酸催化的烯丙基苯与四嗪环化反应的研究

doi:10.12422/j.issn.1006-396X.2025.02.008

摘要/Abstract

摘要：

茚并哒嗪衍生物因具有良好的生物活性，在农药和医药等领域具有广泛的应用前景，因此开发一种快速高效的合成方法越来越受到研究者的关注。设计了一种酸催化的烯丙基苯与四嗪官能化环化反应，对反应中间体进行捕获并使用核磁共振波谱仪对中间体以及产物进行了结构表征。结果表明，该反应经历分子间[4+2]环加成和分子内傅克烷基化反应等历程，实现了一步合成茚并哒嗪衍生物；反应还具有广阔的底物范围和良好的官能团相容性，能够以67%~95%的产率得到一系列的茚并哒嗪衍生物；在克级实验研究中，目标产物的产率可以达到81%，证明了该反应具有潜在的应用价值。

关键词: 烯丙基苯, 茚并哒嗪衍生物, [4+2]环化反应, 傅克反应

Abstract:

Indeno[1,2?d]pyridazine derivatives have wide applications in pesticides,pharmaceuticals,and other fields due to their excellent biological activities.Therefore,the development of rapid and efficient synthetic methods for these compounds has attracted increasing attention from researchers.A novel acid?catalyzed cyclization reaction between allylbenzene and tetrazine was designed.Reaction intermediates were trapped,and their structures,along with those of the products,were characterized using nuclear magnetic resonance spectroscopy.The results indicate that the reaction proceeds through intermolecular [4+2] cycloaddition and intramolecular Friedel?Crafts alkylation processes,enabling one?step synthesis of indeno[1,2?d]pyridazine derivatives.The reaction also exhibits a broad substrate scope and good functional group compatibility,yielding a series of indeno[1,2?d]pyridazine derivatives with 67%~95% yields.In gram scale experiments,the target product was obtained with an 81% yield, demonstrating the potential practical value of this reaction.

Key words: Allylbenzenes, Indeno[1,2?d]pyridazine derivatives, [4+2] Cycloaddition, Friedel?Crafts reaction

中图分类号:

TQ254.1

刘文卿, 王贺, 王欣, 李蕾. 酸催化的烯丙基苯与四嗪环化反应的研究[J]. 石油化工高等学校学报, 2025, 38(2): 62-71.

Wenqing LIU, He WANG, Xin WANG, Lei LI. Study on the Acid⁃Catalyzed Cyclization Reaction of Allylbenzenes and Tetrazine[J]. Journal of Petrochemical Universities, 2025, 38(2): 62-71.

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链接本文: https://journal.lnpu.edu.cn/syhg/CN/10.12422/j.issn.1006-396X.2025.02.008

https://journal.lnpu.edu.cn/syhg/CN/Y2025/V38/I2/62

图/表 15

图1 化合物1b的合成路线

Fig.1 Synthetic route for compound 1b

图2 化合物1k的合成路线

Fig.2 Synthetic route for compound 1k

图3 化合物1g的合成路线

Fig.3 Synthetic route for compound 1g

图4 化合物2的合成路线

Fig.4 Synthetic route for compound 2

图5 化合物3a的合成路线

Fig.5 Synthetic route for compound 3a

图6 化合物3i的合成路线

Fig.6 Synthetic route for compound 3i

图7 化合物3a的1H NMR和13C NMR

Fig.7 1H NMR and 13C NMR of compound 3a

图8 化合物4a的1H NMR和13C NMR

Fig.8 1H NMR and 13C NMR of compound 4a

表1 溶剂对反应产率的影响

Table 1 Effect of different solvents on reaction yield

溶剂	产率/%
二氯甲烷	28
三氯甲烷	10
乙醚	痕量
N,N-二甲基甲酰胺	痕量
乙腈	痕量
二甲基亚砜	痕量

表2 温度对反应产率的影响

Table 2 Effect of different temperatures on reaction yield

温度/℃	产率/%
室温	28
30	33
50	41

表3 催化剂对1j反应产率的影响

Table 3 Effect of different catalyst on 1j reaction yield

序号	催化剂	产率/%
1	Zn(OTf)₂	11
2	特戊酸	8
3	HOTf	74
4	乙酸	痕量
5	AgOTf	14

图9 化合物3a-3h的生成反应和产率

Fig.9 Forming reactions and yields of compounds 3a-3h

图10 化合物3i-3l的生成反应和产率

Fig.10 Forming reactions and yields of compounds 3i-3l

图11 中间体4a的捕捉实验流程

Fig.11 Experimental procedure for capturing intermediate 4a

图12 可能的反应机理

Fig.12 Possible reaction mechanism

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