N,N-二甲基甲酰胺(DMF)促进羟基氮杂环与卤代烃的专一性N-烷基化反应: 直接高效的吡啶酮类化合物合成方法

doi:10.6023/cjoc202102026

摘要/Abstract

在羟基氮杂环化合物与卤代烃的无碱、专一性N-烷基化合成吡啶酮类化合物的反应中,N,N-二甲基甲酰胺(DMF)比其他溶剂具有更好的溶剂效应, 使得该反应可以在更温和条件下得到更高的收率, 而且底物适用范围广. 据机理研究和文献报道, 除了一般的溶剂效应外, DMF还通过在反应中分解出二甲基胺作为碱促进反应进行.

关键词: 羟基氮杂环, 卤代烃, 吡啶酮, N-烷基化, N,N-二甲基甲酰胺(DMF), 溶剂效应

In base-free specificN-alkylation of hydroxylN-heterocycles with organohalides producing pyridone-type products,N,N-dimethylformamide (DMF) was found to be the best solvent for having the most prominent solvent effect among the usual solvents. This not only led to milder reaction conditions and higher yields of the products, but also could broaden the substrate scope of the reaction. Mechanistic studies and the literature revealed that, in addition to the usual solvent effect, DMF can decompose to produce dimethylamine during the reaction, which then works as a base to promote the reaction.

Key words: hydroxylN-heterocycle, organohalide, pyridone, N-alkylation, N,N-dimethylformamide (DMF), solvent effect

引用此文

韩峰, 王婷, 冯斌, 徐清. N,N-二甲基甲酰胺(DMF)促进羟基氮杂环与卤代烃的专一性N-烷基化反应: 直接高效的吡啶酮类化合物合成方法[J]. 有机化学, 2021, 41(7): 2831-2838.

Feng Han, Ting Wang, Bin Feng, Qing Xu. N,N-Dimethylformamide (DMF)-Promoted SpecificN-Alkylation of Hydroxyl N-Heterocycles with Organohalides: A Direct and Efficient Method for Synthesis of Pyridone Derivatives[J]. Chinese Journal of Organic Chemistry, 2021, 41(7): 2831-2838.

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Entry	Solvent (mL)	T/℃	3/4^b	3aa^c/%
1^d	—	100	>99/1	(84)^e
2	DMF (1)	100	>99/1	82
3	MeOH (1)	100	>99/1	13
4	DCE (1)	100	>99/1	60
5	CH₃CN (1)	100	>99/1	59
6	DCM (1)	100	>99/1	58
7	THF (1)	100	>99/1	79 (77)^e
8	Toluene (0.5)	100	>99/1	71 (70)^e
9	1,4-Dioxane (0.5)	100	>99/1	68
10	EtOH (0.5)	100	>99/1	20
11	THF (0.5)	100	>99/1	84
12	DMF (0.5)	100	>99/1	96 (96)^e
13	DMF (0.5)	90	>99/1	91
14	DMF (0.5)	80	>99/1	87
15	DMF (0.5)	60	>99/1	66

Entry	Solvent (mL)	T/℃	3/4^b	3aa^c/%
1^d	—	100	>99/1	(84)^e
2	DMF (1)	100	>99/1	82
3	MeOH (1)	100	>99/1	13
4	DCE (1)	100	>99/1	60
5	CH₃CN (1)	100	>99/1	59
6	DCM (1)	100	>99/1	58
7	THF (1)	100	>99/1	79 (77)^e
8	Toluene (0.5)	100	>99/1	71 (70)^e
9	1,4-Dioxane (0.5)	100	>99/1	68
10	EtOH (0.5)	100	>99/1	20
11	THF (0.5)	100	>99/1	84
12	DMF (0.5)	100	>99/1	96 (96)^e
13	DMF (0.5)	90	>99/1	91
14	DMF (0.5)	80	>99/1	87
15	DMF (0.5)	60	>99/1	66