Diazonium salt nucleophilic aromatic substitution

The third mechanism of nucleophilic aromatic substitution, specific for substitution on aromatic diazonium salts, is shown in Equation 7.95. 

Other general reactions of amines would be nucleophilic displacement, electrophilic aromatic substitution in anilines and substitution via diazonium salts. 

Revision of nucleophilic aromatic substitution with diazonium salts and contrasting cations and radicals. 

In addition to the SNAr mechanism, several other mechanisms are known for nucleophilic aromatic substitutions. For example, an SnI mechanism is relevant for nucleophilic substitution reactions which encounter aromatic diazonium salts. Radical-nucleophilic aromatic substitutions (SrnI) are known in reactions where no electron-withdrawing group is available, whereas a mechanism via a benzyne intermediate is of relevance for substitutions employing NHJ as a nucleophile. 

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... 

Diazonium salts react with various nucleophiles in water (Eq. 11.62).106 In acidic aqueous solution, p-pheny I e ncbis di azo ni um ion reacts with alcohols more rapidly than it does with water.107 In the presence of nucelophiles such as halides, the substitution products are obtained. Furthermore, diazonium salts of aromatic compounds are excellent substrates for palladium-catalyzed coupling reactions such as the Heck-type reactions in water. 

Then the second arene undergoes electrophilic aromatic substitution, with the terminal N of the diazonium salt as the electrophilic atom. When nucleophilic arenes are added to diazonium salts, electrophilic aromatic substitution tends to take place instead of SnI substitution of the diazonium salt. 

Aiyl fluorides and iodides cannot be prepared by direct halogenatlon. The cyano group cannot be Introduced by nucleophilic substitution of of Aromatic chlorine in chlorobenzene but cyanobenzene can be easily obtained from diazonium salt. 

Sandmeyer-type reactions are a useful route to polynitroarylenes with unusual substitution patterns. In these reactions an arylamine is treated with a source of nitrous acid to form an intermediate diazonium salt which is readily displaced on reaction with a suitable nucleophile. Many substituents can be incorporated into the aromatic ring via this method, including the nitro group. 

The Balz-Schiemann and Wallach reactions The Balz-Schiemann reaction (the thermal decomposition of an aryl diazonium salt. Scheme 46) was for many years the only practical method for the introduction of a fluorine atom into an aromatic ring not bearing electron-withdrawing substituents. This reaction, first reported in the late 1800s, was studied in fluorine-18 chemistry as early as 1967 [214]. It involves the generation of an aryl cation by thermal decomposition, which then reacts with solvent, nucleophiles or other species present to produce a substituted aromatic compound. Use of fluorine-18-labelled... 

The Meerwein arylation is at least formally related to the atom transfer method because a net introduction of an aromatic ring and a chlorine across a double bond is accomplished (Scheme 62). Facile elimination of HC1 provides an efficient route to the kinds of substituted styrenes that are frequently prepared by Heck arylations. Standard protocol calls for the generation of an arene diazonium chloride in situ, followed by addition of an alkene (often electron deficient because aryl radicals are nucleophilic) and a catalytic quantity of copper(II) chloride. It is usually suggested that the copper salt operates in a catalytic redox cycle, reducing the diazonium salt to the aryl radical as Cu1 and trapping the adduct radical as Cu11. 

We have already described how nitration leads eventually to aromatic amines by reduction of the nitro group. In the next chapter you will meet the further development of these amines into diazoni-um salts as reagents for nucleophilic aromatic substitution by the S l mechanism with loss of nitrogen. In this chapter we need to address their potential for electrophilic aromatic substitution without the loss of nitrogen as this leads to the important azo dyes. Treatment of the amine with nitrous acid (H0N=0) at around 0°C gives the diazonium salt. 

Heating the diazonium salt below in the presence of methyl acrylate gives a reasonable yield of a chloroacid. Why is this unlikely to be nucleophilic aromatic substitution by the S l mechanism (Chapter 23) Suggest an alternative mechanism that explains the regioselectivity. 

Mechanical addressing can be also used for combinatorial postsynthetical modifications of conductive polymers. Postsynthetical modification was applied to formations of a number of different derivates of polyaniline (Fig. 13.4), the modification was performed by nucleophilic addition (Fig. 13.4), coupling with diazonium salts and by electrophilic aromatic substitution.46... 

As it is well known, nucleophilic substitution of a C-X bond, one of the key synthetic reactions with aliphatic compounds is severely limited with aromatic derivatives, where it occurs thermally only with electron-withdrawing substituted compounds and/or under severe conditions. Alternatives include time honored reactions involving the phenyl radical generated by decomposition of diazonium salts after a reductive step, such as the Meerwein and the Gomberg-Bachmann reactions, as well as the (often photoinitiated) SrnI reaction, where a (usually weak, e.g. carbon-iodine) bond is cleaved after monoelectronic reduction to give an aryl radical as the active inter-mediate that adds to an enolate, cyanide or other nucleophiles (and thus again with an aryl radical as the key intermediate. Scheme S). ... 

Aryl diazonium salts can also undergo coupling reactions with phenol or aromatic amines, which possess nucleophilic OH or NH2 groups, respectively. This electrophilic substitution reaction (with the diazonium salt as the electrophile) produces highly coloured azo compounds. 

SANDMEYER GATTERMANN Aromatic substitution Substitution of an amine group via the diazonium salt by nucleophiles such as Cl, Br, -, cn-R-S, HO, some via cuprous salt catalysis. 

In Chapter 16, we will look at the reactions of substituted benzenes. First we will study reactions that change the nature of the substituent on the benzene ring and we will see how the nature of the substituent affects both the reactivity of the ring and the placement of any incoming substituent. Then we will look at three types of reactions that can be used to synthesize substituted benzenes other than those discussed in Chapter 15— reactions of arene diazonium salts, nucleophilic aromatic substitution reactions, and reactions that involve benzyne intermediates. You will then have the opportunity to design syntheses of compounds that contain benzene rings. 

We have seen that primary arylamines react with nitrous acid to form stable arene-diazonium salts (Section 16.12). Arenediazonium salts are useful to synthetic chemists because the diazonium group can be replaced by a wide variety of nucleophiles. This reaction allows a wider variety of substituted benzenes to be prepared than can be prepared solely from electrophilic aromatic substitution reactions. 

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