偶氮次甲基亚胺与氮杂二烯前体的[4+3]环加成反应构建功能化四氮杂䓬衍生物

doi:10.6023/cjoc202303031

有机化学 ›› 2023, Vol. 43 ›› Issue (9): 3180-3187.DOI: 10.6023/cjoc202303031 上一篇下一篇

研究论文

偶氮次甲基亚胺与氮杂二烯前体的[4+3]环加成反应构建功能化四氮杂䓬衍生物

张晓轲^a^,^c^,^*(), 郑相如^b, 王朝永^a^,^*()

a 重庆大学附属涪陵医院中心实验室重庆 408000
b 重庆医科大学附属第三医院重庆 401120
c 遵义医科大学贵州 563006

收稿日期:2023-03-21 修回日期:2023-05-15 发布日期:2023-06-06
基金资助:
贵州省科技厅基础研究计划(QKHJC-ZK[2023]-495); 重庆市自然科学基金(cstc2021jcyj-bsh0010)

Strategy to Construct Functionalized Tetrazepine Derivatives via [4+3] Annulation Reaction of Azomethine Imine with Azadiene Precursor

Xiaoke Zhang^a^,^c(), Xiangru Zheng^b, Chaoyong Wang^a()

a Central Laboratory, Chongqing University Fuling Hospital, Chongqing 408000
b The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120
c Zunyi Medical University, Guizhou 563006

Received:2023-03-21 Revised:2023-05-15 Published:2023-06-06
Contact: * E-mail: cqwchy@sina.com;xiaokezhang53@163.com
Supported by:
Guizhou Provincial Science and Technology Plan Program(QKHJC-ZK[2023]-495); Chongqing Natural Science Foundation(cstc2021jcyj-bsh0010)

文章分享

1. 233180S.pdf(4845KB)

摘要/Abstract

四氮杂䓬衍生物具有良好的生物活性, 目前, 对于该骨架的构建方法非常有限, 因此, 建立了一种通过氢氧化钾促进α-卤代乙酰腙原位形成1,2-氮杂二烯中间体, 与偶氮次甲基亚胺环合反应合成高度取代的四氮杂䓬衍生物的新方法. 该方法表现出良好的官能团耐受性和底物普适性.

关键词: α-卤代乙酰腙, 偶氮次甲基亚胺, 四氮杂䓬衍生物, 氮杂二烯前体

Tetrazepine derivative exhibits good biological activities. Only a limited method has been devoted to constructing these frameworks to date. Therefore, an efficient and novel way was established for the synthesis of functionalized tetrazepine scaffolds through the cycloaddition reaction of azomethine imine with 1,2-azadiene formed in situ by α-halogeno hydrazones in the presence of KOH. This transformation shows excellent functional group tolerance and substrate scope.

Key words: α-halogeno hydrazone, azomethine imine, tetrazepine derivative, azadiene precursor

引用此文

张晓轲, 郑相如, 王朝永. 偶氮次甲基亚胺与氮杂二烯前体的[4+3]环加成反应构建功能化四氮杂䓬衍生物[J]. 有机化学, 2023, 43(9): 3180-3187.

Xiaoke Zhang, Xiangru Zheng, Chaoyong Wang. Strategy to Construct Functionalized Tetrazepine Derivatives via [4+3] Annulation Reaction of Azomethine Imine with Azadiene Precursor[J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3180-3187.

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

分享此文

图/表 6

Scheme 1. Synthesis of seven-membered heterocyclic skeleton bearing four heteroatoms

Scheme 2. Annulation of azomethine imines with C4 synthons

Entry	Base	Solvent	Yield^b/%
1	Na₂CO₃	CH₂Cl₂	36
2	Cs₂CO₃	CH₂Cl₂	51
3	K₂CO₃	CH₂Cl₂	73
4	Na₂CO₃	CH₂Cl₂	64
5	KOH	CH₂Cl₂	79
6	KO^tBu	CH₂Cl₂	42
7	TEDA	CH₂Cl₂	Trace
8	TEA	CH₂Cl₂	Trace
9	KOH	Et₂O	57
10	KOH	CHCl₃	72
11	KOH	MeCN	75
12	KOH	DMF	63
13	KOH	THF	91
14	KOH	EtOAc	60
15^c	KOH	THF	56
16^d	KOH	THF	89

