多取代2,3-二氢-4-吡啶酮的水相合成

doi:10.6023/cjoc202207032

摘要/Abstract

首次探讨了α-烯酰基二硫缩烯酮与胺的[5C＋1N]水相环合反应, 成功地实现多取代2,3-二氢-4-吡啶酮的水相合成. 研究表明, 在回流水中, (E)-2-(二乙硫基)亚甲基-3-羰基-5-芳基-N-芳基戊-4-烯酰胺1和有机胺2有效地发生[5C＋1N]水相环合反应, 以较好产率合成多取代2,3-二氢-4-吡啶酮3.

关键词: 水相反应, 二硫缩烯酮, 胺, 吡啶酮

For the first time, the aqueous [5C＋1N] annulation of α-alkenoyl ketene dithioacetals and amines for the synthesis of polysubstituted 2,3-dihydropyridin-4(1H)-ones was developed. In boiling water, [5C＋1N] annulation of (E)-2-(bis(ethyl- thio)methylene)-3-oxo-N,5-diarylpent-4-enamides 1 and organic amines 2 smoothly occurred, and polysubstituted 2,3-dihydropyridin-4(1H)-ones 3 was obtained in moderate yields.

Key words: aqueous reaction, ketene dithioacetals, amines, pyridinones

引用此文

王维, 张哲宇, 张雪, 于海丰, 罗辉, 霍东月, 徐玉澎, 赵晓波. 多取代2,3-二氢-4-吡啶酮的水相合成[J]. 有机化学, 2023, 43(2): 742-750.

Wei Wang, Zheyu Zhang, Xue Zhang, Haifeng Yu, Hui Luo, Dongyue Huo, Yupeng Xu, Xiaobo Zhao. Synthesis of Polysubstituted 2,3-Dihydropyridin-4(1H)-one in Water[J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 742-750.

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图/表 7

图1. α-烯酰基-α-羰基二硫缩烯酮的[5C＋1C/N]水相环合反应

Figure 1. [5C＋1C/N] annulation of α-alkenoyl-α-oxo ketone dithioacetals in water

Entry	Molar ratio of 1a∶2a	t/^oC	Time/h	Yield^b/%
1	1∶2	25	24	0 (96)^c
2	1∶2	50	24	0 (91)^c
3	1∶2	70	24	0 (88)^c
4	1∶2	80	24	18 (58)^c
5	1∶2	100	24	41 (29) ^c
6	1∶3	100	14	71
7	1∶3	100	24	69
8	1∶4	100	12	70
9	1∶1	100	24	20 (41)^c^,^d
10	2∶1	100	24	6 (75)^c^,^e

表1. 反应条件优化a

Table 1. Screening of reaction conditionsa

图2. 3a的晶体结构

Figure 2. Crystal structure of 3a

表2. 多取代2,3-二氢-4-吡啶酮3的水相合成a,b

Table 2. Polysubstituted synthesis of 2,3-dihydropyridin-4(1H)-one 3

图3. 克级规模反应

Figure 3. Gram-scale reactions

Cycle number	Reaction time/h	Yield/% of 2a
1	14	60
2	14	59
3	14	60
4	14	58
5	14	56

