无溶剂无催化剂条件下三组分一锅合成2, 4, 6-三芳基嘧啶衍生物的新方法

丁雨昕 马永敏 陈静

引用本文: 丁雨昕, 马永敏, 陈静. 无溶剂无催化剂条件下三组分一锅合成2, 4, 6-三芳基嘧啶衍生物的新方法[J]. 有机化学, 2020, 40(12): 4357-4363. doi: 10.6023/cjoc202005078 shu
Citation:  Ding Yuxin, Ma Yongmin, Chen Jing. Novel Three-Component Annulation for the Synthesis of 2, 4, 6-Triaryl-pyrimidines under Solvent-Free and Catalyst-Free Conditions[J]. Chinese Journal of Organic Chemistry, 2020, 40(12): 4357-4363. doi: 10.6023/cjoc202005078 shu

无溶剂无催化剂条件下三组分一锅合成2, 4, 6-三芳基嘧啶衍生物的新方法

    通讯作者: 马永敏, yongmin.ma@tzc.edu.cn; 陈静, cjmaggie@163.com
  • 基金项目:

    浙江省自然科学基金(No.LY19H300001)、浙江中医药大学校级科研基金(No.2018ZG31)和2019年度高等学校国内访问者“教师专业发展项目”(No.FX2019020)资助项目

摘要: 以1,3-二酮、苯甲醛和醋酸铵为原料,成功地开发了一种简便、高效、无溶剂和催化剂的三组分一锅合成法,高收率地得到了2,4,6-三芳基嘧啶化合物.此方法提供了一条"绿色"合成嘧啶骨架新策略.

English

    1. [1]

      (a) Santos, M. F. C.; Harper, P. M.; Williams, D. E.; Mesquita, J. T.; Pinto, É. G.; da Costa-Silva, T. A.; Hajdu, E.; Ferreira, A. G.; Santos, R. A.; Murphy, P. J. J. Nat. Prod. 2015, 78, 1101.
      (b) Pettit, G. R.; Tang, Y.; Zhang, Q.; Bourne, G. T.; Hooper, J. N. A. J. Nat. Prod. 2013, 76, 420.

    2. [2]

      (a) Hou, J.; Wan, S.; Wang, G.; Zhang, T.; Li, Z.; Tian, Y.; Yu, Y.; Wu, X.; Zhang, J. Eur. J. Med. Chem. 2016, 118, 276.
      (b) Agarwal, A.; Srivastava, K.; Puri, S. K.; Chauhan, P. M. S. Bioorg. Med. Chem. 2005, 13, 4645.
      (c) Parker, W. B. Chem. Rev. 2009, 109, 2880.
      (d) Shipe, W. D.; Sharik, S. S.; Barrow, J. C.; McGaughey, G. B.; Theberge, C. R.; Uslaner, J. M.; Yan, Y.; Renger, J. J.; Smith, S. M.; Coleman, P. J.; Cox, C. D. J. Med. Chem. 2015, 58, 7888.
      (e) Johar, M.; Manning, T.; Kunimoto, D. Y.; Kumar, R. Bioorg. Med. Chem. 2005, 13, 6663.
      (f) Agarwal, A.; Srivastava, K.; Puri, S. K.; Chauhan, P. M. S. Bioorg. Med. Chem. Lett. 2005, 15, 1881.
      (g) Guo, Y.; Li, J.; Ma, J.; Yu, Z.; Wang, H.; Zhu, W.; Liao, X.; Zhao, Y. Chin. Chem. Lett. 2015, 26, 755.
      (h) Chen, W.; Li, Y.; Zhou, Y.; Ma, Y.; Li, Z. Chin. Chem. Lett. 2019, 30, 2160.
      (i) Shao, K.; Zhang, X.; Zhang, X.; Xue, D.; Ma, L.; Zhang, Q.; Liu, H. Chin. J. Chem. 2014, 32, 443.

    3. [3]

      (a) Undheim, K.; Benneche, T. In Comprehensive Heterocyclic Chemistry II, Vol. 6, Eds.: Katritzky, A. R.; Rees, C. W.; Scriven, E. V. F., Pergamon Press, London, 1996, p. 93.
      (b) Brown, D. J.; Evans, R. F.; Cowden, W. B. In The Pyrimidines, Vol. 52, Eds.: Taylor, E. C.; Weissberger, A., John Wiley, New York, 1994.

