- Synthesis of arylhydrazone-based molecular switches using aryldiazonium silica sulfate nanocomposites and analysis of their isomerization
-
A fast and efficient method for the synthesis of a series of arylhydrazones by reacting aryldiazonium silica sulfate nanocomposites with malononitrile, ethyl acetoacetate and dimedone is reported. All reactions were carried out in water at room temperature and the corresponding products were obtained in 77–87% yields. The existence of two kinds of intramolecular hydrogen bonds in the arylhydrazones synthesized using ethyl acetoacetate enables these compounds to be switched by rotation about the hydrazone C[dbnd]N bond, which leads to a reversible isomerization between their E and Z configurations. This switching can be controlled by changing the polarity of the solvents. The E/Z ratio of each synthesized compound was studied in CHCl3 and DMSO. The ratios of the E/Z were calculated using 1H NMR data in both CDCl3 and DMSO?d6, and used to calculate ΔG° for the E-Z isomerization of each synthesized compound in these two solvents. By changing the solvent from CHCl3 to DMSO, the E/Z ratios decreased. The results demonstrated that the ΔG° values for the formation of Z isomers were more negative than those of the E isomers in DMSO. This is why Z isomers are more stable than E isomers in DMSO. The results of density functional theory (DFT) calculations at B3LYP/6–311++G (d,p) level of theory, were in agreement with the experiments and confirmed the increased stability of Z isomers in DMSO. In most cases, DFT calculation in CDCl3 and DMSO indicate that the dipole moments of the Z isomers are significantly higher than those of the E isomers. Finally, the effect of temperature on the E-Z isomerization was studied using dynamic 1H NMR. The findings demonstrated that temperature does not have any significant effect on the E-Z isomerization in CDCl3 and DMSO?d6.
- Abbaspourrad, Alireza,Aghaei, Hamidreza,Chermahini, Alireza Najafi,Khazdooz, Leila,Soltani, Solmaz,Zarei, Amin
-
-
- Novel heterocyclic disazo dyes containing pyrazole and phenylpyrazole. part 1: Synthesis, characterization, solvent polarity and acid-base sensitive characteristics
-
A series of diazotised aniline and aniline derivative compounds were reacted with solution of malononitrile in pyridine at 0–5 °C were obtained 1a-1m compounds. Then 4-arylazo-3,5-diamino-1H-pyrazole (2a-2m) derivatives were synthesized by coupling arylazo malononitrile compounds with hydrazine. Finally, the synthesized pyrazole derivative 2a-2m compounds were again diazotised. By reacting these diazotised compounds with 3-amino-5?hydroxy-1-phenylpyrazole, the new thirteen heterocyclic disazo dyes (3a-3m) were joined the dye literature and the dye industry. The structures of these newly synthesized compounds were characterized using elemental analysis and spectroscopic methods such as Fourier transform infrared spectroscopy-Attenuated total reflectance (FT-IR-ATR), 1H-Nuclear magnetic resonance (1H NMR) spectroscopy and mass spectroscopy. Then solvatochromic properties and solvent effect in dimethyl sulfoxide, dimethyl formamide, acetonitrile, acetic acid, methanol and chloroform were investigated. In addition, the effects of organic and inorganic acids and bases on the absorption spectra of the compounds and the substituent effect of the phenyl ring-bound groups were investigated.
- Demir?al?, Aykut
-
-
- Computer-aided molecular design of pyrazolotriazines targeting glycogen synthase kinase 3
-
Numerous studies have highlighted the implications of the glycogen synthase kinase 3 (GSK-3) in several processes associated with Alzheimer’s disease (AD). Therefore, GSK-3 has become a crucial therapeutic target for the treatment of this neurodegenerative disorder. Hereby, we report the design and multistep synthesis of ethyl 4-oxo-pyrazolo[4,3-d][1–3]triazine-7-carboxylates and their biological evaluation as GSK-3 inhibitors. Molecular modelling studies allow us to develop this new scaffold optimising the chemical structure. Potential binding mode determination in the enzyme and the analysis of the key features in the catalytic site are also described. Furthermore, the ability of pyrazolotriazinones to cross the blood–brain barrier (BBB) was evaluated by passive diffusion and those who showed great GSK-3 inhibition and permeation to the central nervous system (CNS) showed neuroprotective properties against tau hyperphosphorylation in a cell-based model. These new brain permeable pyrazolotriazinones may be used for key in vivo studies and may be considered as new leads for further optimisation for the treatment of AD.
