Nucleophilic aromatic substitution with dialkoxycarbenes

1997 ◽  
Vol 75 (10) ◽  
pp. 1331-1335 ◽  
Author(s):  
Joseph P. Ross ◽  
Philippe Couture ◽  
John Warkentin
Keyword(s):  
Nucleophilic Substitution ◽  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Aromatic Rings ◽  
Aryl Group ◽  
Aryl Fluoride ◽  
Intramolecular Substitution

Dimethoxycarbene, generated at 110 °C by thermolysis of 2,2-dimethoxy-5,5-dimethyl-Δ3-1,3,4-oxadiazoline, displaces fluoride from aromatic rings that are activated with electron-withdrawing groups. Intermolecular substitution on Sanger's reagent and on hexafluorobenzene are reported, together with intramolecular substitution by a dioxycarbene with a tethered aryl group. Keywords: aromatic substitution, aryl(dimethoxy)fluoromethanes, aryl fluoride, dialkoxycarbene, nucleophilic substitution.

Nucleophilic substitution of meso-nitrooctaethylporphyrins

1985 ◽  
Vol 63 (2) ◽  
pp. 406-411 ◽  
Author(s):  
Liang-Chu Gong ◽  
David Dolphin
Keyword(s):  
Nucleophilic Substitution ◽  
Nucleophilic Addition ◽  
Nucleophilic Aromatic Substitution ◽  
Redox Potentials ◽  
Aromatic Substitution ◽  
Halogen Atoms

Nitrooctaethylporphyrins readily undergo nucleophilic aromatic substitution in the presence of HCl or HBr. In the presence of methoxide, nucleophilic addition to give a porphodimethane occurs, followed by autoxidation to the methoxyporphyrin. Unlike the nitrated complexes, the chlorosubstituted porphyrins exhibit redox potentials similar to those of unsubstituted analogs. Meso-halogenated porphyrins do, however, show steric distortion due to the bulk of the halogen atoms.

How Does Nucleophilic Aromatic Substitution in Nitroarenes Really Proceed: General Mechanism

Synthesis ◽  
2017 ◽  
Vol 49 (15) ◽  
pp. 3247-3254 ◽  
Author(s):  
Mieczysław Mąkosza
Keyword(s):  
Ab Initio Calculations ◽  
Ab Initio ◽  
Nucleophilic Substitution ◽  
Experimental Studies ◽  
Secondary Reaction ◽  
Nucleophilic Aromatic Substitution ◽  
General Mechanism ◽  
Primary Process ◽  
Nucleophilic Substitution Of Hydrogen ◽  
Aromatic Substitution

On the basis of previously published experimental studies and ab initio calculations, a general corrected mechanism of nucleophilic aromatic substitution was formulated. It was shown that conventional nucleophilic substitution of halogens is a slow secondary reaction whereas nucleophilic substitution of hydrogen is the fast primary process. The general mechanism embraces both of these alternative and complementary reactions.

scholarly journals ATP-Dependent C–F Bond Cleavage Allows the Complete Degradation of 4-Fluoroaromatics without Oxygen

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Oliver Tiedt ◽  
Mario Mergelsberg ◽  
Kerstin Boll ◽  
Michael Müller ◽  
Lorenz Adrian ◽  
...  
Keyword(s):  
Coenzyme A ◽  
Bond Cleavage ◽  
Nucleophilic Aromatic Substitution ◽  
Transcriptional Level ◽  
Aromatic Substitution ◽  
Complete Degradation ◽  
Thauera Aromatica ◽  
Coa Ligase ◽  
Aryl Fluoride ◽  
Transcriptional Adaptation

