Kinetics of the Reactions of 4-Nitrochlorobenzene with Substituted Phenols in the Presence of Potassium Carbonate

The kinetics of 4-nitrochlorobenzene (4-NCB) reactions with substituted phenols in the presence of potassium carbonate in N,N-dimethylacetamide was studied. Depending substituents, the reactivity of the phenols is changed in the series 3-NO₂> 4-Cl > H > 4-Br > 3-CH₃> 3-NH₂, which is consistent with the series of their acidity. The reaction rates satisfactorily correlate with the pK _avalues of the corresponding substituted phenols. Based on kinetic data (first-order and zero-order reactions with respect to phenol and 4-NCB, respectively, and the consistency of the reactivity and acidity of substituted phenols), the deprotonation of phenols is considered as the rate-determining step of the overall reaction under the test conditions. A reaction scheme was proposed for the synthesis of diaryl ethers in the presence of potassium carbonate. It involves a heterogeneous step of phenol deprotonation, which takes place on the surface of potassium carbonate, and a homogeneous step of the interaction of potassium phenolates with 4-NCB. Under the reaction conditions, the resulting bicarbonate decomposes with the formation of potassium carbonate and with the release of carbon dioxide and water.     

Synthesis of Aryl Ethers by Nonactivated Aromatic Nucleophilic Substitution Reactions

The results of a kinetic study of model reactions between substituted phenols and bromobenzene in the presence of potassium carbonate and the copper(I) chloride–8-hydroxyquinoline catalytic complex in N,N-dimethylformamide are presented. The reactions were found to obey a first-order rate law. Both orbital and charge interactions should be taken into account in a consideration of the effect of the structural characteristics of reactants on the rate of reaction. The kinetics of substitution of the phenoxide anion for an aromatically bound halogen atom in activated and nonactivated systems with the formation of practically valuable aryl ethers were comparatively studied. The results presented provide an opportunity to distinguish the common features and regularities of activated and nonactivated aromatic substitution in the test systems.     

An organoiron approach to thyroid hormone analogues

An approach to thyroid hormone analogues was proposed involving sequential substitution of cationic cyclopentadienyl(1,4-dichlorobenzene)iron(II) complexes with phenoxide/thiophenoxide and hydroxide/amine, followed by decomplexation. Although the selectivity for monosubstitution with phenolates and thiophenolates was poorer than previously observed, it was often possible to control the reaction with sterically less demanding phenolates of intermediate nucleophilicity. The subsequent introduction of a polar substituent into the monosubstituted product was successful with amine nucleophiles. A modified approach, based on the reverse order of substitution was also attempted. Whereas clean monosubstitution with hydroxide/hydroxide equivalents was unsuccessful, cyclopentadienyl(N-alkyl-1-chloro-4-aminobenzene)iron(II) complexes could be prepared in fair yields and further substituted with nucleophiles such as thiophenolates.     

Single‐Electron Transfer in σ‐Complexation Reactions of 2,6‐Dimethoxy‐3,5‐dinitropyridine with Para‐X‐phenoxide Anions in Aqueous Solution

Second‐order rate constants have been measured spectrophotometrically for reactions of 2,6‐dimethoxy‐3,5‐dinitropyridine 1 with 4‐X‐substituted phenoxide anions (X = OMe, Me, H, Cl, and CN) 2a–e in aqueous solution at various temperatures. The effect of phenoxide substituents on the reaction rate was examined quantitatively on the basis of kinetic measurements, leading to nonlinear correlations of Δ^≠H and Δ^≠S with Hammett's substituent constants (σ). Each Hammett plots exhibits two intersecting straight lines for the reactions of 1 with the phenoxide anions 2a–e , whereas the Yukawa–Tsuno plots for the same reactions are linear. The large negative ρ values (?4.03 to ?3.80) obtained for the reactions of 1 with the phenoxide anions possessing an electron‐donating group supports the proposal that the reactions proceed through a single‐electron transfer mechanism.     

