Copper-Catalyzed Domino-Double Annulation of o-Aminobenzamides with 2-Iodoisothiocyanates for the Synthesis of 12H-Benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones.

A facile and efficient copper-catalyzed domino-double annulation strategy was developed from easily accessible o-aminobenzamides and 2-iodoisothiocyanates, which affords a direct pathway for the synthesis of tetracyclic fused 12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones in moderate to good yields without the addition of ligands, bases, and external oxidants. The reaction involves a C-N bond cleavage and the formation of a C-N/C-S bond in one step with the advantages of using an inexpensive copper catalyst and easy operation. Mechanistic studies suggest that this transformation proceeds via intermolecular condensation of o-aminobenzamides with 2-iodoisothiocyanates, followed by an intramolecular Ullmann-type cross-coupling cyclization reaction.

Palladium-Copper-Catalyzed Oxidative Intermolecular [2 + 2 + 2] Coupling-Annulation: Regioselective Synthesis of Multiaryl-Substituted Benzenes.

A palladium-catalyzed intermolecular [2 + 2 + 2] oxidative coupling-annulation of terminal alkenes and alkynes using copper(II) as the oxidant has been developed through direct C-C bond formation. These reactions provide effective access to multiaryl-substituted benzenes with high regioselectivity in the absence of any ligands. The features of this protocol are broad substrate scope, and high atom and step economy. The aggregation-induced emission properties of selected products were further investigated. These synthesized multiaryl-substituted benzenes may be worth exploring for further applications in the fields of advanced functional materials or drugs.

Visible Light-Enhanced [3 + 2] Cycloaddition of N,N-Disubstituted Hydrazines with Organo-Cyanamides: Access to Polysubstituted 1,2,4-Triazol-3-amines.

Visible light-enhanced [3 + 2] cycloaddition of N,N-disubstituted hydrazines with N-cyano-N-aryl-p-toluenesulfonamides is an efficient reaction pathway to polysubstituted 1,2,4-triazol-3-amines. The reaction is performed under mild conditions without the addition of any transition metals. This strategy involves a C(sp3)-H bond activation, a cyano cycloaddition, and the formation of two new C═N bonds. The protocol shows the advantages of good functional group tolerance and broad substrate scope. The late-stage modification experiments provide practical applications in the field of organic synthesis and medicinal chemistry.

Copper-Promoted Aerobic Oxidative [3+2] Cycloaddition Reactions of N,N-Disubstituted Hydrazines with Alkynoates: Access to Substituted Pyrazoles.

A copper-promoted aerobic oxidative [3+2] cycloaddition reaction for the synthesis of various substituted pyrazoles from N,N-disubstituted hydrazines with alkynoates in the presence of bases is developed. This work involves a direct C(sp3)-H functionalization and the formation of new C-C/C-N bonds. In this strategy, inexpensive and easily available Cu2O serves as the promoter and air acts as the green oxidant. The reaction exhibits the advantages of high atom and step economy, high regioselectivity, and easy operation.

DBU-Promoted Deaminative Thiolation of 1H-Benzo[d]imidazol-2-amines and Benzo[d]oxazol-2-amines.

A facile and efficient catalyst-/metal-/oxidant-free DBU-promoted deaminative thiolation reaction of 1H-benzo[d]imidazol-2-amines and benzo[d]oxazol-2-amines has been developed at room temperature conditions in a one-pot protocol. This practical three-component strategy represents a novel and environmentally friendly reaction pathway toward the straightforward synthesis of various 2-thio-1H-benzo[d]imidazoles and 2-thiobenzo[d]oxazoles using carbon disulfide as a sulfur source through C-N bond cleavage and C-S bond formation process. Different types of 1H-benzo[d]imidazol-2-amines, benzo[d]oxazol-2-amines, and organic bromides are suitable substrates. The gram-scale and late-stage modification experiments provide the potential applications based on this methodology in the field of organic and medicinal chemistry.

Metal-Free Temperature-Controlled Intermolecular [3 + 2] Annulation to Access Benzo[d]thiazole-2(3H)-thiones and Benzo[d]thiazol-2(3H)-ones.

A facile access to benzo[d]thiazole-2(3H)-thiones and benzo[d]thiazol-2(3H)-ones has been developed through a temperature-controlled intermolecular [3 + 2] annulation of N,N-disubstituted arylhydrazines with CS2 in the presence of DMSO. This protocol can obviate the prefunctionalization of the starting materials. This direct C-S/C-N bond formation reaction was performed in the absence of any external catalysts, transition metals, bases, ligands, and oxidants with high step economy.

Copper-Catalyzed Phosphorylation of N,N-Disubstituted Hydrazines: Synthesis of Multisubstituted Phosphorylhydrazides as Potential Anticancer Agents.

