One-Pot Metal-Free Synthesis of New 1,2,3-Triazolobenzodiaze-pinones by a Sequential Ugi 4CR/Alkyne-Azide Cycloaddition Reaction

doi:10.6023/cjoc202502039

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (10): 3923-3931.DOI: 10.6023/cjoc202502039 Previous Articles Next Articles

ARTICLES

无金属参与的连续的Ugi四组分/炔烃-叠氮环加成反应一锅合成新型1,2,3-三唑并苯并二氮杂䓬酮

闫艳梅^a^,^*(), 张虹利^a, 原敏^a, 秦睿佳^a, 任振兴^b^,^*(), 何迎春^b^,^*()

^a 太原师范学院化学与材料学院山西晋中 030619
^b 山西大学应用化学研究所太原 030006

收稿日期:2025-02-28 修回日期:2025-05-04 发布日期:2025-06-11
基金资助:
山西省高等学校科技创新计划(2021L427); 山西省青年科学基金(202203021222247); 山西省基础研究计划(202203021221038); 山西省基础研究计划(202403021221183); 太原师范学院大学生创新创业训练计划(CXCY25035)

One-Pot Metal-Free Synthesis of New 1,2,3-Triazolobenzodiaze-pinones by a Sequential Ugi 4CR/Alkyne-Azide Cycloaddition Reaction

Yanmei Yan^a^,^*(), Hongli Zhang^a, Min Yuan^a, Ruijia Qin^a, Zhenxing Ren^b^,^*(), Yingchun He^b^,^*()

^a College of Chemistry and Materials, Taiyuan Normal University, Jinzhong, Shanxi 030619
^b Institute of Applied Chemistry, Shanxi University, Taiyuan 030006

Received:2025-02-28 Revised:2025-05-04 Published:2025-06-11
Contact: * yanyanmei1019@yeah.net; zxren@sxu.edu.cn; heyingchun@sxu.edu.cn
Supported by:
Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi Province(2021L427); Shanxi Provincial Science Foundation for Youths(202203021222247); Fundamental Research Program of Shanxi Province(202203021221038); Fundamental Research Program of Shanxi Province(202403021221183); College Students’ Innovation Program of Taiyuan Normal University(CXCY25035)

1. .pdf(1662KB)

Abstract

A novel and metal-free sequential Ugi-4CR/alkyne-azide cycloaddition reaction towards the synthesis of new 1,2,3-triazolobenzodiazepinones under a mild reaction is reported. The reaction of (E)-2-(1-alkynyl)-3-arylpropenoic acids, 2-azidobenzenamines, aldehydes, and isocyanides produced 1,2,3-triazolobenzodiazepinones by a Ugi 4CR/alkyne-azide cycloaddition sequence in excellent yields ranging from 77% to 92%. Furthermore, simple operation, high atom economy and good to excellent yields all make it useful in synthetic and medicinal chemistry.

Key words: one-pot, metal-free, Ugi 4CR, alkyne-azide cycloaddition, 1,2,3-triazolobenzodiazepinone

Cite this article

Yanmei Yan, Hongli Zhang, Min Yuan, Ruijia Qin, Zhenxing Ren, Yingchun He. One-Pot Metal-Free Synthesis of New 1,2,3-Triazolobenzodiaze-pinones by a Sequential Ugi 4CR/Alkyne-Azide Cycloaddition Reaction[J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3923-3931.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 5

