- Metallacycle-catalyzed SNAr reaction in water: Supramolecular inhibition by means of host-guest complexation
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The performance of a PtII diazapyrenium-based metallacycle as a reusable substoichiometric catalyst for the SNAr reaction between halodinitrobenzenes and sodium azide at rt in aqueous media is reported. The results suggest that the c
- Lopez-Vidal, Eva M.,Fernandez-Mato, Antonio,Garcia, Marcos D.,Perez-Lorenzo, Moises,Peinador, Carlos,Quintela, Jose M.
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- Synthesis of nitrophenyl and fluorophenyl azides and diazides by SNAr under phase-transfer or microwave irradiation: Fast and mild methodologies to prepare photoaffinity labeling, crosslinking, and click chemistry reagents
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Two fast and mild methodologies to prepare nitrophenyl and fluorophenyl azides are presented. These aryl azides are extensively used as crosslinking, photoaffinity labeling, and click chemistry reagents. Substituted aryl azides are prepared by performing a SNAr substitution on halogenated benzenes with a phase-transfer catalyst (PTC) such as tetraethylammonium tetrafluoroborate (TEATFB), the reaction proceeds in several hours under rather mild temperatures (25°C to 70°C). Furthermore, aryl azides are also prepared within minutes under microwave irradiation at slightly higher temperatures (50°C to 70°C). These procedures could be applied in the preparation of other aryl azides. In the case of substituted pentafluoro benzene (pF), the type of products obtained in each reaction depends on the amount of sodium azide and the strength and position of electron-withdrawing substituents (COH, COR, COOR, CN, NO2, or F). A discussion on the mechanisms and the products obtained in these SNAr reactions is presented.
- Leyva, Elisa,Aguilar, Johana,González-Balderas, Regina M.,Vega-Rodríguez, Sarai,Loredo-Carrillo, Silvia E.
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- Thiophenol-formaldehyde triazole causes apoptosis induction in ovary cancer cells and prevents tumor growth formation in mice model
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In the present study a library of thiophenol-formaldehyde-triazole (TFT) derivatives was synthesized and screened against CAOV3, CAOV4 and ES-2 ovary cancer cell lines. Initial screening revealed that five-compounds 5a, 5b, 5j, 5h and 5i inhibited the viability of tested cell lines. Analysis of apoptosis revealed that increase in compound 5a (most active) concentration from 0.25 to 2.0 μM enhanced apoptotic cell proportion. Transwell assay showed reduction in invasive potential of CAOV3 cells on treatment with compound 5a. In wound healing assay increasing the concentration of compound 5a from 0.5 to 2.0 μM caused a significant (P 0.05) decrease in the migration potential. Western blotting showed that compound 5a treatment markedly decreased the level of matrix metalloproteinase (MMP)-2 and ?9 in CAOV3 cells. Treatment of CAOV3 cells with compound 5a caused a marked decrease in Focal Adhesion Kinase (FAK) activation. Tumor growth was inhibited in the compound 5a treated mice markedly than those of untreated group. The tumor metastasis to liver, intestine, spleen and peritoneal cavity was markedly decreased in mice treated with 10 mg/kg dose of compound 5a. Examination of Von Willebrand factor (vWF) expression in liver, intestinal and pulmonary lesions showed a marked decrease in the compound 5a-treated mice. The infiltration of macrophages in the metastatic lesions showed a significant decrease in compound 5a-treated mice. In conclusion, the compound 5a inhibited ovary cancer cell viability and induced apoptosis through decrease in expression of vWF and metalloproteinase, suppression of FAK activation and decrease in infiltration of macrophages. The compound 5a therefore can be investigated further for the treatment of ovary cancer.