表3. 水循环实验

Table 3. Cycle experiment of water

图4. 可能反应机理

Figure 4. Proposed mechanism

参考文献 50

[1]	Butler, R. N.; Coyne, A. G. Chem. Rev. 2010, 110, 6302. doi: 10.1021/cr100162c
[2]	Simon, M. O.; Li, C. J. Chem. Soc. Rev. 2012, 41, 1415. doi: 10.1039/C1CS15222J
[3]	Kitanosono, T.; Masuda, K.; Xu, P. Y.; Kobayashi, S. Chem. Rev. 2018, 118, 679. doi: 10.1021/acs.chemrev.7b00417 pmid: 29218984
[4]	Song, H. X.; Han, Q. Y.; Zhao, C. L.; Zhang, C. P. Green Chem. 2018, 20, 1662. doi: 10.1039/C8GC00078F
[5]	Cao, T. T.; Zhang, W. K.; Qin, F. H.; Kang, Q. Q.; Dong, Y. R.; Li, Q.; Kang, C.; Wei, W. T. ACS Sustainable Chem. Eng. 2020, 8, 16946. doi: 10.1021/acssuschemeng.0c06586
[6]	Sun, K.; Lv, Q. Y.; Chen, X. L.; Qu, L. B.; Yu, B. Green Chem. 2021, 23, 232. doi: 10.1039/D0GC03447A
[7]	Jiang, J.; Xiao, F.; He, W. M.; Wang, L. Y. Chin. Chem. Lett. 2021, 32, 1637. doi: 10.1016/j.cclet.2021.02.057
[8]	Chattopadhyay, A. K.; Hanessian, S. Chem. Commun. 2015, 51, 16437. doi: 10.1039/C5CC05891K
[9]	Chattopadhyay, A. K.; Hanessian, S. Chem. Commun. 2015, 51, 16450. doi: 10.1039/C5CC05892A
[10]	Pepe, A.; Pamment, M.; Kim, Y. S.; Lee, S.; Lee, Mi. J.; Beebe, K.; Filikov, A.; Neckers, L.; Trepel, J. B.; Malhotra, S. V. J. Med. Chem. 2013, 56(21), 8280.
[11]	Eiden, C. G.; Aldrich, C. C. J. Org. Chem. 2017, 82, 7806. doi: 10.1021/acs.joc.7b00847
[12]	Seki, H.; Georg, G. I. Synlett 2014, 25, 2536. doi: 10.1055/s-0034-1378529
[13]	Kim, Y. W.; Georg, G. I. Org. Lett. 2014, 16, 1574.
[14]	Murphy, J. P.; Hadden, M.; Stevenson, P. J. Tetrahedron 1997, 53(34), 11827.
[15]	Igarashi, E.; Sakamoto, K.; Yoshimura, T.; Matsuo, J. I. Tetrahedron Lett. 2019, 60, 13. doi: 10.1016/j.tetlet.2018.11.040
[16]	Ma, D. W.; Sun, H. Y. Org. Lett. 2000, 2, 2503. pmid: 10956532
[17]	Leflemme, N.; Dallemagne, P.; Rault, S. Synthesis 2002, 12, 1740.
[18]	Yang, Y. RSC Adv. 2015, 5, 18894. doi: 10.1039/C4RA14418J
[19]	Yuan, Y.; Li, X.; Ding, K. L. Org. Lett. 2002, 4, 3309. pmid: 12227776
[20]	Pégot, B.; Vo-Thanh, G. Synlett 2005, 1409.
[21]	Lei, C. H.; Wang, D. X.; Zhao, L.; Zhu, J. P.; Wang, M. X. Chem.- Eur. J. 2013, 19, 16981. doi: 10.1002/chem.201303221
[22]	Obydennov, D. L.; El-Tantawy, A. I.; Sosnovskikha, V. Y. J. Org. Chem. 2018, 83, 13776. doi: 10.1021/acs.joc.8b02075 pmid: 30336022
[23]	Svetlik, J.; Kettmanna, V.; Zaleska, B. Tetrahedron Lett. 2005, 46, 5511. doi: 10.1016/j.tetlet.2005.06.059
[24]	Elias, R. S.; Saeed, B. A.; Saour, K. Y.; Al-Masoudi, N. A. Tetrahedron Lett. 2008, 49, 3049. doi: 10.1016/j.tetlet.2008.03.064
[25]	MacDonald, F. K.; Burnell, D. J. J. Org. Chem. 2009, 74, 6973. doi: 10.1021/jo901355e pmid: 19705839
[26]	Ranade, A. R.; Georg, G. I. J. Org. Chem. 2014, 79, 984. doi: 10.1021/jo402445r
[27]	Niphakis, M. J.; Turunen, B. J.; Georg, G. I. J. Org. Chem. 2010, 75, 6793. doi: 10.1021/jo100907u pmid: 20929269
