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SNAr reactions constitute an important pathway for the synthesis of many crucial organic derivatives from polyhaloaromatic compounds. The sluggish nature of the reaction in many cases makes it a challenging pathway and limits its potential appl

The SNAr reaction between 1-chloro-2,4-dinitrobenzene and morpholine was used as a model system to study solvation effects in a series of mixtures involving imidazolium based ionic liquids. Iso-solvation regimes (i.e. a solvent composition regi

The effect of various hydrogen-bond acceptors on the reactions of 1-chloro- and 1-fluoro-2,4-dinitrobenzenes with morpholine in benzene at 30 deg C has been investigated.The reaction of the chloro substrate is not base-catalysed and the additives produced

Reactions of morpholine in dimethyl sulphoxide at unsubstituted ring positions of 1,3,5-trinitrobenzene, and phenyl 2,4,6-trinitrophenyl ether, yield anionic σ-adducts via zwitterionic intermediates. Reactions at the 1-position of phenyl 2,4,6-trinitrophe

We report an experimental study on the effect of solvents on the model SNAr reaction between 1-chloro-2,4-dinitrobenzene and morpholine in a series of pure ionic liquids (IL). A significant catalytic effect is observed with reference to the sam

We herein report an experimental and theoretical study on preferential solvation effects for the reactions of 1-fluoro and 1-chloro-2,4-dinitrobenzene towards morpholine in acetonitrile, water and mixtures of them of varying compositions. A detailed kinet

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A reaction of aromatic halides bearing electron-withdrawing groups with tertiary amines in the presence of an iridium catalyst under blue light irradiation is described. Products of the aromatic substitution of the halide by the dialkylamino fragment are

Prodrugs for targeted tumor therapies have been extensively studied in recent years due to not only maximising therapeutic effects on tumor cells but also reducing or eliminating serious side effects on healthy cells. This strategy uses prodrugs which are safe for normal cells and form toxic metabolites (drugs) after selective reduction by enzymes in tumor tissues. In this study, prodrug candidates (1-36) containing nitro were designed, synthesized and characterized within the scope of chemical experiments. Drug-likeness properties of prodrug candidates were analyzed using DS 2018 to investigate undesired toxicity effects. In vitro cytotoxic effects of prodrug canditates were performed with MTT assay for human hepatoma cells (Hep3B) and prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) as healthy control. Non-toxic compounds (3, 5, 7, 10, 12, 15, 17, 19 and 21–23), and also compounds (1, 2, 5, 6, 9, 11, 14, 16, 20 and 24) which had low toxic effects, were selected to examine their suitability as prodrug canditates. The reduction profiles and kinetic studies of prodrug/Ssap-NtrB combinations were performed with biochemical analyses. Then, selected prodrug/Ssap-NtrB combinations were applied to prostate cancer cells to determine toxicity. The results of theoretical, in vitro cytotoxic and biochemical studies suggest 14/Ssap-NtrB, 22/Ssap-NtrB and 24/Ssap-NtrB may be potential prodrug/enzyme combinations for nitroreductase (Ntr)-based prostate cancer therapy.

Synthesis, temperature-dependent NMR structure investigation and utilization of a new, stable and easily accessible aryl-diadamantylphosphine ligand family is reported. The bulky and electron-rich phosphorus center of the ligand enhances the catalytic activity of palladium in cross-coupling reactions of sterically demanding ortho-substituted aryl halides. In our study, we demonstrated the synthetic applicability of the new phosphine ligands in Buchwald-Hartwig and tosyl hydrazone coupling reactions.

In the presence of a bimetallic Pd/Cu system with 1,10-phenanthroline as the ligand and either air or N-methylmorpholine N-oxide as the oxidant, electron-deficient benzoic acids undergo oxidative decarboxylative coupling with unprotected amines. This operationally simple aniline synthesis is widely applicable with respect to the amine and gives good yields, even on multigram scale. The orthogonality of this reaction to other Pd-catalyzed cross-couplings allows the concise synthesis of multisubstituted arenes by sequential C?C, C?Cl, and C?N functionalizations. Mechanistic investigations suggest the intermediacy of a hypervalent Pd species.