Nucleophilicities of Para‐Substituted Phenoxide Ions in Water and Correlation Analysis

Second‐order rate constants for the reactions of 2‐aryl‐4,6‐dinitrobenzotriazole 1‐oxides 1a‐d with some 4‐X‐substituted phenoxide ions 2a‐d (X = OCH₃, H, Cl, and CN) have been measured in aqueous solution at 20°C. The pK_a values for the σ‐complexation processes of a series of benzotriazole 1a‐d measured in water have been used to determine their electrophilicity parameters E according to the correlation E = –3.20 – 0.662 pK_a (F. Terrier, S. Lakhdar, T. Boubaker, and R. Goumont, J Org Chem, 2005 , 70, 6242–6253). For these reactions, plots of log k versus the electrophilicity parameters E of the benzotriazoles 1a‐d were linear, allowing to derive the nucleophilicity parameters N and s for phenoxide ions as defined by the Mayr equation log k₁ (20°C) = s (E + N) (H. Mayr, M. Patz. Angew Chem, Int Ed Engl 1994 , 33, 938–957). The N values are found to cover a range of nucleophilicity from 6.85 to 10.22, going from 4‐cyanophenoxide 2d for the least reactive ion to 4‐methoxyphenoxide 2a for the most reactive nucleophile. Good linear correlations were found between the nucleophilicity parameters N of phenoxide ions 2a‐d and the pK_a values of their conjugate acids (N = –3.05 + 1.25 pK_a) and the constants of the substituents X (N = 9.21 – 2.51).     

The preparation of N-carboalkoxypyrazoles and N-phenylpyrazoles from C(α)-dianions of carboalkoxyhydrazones and phenylhydrazones

The 1,4-dianions of C(α),N-carboalkoxyhydrazones and C(α),N-phenylhydrazones were prepared in an excess of lithium diisopropylamide (LDA). These dilithiated intermediates resulted from metalation of substituted hydrazones of several all-aliphatic cyclic ketones, aliphatic-aromatic cyclic ketones phenylacetaldehyde, and several substituted propiophenones or acetophenones. The esters utilized for Claisen-type condensations of these dianion intermediates included methyl salicylate, methyl p-hydroxybenzoate, methyl nicotinate and related materials. The condensations were followed by acid-cyclizations to give a variety of N-phenylpyrazoles and N-carboalkoxypyrazoles, most of which are new.     

2,3,8,9-Dibenzo-5,6-(substituted)benzo-1,4-dithio-7-azacyclonona-2,5,8-trienes. Synthesis and mechanistic study

5-(2-Acetamidoaryl)thianthreniumyl perchlorates reacted with potassium hydroxide in methanol at reflux giving 2,3,8,9-dibenzo-5,6-(substituted)benzo-1,4-dithio-7-azacyclonona-2,5,8-trienes 4 in 43 to 75% yields, whereas the reactions of the same compounds with sodium hydride in the absence or in the presence of dimethyl sulfate in refluxing tetrahydrofuran gave N-acetylated and N-methylated 4 in 68 to 96% and 27 to 56% yields, respectively. The mechanism of the formation of the products might be explained by a nucleophilic attack of amide ions 10, 12, and 14 at the ipso-position of the thianthrene ring. A sulfuranyl radical mechanism might be involved in these reactions.     

Electrophilic reactivities of 7-L-4-nitrobenzofurazans in σ-complexation processes: Kinetic studies and structure–reactivity relationships

The second-order rate constants (k) for reaction of 7-chloro-4-nitrobenzofurazan 1 and 7-methoxy-4-nitrobenzofurazan 2 with a series of nitroalkyl anions and several of para-substituted phenoxide anions in aqueous solution at 20 °C have been reported. On the basis of the linear novel approach recently designed by Mayr and coworkers, the electrophilicity parameters E at the C-5 position of the two nitrobenzofurazans 1 and 2 have been quantified and ranked on the comprehensive electrophilicity scale. Mayr's approach was found to correctly predict the rate constants for the addition of phenoxide anions at the C-5 position of 1 and 2 witting a factor of <2. Analysis of the kinetic measurements using Brønsted's model shows that β_nuc values remain remarkably constant for changes in the nature of the substituent and that the σ-complexation process is associated with high Marcus intrinsic barriers. In addition, satisfactory correlations between the log k_exp (k_exp values measured in this work for reactions of benzofurazans 1 and 2 with a series of phenoxide anions in aqueous solution at 20 °C) and log k_calcd (k_calcd values calculated from equation 1 using the electrophilicity parameters E of benzofurazans 1 and 2 and the previously published nucleophilicity parameters N and s_N of the phenoxide anions) with a slope very close to unity have been obtained and discussed.     

