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Synlett 2025; 36(10): 1397-1402
DOI: 10.1055/a-2547-8910
DOI: 10.1055/a-2547-8910
letter
14th EuCheMS Organic Division Young Investigator Workshop
Mechanochemically Driven Radical Nitration of Electron-Rich ortho and para Di- and Trialkoxyarenes Using Iron(III) Nitrate
This work was funded by the European Union, NextGenerationEU through the Recovery and Resilience Plan for Slovakia (Project No. 09I01-03-V04-00018) and by the European Research Council (ERC), CAPELE (101078608). The views and opinions expressed herein are those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them.
Abstract
This study introduces a sustainable mechanochemical approach for the nitration of electron-rich ortho and para di- and trialkoxyarenes using iron(III) nitrate nonahydrate (Fe(NO3)3·9H2O) as a source of nitro radicals. Conventional nitration methods require harsh conditions and hazardous reagents, limiting their application. Herein, mechanochemical activation offers a rapid and efficient alternative with minimal solvent and a reduced reaction time. Screening identified Fe(NO3)3 as the most effective nitrating agent, with successful application with a variety of ortho and para di- and trialkoxyarenes while maintaining high regioselectivity. The scalability and environmental benefits of the method underscore its potential in organic synthesis, advancing a practical, green protocol for radical aromatic nitration.
Key words
radicals - mechanochemistry - nitration - arenes - nitryl radical - iron(III) nitrate - liquid-assisted grindingSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2547-8910.
- Supporting Information
Publication History
Received: 15 December 2024
Accepted after revision: 27 February 2025
Accepted Manuscript online:
27 February 2025
Article published online:
09 April 2025
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- 48 General Procedure A 1.5 mL stainless-steel milling jar was charged with the aromatic compound 1 (1.0 equiv), Fe(NO3)3·9H2O (1.1 equiv) and MeCN (0.3 μL/mg of solid reagents) as a liquid-assisted grinding agent, along with a 6 mm stainless-steel ball. In some cases, the addition of MeCN was unnecessary. The jar was sealed and subjected to ball milling in a shaker mill at a frequency of 30 Hz for 25 min (unless otherwise specified). After milling, the crude reaction mixture was transferred from the jar using dichloromethane, dried over MgSO4, and then filtered. The mixture was further filtered through a short pad of Celite and concentrated under reduced pressure. The product 2 was either isolated at this stage or further purified by silica gel column chromatography using a gradient of hexane and ethyl acetate as the eluent.
- 49 1,4-Dimethoxy-2-nitrobenzene (2a) Yield: 92 mg (quant.); yellow solid; mp 70–72 °C. IR (ATR): 3081, 3033, 2984, 2953, 2851, 1629, 1577, 1524, 1496, 1466, 1353, 1272, 1220, 1190, 1159, 1081, 1038, 1015, 912, 875, 811, 764, 737 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 3.0 Hz, 1 H), 7.11 (dd, J = 9.1, 3.1 Hz, 1 H), 7.03 (d, J = 9.1 Hz, 1 H), 3.92 (s, 3 H), 3.82 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 152.8, 147.3, 139.5, 120.8, 115.1, 110.0, 57.0, 56.0. MS (EI): m/z = 183.0 [M+], 138.0, 107.0, 79.1, 77.1. The characterization data matched those reported in the literature (see Refs. 26 and 50).
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