RESUMO
A novel and efficient base-catalyzed, transition-metal-free method for the synthesis of diheterocyclic compounds connected by an amidine linker, including apart from the common 1,2,3-triazole ring, either an additional pyrimidinedione, 4-nitroimidazole, isoxazole, 1,3,4-triazole, 2-oxochromone or thiazole ring, has been developed. The process was facilitated by a strong base and includes the cycloaddition reaction of 3,3-diaminoacrylonitriles (2-cyanoacetamidines) to heterocyclic azides followed by a Cornforth-type rearrangement to the final products. The reaction is tolerant to various N-monosubstituted 3,3-diaminoacrylonitriles and to different heterocyclic azides. The developed method has a broad scope and can be applied to obtain a variety of N-heteroaryl-1,2,3-triazole-4-carbimidamides with alkyl, allyl, propargyl, benzyl, cycloalkyl, and indolyl substituents at the N1 position .
RESUMO
An efficient base-catalyzed, metal-free method for the synthesis of 5-amino-1,2,3-triazole-4-N-sulfonyl- and arylimidamides, directed by the structure of the amidine group, has been developed. It is based on a previously unknown tandem process involving cycloaddition reaction to 3,3-diaminoacrylonitriles (2-cyanoacetamidines) with aryl(alkyl)sulfonyl or aryl azides and Cornforth-type rearrangement. During the reaction optimization, different factors were found to facilitate the title reaction, which include the use of a strong base and N-mono- or N,N'-disubstituted 3,3-diaminoacrylonitriles. The reaction is tolerant to variously N-monosubstituted and N,N'-disubstituted 3,3-diaminoacrylonitriles and to various aryl- and aryl/alkyl sulfonyl azides. The developed method has a broad scope and can be applied to obtain a variety of 5-amino-1,2,3-triazole-4-carbimidamides bearing at the N1 position alkyl, allyl, propargyl, benzyl, cycloalkyl, and heteroaryl substituents and sulfonyl and aryl substituents at the amidine group. Post-cyclization reactions of prepared 5-amino-1,2,3-triazoles with DMF-DMA DMA-DMF leads to 1,2,3-triazolo[4,5-d]pyrimidines, 8-aza purine analogues demonstrating the applicability of the prepared compounds in organic synthesis.
Assuntos
Azidas , Triazóis , Azidas/química , Reação de Cicloadição , Triazóis/química , CiclizaçãoRESUMO
The reaction of 3,3-diaminoacrylonitriles with DMAD and 1,2-dibenzoylacetylene was studied. It is shown that the direction of the reaction depends on the structure both of acetylene and of diaminoacrylonitrile. In the reaction of DMAD with acrylonitriles bearing a monosubstituted amidine group, 1-substituted 5-amino-2-oxo-pyrrole-3(2H)ylidenes are formed. On the other hand, a similar reaction of acrylonitriles containing the N,N-dialkylamidine group affords 1-NH-5-aminopyrroles. In both cases, pyrroles containing two exocyclic double bonds are formed in high yields. A radically different type of pyrroles containing one exocyclic C=C bond and sp3 hybrid carbon in the cycle is formed in reactions of 3,3-diaminoacrylonitriles with 1,2-diaroylacetylenes. As in reactions with DMAD, the interaction of 3,3-diaminoacrylonitriles with 1,2-dibenzoylacetylene can lead, depending on the structure of the amidine fragment, both to NH- and 1-substituted pyrroles. The formation of the obtained pyrrole derivatives is explained by the proposed mechanisms of the studied reactions.
RESUMO
It was shown that the reaction of 2-cyanothioacetamides with hydrazine involves both cyano- and thioamide groups, and 3,5-diaminopyrazoles are formed. In the reaction of 2-cyano-3-(dimethylamino)-N,N-dimethylprop-2-enethioamides with hydrazine and its derivatives, the interaction proceeds with the participation of cyano- and enamine groups, not affecting the thiocarbamoyl group, and leads to the formation of 4-thiocarbamoylpyrazoles. A synthesis method has been developed and a series of 1-substituted-4-thiocarbamoyl pyrazoles has been thus synthesized. The structure of the reaction products was studied using NMR spectroscopy and mass spectrometry and confirmed by X-ray diffraction analysis.
