A Practical Synthesis of (Z)-N-Vinyl Substituted N,O-Acetals under Continuous Flow Technology

doi:10.6023/cjoc202208016

Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (4): 1550-1558.DOI: 10.6023/cjoc202208016 Previous Articles Next Articles

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利用连续流动技术合成(Z)-N-乙烯基取代N,O-缩醛

李靖鹏^b, 黄顺桃^b, 杨棋^b, 李伟强^b, 刘腾^a^,^*(), 黄超^b^,^*()

a 曲靖师范学院化学与环境科学学院云南曲靖 655011
b 云南民族大学化学与环境学院生物基材料绿色制备技术国家地方联合工程研究中心昆明 650500

收稿日期:2022-08-15 修回日期:2022-09-30 发布日期:2022-11-21
通讯作者: 刘腾, 黄超
基金资助:
国家自然科学基金(21662046); 国家自然科学基金(21202142); 云南省教育厅科研基金(2021Y667); 及云南地方高校科研基金(202101BA070001-049)

A Practical Synthesis of (Z)-N-Vinyl Substituted N,O-Acetals under Continuous Flow Technology

Jingpeng Li^b, Shuntao Huang^b, Qi Yang^b, Weiqiang Li^b, Teng Liu^a(), Chao Huang^b()

a College of Chemistry and Environmental Science, Qujing Normal University, Qujing, Yunnan 655011
b National and Local Joint Engineering Research Center for Green Preparation Technology of Biobased Materials, School of Chemistry and Environment, Yunnan Minzu University, Kunming 650500

Received:2022-08-15 Revised:2022-09-30 Published:2022-11-21
Contact: Teng Liu, Chao Huang
Supported by:
National Natural Science Foundation of China(21662046); National Natural Science Foundation of China(21202142); Scientific Research Fund of Yunnan Provincial Department of Education(2021Y667); Yunnan Local Colleges Research Projects of China(202101BA070001-049)

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Abstract

A novel, efficient and practical route to the preparation of (Z)-N-vinyl five-membered cyclic N,O-acetal derivatives utilized by continuous flow technology has been developed. The tandem cyclization reaction uses Schiff base imine as an intermediate, followed by the addition of hydroxyl group to alkynyl ester under the action of alkali, undergoing a unique intramolecular rearrangement to synthesize acetal derivatives. The whole cascade cyclization process generates a new C—O bond and C—N bond. In addition, the application of continuous flow technology can accurately control the three-component reaction pathway compared with traditional batch reaction, which can inhibit the generation of by-products between two components and provide a series of structurally diverse nitrogen- and oxygen-containing heterocycles in short time with high yields (81%~90%).

Key words: cyclic N,O-acetal, cascade cyclization reaction, control reaction pathway, continuous flow technology, three- component reaction

Cite this article

Jingpeng Li, Shuntao Huang, Qi Yang, Weiqiang Li, Teng Liu, Chao Huang. A Practical Synthesis of (Z)-N-Vinyl Substituted N,O-Acetals under Continuous Flow Technology[J]. Chinese Journal of Organic Chemistry, 2023, 43(4): 1550-1558.

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Fig. & Tab. 6

Scheme 1. Representative bioactive molecules and general strategies

Scheme 2. Simple device of continuous flow synthesis process and instrument picture

Entry	X	T/℃	Time/min	4a^b/%
1	20	r.t.	40	0
2	20	30	40	0
3	20	40	40	23
4	20	50	40	41
5	20	55	40	50
6	20	60	40	66
7	20	65	40	72
8	20	70	40	79
9	20	75	40	85
10	20	80	40	89
11	20	85	40	89
12	20	80	45	89
13	20	80	35	87
14	15	80	40	83
15	10	80	40	79
16	25	80	40	89

Table 1. Optimization of reaction conditionsa

Table 2. Substrate scopea

Scheme 3. Control experiments and gram-scale reaction

Scheme 4. Proposed mechanism

References 9

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利用连续流动技术合成(Z)-N-乙烯基取代N,O-缩醛

A Practical Synthesis of (Z)-N-Vinyl Substituted N,O-Acetals under Continuous Flow Technology

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Fig. & Tab. 6

References 9

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