ABSTRACTComplete biodegradation of the abundant and persistent fluoroaromatics requires enzymatic cleavage of an arylic C–F bond, probably the most stable single bond of a biodegradable organic molecule. While in aerobic microorganisms defluorination of fluoroaromatics is initiated by oxygenases, arylic C–F bond cleavage has never been observed in the absence of oxygen. Here, an oxygen-independent enzymatic aryl fluoride bond cleavage is described during the complete degradation of 4-fluorobenzoate or 4-fluorotoluene to CO2and HF in the denitrifyingThauera aromatica: the ATP-dependent defluorination of 4-fluorobenzoyl-coenzyme A (4-F-BzCoA) to benzoyl-coenzyme A (BzCoA) and HF, catalyzed by class I BzCoA reductase (BCR). Adaptation to growth with the fluoroaromatics was accomplished by the downregulation of a promiscuous benzoate-CoA ligase and the concomitant upregulation of 4-F-BzCoA-defluorinating/dearomatizing BCR on the transcriptional level. We propose an unprecedented mechanism for reductive arylic C–F bond cleavage via a Birch reduction-like mechanism resulting in a formal nucleophilic aromatic substitution. In the proposed anionic 4-fluorodienoyl-CoA transition state, fluoride elimination to BzCoA is favored over protonation to a fluorinated cyclic dienoyl-CoA.IMPORTANCEOrganofluorides are produced as pesticides, pharmaceuticals, and other chemicals and comprise approximately one quarter of all organic compounds in the pharmaceutical and agricultural sectors; they are considered a growing class of environmentally relevant persistent pollutants. Especially in the case of fluoroaromatics, biodegradation is hampered by the extreme stability of the arylic C–F bond. In aerobic microorganisms, degradation proceeds via oxygenase-dependent C–F bond cleavage reactions, whereas the enzymes involved in the degradation of fluoroaromatics at anoxic sites are unknown. Here we report a strategy for the complete biodegradation of a fluoroaromatic to CO2and HF in a denitrifying bacterium via activation to a CoA ester, followed by oxygen-independent arylic C–F bond cleavage catalyzed by an ATP-dependent enzyme. This reaction, in conjunction with a transcriptional adaptation to fluorinated growth substrates, is essential for the anoxic biodegradation of 4-fluorobenzoate/4-F-toluene and probably other fluoroaromatics.

Ironcyclopentadienyl mediated 2-alkyl-2-arylphenylsulphonylacetonitrile synthesis

1995 ◽  
Vol 73 (2) ◽  
pp. 289-295 ◽  
Author(s):  
Alaa S. Abd-El-Aziz ◽  
Christine R. de Denus ◽  
Harold M. Hutton
Keyword(s):  
Nucleophilic Substitution ◽  
Room Temperature ◽  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Efficient Route ◽  
Cyclopentadienyliron Complexes ◽  
Formation Of Complexes

A unique route to the synthesis of 2-alkyl-2-arylphenylsulphonylacetonitriles via the nucleophilic aromatic substitution (SNAr) of chloroarene cyclopentadienyliron complexes with 2-alkyl phenylsulphonylacetonitriles has been investigated. Reactions of chloroarene complexes (1a–d) with 2-alkyl phenylsulphonylacetonitrile (2a,b) in the presence of K2CO3 in DMF at room temperature led to the formation of complexes 3a–d and 4a,c,d in good yields. The use of alkylated phenylsulphonylacetonitriles as nucleophiles in the reactions with the p-dichlorobenzene complex (1e) allowed the formation of the disubstituted complexes (5,6). Photolytic demetallation provided an efficient route to the liberation of the arylated phenylsulphonylacetonitriles 7a–d, 8a,c,d, 9, and 10. Keywords: chloroarene, phenylsulphonylacetonitrile, nucleophilic substitution.

scholarly journals Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

2013 ◽  
Vol 9 ◽  
pp. 791-799 ◽  
Author(s):  
Magnus Liljenberg ◽  
Tore Brinck ◽  
Tobias Rein ◽  
Mats Svensson
Keyword(s):  
Nucleophilic Substitution ◽  
Density Functional ◽  
Reaction Rates ◽  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Functional Theory ◽  
Aromatic Substrates ◽  
Complex Approach ◽  
Mechanistic Analysis ◽  
Rate Limiting

A computational approach using density functional theory to compute the energies of the possible σ-complex reaction intermediates, the “σ-complex approach”, has been shown to be very useful in predicting regioselectivity, in electrophilic as well as nucleophilic aromatic substitution. In this article we give a short overview of the background for these investigations and the general requirements for predictive reactivity models for the pharmaceutical industry. We also present new results regarding the reaction rates and regioselectivities in nucleophilic substitution of fluorinated aromatics. They were rationalized by investigating linear correlations between experimental rate constants (k) from the literature with a theoretical quantity, which we call the sigma stability (SS). The SS is the energy change associated with formation of the intermediate σ-complex by attachment of the nucleophile to the aromatic ring. The correlations, which include both neutral (NH3) and anionic (MeO−) nucleophiles are quite satisfactory (r = 0.93 to r = 0.99), and SS is thus useful for quantifying both global (substrate) and local (positional) reactivity in SNAr reactions of fluorinated aromatic substrates. A mechanistic analysis shows that the geometric structure of the σ-complex resembles the rate-limiting transition state and that this provides a rationale for the observed correlations between the SS and the reaction rate.

