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

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  • 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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