Nucleophilic Aromatic Substitution Of Hydrogen Research Articles

Amination of Nitro-Substituted Heteroarenes by Nucleophilic Substitution of Hydrogen.

An open-air method for the transition metal-free direct amination of nitro(hetero)arenes by anilines is disclosed. In this methodology, an aromatic C-H bond is substituted via oxidative nucleophilic aromatic substitution of hydrogen (ONSH). Density functional theory calculations and mechanistic studies support a dianion pathway with oxidation by molecular oxygen as the rate-limiting step.

Cobalt-Catalyzed Regioselective para-Amination of Azobenzenes via Nucleophilic Aromatic Substitution of Hydrogen.

The metal-catalyzed nucleophilic aromatic substitution of hydrogen (SNArH) via coordination of the substituent on the aromatic ring to the metal catalyst, in terms of reactivity, substrate type, and reaction selectivity, complements the transition metal-catalyzed C-H functionalization that proceeds via C-H metalation but remains an elusive target. Described herein is the development of an unprecedented cobalt-catalyzed para-selective amination of azobenzenes, which is essentially a metal-promoted SNArH process as revealed by Hammett analysis, thus illustrating the concept that coordination of the substituent on the arene ring to the metal catalyst may result in electrophilic activation of the arene ring toward SNArH. This cobalt-catalyzed protocol allows the use of a variety of both aliphatic amines and anilines as aminating reagents, tolerates electronically diverse substituents of azobenzene, and furnishes the corresponding products in good yields with a regiospecific selectivity for para-amination.

Oxidative nucleophilic alkoxylation of nitrobenzenes

Oxidative nucleophilic aromatic substitution of hydrogen in nitroaromatics with potassium alkoxides is reported.

New opportunities for the synthesis of quinoxaline derivatives

Convenient methods for the synthesis of quinoxaline derivatives with the use of nucleophilic aromatic substitution of hydrogen in heteroaromatic part of molecule in conditions of the acid catalysis were elaborated. The reactions of substitution of fluorine with amines in aromatic ring of 6,7-difluoroquinoxaline with the formation of monofluoro derivatives were studied.

Synthesis of dithienoquinazolines from pyrimidines via intramolecular nucleophilic aromatic substitution of hydrogen

The possibility of intramolecular nucleophilic aromatic substitution of hydrogen in the series of 5-[2-(het)aryl-1-benzothiophen-3-yl]-pyrimidines was explored. A convenient method for the synthesis of [1]benzothieno-[3,2-f]thieno[2,3-h]quinazoline and [1]benzothieno-[3,2-f]thieno[3,2-h]quinazoline based on the developed SN H protocol was proposed. The energy parameters (width of the band gap, the energy of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbitals (LUMO)) of benzothieno[3,2-f]-thieno[2,3-h]quinazoline synthesized for the first time were determined based on the data of the absorption spectra and cyclic voltammetry.

2,2′‐Homocoupled Azine N,N′‐Dioxides or Azine N‐Oxides: CDC‐ or SNAr‐Controlled Chemoselectivity

An unprecedented Cu(OAc)2‐ and LiOtBu‐mediated homocoupling of azine N‐oxides to yield 2,2′‐azine N,N′‐dioxides is reported. This is the first instance in which copper has been used to catalyze the homodimerization reaction, especially of 2‐phenylpyridine N‐oxides. In the absence of catalytic copper, the reaction follows an alternative pathway, and instead of dioxides it yields 2,2′‐azine N‐monoxides. This latter protocol works efficiently with a range of N‐heterocyclic oxides of pyridine, 2‐phenylpyridine, quinoline and N‐aryl‐1,2,3‐triazole. It is scalable, offers high regioselectivity and gives the products in moderate to high yields. The observed chemoselectivity between the copper‐assisted and copper‐free protocols is routed through oxidative cross‐dehydrogenative coupling (CDC) and nucleophilic aromatic substitution of hydrogen (SNAr) pathways, respectively.

ChemInform Abstract: Recent Advances in the Field of Nucleophilic Aromatic Substitution of Hydrogen

AbstractReview: 72 refs.

Synthesis and evaluation of antitubercular activity of fluorinated 5-aryl-4-(hetero)aryl substituted pyrimidines

Various 5-(fluoroaryl)-4-(hetero)aryl substituted pyrimidines have been synthesized based on the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SNH) reactions starting from commercially available 5-bromopyrimidine and their antitubercular activity against Mycobacterium tuberculosis H37Rv has been explored. The outcome of the study disclose that, some of the compounds have showed promising activity in micromolar concentration against Mycobacterium tuberculosis H37Rv, Mycobacterium avium, Mycobacterium terrae, and multidrug-resistant strains isolated from tuberculosis patients in Ural region (Russia). The data concerning the ‘structure–activity’ relationship for fluorinated compounds have been discussed.

