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

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

丁雨昕 ^a,b, ,
马永敏 ^{a,b,
,} ,
陈静 ^{a,
,}

a.
浙江中医药大学药学院浙江杭州 310053
b.
台州大学医药化工学院浙江台州 318000

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.

关键词:

English

Novel Three-Component Annulation for the Synthesis of 2, 4, 6-Triaryl-pyrimidines under Solvent-Free and Catalyst-Free Conditions

Ding Yuxin ^a,b, ,
Ma Yongmin ^{a,b,
,} ,
Chen Jing ^{a,
,}

a.
School of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053
b.
School of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou, Zhejiang 318000

Corresponding author: Ma, Yongmin, E-mail: yongmin.ma@tzc.edu.cn; Chen, Jing, E-mail: cjmaggie@163.com

Received Date: 28 May 2020
Revised Date: 28 June 2020
Available Online: 25 December 2020
Fund Project:

Project supported by the Natural Science Foundation of Zhejiang Province (No. LY19H300001), the Zhejiang Chinese Medicinal University Foundation (No. 2018ZG31) and the "Teacher Professional Development Project" for Domestic Visitors of Institutions of Higher Learning in 2019 (No. FX2019020)

Abstract: 2, 4, 6-Triarylpyrimidines were synthesized via a simple, efficient, one-pot, three-component reaction from 1, 3-dikeones, benzaldehydes and ammonium acetate under solvent-free and catalyst-free conditions in good to excellent yields. This "green" methodology provides an eco-friendly protocol for the construction of the pyrimidine framework.

Key words:

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

下载: 全尺寸图片幻灯片

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

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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

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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

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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.

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表 2 反应底物拓展^{a, b}

Table 2. Scope of the substrates


Entry	Product	Ar¹	Ar²	Ar³	Yield^b/%
1	3aa	Ph	Ph	Ph	79, 75^c
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.

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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

English

Novel Three-Component Annulation for the Synthesis of 2, 4, 6-Triaryl-pyrimidines under Solvent-Free and Catalyst-Free Conditions

Corresponding author: Ma, Yongmin, E-mail: yongmin.ma@tzc.edu.cn; Chen, Jing, E-mail: cjmaggie@163.com

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

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

English

Novel Three-Component Annulation for the Synthesis of 2, 4, 6-Triaryl-pyrimidines under Solvent-Free and Catalyst-Free Conditions

Corresponding author: Ma, Yongmin, E-mail: yongmin.ma@tzc.edu.cn; Chen, Jing, E-mail: cjmaggie@163.com

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

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