三氟甲基酰腙N-烃基化反应研究

doi:10.6023/cjoc202011001

摘要/Abstract

探索了三氟甲基酰腙的N-烃基化反应, 得到了一系列N-烃基取代的三氟甲基酰腙衍生物. 其结构经¹H NMR和¹³C NMR、HRMS等确证. 该方法具有反应条件温和、产率高及操作简单等优点, 为合成N-烃基取代的三氟甲基酰腙类化合物提供了一种简单高效的方法.

关键词: 三氟甲基酰腙, 卤代烃, α,β-不饱和酯, N-烃基化

The N-alkylation reaction of trifluoromethylated acylhydrazones was investigated, and a series of N-alkyl trifluoromethyl acylhydrazones were afforded in good yield. Their structures were confirmed by ¹H NMR, ¹³C NMR and HRMS analysis. The strategy has advantages of simple and mild reaction conditions, wide scope of substrates and good yields. This protocol provides an efficient and new method for the synthesis of N-alkyl substituted trifluoromethyl acylhydrazones.

Key words: trifluoromethyl acylhydrazone, halohydrocarbon, α,β-unsaturated ester, N-alkylation

引用此文

杨金宇, 黄丹凤, 王克虎, 王君姣, 苏瀛鹏, 邓周斌, 杨天宇, 胡雨来. 三氟甲基酰腙N-烃基化反应研究[J]. 有机化学, 2021, 41(5): 2029-2037.

Jinyu Yang, Danfeng Huang, Kehu Wang, Junjiao Wang, Yingpeng Su, Zhoubin Deng, Tianyu Yang, Yulai Hu. Study on N-Alkylation Reactions of Trifluoromethylated Acylhydrazones[J]. Chinese Journal of Organic Chemistry, 2021, 41(5): 2029-2037.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 4

