- Solvent-Free Synthesis of Diazocine
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A convenient two-step synthesis of diazocine starting from 2-nitrotoluene is described. The first step, the oxidative dimerization of 2-nitrotoluene, is improved to 95% yield. The second step, the reductive azo cyclization, is performed as a solvent-free reaction with lead powder in a ball mill (51% yield). As a reference, the previously described azo cyclization with Zn/Ba(OH) 2 is investigated in detail. The results explain why in previous experiments the yields are low and extremely dependent on the reaction conditions. In view of potential applications in photopharmacology, we checked the stability under reducing conditions. Diazocine does not react with glutathione, indicating intracellular stability.
- Moormann, Widukind,Langbehn, Daniel,Herges, Rainer
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- Photoswitchable azo‐ and diazocine‐functionalized derivatives of the vegfr‐2 inhibitor axitinib
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In this study, we aimed at the application of the concept of photopharmacology to the approved vascular endothelial growth factor receptor (VEGFR)‐2 kinase inhibitor axitinib. In a previous study, we found out that the photoisomerization of axitinib’s stilbene‐like double bond is unidirectional in aqueous solution due to a competing irreversible [2+2]‐cycloaddition. Therefore, we next set out to azologize axitinib by means of incorporating azobenzenes as well as diazocine moieties as photoresponsive elements. Conceptually, diazocines (bridged azobenzenes) show favorable photoswitching properties compared to standard azobenzenes because the thermodynamically stable Z‐isomer usually is bioinactive, and back isomerization from the bioactive E‐isomer occurs thermally. Here, we report on the development of different sulfur– diazocines and carbon–diazocines attached to the axitinib pharmacophore that allow switching the VEGFR‐2 activity reversibly. For the best sulfur–diazocine, we could verify in a VEGFR‐2 kinase assay that the Z‐isomer is biologically inactive (IC50 >> 10,000 nM), while significant VEGFR‐2 inhibition can be observed after irradiation with blue light (405 nm), resulting in an IC50 value of 214 nM. In summary, we could successfully develop reversibly photoswitchable kinase inhibitors that exhibit more than 40‐fold differences in biological activities upon irradiation. Moreover, we demonstrate the potential advantage of diazocine photoswitches over standard azobenzenes.
- Heintze, Linda,Schmidt, Dorian,Rodat, Theo,Witt, Lydia,Ewert, Julia,Kriegs, Malte,Herges, Rainer,Peifer, Christian
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- Method of preparing 2,2'-binitrobibenzil
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The invention discloses a method of preparing 2,2'-binitrobibenzil by a catalysis method and a preparation method of a catalyst used by the preparation method. The preparation method of 2,2'-binitrobibenzil comprises the steps of taking ortho-nitrobenzyl chloride as a raw material and methyl chloride as a solvent, adding an amine sacrifice agent, taking a noble metal gold loaded nano titanium oxide carrier as the catalyst, performing a reaction under light irradiation, performing sufficient ultrasonic dispersion prior to the reaction, performing solvent reflux in a reaction process, stirring a reaction system in the reaction process to keep the reaction system in a suspension state, and performing solid-liquid separation after reaction completion to obtain a coupled product, namely 2,2'-binitrobibenzil. The preparation method greatly reduces energy consumption caused by a high temperature in the traditional technology, and avoids cost increase and product loss caused by multi-step and multi-time purification; three wastes generated in a production process are few; a technology is concise; a yield of a product is higher; and a green chemistry concept is met.
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Paragraph 0020; 0022
(2017/11/16)
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- New preparation method of o-dinitrodibenzyl
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The invention relates to a preparation method of carbamazepine midbody used as broad spectrum antiepileptic drug and particularly relates to a new preparation method of o-dinitrodibenzyl. The method uses o-nitrobromobenzene as the raw material, and prepares corresponding format reagent, and then reacts with the protected o-nitryl phenethyl alcohol, and the product is prepared. The invention adopts o-nitrobromobenzene as the raw material, the format reagent is prepared; thus the reaction is gentle, the method avoid hydrogen generated in reaction process, and greatly improves the production safety; the reaction yield and the selectivity are better, the raw material utilization rate is higher, the product cost control has well improved; the raw material technique is matured, the market supply is sufficient and the source is wide; the method is simple in technique, convenient to operate, and free from environment pollution.