Rising concern for environment hazards resulting from the use of volatile organic compounds (VOCs) is prompting many chemists to use “green” solvents like water, polyethylene glycol, ionic liquids and deep eutectic solvents (DES). With a few notable exceptions, many of these processes still need to use volatile organic solvents for the workup and isolation of products. In the present report, we demonstrate a “zero VOC” protocol which eliminates the need to use organic solvents for any stage of the reaction. As a proof of concept, nucleophilic aromatic substitution reactions of 1-halo-2,4-dinitrobenzene with secondary amines were carried out in deep eutectic solvents. The reaction workup involved the addition of water for separating the product from the DES. Evaporation of water led to recovery of the DES, which exhibited good recyclability. The reaction in deep eutectic solvents was much faster than that in many other solvents, as confirmed by the kinetic studies. An attempt was made to elucidate the origin of this rate enhancement based on analysis activation parameters and correlation with the polarity parameters. The results show that use of deep eutectic solvents can take chemists a step closer towards the “zero VOC” synthetic strategy.

Abstract: Deep eutectic solvent (DES)/lipase catalyzed efficient synthesis of N-aryl amines from electron deficient aryl chlorides and amines at ambient temperature is reported. Its significant features include excellent yields of products, use of biodegradable, non-toxic and recyclable catalysts, thereby avoiding toxic metal catalyst/solvents making these protocols environmentally benign. Graphical Abstract: [Figure not available: see fulltext.].

An immobilized Pd nanoparticle on silica-starch substrate (PNP-SSS) is introduced as an efficient heterogeneous catalyst in Pd-catalyzed Buchwald–Hartwig C–N cross coupling reaction. A range of aryl amines were synthesized using reaction of aryl halides (chloride, bromide and iodide) and amines using PNP-SSS catalyst in good to excellent yields. The PNP-SSS catalyst shows high catalytic activity in C-N bond formation reaction and it is reusable in this reaction at least for five times without significant decreasing in its catalytic activity.

Taking advantage of Pd(OAc)2-catalyzed dinitration reactions with Bi(NO3)3·5H2O in trifluoroethanol (TFE) and trifluoroacetic acid (TFA), we have developed an efficient and practical method for the synthesis of secondary dinitro-aromatic amines. The products could be applied to the preparation of 5-amine-N-methyl-benzimidazolone, the azo-dyes, economic advantages. The method has also been expanded to the dinitration reaction of some tertiary aromatic amines.

The supported palladium on phosphine-functionalized magnetic nanoparticles (Pd-PFMN) was found to be an efficient magnetically separable catalyst for the Buchwald-Hartwig amination reaction (BHAR) under solvent-free conditions. All of the reactions in the presence of Pd-PFMN catalyst afforded the corresponding products in good to excellent yields. The catalyst can be easily separated from the reaction mixture using an external magnetic field, and it can be reused at least five cycles without significant loss in its initial catalytic activity.

A kinetic study is reported for SNAr reactions of 1-(Y-substituted-phenoxy)-2,4-dinitrobenzenes (1a-1h) with amines in MeCN. The plots of pseudo-first-order rate constant versus amine concentration curve upward, indicating that the reactions are catalyzed by a second amine molecule. The Br?nsted-type plots for the reaction of 1-(4-nitrophenyl)-2,4- dinitrobenzene (1a) with secondary amines are linear with βnuc = 1.10 and 0.85 for the uncatalyzed and catalyzed reactions, respectively, while the Yukawa-Tsuno plots for the reactions of 1a-1h with piperidine result in excellent linear correlations with ρY = 1.85 and r = 0.27 for the uncatalyzed reaction and ρY = 0.73 and r = 0.23 for the catalyzed reaction. The catalytic effect decreases with increasing amine basicity or electron-withdrawing ability of the substituent Y in the leaving group. Activation parameters calculated from the rate constants measured at five different temperatures for the catalyzed reaction of 1a with piperidine are ΔH? = 0.38 kcal/mol and ΔS? = -55.4 cal/(mol K). The catalyzed reaction from a Meisenheimer complex (MC ±) is proposed to proceed through a concerted mechanism with a cyclic transition-state rather than via a stepwise pathway with an anionic intermediate, MC-. Deuterium kinetic isotope effects provide further insight into the nature of the concerted transition state.