The MNDO-PM3 study of the mechanism of nucleophilic substitution of the phenoxide anion for the nitro group in 1,3,5-trinitrobenzene and 2,4,6-trinitrotoluene in the gas phase and in polar solvents

The semi-empirical quantum chemical MNDO-PM3 calculations of the enthalpies of formation of Meisenheimerortho- andipso--complexes of 1,3,5-trinitrobenzene (TNB) and 2,4,6-trinitrotoluene (TNT) with the phenoxide anion in the gas phase and in water are performed within the framework of the point dipole model. Based on the calculated heats and activation barriers to substitution of the nitro group by the phenoxyl group in TNB and TNT, the possibility of the reactions of TNB and TNT with the phenoxide anion in water is shown. These reactions in water occurvia the S_NAr mechanism involving the correspondingipso--complex as an intermediate. In the gas phase, the S_NAr mechanism is impossible, because the reaction is strongly endothermic. In the case of TNT, the exothermic reaction of elimination of a proton from the methyl group by the phenoxide anion competes with nucleophilic substitution in a polar solvent. The activation energy calculated for this exothermic reaction is 8 kcal mol^–1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 624–628, April, 1995.     

A divergent synthesis of dihydropyridazinones,N‐substituted dihydropyrazoles,and O‐substituted pyrazoles

Dihydropyridazinones 4a , 4b , N‐substituted dihydropyrazoles 5b , 5c , 5d , and O‐substituted pyrazoles 6a , 6b , 6c , 6d have been synthesized starting from spirocyclopropanepyrazole derivative 2 . Treatment of 2 with α‐chloro esters, e.g., methyl chloroacetate, ethyl chloroacetate, isopropyl chloroacetate, and tert‐butyl chloroacetate, in potassium carbonate/sodium iodide system caused ring opening and subsequent C‐ or N‐attack nucleophilic substitution to give the corresponding dihydropyridazinones 4a , 4b and N‐substituted dihydropyrazoles 5b , 5c , 5d . On the other hand, in the absence of sodium iodide, O‐substituted pyrazoles 6a , 6b , 6c , 6d were obtained from 2 via an O‐attack nucleophilic substitution. J. Heterocyclic Chem., 2011.     

Alkali Metal and Trimethylsilyl Carbamoselenothioates – Synthesis,Structure, and some Reactions

This paper describes the synthesis and some reactions of potassium, rubidium, cesium and trimethylsilyl carbamoselenothioates. The potassium salts were synthesized in 70–80 % yields by reacting the corresponding thiocarbamoyl chlorides with potassium selenide in acetonitrile. Furthermore, the rubidium and cesium salts were obtained in good yields by treating the trimethylsilyl esters with the corresponding metal fluorides. The crystal structure of acetonitrile‐solvated potassium N,N‐dimethylcarbamoselenothioate consisted of dimeric units, featuring μ‐carbamoselenothioate anions associated with potassium cations that are located on the upper and lower sides of a plane involving two opposing carbamoselenothioate groups. These heavier alkali metal salts readily reacted with alkyl halides to give both S‐ and Se‐alkyl esters. The reaction of the potassium salts with trimethylsilyl chlorides forms S‐ and Se‐trimethylsilyl carbamoselenothioates which are in equilibrium. The reaction of the salts and silyl esters with organo Group‐14 and ‐15 elements halides gave exclusively the corresponding Se‐substituted products in good yields.     