参考文献 18

[1]	Sugiura, M.; Kobayashi, S. Angew. Chem., Int. Ed. 2005, 44, 5176. doi: 10.1002/(ISSN)1521-3773
[2]	(a) Che, Z.; Zhang, S.; Shao, Y.; Fan, L.; Xu, H.; Yu, X.; Zhi, X.; Yao, X. J. Agric. Food Chem. 2013, 61, 5696. doi: 10.1021/jf400536q pmid: 10758285
	(b) Zhou, Y.; Luo, Y.; Yang, Y.-S.; Lu, L.; Zhu, H.-L. Med. Chem. Commun. 2016, 7, 1980. doi: 10.1039/C6MD00263C pmid: 10758285
	(c) Roth, H. S.; Hergenrother, P. J. Curr. Med. Chem. 2016, 23, 201. doi: 10.2174/0929867323666151127201829 pmid: 10758285
	(e) Dimmock, J. R.; Vashishtha, S. C.; Stables, J. P. Eur. J. Med. Chem. 2000, 35, 241. pmid: 10758285
[3]	Silva, A. G.; Zapata-Sudo, G.; Kummerle, A. E.; Fraga, C. A.; Barreiro, E. J.; Sudo, R. T. Bioorg. Med. Chem. 2005, 13, 3431. doi: 10.1016/j.bmc.2005.03.003
[4]	de Figueiredo, L. P.; Ibiapino A.L. do Amaral D. N.; Ferraz, L. S.; Rodrigues T.; Barreiro E. J.; Lima, L. M.; Ferreira F. F. J. Mol. Struct. 2017, 1147, 226. doi: 10.1016/j.molstruc.2017.06.093
[5]	Kümmerle, A. E.; Schmitt, M.; Cardozo, S. V. S.; Lugnier, C.; Villa, P.; Lopes, A. B.; Romeiro, N. C.; Justiniano, H.; Martins, M. A.; Fraga, C. A. M.; Bourguignon, J.-J.; Barreiro, E. J. J. Med. Chem. 2012, 55, 7525. doi: 10.1021/jm300514y
[6]	Rodrigues, D. A.; Ferreira-Silva, G. A.; Ferreira, A. C. S.; Fernandes, R. A.; Kwee, J. K.; Sant'Anna, C. M. R.; Ionta, M.; Fraga, C. A. J. Med. Chem. 2016, 59, 655. doi: 10.1021/acs.jmedchem.5b01525
[7]	Vantomme, G.; Jiang, S.; Lehn, J.-M. J. Am. Chem. Soc. 2014, 136, 9509. doi: 10.1021/ja504813r
[8]	(a) Shih, M.-H.; Xu, Y.-Y.; Yang, Y.-S.; Lin, T.-T. Molecules 2015, 20, 5184. doi: 10.3390/molecules20035184
	(b) Ragnarsson, U. Chem. Soc. Rev. 2001, 30, 205. doi: 10.1039/b010091a
[9]	Kümmerle, A. E.; Raimundo, J. M.; Leal, C. M.; da Silva, G. S.; Balliano, T. L.; Pereira, M. A.; de Simone, C. A.; Sudo, R. T.; Zapata-Sudo, G.; Fraga, C. A. M.; Barreiro, E. J. Eur. J. Med. Chem. 2009, 44, 4004. doi: 10.1016/j.ejmech.2009.04.044 pmid: 19500884
[10]	Oikawa, N.; Müller, C.; Kunz, M.; Lichtenthaler, F. W. Carbohydr. Res. 1998, 309, 269. doi: 10.1016/S0008-6215(98)00137-2
[11]	Zhang, H.; Wang, K.-H.; Wang, J.; Su, Y.; Huang, D.; Hu, Y. Org. Biomol. Chem. 2019, 17, 2940. doi: 10.1039/C9OB00236G
[12]	Mahmoud, N. F. H.; Elsayed, G. A. J. Heterocycl. Chem. 2020, 57, 1845. doi: 10.1002/jhet.v57.4
[13]	(a) Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Aceña, J. L.; Soloshonok, V. A.; Lzawa, K.; Liu, H. Chem. Rev. 2016, 116, 422. doi: 10.1021/acs.chemrev.5b00392
	(b) Vitale, A.; Bongiovanni, R.; Ameduri, B. Chem. Rev. 2015, 115, 8835. doi: 10.1021/acs.chemrev.5b00120
[14]	(a) Liu, X.; Xu, C.; Wang, M.; Liu, Q. Chem. Rev. 2015, 115, 683. doi: 10.1021/cr400473a
	(b) Charpentier, J.; Früh, N.; Togni, A. Chem. Rev. 2015, 115, 650. doi: 10.1021/cr500223h
	(c) Studer, A. Angew. Chem.,Int. Ed. 2012, 51, 8950. doi: 10.1002/anie.201202624
[15]	(a) Ji, X.; Shi, G.; Zhang, Y. Chin. J. Org. Chem. 2019, 39, 929. (in Chinese). doi: 10.6023/cjoc201810033
	(季小明, 史广法, 张扬会, 有机化学, 2019, 39, 929.) doi: 10.6023/cjoc201810033
	(b) Qing, F. Chin. J. Org. Chem. 2012, 32, 815. (in Chinese). doi: 10.6023/cjoc1202021
	(卿凤翎, 有机化学, 2012, 32, 815.) doi: 10.6023/cjoc1202021
	(c) Liang, H.; Xu, G.; Feng, Z.; Wang, Z.; Xu, P. J. Org. Chem. 2019, 84, 60. doi: 10.1021/acs.joc.8b02316
	(d) Wang, J.; Li, F.; Xu, Y.; Wang, J.; Wu, Z.; Yang, C.; Liu, L. Chin. J. Org. Chem. 2018, 38, 1155. (in Chinese). doi: 10.6023/cjoc201709049
	(王晶晶, 李峰, 徐妍, 王娟, 武紫燕, 杨成玉, 刘澜涛, 有机化学, 2018, 38, 1155.) doi: 10.6023/cjoc201709049
[16]	(a) Wang, K.-H.; Shi, B.; Wang, Y.; Wang, J.; Huang, D.; Su, Y.; Hu, Y. Asian J. Org. Chem. 2019, 8, 716. doi: 10.1002/ajoc.v8.5
	(b) Xu, W.; Huang, D.; Wang, K.; Zhao, F.; Zhao, Z.; Hu, Y.; Su, Y.; Hu, Y. Chin. J. Org. Chem. 2020, 40, 922. (in Chinese). doi: 10.6023/cjoc201910011
	(徐炜刚, 黄丹凤, 王克虎, 赵芳霞, 赵转霞, 虎永琴, 苏瀛鹏, 胡雨来, 有机化学, 2020, 40, 922.) doi: 10.6023/cjoc201910011
	(c) Hu, Y.; Huang, D.; Wang, K.; Zhao, F.; Zhao, Z.; Xu, W.; Hu, Y. Chin. J. Org. Chem. 2020, 40, 1689. (in Chinese). doi: 10.6023/cjoc201912006
	(虎永琴, 黄丹凤, 王克虎, 赵芳霞, 赵转霞, 徐炜刚, 胡雨来, 有机化学, 2020, 40, 1689.) doi: 10.6023/cjoc201912006
[17]	(a) Peng, X.; Huang, D.; Wang, K.-H.; Wang, Y.; Wang, J.; Su, Y.; Hu, Y. Org. Biomol. Chem. 2017, 15, 6214. doi: 10.1039/C7OB01299C
	(b) Liu, L.; Huang, D.; Wang, Y.; Wen, L.; Yang, Z.; Su, Y.; Wang, K.; Hu, Y. Chin. J. Org. Chem. 2018, 38, 1469. (in Chinese). doi: 10.6023/cjoc201712036
	(刘丽丽, 黄丹凤, 王玉祥, 文岚, 杨政, 苏瀛鹏, 王克虎, 胡雨来, 有机化学, 2018, 38, 1469.) doi: 10.6023/cjoc201712036
	(c) Zhao, F.; Wang, K.-H.; Wen, L.; Zhao, Z.; Hu, Y.; Xu, W.; Huang, D.; Su, Y.; Wang, J.; Hu, Y. Asian J. Org. Chem. 2020, 9, 1036. doi: 10.1002/ajoc.v9.7
[18]	Du, G.; Huang, D.; Wang, K. H.; Chen, X.; Xu, Y.; Ma, J.; Su, Y.; Hu, Y. Org. Biomol. Chem. 2016, 14, 1492. doi: 10.1039/C5OB02260F

