Efficient Synthesis of Quinazolines and Quinazolinones via Cascade Reactions over Heterogeneous CuMgMn Layered Double Hydroxide without Additives

doi:10.6023/cjoc202601013

Abstract

An efficient catalytic method based on CuMgMn-layered double hydroxide (LDH) is presented for the synthesis of quinazolines and quinazolinones via a cascade reaction between alcohols and diamines. The catalytic system operates without any additives, effectively promoting the cascade reaction and showing excellent performance with a range of alcohol substrates. The results indicate that the Cu and Mn active sites exhibit a synergistic effect in the reaction. Based on a series of control experiments, a plausible catalytic mechanism is proposed. Catalyst stability was confirmed through hot filtration and recycling experiments. When the reaction was scaled up by a factor of 10, both the catalytic activity and product yield remained stable.

Key words: quinazoline, cascade reaction, oxidative coupling, heterogeneous catalysis, additive-free

Cite this article

Man Wu, Jie Yao, Yufu Fang, Weiyou Zhou, Junfeng Qian, Xuan Dai, Mingyang He. Efficient Synthesis of Quinazolines and Quinazolinones via Cascade Reactions over Heterogeneous CuMgMn Layered Double Hydroxide without Additives[J]. Chinese Journal of Organic Chemistry, 2026, 46(8): 3268-3275.

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Fig. & Tab. 8

Scheme 1. A brief survey of previous works and the present work

Entry	Solvent	T/℃	Yield/%
1	Toluene	80	56
2	Acetonitrile	80	58
3	DCE	80	2
4	Trifluorotoluene	80	42
5	Water	80	0
6	Mesitylene	80	41
7	THF	80	22
8	n-Heptane	80	71
9	n-Heptane	50	49
10	n-Heptane	60	60
11	n-Heptane	70	78

Table 1. Optimization of the reaction conditions

Figure 1. Optimization of reaction time and catalyst loading (a) Reaction conditions: 1a (1 mmol), 2a (1 mmol), CuMgMn-LDH (0.2 g), n-heptane (2 mL), O2 (101 kPa), 70 ℃; (b) Reaction conditions: 1a (1 mmol), 2a (1 mmol), CuMgMn-LDH (catalyst), n-heptane (2 mL), O2 (101 kPa), 70 ℃, 14 h

Table 2. Scope of substratesa,b

Entry	Catalyst	Additives	Conv./%	Sel./%
1	CuMgMn-LDH	—	>99	84
2	—	—	Trace	—
3^b	CuMgMn-LDH	—	66	77
4^c	CuMgMn-LDH	—	18	50
5	CuMgAl-LDH	—	64	58
6	Mg₂Al-LDH	—	Trace	—
7	Ni₂Mn-LDH	—	75	58
8	CuMgMn-LDH	BHT^d	Trace	—
9	CuMgMn-LDH	p-Benzoquinone^d	3	—

Table 3. Catalytic results under varied reaction conditionsa

Scheme 2. Proposed reaction pathway

Figure 2. (a) Hot-filtration experiment; (b) Recyclability of Cu- MgMn-LDH in the cascade reaction

