Electrochemical Synthesis of Quinolines

Abstract

This report outlines an intramolecular oxidative annulation process involving N-substituted o-amino phenylacetylene, performed under electrochemical conditions, which yields substituted quinoline in an undivided cell at room temperature. The reaction features mild conditions, requiring neither external oxidants nor metals, and achieves yields that range from good to excellent. Moreover, the synthetic potential of quinoline has been demonstrated resulting in the synthesis of substituted polycyclic isoindolinone and (aza-)isoindolinone compounds.

Key words

oxidative annulation - intramolecular electrochemical synthesis - aromatic enamine - substituted quinoline - polycyclic compounds

Publication History

Received: 31 July 2024

Accepted after revision: 15 August 2024

Accepted Manuscript online:
15 August 2024

Article published online:
25 September 2024

• References and Notes

• 1 Martins P, Jesus J, Santos S, Raposo LR, Roma-Rodrigues C, Baptista PV, Fernandes AR. Molecules 2015; 20: 16852
• 2 Michael JP. Nat. Prod. Rep. 2008; 25: 166
• 3 Rajendran S, Sivalingam K, Karnam Jayarampillai RP, Wang W.-L, Salas Cristian O. Chem. Biol. Drug Des. 2022; 100: 1042
• 4 Balderas-Renteria I, Gonzalez-Barranco P, Garcia A, Banik BK, Rivera G. Curr. Med. Chem. 2012; 19: 4377
• 5 Lewinska G, Sanetra J, Marszalek KW. J. Mater Sci.: Mater. Electron. 2021; 32: 18451
• 6 Ajani OO, Iyaye KT, Ademosun OT. RSC Adv. 2022; 12: 18594
• 7 Zhao Y.-Q, Li X, Guo H.-Y, Shen Q.-K, Quan Z.-S, Luan T. Molecules 2023; 28: 6478
• 8 El-Feky SA. H, Abd El-Samii ZK, Osman NA, Lashine J, Kamel MA, Thabet HK. Bioorg. Chem. 2015; 58: 104
• 9 Soares RR, da Silva JM. F, Carlos BC, da Fonseca CC, de Souza LS. A, Lopes FV, de Paula Dias RM, Moreira PO. L, Abramo C, Viana GH. R, de Pila Varotti F, da Silva AD, Scopel KK. G. Bioorg. Med. Chem. Lett. 2015; 25: 2308
• 10 Baragaña B, Norcross NR, Wilson C, Porzelle A, Hallyburton I, Grimaldi R, Osuna-Cabello M, Norval S, Riley J, Stojanovski L, Simeons FR. C, Wyatt PG, Delves MJ, Meister S, Duffy S, Avery VM, Winzeler EA, Sinden RE, Wittlin S, Frearson JA, Gray DW, Fairlamb AH, Waterson D, Campbell SF, Willis P, Read KD, Gilbert IH. J. Med. Chem. 2016; 59: 9672
• 11 Li L.-H, Niu Z.-J, Liang Y.-M. Chem. Asian J. 2020; 15: 231
• 12 Kumar A, Dhameliya TM, Sharma K, Patel KA, Hirani RV. ChemistrySelect 2022; 7: e202201059
• 13 Xia X.-F, Zhang L.-L, Song X.-R, Liu X.-Y, Liang Y.-M. Org. Lett. 2012; 14: 2480
• 14 Xia X.-F, Zhang G.-W, Wang D, Zhu S.-L. J. Org. Chem. 2017; 82: 8455
• 15 Xia X, He W, Wang D. Adv. Synth. Catal. 2019; 361: 2959
• 16 Punjajom K, Ruengsangtongkul S, Tummatorn J, Paiboonsombat P, Ruchirawat S, Thongsornkleeb C. J. Org. Chem. 2023; 88: 6736
• 17 Möhle S, Zirbes M, Rodrigo E, Gieshoff T, Wiebe A, Waldvogel SR. Angew. Chem. Int. Ed. 2018; 57: 6018
• 18 Jiang Y, Xu K, Zeng C. Chem. Rev. 2018; 118: 4485
• 19 Wiebe A, Gieshoff T, Möhle S, Rodrigo E, Zirbes M, Waldvogel SR. Angew. Chem. Int. Ed. 2018; 57: 5594
• 20 Yan M, Kawamata Y, Baran PS. Chem. Rev. 2017; 21: 13230
• 21 Little RD. J. Org. Chem. 2020; 85: 13375