RESUMO
The reactivity of readily available 4,5-fused-1-sulfonyl-1,2,3-triazoles was examined in the Rh(II)-catalyzed transannulation reaction with nitriles. We have come across the interesting observation that 1-sulfonyl cycloalkeno[d][1,2,3]triazoles that possess ß-hydrogens resist intramolecular ß-hydride migration and could serve as a new source of Rh-iminocarbenoids for intermolecular Rh(II)-catalyzed transannulation reactions. As a result, 1-sulfonyl cyclohexeno-, cyclohepteno-, dihydropyrano-, 5-phenyltetrahydrobenzo-, and 4,5-dihydronaphtho[d]imidazoles were synthesized from various nitriles in good yields. A one-pot methodology has also been executed for the synthesis of NH-imidazoles.
Assuntos
Ródio , Catálise , Imidazóis , Nitrilas/química , Ródio/química , Triazóis/químicaRESUMO
A novel carbenoid-mediated approach to thioisomünchnones was developed by intermolecular copper-catalyzed reactions of diazoacetamides with aromatic and heteroaromatic thioamides bearing a pyrrolidine moiety. The direction of the reaction can be switched toward 2-amino-2-heteroarylacrylamides by replacing the pyrrolidine with an aniline group or by the use of 2-cyano-2-diazoacetamides. The proposed mechanism and DFT calculations allowed us to rationalize the effect of substituents on the reaction direction. Effective methods were found for the synthesis of previously unknown both 2-heteroarylthioisomünchones and 2-heteroarylacrylamides, based on a wide scope of available reagents with a similar structure. Some of the synthesized thioisomünchnones exhibited multicolor fluorescence in the solid state and solutions.
Assuntos
Cobre , Tioamidas , Acrilamidas , Compostos de Anilina , Catálise , Cobre/química , Estrutura Molecular , Pirrolidinas , Tioamidas/químicaRESUMO
N-Sulfonyl amidines bearing 1,2,3-triazole, isoxazole, thiazole and pyridine substituents were successfully prepared for the first time by reactions of primary, secondary and tertiary heterocyclic thioamides with alkyl- and arylsulfonyl azides. For each type of thioamides a reliable procedure to prepare N-sulfonyl amidines in good yields was found. Reactions of 1-aryl-1,2,3-triazole-4-carbothioamides with azides were shown to be accompanied with a Dimroth rearrangement to form 1-unsubstituted 5-arylamino-1,2,3-triazole-4-N-sulfonylcarbimidamides. 2,5-Dithiocarbamoylpyridine reacts with sulfonyl azides to form a pyridine bearing two sulfonyl amidine groups.
RESUMO
The reactions of thioamides with azides in water were studied. It was reliably shown that the reaction of 2-cyanothioacetamides 1 with various types of azides 2 in water in the presence of alkali presents an efficient, general, one-step, atom-economic, and eco-friendly method for the synthesis of 1,2,3-thiadiazol-4-carbimidamides 5 and 1,2,3-triazole-4-carbothioamides 4. This method can be extended to the one-pot reaction of sulfonyl chlorides and 6-chloropyrimidines 2'o with sodium azide, leading to final products in higher yields, that is, avoiding the isolation of unsafe sulfonyl azides. The method was furthermore applied to the reaction of N,N'-bis-(2-cyanothiocarbonyl)pyrazine 1h with sulfonyl azides to afford bicyclic 1,2,3-thiadiazoles 8 and 1,2,3-triazoles 9 connected via a 1,1'-piperazinyl linker. 2-Cyanothioacetamides 1 were also shown to react with aromatic azides in water in the presence of alkali to afford 1-aryl-5-amino-1,2,3-triazole-4-carbothioamides 11. In contrast to aromatic azides and similarly to sulfonyl azides, 6-azidopyrimidine-2,4-diones 2o-q react with cyanothioacetamides to form N-pyrimidin-6-yl-5-dialkylamino-1,2,3-thiadiazole-4-N-l-carbimidamides 12. A mechanism was proposed to rationalize the role of water in changing the reactivity of azides toward 2-cyanothioacetamides.