Entry	Molar ratio of 1a/2a/ base/additive	Base	Additive	Solvent	Time/h	Isolated yield/%
1	1/2/1.5/0	K₂CO₃	—	CH₃CN	61	77
2	1/2/1.5/0.1	K₂CO₃	TBAI	CH₃CN	15	79
3	1/1.5/1.5/0.1	K₂CO₃	TBAI	CH₃CN	24	76
4	1/2.5/1.5/0.1	K₂CO₃	TBAI	CH₃CN	12	88
5	1/3.0/1.5/0.1	K₂CO₃	TBAI	CH₃CN	4	77
6	1/2.5/1/0.1	K₂CO₃	TBAI	CH₃CN	14	78
7	1/2.5/2/0.1	K₂CO₃	TBAI	CH₃CN	11	74
8	1/2.5/1.5/0.2	K₂CO₃	TBAI	CH₃CN	5	80
9	1/2.5/1.5/0.1	K₂CO₃	TBAB	CH₃CN	8	73
10	1/2.5/1.5/0.1	K₂CO₃	TBAC	CH₃CN	10	84
11	1/2.5/1.5/0.1	K₂CO₃	TEBA	CH₃CN	8	85
12	1/2.5/1.5/0.1	K₂CO₃	TBAF	CH₃CN	6	84
13	1/2.5/1.5/0.1	K₂CO₃	18-Crown-6	CH₃CN	11	75
14	1/2.5/1.5/0.1	K₂CO₃	TBAI	DMSO	1	84
15	1/2.5/1.5/0.1	K₂CO₃	TBAI	DCE	36	74
16	1/2.5/1.5/0.1	K₂CO₃	TBAI	DMF	1.5	72
17	1/2.5/1.5/0.1	K₂CO₃	TBAI	1,4-Dioxane	22	81
18	1/2.5/1.5/0.1	K₂CO₃	TBAI	THF	23	76
19	1/2.5/1.5/0.1	K₂CO₃	TBAI	Toluene	52	67
20	1/2.5/1.5/0.1	Cs₂CO₃	TBAI	CH₃CN	2	75
21	1/2.5/1.5/0.1	KOH	TBAI	CH₃CN	29	79
22	1/2.5/1.5/0.1	NaOH	TBAI	CH₃CN	17	54
23	1/2.5/1.5/0.1	LiOH	TBAI	CH₃CN	29	14
24	1/2.5/1.5/0.1	Et₃N	TBAI	CH₃CN	39	52
25	1/2.5/1.5/0.1	DBU	TBAI	CH₃CN	39	trace
26	1/2.5/—/0.1	—	TBAI	CH₃CN	24	0