- Sciú, M. Lourdes,Sebastián-Pérez, Victor,Martinez-Gonzalez, Loreto,Benitez, Rocio,Perez, Daniel I.,Pérez, Concepción,Campillo, Nuria E.,Martinez, Ana,Moyano, E. Laura
-
-
- Iodine-catalyzed diazenylation with arylhydrazine hydrochlorides in air
-
A mild approach to diazenylation of active methylene compounds and N-heterocyclic compounds with arylhydrazine hydrochlorides in the presence of iodine under basic aerobic conditions was developed. The reaction could be executed either under heating or in the presence of blue LED light, though the latter condition was found to be relatively efficient. Presumably, the aryldiazene produced by oxidation of arylhydrazine hydrochloride acts as a nitrogen scavenger of the radical intermediate generated from the active methylene compound in the presence of iodine to produce the diazo compounds. The scope and limitations of the protocol are presented.
- Barak, Dinesh S.,Dighe, Shashikant U.,Avasthi, Ilesha,Batra, Sanjay
-
p. 3537 - 3546
(2018/04/14)
-
- Synthesis, absorption properties and biological evaluation of some novel disazo dyes derived from pyrazole derivatives
-
In this study, 20 novel disazo dyes containing pyrazole derivatives were synthesized by a convenient method. Diazotized aniline and some aniline derivatives were reacted with malononitrile to give 2-arylazomalononitrile derivatives 1(a-e). The synthesized 2-arylazomalononitrile derivatives were reacted with hydrazine and phenyl hydrazine to afford the corresponding 3,5-diamino-4-arylazo-1 H-pyrazole 2(a-e) and 3,5-diamino-4-arylazo-1-phenylpyrazole 3(a-e). Diazotized compounds of 2(a-e)and 3(a-e) reacted with ethylacetoacetate to give 4-arylazo-3-amino-1 H-pyrazole-5-ylazo-ethylacetoacetate 4(a-e) and 4-arylazo-3-amino-1-phenylpyrazole-5-ylazo-ethylacetoacetate 7(ae). The obtained 4(a-e) and 7(a-e) were reacted with hydrazine and phenyl hydrazine to give disazo dyes 5(a-e), 6(a-e), 8(a-e) and 9(a-e), respectively. The synthesized disazo dyes were characterized by spectroscopic techniques as well as elemental analysis. The solvatochromic behaviours of these dyes in various solvents were examined. Acid-base effects on the absorption maxima of the dyes were also reported. Antimicrobial activities of the synthesized novel disazo dyes were investigated.
- Sener, Nesrin,Sener, Izzet,Yavuz, Serkan,Karci, Fikret
-
p. 3003 - 3012
(2015/12/11)
-
- Multistep flow synthesis of 5-amino-2-aryl-2h-[1,2,3]-triazole-4-carbonitriles
-
1,2,3-Triazole has become one of the most important heterocycles in contemporary medicinal chemistry. The development of the copper-catalyzed Huisgen cycloaddition has allowed the efficient synthesis of 1-substituted 1,2,3-triazoles. However, only a few methods are available for the selective preparation of 2-substituted 1,2,3-triazole isomers. In this context, we decided to develop an efficient flow synthesis for the preparation of various 2-aryl-1,2,3-triazoles. Our strategy involves a three-step synthesis under continuous-flow conditions that starts from the diazotization of anilines and subsequent reaction with malononitrile, followed by nucleophilic addition of amines, and finally employs a catalytic copper(II) cyclization. Potential safety hazards associated with the formation of reactive diazonium species have been addressed by inline quenching. The use of flow equipment allows reliable scale up processes with precise control of the reaction conditions. Synthesis of 2-substituted 1,2,3-triazoles has been achieved in good yields with excellent selectivities, thus providing a wide range of 1,2,3-triazoles.
- Jacq, Jér?me,Pasau, Patrick
-
p. 12223 - 12233
(2015/03/31)
-
- Mechanically activated solid-state synthesis of phenylhydrazone derivatives via high-speed ball milling
-
A series of phenylhydrazone derivatives was synthesized from arenediazonium tetrafluoroborates and active methylene compounds under high-speed ball milling. The reaction occurred in the absence of the solvent and products were obtained in good yield within short reaction times (no more than 30 min).