- Jia, Yan,Si, Lihui,Lin, Ruixin,Jin, Hongjuan,Jian, Wenwen,Yu, Qing,Yang, Shuli
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- Design, combinatorial synthesis and biological evaluations of novel 3-amino-1'-((1-aryl-1H-1,2,3-triazol-5-yl)methyl)-2'-oxospiro[benzo[a] pyrano[2,3-c]phenazine-1,3'-indoline]-2-carbonitrile antitumor hybrid molecules
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A combinatorial chemical library of fifty-nine novel 3-amino-1'-((1-aryl-1H-1,2,3-triazol-5-yl)methyl)-2'-oxospiro[benzo[a]pyrano[2,3-c]phenazine-1,3'-indoline]-2-carbonitrile, designed as hybrid molecules of phenazine, pyran, indole and 1,2,3-triazole pharmacophores, were constructed in this study. Cytotoxic evaluation indicated that some compounds exhibited moderate cytotoxicity against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro, in which compound 36 was found to have best antiproliferative activity against the A549 cancer cell line with IC50 value of 5.4 μM. All compounds had low or no effect against L02 and HUVEC non-cancer cell lines. Compound 36 was further confirmed to mainly locate mitochondria in A549 cancer cells via laser-scanning confocal microscopy. Moreover, compound 36 was proved to increase ROS production and induce cell cycle arrest in S phase. Western blot analysis illustrated Bax/Bcl-2 ratio was increased at dose-dependent manner, and both cleaved caspase-3 and cleaved caspase-9 was enhanced by treated with compound 36. All the above evidences in vitro indicated that compound 36 might induce the apoptosis of A549 cancer cells via a mitochondria-dependent pathway.
- Lu, Yuanyuan,Wang, Linlin,Wang, Xiaobing,Xi, Tao,Liao, Jianmin,Wang, Zhixiang,Jiang, Feng
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p. 125 - 141
(2017/04/26)
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- Kinetic study on SNAr reactions of 1-(Y-substituted-phenoxy)-2,4-dinitrobenzenes with Azide ion: Effect of changing nucleophile from hydroxide to Azide ion on reaction mechanism and reactivity
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Second-order rate constants (kN3-) for SNAr reactions of 1-(Y-substituted-phenoxy)-2,4-dinitrobenzenes (2a-2h) with (Formula presented.) in 80 mol % H2O/20 mol % DMSO at 25.0 ± 0.1 °C have been measured spectrophotometrically. The Bronsted-type plot is linear with β1g=-0.38. The Hammett plots correlated with (Formula presented.) constants exhibit highly scattered points. In contrast, the Yukawa-Tsuno plot results in an excellent linear correlation with ρY = 1.02 and r = 0.51, indicating that a negative charge develops partially on the O atom of the leaving Y-substituted-phenoxy moiety in the transition state. Accordingly, the reactions have been concluded to proceed through a stepwise mechanism, in which expulsion of the leaving group occurs in the rate-determining step. Comparison of kN3- with the kOH- values reported previously for the corresponding reactions with OH has revealed that (Formula presented.) is only 6- to 26-fold than OH toward substrates 2a-2h, although the former is over 11 pKa units less basic than the latter. Solvation and polarizability effects have been suggested to be responsible for the unusual reactivity shown by (Formula presented.) and OH. Effects of changing nucleophile from OH to (Formula presented) on reaction mechanism and reactivity are discussed in detail.
- Seo, Hyeon-Ok,Kim, Min-Young,Han, So-Yeop,Um, Ik-Hwan
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p. 1764 - 1768
(2015/07/15)
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- The α-effect in the SNAr reaction of 1-(4-nitrophenoxy)-2,4-dinitrobenzene with anionic nucleophiles: Effects of solvation and polarizability on the α-effect
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A kinetic study on SNAr reactions of 1-(4-nitrophenoxy)-2,4-dinitrobenzene (1a) with various anionic nucleophiles in 80 mol% water-20 mol% DMSO at 25.0 °C is reported. The Bronsted-type plot for the reaction of 1a with a series of substituted phenoxides and HOO- results in an excellent linear correlation with βnuc = 1.17. However, OH- exhibits dramatic negative deviation from the Bronsted-type plot, while N3-, C6H5S-, and butane-2,3-dione monoximate (Ox-) deviate positively from linearity. HOO- is 680-fold more reactive than OH- but does not exhibit the α-effect. In contrast, Ox- is 166-fold more reactive than isobasic 4-Cl-C6H4O- and exhibits the α-effect. Differential solvation effects have been suggested to be responsible for the α-effect in this study, i.e., Ox- exhibits the α-effect, since it is 5.7 kcal/mol less strongly solvated than 4-Cl-C6H4O- in the reaction medium, while HOO- does not show the α-effect due to a strong requirement for partial desolvation before nucleophilic attack. The highly enhanced reactivity of polarizable N3- and C6H5S- and extremely decreased reactivity of nonpolarizable OH- are in accord with the hard-soft acid and base principle.
