N,N-Dimethylformamide (DMF)-Promoted SpecificN-Alkylation of Hydroxyl N-Heterocycles with Organohalides: A Direct and Efficient Method for Synthesis of Pyridone Derivatives

doi:10.6023/cjoc202102026

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (7): 2831-2838.DOI: 10.6023/cjoc202102026 Previous Articles Next Articles

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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

韩峰^a, 王婷^b, 冯斌^a, 徐清^a^,^b^,^*()

a 温州大学化学与材料工程学院浙江温州 325035
b 扬州大学化学化工学院江苏扬州 225002

收稿日期:2021-02-12 修回日期:2021-03-16 发布日期:2021-04-06
通讯作者: 徐清
基金资助:
国家自然科学基金(21672163); 浙江省自然科学杰出青年基金(LR14B020002)

N,N-Dimethylformamide (DMF)-Promoted SpecificN-Alkylation of Hydroxyl N-Heterocycles with Organohalides: A Direct and Efficient Method for Synthesis of Pyridone Derivatives

Feng Han^a, Ting Wang^b, Bin Feng^a, Qing Xu^a^,^b()

a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325035
b School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002

Received:2021-02-12 Revised:2021-03-16 Published:2021-04-06
Contact: Qing Xu
Supported by:
National Natural Science Foundation of China(21672163); Natural Science Foundation of Zhejiang Province for Distinguished Young Scholars(LR14B020002)

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Abstract

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

Cite this article

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

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

N,N-Dimethylformamide (DMF)-Promoted SpecificN-Alkylation of Hydroxyl N-Heterocycles with Organohalides: A Direct and Efficient Method for Synthesis of Pyridone Derivatives

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