16968-19-7Relevant articles and documents
Solvent-Free Synthesis of Diazocine
Moormann, Widukind,Langbehn, Daniel,Herges, Rainer
, p. 3471 - 3475 (2017)
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.
Photoswitchable azo‐ and diazocine‐functionalized derivatives of the vegfr‐2 inhibitor axitinib
Heintze, Linda,Schmidt, Dorian,Rodat, Theo,Witt, Lydia,Ewert, Julia,Kriegs, Malte,Herges, Rainer,Peifer, Christian
, p. 1 - 23 (2020/11/30)
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.
Method of preparing 2,2'-binitrobibenzil
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Paragraph 0020; 0022, (2017/11/16)
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.
New preparation method of o-dinitrodibenzyl
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Paragraph 0009; 0016; 0017; 0018, (2017/07/14)
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.
Heterogeneous photocatalytic C-C coupling: Mechanism of plasmon-mediated reductive dimerization of benzyl bromides by supported gold nanoparticles
Lanterna, Anabel E.,Elhage, Ayda,Scaiano, Juan C.
, p. 4336 - 4340 (2015/09/01)
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.
Synthesis of biologically active seven-membered-ring heterocycles
Reekie, Tristan A.,Kavanagh, Madeline E.,Longworth, Mitchell,Kassiou, Michael
, p. 3211 - 3227 (2013/12/04)
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.
Synthesis of new dibenzo[b,f]azepine derivatives
Balaure, Paul Catalin,Costea, Ion,Iordache, Florin,Draghici, Constantin,Enache, Cristian
scheme or table, p. 935 - 942 (2011/06/21)
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).
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
Suzuki, Hitomi,Mori, Tadashi
, p. 1265 - 1274 (2007/10/03)
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.
ortho-Azobenzenophanes: Photochemical and thermal reactions of [2,2][2,2′]azobenzenophane
Tauer, Erich,Machinek, Reinhard
, p. 1213 - 1216 (2007/10/03)
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.
REACTIVITY OF THE ACIDS OF TRIVALENT PHOSPHORUS AND THEIR DERIVATIVES. PART IV. THE REACTION OF DIALKYLPHOSPHITE ANIONS WITH NITROBENZYL BROMIDES
Witt, Dariusz,Rachon, Janusz
, p. 33 - 48 (2007/10/03)
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.
