四丁基碘化胺介导烷基酰胺与酰肼一锅法构建1,3,4-噁二唑衍生物

doi:10.6023/cjoc202304005

摘要/Abstract

1,3,4-噁二唑衍生物是一类重要的生物活性分子, 表现出良好的抗菌、抗炎和抗癌活性. 该研究发展了一种无碱、无金属条件下, 以酰肼和烷基酰胺为原料, 一锅法构建五元杂环噁二唑的有效合成方法. 反应10 h, 即可以高达85%的收率得到预期的1,3,4-噁二唑衍生物. 该方法具有操作简单、条件温和、副产物少和底物范围广等优点. 并且可以实现克级制备, 展示出良好的实用价值. 机理研究表明酰胺自身电子云的互变异构和四丁基碘化胺(TBAI)以及酰肼羰基的活性作用对反应的发生起到了至关重要的作用.

关键词: 1,3,4-噁二唑, 烷基酰胺, 芳基甲酰肼, 四丁基碘化胺(TBAI), 一锅法

1,3,4-Oxadiazole derivatives are a class of important bioactive molecules, showing good antibacterial, anti-inflam- matory and anticancer activities. In the present study, an efficient one-pot synthetic methodology has been developed for the construction of 1,3,4-oxadiazoles by utilizing acylhydrazine and alkylamide as reactants in the absence of alkaline or metallic catalysts. The expected 1,3,4-oxadiazole derivatives can be obtained with a maximum 85% yield for 10 h. This method has the advantages of simple operation, mild conditions, few by-products and wide range of substrates. And it can achieve gram preparation, showing good practical value. The mechanism study showed that the tautomerism of amide electron cloud, and the activity of tetrabutylammonium iodide (TBAI) and hydrazide carbonyl group played an important role in the reaction.

Key words: 1,3,4-oxadiazole, alkyl amide, arylhydrazide, tetrabutylammonium iodide (TBAI), one-pot

引用此文

景智霞, 杜建喜, 蒋平, 阿布拉江•克依木. 四丁基碘化胺介导烷基酰胺与酰肼一锅法构建1,3,4-噁二唑衍生物[J]. 有机化学, 2023, 43(11): 3930-3938.

Zhixia Jing, Jianxi Du, Ping Jiang, Keyume Ablajan. Tetrabutylammonium Iodide-Mediated One-Pot Construction of 1,3,4-Oxadiazole Derivatives with Alkyl Amide and Hydrazine[J]. Chinese Journal of Organic Chemistry, 2023, 43(11): 3930-3938.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 8

图式1. 1,3,4-噁二唑衍生物的合成

Scheme 1. Synthesis of 1,3,4-oxadiazole derivatives

Entry	Oxidant (equiv.)	Solvent/mL	Temp/℃	Yield^b/%
1	I₂(1)	PhCH₃	100	75
2 3 4 5 6	I₂ (1) I₂ (1) I₂ (1) I₂ (1) I₂ (1)	H₂O DMSO DCE DCE CH₃CH₂OH	100 100 100 90 80	n.d n.d 78 50 n.d
7 8 9 10 11 12 13 14 15 16 17 18 19 20	K₂S₂O₈ (1) NBS (1) NCS (1) TBAI (1) — PhI(OAc)₂ (1) IBX (1) KI (1) NH₄I (1) NaI (1) TBAI (0.5) TBAI (2) TBAI (0.5) TBAI (0.5)	DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE	100 100 100 100 100 100 100 100 100 100 100 100 90 80	n.d 75 n.d 81 n.d n.d n.d n.d n.d n.d 85 79 38 n.d

表1. 反应条件的优化a

Table 1. Optimization of reaction conditions

表2. N-甲基甲酰胺与芳基甲酰肼类的底物拓展a,b

Table 2. Substrate expansion of N-methyl formamide and arylformyl hydrazine

表3. N-甲基乙酰胺与芳基甲酰肼类的底物拓展a,b

Table 3. Substrate expansion of N-methyl acetamide and arylformyl hydrazine

表4. N,N-二甲基丙酰胺与芳基甲酰肼类的底物拓展a,b

Table 4. Substrate expansion of N,N-dimethylpropionamide and arylformylhydrazine

图式2. 克级反应

Scheme 2. Gram-scale reaction

图式3. 自由基捕获实验

Scheme 3. Radical trapping experiments

图式4. TBAI催化芳基甲酰肼和酰胺生成噁二唑环的可能反应机理

Scheme 4. Possible reaction mechanism for the formation of oxadiazole rings from the reaction aryl acylhydrazides and amidescatalyzed by TBAI