- Um, Ik-Hwan,Kim, Min-Young,Cho, Hyo-Jin,Dust, Julian M.,Buncel, Erwin
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p. 1109 - 1114
(2015/10/06)
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- Nucleophilic Substitution Reactions of 2,4-Dinitrophenyl X-Substituted-Benzenesulfonates and Y-Substituted-Phenyl 4-Nitrobenzenesulfonates with Azide Ion: Regioselectivity and Reaction Mechanism
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The second-order rate constants for reactions of 2,4-dinitrophenyl X-substituted-benzenesulfonates (4a-4f) and Y-substituted-phenyl-4-nitrobenzenesulfonates (5a-5f) with N3- ion have been measured spectrophotometrically. The reactions of 4a-4f proceed through S-O and C-O bond fission pathways competitively. Fraction of the S-O bond fission decreases rapidly as the substituent X in the benzenesulfonyl moiety changes from an electron-withdrawing group to an electron-donating group. The Hammett plots for reactions of 4a-4f are linear with ρX=1.87 and 0.56 for the S-O and C-O bond fission, respectively. The fact that the substituent X is further away from the reaction site of the C-O bond fission than that of the S-O bond fission is one reason for the smaller ρX value. The nature of the reaction mechanism (i.e., a stepwise mechanism in which expulsion of the leaving group occurs after the rate-determining step) is also responsible for the smaller ρX value obtained from the C-O bond fission. The Bronsted-type plot for the reactions of 5a-5f is linear with βlg=-0.63, which is typical for reactions reported previously to proceed through a concerted mechanism. Effects of substituents X and Y on regioselectivity and reaction mechanism are discussed in detail.
- Moon, Ji-Hyun,Kim, Min-Young,Han, So-Yeop,Um, Ik-Hwan
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p. 1360 - 1365
(2015/07/15)
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- Nitropyrazoles 15.* Synthesis and some transformations of 1-(2,4-dinitrophenyl)-4-methyl-3,5-dinitropyrazole
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The method for preparation of 1-(2,4-dinitrophenyl)-4-methyl-3,5- dinitropyrazole has been developed. Due to the larger CH-acidity of 4-Me-group compared to 1,4-dimethyl-3,5-dinitropyrazole, 1-(2,4-dinitrophenyl)-4-methyl-3, 5-dinitropyrazole is capable of reacting with substituted benzaldehydes to afford 4-[(E)-2-arylvinyl]-1-(2,4-dinitrophenyl)-3,5-dinitropyrazoles. Under the action of nucleophiles, dinitrophenyl group is detached from the former compounds leading to previously unknown N-unsubstituted 4-[(E)-2-arylvinyl]-3,5- dinitropyrazoles.
- Zaitsev,Vatsadze,Dalinger,Kachala,Nelyubina,Shevelev
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p. 2109 - 2117
(2011/01/11)
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- Nanoparticles and Method to Control Nanoparticle Spacing
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Disclosed herein are novel nanoparticles, particularly metal nanoparticles, such as gold nanoparticles. According to one embodiment of a method disclosed herein nanoparticles are functionalized via ligand exchange reactions. Also disclosed is a method for controlling nanoparticle spacing to produce nanoparticle arrays having defined spacing. Such nanoparticles and arrays thereof are particularly useful in nanoelectronics, nanophotonics, catalysis, sensors, and biotaggents.
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- Ph3P/Br2/n-Bu4NNO2 as an efficient system for the preparation of N-nitrosamines and azides
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The combination PPh3/Br2/n-Bu4NNO2 was developed as a new reagent system for the efficient preparation of N-nitrosamines and azides from the corresponding amines and hydrazine derivatives, respectively, at 0 °C to room temperature, in excellent yields.
