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Synlett 2025; 36(06): 674-678
DOI: 10.1055/a-2384-7081
DOI: 10.1055/a-2384-7081
letter
Thieme Chemistry Journals Awardees 2024
Sequential Copper-Catalyzed Amidation and Hydroxylation for Acetaminophen Synthesis
The work was supported by SK Chemicals (Y.G.K.) and the National Research Foundation of Korea (NRF-2022M3E5F1081320 and RS-2024-00398065) (D.Y.).
Abstract
A sequential Cu-catalyzed amidation and hydroxylation of p-dihalobenzenes is applied to synthesize acetaminophen. This method allows the direct introduction of acetamido and hydroxy groups under acid-free conditions without forming other regioisomers. By using a one-pot process, acetaminophen can be prepared with an overall yield of up to 74%.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2384-7081.
- Supporting Information
Publication History
Received: 15 June 2024
Accepted after revision: 12 August 2024
Accepted Manuscript online:
12 August 2024
Article published online:
10 September 2024
© 2024. Thieme. All rights reserved
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References and Notes
- 1 Jóźwiak-Bebenista M, Nowak JZ. Acta Pol. Pharm. 2014; 71: 11
- 2 Joncour R, Ferreira A, Duguet N, Lemaire M. Org. Process Res. Dev. 2018; 22: 312
- 3 Faizullabhoy M, Wani G. Acetaminophen Market . Global Market Insights; Selbyville: 2023. https://www.gminsights.com/industry-analysis/acetaminophen-market (accessed Jun 2, 2023)
- 4 Rode CV, Vaidya MJ, Chaudhari RV. Org. Process Res. Dev. 1999; 3: 465
- 5 Rode CV, Vaidya MJ, Jaganathan R, Chaudhari RV. Chem. Eng. Sci. 2001; 56: 1299
- 6 Nadgeri JM, Biradar NS, Patil PB, Jadkar ST, Garade AC, Rode CV. Ind. Eng. Chem. Res. 2011; 50: 5478
- 7 Park J, Maier JS, Evans C, Hatzell M, France S, Sievers C, Bommarius AS. Green Chem. 2024; 26: 4079
- 8 Yao C, Wu J, Pan L, Yu L, Luo J, Shan J, Liu J, Lu C, Feng F, Xu X, Lin L, Yue Y, Wang Q, Zhao J, Zhang Q, Li X. Chem. Eng. J. (Amsterdam, Neth.) 2024; 486: 150329
- 9 Luo J, Yao C, Ma D, Chen Y, Tian M, Xie H, Chen R, Wu J, Zhen Y, Pan L, Lu C, Feng F, Xu X, Wang Q, Zhang Q, Li X. Appl. Catal., A 2023; 660: 119198
- 10 Joncour R, Duguet N, Métay E, Ferreira A, Lemaire M. Green Chem. 2014; 16: 2997
- 11 Mane SN, Gadalkar SM, Rathod VK. Ultrason. Sonochem. 2018; 49: 106
- 12 San BH, Ravichandran S, Park K.-s, Subramani VK, Kim KK. ACS Appl. Mater. Interfaces 2016; 8: 30058
- 13 Nishii Y, Ikeda M, Hayashi Y, Kawauchi S, Miura M. J. Am. Chem. Soc. 2020; 142: 1621
- 14 de Almeida LS, de Mattos MS, Esteves PM. Synlett 2013; 24: 603
- 15 Hossain MD, Oyamada J, Kitamura T. Synthesis 2008; 690
- 16 Bhunia S, Pawar GG, Kumar SV, Jiang Y, Ma D. Angew. Chem. Int. Ed. 2017; 56: 16136
- 17 Klapars A, Huang X, Buchwald SL. J. Am. Chem. Soc. 2002; 124: 7421
- 18 Toto P, Gesquière J.-C, Cousaert N, Deprez B, Willand N. Tetrahedron Lett. 2006; 47: 4973
- 19 Sheppard TD. Org. Biomol. Chem. 2009; 7: 1043
- 20 Yanagisawa S, Ueda K, Taniguchi T, Itami K. Org. Lett. 2008; 10: 4673
- 21 Barham JP, Coulthard G, Emery KJ, Doni E, Cumine F, Nocera G, John MP, Berlouis LE. A, McGuire T, Tuttle T, Murphy JA. J. Am. Chem. Soc. 2016; 138: 7402
- 22 Cristau H.-J, Cellier PP, Spindler J.-F, Taillefer M. Chem. Eur. J. 2004; 10: 5607
- 23 Wang Y, Zhou C, Wang R. Green Chem. 2015; 17: 3910
- 24 Lefèvre G, Tlili A, Taillefer M, Adamo C, Ciofini I, Jutand A. Dalton Trans. 2013; 42: 5348
- 25 Mehmood A, Leadbeater NE. Catal. Commun. 2010; 12: 64
- 26 Ren Y, Cheng L, Tian X, Zhao S, Wang J, Hou C. Tetrahedron Lett. 2010; 51: 43
- 27 Paul R, Ali MA, Punniyamurthy T. Synthesis 2010; 4268
- 28 Acetaminophen (1); One-Pot Procedure A pressure tube was backfilled with N2 and then charged with p-bromoiodobenzene (1 mmol), acetamide (62 mg, 1.05 mmol), CsF (608 mg, 4.0 mmol), and CuI (3.8 mg, 0.02 mmol). Argon-sparged THF (2 mL) and DMEDA (22 μL, 0.2 mmol) were added and the tube was carefully sealed. The mixture was vigorously stirred at 130 °C for 24 h, then cooled to r.t. Argon-flushed H2O (6 mL) was added to the mixture and the pressure tube was resealed. The mixture was then heated at 180 °C for 24 h, cooled to r.t., and diluted with EtOAc (30 mL). The aqueous solution was saturated with NH4Cl and the saturated aqueous layer was extracted with EtOAc (3 × 30 mL). The combined organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The organic residue was purified by chromatography [silica gel, hexane–EtOAc (1:4)] to give a white solid; yield: 74%.