Heteroacenes Bearing the Pyrimidine Scaffold: Synthesis, Photophysical and Electrochemical Properties

AbstractA convenient synthetic route to novel 7‐substituted benzo[f]thieno[3,2‐h]quinazoline and 8‐substituted benzo[g,h]dithieno[2,3‐e:3′,2′‐j]perimidine systems, bearing the fused pyrimidine ring, has been advanced. A commercially available 5‐bromopyrimidine was used as the starting material to obtain various polycyclic systems through the sequence of nucleophilic aromatic substitution of hydrogen (the SNH reaction), Suzuki cross‐coupling and oxidative photocyclization. Evidence for the structure of benzo[g,h]dithieno[2,3‐e:3′,2′‐j]perimidines has been obtained by X‐ray crystallographic analysis. Molecular orbital calculations (DFT), as well as redox and optical measurements for all new compounds have been performed. The data show that the reported polycyclic systems have potential for use in organic electronic applications.

Synthesis, and structure–activity relationship for C(4) and/or C(5) thienyl substituted pyrimidines, as a new family of antimycobacterial compounds

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SNH) reactions proved to be a convenient method for the synthesis of C(4) and/or C(5) mono(thienyl) and di(thienyl) substituted pyrimidines from commercially available 5-bromopyrimidine. All new pyrimidines were found to be active in micromolar concentrations in vitro against H37Rv, avium, terrae, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The data for acute in vivo toxicity in mice have been obtained for these compounds which appear to be promising antitubercular agents.

Synthesis, Photophysical and Redox Properties of the D-π-A Type Pyrimidine Dyes Bearing the 9-Phenyl-9H-Carbazole Moiety.

Novel donor-π-acceptor dyes bearing the pyrimidine unit as an electron-withdrawing group have been synthesized by using combination of two processes, based on the microwave-assisted Suzuki cross-coupling reaction and nucleophilic aromatic substitution of hydrogen. Spectral properties of the obtained dyes in six aprotic solvents of various polarities have been studied by ultraviolet-visible and fluorescence spectroscopy. In contrast to the absorption spectra, fluorescence emission spectra displayed a strong dependence from their solvent polarities. The nature of the observed long wavelength maxima has been elucidated by means of quantum chemical calculations. The electrochemical properties of these dyes have been investigated by using cyclic voltammetry, while their photovoltaic performance was evaluated by a device fabrication study. The experimental and calculation data show that all of the dyes can be regarded as potentially good photosensitizers for dye-sensitized solar cells.

ChemInform Abstract: New Data on Heteroarene Thiocyanation by Anodic Oxidation of NH4SCN. The Processes of Electroinduced Nucleophilic Aromatic Substitution of Hydrogen.

AbstractPotentiostatic electrolysis of NH4SCN in an undivided cell is used to perform the anodic thiocyanation of various aromatic substrates under mild conditions.

Dithienoquinazolines – A Convenient Synthesis by the Oxidative Photocyclization of 4,5‐Dithienyl‐Substituted Pyrimidines and Their Photophysical Properties

AbstractA convenient synthetic route to novel thienoacene systems bearing a fused pyrimidine ring has been advanced. The commercially available 5‐bromopyrimidine was used as the starting material to obtain various dithienoquinazoline systems through nucleophilic aromatic substitution of hydrogen (the SNH reaction), Suzuki cross‐coupling, and oxidative photocyclization. The redox and optical properties of some of the new compounds have been investigated. The data obtained show the potential of dithienoquinazoline systems in organic electronic applications.

New data on heteroarene thiocyanation by anodic oxidation of NH4SCN. The processes of electroinduced nucleophilic aromatic substitution of hydrogen

Potentiostatic (galvanostatic) electrolysis of NH4SCN in an undivided cell under mild conditions (25°C, Pt anode, MeCN) was employed to perform the anodic thiocyanation of nitrogen-containing heterocycles with yields up to 95%. The regularities of the process are discussed, which show that it can be considered as electroinduced nucleophilic aromatic substitution of hydrogen.

Synthesis of 5-(het)aryl- and 4,5-di(het)aryl-2-(thio)morpholinopyrimidines from 2-chloropyrimidine via SN H and cross-coupling reactions

It has been shown that various combinations of nucleophilic aromatic substitution of hydrogen (SNH), SNipso and the microwave-assisted Suzuki cross-coupling reactions are a versatile method for the synthesis of 5-(het)aryl-2-(thio)morpholinopyrimidine and 4,5-di(het)aryl-2-(thio)morpholinopyrimidine derivatives. All synthesized pyrimidines were found to be active in micromolar concentrations in vitro against Mycobacterium tuberculosis H37Rv.