Table 1. Optimization of reaction conditionsa

Table 2. Scope with various α-halogeno hydrazones and azomethine iminesa

Scheme 3. Postulated reaction pathway

Scheme 4. Gram-scale experiment of this process

参考文献 19

[1]	For some selected examples: (a) Hu X.; Li, D.; Chu, C.; Li, X.; Wang, X. H.; Jia, Y.; Hua, H. M.; Xu, F. X. Int. J. Mol. Sci. 2018, 19, 3403. doi: 10.3390/ijms19113403 pmid: 33793216
	(b) Xiao Y.; Gong Q.; Wang W. H.; Liu F.; Kong Q. H.; Pan F.; Zhang X. K.; Yu C. Y.; Hu S. S.; Fan F.; Li S. H.; Liu Y. Cancer Cell Int. 2020, 20, 371. doi: 10.1186/s12935-020-01463-w pmid: 33793216
	(c) Dong G. Q.; Liu Y.; Wu Y.; Tu J.; Chen S. Q.; Liu N.; Sheng C. Q. Chem. Commun. 2018, 54, 13535. doi: 10.1039/C8CC07810F pmid: 33793216
	(d) Fu D. J.; Li J.; Yu B. Eur. J. Med. Chem. 2021, 214, 113254. doi: 10.1016/j.ejmech.2021.113254 pmid: 33793216
	(e) Abdel-Halim M.; Sigler S.; Racheed N. A. S.; Hefnawy A.; Fathalla R. K.; Hammam M. A.; Maher A.; Maxuitenko Y. L.; Keeton A. B.; Hartmann R. W.; Engel M.; Piazza G. A.; Abadi A. H. J. Med. Chem. 2021, 64, 4462. doi: 10.1021/acs.jmedchem.0c01120 pmid: 33793216
[2]	(a) Krueger B. W.; Fischer R.; Bertram H. J.; Bretschneider T.; Boehm S.; Krebs A.; Schenke T.; Santel H. J.; Lurssen K.; Schmidt R. R.; Erdelen C.; Wachendorff-Neumann U.; Stendel, W. EP0508126, 1992.
	(b) Muehlebach M.; Cederbaum F.; Cornes D.; Friedmann A. A.; Glock J.; Hall G.; Indolese A. F.; Kloer D. P.; Goupil G. L.; Maetzke T.; Meier H.; Schneider R.; Stoller A.; Szczepanski H.; Wendeborna S.; Widmer H. Pest. Manage. Sci. 2011, 67, 1499. doi: 10.1002/ps.v67.12
	(c) Kamata M.; Yamashita T.; Tokkyo Koho, J. K. JP 2009196966, 2009.
	(d) Kamata M.; Yamashita T.; Kina A.; Tawada M.; Endo S.; Mizukami A.; Sasaki M.; Tani A.; Nakano Y.; Watanabe Y.; Furuyama N.; Funami M.; Amano N.; Fukatsu K. Bioorg. Med. Chem. Lett. 2012, 22, 4769. doi: 10.1016/j.bmcl.2012.05.062
[3]	(a) Kodato S. I.; Wada H.; Saito S.; Takeda M.; Nishibata Y.; Aoe K.; Date T.; Onoda Y.; Tamaki H. Chem. Pharm. Bull. 1987, 35, 80. doi: 10.1248/cpb.35.80
	(b) Mashevskaya I. V.; Makhmudov R. R.; Kuslina L. V.; Mokrushin I. G.; Shurov S. N.; Maslivets A. N. Pharm. Chem. J. 2012, 45, 660. doi: 10.1007/s11094-012-0697-0
	(c) Ibrahim S. M.; Baraka M. M.; El-Sabbagh O. I.; Kothayer H. Med. Chem. Res. 2013, 22, 1488. doi: 10.1007/s00044-012-0102-2
