Castelli MR, Riquiel MM, Machado RP, Vaz SM, Simões de Lima LM, Mancini KC, Marques de Oliveira PC, Morais ÉP, Gontijo VS, da Silva FM. R, D’Alincourt da Fonseca Peçanha D, Castro NG, Neves GA, Giusti-Paiva A, Vilela FC, Orlandi L, Camps I, Veloso MP, Leomil CoelhoL. F, Ionta M, Ferreira-Silva G. Á, Pereira RM, Dardenne LE, Guedes IA, de Oliveira Carneiro Junior W, Quaglio Bellozi PM, Pinheiro de Oliveira AC, Ferreira FF, Pruccoli L, Tarozzi A, Viegas CJr. Eur. J. Med. Chem. 2018; 147: 48
• 16 Thota S, Rodrigues DA, de Sena Murteira Pinheiro P, Lima LM, Fraga CA. M, Barreiro EJ. Bioorg. Med. Chem. Lett. 2018; 28: 2797
• 17 Ye J, Fu S, Zhou S, Li M, Li K, Sun W, Zhai Y. Eur. Polym. J. 2020; 139: 110024
• 18 Reingewertz TH, Meyer T, McIntosh F, Sullivan J, Meir M, Chang Y.-F, Behr MA, Barkan D. Antimicrob. Agents Chemother. 2020; 64: e01899-19
• 19 dos Santos PV. P, Ribeiro CM, Pavan FR, Corbi PP, Bergamini FR. G, Carvalho MA, D’Oliveria KA, Cuin A. J. Mol. Struct. 2021; 1234: 130193
• 20 Xu Z, Ma X, Liao J, Osman SM, Wu S, Luque R. ACS Sustainable Chem. Eng. 2022; 10: 4258
• 21 Kumar G, Bhargava G, Kumar R. Polycyclic Aromat. Compd. 2023; 43: 7238
• 22 Kumar G, Khubone L, Seboletswe P, Manhas N, Makhanya T, Bhargava G, Singh P. ARKIVOC 2023; (viii): 202312167
• 23 Wagh YB, Dalal KS, Padvi SA, Terdale SS, Dalal DS, Mahulikar PP. Polycyclic Aromat. Compd. 2023; 43: 421
• 24 Raghuvanshi DS, Mahulikar PP, Meshram JS. RSC Adv. 2015; 5: 48071
• 25 Patil NB, Bandiwadekar P, Chaturbhuj GU. Results Chem. 2024; 7: 101423
• 26 Gazzi TP, Rotta M, Villela AD, Rodrigues-Junior V, Martinelli LK, Sales FA. M, Sousa EH. S. d, Campos MM, Basso LA, Santos DS, Machado P. J. Braz. Chem. Soc. 2017; 28: 2028
• 27 Hakkimane SS, Shenoy VP, Gaonkar SL, Bairy I, Guru BR. Int. J. Nanomed. 2018; 13: 4303
• 28 Ramadevi P, Singh R, Prajapati A, Gupta S, Chakraborty D. Adv. Chem 2014; 630575
• 29 Oyeneyin OE, Ibrahim A, Ipinloju N, Ademoyegun AJ, Ojo ND. J. Biomol. Struct. Dyn.
• 30 Khalid M, Ali A, Rehman MF. U, Mustaqeem M, Ali S, Khan MU, Asim S, Ahmad N, Saleem M. ACS Omega 2020; 5: 13236
• 31 Khayer K, Haque T. ACS Omega 2020; 5: 4507
• 32 Tsuji Y, Yoshizawa K. ACS Omega 2021; 6: 1339
• 33 Miar M, Shiroudi A, Pourshamsian K, Oliaey AR, Hatamjafari F. J. Chem. Res. 2021; 45: 147
• 34 Kaur I, Jia W, Kopreski RP, Selvarasah S, Dokmeci MR, Pramanik C, McGruer NE, Miller GP. J. Am. Chem. Soc. 2008; 130: 16274
• 35 Aihara J.-i. J. Phys. Chem. A 1999; 103: 7487
• 36 Radhi AH, Du EA, Khazaal FA, Abbas ZM, Aljelawi OH, Hamadan SD, Almashhadani HA, Kadhim MM. NeuroQuantol. 2020; 18 (01) 37
• 37 Azeez YH, Kareem RO, Qader AF, Omer RA, Ahmed LO. Next Mater. 2024; 3: 100184
• 38 Ogunyemi BT, Latona DF, Ayinde AA, Adejoro IA. Adv. J. Chem., Sect. A 2020; 3: 485
• 39 Li P, Bu Y, Ai H. J. Phys. Chem. A 2004; 108: 1200
• 40 Al-Azawi KF, Al-Baghdadi SB, Mohamed AZ, Al-Amiery AA, Abed TK, Mohammed SA, Kadhum AA. H, Mohamad AB. Chem. Cent. J. 2016; 10: 1
• 41 Pritchard H, Skinner H. Chem. Rev. 1955; 55: 745
• 42 Ghosh DC, Islam N. Int. J. Quantum Chem. 2011; 111: 40
• 43 Bendjeddou A, Abbaz T, Gouasmia A, Villemin D. Am. J. Appl. Chem. 2016; 4: 104
• 44 Mushtaq A, Asif R, Humayun WA, Naseer MM. RSC Adv. 2024; 14: 14051
• 45 N′-(Arylmethylene)isonicotinohydrazides 3a–p; General Procedure A solution of the isonicotinohydrazide (2; 1.0 mmol) and the appropriate benzaldehyde 1 (1.0 mmol) in ZnCl₂/urea (50 mol%) DES was stirred at 110 °C for 2–6 min until the reaction was complete (TLC). The solid obtained by adding H₂O to the mixture was collected by filtration with vacuum suction, and purified by crystallization from EtOH. N′-(Phenylmethylene)isonicotinohydrazide (3a) Yellow solid; yield: 96%. IR (ATR): 1518.57, 1562.23, 1599.40, 1682.25, 2222.89, 3024.97, 3199.63 cm^–1. ¹H NMR (600 MHz, DMSO-d ₆): δ = 7.46 (d, J = 6.52 Hz, 3 H), 7.74 (d, J = 5.96 Hz, 2 H), 7.82 (d, J = 5.37 Hz, 2 H), 8.46 (s, 1 H), 8.78 (d, J = 5.26 Hz, 2 H), 12.08 (s, 1 H). ¹³C NMR (150 MHz, DMSO-d ₆): δ = 122.04, 123.65, 127.33, 127.73, 129.36, 130.87, 134.47, 141.01, 149.51, 150.77, 162.06.