Download PDF
Synlett 2014; 25(19): 2765-2768
DOI: 10.1055/s-0034-1379235
letter
© Georg Thieme Verlag Stuttgart · New York

Novel Synthesis of 5-Substituted 5H-Benzo[b]carbazole-6,11-diones via Double Buchwald–Hartwig Reaction

Khrystyna Bolibrukh
a   Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytechnic National University, Bandera Str. 12, Lviv, 79013, Ukraine   Fax: +38(32)2582478   Email: vnovikov@polynet.lviv.ua
,
Omar Khoumeri
b   Aix-Marseille Univ, CNRS, Institut de Chimie Radicalaire ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Bd J. Moulin, Marseille Cedex 05, 13385, France   Fax: +33(4)91794677   Email: patrice.vanelle@univ-amu.fr
,
Svyatoslav Polovkovych
a   Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytechnic National University, Bandera Str. 12, Lviv, 79013, Ukraine   Fax: +38(32)2582478   Email: vnovikov@polynet.lviv.ua
,
Volodymyr Novikov
a   Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytechnic National University, Bandera Str. 12, Lviv, 79013, Ukraine   Fax: +38(32)2582478   Email: vnovikov@polynet.lviv.ua
,
Thierry Terme
b   Aix-Marseille Univ, CNRS, Institut de Chimie Radicalaire ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Bd J. Moulin, Marseille Cedex 05, 13385, France   Fax: +33(4)91794677   Email: patrice.vanelle@univ-amu.fr
,
Patrice Vanelle*
b   Aix-Marseille Univ, CNRS, Institut de Chimie Radicalaire ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Bd J. Moulin, Marseille Cedex 05, 13385, France   Fax: +33(4)91794677   Email: patrice.vanelle@univ-amu.fr
› Author Affiliations
Further Information

Publication History

Received: 23 July 2014

Accepted after revision: 11 September 2014

Publication Date:
16 October 2014 (online)

    Permissions and Reprints All articles of this category


Abstract

2-Bromo-3-(2-bromophenyl)naphthalene-1,4-dione was synthesized as a key precursor to obtain a number of functionalized benzo[b]carbazole-6,11-diones by double Buchwald–Hartwig coupling reaction.

Key words

quinone - anilines - Buchwald–Hartwig reaction - carbazole - one-pot

Supporting Information

    for this article is available online at http://www.thieme-connect.com/products/ejournals/journal/ 10.1055/s-00000083.
  • Supporting Information
 

