Nucleophilic aromatic substitution Meisenheimer complexes

The product of this reaction as its sodium salt is called a Meisenheimer complex after the Ger man chemist Jacob Meisenheimer who reported on their formation and reactions in 1902 A Meisenheimer complex corresponds to the product of the nucleophilic addition stage in the addition-elimination mechanism for nucleophilic aromatic substitution... 

Two of three nitrofluorobenzene isomers react with methoxide, but the third is unreactive. Obtain energies of methoxide anion (at left), ortho, meta and para-nitrofluorobenzene, and the corresponding ortho, meta and para-methoxide anion adducts (so-called Meisenheimer complexes). Calculate the energy of methoxide addition to each of the three substrates. Which substrate is probably unreactive What is the apparent directing effect of a nitro group Does a nitro group have the same effect on nucleophilic aromatic substitution that it has on electrophilic aromatic substitution (see Chapter 13, Problem 4) Examine the structures and electrostatic potential maps of the Meisenheimer complexes. Use resonance arguments to rationalize what you observe. 

The first study of a nucleophilic aromatic substitution in which formation of a Meisenheimer-type complex and its subsequent decomposition were separately observable was reported by Orvik and Bunnett (1970). The study involved the reaction of 2,4-dinitro-l-naphthyl ethyl ether [7] with n-butyl- and t-butylamine in DMSO. The use of DMSO in this kinetic study enabled the rate behaviour to be unambiguously interpreted by avoiding complications due to aggregation phenomena, while stabilizing any a-complexes which are formed. The reaction sequence is given in equation (28). In this OEt... 

Pseudobase formation by nucleophilic addition to heteroaromatic cations is closely related to the long-known Meisenheimer complex formation by nucleophilic addition to an electron-deficient neutral aromatic molecule.20-25 In both cases nucleophilic attack on an electron-deficient aromatic ring produces a c-complex—an anionic Meisenheimer complex or a neutral pseudobase molecule. Despite the intense interest over the past few years in Meisenheimer complexes as models for er-complex intermediates in nucleophilic aromatic substitution reactions, there has been little overt recognition of the relationship between Meisenheimer complexes and pseudobases derived from heteroaromatic cations. In this regard, it is interesting that the pseudobase 165, which can be regarded as the complex intermediate that would be expected for an SNAr reaction between the l-methyl-4-iodoquinolinium cation and hydroxide ion, has been spectroscopically characterized.89... 

The reaction is a nucleophilic aromatic substitution. The intermediate Meisenheimer complex is stabilized by the -NO2 group. 

Nucleophilic aromatic substitution for heteroatom nucleophiles through electrochemical oxidation of intermediate a-complexes (Meisenheimer complexes) in simple nitroaromatic compounds has been reported, see Gallardo, 1. Guirado, G. Marquet, J. J. Org. Chem. 2002, 67, 2548. 

However, 4-chlorobenzoyl-CoA dehalogenase is also a member of the enoyl-CoA hydratase superfamily. The mechanism of its reaction involves nucleophilic aromatic substitution in which an active site Asp adds to the 4-position of the benzoyl ring to necessarily form a Meisenheimer complex this Meisenheimer complex is an analog of a thioester enolate anion. Although the Meisenheimer complex cannot be observed for displacement of chloride from 4-chlorobenzoyl-CoA due to the rate constants for formation and decomposition of the intermediate, the Meisen-... 

The anionic a complexes formed between polynitroaromatic compounds and bases (1, 2), commonly known as Meisenheimer complexes, are used as models of the reaction intermediates that are considered to be formed in activated nucleophilic aromatic substitution reactions (3-6), as well as being of intrinsic interest. Thus, numerous studies describe the formation and transformation of such a complexes (7-14). As a result, a variety of structural types of these species have been characterized and subjected to detailed investigation. A number of theoretical studies relating to these species have also been reported (15). 

The Meisenheimer complexes have been widely observed in nucleophilic aromatic substitution reactions. 

The kinetics of nucleophilic aromatic substitution is almost always second order—first order in nucleophile and first-order in the aromatic electrophile. The intermediate structure is called the Meisenheimer complex (or Jackson-Meisenheimer complex). The Meisenheimer complex can sometimes be directly observed at low temperatures. In aprotic sol-... 

Next, look at the substrate to determine if all three criteria are present for a nucleophilic aromatic substitution (1) there is a leaving group (chloride), (2) there is a nitro group, and (3) the nitro group is ortho to the leaving group. All three criteria are met, so the mechanism is likely to be S Ar, which proceeds through a Meisenheimer complex. 

Meisenheimer complex 899 moderate activators 881 moderate deactivators 882 nitration 866 nitronium ion 866 nucleophilic aromatic substitution 898... 

Meisenheimer complex (p. 675) nucleophilic aromatic substitution (p. 675) [wjparacyclophane (p. 628)... 

Meisenheimer complex (Section 14.12) The intermediate in nucleophilic aromatic substitution formed by the addition of a nucleophile to an aromatic compound activated by electron-withdrawing groups, often NO2. 

We have been interested in the reactions of nucleophiles with nitro-activated aromatics for some time (1). These reactions lead typically to complexes known as anionic a-complexes or Meisenheimer complexes (2, 3). One of our main purposes was to use these reactions as models for elementary steps in nucleophilic aromatic substitution and draw mechanistic conclusions from them (1, 4). 

On the other hand, nucleophilic aromatic substitution in the LNH3 proceeds/gives evidence of an isolatable Meisenheimer complex intermediate, flhat is, S jfAR),... 

The reaction is a nucleophilic aromatic substitution proceeding through an intermediary addition product (Meisenheimer complex). It occurs under mild conditions only when the benzene ring structure is stabilized by electron-withdrawing substituents on the ring (cf. Reaction 1.37). 

Meisenheimer complex (Section 9.9) The intermediate in a nucleophilic aromatic substitution reaction, formed by addition of a nucleophile to a halo-substituted aromatic ring. 

The outcome of the regioconservative reactions is vaguely attributed to a "direct displacement" process or to a "chelation-driven nucleophilic aromatic ipso substitution". Presumably both times the authors refer to the well-known two-step addition/elimination mechanism of nucleophilic aromatic substitution. However, to make this option practically feasible, the haloarene has to be activated by powerful electron-acceptors, in particular, nitro groups (as in 2- or 4-halonitroarenes) or by ring-incorporated nitrogen (as in 2- or 4-halopyridines). Without that, the crucial Meisenheimer complex is energetically out of reach. 

The situation is different for aromatic nucleophilic substitution (14) where the transition state will be like a Meisenheimer complex with its negative... 

Because of the presence of nitrogen in the aromatic ring, electrons in pyridine are distributed in such a way that their density is higher in positions 3 and 5 (the P-positions). In these positions, electrophilic substitutions such as halogenation, nitration, and sulfonation take place. On the contrary, positions 2, 4, and 6 (a- and y-positions, respectively) have lower electron density and are therefore centers for nucleophilic displacements such as hydrolysis or Chichibabin reaction. In the case of 3,5-dichlorotrifluoropyridine, hydroxide anion of potassium hydroxide attacks the a- and y-positions because, in addition to the effect of the pyridine nitrogen, fluorine atoms in these position facilitate nucleophilic reaction by decreasing the electron density at the carbon atoms to which they are bonded. In a rate-determining step, hydroxyl becomes attached to the carbon atoms linked to fluorine and converts the aromatic compound into a nonaromatic Meisenheimer complex (see Surprise 67). To restore the aromaticity, fluoride ion is ejected in a fast step, and hydroxy pyridines I and J are obtained as the products [58],... 

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