- Iranpoor, Nasser,Firouzabadi, Habib,Nowrouzi, Najmeh
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p. 4242 - 4244
(2008/09/20)
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- A mild dehydrazination reaction of arylhydrazines using nitric oxide in the presence of oxygen
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A new dehydrazination reaction of arylhydrazines using nitric oxide and oxygen as a mild nitrosating agent is described. Taking advantage of non-aqueous and non-acidic medium appears to cause this novel selectivity as a counterpart of the azide synthesis by the conventional methods. The generally and reaction mechanism were also investigated.
- Matsuya, Yuji,Itoh, Takashi,Nagata, Kazuhiro,Ohsawa, Akio
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p. 15701 - 15710
(2007/10/03)
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- Kinetics and mechanism of the reaction of nitrous acid with 2,4-dinitrophenylhydrazine
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Arylhydrazines react with excess nitrous acid to form mixtures of the diazonium ion and aryl azide. By use of the weakly basic 2,4- dinitrophenylhydrazine (DNP), pKa = 1.55, information about the mechanism of the diazotisation reaction has been obtained. Three successive stages can be observed. The initial reaction consists of parallel nitrosations by N2O3 and NO+ of the free base DNP at the terminal nitrogen. This is followed by a stage with the rate independent of [HNO2], almost certainly a tautomerisation, probably to form ArN=NNHOH and ArNHN=NOH. The former is converted to ArN3 while the latter undergoes a further electrophilic nitrosation by NO+ of a conjugate base species to yield a di-N,N′-nitrosoarylhydrazine, a precursor to the diazonium ion.
- Bernheim, Pierre,Dobos, Agnes,Doherty, Anne M. M.,Haine, Neil,Stedman, Geoffrey
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p. 275 - 280
(2007/10/03)
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- 5-Imino-1,4,5,6-tetrahydro-1,2,3,4-tetrazines Formed from 5-Alkylidene-4,5-dihydro-1H-tetrazoles and Electrophilic Azides
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The electrophilic azides 1 react with the 5-alkylidenedihydrotetrazoles 8 already at low temperatures to produce high yields of the novel 5-iminotetrahydro-1,2,3,4-tetrazines 10 besides molecular nitrogen.The configurations of (Z)-10a, (E)-10c, (Z)-10d, a
- Quast, Helmut,Regnat, Dieter,Balthasar, Juergen,Banert, Klaus,Peters, Eva-Maria,et al.
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p. 409 - 416
(2007/10/02)
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- REACTIVITY OF NUCLEOPHILES IN DIMETHYL SULFOXIDE AND ITS COMPARISON WITH NUCLEOPHILIC REACTIVITY IN PROTIC MEDIUM
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Reactions of 2,4-dinitrophenyl acetate and 2,4-dinitrofluorobenzene as model substrates with 12 nucleophiles have been studied in dimethyl sulfoxide.The rate constants obtained have been discussed with regard to the nucleophilic reactivity differences in dimethyl sulfoxide and protic solvents inclusive of the different manifestations of the charge of nucleophiles.The applicability of an earlier-suggested correlation equation to the data obtained has been verified.The reaction medium markedly affects the reactivity of nucleophiles, the effect of charge being substantially greater in aprotic solvents (electrostatic interaction) than in protic ones (solvation).In spite of these differences the correlation with application of an empirical nucleophilicity scale suggested earlier is satisfactory, the regression coefficients obtained reflect changes in the nature of medium.
- Zima, Vitezslav,Pytela, Oldrich,Kavalek, Jaromir,Vecera, Miroslav
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p. 2715 - 2720
(2007/10/02)
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- Micellar Catalysis of Organic Reactions. XXVI SNAr Reactions of Azide Ions
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The azidodehalogenation of a number of aromatic compounds has been studied in the presence of micelles of cetyltrimethylammonium bromide (ctab).The variation of the observed rate of reaction with ctab concentration has been treated by using the model of R
- Broxton, Trevor J.,Christie, John R.,Chung, Roland P.-T.
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p. 855 - 864
(2007/10/02)
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- A STUDY OF NUCLEOPHILICITY IN SELECTED SYSTEMS
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Kinetic studies have been carried out of the reactions of 15 nucleophiles with 2,4-dinitrophenyl acetate and 14 nucleophiles with 2,4-dinitrofluorobenzene in 52percent (w/w) methanol at 25 deg C.The rate constant values obtained and literature data have been treated by the factor analysis.It has been found that the description of nucleophilicity at least needs two factors.The nucleophiles studied are divided into two groups (ionic and nitrogen-containing ones).In each group, the nucleophilic properties are affected by linear combination of both factors.
