Ionic liquid-assisted synthesis of pyrrole derivative: a green and sustainable method
B * , Preeti Jain C , Ankush Thakur D , Sobhi M. Gomha E * and Swati Rani F *
A
B
C
D
E
F
Handling Editor: Jenny Pringle
Abstract
Green synthesis is attracting researchers worldwide because of its unique features and environmental benefits. Scientists are inventing novel ionic liquids (ILs) and refining their properties for use in green chemistry and synthesis, such as in green and sustainable solvents and catalysts. Owing to their unique properties, they have been widely used as green catalysts and solvent systems to develop various significant heterocycles. Among aza-heterocycles, pyrrole derivatives are regarded for their versatility in medication development and research. Organic chemists have developed pyrrole-based frameworks employing ILs as solvents and catalysts, achieving major green and sustainable synthesis goals. This study focuses on the literature (2001–24) on pyrrole and its derivatives synthesised by using ILs as solvents and catalysts.
Keywords: green catalyst, green solvent, ionic liquids, imidazolium-based ionic liquids, pyrrole derivatives, room temperature ionic liquids, solvent-free reactions, sustainable method.
References
2 Matlack A. Some recent trends and problems in green chemistry. Green Chem 2003; 5(1): G7-G12.
| Crossref | Google Scholar |
3 Remsing RC, Wildin JL, Rapp AL, Moyna G. Hydrogen bonds in ionic liquids revisited: 35/37Cl NMR studies of deuterium isotope effects in 1-n-butyl-3-methylimidazolium chloride. J Phys Chem B 2007; 111(40): 11619-11621.
| Crossref | Google Scholar | PubMed |
4 Ma Y, Yang Y, Li T, Hussain S, Zhu M. Deep eutectic solvents as an emerging green platform for the synthesis of functional materials. Green Chem 2024; 26(7): 3627-3669.
| Google Scholar |
5 Sharma P, Sharma S, Kumar H. Introduction to ionic liquids, applications and micellization behavior in presence of different additives. J Mol Liq 2024; 393: 123447.
| Crossref | Google Scholar |
6 Laszlo JA, Compton DL. α‐Chymotrypsin catalysis in imidazolium‐based ionic liquids. Biotechnol Bioeng 2001; 75(2): 181-186.
| Crossref | Google Scholar | PubMed |
7 Jutz F, Andanson JM, Baiker A. Ionic liquids and dense carbon dioxide: a beneficial biphasic system for catalysis. Chem Rev 2011; 111(2): 322-353.
| Crossref | Google Scholar | PubMed |
8 Rogers RD, Seddon KR. Ionic liquids—solvents of the future? Science 2003; 302(5646): 792-793.
| Crossref | Google Scholar | PubMed |
9 Brevet D, Jouannin C, Tourné-Péteilh C, Devoisselle JM, Vioux A, Viau L. Self-encapsulation of a drug-containing ionic liquid into mesoporous silica monoliths or nanoparticles by a sol–gel process. RSC Adv 2016; 6(86): 82916-82923.
| Google Scholar |
10 Attri P, Kim M, Choi EH, Cho AE, Koga K, Shiratani M. Impact of an ionic liquid on protein thermodynamics in the presence of cold atmospheric plasma and gamma rays. Phys Chem Chem Phys 2017; 19(37): 25277-25288.
| Crossref | Google Scholar | PubMed |
11 Zhu M. Ionic-liquid/metal–organic-framework composites: synthesis and emerging sustainable applications. Inorg Chem Front 2025; 12(1): 39-84.
| Google Scholar |
12 Zhu M, Yang Y. Poly (ionic liquid)s: an emerging platform for green chemistry. Green Chem 2024; 26: 5022-5102.
| Google Scholar |
13 Baltazzi E, Krimen LI. Recent advances in the chemistry of pyrrole. Chem Rev 1963; 63(5): 511-556.
| Google Scholar |
14 Philkhana SC, Badmus FO, Dos Reis IC, Kartika R. Recent advancements in pyrrole synthesis. Synthesis 2021; 53(9): 1531-1555.