An efficient copper-catalyzed aerobic oxidative cross-dehydrogenative coupling reaction for the synthesis of multisubstituted phosphorylhydrazides from N,N-disubstituted hydrazines and hydrogen phosphoryl compounds is accomplished. The reaction proceeds under mild conditions without the addition of any external oxidants and bases. This work reported here represents a direct P(═O)-N-N bond formation with the advantages of being operationally simple, good functional group tolerance, and high atom and step economy. Furthermore, the selected compounds exhibit potential inhibitory activity against tumor cells, which can be used in the field of screening of anticancer agents as new chemical entities.

Metal- and Oxidant-Free Green Three-Component Desulfurization and Deamination Condensation Approach to Fully Substituted 1H-1,2,4-Triazol-3-amines and Their Photophysical Properties.

A metal- and oxidant-free three-component desulfurization and deamination condensation of amidines, isothiocyanates, and hydrazines for the synthesis of structurally diverse fully substituted 1H-1,2,4-triazol-3-amines is described. The reaction proceeds without the requirement of any external catalysts, metals, ligands, or oxidants. This [2 + 1 + 2] cyclization strategy involves C-N and C-S bond cleavage and the formation of new C-N bonds in one pot. This transformation provides a series of full substituted 1H-1,2,4-triazol-3-amines with advantages of a broad substrates scope, mild reaction conditions, environmental friendliness, and easy gram-scale applications. The fluorescence and aggregation-induced emission (AIE) properties of selected products were further tested. These synthesized 1H-1,2,4-triazol-3-amines may be worth investigating for further applications in the fields of organic chemistry, medicinal chemistry, and optical materials.

Molluscicides against the snail-intermediate host of Schistosoma: a review.

Schistosomiasis, a neglected tropical disease (NTD), is one of the most prevalent parasitoses in the World. Certain freshwater snail species are the intermediate host in the life cycle of schistosome species. Controlling snails employing molluscicides is an effective, quick, and convenient intervention strategy to prevent the spread of Schistosoma species in endemic regions. Advances have been made in developing both synthetic molluscicides and molluscicides derived from plants. However, at present, the development of molluscicides is not adapted to the actual demand for snails and schistosoma controlling. We undertake a systematic review of exploitation and application of synthetic molluscicides and molluscicides derived from plants to combat intermediate host snails. The detailed molluscicidal activity, structure-activity relationship, structural feature, and possible mechanism of some molluscicides are also highlighted, which may afford an important reference for the design of new, more effective molluscicides with low environmental impact and realize the aim of controlling schistosome at transmission stages.

Synthesis of Purine Analogues: Photocatalyst-Free Visible-Light-Enhanced Annulation Approach to Pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines.

A new photocatalyst-free visible-light-enhanced strategy for the synthesis of pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines via the formation of electron donor-acceptor (EDA) complexes is reported. The in situ generated pyrazolthiourea intermediates from 1H-pyrazol-3-amines and isothiocyanates undergo formal [4 + 2] annulation with 1,1,3,3-tetramethylguanidines (TMG) to deliver the corresponding products involved in three C-N bond formations in a one-pot protocol. The formation of EDA complex from pyrazolthiourea and TMG is confirmed by UV-vis spectroscopy and 1H NMR experiments. Moreover, this mild reaction proceeds in the absence of any external transition metals, oxidants, bases, and ligands. This efficient methodology for the synthesis of purine analogues pyrazolo[1,5-a][1,3,5]triazine-2,4-diamines provides potential synthetic applications in the field of drug research and development.

Visible-Light-Catalyzed [3 + 1 + 2] Coupling Annulations for the Synthesis of Unsymmetrical Trisubstituted Amino-1,3,5-triazines.

A visible-light catalyzed [3 + 1 + 2] annulation for the synthesis of unsymmetrical trisubstituted amino-1,3,5-triazines from amidines, isothiocyanates, and 1,1,3,3-tetramethylguanidines has been developed. This method exhibits the advantages of easily available starting materials, insensitive to air and moisture, wide substrate scopes, high step economy, mild, metal- and ligand-free conditions, which has potential applications in the organic, medicinal, and material chemistry.

Photodriven Photocatalyst/Metal-Free Direct C-C/C-N Bond Formation: Synthesis of Indoles via EDA Complexes.

The photodriven direct C-C/C-N bond formation initiated by electron donor-acceptor (EDA) complexes for the synthesis of indoles has been accomplished via [3+2] annulations of secondary arylamines with alkynes using IC4F9 as oxidants in the absence of any photocatalysts and metals. This green transformation exhibits the advantages of operational simplicity, good functional tolerances, and mild reaction conditions. The in situ generated EDA complexes derived from arylamines with alkynes were characterized by UV-vis absorption spectrometry and NMR titration experiments.

Visible-Light-Promoted Three-Component Coupling Annulation: Synthesis of 2-Iminothiazolidin-4-ones via in Situ Formed Electron Donor-Acceptor Complexes.

