Qiuhua Zhu

A new series of C-6 unsubstituted tetrahydropyrimidines: convenient one-pot chemoselective synthesis, aggregation-induced and size-independent emission characteristics.

A new series of C-6 unsubstituted tetrahydropyrimidines 6 have been directly synthesized via a convenient urea-catalyzed chemoselective five-component reaction (5CR) under mild conditions. Compounds 6 show typical aggregation-induced emission enhancement (AIEE) characteristics because they are practically no emissive in solution but emit blue or green fluorescence in aggregates with fluorescence yield up to 93%. One of the 5CR products, 6aa, exhibits blue- and green-fluorescence aggregates (bf- and gf-aggregates). The bf- and gf-aggregates are prepared under different conditions and proved to result from different J-aggregations by single-crystal X-ray analysis. In addition, the bf- and gf-aggregates of 6aa show unusual size-independent emission (SIE) characteristics because their maximum emission wavelengths in different sizes (suspension particles, film, powder and crystals) are the same, 434 and 484 nm, respectively. Based on the obtained experimental results, the 5CR mechanism, the origins of AIEE and SIE characteristics are discussed.

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 synthesis 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 R(3). 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.

Reversible thermo-stimulus solid-state fluorescence-colour/on–off switching and uses as sensitive fluorescent thermometers in different temperature ranges

Two polymorphs of a tetrahydropyrimidine-based fluorophore with aggregation-induced emission characteristics show unusual sensitive and reversible thermo-stimulus solid-state fluorescence-switching, and can be used as a new type of fluorescence-ratiometric/on–off thermometer in different temperature ranges when excited at different red-edge excitation wavelengths.

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 (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.

Copper-induced fluorescence enhancement and particle-size decrease of a C-6 unsubstituted tetrahydropyrimidine racemate

Fluorescence enhancement and particle-size control of organic fluorophores are of general interest owing to their wide applications. We recently developed a convenient five-component reaction (5CR) for the synthesis of a novel class of racemates, C-6 unsubstituted tetrahydropyrimidines with strong aggregation-induced emission (AIE) properties. The copper-induced fluorescence enhancement and particle-size decrease of the racemate dimethyl 2-(4-hydroxy-3-methoxyphenyl)-1,3-diphenyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (THP-1), one of the 5CR products, were investigated in this paper. THP-1 shows useful AIE properties, which have attracted great attention recently, and the unusual size-independent emission (SIE) properties reported in our previous work. The fluorescence intensity of THP-1 increased upon adding Cu2+ and a good linear relationship between the fluorescence intensity at the peak position and the Cu2+ concentration was observed in the range of 0–80 μM of Cu2+. The fluorescence response to Cu2+ is highly selective over other common transition metal ions. Most importantly, the suspension particle sizes of THP-1 were found to gradually decrease upon adding Cu2+. This method for controlling organic particle-size is completely different from conventional ones. The investigation results of the influences of Cu2+ on the optical properties and particle sizes of THP-1 in ethanol–water suspensions as well as the molecular stacking mode in the single-crystal of THP-1 indicate that the copper-induced fluorescence enhancement and particle-size decrease are expected to result from the coordination-induced dissociation of intermolecular O–H⋯O bonds connecting non-emissive groups. In addition, THP-1 shows no cytotoxicity in EC109 cells at concentrations below 30 μM. These useful and interesting properties of THP-1 are expected to be very helpful for new probe design, theoretical research on the relationship between intermolecular hydrogen bonds and optical properties, as well as practical applications in organic particle-size control and chemical/biological fluorescence probes.

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.

A hydrophobic organelle probe based on aggregation-induced emission: Nanosuspension preparation and direct use for endoplasmic reticulum imaging in living cells

Organic fluorophores have a wide range of biological uses and are usually needed to be prepared as water-soluble compounds or nanoparticles for applications in aqueous biosystems owing to their hydrophobic properties, which often is a complex, time-consuming and high-cost process. Here, the nanoparticle preparation of hydrophobic fluorophores and their application in cell imaging have been investigated. It was found: a) fetal bovine serum (FBS) shows an excellent dispersion effect on hydrophobic small-molecule organic compounds; b) a hydrophobic C6-unsubstituted tetrahydropyrimidine (Me-THP-Naph) can be prepared as nanosuspensions utilizing cell culture medium with 10% FBS and directly be used as a specific real-time imaging probe for the endoplasmic reticulum (ER), a dynamic organelle playing a crucial role in many cellular processes. Compared with existing ER-targeted organic fluorescent probes, Me-THP-Naph, a product of an efficient five-component reaction that we developed, has unconventional aggregation-induced emission characteristics and shows advantages of low cost, long-term staining, good photostability, high signal-to-noise ratio and excellent biocompatibility, which make it a potential specific probe for real-time ER imaging. More importantly, this work affords a simple strategy for direct application of hydrophobic organic compounds in aqueous biological systems.

Acid-mediated sulfonylation of arylethynylene bromides with sodium arylsulfinates: synthesis of (E)-1,2-bis(arylsulfonyl)ethylenes and arylacetylenic sulfones

A solvent-dependent sulfonylation of arylethynylene bromides with sodium arylsulfinates has been developed. The (E)-1,2-bis(arylsulfonyl)ethylenes were formed in DMSO, while the arylacetylenic sulfones were obtained in toluene. Utilizing simple and readily available starting materials, the sulfonylation products were generated with good selectivities and yields without the need for a metal catalyst or oxidant.

Synthesis of pyrrolo[1,2-a]quinoxalines via copper or iron-catalyzed aerobic oxidative carboamination of sp3C–H bonds

An aerobic oxidative carboamination of sp3C–H bonds with 2-(1H-pyrrol-1-yl)anilines has been developed. The oxidative carboamination processes utilized simple and readily available starting materials to produce pyrrolo[1,2-a]quinoxalines in good to moderate yields. The transformations also featured inexpensive metal catalysts (copper or iron) and a green oxidant (O2).