RESUMO
High yield solvent-base-controlled, transition metal-free synthesis of 4,5-functionalized 1,2,3-thiadiazoles and 1,2,3-triazoles from 2-cyanothioacetamides and sulfonyl azides is described. Under diazo transfer conditions in the presence of a base in an aprotic solvent 2-cyanothioacetamides operating as C-C-S building blocks produce 5-amino-4-cyano-1,2,3-thiadiazoles exclusively. The use of alkoxide/alcohol system completely switches the reaction course due to the change of one of the reaction centers in the 2-cyanothioacetamide (C-C-N building block) resulting in the formation of 5-sulfonamido-1,2,3-triazole-4-carbothioamide sodium salts as the only products. The latter serve as good precursors for 5-amino-1,2,3-thiadiazole-4-carboximidamides, the products of Cornforth-type rearrangement occurring in neutral protic medium or under acid conditions. According to DFT calculations (B3LYP/6-311+G(d,p)) the rearrangement proceeds via intermediate formation of a diazo compound, and can be catalyzed by acids via the protonation of oxygen atom of the sulfonamide group.
RESUMO
Reactions of ß-azolyl enamines and nitrile oxides were studied by both experimental and theoretical methods. (E)-ß-(4-Nitroimidazol-5-yl), (5-nitroimidazol-4-yl) and isoxazol-5-yl enamines smoothly react regioselectively at room temperature in dioxane solution with aryl, pyridyl, and cyclohexylhydroxamoyl chlorides without a catalyst or a base to form 4-azolylisoxazoles as the only products in good yields. The intermediate 4,5-dihydroisoxazolines were isolated as trans isomers during the reaction of (E)-ß-imidazol-4-yl enamines with aryl and cyclohexylhydroxamoyl chlorides. Stepwise and concerted pathways for the reaction of ß-azolyl enamines with hydroxamoyl chlorides were considered and studied at the B3LYP/Def2-TZVP level of theory combined with D3BJ dispersion correction. The reactions of benzonitrile oxide with both E- and Z-imidazolyl enamines have been shown to proceed stereoselectively to form trans- and cis-isoxazolines, respectively. The preference of E-isomers over Z-isomers, driven by the higher stability of the former, apparently controls the stereoselectivity of the investigated cycloaddition reaction with benzonitrilе oxide. Based on the reactivity of azolyl enamines towards hydroxamoyl chlorides, a novel, effective catalyst-free method was elaborated to prepare 4-azolyl-5-substituted isoxazoles that are otherwise difficult to obtain.
RESUMO
Chain-growth catalyst-transfer polycondensations of AB-type monomers is a new and rapidly developing tool for the preparation of well-defined π-conjugated (semiconducting) polymers for various optoelectronic applications. Herein, we report the Pd/PtBu3-catalyzed Negishi chain-growth polycondensation of AB-type monomers, which proceeds with unprecedented TONs of above 100,000 and TOFs of up to 280â s(-1). In contrast, related AA/BB-type step-growth polycondensation proceeds with two orders of magnitude lower TONs and TOFs. A similar trend was observed in Suzuki-type polycondensation. The key impact of the intramolecular (vs. intermolecular) catalyst-transfer process on both polymerization kinetics and catalyst lifetime has been revealed.
