Nucleophilic Aromatic Substitution Diazonium Ions

Although aromatic halides are inert to both SN1 and SN2 reactions (see Chapter 8), aromatic diazonium ions can act as the electrophilic partner in a nucleophilic substitution reaction. These ions are highly reactive because the leaving group, N2, is an extremely weak base  

The mechanisms for these reactions are not well understood, but there is evidence that some actually follow an Sn 1 pathway. Many others are known to involve radicals (odd electron species). We will not be concerned with the details of the various mechanisms here. 

The diazo group can be replaced by a number of different nucleophiles. Although several different mechanisms may operate, it is easiest to remember the reactions if you consider them all to be simple nucleophilic substitutions, even though most are not. The following equations provide examples of the various substitutions that can be accomplished with diazonium ions. 

The diazo group can be replaced with chlorine or bromine by reaction with cuprous chloride or cuprous bromide. [The Cu(l) aids in the formation of the radicals that are involved in these particular reactions.] 

The diazo group can be replaced with iodine by reaction with potassium iodide  

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The first widely used intermediates for nucleophilic aromatic substitution were the aryl diazonium salts. Aryl diazonium ions are usually prepared by reaction of an aniline with nitrous acid, which is generated in situ from a nitrite salt.81 Unlike aliphatic diazonium ions, which decompose very rapidly to molecular nitrogen and a carbocation (see Part A, Section 4.1.5), aryl diazonium ions are stable enough to exist in solution at room temperature and below. They can also be isolated as salts with nonnucleophilic anions, such as tetrafluoroborate or trifluoroacetate.82 Salts prepared with 0-benzenedisulfonimidate also appear to have potential for synthetic application.83... 

Chapter 11 focuses on aromatic substitution, including electrophilic aromatic substitution, reactions of diazonium ions, and palladium-catalyzed nucleophilic aromatic substitution. Chapter 12 discusses oxidation reactions and is organized on the basis of functional group transformations. Oxidants are subdivided as transition metals, oxygen and peroxides, and other oxidants. 

There are several mechanisms by which net nucleophilic aromatic substitution can occur. In this section we discuss the addition-elimination mechanism and the elimination-addition mechanisms. The mechanism, which involves radical intermediates, is discussed in Chapter 11. Substitutions via organometallic intermediates and via aryl diazonium ions are considered in Chapter 11 of Part B. 

Existing textbooks usually fail to show how common mechanistic steps link seemingly disparate reactions, or how seemingly similar transformations often have wildly disparate mechanisms. For example, substitutions at carbonyls and nucleophilic aromatic substitutions are usually dealt with in separate chapters in other textbooks, despite the fact that the mechanisms are essentially identical, and aromatic substitutions via diazonium ions are often dealt with in the same chapter as SrnI substitution reactions This textbook, by contrast, is organized according to mechanistic types, not according to overall transformations. This... 

The replacement of an electrofugic atom or group at a nucleophilic carbon atom by a diazonium ion is called an azo coupling reaction. By far the most important type of such reactions is that with aromatic coupling components, which was discovered by Griess in 1861 (see Sec. 1.1). It is a typical electrophilic aromatic substitution, called an arylazo-de-hydrogenation in the systematic IUPAC nomenclature (IUPAC 1989c, see Sec. 1.2). 

Synthetically important substitutions of aromatic compounds can also be done by nucleophilic reagents. There are several general mechanism for substitution by nucleophiles. Unlike nucleophilic substitution at saturated carbon, aromatic nucleophilic substitution does not occur by a single-step mechanism. The broad mechanistic classes that can be recognized include addition-elimination, elimination-addition, and metal-catalyzed processes. (See Section 9.5 of Part A to review these mechanisms.) We first discuss diazonium ions, which can react by several mechanisms. Depending on the substitution pattern, aryl halides can react by either addition-elimination or elimination-addition. Aryl halides and sulfonates also react with nucleophiles by metal-catalyzed mechanisms and these are discussed in Section 11.3. 

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. 

In this paper reactions of aromatic, heteroaromatic and related diazonium ions with nucleophiles are dia ussed. In such reactions substitution by the diazonium ion of an electrofugic atom or group bonded to carbon takes place. Occasionally reference is made to N- and P-coupling. In Section 4 the respective substitution at nitrogen (formation of diazoamino compounds) is included for comparative purposes. 

In the mechanism for electrophilic aromatic substitution with a diazonium ion as the electrophile, why does nucleophilic attack occur on the terminal nitrogen atom of the diazonium ion rather than on the nitrogen atom bonded to the benzene ring ... 

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