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DOI: 10.1055/a-2695-8406
Recent Advancements in Nitration of Anilines Utilizing Diverse Nitrating Agents
Authors
Supported by: NIT Uttarakhand for Institute
Funding Information NIT Uttarakhand
Abstract
Nitroarenes are important intermediates in the synthesis of dyes, pharmaceuticals, and functional materials. The nitro group serves as a key precursor to amines, which have been widely employed in ortho-C(sp²)–H bond activation. Although the conventional electrophilic nitration of aniline using a strong acid mixture is well established, it suffers from several drawbacks, including the generation of acidic waste, low yields, poor selectivity, over-nitration, and limited functional group tolerance. As an alternative, transition-metal-catalyzed, directing-group-assisted regiospecific ortho-nitration of arene C–H bonds has emerged as a more efficient, convenient, atom- and step-economical approach that can proceed under mild conditions. In addition, various transition metal nitrates have demonstrated potential in the selective electrophilic nitration of anilines. However, ortho/para-mixtures of regioisomers are obtained in some cases. This review article summarizes all such recent advancements in the nitration reaction of protected anilines using a range of nitrating agents.
Publication History
Received: 18 July 2025
Accepted after revision: 04 September 2025
Accepted Manuscript online:
04 September 2025
Article published online:
09 October 2025
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References
- 1 Nepali K, Lee H-Y, Liou J-P. J Med Chem 2019; 62: 2851
- 2 Feng G, Zhu M, Liu L, Li C. Green Chem 2019; 21: 1769
- 3 Benkhaya S, M’rabet S, El Harfi A. Heliyon 2020; 6: e03271
- 4 Nataraj N, Chen T-W, Akilarasan M. et al. Chem Eng J 2022; 446: 137025
- 5 A. N. M, E. C. I, C. N. A, et al. Int Res Mater Environ 2024; 4: 12
- 6 Ono N. The Nitro Group in Organic Synthesis. Weinheim: Wiley-VCH; 2001
- 7 Ju K-S, Parales RE. Microbiol Mol Biol Rev 2010; 74: 250
- 8 Noriega S, Cardoso-Ortiz J, López-Luna A, Cuevas-Flores MDR, De La Torre FJA. Pharm 2022; 15: 717
- 9 Langer P. Synlett 2024; 35: 2063
- 10 Booth G. Ullmann’s Encyclopedia of Industrial Chemistry. Wiley-VCH, Ed.; Wiley; 2000
- 11 Dubey SK, Singh AK, Singh H. et al. J Med Chem 1978; 21: 1178
- 12 Fonseca T, Gigante B, Gilchrist TL. Tetrahedron 2001; 57: 1793
- 13 Dohle W, Staubitz A, Knochel P. Chem Eur J 2003; 9: 5323
- 14 Yang X, Xi C, Jiang Y. Tetrahedron Lett 2005; 46: 8781
- 15 Yan G, Yang M. Org Biomol Chem 2013; 11: 2554
- 16 Wylie L, Innocenti P, Whelligan DK, Hoelder S. Org Biomol Chem 2012; 10: 4441
- 17 Brickman M, Ridd JH. J Chem Soc 1965; 0: 6845
- 18 Hartshorn SR, Ridd JH. J Chem Soc B 1968; 0: 1063
- 19 Olah GA, Malhotra R, Narang SC. World Scientific Series in 20th Century Chemistry. Vol. 11. World Scientific Publishing Company; 2003: 975
- 20 Patra S, Mosiagin I, Giri R, Katayev D. Synthesis 2022; 54: 3432