RESUMO
Novel self-condensation of 3-(azol-5-yl)-1,1-dimethylenamines has been found to form new C-C bonds leading to 2,4-(1,2,3-triazole-1,2,3-thiadiazole-3-phenylisothiazole)-(1E,3Z)-5-yl-butadiene-1-amines. The discovered reaction represents a new example of C-H functionalization in unsaturated systems and can serve an efficient synthetic approach to rational design of new 2,4-(diazole-5-yl)-dieneamines.
Assuntos
Compostos de Bifenilo/química , Diaminas/química , Imidazóis/química , Acetilação , Diaminas/síntese química , Desenho de Fármacos , Especificidade por SubstratoRESUMO
Here, we report that the reaction of enaminones, from a class of azole series, with sulfonyl azides leads to a difficult-to-separate mixture of two pairs of compounds: (1) 4-azoloyl-NH-1,2,3-triazoles with sulfonamides and (2) azolyl diazoketones with N-sulfonamidines, as a result of the implementation of two competing reactions. On one hand, the electron-donating methyl or methoxy group in the aryl para-position of arylsulfonyl azides favors the production of NH-1,2,3-triazoles together with sulfonamides. On the other hand, the use of highly electrophilic 4-nitrophenylsulfonyl azide promotes the formation of diazoketones and sulfonamidines. It is shown that the direction of each reaction is not only controlled by the nature of the initial enaminones and sulfonyl azides but also depends on the tested solvent. The problem of removing sulfonamides and amidines from the desired products was solved for the first time using new water-soluble enaminones. Based on the experimental and computational studies, the factors contributing to the selective course of alternative reactions were identified, and methods for the synthesis of azoloyl-NH-1,2,3-triazoles and azolyl diazoketones were developed. Density functional theory (DFT) results have shown that the 1,3-dipolar cycloaddition is totally driven toward one single regioisomer with a high asynchronous bond formation, and the introduction of an electron-deficient group in sulfonyl azides induces faster cycloaddition. Additionally, DFT calculations were used to gain further mechanistic insights on the reaction studied here.
RESUMO
This work deals with the synthesis and evaluation of fungicidal activity of benzimidazole derivatives, which are structural analogues of commercial anti-tubulin fungicides. A number of N-acyl and N-thioacyl derivatives of 2-amino-1H-benzo[d]imidazole were prepared, and their fungicidal activity against 13 strains of phytopathogenic fungi was studied. The most active compounds against the majority of the studied strains were 3a, 4l, and 4o, and the EC50 values of these compounds were in the range 2.5-20 µg/mL. Compound 3a showed the highest activity against the P. infestans strain, the growth of which is not suppressed by carbendazim. The formation of ligand-receptor complexes of various tautomeric forms of the studied benzimidazoles with homologous models of ß-tubulins of B. cinerea, F. oxysporum, and P. infestans was modeled. Induced fit docking has been used for the simulation. The obtained data suggest the possibility of binding of benzimidazole fungicides to ß-tubulin in the â³nocodazole cavityâ³ in the tautomeric form bearing a double exocyclic CâN bond. The importance of the formation of hydrogen bonds of benzimidazoles with the amino acid residue Val236 along with the Glu198 residue is also revealed in the present study.
Assuntos
Fungicidas Industriais , Tubulina (Proteína) , Fungos , Fungicidas Industriais/farmacologia , Imidazóis , Simulação de Acoplamento MolecularRESUMO
Atypical dopamine reuptake inhibitors, such as modafinil, are used for the treatment of sleeping disorders and investigated as potential therapeutics against cocaine addiction and for cognitive enhancement. Our continuous effort to find modafinil analogues with higher inhibitory activity on and selectivity toward the dopamine transporter (DAT) has previously led to the promising thiazole-containing derivatives CE-103, CE-111, CE-123, and CE-125. Here, we describe the synthesis and activity of a series of compounds based on these scaffolds, which resulted in several new selective DAT inhibitors and gave valuable insights into the structure-activity relationships. Introduction of the second chiral center and subsequent chiral separations provided all four stereoisomers, whereby the S-configuration on both generally exerted the highest activity and selectivity on DAT. The representative compound of this series was further characterized by in silico, in vitro, and in vivo studies that have demonstrated both safety and efficacy profile of this compound class.
Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/antagonistas & inibidores , Inibidores da Captação de Dopamina/farmacologia , Modafinila/análogos & derivados , Modafinila/farmacologia , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia , Tiazóis/farmacologia , Animais , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Inibidores da Captação de Dopamina/síntese química , Inibidores da Captação de Dopamina/metabolismo , Inibidores da Captação de Dopamina/farmacocinética , Células HEK293 , Humanos , Masculino , Modafinila/metabolismo , Modafinila/farmacocinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/antagonistas & inibidores , Ligação Proteica , Ratos Sprague-Dawley , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Inibidores da Recaptação de Serotonina e Norepinefrina/síntese química , Inibidores da Recaptação de Serotonina e Norepinefrina/metabolismo , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacocinética , Estereoisomerismo , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/metabolismo , Tiazóis/farmacocinéticaRESUMO
Poly(4-vinylpyridine)-block-poly(4-iodo-styrene), P4VP-b-PS(I), block copolymers obtained by iodination of readily available P4VP-b-PS block copolymers strongly adhere to variety of polar substrates including Si wafers, glasses, or metal oxide surfaces by a polar P4VP block, forming polymer brushes of moderately stretched PS(I) chains. Kumada catalyst-transfer polycondensation (KCTP) from the P4VP-b-PS(I) brushes results into planar brushes of the graft copolymer in which relatively short ( approximately 10 nm) poly(3-hexylthiophene), P3HT, grafts emanate from the surface-tethered PS(I) chains. Grafting of the P3HT leads to significant stretching of the PS(I) backbone as a result of increased excluded volume interactions. Specific adsorption of the P4VP block to polar surfaces was utilized in this work to pattern the P4VP(25)-b-PS(I)(350) brush. The microscopically structured P4VP(25)-b-PS(I)(350) brush was converted into the respectively patterned P4VP-PS(I)-g-P3HT one using KCTP. We also demonstrated that KCTP from functional block copolymers is an attractive option for nanostructuring with polymer brushes. P4VP(75)-b-PS(I)(313) micelles obtained in selective solvent for the PS(I) block form a quasi-ordered hexagonal array on Si wafer. The P4VP(75)-b-PS(I)(313) monolayer preserves the characteristic quasi-regular arrangement of the micelles even after extensive rinsing with various solvents. Although the grafting of P3HT from the nanopatterned P4VP(75)-b-PS(I)(313) brush destroys the initial order, the particulate morphology in the resulting film is preserved. We believe that the developed method to structured brushes of conductive polymers can be further exploited in novel stimuli-responsive materials, optoectronic devices, and sensors.
Assuntos
Poliestirenos/química , Polivinil/química , Tiofenos/química , Catálise , Microscopia de Força Atômica , Nanoestruturas/química , Poliestirenos/síntese química , Polivinil/síntese química , Dióxido de Silício/química , Propriedades de Superfície , Tiofenos/síntese químicaRESUMO
Herein, we present a new paradigm in the engineering of nanostructured hybrids between conjugated polymer and inorganic materials via a chain-growth surface-initiated Kumada catalyst-transfer polycondensation (SI-KCTP) from particles. Poly(3-hexylthiophene), P3HT, a benchmark material for organic electronics, was selectively grown by SI-KCTP from (nano)particles bearing surface-immobilized Ni catalysts supported by bidentate phosphorus ligands, that resulted in hairy (nano)particles with end-tethered P3HT chains. Densely grafted P3HT chains exhibit strongly altered optical properties compared to the untethered counterparts (red shift and vibronic fine structure in absorption and fluorescence spectra), as a result of efficient planarization and chain-aggregation. These effects are observed in solvents that are normally recognized as good solvents for P3HT (e.g., tetrahydrofurane). We attribute this to strong interchain interactions within densely grafted P3HT chains, which can be tuned by changing the surface curvature (or size) of the supporting particle. The hairy P3HT nanoparticles were successfully applied in bulk heterojunction solar cells.
