Resonance nucleophilic aromatic substitution

Nucleophilic aromatic substitution occurs only if the aromatic ring has an electron-withdrawing substituent in a position ortho or para to the leaving group. The more such substituents there are, the faster the reaction. As shown in Figure 16.18, only ortho and para electron-withdrawing substituents stabilize the anion intermediate through resonance a meta substituent offers no such resonance stabilization. Thus, p-ch oronitrobenzene and o-chloronitrobenzene react with hydroxide ion at 130 °C to yield substitution products, but m-chloronitrobenzene is inert to OH-. 

Figure 16.18 Nucleophilic aromatic substitution on nitrochlorobenzenes. Only in the ortho and para intermediates is the negative charge stabilized by a resonance interaction with the nitro group, so only the ortho and para isomers undergo reaction.

Similarly, those reactions that are strongly assisted by withdrawal of electrons from the reaction site, such as nucleophilic aromatic substitution, give a poor fit to a Hammett plot for the substituents that are capable of withdrawing electrons by delocalization (—N02, —N2 , —C=N, and so on). An example is Reaction 16 in Table 26-7. To correlate reactivity data with structures where strong resonance effects operate, different sets of substituent constants are required.1... 

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. 

One solution for this problem, the most optimistic, suggested the existence of three independent sets of o--constants. The first set, the Hammett constants, would be applicable to side-chain reactions in which resonance interactions between the substituent and the side-chain were either small or insignificant. The second set, the w-constants, would apply to side-chain reactions of phenols and anilines and nucleophilic aromatic substitution reactions in which a negative charge was introduced in the aromatic nucleus (Miller, 1956). A third set, the c7+-constants, would apply to electrophilic substitution and electrophilic side-chain reactions for which resonance interactions between the reaction site and the substituent were important. 

A-4. Write a mechanism using resonance structures to show how a nitro group directs ortho, para in nucleophilic aromatic substitution. 

During my early years as an assistant professor at the University of Kentucky, I demonstrated the synthesis of a simple quinone methide as the product of the nucleophilic aromatic substitution reaction of water at a highly destabilized 4-methoxybenzyl carbocation. I was struck by the notion that the distinctive chemical reactivity of quinone methides is related to the striking combination of neutral nonaromatic and zwitterionic aromatic valence bond resonance structures that contribute to their hybrid resonance structures. This served as the starting point for the interpretation of the results of our studies on nucleophile addition to quinone methides. At the same time, many other talented chemists have worked to develop methods for the generation of quinone methides and applications for these compounds in organic syntheses and chemical biology. The chapter coauthored with Maria Toteva presents an overview of this work. 

Mechanism of nucleophilic aromatic substitution. The reaction occurs in two steps and involves a resonance-stabilized carbanion intermediate. 

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