Metal-Free Amidation and Selenoamidation of 2-Methylquinolines with Secondary Amines Using Selenium Dioxide, and Antibacterial Evaluation of the Products

Abstract

We report a metal-free protocol for the amidation and selenoamidation of 2-methylquinolines by using selenium dioxide as the key reagent. This method offers several advantages, including ease of operation, a short reaction time (15 min), and moderate to excellent yields (50–90%). The method demonstrates a broad substrate tolerance, including various secondary amines and 2-methyl heterocycles such as pyridine and benzothiazole. The applicability of the method was further highlighted through late-stage functionalization of ciprofloxacin, yielding a bioactive hybrid molecule with a remarkable MIC value of 0.195 μg/mL.

Key words

methylquinolines - amidation - selenoamidation - selenium dioxide - metal-free reaction

Publikationsverlauf

Eingereicht: 18. November 2024

Angenommen nach Revision: 21. Januar 2025

Artikel online veröffentlicht:
06. März 2025

• References and Notes

• 1 Matada BS, Pattanashettar R, Yernale NG. Bioorg. Med. Chem. 2021; 32: 115973
• 2 Narender P, Srinivas U, Ravinder M, Ananda Rao B, Ramesh C, Harakishore K, Gangadasu B, Murthy US. N, Jayathirtha Rao V. Bioorg. Med. Chem. 2006; 14: 4600
• 3 Shiraki H, Kozar MP, Melendez V, Hudson TH, Ohrt C, Magill AJ, Lin AJ. J. Med. Chem. 2011; 54: 131
• 4 Jafari F, Baghayi H, Lavaee P, Hadizadeh F, Soltani F, Moallemzadeh H, Mirzaei S, Aboutorabzadeh SM, Ghodsi R. Eur. J. Med. Chem. 2019; 164: 292
• 5 Carta A, Briguglio I, Piras S, Corona P, Boatto G, Nieddu M, Giunchedi P, Marongiu ME, Giliberti G, Iuliano F, Blois S, Ibba C, Busonera B, La Colla P. Bioorg. Med. Chem. 2011; 19: 7070
• 6 Krafts K, Hempelmann E, Skórska-Stania A. Parasitol. Res. 2012; 111: 1
• 7 Falk NP, Hughes SW, Rodgers BC. Am. Fam. Physician 2016; 94: 454
• 8 https://www.fiercepharma.com/pharma/fda-approves-cometriq-to-treat-rare-type-of-thyroid-cancer (accessed Feb 7, 2025)
• 9 Latha DS, Yaragorla S. Eur. J. Org. Chem. 2020; 2020: 2155
• 10 Parveen N, Muthukumar A, Sekar G. Adv. Synth. Catal. 2019; 361: 4255
• 11 Wolfe JF, Portlock DE, Feuerbach DJ. J. Org. Chem. 1974; 39: 2006
• 12 Shang R, Yang Z.-W, Wang Y, Zhang S.-L, Liu L. J. Am. Chem. Soc. 2010; 132: 14391
• 13 Liu M, Chen X, Chen T, Yin S.-F. Org. Biomol. Chem. 2017; 15: 2507
• 14 Verhaeghe P, Rathelot P, Gellis A, Rault S, Vanelle P. Tetrahedron 2006; 62: 8173
• 15 Xie H, Liao Y, Chen S, Chen Y, Deng G.-J. Org. Biomol. Chem. 2015; 13: 6944
• 16 Upadhyay R, Rana R, Maurya SK. ChemCatChem 2021; 13: 1867
• 17 Bao Y.-S, Zhaorigetu B, Agula B, Baiyin M, Jia M. J. Org. Chem. 2014; 79: 803-808
• 18 Makhal PN, Dayare LN, Chilvery S, Devi P, Sujat Shaikh A, Sharma A, Negi A, Godugu C, Rao Kaki V. Bioorg. Chem. 2024; 151: 107677
• 19 Makhal PN, Dannarm SR, Shaikh AS, Sonti R, Rao Kaki V. ChemistrySelect 2022; 7: e202200933
• 20 Makhal PN, Sood A, Shaikh AS, Dayare LN, Khatri DK, Rao Kaki V. RSC Med. Chem. 2023; 14: 2677
• 21 Waitkins GR, Clark CW. Chem. Rev. 1945; 36: 235
• 22 Sonoda N, Yamamoto Y, Murai S, Tsutsumi S. Chem. Lett. 1972; 1: 229
• 23 2-(Morpholin-4-ylcarbonyl)quinoline (3a); Typical Procedure A 25 mL closed tube was charged with 2-methylquinoline (0.1 mL, 0.69837 mmol, 1 equiv), morpholine (0.14 mL, 0.5587 mmol, 0.8 equiv), and SeO₂ (0.155 g, 1.3967 mmol, 2 equiv). DMSO (1 mL) was added, and the resultant mixture was heated at 100 °C for 1 h until the reaction was complete (TLC). The mixture was then extracted with CH₂Cl₂, and the organic layer was collected, dried (Na₂SO₄), and concentrated under reduced pressure to give a crude residue. The residue was purified by column chromatography [silica gel, EtOAc–hexane (3:7)] to give a yellow solid; yield: 89.0 mg (90%); mp 96–98 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.3 (dd, J = 8.5, 0.9 Hz, 1 H), 8.1 (dq, J = 8.4, 1.0 Hz, 1 H), 7.9–7.8 (m, 1 H), 7.80–7.74 (m, 2 H), 7.6 (ddd, J = 8.1, 6.9, 1.2 Hz, 1 H), 3.9–3.8 (m, 4 H), 3.8–3.7 (m, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 167.6, 153.3, 146.5, 137.3, 130.2, 129.8, 128.1, 127.7, 127.7, 120.1, 67.1, 66.9, 47.9, 42.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₄H₁₅N₂O₂: 243.1128; found: 243.1127.