References 21

[1]	(a) Leśniewska, A.; Przybylski, P. Eur. J. Med. Chem. 2024, 275, 116556.
	(b) Ouvry, G. Bioorg. Med. Chem. 2022, 57, 116650.
[2]	(a) Vachhani, D. D.; Kumar, A.; Modha, S. G.; Sharma, S. K.; Parmar, V. S.; Van der Eycken, E. V. Eur. J. Org. Chem. 2013, 1223. pmid: 18367615
	(b) Hanson, S. M.; Czajkowski, C. J. Neurosci. 2008, 28, 3490. doi: 10.1523/JNEUROSCI.5727-07.2008 pmid: 18367615
	(c) Snyder, P. J.; Werth, J.; Giordani, B.; Caveney, A. F.; Feltner, D.; Maruff, P. Hum. Psychopharmacol. Clin. Exp. 2005, 20, 263. pmid: 18367615
	(d) Watanabe, M.; Maemura, K.; Kanbara, K.; Tamayama, T.; Hayasaki, H. Int. Rev. Cytol. 2002, 213, 1. pmid: 18367615
	(e) Levine, J.; Cole, D. P.; Chengappa, K. N. R.; Gershon, S. Depression Anxiety 2001, 14, 94. pmid: 18367615
[3]	(a) Barlow, T. M. A.; Tourwé, D.; Ballet, S. Eur. J. Org. Chem. 2017, 4678. pmid: 2979741
	(b) Olkkola, K.; Ahonen, J. Modern Anesthetics, Springer, Berlin, 2008, p. 335. pmid: 2979741
	(c) Hurley, L. H.; Reck, T.; Thurston, D. E.; Langley, D. R.; Holden, K. G.; Hertzberg, R. P.; Hoover, J. R.; Gallagher, G. Jr; Faucette, L. F. Chem. Res. Toxicol. 1988, 1, 258. pmid: 2979741
[4]	Shafie, A.; Mohammadi-Khanaposhtani, M.; Asadi, M.; Rahimi, N.; Ranjbar, P. R.; Ghasemi, J. B.; Larijani, B.; Mahdavi, M.; Shafaroodi, H.; Dehpour, A. R. Mol. Diversity 2020, 24, 179.
[5]	Biagi, G.; Giorgi, I.; Livi, O.; Scartoni, V.; Velo, S.; DeSantis, B.; Martinelli, A.; Martini, C.; Senatore G. Farmaco 1996, 51, 13.
[6]	(a) Sharpless, K. B.; Manetsch, R. Expert Opin. Drug Discovery 2006, 1, 525. pmid: 19648009
	(b) Mohapatra, D. K.; Maity, P. K.; Shabab, M.; Khan, M. I. Bioorg. Med. Chem. Lett. 2009, 19, 5241. doi: 10.1016/j.bmcl.2009.06.107 pmid: 19648009
[7]	(a) Bertelli, L.; Biagi, G.; Giorgi, I.; Livi, O.; Manera, C.; Scartoni, V.; Martini, C.; Giannaccini, G.; Trincavelli, L.; Barili, P. L. Farmaco 1998, 53, 305. pmid: 23697376
	(b) Akritopoulo-Zanze, I.; Gracias, V.; Djuric, S. W. Tetrahedron Lett. 2004, 45, 8439. pmid: 23697376
	(c) Granger, B. A.; Kaneda, K.; Martin, S. F. Org. Lett. 2011, 13, 4542. doi: 10.1021/ol201739u pmid: 23697376
	(d) Granger, B. A.; Wang, Z.; Kaneda, K.; Fang, Z.; Martin, S. F. ACS Comb. Sci. 2013, 15, 379. doi: 10.1021/co400055b pmid: 23697376
	(d) Feng, Y. K.; Wang, H.; Cui, M. X.; Sun, R.; Wang, X.; Chen, Y.; Li, L. Chin. J. Org. Chem. 2023, 43, 2913 (in Chinese). pmid: 23697376
	(冯莹珂, 王贺, 崔梦行, 孙然, 王欣, 陈阳, 李蕾, 有机化学, 2023, 43, 2913.) doi: 10.6023/cjoc202303004 pmid: 23697376
[8]	Asgari, M. S.; Soheilizad, M.; Ranjbar, P. R.; Larijani, B.; Rahimi, R.; Mahdavi, M. Tetrahedron Lett. 2019, 60, 583.
[9]	Chen, K. C.; Barve, I. J.; Sun, C. M. Org. Lett. 2020, 22, 428.
[10]	Mazur, M. O.; Zhelavskyi, O. S.; Zviagin, E. M.; Shishkina, S. V.; Musatov, V. I.; Kolosov, M. A.; Shvets, E. H.; Andryushchenko, A. Y.; Chebanov, V. A. Beilstein J. Org. Chem. 2021, 17, 678.
[11]	(a) Dömling, A.; Wang, W.; Wang, K. Chem. Rev. 2012, 112, 3083. pmid: 35822540
	(b) Dömling, A. Chem. Rev. 2006, 106, 17. pmid: 35822540
	(c) Dömling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168. pmid: 35822540
	(d) Brandes, D. S.; Ellman, J. A. Chem. Soc. Rev. 2022, 51, 6738. doi: 10.1039/d2cs00012a pmid: 35822540
	(e) Wu, P.; Givskov, M.; Nielsen, T. E. Chem. Rev. 2019, 119, 11245. doi: 10.1021/acs.chemrev.9b00214 pmid: 35822540
[12]	Touré, B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439.
[13]	(a) Ugi, I. Isonitrile Chemistry, Academic press, New York, 1971. pmid: 39670166
	(b) Gulevich, A. V.; Zhdanko, A. G.; Orru, R. V. A.; Nenajdenko, V. G. Chem. Rev. 2010, 110, 5235. doi: 10.1021/cr900411f pmid: 39670166
	(c) Wang, Y.; Kumar, R. K.; Bi, X. Tetrahedron Lett. 2016, 57, 5730. pmid: 39670166
	(d) Giustiniano, M.; Basso, A.; Mercalli, V.; Massarotti, A.; Novellino, E.; Tron, G. C.; Zhu, J. Chem. Soc. Rev. 2017, 46, 1295. pmid: 39670166
	(e) Zavarise, C.; Cintrat, J. C.; Romero, E.; Sallustrau, A. RSC Adv. 2024, 14, 39253. doi: 10.1039/d4ra04152f pmid: 39670166
[14]	(a) Dömling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168.
	(b) Wessjohann, L. A.; Rhoden, C. R. B.; Rivera, D. G.; Vercillo, O. E. Top. Heterocycl. Chem. 2010, 23, 199.
	(c) Tron, G. C. Eur. J. Org. Chem. 2013, 1849.
[15]	(a) Wang, Y.; Patil, P.; Kurpiewska, K.; Kalinowska-Tluscik, J.; Dömling, A. Org. Lett. 2019, 21, 3533. pmid: 29087201
	(b) Li, Y.; Meng, J. P.; Lei, J.; Chen, Z. Z.; Tang, D. Y.; Zhu, J.; Zhang, J.; Xu, Z. G. ACS Comb. Sci. 2017, 19, 324. pmid: 29087201
	(c) Singh, K.; Malviya, B. K.; Jaiswal, P. K.; Verma, V. P.; Chimni, S. S.; Sharma, S. Org. Lett. 2019, 21, 6726. pmid: 29087201
	(d) Balalaie, S.; Mirzaie, S.; Nikbakht, A.; Hamdan, F.; Rominger, F.; Navari, R.; Bijanzadeh, H. R. Org. Lett. 2017, 19, 6124. doi: 10.1021/acs.orglett.7b02603 pmid: 29087201
	(e) Liu, C.; Song, L. L.; Meervelt, L. V.; Peshkov, V. A.; Li, Z. H. Org. Lett. 2021, 23, 5065. pmid: 29087201
	(f) Wu, X. B.; Shi, J. X.; Ou, Y. M.; Jiang, H. J.; Fang, Y. J.; Wang, Q. M.; Gao, Q.; Yu, J. Sci. China Chem. 2024, 67, 576. pmid: 29087201
	(g) Tang, X.; Tao, Q. Q.; Song, L. L.; Van der Eycken, E. V. Org. Chem. Front. 2024, 11, 4895. pmid: 29087201
[16]	(a) Yan, Y. M.; Tong, H. B.; Ren, Z. X.; Zhang, H. L.; Wang, J.; He, Y. C.; Wang, Y. Z. Org. Lett. 2025, 27, 1216. pmid: 26759921
	(b) He, Y. C.; Yan, Y. M.; Ren, Z. X.; Wang, Y. Z.; Yu, Q.; Xiong, J.; Wang, M. L. Adv. Synth. Catal. 2021, 363, 1038. pmid: 26759921
	(c) Yan, Y. M.; Rao, Y.; Ding, M. W. J. Org. Chem. 2016, 81, 1263. doi: 10.1021/acs.joc.5b02575 pmid: 26759921
	(d) Yan, Y. M.; Wang, M. L.; Liu, Y. L.; He Y. C. Tetrahedron 2020, 76, 131389. pmid: 26759921
	(e) Yan, Y. M.; Li, H. Y.; Zhang, M.; Wang, R. X.; Zhou, C. G.; Ren, Z. X.; Ding, M. W. Synlett 2020, 31, 73. pmid: 26759921
[17]	Rahul, P.; Thomas, J.; Dehaen, W.; John, J. Molecules 2023, 28, 308.
[18]	Salvador, C. E. M.; Pieber, B.; Neu, P. M.; Torvisco, A.; Andrade, C. K. Z.; Kappe, C. O. J. Org. Chem. 2015, 80, 4590. doi: 10.1021/acs.joc.5b00445 pmid: 25842982
[19]	Zakharova, E. A.; Shmatova, O. I.; Kutovaya, I. V.; Khrustalev, V. N.; Nenajdenko, V. G. Org. Biomol. Chem. 2019, 17, 3433. doi: 10.1039/c9ob00229d pmid: 30874270
[20]	Vroemans, R.; Bamba, F.; Winters, J.; Thomas, J.; Jacobs, J.; Meer- velt, L. V.; John, J.; Dehaen, W. Beilstein J. Org. Chem. 2018, 14, 626. doi: 10.3762/bjoc.14.49 pmid: 29623124
[21]	(a) Rossi, R.; Bellina, F.; Bechini, C.; Mannina, L.; Vergamini, P. Tetrahedron 1998, 54, 135.
	(b) Zhou, L. J.; Wu, X. X.; Yang, X.; Mou, C. L.; Song, R. J.; Yu, S. Y.; Chai, H. F.; Pan, L. T.; Jin, Z. C.; Chi, Y. G. R. Angew. Chem., Int. Ed. 2020, 59, 1557.

