Nucleophilic aromatic Meisenheimer complexe

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... 

The benzene anion formed as shown by nucleophilic attack on an aromatic ring is called a Meisenheimer complex. 

Meisenheimer complex (Section 16.7) An intermediate formed by addition of a nucleophile to a halo-substituted aromatic ring. 

In the first mechanism (equation 74) the nucleophile function attacks the aromatic ring in an ipso-type displacement involving a Meisenheimer complex intermediate243,244, and leads to the rearranged product after expulsion of sulfinate anion (X-). This mechanism should be favoured by the presence of an electron-withdrawing substituent in conjugation with the anion. The second mechanism (equation 75) involves a direct displacement of sulfinate anion (X ) by Y-, without involvement of the aromatic n electrons. 

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

In the absence of nucleophile, neither the 412 nm species nor the formation of the radical anion, nor that of the photosubstitution product is found. It is concluded therefore that the 412 nm species results from some kind of interaction between the (excited) aromatic compound and the nucleophilic reagent. The character of this aromatic compound-nucleophile-complex is as yet unknown. However, in our present view, the nature of the complex has to allow for the formation of both the radical anion and the photosubstitution product(s). An attractive possibility for this complex remains the a-complex, in formal analogy with the Meisenheimer complexes in the thermal nucleophilic reactions with aromatic compounds. An exciplex forms another possibility. 

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... 

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],... 

Thus, carbon 1 of 2,4-dinitrohalobenzene has the lowest electron density, and the halogen in position 1 is easily displaced by a nuclephile in a rate-determining step of an SNAr reaction with hydroxide, alkoxide, and primary or secondary amino compounds [94]. As the nucleophile becomes attached to the carbon, the compound is converted to an unstable nonaromatic species, the Meisenheimer complex [91]. Restoration of aromaticity facilitates elimination of the halogen in a fast step, in this particular case giving 2,4-dinitroanisole. 

The concept of pseudobase formation by heteroaromatic cations is intimately related to the covalent hydration of heteroaromatic molecules16-19 and to Meisenheimer complex formation,20-25 although this relationship has not generally been emphasized in the literature until recently26,27. All such reactions involve the formation of -complexes by nucleophilic addition to electron-deficient aromatic species, and yet, extensive reviews of covalent hydration16-19 and of Meisenheimer complex formation20-25 have neither explicitly recognized their mutual relationship nor considered pseudobase formation. 

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... 

Meisenheimer complex formation as separate reactions. Meisenheimer complexes can be considered as the anionic pseudobases derived from neutral aromatic molecules, and in this light it is clear that heterocyclic Meisenheimer complexes are appropriately considered in the current Review. By so doing, it is hoped that attention can be drawn to potentially mutual benefits that may be derived from comparative studies of neutral and anionic pseudobases. Certainly, the spectroscopic techniques applicable to the study of pseudobase and Meisenheimer complex formation are identical. Quantitative studies of substituent effects and structural effects on rates and equilibria for nucleophilic addition should be relevant both to neutral and to anionic e-complex formation. The general rules enunciated by Strauss23,318 and Fendler319 for the prediction of the relative stabilities of Meisenheimer complexes should be directly applicable to analogous pseudobases. Terrier et al.2n have made an important contribution in this area with a detailed comparison of kinetic and thermodynamic parameters for formation of a benzofuroxan Meisenheimer complex and an isoquinoline pseudobase. 

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. 

Nucleophilic substitutions on an aromatic ring proceed by the addition lelimination mechanism shown in Figure 16.18. The attacking nucleophile first adds to the electron-deficient aryl halide, forming a resonance-stabilized negatively charged intermediate called a Meisenheimer complex. Halide ion is then eliminated in the second step. 

Meisenheimer adduct A cyclohexadienyl derivative formed as Fewis adduct from a nucleophile (Fewis base) and an AROMATIC or heteroaromatic compound, also called Jackson-Meisenheimer adduct. In earlier usage the term Meisenheimer complex was restricted to the typical Meisenheimer alkoxide adducts of nitro-substituted aromatic ethers, for example... 

The destabilization of sp -bound fluorine by p-jt repulsion activates fluorinated aromatic compounds totvard nucleophilic attack and subsequent substitution. The susceptibility of the carbon center toward nucleophiles is also enhanced by the negative inductive (—T) effect of fluorine. In particular, if the aromatic compound is also activated by —M electron-withdrawing substituents, for example a nitro or cyano group, in the ortho or para positions the fluorine is easily replaced by a variety of nucleophiles even under very mild conditions via a resonance stabilized Meisenheimer complex (Scheme 2.39). The ease of nucleophilic halogen replacement - F > Cl > Br > I - is in the opposite order to that for aliphatic nucleophilic substitution. 

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