二氟甲基取代的1,2,4-三氮唑啉化合物的合成

doi:10.6023/cjoc202403020

摘要/Abstract

探索了在碱的作用下, 由二氟甲基溴代腙原位生成的二氟甲基腈亚胺与3-亚胺基氧化吲哚的1,3-偶极环加成反应. 在温和的反应条件下, 以高达97%的产率和优异的区域选择性成功地合成了37个二氟甲基取代的螺1,2,4-三氮唑啉氧化吲哚类化合物. 该方法为合成二氟甲基取代的1,2,4-三氮唑啉化合物提供了一种新方法, 进一步拓展了二氟甲基腈亚胺在1,3-偶极环加成反应中的应用范围

关键词: 1,2,4-三氮唑啉, 二氟甲基, 二氟甲基溴代腙, 1,3-偶极环加成, 合成

A 1,3-dipolar cycloaddition of difluoromethyl nitrile imines generated in situ from difluoroacetohydrazonoyl bromides with 3-iminooxindoles in the presence of base is described. Under mild reaction conditions, thirty-seven difluoro- methyl substituted spiro 1,2,4-triazoline oxindole compounds were successfully synthesized in up to 97% yield with excellent regioselectivity. This method provides a new method for the synthesis of difluoromethyl substituted 1,2,4-triazoline compounds, and further expands the application range of difluoromethyl nitrile imines in 1,3-dipolar cycloaddition reactions

Key words: 1,2,4-triazolines, difluoromethyl, difluoroacetohydrazonoyl bromides, 1,3-dipolar cycloaddition, synthesis

引用此文

樊莹, 黄丹凤, 马虎, 白祖瑜, 王克虎, 王君姣, 胡雨来. 二氟甲基取代的1,2,4-三氮唑啉化合物的合成[J]. 有机化学, 2024, 44(9): 2820-2831.

Ying Fan, Danfeng Huang, Hu Ma, Zuyu Bai, Ke-Hu Wang, Junjiao Wang, Yulai Hu. Synthesis of Difluoromethyl Substituted 1,2,4-Triazoline Compounds[J]. Chinese Journal of Organic Chemistry, 2024, 44(9): 2820-2831.

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图/表 7

图1. 含有1,2,4-三氮唑和1,2,4-三氮唑啉结构骨架的有机功能化合物

Figure 1. Organic functional compounds containing 1,2,4-tria- zole and 1,2,4-triazoline skeletons

图式1. 二氟甲基取代的1,2,4-三氮唑类化合物的合成方法

Scheme 1. Synthetic method of difluoromethyl substituted 1,2,4-triazole compounds

图式2. 二氟甲基卤代腙与碳氮双键的1,3-偶极环加成反应

Scheme 2. 1,3-Dipolar cycloadditions of difluoroacetohydrazonoyl halides with C=N double bonds

Entry	n(1a)∶n(2a)∶n(base)	Base	Time/h	Temp/℃	Solvent	Isolated yield/%
1	1.2/1.0/1.2	K₂CO₃	9	35	CH₃CN	53
2	1.2/1.0/1.2	K₂CO₃	9	35	EtOH	85
3	1.2/1.0/1.2	K₂CO₃	9	35	1,4-Dioxane	90
4	1.2/1.0/1.2	K₂CO₃	9	35	THF	81
5	1.2/1.0/1.2	K₂CO₃	9	35	DCE	70
6	1.2/1.0/1.2	K₂CO₃	9	35	DCM	68
7	1.2/1.0/1.2	K₂CO₃	9	35	Toluene	69
8	1.3/1.0/1.3	K₂CO₃	9	35	1,4-Dioxane	95
9	1.5/1.0/1.5	K₂CO₃	9	35	1,4-Dioxane	89
10	1.1/1.0/1.1	K₂CO₃	9	35	1,4-Dioxane	68
11	1.3/1.0/1.3	Na₂CO₃	12	35	1,4-Dioxane	76
12	1.3/1.0/1.3	NaHCO₃	14	35	1,4-Dioxane	64
13	1.3/1.0/1.3	KOH	13	35	1,4-Dioxane	70
14	1.3/1.0/1.3	Et₃N	24	35	1,4-Dioxane	35
15	1.3/1.0/1.3	DBU	24	35	1,4-Dioxane	48
16	1.3/1.0/1.3	K₂CO₃	11	25	1,4-Dioxane	80
17	1.3/1.0/1.3	K₂CO₃	8	45	1,4-Dioxane	76

表1. 二氟甲基溴代腙与3-(N-苯基)亚胺基氧化吲哚的1,3-偶极环加成的反应条件优化a

Table 1. Optimization of conditions for the 1,3-dipolar cycloadditions of difluoroacetohydrazonoyl bromides with 3-iminooxindoles

表2. 二氟甲基溴代腙的适用范围a

Table 2. Scope of difluoroacetohydrazonoyl bromides

表3. 二氟甲基溴代腙的适用范围a

Table 3. Scope of difluoroacetohydrazonoyl bromides

图式3. 二氟甲基溴代腙和3-(N-苯基)亚胺基氧化吲哚的1,3-偶极环加成反应可能的反应机理

Scheme 3. Possible mechanism of 1,3-dipolar cycloaddition of difluoroacetohydrazonoyl bromide and 3-(N-phenyl)iminoox- indole

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