Entry	Compound	R¹	R²	R³	R⁴	Yield^a/%
1	6a	Ph	H	4-ClC₆H₄	t-Bu	88
2	6b	Ph	H	4-CH₃C₆H₄	t-Bu	80
3	6c	Ph	H		t-Bu	85
4	6d	Ph	H		t-Bu	86
5	6e	Ph	H	C₆H₅	t-Bu	82
6	6f	Ph	H	4-CF₃C₆H₄	t-Bu	0
7	6g	Ph	H	4-NO₂C₆H₄	t-Bu	0
8	6h	Ph	H	3-CH₃C₆H₄	t-Bu	80
9	6i	Ph	H	3-ClC₆H₄	t-Bu	87
10	6j	Ph	H	2-ClC₆H₄	t-Bu	78
11	6k	Ph	H	CH₃CH₂CH₂	t-Bu	90
12	6l		H	4-ClC₆H₄	t-Bu	0
13	6m	4-CH₃C₆H₄	H	4-ClC₆H₄	t-Bu	77
14	6n	4-FC₆H₄	H	4-ClC₆H₄	t-Bu	91
15	6o	Ph	4-CH₃	4-ClC₆H₄	t-Bu	92
16	6p	Ph	4-Br	4-ClC₆H₄	t-Bu	0
17	6q	Ph	4-CH₃	4-ClC₆H₄	c-C₆H₁₁	91
18	6r	Ph	4-CH₃	4-ClC₆H₄	PhCH₂	90
19	6s	n-Pr	H	4-ClC₆H₄	t-Bu	91

