Synthesis of Quinazoline through Ruthenium-Catalyzed Hydrogen Transfer/Annulation Reaction between 2-Nitrobenzyl Alcohol and Benzylamine

doi:10.6023/cjoc202503014

Abstract

A novel method for synthesis of quinazoline through the hydrogen transfer/annulation reaction using 2-nitrobenzyl alcohol and benzylamine as starting materials is presented. The reaction is catalyzed by a ruthenium(II) complex bearing a N-heterocyclic carbene nitrogen phosphine (CNP) ligand. The pronounced α-donating capacity of the carbene within the CNP ligand of the catalyst plays a crucial role in stabilizing the catalytically active species. Additionally, the hemilability of the nitrogen facilitates the creation of coordination vacancies, which are essential for the activation of reaction substrate molecules. The synergistic interplay between these two functionalities markedly enhances catalytic efficiency. This catalytic system shows the significant catalytic activity and selectivity, along with a broad substrate adaptability. All substrates yield the target product in good to excellent yields with the maximum yield reaching 95%. Control experiments have substantiated that benzaldehyde and phenylmethanimine may serve as intermediates in the reaction, thereby reinforcing the role of benzylamine as both a hydrogen donor and a nitrogen source in the process.

Key words: hydrogen transfer/annulation reaction, ruthenium complex, quinazoline

Cite this article

Ling Zhao, Xiaohui Zhu, Hua Chen, Xueli Zheng, Weichao Xue, Jiaqi Xu, Haiyan Fu, Ruixiang Li. Synthesis of Quinazoline through Ruthenium-Catalyzed Hydrogen Transfer/Annulation Reaction between 2-Nitrobenzyl Alcohol and Benzylamine[J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2836-2847.

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Entry	Deviation from the standard conditions	Yield/%
1	None	77 (65)^c
2	No base	38
3	K₃PO₄ instead of K₂HPO₄	47
4	Na₂HPO₄ instead of K₂HPO₄	51
5	DMF instead of DMSO	67
6	o-Xylene instead of DMSO	50
7	PhCl instead of DMSO	48
8	120 ℃	54
9	κ³-CNP-Ru instead of κ²-CP-Ru	75
10	[RuH(CO)(PPh₃)₃Cl instead of κ²-CP-Ru	49

Entry	Deviation from the standard conditions	Yield/%
1	None	77 (65)^c
2	No base	38
3	K₃PO₄ instead of K₂HPO₄	47
4	Na₂HPO₄ instead of K₂HPO₄	51
5	DMF instead of DMSO	67
6	o-Xylene instead of DMSO	50
7	PhCl instead of DMSO	48
8	120 ℃	54
9	κ³-CNP-Ru instead of κ²-CP-Ru	75
10	[RuH(CO)(PPh₃)₃Cl instead of κ²-CP-Ru	49

钌催化邻硝基苯甲醇与苄胺的转移氢化/环化反应合成喹唑啉