Assuntos
Níquel/química , Tiofenos/síntese química , Catálise , Nanoestruturas/química , Tamanho da Partícula , Propriedades de Superfície , Tiofenos/químicaRESUMO
Graft work: The first surface-initiated and site-specific palladium-catalyzed Suzuki polycondensation that allows selective grafting and patterning of semiconducting and emissive poly[9,9-bis(2-ethylhexyl)fluorene] (1) at room temperature is developed (see scheme). The patterning is demonstrated by AFM (see image).
RESUMO
p-Type molecular doping of organic materials with high ionization energies (IEs) of above 5.50 eV is still a challenge, limiting the use of doping in high-performance organic light-emitting diodes (OLEDs). Here, we investigate the molecular dopant hexacyano-trimethylene-cyclopropane (CN6-CP) with a high electron affinity of 5.87 eV as p-dopant in OLEDs. We show that CN6-CP can be used not only as a dopant in the traditional hole transport material 4,4'-cyclohexylidenebis[ N, N-bis(4-methylphenyl)benzenamine] (TAPC, IE = 5.50 eV) but also effectively dopes the host material tris(4-carbazoyl-9-ylphenyl)amine (TCTA, IE = 5.85 eV), reaching a conductivity of 1.86 × 10-4 S/cm at a molar ratio of 0.25. Using CN6-CP-doped TAPC as hole injection and transport layer, we achieve a low driving voltage of 2.92 V at the practical brightness of 1000 cd/m2 and 3.18 V at a current density of 10 mA/cm2 for a green phosphorescent OLED based on bis[2-(2-pyridinyl- N)phenyl- C](acetylacetonato)iridium(III) (Ir(ppy)2(acac)), together with a maximum external quantum efficiency of 18% and a luminous efficacy of 78 lm/W. The device also exhibits a very low efficiency roll-off at high luminance. Further, by directly adopting CN6-CP-doped TCTA as the injection/transport layer, the driving voltage drops to 2.78 V at 1000 cd/m2 and 2.93 V at 10 mA/cm2. Moreover, conductivity and absorption measurements suggest that CN6-CP could also dope CBP with an IE as high as 6.05 eV. The results show that CN6-CP is an excellent p-type dopant for efficient OLEDs and possesses great potential for future application in organic optoelectronic devices.
RESUMO
Highly efficient 2D (interfacial) doping of organic semiconductors, poly(3-hexylthiophene) (P3HT) and TIPS-pentacene, was achieved by a polyelectrolyte-supported layer-by-layer assembly of the dual-mode functional dopant CN6-CPâ¢-K+, having an anionic group for its fixation onto oppositely charged surfaces/molecules as well as electron-deficient groups providing its p-doping ability. Polyelectrolyte-supported dopant layers were used to generate conductive channels at the bottom or at the top of semiconducting films. Unlike to the case of sequentially processed P3HT films doped by F4TCNQ ( Moulé , J. Chem. Mater. 2015 , 27 , 5765 ; Koech , P. K. J. Mater. Chem. C 2013 , 1 , 1876 ; Schwartz , B. J. J. Phys. Chem. Lett. 2015 , 6 , 4786 ), the use of more polar CN6-CPâ¢-K+ dopant and ultrathin polycation separation interlayer enables predominantly interfacial kind of doping placement with no or minimal intercalation of the dopant into the semiconductor bulk. The layered structure of the doped film was proved by transmission electron microscopy of the cross-section and it agrees well with other data obtained in this work. The interfacial doping enabled an impressive conductivity of 13 S/cm even for ultrathin P3HT films. We propose to explain the superior efficiency of the interfacial doping compared to the bulk doping in terms of unperturbed morphology of the semiconductor and high mobility of charge carriers, which are spatially separated from the dopant phase.