Entry	Compound	R¹	R²	R³	R⁴	Yield^a/%
1	6a	Ph	H	4-ClC₆H₄	t-Bu	88
2	6b	Ph	H	4-CH₃C₆H₄	t-Bu	80
3	6c	Ph	H		t-Bu	85
4	6d	Ph	H		t-Bu	86
5	6e	Ph	H	C₆H₅	t-Bu	82
6	6f	Ph	H	4-CF₃C₆H₄	t-Bu	0
7	6g	Ph	H	4-NO₂C₆H₄	t-Bu	0
8	6h	Ph	H	3-CH₃C₆H₄	t-Bu	80
9	6i	Ph	H	3-ClC₆H₄	t-Bu	87
10	6j	Ph	H	2-ClC₆H₄	t-Bu	78
11	6k	Ph	H	CH₃CH₂CH₂	t-Bu	90
12	6l		H	4-ClC₆H₄	t-Bu	0
13	6m	4-CH₃C₆H₄	H	4-ClC₆H₄	t-Bu	77
14	6n	4-FC₆H₄	H	4-ClC₆H₄	t-Bu	91
15	6o	Ph	4-CH₃	4-ClC₆H₄	t-Bu	92
16	6p	Ph	4-Br	4-ClC₆H₄	t-Bu	0
17	6q	Ph	4-CH₃	4-ClC₆H₄	c-C₆H₁₁	91
18	6r	Ph	4-CH₃	4-ClC₆H₄	PhCH₂	90
19	6s	n-Pr	H	4-ClC₆H₄	t-Bu	91

无金属参与的连续的Ugi四组分/炔烃-叠氮环加成反应一锅合成新型1,2,3-三唑并苯并二氮杂䓬酮

One-Pot Metal-Free Synthesis of New 1,2,3-Triazolobenzodiaze-pinones by a Sequential Ugi 4CR/Alkyne-Azide Cycloaddition Reaction

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 5

References 21

Related Articles 15

Recommended Articles

Metrics

Comments

Entry	Solvent	Temp./℃	Yield^a/%
1	MeOH	r.t.	0
2	MeOH	65	0
3	Toluene	80	88
4	DMSO	80	70
5	DMF	80	80
6	Water	80	0
7	i-PrOH	80	0
8	1,4-Dioxane	80	60
9	CH₃CN	80	0
10	EtOH	80	0
11	Toluene	110	78