[4]	Almerico A. M.; Mingoia F.; Diana P.; Barraja P.; Lauria A.; Montalbano A.; Cirrincione G.; Dattolo G. J. Med. Chem. 2005, 48, 2859. pmid: 15828824
[5]	(a) Gupta C. M.; Bhaduri A. P.; Khanna N. M. J. Med. Chem. 1968, 11, 392. pmid: 5663640
	(b) Ghorab M. M.; Heiba H. I.; El-gawish M. A. Phosphorus, Sulfur Silicon Relat. Elem. 1995, 106, 85. doi: 10.1080/10426509508027893 pmid: 5663640
	(c) Hamama W. S.; El-Bana G. G.; Shaaban S.; Zoorob H. H. J. Heterocycl. Chem. 2018, 55, 971. doi: 10.1002/jhet.v55.4 pmid: 5663640
[6]	(a) Maggio B.; Raffa D.; Raimondi M. V.; Cascioferro S.; Plescia F.; Tolomeo M.; Barbusca E.; Cannizzo G.; Mancuso S.; Daidone G. Eur. J. Med. Chem. 2008, 43, 2386. doi: 10.1016/j.ejmech.2008.01.007
	(b) Maggio B.; Raffa D.; Raimondi M. V. ARKIVOC 2006, xv, 120.
	(c) Vahedi H.; Rajabzadeh G.; Farvandi F. Chin. Chem. Lett. 2010, 21, 1419. doi: 10.1016/j.cclet.2010.07.006
	(d) Darehkordi A.; Khorasani F. N.; Mohammadi M.; Kazemi E. Monatsh. Chem. 2020, 151, 1835. doi: 10.1007/s00706-020-02703-5
[7]	For selected examples, see: (a) Zhou M. B.; Song, R. J.; Wang, C. Y.; Li, J. H. Angew. Chem., Int. Ed. 2013, 52, 10805. doi: 10.1002/anie.201304902
	(b) Feng J. J.; Lin T. Y.; Wu H. H.; Zhang J. L. J. Am. Chem. Soc. 2015, 137, 3787. doi: 10.1021/jacs.5b01305
	(c) Liu L. L.; Chiu P. Chem. Commun. 2011, 47, 3416. doi: 10.1039/c1cc00087j
	(d) Gao H. Y.; Wu X. X.; Zhang J. L. Chem. Commun. 2010, 46, 8764. doi: 10.1039/c0cc02778b
[8]	Kumari Y. B. Heterocycl. Commun. 2007, 13, 177.
[9]	Li Z. F.; Li S. K.; Kan T. J.; Wang X. Y.; Xin X.; Hou Y. L.; Gong P. Adv. Synth. Catal. 2020, 362, 2626. doi: 10.1002/adsc.v362.13
[10]	(a) Huisgen R.; Fleischmann R.; Eckell A. Tetrahedron Lett. 1960, 1, 1.
	(b) Breugst M.; Reissig H. U. Angew. Chem., Int. Ed. 2020, 59, 12293. doi: 10.1002/anie.v59.30
	(c) Yue G. Z.; Liu B. Chin. J. Org. Chem. 2020, 40, 3132. (in Chinese) doi: 10.6023/cjoc202005092
	(乐贵洲, 刘波, 有机化学, 2020, 40, 3132.) doi: 10.6023/cjoc202005092
[11]	(a) Bakthadoss M.; Agarwal V. ChemistrySelect 2018, 3, 6960. doi: 10.1002/slct.v3.24
	(b) Choi A.; Castle J.; Saruengkhanphasit R.; Coldham I. Synthesis 2020, 1273.
	(c) Sandmeier T.; Sievertsen N.; Carreira E. M. Helv. Chim. Acta 2020, 103, e2000058. doi: 10.1002/hlca.v103.6