Synthesis and antituberculosis activity of novel 5-styryl-4-(hetero)aryl-pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and SNH reactions

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SNH) reactions proved to be a convenient method for the synthesis of 5-styryl-4-(hetero)aryl substituted pyrimidines from commercially available 5-bromopyrimidine. All intermediate 5-bromo-4-(hetero)aryl substituted pyrimidines and also the targeted 5-styryl-4-(hetero)arylpyrimidines were found to be active in micromolar concentrations in vitro against Mycobacterium tuberculosis H37Rv, avium, terrae, and multi-drug-resistant strain isolated from tuberculosis patients in Ural region (Russia). It has been found that some of these compounds possess a low toxicity and have a bacteriostatic effect, comparable and even higher with that of first-line antituberculosis drugs.

Microwave-assisted palladium-catalyzed C–C coupling versus nucleophilic aromatic substitution of hydrogen (SNH) in 5-bromopyrimidine by action of bithiophene and its analogues

5-Bromopyrimidine reacts with 2,2′-bithiophene, [2,2′:5′,2″]terthiophene and 2-phenylthiophene in the presence of a palladium catalyst to give 5-(het)aryl substituted pyrimidines due to the palladium-catalyzed aryl–aryl C–C coupling. However 5-bromo-4-(het)aryl-pyrimidines have been prepared from the same starting materials through the SNH-reaction catalyzed by a Lewis acid. Conditions for both types of reactions were optimized. All components of the reaction mixtures, including by-products, have been elucidated by gas–liquid chromatography/mass-spectrometry. Evidence for the structure of 4- and 5-bithiophenyl-substituted pyrimidines has first been obtained by means of X-ray crystallography analysis. Molecular orbital calculations (TDDFT), as well as the redox and optical measurements for all new compounds have also been performed.

Direct β-amination reaction in porphyrin systems—a simple route to compounds containing two nitrogen substituents at both β-positions of the same pyrrole unit

The direct β-amination of porphyrin derivatives is described. 2-Nitro-meso-tetraarylporphyrins (zinc and copper complexes) react with N,N,N-trimethylhydrazinium iodide (TMHI) in the presence of a base (KOH/DMSO system, ca 70–80°C) to give products of nucleophilic aromatic substitution of hydrogen. In this process, the nucleophilic replacement of a H-atom by an NH2 group takes place. The products obtained, bearing two neighbouring nitrogen substituents on the same pyrrole ring, are valuable intermediates for various synthetic uses.

Combination of the Suzuki–Miyaura cross-coupling and nucleophilic aromatic substitution of hydrogen ([formula omitted]) reactions as a versatile route to pyrimidines bearing thiophene fragments

It has been shown that combination of the Suzuki–Miyaura cross-coupling and nucleophilic aromatic substitution of hydrogen is a versatile method for the synthesis of 4-(thiophen-2-yl)-, 5-(thiophen-2-yl)-, and 4,5-di(thiophen-2-yl) substituted pyrimidines from the commercially available 5-bromopyrimidine. The SNH (AE)- and SNH (AO)-reactions of 5-bromopyrimidine with thiophene and 2-bromothiophene have been studied by gas–liquid chromatography/mass-spectrometry. The structures of intermediate σH-adducts, as well as thiophene-(thiophenyl)pyrimidine and bithiophene-(thiophenyl)pyrimidine dyads have first been established by X-ray crystallography analysis.

Synthesis of chelating polymer sorbents by using the S methodology

AbstractThe article describes a new synthetic approach to modify the structure of phenol‐formaldehyde and resorcinol‐formaldehyde resins, which enables one to functionalize a polymer matrix by using the S (nucleophilic aromatic substitution of hydrogen) methodology. Direct heteroarylation of phenol (resorcinol) fragments in polymer chains with 1,2,4‐triazine derivatives illustrates a new synthetic method in the polymer chemistry. The feature of this methodology is that it provides an opportunity to accomplish direct one‐pot polymer transformations by incorporating of rather complicated chelating groups through the displacement of hydrogen in phenol moieties. It has been shown that in order to obtain chemically modified polymers on the basis of phenol‐formaldehyde and resorcinol‐formaldehyde resins with a high degree of substitution with chelating units, a polymer matrix has to react with 3‐(pyridin‐2′‐yl)‐1,2,4‐triazin‐5(2H)‐one. Also, it has been found that polymer sorbents with a high selectivity can be obtained by using the template method. Targeted synthesis of model compounds, as structural units of the chelating polymers, and elucidation of the structure of their complexes with copper (II) ions have shown that the most plausible type of coordination is formation of the bridge 1 : 1 complexes of the α,α′‐bipyridinyl type. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012