参考文献 27

[1]	(a) Fan, Y.; He, Y.; Liu, X.; Hu, T.; Ma, H.; Yang, X.; Luo, X.; Huang, G. J. Org. Chem. 2016, 81, 6820. doi: 10.1021/acs.joc.6b01135
	(b) Bozorov, K.; Nie, L. F.; Zhao, J.; Aisa, H. A. Eur. J. Med. Chem. 2017, 140, 465. doi: 10.1016/j.ejmech.2017.09.039
	(c) Liu, S.; Zhao, Z.; Wang, Y. Chem.-Eur. J. 2019, 25, 2423. doi: 10.1002/chem.v25.10
	(d) Bostrom, J.; Hogner, A.; Llinas, A.; Wellner, E.; Plowright, A. T. J. Med. Chem. 2012, 55, 1817. doi: 10.1021/jm2013248
[2]	(a) Aksenov, A. V.; Khamraev, V.; Aksenov, N. A.; Kirilov, N. K.; Domenyuk, D. A.; Zelensky, V. A.; Rubin, M. RSC Adv. 2019, 9, 6636. doi: 10.1039/C9RA00976K pmid: 24972008
	(b) Abd-Ellah, H. S.; Abdel-Aziz, M.; Shoman, M. E.; Beshr, E. A.; Kaoud, T. S.; Ahmed, A. F. Bioorg. Chem. 2016, 69, 48. doi: S0045-2068(16)30136-5 pmid: 24972008
	(c) Boudreau, M. A.; Ding, D.; Meisel, J. E.; Janardhanan, J.; Spink, E.; Peng, Z.; Qian, Y.; Yamaguchi, T.; Testero, S. A.; O'Daniel, P. I.; Leemans, E.; Lastochkin, E.; Song, W.; Schroeder, V. A.; Wolter, W. R.; Suckow, M. A.; Mobashery, S.; Chang, M. ACS Med. Chem. Lett. 2020, 11, 322. doi: 10.1021/acsmedchemlett.9b00379 pmid: 24972008
	(d) Padejjar Vasantha, S.; Poojary, B.; Bistuvalli Chandrashekarappa, R. J. Chin. Chem. Soc. 2019, 66, 638. doi: 10.1002/jccs.2019.66.issue-6 pmid: 24972008
	(e) Wang, P. Y.; Zhou, L.; Zhou, J.; Wu, Z. B.; Xue, W.; Song, B. A.; Yang, S. Bioorg. Med. Chem. Lett. 2016, 26, 1214. doi: 10.1016/j.bmcl.2016.01.029 pmid: 24972008
	(f) Valente, S.; Trisciuoglio, D.; Luca, T. D.; Nebbioso, A.; Labella, D.; Lenoci, A.; Bigogno, C.; Dondio, G.; Miceli, M.; Brosch, G.; Bufalo, D. D.; Altucci, L.; Mai, A. J. Med. Chem. 2014, 57, 6259. doi: 10.1021/jm500303u pmid: 24972008
[3]	(a) Najare, M. S.; Patil, M. K.; Nadaf, A. A.; Mantur, S.; Garbhagudi, M.; Gaonkar, S.; Inamdar, S. R.; Khazi, I. A. M. J. Mol. Struct. 2020, 1199.
	(b) Liu, Y.; Xing, K. Q.; Deng, J. Y.; Zhu, M. X.; Wang, X. Y.; Zhu, W. G. Chin. Chem. Lett. 2007, 18, 573. doi: 10.1016/j.cclet.2007.03.028
[4]	(a) Weng, C.; Liu, Z.; Guo, H.; Tan, S. Macromol. Chem. Phys. 2017, 218, 170094.
	(b) Chwarzer, K.; Tullmann, C. P.; Grassl, S.; Gorski, B.; Brocklehurst, C. E.; Knochel, P. Org. Lett. 2020, 22, 1899. doi: 10.1021/acs.orglett.0c00238
	(c) Hou, R. B.; Su, J. Y.; Zhang, L. L.; Li, D. F.; Xia, Y. J. Chem. Res. 2019, 43, 3.
