Study on N-Alkylation Reactions of Trifluoromethylated Acylhydrazones

doi:10.6023/cjoc202011001

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (5): 2029-2037.DOI: 10.6023/cjoc202011001 Previous Articles Next Articles

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三氟甲基酰腙N-烃基化反应研究

杨金宇¹, 黄丹凤¹, 王克虎¹, 王君姣¹, 苏瀛鹏¹, 邓周斌¹, 杨天宇¹, 胡雨来¹^,^*()

1 西北师范大学化学化工学院兰州 730070

收稿日期:2020-11-02 修回日期:2020-12-24 发布日期:2021-02-07
通讯作者: 胡雨来
基金资助:
国家自然科学基金(21662030); 国家自然科学基金(22061037)

Study on N-Alkylation Reactions of Trifluoromethylated Acylhydrazones

Jinyu Yang¹, Danfeng Huang¹, Kehu Wang¹, Junjiao Wang¹, Yingpeng Su¹, Zhoubin Deng¹, Tianyu Yang¹, Yulai Hu¹^,^*()

1 College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070

Received:2020-11-02 Revised:2020-12-24 Published:2021-02-07
Contact: Yulai Hu
About author:
* Corresponding author. E-mail: huyl@nwnu.edu.cn
Supported by:
National Natural Science Foundation of China(21662030); National Natural Science Foundation of China(22061037)

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Abstract

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

Cite this article

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.

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References 18

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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

三氟甲基酰腙N-烃基化反应研究

Study on N-Alkylation Reactions of Trifluoromethylated Acylhydrazones

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