Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to ,-diheteroarylcarbamidines.

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 -monosubstituted 3,3-diaminoacrylonitriles and to different heterocyclic azides.

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives.

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)-,-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.

Tandem Cycloaddition of Azides to 3,3-Diaminoacrylonitriles (2-Cyanoacetamidines) and Cornforth-Type Rearrangement as an Approach to 5-Amino-1,2,3-triazole-4--substituted Imidamides.

An efficient base-catalyzed, metal-free method for the synthesis of 5-amino-1,2,3-triazole-4--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 -mono- or ,'-disubstituted 3,3-diaminoacrylonitriles.

Synthesis of Non-Aromatic Pyrroles Based on the Reaction of Carbonyl Derivatives of Acetylene with 3,3-Diaminoacrylonitriles.

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(2)ylidenes are formed.

Rhodium-Catalyzed Transannulation of 4,5-Fused 1-Sulfonyl-1,2,3-triazoles with Nitriles. The Selective Formation of 1-Sulfonyl-4,5-fused Imidazoles versus Secondary C-H Bond Migration.

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[][1,2,3]triazoles that possess β-hydrogens resist intramolecular β-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[]imidazoles were synthesized from various nitriles in good yields.

Thioisomünchnones versus Acrylamides via Copper-Catalyzed Reaction of Thioamides with Diazocarbonyl Compounds.

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.

Selective Synthesis of Azoloyl -1,2,3-Triazoles and Azolyl Diazoketones: Experimental and Computational Insights.

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--1,2,3-triazoles with sulfonamides and (2) azolyl diazoketones with -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 -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.

Synthesis, Fungicidal Activity, and Molecular Docking of 2-Acylamino and 2-Thioacylamino Derivatives of 1-benzo[]imidazoles as Anti-Tubulin Agents.

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 -acyl and -thioacyl derivatives of 2-amino-1-benzo[]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 , , and , and the EC values of these compounds were in the range 2.

Regioselective synthesis of heterocyclic -sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides.

-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 -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--sulfonylcarbimidamides.

Structure-Activity Relationships of Novel Thiazole-Based Modafinil Analogues Acting at Monoamine Transporters.

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.

Water/Alkali-Catalyzed Reactions of Azides with 2-Cyanothioacetamides. Eco-Friendly Synthesis of Monocyclic and Bicyclic 1,2,3-Thiadiazole-4-carbimidamides and 5-Amino-1,2,3-triazole-4-carbothioamides.

The reactions of thioamides with azides in water were studied. It was reliably shown that the reaction of 2-cyanothioacetamides with various types of azides 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 and 1,2,3-triazole-4-carbothioamides . This method can be extended to the one-pot reaction of sulfonyl chlorides and 6-chloropyrimidines with sodium azide, leading to final products in higher yields, that is, avoiding the isolation of unsafe sulfonyl azides.

High Electron Affinity Molecular Dopant CN6-CP for Efficient Organic Light-Emitting Diodes.

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.

Layer-by-Layer Assembly Enabled by the Anionic p-Dopant CN6-CPK: a Route to Achieve Interfacial Doping of Organic Semiconductors.

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-CPK, 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.

Hexacyano-[3]-radialene anion-radical salts: a promising family of highly soluble p-dopants.

Organic and inorganic salts of the hexacyano-[3]-radialene anion-radical are readily available and thermally stable compounds (up to ∼180 °C). The tetrabutylammonium salt exhibits an extremely high solubility in a range of solvents (>300 mg l in CHCl) and acts as an efficient p-dopant for poly(3-hexylthiophene) to provide composite films with a conductivity above 2 S cm.

Heterocyclic Analogues of Modafinil as Novel, Atypical Dopamine Transporter Inhibitors.

Modafinil is a wake promoting compound with high potential for cognitive enhancement. It is targeting the dopamine transporter (DAT) with moderate selectivity, thereby leading to reuptake inhibition and increased dopamine levels in the synaptic cleft. A series of modafinil analogues have been reported so far, but more target-specific analogues remain to be discovered.

A novel heterocyclic compound improves working memory in the radial arm maze and modulates the dopamine receptor D1R in frontal cortex of the Sprague-Dawley rat.

A series of compounds have been shown to enhance cognitive function via the dopaminergic system and indeed the search for more active and less toxic compounds is continuing. It was therefore the aim of the study to synthetise and test a novel heterocyclic compound for cognitive enhancement in a paradigm for working memory. Specific and effective dopamine re-uptake inhibition DAT (IC50=4,1±0,8μM) made us test this compound in a radial arm maze (RAM) in the rat.

Switchable Synthesis of 4,5-Functionalized 1,2,3-Thiadiazoles and 1,2,3-Triazoles from 2-Cyanothioacetamides under Diazo Group Transfer Conditions.

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.

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides.

Reactions of β-azolyl enamines and nitrile oxides were studied by both experimental and theoretical methods. ()-β-(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 isomers during the reaction of ()-β-imidazol-4-yl enamines with aryl and cyclohexylhydroxamoyl chlorides.

High Conductivity in Molecularly p-Doped Diketopyrrolopyrrole-Based Polymer: The Impact of a High Dopant Strength and Good Structural Order.

[3]-Radialene-based dopant CN6-CP studied herein, with its reduction potential of +0.8 versus Fc/Fc+ and the lowest unoccupied molecular orbital level of -5.87 eV, is the strongest molecular p-dopant reported in the open literature, so far.

A Novel Heterocyclic Compound CE-104 Enhances Spatial Working Memory in the Radial Arm Maze in Rats and Modulates the Dopaminergic System.

Various psychostimulants targeting monoamine neurotransmitter transporters (MATs) have been shown to rescue cognition in patients with neurological disorders and improve cognitive abilities in healthy subjects at low doses. Here, we examined the effects upon cognition of a chemically synthesized novel MAT inhibiting compound 2-(benzhydrylsulfinylmethyl)-4-methylthiazole (named as CE-104). The efficacy of CE-104 in blocking MAT [dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter] was determined using in vitro neurotransmitter uptake assay.

Influence of Semiconductor Thickness and Molecular Weight on the Charge Transport of a Naphthalenediimide-Based Copolymer in Thin-Film Transistors.

The N-type semiconducting polymer, P(NDI2OD-T2), with different molecular weights (MW=23, 72, and 250 kg/mol) was used for the fabrication of field-effect transistors (FETs) with different semiconductor layer thicknesses. FETs with semiconductor layer thicknesses from ∼15 to 50 nm exhibit similar electron mobilities (μ's) of 0.2-0.

Palladium-catalyzed chain-growth polycondensation of AB-type monomers: high catalyst turnover and polymerization rates.

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 280 s(-1). In contrast, related AA/BB-type step-growth polycondensation proceeds with two orders of magnitude lower TONs and TOFs.

Self condensation of enamines mediated by acetylation. A novel approach to 1-(azol-5-yl)-(1E,3Z)-butadiene-4-N,N-dimethylamines.

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.

"Hairy" poly(3-hexylthiophene) particles prepared via surface-initiated Kumada catalyst-transfer polycondensation.

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.

Grafting of polyfluorene by surface-initiated Suzuki polycondensation.

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).