  • References and Notes

  • 1 Thomson RH. Naturally Occurring Quinones IV . Chapman and Hall; London: 1997: 583
    CrossrefSearch in Google Scholar
  • 5 Thomson RH. Naturally Occuring Quinones IV . Blackie Academic; London: 1997
    Search in Google Scholar
  • 8 Cheun-Arom T, Chanvorachote P, Sirimangkalakitti N, Chuanasa T, Saito N, Abe I, Suwanborirux K. J. Nat. Prod. 2013; 76: 1468
    CrossrefSearch in Google Scholar
  • 14 2-Bromo-3-(2-bromophenyl)naphthalene-1,4-dione (3) To a mixture of 2,3-dibromonaphthalene-1,4-dione (0.786 g, 2.49 mmol) and boronic acid (0.5 g, 2.49 mol%) in toluene (10 mL) was added Pd(PPh3)4 (0.172 g, 0.15 mmol) and 2 M aq Na2CO3 solution (5 mL). The resulting mixture was stirred at 80 °C overnight. After cooling the mixture was diluted with CH2Cl2, washed 3 times with H2O, and dried over MgSO4. After filtration and evaporation, the crude product was purified by silica gel chromatography (CH2Cl2–PE, 5:5) giving 3 as yellow crystals, mp 126 °C, yield 1.2 g (62%). 1H NMR (200 MHz, CDCl3): δ = 7.22 (dd, 1 H, J = 7.4, 1.8 Hz, ArH), 7.30–7.49 (m, 2 H, ArH), 7.7 (dd, 1 H, J = 7.9, 1.2 Hz, ArH), 7.76–7.85 (m, 2 H, Ar), 8.14–8.27 (m, 2 H, ArH). 13C NMR (50 MHz, CDCl3): δ = 122.0 (C), 127.6 (2 × CH), 127.8 (CH), 128.3 (C), 129.9 (CH), 130.8 (CH), 131.3 (C), 131.7 (C), 132.9 (CH), 134.3 (CH), 134.7 (CH), 136.2 (C), 140.4 (C), 150.2 (C), 178.0 (CO), 180.6 (CO). Anal. Calcd for C16H8Br2O2: C, 49.02; H, 2.06. Found: C, 49.65; H, 1.98.
  • 16 General Procedure for the Double Buchwald–Hartwig Reaction for the Synthesis of 5-Substituted 5H-benzo[b]carbazole-6,11-diones 6a–k A mixture of 2-bromo-3-(2-bromophenyl)naphthalene-1,4-dione (3, 0.1 g, 0.25 mmol), aniline (1.5 g, 0.38 mmol equiv) in toluene (10 mL), K2CO3 (105 g, 0.76 mmol), Pd(OAc)2 (0.0098 g, 0.05 mmol), and BINAP (0.042 g, 0.06 mmol) was placed in a 4 mL sealed vial in a Biotage microwave-reactor cavity. The mixture was irradiated at 100 °C for 2 h. After cooling, the reaction mixture was diluted with CH2Cl2, washed with H2O (3 × 40 mL), and dried over MgSO4. After filtration and evaporation, the crude product was purified by silica gel chromatography (CH2Cl2–PE, 5:5). 5-(4-Nitrophenyl)-5H-benzo[b]carbazole-6,11-dione (6a) Yellow solid; mp 287 °C. 1H NMR (200 MHz, CDCl3): δ = 7.15–7.20 (m, 1 H, ArH), 7.44–7.50 (m, 2 H, ArH), 7.65–7.79 (m, 5 H, ArH), 8.05 (dd, 2 H, J = 7.0, 1.7 Hz, ArH), 8.25 (dd, 2 H, J = 7.0, 1.0 Hz, ArH), 8.46–8.56 (m, 2 H, ArH). 13C NMR (50 MHz, CDCl3): δ = 111.5 (CH), 124.1 (C), 124.2 (CH), 124.9 (2 × CH), 125.3 (CH), 126.7 (2 × CH), 128.4 (CH), 129.0 (2 × CH), 133.3 (2 × C), 133.5 (CH), 133.9 (C), 134.3 (CH), 135.3 (C), 140.5 (C), 142.5 (C), 147.9 (C), 177.7 (CO), 181.7 (CO). Anal. Calcd for C22H12N2O4: C, 71.74; H, 3.28; N, 7.61. Found: C, 71.66; H, 3.22; N, 7.61.
  • 17 Compounds 5a,b were formed by the same protocol but using Cs2CO3 as base. 2-(2-Bromophenyl)-3-(4-nitrophenylamino)naphthlene-1,4-dione (5a) Orange solid; mp 220 °C. 1H NMR (200 MHz, CDCl3): δ = 6.84 (d, 2 H, J = 8.9 Hz, ArH), 6.89–7.14 (m, 3 H, ArH), 7.31 (dd, 1 H, J = 8.0, 0.7 Hz, ArH), 7.70–7.87 (m, 4 H, ArH), 7.89 (s, 1 H, NH), 8.20 (dd, 2 H, J = 7.6, 1.4 Hz, ArH). 13C NMR (50 MHz, CDCl3) :δ = 119.4 (C), 122.8 (2 × CH), 123.5 (2 × CH), 124.6 (CH), 126.7 (CH), 127.2 (CH), 127.3 (CH), 129.9 (CH), 130.2 (C), 132.3 (CH), 133.0 (CH), 133.1 (C), 133.2 (C), 134.0 (C), 134.4 (CH), 140.8 (C), 143.1 (C), 143.7 (C), 181.6 (CO), 182.4 (CO). Anal. Calcd for C22H13BrN2O4: C, 58.82; H, 2.92; N, 6.24. Found: C, 85.77; H, 2.87; N, 6.33. 2-(2-Bromophenyl)-3-(phenylamino)naphthalene-1,4-dione (5b) Red solid; mp 161 °C.1H NMR (200 MHz, CDCl3): δ = 6.78–6.99 (m, 7 H, ArH), 7.24 (d, 1 H, J = 9.6 Hz, ArH), 7.69–7.82 (m, 3 H, ArH), 8.18 (dd, 2 H, J = 7.6, 1.4 Hz, ArH). 13H NMR (50 MHz, CDCl3): δ = 116.3 (C), 124.5 (2 × CH), 125.2 (CH), 125.3 (C), 126.5 (CH), 126.6 (CH), 127.0 (CH), 127.9 (2 × CH), 129.0 (CH), 130.4 (C), 132.3 (CH), 132.5 (CH), 132.8 (CH), 133.5 (C), 134.5 (C), 135.1 (CH), 136.9 (C), 141.9 (C), 181.6 (CO), 188.9 (CO).