| Crossref | Google Scholar | PubMed |
15 Nakano H, Umio S, Kariyone K, Tanaka K, Kishimoto T, Noguchi H. Total synthesis of pyrrolnitrin, a new antibiotic. Tetrahedron Lett 1966; 7(7): 737-740.
| Crossref | Google Scholar | PubMed |
16 Gupton JT (2006) Pyrrole natural products with antitumor properties. In: Lee M, editor. Heterocyclic Antitumor Antibiotics. Topics in Heterocyclic Chemistry. Vol 2. Springer; 2006. pp. 53–92. 10.1007/7081_019
17 Gholap SS. Pyrrole: an emerging scaffold for construction of valuable therapeutic agents. Eur J Med Chem 2016; 110: 13-31.
| Crossref | Google Scholar | PubMed |
18 Sarma HK, Sharma BK, Tiwari SC. A novel calcimycin antibiotic from Gram-positive actinomycete Frankia microsymbiont. Curr Sci – Bangalore 2003; 85(10): 1401-1403.
| Google Scholar |
19 Kulkarni SK, Singh VP. Licofelone – a novel analgesic and anti-inflammatory agent. Curr Top Med Chem 2007; 7(3): 251-263.
| Crossref | Google Scholar | PubMed |
20 Joudeh J, Claxton D. Obatoclax mesylate: pharmacology and potential for therapy of hematological neoplasms. Expert Opin Investig Drugs 2012; 21(3): 363-373.
| Crossref | Google Scholar | PubMed |
21 Deeks ED, Keating GM. Sunitinib. Drugs 2006; 66: 2255-2266.
| Crossref | Google Scholar | PubMed |
22 Brogden RN, Heel RC, Speight TM, Avery GS. Tolmetin: a review of its pharmacological properties and therapeutic efficacy in rheumatic diseases. Drugs 1978; 15: 429-450.
| Crossref | Google Scholar | PubMed |
23 Wilkerson WW, Copeland RA, Covington M, Trzaskos JM. Anti-inflammatory 4,5-diarylpyrroles. 2. Activity as a function of cyclooxygenase-2 inhibition. J Med Chem 1995; 38(20): 3895-3901.
| Crossref | Google Scholar | PubMed |
24 Wurz RP, Charette AB. Doubly activated cyclopropanes as synthetic precursors for the preparation of 4-nitro-and 4-cyano-dihydropyrroles and pyrroles. Org Lett 2005; 7(12): 2313-2316.
| Crossref | Google Scholar | PubMed |
25 Sobenina LN, Vasil’tsov AM, Petrova OV, Petrushenko KB, Ushakov IA, Clavier G, et al. General route to symmetric and asymmetric meso-CF3-3 (5)-aryl (hetaryl)-and 3,5-diaryl (dihetaryl)-BODIPY dyes. Org Lett 2011; 13(10): 2524-2527.
| Crossref | Google Scholar | PubMed |
26 D’Silva C, Walker DA. Acid‒base catalysis in the synthesis of arylmethylene and alkylmethine pyrroles. J Org Chem 1998; 63: 6715-6718.
| Google Scholar |
27 Gelling VJ, Wiest MM, Tallman DE, Bierwagen GP, Wallace GG. Electroactive-conducting polymers for corrosion control: studies of poly (3-octyl pyrrole) and poly (3-octadecyl pyrrole) on aluminum 2024-T3 alloy. Prog Org Coat 2001; 43(1–3): 149-157.
| Google Scholar |
28 Davidson D. An extension of Knorr’s pyrrole synthesis. J Org Chem 1938; 3(4): 361-364.
| Google Scholar |
29 Duc DX, Chung NT. Recent developments in the synthesis of thiazoles. Curr Org Synth 2022; 19(6): 702-730.
| Crossref | Google Scholar | PubMed |
30 Knorr L. Synthese von Pyrrolderivaten. Ber Dtsch Chem Ges 1884; 17(2): 1635-1642 [In German].
| Crossref | Google Scholar |
31 Paal C. Synthese von Thiophen- und Pyrrolderivaten. Ber Dtsch Chem Ges 1885; 18(2): 2251-2254 [In German].
| Crossref | Google Scholar |
32 Alvi S, Hasan A, Ali R. Paal–Knorr pyrroles synthesis: a green perspective. Polycycl Aromat Comp 2024; 44(5): 3558-3575.
