Synlett 2013; 24(16): 2089-2094
DOI: 10.1055/s-0033-1339800
letter
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed Sequential N-Arylation and Aerobic Oxidation: Synthesis of Quinazoline Derivatives

Qing Liu
a   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China   Fax: +86(10)62781695   Email: fuhua@mail.tsinghua.edu.cn
,
Yufen Zhao
a   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China   Fax: +86(10)62781695   Email: fuhua@mail.tsinghua.edu.cn
,
Hua Fu*
a   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China   Fax: +86(10)62781695   Email: fuhua@mail.tsinghua.edu.cn
b   Key Laboratory of Chemical Biology (Guangdong Province), Graduate School of Shenzhen, Tsinghua University, Shenzhen 518057, P. R. of China
,
Changmei Cheng*
a   Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China   Fax: +86(10)62781695   Email: fuhua@mail.tsinghua.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 15 July 2013

Accepted after revision: 06 August 2013

Publication Date:
27 August 2013 (online)


Abstract

A novel and efficient copper-catalyzed cascade method for the synthesis of quinazoline derivatives has been developed. The protocol uses readily available substituted (2-bromophenyl)methylamines and amidine hydrochlorides as the starting materials, inexpensive CuBr as the catalyst, and economical and environment friendly air as the oxidant, and the corresponding quinazoline derivatives were obtained in moderate to good yields. The procedure underwent sequential intermolecular N-arylation, intramolecular nucleophilic substitution and aerobic oxidation.

Supporting Information

 
  • References and Notes

    • 1a Foster A, Coffrey HA, Morin MJ, Rastinejad F. Science 1999; 286: 2507
    • 1b Kunes J, Pour M, Waisser K, Slosarek M, Janota J. Farmaco 2000; 55: 725
    • 1c el-Sherbeny MA, Gineinah MM, Nasr MN, el-Shafeith FS. Arzneim.-Forsch. 2003; 53: 206
  • 2 Malecki N, Caroto P, Rigo B, Groosens JF, Houssin R, Bailly C, Henichart JP. Bioorg. Med. Chem. 2004; 12: 641
  • 3 Bedi PM. S, Kumar V, Mahajan MP. Bioorg. Med. Chem. Lett. 2004; 14: 5211
  • 4 Kotsuki H, Sakai H, Morimoto H, Suenaga H. Synlett 1999; 1993
    • 5a Lewis JC, Wiedemann SH, Bergman RG, Ellman JA. Org. Lett. 2004; 6: 35
    • 5b Wiedemann SH, Ellman JA, Bergman RG. J. Org. Chem. 2006; 71: 1969
    • 6a Connolly DJ, Cusak D, O’Sullivan TP, Guiry PJ. Tetrahedron 2005; 61: 10153
    • 6b Fekner T, Müuller-Bunz H, Guiry PJ. Org. Lett. 2006; 8: 5109
    • 6c Coskun N, Cetin M. Tetrahedron 2007; 63: 2966
    • 6d Hioki H, Matsushita K, Nakamura S, Horiuchi H, Kubo M, Harada K, Fukuyama Y. J. Comb. Chem. 2008; 10: 620
    • 7a Ferrini S, Ponticelli F, Taddei M. Org. Lett. 2007; 9: 69
    • 7b Yoon DS, Han Y, Stark TM, Haber JC, Gregg BT, Stankovich SB. Org. Lett. 2004; 6: 4775

      For recent reviews on copper-catalyzed cross-couplings, see:
    • 8a Surry DS, Buchwald SL. Chem. Sci. 2010; 1: 13
    • 8b Monnier F, Taillefer M. Angew. Chem. Int. Ed. 2009; 48: 6954
    • 8c Ma D, Cai Q. Acc. Chem. Res. 2008; 41: 1450
    • 8d Evano G, Blanchard N, Toumi M. Chem. Rev. 2008; 108: 3054
    • 8e Beletskaya IP, Cheprakov AV. Coord. Chem. Rev. 2004; 248: 2337
    • 8f Ley SV, Thomas AW. Angew. Chem. Int. Ed. 2003; 42: 5400
    • 8g Rao H, Fu H. Synlett 2011; 745 ; and references cited therein
    • 9a Huang C, Fu Y, Fu H, Jiang Y, Zhao Y. Chem. Commun. 2008; 6333
    • 9b Wang C, Li S, Liu H, Jiang Y, Fu H. J. Org. Chem. 2010; 75: 7936
    • 9c Liu X, Fu H, Jiang Y, Zhao Y. Angew. Chem. Int. Ed. 2009; 48: 348
    • 9d Wang F, Liu H, Fu H, Jiang Y, Zhao Y. Org. Lett. 2009; 11: 2469
    • 9e Gong X, Yang H, Liu H, Jiang Y, Zhao Y, Fu H. Org. Lett. 2010; 12: 3128
    • 9f Xu S, Lu J, Fu H. Chem. Commun. 2011; 47: 5596
    • 9g Liu T, Wang R, Yang H, Fu H. Chem. Eur. J. 2011; 17: 6765