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Paragraph 0009; 0016; 0017; 0018
(2017/07/14)
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- Heterogeneous photocatalytic C-C coupling: Mechanism of plasmon-mediated reductive dimerization of benzyl bromides by supported gold nanoparticles
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The use of gold nanoparticles supported on TiO2 (Au@TiO2) as photocatalysts was extended to include photoinduced reductive C-C coupling. Surface plasmon excitation of supported AuNPs in the presence of an amine leads to the C-C coupling of a variety of substituted benzyl bromides at room temperature with good yields in a free radical-mediated reaction. The overall efficiency of the C-C coupling is largely dependent on the nature of the amine used.
- Lanterna, Anabel E.,Elhage, Ayda,Scaiano, Juan C.
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p. 4336 - 4340
(2015/09/01)
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- Synthesis of biologically active seven-membered-ring heterocycles
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Seven-membered rings that contain one or more heteroatoms are interesting motifs for organic synthesis. In addition to their synthetic interest, they play an important role in industrial and pharmaceutical chemistry with generally increased central nervous system activity when flanked by aromatic rings. Herein we report a brief summary of some key methods of preparation for seven-membered-ring heterocycles and how they have been applied to the synthesis of commercially desirable products. We then detail new methods that we have developed for the synthesis of biologically active compounds containing this motif. Georg Thieme Verlag Stuttgart New York.
- Reekie, Tristan A.,Kavanagh, Madeline E.,Longworth, Mitchell,Kassiou, Michael
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p. 3211 - 3227
(2013/12/04)
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- Synthesis of new dibenzo[b,f]azepine derivatives
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This work is focused on synthesis and chemical characterization of new polycyclic compounds having dibenzo[b,f] azepine and 10,11-dihydrodibenzo[b,f] azepine moieties. We report the synthesis of four new compounds, obtained by reacting 5H-dibenzo[b,f]azepine-5-carbonyl chloride and 10,11-dihydro-5H- dibenzo[b,f]azepine-5-carbonyl chloride with 1-phenylpiperazine, and pyrrolidine, respectively. The newly synthesized compounds were characterized using chromatographic and spectroscopic methods (HPLC-UV-VIS 1H-NMR, 13C-NMR, mass spectrometry by ESI technique).
- Balaure, Paul Catalin,Costea, Ion,Iordache, Florin,Draghici, Constantin,Enache, Cristian
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scheme or table
p. 935 - 942
(2011/06/21)
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- Ozone-mediated nitration of bicumene and derivatives with nitrogen dioxide. Preferential mesolytic bond cleavage over nuclear nitration in evidence for the electron transfer nature of the kyodai-nitration of arenes
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The ozone-mediated reaction of bicumene and some derivatives 1 with nitrogen dioxide in dichloromethane at low twmperatures resulted in the facile cleavage of the central C-C bond to give the corresponding benzyl nitrate and its descendants 4-6. mesolytic bond cleavage occured almost exclusively over nuclear substitution at temperatures as low as -20 deg C, especially at low concentration (2 x 10-3 mol dm-3).This result may be rationalized in terms of initial electron transfer between the aromatic substrate and nitrogen trioxide in situ to form the aromatic radical cation, which then undergoes C-C bond scission at the benzylic position.In contrast, bibenzyl 2a is simply nitrated on the aromatic ring under similar conditions, giving the expected nitration products 7 and 8a-c along with a small amount of benzaldehyde 9.Results obtained from semi-empirical calculations and cyclic voltammetry are also in accord with the electron transfer nature of the reaction.The C-Si bond fission of benzyltrimethylsilane, C-C bond fragmentation of cyclic acetals of aromatic carbonyl compounds as well as side-chain reactions of toluene and derivatives, have all previously been observed under certain conditions of the kyodai-nitration and can be understood on a similar basis as described above.The possible involment of electron transfer processes in aromatic nitration with acetyl nitrate has also been suggested.