| Google Scholar |
33 Zhu Y, Rabindranath AR, Beyerlein T, Tieke B. Highly luminescent 1,4-diketo-3,6-diphenylpyrrolo [3,4-c] pyrrole-(DPP-) based conjugated polymers prepared upon Suzuki coupling. Macromolecules 2007; 40(19): 6981-6989.
| Google Scholar |
34 Kucukdisli M, Ferenc D, Heinz M, Wiebe C, Opatz T. Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones. Beilstein J Org Chem 2014; 10(1): 466-470.
| Crossref | Google Scholar | PubMed |
35 Clauson-Kaas N, Tyle Z, Rottenberg M, Stenhagen E, Östling S. Preparation of cis and trans 2,5-dimethoxy-2-(acetamidomethyl)-2,5-dihydrofuran, of cis and trans 2,5-dimethoxy-2-(acetamidomethyl)-tetrahydrofuran and of 1-phenyl-2-(acetamidomethyl)-pyrrole. Acta Chem Scand 1952; 6: 667-670.
| Crossref | Google Scholar |
36 Barton DH, Zard SZ. A new synthesis of pyrroles from nitroalkenes. J Chem Soc Chem Commun [16] 1985; 1098-1100.
| Crossref | Google Scholar |
37 Kaur N. Ionic liquids: promising but challenging solvents for the synthesis of N-heterocycles. Mini-Rev Org Chem 2017; 14(1): 3-23.
| Crossref | Google Scholar |
38 Kaur N. Ionic liquid promoted eco-friendly and efficient synthesis of six-membered N-polyheterocycles. Curr Org Synth 2018; 15(8): 1124-1146.
| Crossref | Google Scholar |
39 Azad I, Hassan F, Saquib M, Ahmad N, Khan AR, Al-Sehemi AG, Nasibullah M. A critical review on advances in the multicomponent synthesis of pyrroles. Orient J Chem 2018; 34(4): 1670.
| Crossref | Google Scholar |
40 Singh DK, Kumar R. Clauson-Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach. Beilstein J Org Chem 2023; 19(1): 928-955.
| Crossref | Google Scholar | PubMed |
41 Sharma S, Sharma P, Budhalakoti B, Kumar A, Singh K, Kumar Kamboj R, Bhatrola K. Exploring the impact of ionic liquids on pyrazole derivatives synthesis: a critical review. ChemistrySelect 2024; 9(31): e202401925.
| Crossref | Google Scholar |
42 Jorapur YR, Lee CH, Chi DY. Mono-and dialkylations of pyrrole at C2 and C5 positions by nucleophilic substitution reaction in ionic liquid. Org Lett 2005; 7(7): 1231-1234.
| Crossref | Google Scholar | PubMed |
43 Jorapur YR, Chi DY. Intramolecular cycloalkylation of pyrrole in ionic liquids and immobilized ionic liquids. Bull Korean Chem Soc 2011; 32(spc8): 3130-3132.
| Google Scholar |
44 Aydogan F, Yolacan C. Clauson-Kaas pyrrole synthesis catalyzed by acidic ionic liquid under microwave irradiation. J Chem 2013; 2013(1): 976724.
| Crossref | Google Scholar |
45 Li D, Zang H, Wu C, Yu N. 1-Methylimidazolium hydrogen sulfate catalyzed convenient synthesis of 2,5-dimethyl-N-substituted pyrroles under ultrasonic irradiation. Ultrason Sonochem 2013; 20(5): 1144-1148.
| Crossref | Google Scholar | PubMed |
46 Naeimi H, Dadaei M. Efficient and green synthesis of N‐aryl pyrroles catalyzed by ionic liquid [H‐NMP][HSO4] in water at room temperature. J Chin Chem Soc 2014; 61(10): 1127-1132.
| Crossref | Google Scholar |
47 Naeimi H, Dadaei M. Microwave promoted green synthesis of pyrroles using N-methyl-2-pyrrolidonium hydrogen sulfate as an efficient catalyst under solvent-free condition. Iran J Sci Technol Trans Sci 2018; 42: 1241-1246.
