Addition of Benzyne to 2-Hydroxypyrimidine to Synthesize 2-Aryloxypyrimidine Derivatives under Mild Conditions

doi:10.6023/cjoc202206011

Abstract

Pyrimidine aryl ether derivatives have attracted widespread attention from chemists for their diverse biological activity and pharmacological properties. In this paper, a series of pyrimidine-2-arylether derivatives were synthesized with moderate to good yield by using 2-(trimethylsilyl)phenyl trifluoromethanesulfonate as a source of benzyne to react with 2-hydroxypyrimidine. Compared with the traditional method, this method has the advantages of transition-metal-free, easy preparation of 2-aryloxypyrimidine derivatives, wide functional group compatibility and high yield.

Key words: benzyne, pyrimidine derivatives, nucleophilic addition, 2-phenoxy pyrimidine

Cite this article

Wenpeng Wang, Chunhong Yang, Haichao Liu, Xicun Wang, Zhengjun Quan. Addition of Benzyne to 2-Hydroxypyrimidine to Synthesize 2-Aryloxypyrimidine Derivatives under Mild Conditions[J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3835-3842.

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Entry	Additive	Base	Solvent	Yield^b/%
1	KF/18-crown-6	—	CH₃CN	28
2	KF/18-crown-6	—	DCM	11
3	KF/18-crown-6	—	THF	36
4	KF/18-crown-6	—	DME	23
5	KF/18-crown-6	—	DCE	14
6	KF/18-crown-6	—	Dioxane	43
7	KF/18-crown-6	—	Toluene	47
8^c	CsF	—	Toluene	60
9	TBAT	—	Toluene	38
10	TBAF	—	Toluene	45
11	CsF	Cs₂CO₃	Toluene	81
12	CsF	K₂CO₃	Toluene	72
13	CsF	^tBuOK	Toluene	69
14	CsF	Et₃N	Toluene	61
15^d	CsF	Cs₂CO₃	Toluene	81
16^e	CsF	Cs₂CO₃	Toluene	74
17^f	CsF	Cs₂CO₃	Toluene	79
18^g	CsF	Cs₂CO₃	Toluene	71
19^h	CsF	Cs₂CO₃	Toluene	82

Entry	Additive	Base	Solvent	Yield^b/%
1	KF/18-crown-6	—	CH₃CN	28
2	KF/18-crown-6	—	DCM	11
3	KF/18-crown-6	—	THF	36
4	KF/18-crown-6	—	DME	23
5	KF/18-crown-6	—	DCE	14
6	KF/18-crown-6	—	Dioxane	43
7	KF/18-crown-6	—	Toluene	47
8^c	CsF	—	Toluene	60
9	TBAT	—	Toluene	38
10	TBAF	—	Toluene	45
11	CsF	Cs₂CO₃	Toluene	81
12	CsF	K₂CO₃	Toluene	72
13	CsF	^tBuOK	Toluene	69
14	CsF	Et₃N	Toluene	61
15^d	CsF	Cs₂CO₃	Toluene	81
16^e	CsF	Cs₂CO₃	Toluene	74
17^f	CsF	Cs₂CO₃	Toluene	79
18^g	CsF	Cs₂CO₃	Toluene	71
19^h	CsF	Cs₂CO₃	Toluene	82

温和条件下苯炔与2-羟基嘧啶加成合成2-芳氧基嘧啶类衍生物