Nucleophilic aromatic substitution intermediate complexes

Antidepressant activity is retained when the two carbon bridge in imipramine is replaced by a larger, more complex, function. Nucleophilic aromatic substitution on chloropyridine 31 by means of p-aminobenzophenone (32) gives the bicyclic intermediate 33. Reduction of the nitro group (34), followed by intramolecular Schiff base formation gives the required heterocyclic ring system 35. Alkylation of the anion from 35 with l-dimethylamino-3-chloropropane leads to tampramine 36 [8]. 

Sn2 nucleophilic aromatic substitution 2. The intermediate complex mechanism... 

The available experimental results are completely in accord with this formulation. Both of these limiting conditions have been observed experimentally, and plots of both k versus [B]0 and k versus [R2NH]0 have been shown to have characteristics consistent with this proposed mechanism. These observations thus constitute very convincing evidence for the intermediate complex mechanism in nucleophilic aromatic substitution. 

Amination of aromatic nitro compounds is a very important process in both industry and laboratory. A simple synthesis of 4-aminodiphenyl amine (4-ADPA) has been achieved by utilizing a nucleophilic aromatic substitution. 4-ADPA is a key intermediate in the rubber chemical family of antioxidants. By means of a nucleophibc attack of the anilide anion on a nitrobenzene, a o-complex is formed first, which is then converted into 4-nitrosodiphenylamine and 4-nitrodiphenylamine by intra- and intermolecular oxidation. Catalytic hydrogenation finally affords 4-ADPA. Azobenzene, which is formed as a by-product, can be hydrogenated to aniline and thus recycled into the process. Switching this new atom-economy route allows for a dramatic reduction of chemical waste (Scheme 9.9).73 The United States Environmental Protection Agency gave the Green Chemistry Award for this process in 1998.74... 

This chapter covers reactions in which coordination of a transition metal to the ir-system of an arene ring activates the ring toward addition of nucleophiles, to give V-cyclohexadienyl-metal complexes (1 Scheme 1). If an electronegative atom is present in the ipso position, elimination of that atom (X in 1) leads to nucleophilic aromatic substitution (path a). Reaction of the intermediate with an electrophile (E+) can give disubstituted 1,3-cyclohexadiene derivatives (path b). If a hydrogen occupies the ipso posi-... 

In the original process using tin amides, transmetallation formed the amido intermediate. However, this synthetic method is outdated and the transfer of amides from tin to palladium will not be discussed. In the tin-free processes, reaction of palladium aryl halide complexes with amine and base generates palladium amide intermediates. One pathway for generation of the amido complex from amine and base would be reaction of the metal complex with the small concentration of amide that is present in the reaction mixtures. This pathway seems unlikely considering the two directly observed alternative pathways discussed below and the absence of benzyne and radical nucleophilic aromatic substitution products that would be generated from the reaction of alkali amide with aryl halides. 

It was recently reported that the nucleophilic aromatic substitution of equation 11 occurs efficiently within the photoionized van der Waals complex C6H5C1—NH3 52, an interesting case of intracluster reaction (see Section II.A.3.c). Thus, selective ionization of the van der Waals complex C6H5C1—NH3 prepared in a supersonic molecular beam led to the efficient production of C6H5NH3 and Cl via the intermediate C6H5Cl+ -NH3 complex. 

An intermediate in electrophilic aromatic substitution or nucleophilic aromatic substitution with a sigma bond between the electrophile or nucleophile and the former aromatic ring. The sigma complex bears a delocalized positive charge in electrophilic aromatic substitution and a delocalized negative charge in nucleophilic aromatic substitution, (p. 756)... 

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). 

Nucleophilic Aromatic Substitution For Hydrogen Oxidation of a-Complex Intermediates... 

Processes involving a single-electron transfer (SET) step and cation-radical intermediates can occur in the reactions of X - or X -iodanes with electron-rich organic substrates in polar, non-nucleophilic solvents. Kita and coworkers first found that the reactions of p-substituted phenol ethers 29 with [bis(trifluoroacetoxy)iodo]benzene in the presence of some nucleophiles in fluoroalcohol solvents afford products of nucleophilic aromatic substitution 31 via a SET mechanism (Scheme 1.5) [212,213]. On the basis of detailed UV and ESR spectroscopic measurements, it was confirmed that this process involves the generation of cation-radicals 30 produced by SET oxidation through the charge-transfer complex of phenyl ethers with the hypervalent iodine reagent [213,214],... 

Two examples of nucleophilic aromatic substitution for hydrogen reactions were described from which we have proposed two new atomically efficient processes for the manufacturing of commercially relevant aromatic amines. Our mechanistic studies have revealed that the direct oxidation of a-complex intermediates by either nitro groups or O2 can eliminate the need for chlorination of benzene as a starting point for the manufacturing of aromatic amines. Accordingly, these reactions demonstrate the key objective of alternate chemical design which is not to make the waste in the first place. 

The preceding explanation would seem to explain most of the data in Table 8.21, but there is one apparent discrepancy. We might have expected the methoxy substituent to be electron-donating, but it gives the same product orientation as does trifluoromethyl. This intuitive expectation of the substituent effect of methoxy is based primarily on its influence on electrophilic aromatic substitution (SeAr) and on nucleophilic aromatic substitution (SwAr) reactions, both of which involve attachment of a species to an aromatic ring to form a cr complex. In contrast, the carbanionic intermediates presumed to be formed in the benzyne reaction have the nonbonded pair of electrons in... 

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