- Zima, Vitezslav,Pytela, Oldrich,Vecera, Miroslav
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p. 814 - 821
(2007/10/02)
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- AZIDE SYNTHESIS WITH STABLE NITROSYL SALTS
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Aryl and acyl hydrazines were converted to azides in excellent yields by an equimolar amount of nitrosyl terafluoroborate or nitrosyl sulfate.
- Pozsgay, Vince,Jennings, Harold J.
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p. 5091 - 5092
(2007/10/02)
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- Facile One-Pot Synthesis of 2,1,3-Benzoxadiazole N-Oxide (Benzofuroxan) Derivatives Under Phase-Transfer Catalysis
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Several 2,1,3-benzoxadiazole N-oxide (benzofuroxan) derivatives are synthesized from the corresponding o-chloronitrobenzenes in a one-pot operation by stirring with sodium azide in dichloroethane in the presence of benzyl tributylammonium bromide as a pha
- Ayyangar, N. R.,Madan Kumar, S.,Srinivasan, K. V.
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p. 616 - 618
(2007/10/02)
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- FACILE SYNTHESIS OF AZIDES: CONVERSION OF HYDRAZINES USING DINITROGEN TETROXIDE
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Various hydrazines such as aryl-, carbonyl-, and sulfonylhydrazine were reacted with dinitrogen tetroxide to give the corresponding azides in excellent yields under mild conditions at low temperature (-20 to ca.-40 deg C) in acetonitrile.
- Kim, Yong Hae,Kim, Kweon,Shim, Sung Bo
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p. 4749 - 4752
(2007/10/02)
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- Pyrolysis of Aryl Azides. VII. Interpretation of Hammett Correlations of Rates of Pyrolysis of Substituted 2-Nitroazidobenzenes
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Rates and products of pyrolysis have been obtained for ten 2-nitroazidobenzenes with 4- or 5-substituents.Rate data at 100 deg C are correlated with Hammett constants of the 4- and 5-substituents, with respect to both the azido (A) and nitro (N) reaction
- Dyall, Leonard K.
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- KINETICS OF THE AZIDIZATION OF 2,4-DINITROHALOGENOBENZENES WITH TETRAETHYLAMMONIUM AZIDE IN ACETONITRILE AND MIXED ACETONITRILE-DIOXANE SOLVENT
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The kinetics of the reaction of 2,4-dinitrohalogenobenzenes (chlorine, bromine, and iodine derivatives) with tetraethylammonium azide in acetonitrile and in a mixed acetonitrile-dioxane solvent (80 vol. percent dioxane) were studied.It was established tha
- Sinev, V. V.,Plokhikh, G. V.
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p. 1973 - 1978
(2007/10/02)
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- KINETICS OF THE REACTION OF 2,4-DINITROCHLOROBENZENE WITH TETRAETHYLAMMONIUM AZIDE IN THE ACETONITRILE-DIOXANE BINARY SOLVENT SYSTEM
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The kinetics of the azidization of 2,4-dinitrochlorobenzene with tetraethylammonium azide in the acetonitrile-dioxane binary solvent system (0-85 vol. percent of dioxane) were studied in the range of 293-313 deg K.An analysis of the obtained results was m
- Sinev, V. V.,Plokhikh, G. V.
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p. 1978 - 1982
(2007/10/02)
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- Macrocyclic Quaternary Ammonium Salts, IV. Catalysis of Nucleophilic Aromatic Substitutions by Azide as Nucleophile
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The macrotricyclic ammonium salt 2 indeed catalyzes the bimolecular nucleophilic substitution of the halonitroarenes 3 - 7 by azide.The kinetic analysis supports the view that azide anion is included into the molecular cavity of the anion host 2 prior to
- Schmidtchen, Franz P.