[5]	(a) Stabile, P.; Lamonica, A.; Ribecai, A.; Castoldi, D.; Guercio, G.; Curcuruto, O. Tetrahedron Lett. 2010, 51, 4801.
	(b) Li, M. F.; Wang, R.; Hao, W. J.; Jiang, B. Chin. J. Org. Chem. 2020, 40, 1540. (in Chinese) doi: 10.6023/cjoc202002029
	(李梦帆, 王榕, 郝文娟, 姜波, 有机化学, 2020, 40, 1540.) doi: 10.6023/cjoc202002029
	(c) Zhang, X.; He, J.; Cao, S. Asian J. Org. Chem. 2019, 8, 279. doi: 10.1002/ajoc.v8.2
	(d) Fugard, A. J.; Thompson, B. K.; Slawin, A. M.; Taylor, J. E.; Smith, A. D. Org. Lett. 2015, 17, 5824. doi: 10.1021/acs.orglett.5b02997
	(e) Green, L.; Livingstone, K.; Bertrand, S.; Peace, S.; Jamieson, C. Chem.-Eur. J. 2020, 26, 14866. doi: 10.1002/chem.v26.65
[6]	(a) Gao, Q.; Liu, S.; Wu, X.; Zhang, J.; Wu, A. Org. Lett. 2015, 17, 2960. doi: 10.1021/acs.orglett.5b01241
	(b) Shivi, B.; Monika, G. J. Chem. Pharm. Res. 2011, 3, 137.
[7]	Li, Q.; Tao, Y.; Xu, D.; Zhang, H.; Duan, L. J. Chin. Chem. Soc. 2014, 61, 665. doi: 10.1002/jccs.v61.6
[8]	(a) Niu, P.; Kang, J.; Tian, X.; Song, L.; Liu, H.; Wu, J.; Yu, W.; Chang, J. J. Org. Chem. 2015, 80, 1018. doi: 10.1021/jo502518c pmid: 31368711
	(b) Chauhan, J.; Ravva, M. K.; Sen, S. Org. Lett. 2019, 21, 6562. doi: 10.1021/acs.orglett.9b02542 pmid: 31368711
[9]	Wang, Q.; Wang, X.; Liu, Q.; Xie, G.; Ding, S.; Wang, X.; Fan, H. Org. Chem. Front. 2020, 7, 3912. doi: 10.1039/D0QO01068E
[10]	Fugard, A. J.; Thompson, B. K.; Slawin, A. M.; Taylor, J. E.; Smith, A. D. Org. Lett. 2015, 17, 5824. doi: 10.1021/acs.orglett.5b02997
[11]	Lu, F.; Gong, F.; Li, L. Eur. J. Org. Chem. 2020, 3257.
[12]	(a) Li, A. F.; Ruan, Y. B.; Jiang, Q. Q.; He, W. B.; Jiang, Y. B. Chem.-Eur. J. 2010, 16, 5794. doi: 10.1002/chem.v16:19 pmid: 31368711
	(b) Pouliot, M. F.; Angers, L.; Hamel, J. D.; Paquin, J. F. Org. Biomol. Chem. 2012, 10, 988. doi: 10.1039/C1OB06512B pmid: 31368711
	(c) Chauhan, J.; Ravva, M. K.; Sen, S. Org. Lett. 2019, 21, 6562. doi: 10.1021/acs.orglett.9b02542 pmid: 31368711
[13]	Yu, W.; Huang, G.; Zhang, Y. T.; Liu, H. X.; Dong, L. H.; Yu, X. J.; Li, Y. J.; Chang, J. B. J. Org. Chem. 2013, 78, 10337. doi: 10.1021/jo401751h
[14]	Wang, L.; Wang, Y. Y; Chen, Q.; He, M. Y. Tetrahedron Lett. 2018, 59, 1489. doi: 10.1016/j.tetlet.2018.03.005
[15]	Wang, Q.; Wang, X.; Liu, Q.; Xie, G.; Ding, S.; Wang, X. X; Fan, H. Org. Chem. Front. 2020, 7, 3912. doi: 10.1039/D0QO01068E