The reactions of the title compounds with phenoxides, secondary alicyclic (SA) amines, and pyridines, in 44 wt% ethanol-water, at 25°C and an ionic strength of 0.2 M, were subjected to kinetic and product studies. From analytical techniques (HPLC and NMR), two pathways were detected (nucleophilic attack at the phosphoryl center and at the C-1 aromatic carbon) for the reactions of all the nucleophiles with the phosphate (2) and for the pyridinolysis of the thionophosphate (1). Only aromatic nucleophilic substitution was found for the reactions of 1 with phenoxides and SA amines. For the dual reactions, the nucleophilic rate constants (kN) were separated in two terms: documentclass{article}usepackage{amssymb} pagestyle{empty}begin{document}k-{rm N}^{rm P}end{document} and documentclass{article}usepackage{amssymb}pagestyle{empty}begin{document}k-{ rm N}^{{rm Ar}}end{document}, which are the rate constants for the corresponding electrophilic centers. The absence of a break in the Bronsted-type plots for the attack at P is consistent with concerted mechanisms. The Bronsted slopes, βAr 0.32-0.71, for the attack at the aromatic C-1, are in agreement with stepwise mechanisms where formation of a Meisenheimer complex is the rate-determining step. 2013 Wiley Periodicals, Inc. Int J Chem Kinet 45: 202-211, 2013 Copyright

Pseudo-first-order rate constants (kobsd) have been measured spectrophotometrically for nucleophilic substitution reactions of 1-X-2,4-dinitrobenzenes (1a-d, X = F, Cl, Br, I) with various primary and secondary amines in MeCN and H2O

The 2,4-dinitrophenoxy derivatives 12-16 and the 5-nitro-2-pyridyloxy derivatives 18-22 were prepared. The products were identified by elemental analysis, IR, and NMR. The reaction of 12-16 and 18-22 with morpholine as nucleophile in CH3CN occu

The viability of the oxidative alkylamination process for the derivatization of electron-deficient carboaromatics has been investigated. 1,3-Dinitrobenzene, 1-nitronaphthalene, and 1,5- and 1,8-dinitronaphthalenes have shown to react with a wide range of alkylamines in the presence of an oxidant (KMnO4, AgMnO4, AgPy2MnO4) to give access to the corre sponding N-alkyl-nitroarenamines in moderate to good yields. Nitroarenes are more reactive than azines towards alkylamines.

(Chemical Equation Presented) A kinetic study is reported for nucleophilic substitution reactions of 2,4-dinitro-1-fluorobenzene (DNFB) with a series of secondary amines in MeCN and H2O at 25.0°C. The reaction in MeCN results in an upward curva

This paper details new copper-catalyzed electrophilic amination reactions of diorganozinc reagents using O-benzoyl hydroxylamines as electrophilic nitrogen sources that may be accessed in one step. Simple and functionalized aryl, heteroaryl-, benzyl, n-alkyl, sec-alkyl, and tert-alkyl nucleophiles couple with R2NOC(O)Ph and RHNOC(O)Ph reagents in the presence of catalytic quantities of copper salts to provide tertiary and secondary amines, respectively, in generally good yields. In many cases, the product may be isolated analytically pure after a simple extractive workup. The amination process is shown to tolerate a significant degree of steric demand. The amination of nominally unreactive Caryl-H bonds via a sequential directed ortho metalation/transmetalation/catalytic amination reaction sequence is detailed. The direct Cu-catalyzed amination of Grignard reagents using cocatalysis by ZnCl2 is described.

Three series of benzimidazole N-oxide derivatives were developed and were examined for their activity against trypanosomatid parasites (Trypanosoma cruzi and Leishmania spp.). 2H-Benzimidazole 1,3-dioxides displayed remarkable in vitro activities against

(Chemical Equation Presented). The copper-catalyzed electrophilic amination of functionalized diarylzinc reagents with O-acyl hydroxylamines allows for the preparation of functionalized tertiary arylamines in high yields, and is noteworthy for the mild re

Useful yields are achieved in the regioselective direct formation of anilines and aromatic amides through hydrogen nucleophilic aromatic photosubstitution of m-dinitrobenzene with primary amines and amides, promoted by fluoride anion.