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p. 725 - 731
(2007/10/02)
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- Nucleophilic Aromatic Substitution promoted by Lipophilic Quaternary Onium Salts under Phase-transfer Conditions and in Low Polarity Anhydrous Solvents. A Kinetic Study
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A kinetic study of aromatic nucleophilic substitutions by N3(1-) and SCN(1-) has been carried out under phase-transfer catalysis (p.t.c.) conditions and in anhydrous chlorobenzene in the presence of hexadecyltributylphosphonium azide and thiocyanate.Under p.t.c. conditions, reactions follow a pseudo-first-order kinetic equation, and kobs is linearly related to the nucleophile concentration in the organic phase.In most reactions, the rate-determining step is attack by the nucleophile on the substrate.However in a few cases the process is controlled by diffusion ofthe anions through the interface.Passing from p.t.c. conditions to chlorobenzene solution leads to 5-7- and 2-3-fold increases in reaction rates with N3(1-) and SCN(1-), respectively.This behaviour is analogous to that observed in the aliphatic series, and is probably due to the limited number of water molecules accompanying the anions in the organic phase under p.t.c. conditions.Nucleofugicity scales are related to the polarizability of the nucleophile, and with N3(1-) and SCN(1-) they are F>>Br>=I>=Cl and Br>I>F>=Cl, respectively.Reaction products, including those derived from successive decomposition of N3 and SCN groups, have been identified.
- Landini, Dario,Maia, Angelamaria,Montanari, Fernando
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p. 461 - 466
(2007/10/02)
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- Micellar Catalysis of Organic Reactions. IX. The Reaction of Sodium Azide with Activated Aromatic Halides and the Subsequent Decomposition of the Initially Formed Aryl Azide
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The effect of micelles of cetyltrimethylammonium bromide on the SNAr reaction of azide ions with 1-halogeno-2,4-dinitrobenzenes and on the subsequent decomposition of the aryl azide product has been measured.The nucleophilic aromatic substituti
- Broxton, Trevor J.,Jakovljevic, Anton C.
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p. 2557 - 2560
(2007/10/02)
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- REACTION OF AROMATIC COMPOUNDS WITH NUCLEOPHILIC REAGENTS IN LIQUID AMMONIA. II. NUCLEOPHILIC SUBSTITUTION IN NITROHALOGENO AND POLYFLUORINATED AROMATIC COMPOUNDS
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The possibility of aromatic nucleophilic substitution in liquid ammonia was investigated for the case of the reaction of p-nitrochlorobenzene, 2,4-dinitrochlorobenzene, hexafluorobenzene, bromopentafluorobenzene, pentafluorobenzene, and octafluoronaphthalene with a series of charged nucleophiles (potassium hydroxide and sulphite, alcoholates, sodium azide, thiophenolate, phenolate, and sulfide) at -70 to -33 deg C.It was shown that alkyl ethers of p-nitrophenol, phenyl p-nitrophenyl sulfide, 2,4-dinitrophenyl azide, polyfluorinaqted phenols, and their ethers can be obtained with good yields.Comparisons of the results with published data on the rate of the same reactions in other solvents shows that liquid ammonia is highly effective as a solvent for aromatic nucleophilic substitution reactions and in some cases makes it possible to avoid side processes.
- Shtark, A. V.,Kizner, T. A.,Shteingarts, V. D.
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p. 2051 - 2056
(2007/10/02)
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- Micellar Catalysis of Nucleophilic Aromatic Substitution Reaction Between Anionic Nucleophiles and Aromatic Substrates Containing Anionic Substituents
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Rate constants for SNAr reactions between anionic nucleophiles and aromatic substrates bearing anionic substituents in the presence and absence of micelles of cetyltrimethylammonium bromide (ctab) have been measured.Micellar catalysis of this class of reaction seems to be of the same order of magnitude as for SNAr reactions between anionic nucleophiles and dipolar organic substrates.Micellar catalysis of SNAr reactions of the ambident nitrite ion has also been studied.The magnitude of catalysis of SNAr reactions of sodium nitrite by micelles of ctab is largecompared to that for SNAr reactions of hydroxide ions or azide ions.This suggests that nitrite ion is well solubilized by micelles of ctab and some consequences of this in biological systems are discussed.The ambident behaviour of nitrite ion in aqueous micellar solution towards organic substrates seems to mirror that in methanolic solution.
- Broxton, Trevor J.
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p. 969 - 979
(2007/10/02)
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