[1]	Zhiyong Xu, Xiaohui Lin, Yuanyuan Zhu, Shuangshuang Zhang, Jiao Long, Shuangxi Gu. A Novel Synthetic Process of Daprodustat^★ [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3335-3342.
[2]	Yuhan Zhao, Huimin Ma, Shulin Ge, Lingbin Kong. Iodine-Catalyzed Intermolecular Cyclopropanation of Olefins with Active Methylene Compounds [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3469-3477.
[3]	Lianji Zhang, Bingfu Wang, Dalong Pan, Cuiping Wang, Yuhui Zhao, Haijun Chi, Yan Dong, Wanguo Wei, Zhiqiang Zhang. Acetic Acid-Mediated Metal-Free Oxidative C—H Cross-Coupling of Imidazopyridines and Glyoxal Hydrates [J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2923-2931.
[4]	Haojie Ma, Fengyuan Zhou, Yumeng He, Xiaoqiang Zhou, Zhou Sun, Yuqi Zhang. Iodine-Promoted Intermolecular Cyclization for the Synthesis of 2-Phenylquinazolines [J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2157-2162.
[5]	Mengqin Liu, Yiting Chen, Juyuan Zhang, Heye Zhou, Tao Qin, Bin Liu. Efficient Synthesis of Diaryl Sulfides via Three Component Cross Coupling [J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1283-1296.
[6]	Zheng Wang, Yuqin Lan, Zhiyi Zhou, Yingzi Tan, Zongcheng Wang. Selenium Mediated Cyclization Reaction of Isonitriles with o-Aminophenols to Synthesize 2-Aminobenzoxazoles [J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1379-1385.
[7]	Ruifeng Cao, Lin Xiao, Tianyu Long, Jiadong Gu, Yanghua Li, Han-Han Kong, Qing-Qing Yang, Nianyu Huang, Long Wang. Metal-Free Cascade Isocyanide Phosphorylation/Cyclization to Synthesize 2-Phosphinoylindoles [J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3856-3865.
[8]	Guiling Xie, Sudhakar Reddy Mopuri, Jie Li, Yuanyong Yang, Tie-Gen Chen. One-Pot Transition-Metal-Free Synthesis of Carboline Derivatives via Dual C—N Bond Formation [J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3824-3837.
[9]	Zhenru Huang, Guoshun Jin, Tianyu Chen, Bin Feng, Xinkang Shi, Minfang Chen, Lusheng Hua, Qing Xu. Efficient Construction of Quinoxaline Derivatives by Cesium Hydroxide-Catalyzed Mild Aerobic Annulation Reaction [J]. Chinese Journal of Organic Chemistry, 2024, 44(9): 2933-2942.
[10]	Yushen Gao, Yuanyuan Gao, An'an Zhang, Lu Li, Weizhi Geng, Fenghua Zhang, Fei Li, Lantao Liu. BF₃•OEt₂ Mediated Intramolecular Cyclization of 2-Alkynylanilines Approach to 3-Sulfenylindoles [J]. Chinese Journal of Organic Chemistry, 2024, 44(9): 2785-2795.
[11]	Rou Ding, Siyu Shi, Chao Ma, Wei Wei, Yufen Lü. Metal-Free 1,8-Diazabicyclo(5.4.0)-undec-7-ene Mediated Synthesis of α-Acetal Amides through Reaction of Glyoxylic Acid Acetalde with Aryl Isothiocyanates [J]. Chinese Journal of Organic Chemistry, 2024, 44(7): 2216-2222.
[12]	Yongsheng Tian, Lanfeng Wei, Jiawei Huang, Yu Wei, Liang Xu, Shuai Liu. Deboronative Selenylation, Bromination, or Hydroxylation of Organic Boronic Acids Facilitated by Tetrabutylammonium Tribromide under Transition Metal-Free Conditions [J]. Chinese Journal of Organic Chemistry, 2024, 44(6): 1987-1997.
[13]	Dongdong Chen, Xufeng Yang. One-Pot Synthesis of Tetrahydro-2H-selenopyran Derivatives from Benzalacetones, Elemental Selenium, and Sodium Borohydride [J]. Chinese Journal of Organic Chemistry, 2024, 44(5): 1641-1648.
[14]	Guodong Ju, Guangyu Zhou, Yingsheng Zhao. Transition-Metal-Free Regioselective Thiocyanation of Triisopropylsilane (TIPS)-Protected Phenols [J]. Chinese Journal of Organic Chemistry, 2024, 44(4): 1327-1336.
[15]	Yunhui Wan, Fumei Yang, Minghan Chen, Deli Sun, Danfeng Ye. Esterification of N-Benzyl-N-t-butoxycarbonyl-amides and Unsaturated Alcohol under Transition Metal-Free Conditions [J]. Chinese Journal of Organic Chemistry, 2024, 44(4): 1293-1300.