Twenty-two 2,4-dinitroanilines were synthesised and their pK(a) values were determined. The 2,4-dinitroanilines and their protonated forms were studied by 15N NMR spectroscopy. The relations between the 15N NMR chemical shifts and the pK(a) values of the 2,4-dinitroanilines and their salts were found to be linear. The deprotonation reaction of N-methyl-2,4- dinitroanilines and N-methyl-2,4,6-trinitroaniline by MTBD was successful only for the latter and yielded protonated MTBD molecule and the anion in which the electrons are strongly delocalised. The kinetic parameters of the 2,4-dinitroanilines in reactions with hydroxide ions in mixed solvent DMSO:water (95:5, v/v) were determinated and discussed. (C) 2000 Elsevier Science B.V.

The use of chemical probes for the characterization of chemical properties was explored for completely non-aqueous aprotic binary solvent mixtures. The Dimroth-Reichardt ET(30) betaine dye, 4-nitrophenol, 4-nitroanisole, 4-nitroaniline and N,N-

The kinetics of the reactions of 1-fluoro-2,4-dinitrobenzene with morpholine and piperidine were studied at 25°C in several binary solvent mixtures of the polar aprotic hydrogen bond acceptor solvent + chloroform or dichloromethane type, which, in some ca

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The rates of morpholine-desulfonylation of 2,4-dinitrophenyl-4'-substituted phenylsulfones (1-6: aryl = 4-Y-C6H4, Y = H, CH3, OCH3, Br, Cl and NO2) have been measured in methanol at different temperatures (25 deg C-40 deg C) and the activation parameters were calculated.A good Hammett correlation was obtained with ρ values of 0.43-0.75.The plot ΔH(excit.) versus ΔS(excit.) gave an isokinetic temperature at 339 deg K.

The reactions of 2,6-dinitrophenyl phenyl ether and of 6-methyl-2,4-dinitrophenyl phenyl ether with piperidine, morpholine, butylamine and benzylamine are base catalysed in both dimethyl sulfoxide and acetonitrile.The reaction of 2-phenoxy-3,5-dinitropyridine with aniline is base catalysed in acetonitrile, but not in dimethyl sulfoxide, and its reactions with piperidine, morpholine, butylamine and benzylamine in acetonitrile are also base catalysed.The results are discussed in terms of the prevailing theories of aromatic nucleophilic substitution reactions.Increasein activation of the substrate increases the k2/k-1 and k3/k-1 ratios.For ortho substituents, steric/stereoelectronic effects in the transition state reduce both k-1, the rate constant for the decomposition of the zwitterionic intermediate to reactants, and k2 and k3, the rate constants for its decomposition to products.When the substrate has two ortho groups the different behaviour of primary and secondary amines found with substrates containing only one ortho-nitro group is not observed.

Aminolysis of O-(2,4-dinitrophenyl) derivatives of benzophenone oxime and 4'-bromobenzophenone oxime with piperidine and morpholine has been studied in benzene at 35 +/- 0.1 deg C.These reactions show inverse temperature effect and third order dependence on amine.The results have been explained on the basis of electrophilic catalysis by homoconjugated acids.It has been concluded from these results that third order dependence on cyclic amines and second order on noncyclic amine is usually noted for aminolysis reactions in benzene.

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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.

Kinetics of hydrolysis of N-(2,4-dinitrophenoxy)-9,10-dihydroanthracene-9,10-endo-α,β-succinimide with hydroxide ion, piperidine, cyclohexylamine and morpholine has been studied in 1:4 aqueous acetonitrile at 35 +/- 0.1 deg C.Evidence for base catalysis has been obtained for reactions with hydroxide ion and piperidine.Ralative ease of detachment of the nucleofuge from the intermediate complex seems to account for the absence of base catalysis in the case of morpholine and cyclohexylamine.

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.