A novel and efficient three-component coupling annulation strategy for the synthesis of 2-iminothiazolidin-4-ones from amines, isothiocyanates, and alkyl acetylenedicarboxylates under visible-light irradiation conditions has been demonstrated. In this transformation, the in situ formed photoactive electron donor-acceptor (EDA) complexes facilitate the reaction and smoothly generate the corresponding products with a high adaptability under mild conditions. This protocol provides a cost-efficient and practical route to 2-iminothiazolidin-4-ones and promotes potential applications on the synthetic drugs.

Direct Photocatalytic S-H Bond Cyanation with Green "CN" Source.

Herein we report a novel C-S bond cleavage and reconstruction strategy for the synthesis of thiocyanates through direct photocatalytic S-H bond cyanation from thiols and inorganic thiocyanate salts. In our strategy, the unprecedented example of cutting off C-S bond of SCN- to deliver the green "CN" sources is demonstrated. This transformation features nontoxic and inexpensive "CN" sources, available starting materials, metal-/base-/ligand-/peroxide-free, high step economy and mild conditions. It leads to the construction of various thiocyanates and some medicinally and biologically active thiocyanate-containing molecules.

Visible Light-Promoted Three-Component Tandem Annulation for the Synthesis of 2-Iminothiazolidin-4-ones.

Described is a visible light-promoted three-component tandem annulation of amines, aryl/alkyl isothiocyanates, and α-bromoesters to form 2-iminothiazolidin-4-ones in the absence of metal and photocatalyst at room temperature. This [1 + 2 + 2] cyclization strategy involves visible light-promoted C-S/C-N bond formation and features a powerful approach to the synthesis of 2-iminothiazolidin-4-ones with broad substrate scope, excellent functional group tolerance, mild reaction conditions, step-economy, and simple operation, which also has potential applications in the pharmaceutical industry. UV-vis spectroscopy indicates that an in situ-generated H-bonding electron donor-acceptor (EDA) complex probably acts as the photocatalyst, facilitating the reaction process.

Photoisomerization Mechanism of Ruthenium Sulfoxide Complexes: Role of the Metal-Centered Excited State in the Bond Rupture and Bond Construction Processes.

Phototriggered intramolecular isomerization in a series of ruthenium sulfoxide complexes, [Ru(L)(tpy)(DMSO)](n+) (where tpy=2,2':6',2''-terpyridine; DMSO=dimethyl sulfoxide; L=2,2'-bipyridine (bpy), n=2; N,N,N',N'-tetramethylethylenediamine (tmen) n=2; picolinate (pic), n=1; acetylacetonate (acac), n=1; oxalate (ox), n=0; malonate (mal), n=0), was investigated theoretically. It is observed that the metal-centered ligand field ((3) MC) state plays an important role in the excited state S→O isomerization of the coordinated DMSO ligand. If the population of (3) MCS state is thermally accessible and no (3) MCO can be populated from this state, photoisomerization will be turned off because the (3) MCS excited state is expected to lead to fast radiationless decay back to the original (1) GSS ground state or photodecomposition along the Ru(2+) -S stretching coordinate. On the contrary, if the population of (3) MCS (or (3) MCO ) state is inaccessible, photoinduced S→O isomerization can proceed adiabatically on the potential energy surface of the metal-to-ligand charge transfer excited states ((3) MLCTS →(3) MLCTO ). It is hoped that these results can provide valuable information for the excited state isomerization in photochromic d(6) transition-metal complexes, which is both experimentally and intellectually challenging as a field of study.

Discovery of molluscicidal and cercaricidal activities of 3-substituted quinazolinone derivatives by a scaffold hopping approach using a pseudo-ring based on the intramolecular hydrogen bond formation.

Discovery of novel topological agents against Oncomelania hupensis snails and cercariae remains a significant challenge in current Schistosomiasis control. A pseudo-ring formed from salicylanilide by an intramolecular hydrogen bond led to the discovery of 3-substituted quinazolinone derivatives which showed a potent molluscicidal and cercaricidal activities.

Design, synthesis, and cercaricidal activity of novel high-efficient, low-toxic self-spreading PEG-N-salicylanilide derivatives against cercariae larvae of Schistosome Japonicum floating on the water surface.

Novel cercaricides of PEG-N-salicylanilide derivatives that could self-spread and float on the water surface were designed and synthesized according to the particular habit of cercariae larvae of Schistosome japonicum. The structures of the cercaricides were characterized by the infrared spectra (IR), magnetic resonance ((1) H NMR), and mass spectrum (MS). The images of the floating cercaricides on the water surface were investigated by the Brewster angle microscopy (BAM). When the cercaricides were dropped on the water surface, they could spread along the air-water interface automatically and form thin membranes floating on the water surface immediately. The lethality rate of cercariae for 5a and 6a was more than 90% in 120 min at a surface concentration of 0.008 mg/cm(2) . The non-ionic surfactant-cercaricides not only showed strong cercaricidal activities against the cercariae larvae but also exhibited low toxicities, which offered an effective and environment-friendly approach for the reduction of population infection rate and the realization of schistosome control.