- Zhu, Xingyi,Chen, Yuanyuan,Chen, Yuhe,Wang, Jue,Su, Weike
-
p. 621 - 626
(2014/07/21)
-
- Synthesis, characterization and density functional theory investigations of the electronic, photophysical and charge transfer properties of donor-bridge-acceptor triaminopyrazolo[1,5-a]pyrimidine dyes
-
We have synthesized multifunctional dyes 3-(4-methyl-phenylazo)-6-(4-nitro- phenylazo)-2,5,7-triaminopyrazolo[1,5-a]pyrimidine (4a) and 3-(4-methyl- phenylazo)-6-(4-acetyl-phenylazo)-2,5,7-triaminopyrazolo[1,5-a]pyrimidine (4b), then characterized by IR, 1H NMR and 13C NMR techniques. The ground state geometries have been computed by using density functional theory at B3LYP/6-31Ga?- level of theory. The absorption spectra have been calculated by using time dependent density functional theory with and without solvent. The highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs) are delocalized and localized on throughout the backbone, respectively. Solvent also play important role towards elevating the dipole moment. Significant red shift in absorption wavelengths have been observed in methanol compared to without solvent. We discussed the electron injection, electronic coupling constant and light harvesting efficiency.
- Al-Sehemi, Abdullah G.,Irfan, Ahmad,Fouda, Ahmed M.
-
p. 223 - 229
(2013/07/19)
-
- Regiospecific synthesis of 6-aryl-3-cyano-5-alkylamino/arylamino-1-p-tolyl- 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones via iminophosphorane-mediated annulation
-
An efficient and straightforward approach to the synthesis of 6-aryl-3-cyano-5-alkylamino-1-p-tolyl-IH- pyrazolo[4,3-d]pyrimidin-7(6H)-ones 8 has been developed from the readily commercially available starting materials 4-methylaniline and malononitrile i
- Wu, Ming-Hu,Hu, Ji-Huan,Sheil, Dong-Sheng,Brémond, Paul,Guo, Haibing
-
experimental part
p. 5112 - 5120
(2010/08/20)
-
- Efficient routes to pyrazolo[3,4-e][1,2,4]triazines and a new ring system: [1,2,4]triazino[5,6-d][1,2,3]triazines
-
Arylhydrazonomalononitriles 1a,b react with Phenylhydrazine to yield amidrazones 2a,b that cyclize to give 2-aryl-5-phenylhydrazono-2,5-dihydro-[1,2, 4]-triazine-6-carbonitriles 5a,b upon reaction with dimethylformamide dimethylacetal (DMFDMA). Refluxing 5a,b in glacial acetic acid resulted in the formation of the pyrazolo-1,2,4-triazines 6a,b. Compounds 6a,b were also formedupon treatment of 3-amino-4-phenylhydrazono-1-phenyl-2-pyrazolin-5-ones 7a,b with DMFDMA. Reacting these triazinyl arylhydrazononitriles 5a,b with hydroxylamine hydrochloride in ethanolic sodium acetate afforded amidrazones 8a,b that are readily cyclized in refluxing dimethylformamide into [1,2,4]triazino[1,2,3]triazines 10a,b.
- Al-Matar, Hamad Mohamed,Khalil, Khaled Dessouky,Al-Dorri, Doa'A Mohamed,Elnagdi, Mohamed Helmy
-
experimental part
p. 3302 - 3310
(2010/09/15)
-
- Synthesis and antimicrobial activity studies of some novel substituted phenylhydrazono-1H-tetrazol-5-ylacetonitriles
-
In this study, some substituted phenylhydrazono-1H-tetrazol-5-yl- acetonitriles have been synthesized (2a-o, 2a and 2k are known compounds). The synthesized compounds were characterized by spectroscopic methods [Fourier-transform infrared (FTIR), nuclear magnetic resonance (NMR), mass spectroscopy (MS)]. In addition, antimicrobial activities of synthesized compounds were investigated against Bacillus cereus RSKK 863, Escherichia coli ATCC 3521, Pseudomonas aeruginosa ATCC 2921, and Staphylococcus aureus TP32. These compounds had antimicrobial effect against these bacteria (except for 21). Birkhaeuser Boston 2009.
- Yavuz, Serkan,Aydin, Oezlem,Cete, Servet,Disli, Ali,Yildirir, Yilmaz
-
scheme or table
p. 120 - 126
(2010/12/20)
-
- 4-Arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects
-
In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. Enzyme kinetics studies with the lead compound and X-ray crystallography of an inhibitor-CDK2 complex demonstrated that its mode of inhibition is competitive. Functional kinase assays confirmed the selectivity toward CDKs, with a preference for CDK9-cyclin T1. The most potent inhibitor, 4-[(3,5-diamino-1H-pyrazol-4-yl) diazenyl]phenol 31b (CAN508), reduced the frequency of S-phase cells of the cancer cell line HT-29 in antiproliferation assays. Further observed cellular effects included decreased phosphorylation of the retinoblastoma protein and the C-terminal domain of RNA polymerase II, inhibition of mRNA synthesis, and induction of the tumor suppressor protein p53, all of which are consistent with inhibition of CDK9.