    4. [4]

      (a) Gompper, R.; Mair, H.-J.; Polborn, K. Synthesis 1997, 696.
      (b) Bassani, D. M.; Lehn, J. A.; Baum, G.; Fenske, D. Angew. Chem., Int. Ed. 1997, 36, 1845.
      (c) Zhao, F.; Zhao, X.; Peng, B.; Gan, F.; Yao, M.; Tan, W.; Dong, J.; Zhang, Q. Chin. Chem. Lett. 2018, 29, 1692.

    5. [5]

      (a) Wong, K.-T.; Hung, T. S.; Lin, Y.; Wu, C.-C.; Lee, G.-H.; Peng, S.-M.; Chou, C. H.; Su, Y. O. Org. Lett. 2002, 4, 513.
      (b) Li, L.; Fang, Y.; Chen, H.; Zhang, Y. Chin. J. Chem. 2012, 30, 1144.

    6. [6]

      (a) Harriman, A.; Ziessel, R. Coord. Chem. Rev. 1998, 171, 331.
      (b) Harriman, A.; Ziessel, R. Chem. Commun. 1996, 32, 1707.

    7. [7]

      (a) Dodson, R. M.; Seyler, J. K. J. Org. Chem. 1951, 16, 461.
      (b) Guo, W. Chin. Chem. Lett. 2016, 27, 47.
      (c) Chu, X. Q.; Cao, W.-B.; Xu, X.-P.; Ji, S.-J. J. Org. Chem. 2017, 82, 1145.

    8. [8]

      Yuan, J.; Li, J.; Wang, B.; Sun, S.; Cheng, J. Tetrahedron Lett. 2017, 58, 4783. doi: 10.1016/j.tetlet.2017.11.020

    9. [9]

      Wang, P.; Zhang, X.; Liu, Y.; Chen, B. Asian J. Org. Chem. 2019, 8, 1122. doi: 10.1002/ajoc.201900248

    10. [10]

      (a) Deibl, N.; Ament, K.; Kempe, R. J. Am. Chem. Soc. 2015, 137, 12804.
      (b) Bule, M. H.; Esfandyari, R.; Tafesse, T. B.; Amini, M.; Faramarzi, M. A.; Abdollahi, M. J. Chem. Pharm. Res. 2019, 11, 27
      (c) Shi, T.; Qin, F.; Q. Zhang, Li, W. Org. Biomol. Chem. 2018, 16, 9487.

    11. [11]

      Liu, D.; Guo, W.; Wu, W.; Jiang, H. J. Org. Chem. 2017, 82, 13609. doi: 10.1021/acs.joc.7b02113

    12. [12]

      (a) Martínez, A. G.; Fernandez, A. H.; Alvarez, R. M.; Losada, M. C. S.; Vilchez, D. M.; Subramanian, L. R.; Hanack, M. Synthesis 1990, 881.
      (b) Fuji, M.; Obora, Y. Org. Lett. 2017, 19, 5569.
      (c) Su, L.; Sun, K.; Pan, N.; Liu, L.; Yin, S. F. Org. Lett. 2018, 20, 3399.

    13. [13]

      Schomaker, J. M.; Delia, T. J. J. Org. Chem. 2001, 66, 7125. doi: 10.1021/jo010573+

    14. [14]

      Adib, M.; Mahmoodi, N.; Mahdavi, M.; Bijanzadeh, H. R. Tetrahedron Lett. 2006, 47, 9365. doi: 10.1016/j.tetlet.2006.10.090

    15. [15]

      Seki, M.; Kubota, H.; Matsumoto, K.; Kinumaki, A.; Date, T.; Okamura, K. J. Org. Chem. 1993, 58, 6354. doi: 10.1021/jo00075a032

    16. [16]

      Heravi, M. M.; Sadjadi, S.; Oskooie, H. A.; Shoar, R. H.; Bamoharram, F. F. Tetrahedron Lett. 2009, 50, 662. doi: 10.1016/j.tetlet.2008.11.105

    17. [17]

      Ding, Y. X.; Ma, R. C.; Hider, R. C.; Ma, Y. M. Asian J. Org. Chem. 2020, 9, 242. doi: 10.1002/ajoc.201900700

    18. [18]

      Itami, K.; Yamazaki, D.; Yoshida, J. J. Am. Chem. Soc. 2004, 126, 15396. doi: 10.1021/ja044923w

    19. [19]

      Komatsu, R.; Nakao, K.; Sasabe, H.; Komatsu, R.; Hayasaka, Y.; Ohsawa, T.; Kido, J. J. Adv. Opt. Mater. 2017, 5, 1600675. doi: 10.1002/adom.201600675

