One-Pot Synthesis of Dicarbazolyl(aryl)methanols Based on α-Keto Acids

Abstract

In this work, carbazoles, one of the most important types of nitrogenous compounds, were used as substrates to synthesize dicarbazolyl(aryl)methanols in moderate to excellent yields (up to 95%). This simple and efficient strategy can regioselectively form an sp³ quaternary carbon with two large sterically hindered carbazole rings, one benzene ring, and an active hydroxy group in a one-pot reaction. The resulting triarylmethanes are all new products, and have high potential as building blocks for medicinal chemistry or materials science.

Key words

one-pot reaction - carbazoles - keto acids - triarylmethanes - dicarbazolylmethanols

Publication History

Received: 04 August 2024

Accepted after revision: 02 September 2024

Accepted Manuscript online:
02 September 2024

Article published online:
30 September 2024

• References and Notes

• 1a Al-Azzawi AG. S, Aziz SB, Dannoun EM. A, Iraqi A, Nofal MM, Murad AR, Hussein AM. Polymers (Basel, Switz.) 2022; 15: 164
• 1b Allen LA. T, Natho P. Org. Biomol. Chem. 2023; 21: 8956
• 1c Wang Y, Li M. Curr. Opin. Electrochem. 2022; 33: 100952
• 1d Tan MA, Sharma N, An SS. A. Antioxidants 2022; 11: 493
• 2 Huang X, Wang M, Zhong S, Xu B. ACS Omega 2023; 8: 26699
• 3 Kadnor VA. Croat. Chem. Acta 2022; 95: 39
• 4a Akiyama R, Sugaya M, Shinozaki H, Yamamoto T. Synth. Commun. 2019; 49: 1193
• 4b Zhou Y, Xu X.-P, Ji S.-J. Org. Lett. 2019; 21: 2039
• 4c Zhou Q, Cobb KM, Tan T, Watson MP. J. Am. Chem. Soc. 2016; 138: 12057
• 4d Zhang M, Shvetsova O, De Bo G. J. Org. Chem. 2020; 85: 2770
• 4e Ye G, Doumon NY, Rousseva S, Liu Y, Abdu-Aguye M, Loi MA, Hummelen JC, Koster LJ. A, Chiechi RC. ACS Appl. Energy Mater. 2019; 2: 2197
• 4f Ye C, Qin A, Tang BZ. Macromolecules 2022; 55: 5353
• 4g Tu X, Chen X, Zhang D, Gao M, Liang J, Bao G, Zhang J, Peng S, Zhang X, Zeng Z, Su Y. Eur. J. Med. Chem. 2021; 211: 113020
• 5 Ma F, Wu X.-T, Miao L.-W, Sun F, Jiang Y.-J, Chen P. Adv. Synth. Catal. 2022; 364: 3477
• 6a Wu X.-T, Xiao E.-K, Ma F, Yin J, Wang J, Chen P, Jiang Y.-J. J. Org. Chem. 2021; 86: 6734
• 6b Xiao E.-K, Wu X.-T, Ma F, Feng X, Chen P, Jiang Y.-J. Org. Lett. 2020; 23: 449
• 6c Xiao E.-K, Wu X.-T, Ma F, Miao L.-W, Jiang Y.-J, Chen P. Chem. Commun. 2021; 57: 7148
• 7a Xie L.-Y, Bai Y.-S, Xu X.-Q, Peng X, Tang H.-S, Huang Y, Lin Y.-W, Cao Z, He W.-M. Green Chem. 2020; 22: 1720
• 7b Yu X, Geng S, Liu G, Guo W, Wang J. J. Organomet. Chem. 2019; 879: 139
• 7c Wang F, Feng H, Li H, Miao T, Cao T, Zhang M. Chin. Chem. Lett. 2020; 31: 1558
• 7d Wang X.-Z, Zeng C.-C. Tetrahedron 2019; 75: 1425
• 8a Guan R, Bennett EL, Huang Z, Xiao J. Green Chem. 2022; 24: 2946
• 8b Li J, Zou D, Wang B, İşcan A, Jin H, Chen L, Zhou F, Walsh PJ, Liang G. Org. Chem. Front. 2022; 9: 3854
• 8c Chaubey SA, Mishra JS, Mishra R. ACS Omega 2018; 3: 9607
• 8d Lafzi F, Kilic H, Saracoglu N. J. Org. Chem. 2019; 84: 12120
• 8e Okuda Y, Nagaoka M, Yamamoto T. ChemCatChem 2020; 12: 6291
• 9a Westwood MT, Lamb CJ. C, Sutherland DR, Lee A.-L. Org. Lett. 2019; 21: 7119
• 9b Shi X, Chen X, Wang M, Zhang X, Fan X. J. Org. Chem. 2018; 83: 6524
• 9c Dey N. ACS Appl. Bio Mater. 2021; 4: 6893
• 9d Gupta SK. S, Mishra S. J. Phys. Chem. A 2011; 115: 4616
• 10 Bis(9H-carbazol-3-yl)(aryl)methanols 3: General Procedure A mixture of the appropriate carbazole derivative 1 (0.125 mmol), AgOTf (20 mol%), TFA (1 equiv), and the appropriate α-keto acid 2 (0.124 mmol) were added to a sealed tube. For carbazole derivatives 1a and 1t, DCE (2 mL) was also added to help to dissolve the substrate. The mixture was stirred at 80 °C for 8–20 h until the carbazole derivative was consumed (TLC). The mixture was then cooled to r.t., and the reaction was quenched with sat. aq NaHCO₃ (40 mL). The resultant mixture was extracted with EtOAc (2 × 40 mL), and the combined organic extracts were washed with sat. brine (30 mL), dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, hexane–EtOAc gradient). Bis(9-methyl-9H-carbazol-3-yl)(phenyl)methanol (3a) White solid; yield: 50.9 mg (87%). ¹H NMR (500 MHz, CDCl₃): δ = 8.08 (s, 2 H), 7.97 (d, J = 8.0 Hz, 2 H), 7.48–7.42 (m, 6 H), 7.40 (d, J = 8.0 Hz, 2 H), 7.37–7.30 (m, 5 H), 7.18 (t, J = 7.5 Hz, 2 H), 3.85 (s, 6 H), 3.08 (br s, 1 H). ¹³C NMR (151 MHz, CDCl₃): δ = 148.4, 141.6, 140.3, 138.7, 128.3, 128.0, 127.1, 126.5, 125.8, 123.0, 122.3, 120.6, 120.0, 119.0, 108.6, 107.9, 83.0, 29.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₃₃H₂₇N₂O: 467.2118; found: 467.2121.
• 11a Bogonda G, Kim HY, Oh K. Org. Lett. 2018; 20: 2711
• 11b Suresh R, Kumaran RS, Senthilkumar V, Muthusubramanian S. RSC Adv. 2014; 4: 31658
• 11c Penteado F, Lopes EF, Alves D, Perin G, Jacob RG, Lanardao EJ. Chem. Rev. 2019; 119: 7113