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.

Mechanism of nucleophilic substitution reactions of 4-(4ˊ-nitro)phenylnitrobenzofurazan ether with aniline in acetonitrile.

2017 ◽  
Vol 2 (10) ◽  
Author(s):  
K. Gbayo ◽  
C. Isanbor ◽  
K. Lobb ◽  
O. Oloba-Whenu
Keyword(s):  
Density Functional Theory ◽  
Nuclear Magnetic Resonance ◽  
Density Functional ◽  
Theoretical Study ◽  
Activation Parameters ◽  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Substitution Reactions ◽  
Functional Theory ◽  
Nmr Techniques

Abstract Rate constants and activation parameters obtained for the nucleophilic aromatic substitution reactions (SNAr) of 4-substitutedphenoxy-7-nitrobenzoxadiazole (1) with aniline in acetonitrile at varying temperature using Nuclear Magnetic Resonance (NMR) techniques were reported. These results were compared with the theoretical study which identifies transformations and intermediates using Density Functional Theory (DFT).

scholarly journals Desulfination by 2′-hydroxybiphenyl-2-sulfinate desulfinase proceeds via electrophilic aromatic substitution by the cysteine-27 proton

2017 ◽  
Vol 8 (7) ◽  
pp. 5078-5086 ◽  
Author(s):  
Inacrist Geronimo ◽  
Shawn R. Nigam ◽  
Christina M. Payne
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Electrophilic Substitution ◽  
Electrophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Functional Theory ◽  
Rate Limiting

Density functional theory shows that the rate-limiting desulfination step in biodesulfurization involves concerted electrophilic substitution with the Cys-27 proton.

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.

Using degrees of rate control to improve selective n-butane oxidation over model MOF-encapsulated catalysts: sterically-constrained Ag3Pd(111)

2016 ◽  
Vol 188 ◽  
pp. 21-38 ◽  
Author(s):  
Sean T. Dix ◽  
Joseph K. Scott ◽  
Rachel B. Getman ◽  
Charles T. Campbell
Keyword(s):  
Rate Control ◽  
Density Functional ◽  
Bimetallic Nanoparticles ◽  
Reaction Rates ◽  
Process Conditions ◽  
Functional Theory ◽  
Microkinetic Model ◽  
Powerful Approach ◽  
Metal Organic ◽  
Catalytic Metal

Metal nanoparticles encapsulated within metal organic frameworks (MOFs) offer steric restrictions near the catalytic metal that can improve selectivity, much like in enzymes. A microkinetic model is developed for the regio-selective oxidation of n-butane to 1-butanol with O2 over a model for MOF-encapsulated bimetallic nanoparticles. The model consists of a Ag3Pd(111) surface decorated with a 2-atom-thick ring of (immobile) helium atoms which creates an artificial pore of similar size to that in common MOFs, which sterically constrains the adsorbed reaction intermediates. The kinetic parameters are based on energies calculated using density functional theory (DFT). The microkinetic model was analysed at 423 K to determine the dominant pathways and which species (adsorbed intermediates and transition states in the reaction mechanism) have energies that most sensitively affect the reaction rates to the different products, using degree-of-rate-control (DRC) analysis. This analysis revealed that activation of the C–H bond is assisted by adsorbed oxygen atoms, O*. Unfortunately, O* also abstracts H from adsorbed 1-butanol and butoxy as well, leading to butanal as the only significant product. This suggested to (1) add water to produce more OH*, thus inhibiting these undesired steps which produce OH*, and (2) eliminate most of the O2 pressure to reduce the O* coverage, thus also inhibiting these steps. Combined with increasing butane pressure, this dramatically improved the 1-butanol selectivity (from 0 to 95%) and the rate (to 2 molecules per site per s). Moreover, 40% less O2 was consumed per oxygen atom in the products. Under these conditions, a terminal H in butane is directly eliminated to the Pd site, and the resulting adsorbed butyl combines with OH* to give the desired 1-butanol. These results demonstrate that DRC analysis provides a powerful approach for optimizing catalytic process conditions, and that highly selectivity oxidation can sometimes be achieved by using a mixture of O2 and H2O as the oxidant. This was further demonstrated by DRC analysis of a second microkinetic model based on a related but hypothetical catalyst, where the activation energies for two of the steps were modified.

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.

Facile Synthesis of Triarylmethanimine Promoted by a Lewis Acid - Base Pair: Theoretical and Experimental Studies

2012 ◽  
Vol 65 (10) ◽  
pp. 1390 ◽  
Author(s):  
Yan Liu ◽  
Qiwu Yang ◽  
Dongling Hao ◽  
Wenqin Zhang
Keyword(s):  
Lewis Acid ◽  
Base Pair ◽  
Density Functional ◽  
Electronic Effect ◽  
Functional Group ◽  
Experimental Studies ◽  
Acid Base ◽  
Functional Theory ◽  
Mechanistic Analysis ◽  
Work Up

An efficient method for triarylmethanimine synthesis promoted by a Lewis acid–base pair (AlCl3–Et3N) was designed using mechanistic analysis with the aid of density functional theory. A series of triarylmethanimines were successfully prepared under mild conditions in good to excellent yields with a simple work-up procedure. The promoter, the Lewis acid–base pair (AlCl3–Et3N), is inexpensive, efficient, and shows good functional group tolerance. The experimental results show that the electronic effect played a significant role, i.e. the reactions proceeded smoothly when electron-sufficient arylamines and electron-deficient ketones were used as substrates.

Reactions of 1-substituted 2,4,6-trinitrobenzenes with nucleophiles

1979 ◽  
Vol 44 (5) ◽  
pp. 1453-1459 ◽  
Author(s):  
Jaromír Kaválek ◽  
Ahmad Ashfaq ◽  
Vojeslav Štěrba
Keyword(s):  
Methyl Ether ◽  
Rate Constants ◽  
Equilibrium Constants ◽  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Phenyl Ester ◽  
Methyl Derivative ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

Rate constants have been determined of nucleophilic aromatic substitution of 2,4,6-trinitrophenyl methyl ether (Ia), 2,4,6-trinitrophenyl ethanoate (Ic), 2,4,6-trinitrochlorobenzene (Ib), 2,4,6-trinitrodiphenyl ether (Id), 2,4,6-trinitro-4'-bromodiphenyl ether (Ie), 2,3',4,6-tetranitrodiphenyl ether (If) and 2,4,4',6-tetranitrodiphenyl ether (Ig) with methoxide, ethanoate and methyl cyanoethanoate (II) anions in methanol. For the compounds Ia,b rate and equilibrium constants of addition of the anion II(-) at positions 3 and 5 have been measured, too. In reactions of the compounds Ia to Ig with ethanoate anion the first (rate-limiting) step produces the phenyl ester Ic which reacts with a further ethanoate anion to give 2,4,6-trinitrophenol (Ih) and ethanoic anhydride. In reactions of the bromo derivative Ie and, to a still larger extent, compound Id the methyl derivative Ia is formed besides the compound Ih.

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