Scheme 3. Scale-up reaction

References 12

[1]	(a) Tan, L.; Wu, C. Y.; Zhang, J. F.; Yu, Q. W.; Wang, X. Y.; Zhang, L. L.; Ge, M. Y.; Wang, Z. J.; Ouyang, L.; Wang, Y. X. J. Med. Chem. 2023, 66, 3588.
	(b) Wellaway, C. R.; Baldwin, I. R.; Bamborough, P.; Barker, D.; Bartholomew, M. A.; Chung, C. W.; Dümpelfeld, B.; Evans, J. P.; Fazakerley, N. J.; Homes, P.; Keeling, S. P.; Lewell, X. Q.; McNab, F. W.; Morley, J.; Needham, D.; Neu, M.; van Oosterhout, A. J. M.; Pal, A.; Reinhard, F. B. M.; Rianjongdee, F.; Robertson, C. M.; Rowland, P.; Shah, R. R.; Sherriff, E. B.; Sloan, L. A.; Teague, S.; Thomas, D. A.; Wellaway, N.; Wojno-Picon, J.; Woolven, J. M.; Coe, D. M. J. Med. Chem. 2022, 65, 633.
	(c) Wu, Y. D.; Liu, N.; Qi, M. F.; Qiao, H. H.; Lu, X. L.; Ma, L.; Zhou, Y. R.; Zhang, F. L. Org. Lett. 2021, 23, 3923.
	(d) Ma, J. T.; Wang, L. S.; Chai, Z.; Chen, X. F.; Tang, B. C.; Chen, X. L.; He, C.; Wu, Y. D.; Wu, A. X. Chem. Commun. 2021, 57, 5414.
	(e) Jiang, S.; Cao, W. B.; Xu, X. P.; Ji, S. J. Org. Lett. 2021, 23, 6740.
[2]	(a) Portela-Cubillo, F.; Scott, J. S.; Walton, J. C. Chem. Commun. 2008, 2935.
	(b) Portela-Cubillo, F.; Scott, J. S.; Walton, J. C. J. Org. Chem. 2009, 74, 4934.
	(c) Laha, J. K.; Patel, K. V.; Tummalapalli, K. S. S.; Dayal, N. Chem. Commun. 2016, 52, 10245.
	(d) Abe, T.; Kida, K.; Yamada, K. Chem. Commun. 2017, 53, 4362.
	(e) Li, Q.; Huang, Y.; Chen, T. Q.; Zhou, Y. B.; Xu, Q.; Yin, S. F.; Han, L. B. Org. Lett. 2014, 16, 3672.
[3]	(a) Mori, T.; Ishii, C.; Kimura, M. Org. Process Res. Dev. 2019, 23, 1709.
	(b) Parua, S.; Sikari, R.; Sinha, S.; Chakraborty, G.; Mondal, R.; Paul, N. D. J. Org. Chem. 2018, 83, 11154.
	(c) Chakrabarti, K.; Maji, M.; Kundu, S. Green Chem. 2019, 21, 1999.
	(d) Wei, D.; Dorcet, V.; Darcel, C.; Sortais, J. B. ChemSusChem 2019, 12, 3078.
[4]	(a) Saha, M.; Mukherjee, P.; Das, A. R. Tetrahedron Lett. 2017, 58, 2044.
	(b) Das, S.; Mondal, R.; Chakraborty, G.; Guin, A. K.; Das, A.; Paul, N. D. ACS Catal. 2021, 11, 7498.
	(c) Hu, J. M.; Li, M. J.; Wan, J.; Sun, J. N.; Gao, H.; Zhang, F.; Zhang, Z. B. Org. Biomol. Chem. 2022, 20, 2852.
	(d) Gujjarappa, R.; Maity, S. K.; Hazra, C. K.; Vodnala, N.; Dhiman, S.; Kumar, A.; Beifuss, U.; Malakar, C. C. Eur. J. Org. Chem. 2018, 2018, 4628.
[5]	(a) Wu, Y.; Zhang, L.; Liu, H.; Wang, Y.; Wang, C.; Hu, Z.; Zhang, Z. Catal. Sci. Technol. 2024, 14, 4366.
	(b) Zhou, X.; Qian, F.; Zhou, W. Y.; Wang, A. W.; Hou, T.; Tian, X. T.; Ji, S. L.; He, M. Y.; Qian, J. F. Org. Biomol. Chem. 2024, 22, 4494.
	(c) Wani, A. A.; Bhujbal, S. M.; Sherpa, D.; Kathuria, D.; Chou- rasiya, S. S.; Sahoo, S. C.; Bharatam, P. V. Org. Biomol. Chem. 2025, 23, 343.
	(d) Dutta, B.; Kommula, B.; Kanwar, K.; Guha, A. K.; Gautam, U. K.; Sarma, D. Green Chem. 2025, 27, 7160.
[6]	(a) Wang, A. W.; Zhou, X.; Yu, Q. R.; Chen, Y. J.; Bian, J. J.; Qian, J. F.; Chen, Q.; He, M. Y.; Zhou, W. Y. J. Catal. 2025, 450, 116318.
	(b) Zhou, X.; Wang, A. W.; Wang, X.; Hou, T.; Zhou, W. Y.; Qian, J. F.; Cui, J.; He, M. Y. ACS Sustain. Chem. Eng. 2025, 13, 5569.
	(c) Wang, A. W.; Huang, J. Y.; Zhao, C. S.; Fan, Y.; Qian, J. F.; Chen, Q.; He, M. Y.; Zhou, W. Y. Green Chem. 2024, 26, 353.
	(d) Zhou, W. Y.; Tian, P.; Sun, F. A.; He, M. Y.; Chen, Q. J. Catal. 2016, 335, 105.
[7]	(a) Huang, W.; Ma, B. C.; Lu, H.; Li, R.; Wang, L.; Landfester, K.; Zhang, K. A. I. ACS Catal. 2017, 7, 5438.
	(b) Zhao, J.; Sun, H.; Lu, Y.; Li, J.; Yu, Z.; Zhu, H.; Ma, C.; Meng, Q.; Peng, X. Green Chem. 2022, 24, 8503.
[8]	(a) Wang, Y. G.; Meng, X.; Chen, G. X.; Zhao, P. Q. Catal. Commun. 2018, 104, 106.
	(b) Song, T.; Ren, P.; Ma, Z. M.; Xiao, J. L.; Yang, Y. ACS Sustain. Chem. Eng. 2020, 8, 267.
	(c) Yao, N.; Bi, X. R.; Zhang, L. P.; Tao, L. Y.; Zhao, P. Q.; Meng, X.; Liu, X. Mol. Catal. 2021, 504, 111499.
	(d) Wierzbicki, S.; Douglin, J. C.; Kostuch, A.; Dekel, D. R.; Kruczala, K. J. Phys. Chem. Lett. 2020, 11, 7630.
[9]	(a) Pan, K.; Yu, F.; Liu, Z.; Zhou, X.; Sun, R.; Li, W.; Zhao, H.; Liu, M.; Guo, X.; Dai, B. Environ. Chem. Eng. 2022, 10, 108030.
	(b) Chen, H.; Lin, W. W.; Zhang, Z. H.; Yang, Z. Z.; Jie, K. C.; Fu, J.; Yang, S. Z.; Dai, S. Chem. Sci. 2020, 11, 5766.
[10]	Zhou, Y.; Yao, J.; Yan, J.; Dai, X.; Wang, A.; Zhou, X.; Zhou, W. Tetrahedron 2025, 187, 134908.
[11]	(a) Xu, W.; Jin, Y.; Liu, H.; Jiang, Y.; Fu, H. Org. Lett. 2011, 13, 1274.
	(b) Dapper, L. H.; Mena, V. T.; Rambo, M. W.; Santos, F. B.; Pineda, N. R.; Iglesias, B. A.; Piquini, P. C.; Silva, M. S.; Lenardão, E. J.; Penteado, F. ACS Sustainable Chem. Eng. 2024, 12, 10276.
	(c) Yang, J.; Xie, Z.; Chen, Z.; Jin, L.; Li, Q.; Le, Z. J. Heterocycl. Chem. 2021, 58, 1496.
[12]	Chen, T.; Yang, H.; Li, S.; Xie, J.; Wei, L., Yang, L. Tetrahedron Lett. 2023, 131, 154788.

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