  • 图 1  代表性的2, 4, 6-三取代嘧啶化合物

    Figure 1  Representative 2, 4, 6-trisubstituted pyrimidines

    图式 1  2, 4, 6-三取代嘧啶化合物的合成方法

    Scheme 1  Synthetic approaches to 2, 4, 6-trisubstituted pyrimidines

    图式 2  二苯甲酰甲烷与芳杂环醛的反应

    Scheme 2  1, 3-Diphenylpropane-1, 3-dione reacted with hetero- aryl aldehydes

    图式 3  合成2, 4, 6-三芳基嘧啶类化合物可能的反应机理

    Scheme 3  Possible mechanism for the synthesis of 2, 4, 6-triaryl- pyrimidines

    表 1  反应条件的优化a

    Table 1.  Optimization of the reaction conditions

    Entry Solvent “N” source “N” source/ equiv. Time/h t/℃ Yield/%
    1 NH4OAc 3 26 120 79
    2 Ammonium formate 3 26 120 18
    3 NH4Cl 3 26 120 19
    4 Benzylamine 3 26 120 Trace
    5 NH3•H2O 3 26 120 NR
    6 DMSO NH4OAc 3 26 120 NR
    7 DMF NH4OAc 3 26 120 NR
    8 CH3CN NH4OAc 3 26 120 19
    9 PhMe NH4OAc 3 26 120 61
    10 NH4OAc 1 26 120 20
    11 NH4OAc 2 26 120 28
    12 NH4OAc 4 26 120 71
    13 NH4OAc 5 26 120 70
    14 NH4OAc 3 26 40 NR
    15 NH4OAc 3 26 80 NR
    16 NH4OAc 3 26 100 NR
    17 NH4OAc 3 26 110 50
    18 NH4OAc 3 26 130 71
    19 NH4OAc 3 4 120 NR
    20 NH4OAc 3 6 120 20
    21 NH4OAc 3 12 120 53
    22 NH4OAc 3 20 120 60
    23 NH4OAc 3 30 120 81
    a Reaction conditions: 1a (1 mmol), 2a (1 mmol) and “N” source at the indicated amount in a sealed tube at the indicated reaction time and temperatures.
    下载: 导出CSV

    表 2  反应底物拓展a, b

    Table 2.  Scope of the substrates

    Entry Product Ar1 Ar2 Ar3 Yieldb/%
    1 3aa Ph Ph Ph 79, 75c
    2 3ab Ph Ph 2-ClC6H4 60
    3 3ac Ph Ph 2-BrC6H4 59
    4 3ad Ph Ph 3-MeC6H4 81
    5 3ae Ph Ph 3-MeOC6H4 51
    6 3af Ph Ph 3-BrC6H4 80
    7 3ag Ph Ph 4-MeC6H4 84
    8 3ah Ph Ph 4-NO2C6H4 0
    9 3ai Ph Ph 4-FC6H4 81
    10 3aj Ph Ph 4-ClC6H4 86
    11 3ak Ph Ph 4-BrC6H4 85
    12 3ba 4-MeC6H4 Ph Ph 83
    13 3ca 4-ClC6H4 Ph Ph 84
    14 3da 4-BrC6H4 Ph Ph 81
    15 3ea 3-ClC6H4 Ph Ph 79
    16 3fa 4-MeC6H4 4-MeC6H4 Ph 85
    17 3ga 4-FC6H4 4-FC6H4 Ph 81
    18 3ha 4-ClC6H4 4-ClC6H4 Ph 85
    19 3ia 4-BrC6H4 4-BrC6H4 Ph 86
    20 3ja 4-ClC6H4 4-MeC6H4 Ph 82
    21 3ka 3-FC6H4 3-FC6H4 Ph 82
    22 3la 3-ClC6H4 3-ClC6H4 Ph 83
    23 3ma 3-BrC6H4 3-BrC6H4 Ph 80
    24 3na 2-MeC6H4 2-MeC6H4 Ph 0
    25 3oa 2-FC6H4 2-FC6H4 Ph 0
    26 3pa 2-ClC6H4 2-ClC6H4 Ph 0
    27 3kl 3-FC6H4 3-FC6H4 3-FC6H4 80
    a Reaction condiions: 1 (1 mmol), 2 (1 mmol) and NH4OAc (3 mmol), 120 ℃, 26 h; b Isolated yield; c10 mmol scale.
    下载: 导出CSV
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  • 发布日期:  2020-12-25
  • 收稿日期:  2020-05-28
  • 修回日期:  2020-06-28
  • 网络出版日期:  2020-07-22
通讯作者: 陈斌, bchen63@163.com
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