• 22 General Procedure for Electrochemical Quinoline Synthesis Into the undivided cell were taken N-substituted o-amino phenylacetylene 1a, KI (1 equiv), 5 mL of DMF–H₂O (99:1). The mixture was stirred under constant current (10 mA) with a C anode and a C cathode in an undivided cell at room temperature for 6 h. After the completion of reaction as monitored on TLC, the reaction was quenched with cold water and extracted with EtOAc. The combined organic layer was dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The product was purified by flash column chromatography using PE and EtOAc as solvent as eluent.Compound 2: 84% yield, yellow solid, mp 124–126 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.24 (d, J = 8.6 Hz, 1 H), 7.87–7.81 (m, 3 H), 7.75 (t, J = 1.7 Hz, 1 H), 7.64 (ddd, J = 8.7, 6.0, 1.1 Hz, 2 H), 7.57–7.38 (m, 6 H), 3.91 (q, J = 7.1 Hz, 2 H), 0.86 (t, J = 7.2 Hz, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 195.46, 166.74, 155.93, 148.13, 147.48, 141.97, 136.58, 134.56, 134.52, 131.96, 130.21, 129.75, 129.16, 129.06, 128.94, 128.40, 126.95, 125.96, 123.36, 123.27, 62.16, 13.35. IR (neat): 3062, 2982, 1722, 1672, 1581 cm^–1. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₅H₁₈ClNO₃: 416.1048; found: 416.1060.
• 23 Mitobe K, Kawasaki-Takasuka T, Agou T, Kubota T, Yamazaki T. J. Fluorine Chem. 2019; 218: 36
• 24 Chollet A, Stigliani J, Pasca MR, Mori G, Lherbet C, Constant P, Quémard A, Bernadou J, Pratviel G, Bernardes-Génisson V. Chem. Biol. Drug Des. 2016; 88: 740
• 25 Viña D, del Olmo E, Lopez-Pérez JL, San Feliciano A. Tetrahedron 2009; 65: 1574
• 26 Aitha A, Payili N, Rekula SR, Yennam S, Anireddy JS. ChemistrySelect 2017; 2: 7246
• 27 General Procedure for the Synthesis of IsoindolinoneInto the RB were taken substituted quinoline 2aa, 2ad, 2ae, or 2af and hydrazine hydrate (5 equiv). To this EtOH was added and kept under reflux. The reaction was stirred for 12–24 h. After completion of the reaction as monitored on TLC, it was quenched with water and extracted with EtOAc. The combined organic layer was dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The product was purified by flash column chromatography using PE and EtOAc as eluent. Compound 2aa: 71% yield, yellow solid, mp 252–254 °C. ¹H NMR (600 MHz, DMSO): δ = 8.15 (d, J = 8.4 Hz, 1 H), 7.97 (dd, J = 6.5, 2.9 Hz, 2 H), 7.91–7.81 (m, 2 H), 7.60–7.56 (m, 1 H), 7.51 (ddd, J = 15.4, 8.3, 3.6 Hz, 5 H), 7.18 (t, J = 8.9 Hz, 2 H), 4.38 (s, 2 H). ¹³C NMR (150 MHz, DMSO): δ = 163.66, 162.71, 161.09, 160.45, 155.02, 154.93, 149.02, 141.50, 137.42, 134.99, 131.66, 130.40, 129.17, 128.68, 127.63, 127.45, 124.46, 120.27, 120.03, 115.36, 115.21, 88.41. IR (neat): 3399, 3060, 2920, 1720, 1656, 1570 cm^–1. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₃H₁₆FN₃O₂: 386.1300; found: 386.1271.
• 28 General Procedure for the Synthesis of (Aza-)Isoindolinone Into the RB were taken substituted quinoline 2ab, 2ac, or 2ag and hydroxylamine hydrochloride (10 equiv). To this, Et₃N (10 equiv) was added followed by addition of ethanol under reflux conditions. The reaction was stirred for 12 h. After completion of the reaction as monitored on TLC, it was quenched with water and extracted with EtOAc. The combined organic layer was dried with anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The product was purified by flash column chromatography using PE and EtOAc as eluent.Compound 2ab: 79% yield, white solid, mp 210–212 °C. ¹H NMR (400 MHz, DMSO): δ = 9.98 (s, 1 H), 8.16 (d, J = 8.5 Hz, 1 H), 7.90 (dt, J = 15.0, 10.4 Hz, 5 H), 7.63–7.41 (m, 8 H). ¹³C NMR (100 MHz, DMSO): δ = 161.54, 154.81, 153.48, 149.08, 137.29, 137.23, 133.14, 131.88, 131.47, 130.37, 130.02, 129.28, 128.78, 128.54, 128.47, 127.87, 127.57, 124.31, 120.09, 119.37, 88.11. IR (neat): 3450, 3063, 2922, 1705, 1618, 1564 cm^–1. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₂₃H₁₅ClN₂O₃: 403.0844; found: 403.0827.
• 29 Tang S, Gao X, Lei A. Chem. Commun. 2017; 53: 3354