American Chemical Society
co6b00038_si_002.cif (19.49 kB)

Efficient Synthesis of a Series of Novel Octahydroquinazoline-5-ones via a Simple on-Water Urea-Catalyzed Chemoselective Five-Component Reaction

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posted on 2016-06-29, 00:00 authored by Sichao Zheng, Shufang Zhong, Zhipeng Chen, Wenhua Chen, Qiuhua Zhu
Multicomponent reactions (MCRs) have become a powerful tool for drug discovery and development owing to their advantages of fast and efficient construction of a large library of products with complexity and diversity. However, conventional MCRs usually proceed in environmentally unfriendly organic solvents rather than in water, a green solvent used by nature for biological chemistry. Herein, a simple and efficient on-water urea-catalyzed chemoselective five-component reaction (5CR) has been developed for the synthesis of a series of novel octahydroquinazoline-5-ones (6), the derivatives of quinazolinones possessing diverse biological activities. The molecular structure of 6{1,1,12} has been confirmed by single-crystal X-ray diffraction. The 5CR can proceed at room temperature under normal atmospheric pressure in good yields and afford a large library of octahydroquinazoline-5-ones with various aromatic and aliphatic substituents at N-1, C-2, and N-3. In addition, a green method has been developed for the synthesis of enaminones, important intermediates in the 5CR and in synthetic chemistry.