| Crossref | Google Scholar |
48 Nguyen HT, Thi Le NP, Nguyen Chau DK, Tran PH. New nano-Fe3O4-supported Lewis acidic ionic liquid as a highly effective and recyclable catalyst for the preparation of benzoxanthenes and pyrroles under solvent-free sonication. RSC Adv 2018; 8(62): 35681-35688.
| Crossref | Google Scholar | PubMed |
49 Shekarchi M, Behbahani FK. [Bmim] HSO4 loaded on graphene oxide: a green and retrievable nanocatalyst for the synthesis of polysubstituted pyrroles; some of which are fluorinated. Lett Org Chem 2021; 18(4): 294-302.
| Crossref | Google Scholar |
50 Meshkatalsadat MH, Mahmoudi A, Lotfi S, Pouramiri B, Foroumadi A. Green and four-component cyclocondensation synthesis and in silico docking of new polyfunctionalized pyrrole derivatives as the potential anticholinesterase agents. Mol Divers 2022; 26: 3021-3035.
| Crossref | Google Scholar | PubMed |
51 Yavari I, Kowsari E. Task-specific basic ionic liquid: a reusable and green catalyst for one-pot synthesis of highly functionalized pyrroles in aqueous media. Synlett 2008; 2008(6): 897-899.
| Google Scholar |
52 Yavari I, Kowsari E. Efficient and green synthesis of tetrasubstituted pyrroles promoted by task-specific basic ionic liquids as catalyst in aqueous media. Mol Divers 2009; 13: 519-528.
| Crossref | Google Scholar | PubMed |
53 Nourmohammadian F, Shamekhi SS. Mixture of ionic liquids as novel media for green synthesis of diketopyrrolopyrrole pigments. Prog Color Color Coat 2012; 6(2): 81-86.
| Crossref | Google Scholar |
54 Sémeril D, Olivier-Bourbigou H, Bruneau C, Dixneuf PH. Alkene metathesis catalysis in ionic liquids with ruthenium allenylidene salts. Chem Commun 2002; 2: 146-147.
| Crossref | Google Scholar | PubMed |
55 Meshram HM, Prasad BRV, Kumar DA. A green approach for efficient synthesis of N-substituted pyrroles in ionic liquid under microwave irradiation. Tetrahedron Lett 2010; 51(27): 3477-3480.
| Crossref | Google Scholar |
56 Kathiravan S, Raghunathan R. Synthesis of pyrrolo [2,3-a] pyrrolizidino derivatives through intramolecular 1,3-dipolar cycloaddition in ionic liquid medium. Synth Commun 2013; 43(1): 147-155.
| Crossref | Google Scholar |
57 Nourmohammadian F, Shamekhi SS. An efficient pathway to synthesize diketopyrrolopyrrole pigments in ionic liquids. Lett Org Chem 2013; 10(2): 131-138.
| Crossref | Google Scholar |
58 Shamekhi SS, Nourmohammadian F. Microwave‐assisted synthesis of diketopyrrolopyrrole pigments in ionic liquid. Pigm Resin Technol 2013; 42(4): 215-222.
| Google Scholar |
59 Zhang MM, Lu L, Zhou YJ, Wang XS. Iodine-catalyzed synthesis of pyrrolo [1,2-a] quinazoline-3 a-carboxylic acid derivatives in ionic liquids. Res Chem Intermed 2013; 39: 3327-3335.
| Crossref | Google Scholar |
60 Xia L, Idhayadhulla A, Lee YR, Kim SH, Wee YJ. Microwave-assisted synthesis of diverse pyrrolo [3,4-c] quinoline-1,3-diones and their antibacterial activities. ACS Comb Sci 2014; 16(7): 333-341.
| Crossref | Google Scholar | PubMed |
61 Shahvelayati AS, Ghazvini M, Yadollahzadeh K, Delbari AS. A phosphine-mediated synthesis of 2, 3, 4,5-tetra-substituted N-hydroxypyrroles from α-oximino ketones and dialkyl acetylenedicarboxylates under ionic liquid green-media. Comb Chem High Throughput Screen 2018; 21(1): 14-18.