The kinetics of the reactions of 1-chloro-2,4-dinitrobenzene and 1-fluoro-2,4-dinitrobenzene with piperidine, butylamine, and morpholine in the presence of β-cyclodextrin (CD) was studied.There is an increase in the observed rate constant for the reactions of the first two amines at pH AH when CD is added, but there is no change in the rate for these two reactions at pH > pKAH and for the reaction of morpholine either at pH AH or at pH > pKAH.The three amines (A) as well as their conjugated acids (AH) form inclusion complexes with the CD.The association equilibrium constants for the amines are 50.3, and 17 M-1 for piperidine, butylamine, and morpholine, respectively.Part of the observed catalysis is attributed to the fact that the amines and the complexed amines (ACD) react with the substrate at similar rates and at constant pH, the ratio (A + ACD)/(AH + AHCD) increases with the concentration of CD.Besides that, the complexed substrates react with the complexed amines at faster rates than that of the free substrate with the free amine.The latter reaction is not detected in the reactions at high pH and in the reactions of morpholine.

The N-oxides of N-(2,4-dinitrophenyl)-piperidines and -morpholine undergo thermal rearrangement to the substituted hydroxylamines.The kinetics of the rearrangement were studied in aprotic solvents at four or five temperatures.Steric and polar factors have

The kinetics of the reactions of 1-chloro- and 1-fluoro-2,4-dinitrobenzene with morpholine have been studied in dimethyl sulphoxide, dimethylformamide, and nitromethane.The results confirm that the decomposition of the intermediate to products by the uncatalysed path takes place by a unimolecular mechanism.The kinetics of the reactions of 2,4-dinitroanisole with n-butylamine and piperidine in dipolar aprotic solvents have been determined.They show that when primary amines are the nucleophiles, reaction by the uncatalysed path does not occur by the unimolecular mechanism, but by the specific base-general acid (SB-GA) route.The reactions in dimethyl sulphoxide give another example of secondary amines reacting by a base catalysis mechanism whereas the corresponding reaction of a primary amine of the same basicity is not base-catalysed.In a search for electrophilic catalysis the effects of lithium, trialkylammonium, and tetraalkylammonium ions on the reactions of piperidine with 2,4-dinitroanisole and of morpholine with 2,4-dinitrophenyl phenyl ether in dimethyl sulphoxide were investigated.No catalysis was found and a tentative reason is given.When aniline reacts with 2,4,6-trinitrophenyl methyl ether in dimethyl sulphoxide, 82percent of the reaction occurs at the methyl carbon atom, and when the substrate is 2,4,6-trinitrophenyl phenyl ether the reaction is not base-catalysed.The first two observations of the change from base-catalysed to uncatalysed aromatic nucleophilic substitution reactions brought about by a change from protic to dipolar aprotic solvent are recorded.

The reaction of 1-chloro-2,4-dinitrobenzene with aniline in acetonitrile is catalysed by R4NY where Y is Cl, Br, I, or toluene-p-sulphonate, but not by 1,4-diazabicyclooctane (DABCO).When the nucleophile is changed to n-butylamine or morpholine, addition of tetraethylammonium chloride has only a small effect; the reactions of all three nucleophiles are not catalysed by tetraethylammonium perchlorate.The reaction of 1-fluoro-2,4-dinitrobenzene with aniline is strongly catalysed by tetraethylammonium chloride, to a lesser extent by the bromide and toluene-p-sulphonate and also by trimethylamine hydrochloride, but not by tetraethylammonium perchlorate.The reactions of morpholine with 1-fluoro-2,4-dinitrobenzene and piperidine with 2,4-dinitrophenyl phenyl ether are not catalysed by amine salts.The results are consistent with the formation and stabilisation of the intermediate formed in aromatic nucleophilic substitution reactions by the anions of the salts, when the nucleophile is aniline

For base-catalysed aromatic nucleophilic substitution reactions in benzene, catalysis by added base is observed irrespective of whether the catalyst is a stronger or a weaker base than the nucleophile.In acetonitrile, catalysis is only observed if the catalyst has either approximately the same strength or is a stronger base than the nucleophile.These observations are shown to indicate a difference in the mechanism of catalysis in the two solvents.