[12]	(a) Li Z.; Yu H.; Liu Y.; Zhou L.; Sun Z.; Guo H. Adv. Synth. Catal. 2016, 358, 1880. doi: 10.1002/adsc.v358.12 pmid: 29215289
	(b) Zhou L.; Yuan C.; Zhang C.; Zhang L.; Gao Z.; Wang C.; Liu H.; Wu Y.; Guo H. Adv. Synth. Catal. 2017, 359, 2316. doi: 10.1002/adsc.v359.13 pmid: 29215289
	(c) Zhu C. Z.; Feng J. J.; Zhang J. Chem. Commun. 2017, 53, 4688. doi: 10.1039/C7CC02078C pmid: 29215289
	(d) Yu L.; Zhong Y.; Yu J.; Gan L.; Cai Z.; Wang R.; Jiang X. Chem. Commun. 2018, 54, 2353. doi: 10.1039/C7CC09640B pmid: 29215289
	(e) Cheng X.; Cao X.; Xuan J.; Xiao W. J. Org. Lett. 2018, 20, 52. doi: 10.1021/acs.orglett.7b03344 pmid: 29215289
[13]	(a) Wei L.; Wang Z. F.; Yao L.; Qiu G. F.; Tao H. Y.; Li H.; Wang C. J. Adv. Synth. Catal. 2016, 358, 3955. doi: 10.1002/adsc.v358.24
	(b) Wang Y. F.; Zhu L. P.; Wang M. R.; Xiong J.; Chen N. N.; Feng X.; Xu Z. Q.; Jiang X. X. Org. Lett. 2018, 20, 6506. doi: 10.1021/acs.orglett.8b02828
[14]	(a) Li Z.; Feng Y. L.; Hou Z. F.; Zhang L.; Yang W. J.; Wu Y.; Xiao Y. M.; Guo H. C. RSC Adv. 2015, 5, 34481. doi: 10.1039/C5RA04374C
	(b) Mei G. J.; Zhu Z. Q.; Zhao J. J.; Bian C. Y.; Chen J.; Chen R. W.; Shi F. Chem. Commun. 2017, 53, 2768. doi: 10.1039/C6CC09775H
	(c) Li C.; Wang C. S.; Li T. Z.; Mei G. J.; Shi F. Org. Lett. 2019, 21, 598. doi: 10.1021/acs.orglett.8b03604
	(d) Yuan C. H.; Zhou L. J.; Xia M. R.; Sun Z. H.; Wang D. Q.; Guo H. C. Org. Lett. 2016, 18, 5644. doi: 10.1021/acs.orglett.6b02885
	(e) Na R.; Jing C.; Xu Q.; Jiang H.; Wu X.; Shi J. J. Am. Chem. Soc. 2011, 133, 13341.
	(f) Wang M.; Huang Z. J.; Xu J. F.; Chi Y. R. J. Am. Chem. Soc. 2014, 136, 1214. doi: 10.1021/ja411110f
	(g) Na R.; Jing C. F.; Xu Q. H.; Jiang H.; Wu X.; Shi J. Y.; Zhong J. C.; Wang M.; Benitez D.; Tkatchouk E.; Goddard W. A.; Guo H. C.; Kwon O. J. Am. Chem. Soc. 2011, 133, 13337. doi: 10.1021/ja200231v
	(h) Hu X. Q.; Chen J. R.; Gao S.; Feng B.; Lu L. Q.; Xiao W. J. Chem. Commun. 2013, 49, 7905. doi: 10.1039/c3cc43888k
	(i) Yang W. J.; Yuan C. H.; Liu Y.; Mao B. M.; Sun Z. H.; Guo H. C. J. Org. Chem. 2016, 81, 7597. doi: 10.1021/acs.joc.6b01296
[15]	(a) Jin Q.; Zhang J.; Jiang C.; Zhang D.; Gao M.; Hu S. J. Org. Chem. 2018, 83, 8410. doi: 10.1021/acs.joc.8b01055
	(b) Hu X. Q.; Chen J. R.; Gao S.; Feng B.; Lu L. Q.; Xiao W. J. Chem. Commun. 2013, 49, 7906.
	(c) Zhi Y.; Zhao K.; Shu T.; Enders D. Synthesis 2016, 48, 240.