- Suzuki, Hitomi,Mori, Tadashi
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p. 1265 - 1274
(2007/10/03)
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- ortho-Azobenzenophanes: Photochemical and thermal reactions of [2,2][2,2′]azobenzenophane
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The cyclic azo compounds 6 and 7 were synthesized. The chemical properties of 6 were investigated. Irradiation of the trans,trans form 6t,t leads to isomerization to the trans,cis form 6t,c and to the cis,cis form 6c,c. Compounds 6t,c and 6c,c can be isolated. However, thermally, 6t,c and 6c,c react slowly back to 6t,t. All attempts to convert 6 by light into the tetraazetidine 10 have been unsuccessful until now. In boiling toluene 6 undergoes an interesting rearrangement, namely a ring contraction, during which an azo group is cleaved with formation of an indole ring and a primary amino group. VCH Verlagsgesellschaft mbH, 1996.
- Tauer, Erich,Machinek, Reinhard
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p. 1213 - 1216
(2007/10/03)
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- REACTIVITY OF THE ACIDS OF TRIVALENT PHOSPHORUS AND THEIR DERIVATIVES. PART IV. THE REACTION OF DIALKYLPHOSPHITE ANIONS WITH NITROBENZYL BROMIDES
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The reaction of o-, m- and p-nitrobenzyl bromide with sodium dimethylphosphite as well as sodium diisopropylphosphite in THF and alcohols as the solvent is described.According to the constitution of the starting materials and the solvents used, the formation of the P-C bond, debromination or dimerization occurs.The principal process in o- and p-nitrobenzyl bromide and >P-O- anion systems is believed to be X-philic substitution, the dimer is formed through a secondary process via SET from the nitrobenzyl anion to nitrobenzyl bromide.Electron-transfer and proton-transfer processes in the nitrobenzyl bromide->P-O- systems are also discussed.Key words: o-, m- and p-nitrobenzyl bromides, dialkyl phosphites, Michaelis-Becker reaction, X-philic substitution, SET.
- Witt, Dariusz,Rachon, Janusz
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- Elektrosynthese von 2,2'-Dinitrobenzyl aus 2-Nitrobenzylbromid. Mechanistische und praeparative Untersuchungen
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The mechanism of the electrochemical reduction of 2-nitrobenzyl halides in aprotic media has been reinvestigated by electroanalytical methods (dc-polarography, cyclic voltammetry, potentiostatic coulometry, rotating ring-disk electrode), by using NICHOLSON-SHAIN criteria and product analysis by gas chromatography.The cathodic reduction of 2-nitrobenzyl halides proceeds via the mechanism EC1irr.On the basis of cyclic voltammetric data the rate constant of the cleavage of the anion radical of 2-nitrobenzyl bromide (k1 = 59,6 sec-1) and of 4-nitrobenzyl bromide (k1 = 144 sec-1) in 0,1M (C2H5)4NClO4/acetonitrile at 25 deg C has been determined.The one-electron reduction of 2-nitrobenzyl halides and the subsequent decomposition of the anion radical lead to the neutral 2-nitrobenzyl radical, which dimerizes to 2,2'-dinitrodibenzyl.The electropreparative investigations by galvanostatic and potentiostatic electrolyses showed that the best method of electrosynthesis of 2,2'-dinitrodibenzyl from 2-nitrobenzyl bromide is the controlled-potential electrolysis (mercury pool-electrode, 0,1M (C2H5)4NClO4/acetonitrile, E = -1.0...-1.1V (SCE), Q = 1.1 Faraday per mole, yield 93-95percent).
- Vieth, B.,Jugelt, W.,Pragst, F.
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p. 338 - 352
(2007/10/02)
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- Method for preparing nitrobibenzyl systems
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Method for preparing bibenzyl systems with nitro groups as substituents. Toluene derivates with nitro groups are coupled oxidatively in methanolic alkali solution under influence of metal catalysts. The oxidation is preferably done with air. As catalysts metal acetonylacetonates are used. The metal can be Ni, Cu, Co, Mn, Cr or Ti. This catalyst can be used together with a crown ether. Another suitable catalyst is a metal tetraphenylporphin of porfyrin type where the metal can be Ni, vanadium (V=O) or Fe(FeIII).
