Aromatic substitution structure-reactivity relationships

Electrophilic aromatic substitution reactions are important for synthetic purposes and also are one of the most thoroughly studied classes of organic reactions from a mechanistic point of view. The synthetic aspects of these reactions are discussed in Chapter 11 of Part B. The discussion here will emphasize the mechanisms of several of the most completely studied reactions. These mechanistic ideas are the foundation for the structure-reactivity relationships in aromatic electrophilic substitution which will be discussed in Section 10.2... 

Other matters that are important include the ability of the electrophile to select among the alternative positions on a substituted aromatic ring. The relative reactivity of different substituted benzenes toward various electrophiles has also been important in developing a firm understanding of electrophilic aromatic substitution. The next section considers some of the structure-reactivity relationships that have proven to be informative. 

A substantial body of data, including reaction kinetics, isotope effects, and structure-reactivity relationships, has permitted a thorough understanding of the steps in aromatic nitration. As anticipated from the general mechanism for electrophilic substitution, there are three distinct steps ... 

This chapter is concerned with reactions that introduce or replace substituent groups on aromatic rings. The most important group of reactions is electrophilic aromatic substitution. The mechanism of electrophile aromatic substitution has been studied in great detail, and much information is available about structure-reactivity relationships. There are also important reactions which occur by nucleophilic substitution, including reactions of diazonium ion intermediates and metal-catalyzed substitution. The mechanistic aspects of these reactions were discussed in Chapter 10 of Part A. In this chapter, the synthetic aspects of aromatic substitution will be emphasized. 

Peijnenburg, W.J., Debeer, K.G., Dehaan, M.W., Denhollander, H.A., Stegeman, M.H. and Verboom, H. (1992b). Development of a Structure-Reactivity Relationship for the Photohydrolysis of Substituted Aromatic Halides. Environ.Sci.Technol., 26,2116-2121. 

Electrophilic aromatic substitution is a situation in which it is useful to discuss TS structure in terms of a reaction intermediate. The ortho, para, and meta directing effects of aromatic substituents were among the first structure-reactivity relationships to be developed in organic chemistry. Certain functional groups activate aromatic rings toward substitution and direct the entering electrophile to the ortho and para positions, whereas others are deactivating and lead to substitution in the meta position. The bromination of methoxybenzene (anisole), benzene, and nitrobenzene can serve as examples for discussion. 

The general mechanistic framework outlined in this section can be elaborated by other details to more fully describe the mechanisms of the individual electrophilic substitutions. The question of the identity of the active electrophile in each reaction is important. We have discussed the case of nitration in which, under many circumstances, the electrophile is the nitronium ion. Similar questions about the structure of the active electrophile arise in most of the other substitution processes. Another issue that is important is the ability of the electrophile to select among the alternative positions on a substituted aromatic ring position selectivity). The relative reactivity and selectivity of substituted benzenes toward various electrophiles is important in developing a firm understanding of EAS. The next section considers some of the structure-reactivity relationships that have proven to be informative. 

The effect that substituents already present have on electrophilic aromatic substitution reactions represents an area of structure-reactivity relationships that has been under study since about 1870. The classification of substituents as activating and ortfto-para-directing or deactivating and mete-directing has been known since those early studies. A basic understanding of these substituent effects became possible when ideas about electronic interactions and resonance theory were... 

The silyl group directs attacking electrophiles such as the proton or bromine to the substituted position. It is thus a strongly directing group. Structure-reactivity relationships indicate that the mechanism is similar to an aromatic substitution... 

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