The ambident electrophilic behavior of 5‐nitro‐3‐X‐thiophenes in σ‐complexation processes

Kinetics of the reactions of 3,5‐dinitrothiophene 1 and 3‐cyano‐5‐nitrothiophene 2 with a series of parasubstituted phenoxide anions 3a–c have been investigated in aqueous solution at 20°C. Two unsubstituted electrophilic centers (C(2) and C(4)) of the two thiophenes have been identified. The Fukui functions correctly predict the C(2) and C(4) atoms as the most electrophilic centers of these electron‐deficient thiophenes 1 and 2 . Analysis of the experimental data in terms of Brønsted relationships reveals that the reaction mechanism likely involves a single‐electron transfer (SET) process. The excellent correlations upon plotting the rate constants versus the oxidation potentials E^o values is an additional evidence that reactions between thiophenes and phenoxide anions are proceeding through an initial electron transfer. It is of particular interest to note that the systems studied in this paper provide a rare example of a SET mechanism in σ‐complexation reactions. According to the free energy relationship log k = s(N + E) (Angew. Chem., Int. Ed. Engl., 1994, 33, 938–957), the electrophilicity parameters E of the C‐4 and C‐2 positions of the thiophenes have been determined and compared with the reactivities of other ambident electrophiles. On the other hand, the second‐order rate constants for the reactions of these thiophenes with the hydroxide ion has been measured in water and 50% water–50% acetonitrile and found to agree with those calculated theoretically using Mayr's equation from the E values determined in this work and from the previously published N and s parameters of OH⁻.     

The effect of <Emphasis Type="Italic">O</Emphasis>-nucleophiles structure on the features of halogen substitution in heterogeneous systems

The formation of diphenyl ether derivatives during interaction of 4-nitrochlorobenzene and substituted phenols in a heterogeneous system [DMF in the presence of potassium carbonate and iron(III) oxide] has been studied.     

Reaction of 3‐substituted and 4‐bromo‐3‐substituted isoquinolin‐1‐(2h)‐ones with propargyl bromide

Isoquinolinones were brominated using N‐bromosuccinimide in dimethylformamide at room temperature to give 4‐bromo‐3‐substituted isoquinolin‐1‐(2H)‐ones. The reaction of these isoquinolinones with propargyl bromide in the presence of anhydrous potassium carbonate yielded N and O‐alkylated products.     

Preparation of 1,2- and 1,4-dihydro derivatives of 6,7-dimethyl-2,3-diphenylquinoxaline via its dianion formed by reductive metallation

Treatment of 6,7-dimethyl-2,3-diphenylquinoxaline with sodium in tetrahydrofuran formed a monomeric dianion. The chemical behavior of this dianion was investigated by a variety of reagents. As the result, alkylation reactions gave 1,2-dihydro derivatives, while acylation reactions occured at 1,4-positions. Annulation of the pyrazine ring system was accomplished by treating the dianion with oligomethylene dichlorides, Cl(CH₂) _n Cl, n = 2–4.     

Persistent Room-Temperature Radicals from Anionic Naphthalimides: Spin Pairing and Supramolecular Chemistry

N-Substituted naphthalimides (NNIs) have been shown to exhibit highly efficient and persistent room-temperature phosphorescence from an NNI-localized triplet excited state, when the N-substitution is a sufficiently strong donor and mediates an intramolecular charge-transfer (ICT) state upon photo-excitation. This work shows that, when the electron-donating ability of the N-substitution is further increased in the presence of a carbanion or phenoxide, spontaneous electron transfer (ET) occurs and results in radical anions, verified with electron-paramagnetic resonance (EPR) spectroscopy. However, the EPR-active anion is surprisingly persistent and impervious to nucleophilic and radical reactions under anionic conditions. The stability is thought to originate from an intramolecular spin pairing between the N-donor and the NI acceptor post ET, which is demonstrated in supramolecular chemistry.     