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- Investigations about the Reducing Properties of Dimeric Dihydropyridines
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The reaction of a series of bis- derivatives P2 with some benzyl halides, trans-1,2-dibromoethane and several heteroaromatic cations Q+ was investigated in acetonitrile/toluene with electrochemical and kinetic methods.For substrates with a reduction potential between -0.9 and -1.5 V the reaction occurs via the ratedetermining dissociation of P2 into free radicals P. as the real reducing agents, which transform the benzyl halides into the corresponding 1,2-diarylethanes and Q+ into the corresponding dimeric product Q2.For thereduction of trans-1,2-dibromocyclohexane to cyclohexene a simultaneous transfer of two electrons to the substrate combined with the dissociation of P2 into two pyridinium ions P+ is proposed.In the case of a reduction potential more positive than -0.9 V (e.g. nitro substituted benzyl halides) P2 itself can act as the reducing agent with an increased reaction rate.With pyrylium ions Q+ a product P-Q was detected by voltammetry and mass spectroscopy.In this case an electrophilic attack onto P2 instead of the electron transfer from P2 to Q+ cannot be excluded.
- Pragst, F.,Santrucek, M.
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- Electrochemistry of Organic Cations. VI. Investigations about the Cathodic Cleavage of Some Pyridinium and Triazolium Ions
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The electrochemical reduction of some N-acylamino-, N-amino-, N-benzyl- and N-phenacyl-substituted pyridinium and triazolium ions is investigated in acetonitrile by voltammetric methods and potentiostatic electrolyses.The acylaminopyridinium ions 1 and the arylaminopyridinium ions 3 are cathodically cleaved into the pyridine derivative and the carboxylic amide or the aromatic amine.In the case of the 1-benzyl-4-acylaminotriazolium ions 5 the reductive formation of hydrogen from the acidic N-acylamino group is preferred and the corresponding ylide is formed, which reacts at more negative potential by splitting off the benzyl group.The reduction of the N-phenacylpyridinium ion 7d occurs with splitting off the phenacyl radical, which dimerizes to 1,2-dibenzoylethane in a good yield.In the case of N-benzyl- and N-p-cyanobenzylpyridinium ions the cathodic dimerization to the corresponding bisdihydropyridines was found, whereas the electrolysis of the N-nitrobenzylpyridinium ions occurs with cleavage of the N-substituent-bond, which is initiated by the primary formation of the nitrophenyl anion radical.It follows from electrogenerated chemiluminescence experiments that the cleavage of the cations 1 and 5 occurs with the uptake of one electron.
- Pragst, F.,Henrion, A.,Abraham, W.,Michael, G.
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p. 1071 - 1086
(2007/10/02)
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- SPECIFIC ORTHO ORIENTATION IN THE VICARIOUS SUBSTITUTION OF HYDROGEN IN AROMATIC NITRO COMPOUNDS WITH CARBANION OF CHLOROMETHYL PHENYL SULFONE
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Vicarious nucleophilic substitution of hydrogen atoms in nitroarenes with chloromethylphenyl sulfone proceeds selectively ortho to the nitro group when carried out in t-BuOK/THF base/solvent system.In the majority of 3-substituted nitrobenzene derivatives substitution occurs at the most hindered position 2.These conditions offer an efficient method of synthesis of 2,6 and 2,3-disubstituted nitrobenzene derivatives.
- Makosza, M.,Glinka, T.,Kinowski, A.
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p. 1863 - 1868
(2007/10/02)
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- Cyclic Azo Dioxides. Synthesis and Properties of Bis(o-nitrosobenzyl) Derivatives
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Several cyclic azo dioxides have been prepared by oxidation of the corresponding diamines with sodium tungstate-hydrogen peroxide in ethanol-water: 4 (related to o,o'-dinitrosobibenzyl), 8 (related to bis(o-nitrosobenzyl)ether), 14 (related to bis(o-nitrosobenzyl)amine), 13 (the trifluoroacetate salt of 14), 12a and 12b (the N-carbomethoxy and N-carbo-tert-butoxy derivatives of 14).In solution the azo dioxides are in equilibrium (Ke) with the corresponding dinitroso forms: Ke increases with decreasing polarity of solvent and with increasing temperature.For azo dioxide 4 in dioxane at 25 deg C Ke = 0.18, Δ H0 = 7.09 +/- 0.47 kcal mol-1, and Δ S0 = 20.4 cal mol-1 deg-1.The azo dioxides decompose at elevated temperatures (>100 deg C); azo dioxide 14 is converted to 2-(o-nitrosobenzyl)indazole (15) in refluxing methylene chloride.
- Smith, Mark A.,Weinstein, Barry,Greene, Frederick D.
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p. 4597 - 4602
(2007/10/02)
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