3-(三氟甲基)吡唑类化合物的合成

doi:10.6023/cjoc202302026

摘要/Abstract

探索了三氟甲基溴代腙与炔酮、炔酯和炔酰胺的[3+2]环加成反应, 以中等至优异的产率得到了一系列3-(三氟甲基)吡唑类化合物. 该方法具有区域选择性高、官能团兼容性强、操作简单和反应条件温和等特点, 为合成3-(三氟甲基)吡唑类化合物提供了一种高效的新方法.

关键词: 三氟甲基, 吡唑, 腈亚胺, 三氟甲基溴代腙, [3+2]环加成

The [3+2] cycloaddition reactions of trifluoroacetohydrazonoyl bromides with ynones, alkynoates and aynamides have been developed, and a series of 3-trifluoromethylpyrazole derivatives were obtained in medium to excellent yields. The noble features of this protocol include excellent regioselectivity, good functional group tolerance, mild reaction conditions and simple operation. It provides an efficient and practical method for the synthesis of 3-trifluoromethylpyrazoles.

Key words: trifluoromethyl group, pyrazoles, acetonitrile imines, trifluoroacetohydrazonoyl bromides, [3+2] cycloaddition

引用此文

马虎, 黄丹凤, 王克虎, 唐朵朵, 冯杨, 任园园, 王君娇, 胡雨来. 3-(三氟甲基)吡唑类化合物的合成[J]. 有机化学, 2023, 43(9): 3257-3267.

Hu Ma, Danfeng Huang, Kehu Wang, Duoduo Tang, Yang Feng, Yuanyuan Reng, Junjiao Wang, Yulai Hu. Synthesis of 3-Trifluoromethylpyrazole Derivatives[J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3257-3267.

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图/表 7

图1. 一些含有3-(三氟甲基)吡唑结构单元的医药和农药分子

Figure 1. Some drugs and pesticide molecules containing 3-trifluoromethylpyrazole moiety

图式1. 三氟甲基溴代腙与碳碳叁键的[3+2]环加成反应

Scheme 1. [3+2] cycloaddition reaction of trifluoroacetohydrazonoyl bromide with carbon-carbon triple bond

Entry	Molar ratio of 1a∶2a∶Base	Base	Time/h	Temp./℃	Solvent	Isolated yield/%
1	1.0∶1.0∶1.0	K₂CO₃	2	25	CH₃CN	65
2	1.0∶1.0∶1.2	K₂CO₃	2	25	CH₃CN	70
3	1.0∶1.0∶1.5	K₂CO₃	2	25	CH₃CN	67
4	1.2∶1.0∶1.2	K₂CO₃	2	25	CH₃CN	79
5	1.3:1.0∶1.3	K₂CO₃	4	25	CH₃CN	84
6	1.5∶1.0∶1.5	K₂CO₃	4	25	CH₃CN	92
7	1.5∶1.0∶1.5	Cs₂CO₃	2	25	CH₃CN	46
8	1.5∶1.0∶1.5	Na₂CO₃	9	25	CH₃CN	38
9	1.5∶1.0∶1.5	Et₃N	24	25	CH₃CN	15
10	1.5∶1.0∶1.5	DBU	24	25	CH₃CN	N.R.
11	1.5∶1.0∶1.5	K₂CO₃	4	25	THF	84
12	1.5∶1.0∶1.5	K₂CO₃	4	25	1,4-Dioxane	64
13	1.5∶1.0∶1.5	K₂CO₃	5	25	Toluene	76
14	1.5∶1.0∶1.5	K₂CO₃	4	25	DCM	53

表1. 三氟甲基溴代腙与炔酮的反应条件优化a

Table 1. Optimization of reaction conditions of trifluoroacetohydrazonoyl bromides with alkynones

表2. 三氟甲基溴代腙和炔酮的[3+2]环加成反应a

Table 2. [3+2] cycloaddition of trifluoroacetohydrazonoyl bromides with ynones

表3. 三氟甲基溴代腙和炔酯的[3+2]环加成反应a

Table 3. [3+2] cycloaddition of trifluoroacetohydrazonoyl bromide with alkynates

表4. 三氟甲基溴代腙和炔酰胺的[3+2]环加成反应a

Table 4. [3+2] cycloaddition of trifluoroacetohydrazonoyl bromide with ynamides

图式2. 三氟甲基溴代腙和炔酮的[3+2]环加成反应可能的反应机理

Scheme 2. Proposed mechanism of [3+2] cycloaddition of trifluoroacetohydrazonoyl bromide with ynone

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