Entry	Molar ratio of 1a/2a/ base/additive	Base	Additive	Solvent	Time/h	Isolated yield/%
1	1/2/1.5/0	K₂CO₃	—	CH₃CN	61	77
2	1/2/1.5/0.1	K₂CO₃	TBAI	CH₃CN	15	79
3	1/1.5/1.5/0.1	K₂CO₃	TBAI	CH₃CN	24	76
4	1/2.5/1.5/0.1	K₂CO₃	TBAI	CH₃CN	12	88
5	1/3.0/1.5/0.1	K₂CO₃	TBAI	CH₃CN	4	77
6	1/2.5/1/0.1	K₂CO₃	TBAI	CH₃CN	14	78
7	1/2.5/2/0.1	K₂CO₃	TBAI	CH₃CN	11	74
8	1/2.5/1.5/0.2	K₂CO₃	TBAI	CH₃CN	5	80
9	1/2.5/1.5/0.1	K₂CO₃	TBAB	CH₃CN	8	73
10	1/2.5/1.5/0.1	K₂CO₃	TBAC	CH₃CN	10	84
11	1/2.5/1.5/0.1	K₂CO₃	TEBA	CH₃CN	8	85
12	1/2.5/1.5/0.1	K₂CO₃	TBAF	CH₃CN	6	84
13	1/2.5/1.5/0.1	K₂CO₃	18-Crown-6	CH₃CN	11	75
14	1/2.5/1.5/0.1	K₂CO₃	TBAI	DMSO	1	84
15	1/2.5/1.5/0.1	K₂CO₃	TBAI	DCE	36	74
16	1/2.5/1.5/0.1	K₂CO₃	TBAI	DMF	1.5	72
17	1/2.5/1.5/0.1	K₂CO₃	TBAI	1,4-Dioxane	22	81
18	1/2.5/1.5/0.1	K₂CO₃	TBAI	THF	23	76
19	1/2.5/1.5/0.1	K₂CO₃	TBAI	Toluene	52	67
20	1/2.5/1.5/0.1	Cs₂CO₃	TBAI	CH₃CN	2	75
21	1/2.5/1.5/0.1	KOH	TBAI	CH₃CN	29	79
22	1/2.5/1.5/0.1	NaOH	TBAI	CH₃CN	17	54
23	1/2.5/1.5/0.1	LiOH	TBAI	CH₃CN	29	14
24	1/2.5/1.5/0.1	Et₃N	TBAI	CH₃CN	39	52
25	1/2.5/1.5/0.1	DBU	TBAI	CH₃CN	39	trace
26	1/2.5/—/0.1	—	TBAI	CH₃CN	24	0