无金属条件下酰胺和酯参与的2-取代苯并噁唑衍生物的合成

doi:10.6023/cjoc202111031

摘要/Abstract

2-取代苯并噁唑是一类重要的杂环骨架, 因其特有的生理活性在医药中有广泛应用. 以三氯化磷和碘为促进剂, 一锅法实现多种惰性酰胺和酯对苯并噁唑衍生物的C(2)位官能团化, 为无金属条件下一系列2-取代苯并噁唑衍生物的合成提供了简单高效的新方法. 同时考察了不同酰胺和酯类化合物的反应活性, 结果表明在该体系下酰胺的反应活性高于酯的反应活性. 该方法具有条件简单、成本低廉以及良好的底物范围等优点, 并提出了可能的反应机理.

关键词: 2-取代苯并噁唑, 酰胺, 酯, 无金属, 三氯化磷

2-Substituted benzoxazoles are important heterocyclic motifs due to their wide application in pharmacology. A PCl₃-mediated C(2)-functionalization of benzoxazole derivatives with inert amides and esters under metal-free conditions was reported. By using PCl₃/I₂ combination, various 2-substituted benzoxazoles could be synthesized via the arylation or alkylation of benzoxazoles with amides and esters in the presence of water. What’s more, the reactivity between amides and esters was also investigated. The primary results indicated that amides have higher reactivity than esters under this system. This method features a broad substrate scope, simple condition and low-cost. A plausible mechanism was also proposed.

Key words: 2-substituted benzoxazoles, amide, ester, metal-free, phosphorus trichloride

引用此文

李芳绍, 肖晶, 吴小芳, 王晓熠, 邓金凤, 唐子龙. 无金属条件下酰胺和酯参与的2-取代苯并噁唑衍生物的合成[J]. 有机化学, 2022, 42(6): 1778-1785.

Fangshao Li, Jing Xiao, Xiaofang Wu, Xiaoyi Wang, Jinfeng Deng, Zilong Tang. Metal-Free Formation of 2-Substitued Benzoxazoles with Amides and Esters[J]. Chinese Journal of Organic Chemistry, 2022, 42(6): 1778-1785.

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图/表 9

图式1. 无过渡金属参与的2-取代苯并噁唑的制备

Scheme 1. Synthesis of 2-substituted benzoxazoles under transition-metal-free conditions.

Entry	PCl₃/equiv.	V(H₂O)/μL	Solvent	Yield^b/%
1	1.2	50	DCE	52
2	1.0	50	DCE	82
3	0.8	50	DCE	70
4	1.0	65	DCE	49
5	1.0	35	DCE	46
6	1.0	0	DCE	0
7	1.0	50	CH₃CN	54
8	1.0	50	Toluene	65
9	1.0	50	PhCl	60
10	1.0	50	DMF	Trace
11	1.0	50	DCE	62^c
12	1.0	50	DCE	21^d
13	1.0	50	DCE	66^e
14	0	50	DCE	0
15	1.0	50	DCE	43^f

表1. 模型反应的条件优化a

Table 1. Optimization of the model reaction conditions

表2. 酰胺对苯并噁唑C(2)位官能团化a

Table 2. C(2) functionalization of benzoxazoles with amides

表3. 酯对苯并噁唑C(2)位官能团化a

Table 3. C(2) Functionalization of benzoxazoles with esters

表4. 不同类型酰胺和酯的反应活性考察a

Table 4. Studies on the reactivity of different amides and esters

表5. 含酯和酰胺基团底物的反应活性考察a

Table 5. Studies on the reactivity of substrates containing both ester and amide groups

图式2. N,N-二甲基苯甲酰胺和苯甲酸甲酯与苯并噁唑的放大反应

Scheme 2. Scale-up reactions of benzoxazole with N,N-dimethylbenzamide and methyl benzoate

图式3. 反应机理的探索

Scheme 3. Exploration of reaction mechanism

图式4. 酰胺或酯与苯并噁唑反应的可能机理

Scheme 4. Possible mechanism for the reaction of benzoxazoles with amides or esters

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