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

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 (<b>6</b>), the derivatives of quinazolinones possessing diverse biological activities. The molecular structure of <b>6</b>{<i>1,1,12</i>} 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

Racemates Have Much Higher Solid-State Fluorescence Efficiency than Their Levo- and Dextrorotary Enantiomers

C6-unsubstituted tetrahydropyrimidines (THPs) are compounds with a chiral carbon and strong aggregation-induced emission. The fluorescence properties of their racemates have been studied in detail, but those of their enantiomers have not. The solid-state fluorescence properties of the racemates and enantiomers of four chiral tetrahydropyrimidines (THPs <b>1</b>–<b>4</b>) have been investigated by the steady-state and time-resolved fluorescence, single-crystal X-ray structures, and HOMOs and LUMOs of their seven racemic (three of them are polymorphs), four <i>R</i>- and three <i>S</i>-enantiomeric crystals. It was found that the <i>R</i>- and <i>S</i>-enantiomers of <b>1</b>–<b>4</b> can self-assemble as <i>RS</i>-paired, <i>RS</i>-, or <i>RR</i>/<i>SS</i>-overlapped mode in their racemates and as the same <i>RR</i>/<i>SS</i>-overlapped mode in their <i>R</i>- and <i>S</i>-enantiomers. Unexpectedly, the solid-state fluorescence quantum yields (Φ_SF) of racemic <b>1</b>–<b>4</b> could increase to 93, 48, 80, and 100%, respectively, via a suitable heteroenantiomeric self-assembly, but the Φ_SF values of their seven enantiomers are only 25–46%, owing to much larger nonradiative rate constants than those of their racemates. This means that heteroenantiomeric self-assembly can be used as a new efficient method enhancing Φ_SF values. The advantage of racemates is first reported and expected to encourage the development and application of racemates as a new kind of fluorescent materials

One-Pot Synthesis and Structure–Property Relationship of Aminomaleimides: Fluorescence Efficiencies in Monomers and Aggregates Easily Tuned by Switch of Aryl and Alkyl

Organic fluorophores have attracted great interest owing to their wide applications. They usually contain an electron-conjugated system with an aromatic moiety and show high emission in dilute solutions but weaker or even no emission upon aggregation. Here, a simple one-pot, three-component reaction (3CR) (method I) for the synthesis of various di- and monosubstituted aminomaleimides (DAMIs and MAMIs) has been developed, and the reported 3CR (method II) has been found to be efficient only for the synthesis of MAMIs with R² = alkyl. Twelve AMIs were designed and synthesized for investigation of the influence of structures on their optical properties in monomers and aggregates. It was found that alkyl MAMIs, alkyl DAMIs, and aryl AMIs/DAMIs show very different fluorescence efficiencies in different solvents, and only MAMIs with butyl and oleyl show high emissions in powders similar to those in nonpolar solutions. Single-crystal structures indicate that their fluorescence efficiencies in aggregates mainly correlate with molecular packing modes. The efficient synthesis method, the sensitive fluorescence on–off response to protic solvents or polar solvents, and the unusual high emissions of AMI without any aromatic moiety in both monomer and aggregates are expected to attract great interest in the fields of application and theory

Development of Four-Component Synthesis of Tetra- and Pentasubstituted Polyfunctional Dihydropyrroles: Free Permutation and Combination of Aromatic and Aliphatic Amines

We previously reported the novel efficient proton/heat-promoted four-component reactions (4CRs) of but-2-ynedioates, two same/different primary amines, and aldehydes for the <b>s</b>ynthesis of tetra- and pentasubstituted polyfunctional dihydropyrroles. If aromatic and aliphatic amines were used as reagents, four different series of products should be obtained via the permutation and combination of aromatic and aliphatic primary amines. However, only three/two rather four different series of tetra-/pentasubstisuted dihydropyrroles could be prepared via the proton/heat-promoted 4CRs. Herein, Cu­(OAc)₂·H₂O, a Lewis acid being stable in air and water, was found to be an efficient catalyst for the 4CR synthesis of all the four different series of tetra-/pentasubstisuted dihydropyrroles. The copper-catalyzed 4CR could produce target products at room temperature in good to excellent yields. Interestingly, benzaldehyde, in addition to being used as a useful reactant for the synthesis of pentasubstituted dihydropyrroles, was found to be an excellent additive for preventing the oxidation of aromatic amines with copper­(II) and ensuring the sooth conduct of the 4CRs for the synthesis of tetrasubstituted dihydropyrroles with aryl R³. In addition, salicylic acid was found to be needed to increase the activities and yields of the copper-catalyzed 4CRs for the synthesis of petasubstituted diyhydropyrroles. On the basis of experimental results, the enamination/amidation/intramolecular cyclization mechanism was proposed and amidation is expected to be the rate-limited step in the copper-catalyzed 4CRs

Development of Four-Component Synthesis of Tetra- and Pentasubstituted Polyfunctional Dihydropyrroles: Free Permutation and Combination of Aromatic and Aliphatic Amines

We previously reported the novel efficient proton/heat-promoted four-component reactions (4CRs) of but-2-ynedioates, two same/different primary amines, and aldehydes for the <b>s</b>ynthesis of tetra- and pentasubstituted polyfunctional dihydropyrroles. If aromatic and aliphatic amines were used as reagents, four different series of products should be obtained via the permutation and combination of aromatic and aliphatic primary amines. However, only three/two rather four different series of tetra-/pentasubstisuted dihydropyrroles could be prepared via the proton/heat-promoted 4CRs. Herein, Cu­(OAc)₂·H₂O, a Lewis acid being stable in air and water, was found to be an efficient catalyst for the 4CR synthesis of all the four different series of tetra-/pentasubstisuted dihydropyrroles. The copper-catalyzed 4CR could produce target products at room temperature in good to excellent yields. Interestingly, benzaldehyde, in addition to being used as a useful reactant for the synthesis of pentasubstituted dihydropyrroles, was found to be an excellent additive for preventing the oxidation of aromatic amines with copper­(II) and ensuring the sooth conduct of the 4CRs for the synthesis of tetrasubstituted dihydropyrroles with aryl R³. In addition, salicylic acid was found to be needed to increase the activities and yields of the copper-catalyzed 4CRs for the synthesis of petasubstituted diyhydropyrroles. On the basis of experimental results, the enamination/amidation/intramolecular cyclization mechanism was proposed and amidation is expected to be the rate-limited step in the copper-catalyzed 4CRs