      For selected papers on the copper-catalyzed synthesis of N-heterocycles, see:
    • 10a Wu Z, Huang Q, Zhou X, Yu L, Li Z, Wu D. Eur. J. Org. Chem. 2011; 5242
    • 10b Wan C, Zhang J, Wang S, Fan J, Wang Z. Org. Lett. 2010; 12: 2338
    • 10c Zou B, Yuan Q, Ma D. Angew. Chem. Int. Ed. 2007; 46: 2598
    • 10d Yuan X, Xu X, Zhou X, Yuan J, Mai L, Li Y. J. Org. Chem. 2007; 72: 1510
    • 10e Evindar G, Batey RA. J. Org. Chem. 2006; 71: 1802
    • 10f Martin R, Rivero MR, Buchwald SL. Angew. Chem. Int. Ed. 2006; 45: 7079
    • 10g Bonnaterre F, Bois-Choussy M, Zhu J. Org. Lett. 2006; 8: 4351
    • 10h Altenhoff G, Glorius F. Adv. Synth. Catal. 2004; 346: 1661
    • 10i Qu Y, Pan L, Wu Z, Zhou X. Tetrahedron 2013; 69: 1717
    • 10j Liu T, Fu H. Synthesis 2012; 44: 280 ; and references cited therein
  • 11 General Procedure for the Synthesis of Compounds 3a–v: A 25-mL Schlenk tube was charged with a magnetic stirrer and DMSO (2.0 mL). Substituted (2-bromophenyl)methylamine 1 (0.5 mmol), amidine hydrochloride 2 (1.0 mmol), CuBr (0.1 mmol, 14.2 mg), and K2CO3 (1.5 mmol, 207 mg) were added to the tube. The mixture was stirred at 80–120 °C under nitrogen atmosphere for 24 h, and then under air for 0.5 h. The resulting mixture was cooled to r.t. and filtered, and the solid was washed with EtOAc three times (3 × 3 mL). The combined filtrate was concentrated by the rotary evaporator, and the residue was purified by column chromatography on silica gel using petroleum ether–EtOAc as eluent to give the desired target product. Three representative examples are shown as follows: Quinazolin-2-amine (3j); (Ref. 12): Eluent: petroleum ether–EtOAc (1:3). Yield: 49.3 mg (68%); yellow solid. 1H NMR (300 MHz, DMSO-d 6): δ = 9.10 (s, 1 H), 7.77 (d, J = 8.1 Hz, 1 H), 7.66 (t, J = 7.2 Hz, 1 H), 7.43 (d, J = 8.1 Hz, 1 H), 7.19 (t, J = 7.2 Hz, 1 H), 6.91 (s, 2 H). 13C NMR (75 MHz, DMSO-d 6): δ = 162.8, 161.4, 152.3, 134.5, 128.3, 125.0, 122.4, 120.0. ESI–MS: m/z = 146.3 [M + H]+. 2-(4-Chlorophenyl)-6-methoxyquinazoline (3q); (Ref. 13): Eluent: petroleum ether–EtOAc (10:1 → 5:1). Yield: 90.5 mg (67%); white solid. 1H NMR (300 MHz, CDCl3): δ = 9.31 (s, 1 H), 8.50 (d, J = 9.0 Hz, 2 H), 7.95 (d, J = 9.3 Hz, 1 H), 7.54 (dd, J = 9.3, 2.7 Hz, 1 H), 7.47 (d, J = 6.9 Hz, 2 H), 7.11 (d, J = 2.7 Hz, 1 H), 3.95 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 158.9, 158.5, 147.0, 136.8, 136.4, 130.2, 129.6, 128.9, 127.4, 124.6, 104.0, 55.8. ESI–MS: m/z = 271.2 [M + H]+. 7-Fluoro-2-phenylquinazoline (3u); (Ref. 14): Eluent: petroleum ether–EtOAc (10:1). Yield: 56.0 mg (50%); white solid. 1H NMR (300 MHz, CDCl3): δ = 9.40 (s, 1 H), 8.59–8.62 (m, 2 H), 7.88–7.91 (m, 1 H), 7.70–7.77 (m, 1 H), 7.51–7.55 (m, 3 H), 7.36–7.40 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ = 166.0 (J = 255.8 Hz), 161.9, 160.0, 152.5 (d, 3 J = 13.6 Hz), 137.8, 131.1, 129.8 (d, J = 10.8 Hz), 128.8, 121.0, 118.0 (d, J = 25.1 Hz), 112.6 (d, J = 20.8 Hz). ESI–MS: m/z = 225.2 [M + H]+.
  • 12 Huang X, Yang H, Fu H, Qiao R, Zhao Y. Synthesis 2009; 2679
  • 13 Malakar CC, Baskakova A, Conrad J, Beifuss U. Chem. Eur. J. 2012; 18: 8882
  • 14 Truong VL, Morrow M. Tetrahedron Lett. 2010; 51: 758