| Crossref | Google Scholar | PubMed |
62 Khaligh NG, Mihankhah T, Johan MR, Titinchi SJ. Microwave-assisted synthesis of pyrrolidinone derivatives using 1,1’-butylenebis (3-sulfo-3H-imidazol-1-ium) chloride in ethylene glycol. Green Process Synth 2019; 8(1): 373-381.
| Crossref | Google Scholar |
63 Mondal P, Chatterjee S, Bhaumik A, Maity S, Ghosh P, Mukhopadhyay C. Creation of DABCO‐based amphoteric ionic liquid supported TiO2 nanoparticles: execution of amplified catalytic properties on microwave‐assisted synthesis of N‐substituted pyrroles. ChemistrySelect 2019; 4(11): 3140-3150.
| Crossref | Google Scholar |
64 Pervaram S, Ashok D, Reddy CVR, Sarasija M, Ganesh A. Ionic liquid mediated one-pot multicomponent synthesis of methyl 1,2-diaryl-4-hydroxy-5-oxo-2,5-dihydro-1h-pyrrole-3-carboxylates. Chem Data Collect 2020; 29: 100508.
| Crossref | Google Scholar |
65 Nguyen HT, Ngo DKT, Chau KDN, Tran PH. Imidazolium triflate ionic liquid improves the activity of ZnCl2 in the synthesis of pyrroles and ketones. Org Prep Proced Int 2021; 53(2): 157-165.
| Crossref | Google Scholar |
66 Mamaghani M, Ansar S, Jahanshahi P. A convergent one-pot synthesis of novel pyrrole-pyridopyrimidines hybrids using 1-carboxymethyl-2,3-dimethylimidazolium iodide {[cmdmim] I} as a recyclable catalyst. Polycycl Aromat Comp 2022; 42(8): 5217-5230.
| Google Scholar |
67 Ranu BC, Dey SS. An efficient synthesis of pyrroles by a one-pot, three-component condensation of a carbonyl compound, an amine and a nitroalkene in a molten ammonium salt. Tetrahedron Lett 2003; 44(14): 2865-2868.
| Crossref | Google Scholar |
68 Wang B, Gu Y, Luo C, Yang T, Yang L, Suo J. Pyrrole synthesis in ionic liquids by Paal–Knorr condensation under mild conditions. Tetrahedron Lett 2004; 45(17): 3417-3419.
| Crossref | Google Scholar |
69 Portela-Cubillo F, Scott JS, Walton JC. Microwave-assisted preparations of dihydropyrroles from alkenone O-phenyl oximes. Chem Commun (Cambridge, England) 2007; 39: 4041-4043.
| Crossref | Google Scholar | PubMed |
70 Qin J, Zhang J, Wu B, Zheng Z, Yang M, Yu X. Efficient and mild protocol for the synthesis of 4(3)‐substituted 3(4)‐nitro‐1H‐pyrroles and 3‐substituted 4‐methyl‐2‐tosyl‐1H‐pyrroles from nitroolefins and tosylmethyl isocyanide in ionic liquids. Chin J Chem 2009; 27(9): 1782-1788.
| Crossref | Google Scholar |
71 Meshram HM, Babu BM, Kumar GS, Thakur PB, Bangade VM. Catalyst-free four-component protocol for the synthesis of substituted pyrroles under reusable reaction media. Tetrahedron Lett 2013; 54(19): 2296-2302.
| Crossref | Google Scholar |
72 Yadav VD, Dighe SU, Batra S. Synthesis of N-alkyl pyrroles via decarboxylation/dehydration in neutral ionic liquid under catalyst-free conditions. RSC Adv 2014; 4(101): 57587-57590.
| Crossref | Google Scholar |
73 He YH, Wang GQ, Xu KL, Guan Z. An efficient procedure for the synthesis of polysubstituted pyrroles in an ionic liquid. Z Naturforsch B 2011; 66(2): 191-196.
| Crossref | Google Scholar |
74 Khan MU, Rather RA, Siddiqui ZN. Design, characterization and catalytic evaluation of halometallic ionic liquid incorporated Nd2O3 nanoparticles ([smim][FeCl4]−@Nd2O3) for the synthesis of N-aryl indeno pyrrole derivatives. RSC Adv 2020; 10(73): 44892-44902.
| Crossref | Google Scholar | PubMed |