- Kry?tof, Vladimír,Canka?, Petr,Fry?ová, Iveta,Slouka, Jan,Kontopidis, George,D?ubák, Petr,Hajdúch, Marián,Srovnal, Josef,De Azevedo Jr., Walter F.,Orság, Martin,Paprská?ová, Martina,Rol?ík, Jakub,Látr, Ale?,Fischer, Peter M.,Strnad, Miroslav
-
p. 6500 - 6509
(2007/10/03)
-
- On the chemistry of cinnoline I. synthesis and reactions of (4-Amino-cinnolin-3-yl)-p-tolyl-methanones
-
The synthesis of a series of (4-Amino-cinnolin-3-yl)-p-tolyl-methanones from aryl-hydrazonomalononitrile in a one step procedure is reported. The (4-amino-cinnolin-3-yl)-p-tolyl-methanones could be annelated to the corresponding 1,2-dihydro-4-(p-tolyl)-2-oxopyrido[3,2-c]cinnoline derivatives via (4-acetamido-cinnolin-3-yl)-p-tolyl-methanones. Treatment of 1,2-dihydro-9-methyl-4-(p-tolyl)-pyrido[3,2-c]cinnoline-2-one with POCl1 and P2S5 gave 2-chloro-9-methyl-4-(p-tolyl)-pyrido[3,2-c]cinnoline and 1,2-dihydro-9-methyl-4-(p-tolyl)-pyrido[3,2-c]cinnoline-2-thione. Treatment of the ketone with malononitrile afforded 2-amino-3-cyano-9-methyl-4-(p-tolyl)-pyrido[3,2-c]cinnoline. Using these ketones, a facile and convenient route towards substituted pyrimidino[5,4-c]-cinnolines was developed. Chemical and spectroscopic evidences for the structures of the new compounds are presented.
- Amer, Atef M.,El-Bermaui, Mohamed A.,Ahmed, Ahmed F. S.,Soliman, Somya M.
-
p. 1409 - 1418
(2007/10/03)
-
- Reactions with hydrazonoyl halides XIX1: Synthesis of some pyrazole and 5-arylazothiazole derivatives
-
Hydrazonoyl chlorides 1 reacted with 2-aryl-1-cyano-1-thiazol-2-ylethenes 2 in presence of triethylamine to give the cycloadducts 4. which were converted to the corresponding pyrazoles 5 by the action of sodium methoxide. The reaction of hydrazonoyl halides 1 and 6 with each of 2-arylidene-2-cyanoethanethioamides 7 and 2-arylhydrazono-2-cyanoethanethioamides 14 in ethanolic triethylamine or ethanolic sodium hydroxide solutions, has been investigated. Structures of all the products were established on the basis of their spectral data and alternative synthesis.
- Zohdi, Hussein F.,Rateb, Nora M.,Abdelhamid, Abdou O.
-
p. 103 - 117
(2007/10/03)
-
- Tetratetrazole Macrocycles
-
A synthetic route to tetratetrazole macrocycles which allows for variation in cavity size is described.
- Butler, Richard N.,Quinn, K. Fergal,Welke, Birgit
-
p. 1481 - 1482
(2007/10/02)
-
- Mechanism of the Reaction of 1,3-Diaryltriazenes with Tetracyanoethylene in the Presence of Acetic Acid
-
The mechanism for the reaction of 1,3-diaryltriazenes with tetracyanoethylene (TCNE) in the presence of acetic acid, giving Schiff's bases and arylhydrazonomalonitriles, has been investigated.The intermediacy of arylazomalononitriles was confirmed by crossover experiments using an arylamine different from the component of the triazene.The route to the azo compounds via TCNE-triazene adducts had already been established by a tracer experiment using an 15N-labelled triazene.However, the crossover experiments, as well as the result of the reaction of a triazene with the TCNE-2,6-dimethylaniline adduct, revealed an alternative route via TCNE-ArNH2 adducts in the presence of acetic acid.
- Mitsuhashi, Tsutomu
-
p. 1495 - 1500
(2007/10/02)
-