[28]	Gouault, N.; Roch, M. L.; Cheignon, A.; Uriac, P.; David, M. Org. Lett. 2011, 13, 437.
[29]	Trinh, T. T. H.; Nguyen, K. H.; Amaral, P. A.; Gouault, N. Beilstein J. Org. Chem. 2013, 9, 2042. doi: 10.3762/bjoc.9.242
[30]	Pan, L.; Bi, X. H.; Liu, Q. Chem. Soc. Rev. 2013, 42, 1251. doi: 10.1039/C2CS35329F
[31]	Pan, L.; Liu, Q. Synlett 2011, 22, 1073.
[32]	Bi, X. H.; Dong, D. W.; Liu, Q.; Pan, W.; Zhao, L.; Li, B. J. Am. Chem. Soc. 2005, 127, 4578. doi: 10.1021/ja043023c
[33]	Zhang, L.; Liang, F. S.; Cheng, X.; Liu, Q. J. Org. Chem. 2009, 74, 899. doi: 10.1021/jo802318p pmid: 19053616
[34]	Zhao, X. B.; Wang, Y. M.; Yu, H. F.; Lv, Y. C.; Jiang, S. A.; Wang, N. Tetrahedron 2021, 97, 132427. doi: 10.1016/j.tet.2021.132427
[35]	Dong, D. W.; Bi, X. H.; Liu, Q.; Cong, F. D. Chem. Commun. 2005, 3580.
[36]	Gui, Q. W.; Wang, B. B.; Zhu, S.; Li, F. L.; Zhu, M. X.; Yi, M.; Yu, J. L.; Wu, Z. L.; He, W. M. Green Chem. 2021, 23, 4430. doi: 10.1039/D1GC01017D
[37]	Wu, Y.; Chen, J. Y.; Ning, J.; Jiang, X.; Deng, J.; Deng, Y.; Xu, R.; He, W. M. Green Chem. 2021, 23, 3950. doi: 10.1039/D1GC00562F
[38]	Gui, Q.W.; Teng, F.; Li, Z. C.; Xiong, Z. Y.; Jin, X. F.; Lin, Y. W.; Cao, Z.; He, W. M. Chin. Chem. Lett. 2021, 32, 1907. doi: 10.1016/j.cclet.2021.01.021
[39]	Yu, H. F.; Liao, P. Q.; Mei, Z. M. Synthesis, 2021, 52, 2111. doi: 10.1055/s-0040-1707999
[40]	Yu, H. F.; Wang, K. H.; Zhang, X.; Wang, W. J. Synthesis 2021, 53, 1989. doi: 10.1055/s-0040-1706658
[41]	Yu, H. F.; Zhao, L. J.; Diao, Q. P.; Li, T. C.; Liao, P. Q.; Hou, D. Y.; Xin, G. Synlett 2017, 28, 1828. doi: 10.1055/s-0036-1588982
[42]	Dong, D. W.; Ouyang, Y.; Yu, H. F.; Liu, Q.; Liu, J.; Wang, M.; Zhu, J. J. Org. Chem. 2005, 70, 4535. doi: 10.1021/jo050271y
[43]	Yu, H. F.; Liao, P. Q. Tetrahedron Lett. 2016, 57, 2868. doi: 10.1016/j.tetlet.2016.05.062
[44]	Qi, F.; Yu, H. F.; Wang, Y. N.; Lv, Y.; Li, Y. X.; Han, L.; Wang, R.; Feng, X. N. Synth. Commun. 2017, 47, 2220. doi: 10.1080/00397911.2017.1368084
[45]	Hu, X. Y.; Yu, H. F.; Wang, W. J.; Jiang, S. A.; Liu, Q.; He, J. Chin. J. Org. Chem. 2019, 39, 3183. (in Chinese) doi: 10.6023/cjoc201904002
	(胡小宇, 于海丰, 王文举, 姜思傲, 刘奇, 何洁, 有机化学, 2019, 39, 3183.) doi: 10.6023/cjoc201904002
[46]	Zhao, Y. H.; Yu, H. F.; Liao, P. Q.; Wang, W. J. Chem. Res. Chin. Univ. 2020, 36, 847. doi: 10.1007/s40242-019-0011-8
[47]	Zhao, X. B.; Jiang, S. A.; Wang, N.; Yu, H. F. Synth. Commun. 2020, 50, 3404. doi: 10.1080/00397911.2020.1801747
[48]	Jia, J.; Su, Y.; Yu, H. F.; Du, H. T.; Mei, Z. M. Synth. Commun. 2021, 51, 1581.
[49]	Yu, H. F.; Zhang, Z. Y.; Zhang, X.; Xu, Y. P.; Huo, D. Y.; Zhang, L. Y.; Wang, W. J. J. Org. Chem. 2022, 87, 2985. doi: 10.1021/acs.joc.1c02825
[50]	CCDC 2163176 (3a) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/datarequest/cif