	(d) Chen L.; Yang G. M.; Wang J.; Jia Q. F.; Wei J.; Du Z. Y. RSC Adv. 2015, 5, 76697.
[16]	For selected examples, see: (a) Zhang X. K.; Pan, Y.; Wang, H. B.; Liang, C.; Ma, X. F.; Jiao, W.; Shao, H. W. Adv. Synth. Catal. 2021, 363, 459. doi: 10.1002/adsc.v363.2 pmid: 26974596
	(b) Chen J. R.; Dong W. R.; Candy M.; Pan F. F.; Jörres M.; Bolm C. J. Am. Chem. Soc. 2012, 134, 6924. doi: 10.1021/ja301196x pmid: 26974596
	(c) Huang R.; Chang X.; Li J.; Wang C. J. J. Am. Chem. Soc. 2016, 138, 3998. doi: 10.1021/jacs.6b01008 pmid: 26974596
	(d) Quan B. X.; Zhuo J. R.; Zhao J. Q.; Zhang M. L.; Zhou M. Q.; Zhang X. M.; Yuan W. C. Org. Biomol. Chem. 2020, 18, 1886. doi: 10.1039/C9OB02733E pmid: 26974596
	(f) Chen B.; Chu W. D.; Liu Q. Z. RSC Adv. 2019, 9, 1487. doi: 10.1039/c8ra08909d pmid: 26974596
	(g) Huang R.; Chang X.; Li J.; Wang C. J. J. Am. Chem. Soc. 2016, 138, 3998. doi: 10.1021/jacs.6b01008 pmid: 26974596
	(h) Yin W. H.; Fang L.; Wang Z. Y.; Gao F.; Li Z. F.; Wang Z. Y. Org. Lett. 2020, 21, 7361. doi: 10.1021/acs.orglett.9b02661 pmid: 26974596
	(i) Cao W. B.; Xu X. P.; Ji S. J. Org. Biomol. Chem. 2017, 15, 1651. doi: 10.1039/C6OB02362B pmid: 26974596
	(j) Zhong X. G.; Lv J.; Luo S. Org. Lett. 2015, 17, 1561. doi: 10.1021/acs.orglett.5b00445 pmid: 26974596
	(k) Deng Y. M.; Pei C.; Arman H.; Dong K. Y.; Xu X. F.; Doyle M. P. Org. Lett. 2016, 18, 5884. doi: 10.1021/acs.orglett.6b02965 pmid: 26974596
[17]	Zhao H. W.; Pang H. L.; Tian T.; Li B.; Chen X. Q.; Song X. Q.; Meng W.; Yang Z.; Liu Y. Y.; Zhao Y. D. Adv. Synth. Catal. 2016, 358, 1826. doi: 10.1002/adsc.201600093
[18]	Cheng B.; Li Y. T.; Wang T. M.; Zhang X. P.; Li H.; Li Y.; Zhai H. B. Chem. Commun. 2019, 55, 14606. doi: 10.1039/C9CC08326J
[19]	Zhang X. K.; Wang H. B.; Li Z. W.; Shu Y.; Gan S. Zhang X. F.; Shao H. W.; Wang C. Y. ACS Omega 2022, 7, 40963. doi: 10.1021/acsomega.2c04127

偶氮次甲基亚胺与氮杂二烯前体的[4+3]环加成反应构建功能化四氮杂䓬衍生物

Strategy to Construct Functionalized Tetrazepine Derivatives via [4+3] Annulation Reaction of Azomethine Imine with Azadiene Precursor

RichHTML

PDF

补充材料

可视化

摘要/Abstract

引用此文

分享此文

图/表 6

参考文献 19

相关文章 2

编辑推荐

相关统计

本文评价

[1]	华庭碧, 阳青青, 肖文精. C,N-环状偶氮次甲基亚胺参与的反应研究进展[J]. 有机化学, 2020, 40(11): 3559-3595.
[2]	乐贵洲, 刘波. 1,3-偶极子[3+n](n≥3)环加成反应的研究进展[J]. 有机化学, 2020, 40(10): 3132-3153.