Methylsulfone as a leaving group for synthesis of hyperbranched poly(arylene pyrimidine ether)s by nucleophilic aromatic substitution

RSC Advances ◽  
2015 ◽  
Vol 5 (17) ◽  
pp. 12821-12823 ◽  
Author(s):  
Yue Guan ◽  
Chunbo Wang ◽  
Daming Wang ◽  
Guodong Dang ◽  
Chunhai Chen ◽  
...  
Keyword(s):  
Nucleophilic Substitution ◽  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Hyperbranched Poly ◽  
Leaving Group

Using a novel leaving group, methylsulfone activated by pyrimidine, 4,6-dichloro-2-(methylsulfonyl)pyrimidine was used to synthesize two new hyperbranched poly(arylene pyrimidine ether)s with diphenol via a nucleophilic substitution polymerization.

scholarly journals Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

2016 ◽  
Vol 12 ◽  
pp. 192-197 ◽  
Author(s):  
Javier Ajenjo ◽  
Martin Greenhall ◽  
Camillo Zarantonello ◽  
Petr Beier
Keyword(s):  
Nucleophilic Substitution ◽  
Title Compound ◽  
Fluorine Atom ◽  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Vicarious Nucleophilic Substitution ◽  
Direct Fluorination ◽  
Nitrogen Nucleophiles

3-Fluoro-5-nitro-1-(pentafluorosulfanyl)benzene was prepared by three different ways: as a byproduct of direct fluorination of 1,2-bis(3-nitrophenyl)disulfane, by direct fluorination of 4-nitro-1-(pentafluorosulfanyl)benzene, and by fluorodenitration of 3,5-dinitro-1-(pentafluorosulfanyl)benzene. The title compound was subjected to a nucleophilic aromatic substitution of the fluorine atom with oxygen, sulfur and nitrogen nucleophiles affording novel (pentafluorosulfanyl)benzenes with 3,5-disubstitution pattern. Vicarious nucleophilic substitution of the title compound with carbon, oxygen, and nitrogen nucleophiles provided 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzenes substituted in position four.

Synthesis of Hydrazinylpyridines via Nucleophilic Aromatic Substitution and Further Transformation to Bicyclo[2.2.2]octenes Fused with Two N-Aminosuccinimide Moieties

Synthesis ◽  
2020 ◽  
Author(s):  
Krištof Kranjc ◽  
Jernej Ekar
Keyword(s):  
Nucleophilic Substitution ◽  
Hydrazine Hydrate ◽  
Diethyl Ether ◽  
Water Solubility ◽  
Halogen Bond ◽  
Bidentate Ligand ◽  
Nucleophilic Aromatic Substitution ◽  
Thick Wall ◽  
Aromatic Substitution ◽  
User Friendly

AbstractEfficient and reliable synthesis of substituted hydrazinylpyridines in thick-wall ACE tubes via nucleophilic substitution of a chlorine substituent in different chloropyridines is presented. Hydrazine hydrate and alkylhydrazines were used as nucleophiles and simple alcohols and diethyl ether were the only organic solvents necessary, making the process environmentally and user friendly, potentially reaching 100% atomic efficiency. In the next step, transformations of succinic anhydride moieties fused to the bicyclo[2.2.2]octene framework into succinimide moieties via nucleophilic substitution of oxygens were conducted. As nucleophiles two of the synthesized hydrazinylpyridines (2-hydrazinyl-3-nitropyridine and 2-hydrazinyl-5-nitropyridine) and also hydrazine hydrate, phenylhydrazine, and 4-nitrophenylhydrazine were used. Reactions were again carried out in ACE tubes and only simple alcohols, diethyl ether, and acetone were needed as solvents. One of the prepared bicyclo[2.2.2]octene adducts displayed water solubility thus being a promising candidate for future studies as a novel bidentate ligand for various metal cations in aqueous solutions or acting as an unprecedented halogen bond acceptor.

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