- 21 Yan G, Yang M. Org Biomol Chem 2013; 11: 2554
- 22 Patel SS, Patel DB, Patel HD. ChemistrySelect 2021; 6: 1337
- 23 Mellor JM, Mittoo S, Parkes R, Millar RW. Tetrahedron 2000; 56: 8019
- 24 Dinçtürk S, Ridd JH. J Chem Soc Perkin Trans 2 1982; 965
- 25 Iranpoor N, Firouzabadi H, AliZolfigol M. Synth Commun 1998; 28: 2773
- 26 He K, Zhang T, Zhang S. et al. Org Lett 2019; 21: 5030
- 27 Mudithanapelli C, Dhorma LP, Kim M. Org Lett 2019; 21: 3098
- 28 Song L-R, Fan Z, Zhang A. Org Biomol Chem 2019; 17: 1351
- 29 Kloeckner U, Nachtsheim BJ. Chem Commun 2014; 50: 10485
- 30 Li Y-X, Li L-H, Yang Y-F. et al. Chem Commun 2014; 50: 9936
- 31 Düsel SJS, König B. J Org Chem 2018; 83: 2802
- 32 Dai E, Dong Y, Kong R. et al. Synth Commun 2020; 50: 1687
- 33 Kianmehr E, Nasab SB. Eur J Org Chem 2018; 2018: 6447
- 34 Xie D-X, Yu H-J, Liu H, Xue W-C, Qin Y-S, Shao G. Tetrahedron 2019; 75: 1157
- 35 Patel SS, Patel DB, Poddar AK. et al. J Mol Struct 2023; 1280: 135039
- 36 Kilpatrick B, Heller M, Arns S. Chem Commun 2013; 49: 514
- 37 Chaudhary P, Gupta S, Muniyappan N, Sabiah S, Kandasamy J. J Org Chem 2019; 84: 104
- 38 Ji Y, Yan H, Jiang Q. Eur J Org Chem 2015; 2015: 2051
- 39 Guo X, Lv C, Mahmood Q, Zhou L, Xu G, Wang Q. Org Chem Front 2019; 6: 3401
- 40 Hernando E, Castillo RR, Rodríguez N, Gómez Arrayás R, Carretero JC. Chem Eur J 2014; 20: 13854
- 41 Bharadwaj SK, Boruah PK, Gogoi PK. Catal Commun 2014; 57: 124
- 42 Botla V, Ramana DV, Chiranjeevi B, Chandrasekharam M. ChemistrySelect 2016; 1: 3974
- 43 Wang C-M, Tang K-X, Gao T-H, Chen L, Sun L-P. J Org Chem 2018; 83: 8315
- 44 Gao Y, Mao Y, Zhang B, Zhan Y, Huo Y. Org Biomol Chem 2018; 16: 3881
- 45 Liu S, Gan Z, Jiang M. et al. JACS Au 2024; 4: 4899
- 46 Zheng Y, Hu Q-Q, Huang Q, Xie Y. Org Lett 2024; 26: 3316
- 47 Zheng Y, Liu Z, Ying Z, Xie Y. J Org Chem 2025; 90: 6926
- 48 Boddapati SNM, Tamminana R, Senapathi HJ. et al. J Mol Struct 2025; 1329: 141409
- 49 Andrejčák S, Dudáš P, Májek M. Synlett 2025; 36: 1397
- 50 Wan Y, Zhang Z, Ma N, Bi J, Zhang G. J Org Chem 2019; 84: 780
- 51 Pawar GG, Brahmanandan A, Kapur M. Org Lett 2016; 18: 448
- 52 Nageswar Rao D, Rasheed S, Raina G. et al. J Org Chem 2017; 82: 7234
- 53 Vinayak B, Chandrasekharam M. Org Lett 2017; 19: 3528
- 54 Reddy Depa M, Potla S, Narkhede UC, Jadhav VD, Vidavalur S. Tetrahedron Lett 2020; 61: 152223
- 55 Iqbal Z, Joshi A, De SR. Synth Commun 2023; 53: 557
- 56 Lu Y, Li Y, Zhang R, Jin K, Duan C. Tetrahedron 2013; 69: 9422
- 57 Loera-Garcia BV, Leyva-Ramos S, Cardoso-Ortiz J. et al. Curr Org Synth 2025; 22: 234
- 58 Fan X, Zhao Y, Liu L, Wang H. Chin J Chem 2023; 41: 1589
- 59 Natarajan P, Chaudhary R, Rani N, Sakshi, Venugopalan P. Tetrahedron Lett 2020; 61: 151529
- 60 Blum SP, Nickel C, Schäffer L, Karakaya T, Waldvogel SR. ChemSusChem 2021; 14: 4936
- 61 Ma W, McBride JT, Phillips RS. Tetrahedron Lett 2025; 159: 155515
- 62 Sun Y, Shi H, He J. et al. J Org Chem 2025; 90: 2328
- 63 Yang T, Li X, Deng S. et al. JACS Au 2022; 2: 2152