[16]	Shu, W. M.; Zhang, X. Zhang, X. X.; Li, M.; Wang, A. J.; Wu, A. X. J. Org. Chem. 2019, 84, 14919. doi: 10.1021/acs.joc.9b02250
[17]	Wang, S.; Wang, K.; Kong, X.; Zhang, S.; Jiang, G.; Ji, F. Adv. Synth. Catal. 2019, 361, 3986. doi: 10.1002/adsc.v361.17
[18]	(a) Wang, Q.; Mgimpatsang, K. C.; Konstantinidou, M.; Shishkina, S. V.; Dömling, A. Org. Lett. 2019, 21, 7320. doi: 10.1021/acs.orglett.9b02614
	(b) Zhang, L.; Yu, Y.; Tang, Q.; Yuan, J.; Ran, D.; Tian, B.; Pan, T.; Gan, Z. Synth. Commun. 2019, 50, 423. doi: 10.1080/00397911.2019.1700521
[19]	(a) Suresh, D.; Kanagaraj, K.; Pitchumani, K. Tetrahedron Lett. 2014, 55, 3678. doi: 10.1016/j.tetlet.2014.05.004
	(b) Wang, Y.; Meng, Xu.; Yang, Y. T.; Chen, B. H. Chem. Commun. 2015, 51, 1907.
[20]	Majji, G.; Rout, S. K.; Guin, S.; Gogoi, A.; Patel, B. K. RSC Adv. 2014, 4, 5357. doi: 10.1039/c3ra44897e
[21]	Su, X. L.; Ye, L.; Chen, J. J.; Liu, X. D.; Jiang, S. P.; Jiang, F. L.; Liu, X. Y. Angew. Chem., Int. Ed. 2021, 60, 380. doi: 10.1002/anie.v60.1
[22]	Zou, L. H.; Reball, J.; Mottweiler, J.; Bolm, C. Chem. Commun. 2012, 48, 11307. doi: 10.1039/c2cc36711d
[23]	(a) Zhang, Q. W.; Wang, B.; Ma, H. F.; Ablajan, K. New J. Chem. 2019, 43, 17000. doi: 10.1039/C9NJ03076J
	(b) Jia, Y. F.; Ablajan, K. Adv. Synth. Catal. 2023, 365, 244. doi: 10.1002/adsc.v365.2
	(c) Liang, J.; Ma, H. F.; Ablajan, K. Chin. J. Org. Chem. 2019, 39, 3169. doi: 10.6023/cjoc201904028
[24]	(a) Siwach, A.; Verma, P. K. BMC Chem. 2020, 14, 70. doi: 10.1186/s13065-020-00721-2 pmid: 33372629
	(b) Gao, P.; Wang, J.; Bai, Z.; Cheng, H.; Xiao, J.; Lai, M.; Yang, D.; Fan, M. Tetrahedron Lett. 2016, 57, 4616. doi: 10.1016/j.tetlet.2016.09.007 pmid: 33372629
	(c) Dong, D. Q.; Zhang, H.; Wang, Z. L. RSC Adv. 2017, 7, 3780. doi: 10.1039/C6RA26387A pmid: 33372629
	(d) Li, L. X.; Dong, D. Q.; Hao, S. H.; Wang, Z. L. Tetrahedron Lett. 2018, 59, 1517. doi: 10.1016/j.tetlet.2018.03.023 pmid: 33372629
[25]	Zahra, D. G.; Karim, A. D. J. Chin. Chem. Soc. 2020, 67, 1446. doi: 10.1002/jccs.v67.8
[26]	Gnanasekaran, K. K.; Nammalwar, B.; Murie, M.; Bunce, R. A. Tetrahedron Lett. 2014, 55, 6776. doi: 10.1016/j.tetlet.2014.10.028
[27]	Polshettiwar, V.; Varma, R. S. Tetrahedron Lett. 2008, 49, 879. doi: 10.1016/j.tetlet.2007.11.165