Synthesis,crystal structures,and superoxide dismutase activity of two isostructural copper(II)–zinc(II) complexes derived from N,N′-bis(4-methoxysalicylidene)cyclohexane-1,2-diamine

Two new isostructural copper(II)–zinc(II) complexes, [CuZnLBr₂] (1) and [CuZnLCl₂] (2) (H₂L = N,N′-bis(4-methoxysalicylidene)cyclohexane-1,2-diamine), have been synthesized and characterized by elemental analyses, infrared spectroscopy, and single-crystal X-ray diffraction. Both complexes crystallize in the P-1 space group. The Cu in each complex is four-coordinate square planar with two imines and two phenolates of L. The Zn in each complex is four-coordinate tetrahedral with two phenolates of L and two halides (Br for 1 and Cl for 2). The superoxide dismutase (SOD) activity of the complexes indicates that both complexes are rudimentary models for SOD.     

Anil-Synthese. 20. Mitteilung. Über die Herstellung von Stilbenyl-Derivaten des 1,2,4,-Oxadiazols

Preparation of Stilbenyl Derivatives of 1,2,4-Oxadiazoles Schiffs bases derived from 3- and 5-(p-formylphenyl)-phenyl-1,2,4-oxadiazoles and chloroanilines are reacted with various p-tolyl substituted aromatic heterocycles in the presence of dimethylformamide and potassium hydroxide to yield the corresponding heterocyclic substituted stilbenes (‘Anil synthesis’). The reactivity of 5-[4-(chlorophenylimino-methyl)phenyl]-3-phenyl-1,2,4-oxadiazoles is very low and side reactions will predominate.     

Reactions of aniline with alkali metal diphenylketyls and dianions derived from benzophenone and Michler’s ketone

Potassium diphenylketyl and benzophenone dianion react with aniline to afford N-(diphenylmethylene) aniline. Under analogous conditions, the corresponding sodium and lithium derivatives undergo disproportionation with formation of triphenylmethanol, benzoic acid, and diphenylmethanol. The condensation of potassium and sodium bis(4-dimethylaminophenyl)ketyls and salts with Michlers ketone dianion leads to formation of N-[bis(4-dimethylaminophenyl)methylene]aniline, while lithium bis(4-dimethylaminophenyl)-ketyl and Michlers ketone dilithium salt are reduced to bis(4-dimethylaminophenyl)methanol.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 12, 2004, pp. 1836–1839.Original Russian Text Copyright © 2004 by Turaeva, Kurbatov.     

Aminoacids in the synthesis of heterocyclic systems. The synthesis of methyl 2-acetylamino-3-dimethylaminopropenoate and 2-(N-methyl-N-trifluoroacetyl)amino-3-dimethylaminopropenoate and their application in the synthesis of heterocyclic compounds

Methyl (Z)-2-acetylamino-3-dimethylaminopropenoate (3) was prepared from N-acetylglycine (1), which was converted with N,N-dimethylformamide and phosphorus oxychloride into 4-dimethylaminomethylene-2-methyl-5(4H)-oxazolone (2), followed by treatment with methanol in the presence of potassium carbonate, into 3. The compound 3 was shown to be a versatile reagent in the synthesis of various heterocyclic systems. With N-nucleophiles, such as heterocyclic amines 4, either methyl 2-acetylamino-3-heteroarylaminopropenoates 5 or fused pyrimidinoncs 6 were formed, dependent on the reaction conditions and/or heterocyclic substituents: C-nuclcophiles with an active or potentially active methylene group, such as 1,3-dicarbonyl compounds 7, 8 and 9, substituted phenols 10a,b, naphthols 11, 12a-c, and substituted coumarin 13a, afforded substituted pyranones 20 and 22, and fused pyranones 21, 23–26. The nitrogen containing heterocycles 14–19 produced pyranoazines 27–31 and pyranoazole 32. In all of these systems the acetylamino group is attached at position 3 of the newly formed pyranone ring. The orientation around the double bond for methyl (Z)-2-(N-methyl-N-trifluo-roacetyl)-3-dimethylaminopropenoate (36) was established by X-ray analysis.