Diazonium cations nucleophilic substitution

In a classic study in 1940, Crossley and coworkers demonstrated that the rates of nucleophilic substitution of the diazonio group of the arenediazonium ion in acidic aqueous solution were independent of the nucleophile concentration, and that these rates were identical with the rate of hydrolysis. Since that time it has therefore been accepted without question that these reactions proceed by a DN + AN mechanism, i.e., that they consist of a rate-determining irreversible dissociation of the diazonium ion into an aryl cation and nitrogen followed by rapid reactions of the cation with water or other nucleophiles present in solution (Scheme 8-6). 

The stabilities of pyridine-2- and -4-diazonium ions resemble those of aliphatic rather than benzenoid diazonium cations. Benzenediazonium ions are stabilized by mesomerism which involves electron donation from the ring, but such electron donation is unfavorable in 2- and 4-substituted pyridines. On formation, pyridine diazonium cations normally immediately react with the aqueous solvent to form pyridones. However, by carrying out the diazotization in concentrated HC1 or HBr, useful yields of chloro- and bromopyridines 752 can be obtained. Iodinated pyridines can be obtained in good yield using the Sandmeyer reaction. Aminopyridazines and -pyrazines, 2- and 4-aminopyrimidines, and amino-1,2,4-triazines behave similarly. Nucleophilic fluorination via the BalzSchiemann reaction of diazonium fluoroborates yields fluoropyridines, including 2-fluoropyridines. Fluoroborates can also be converted into fluoro compounds by ultraviolet irradiation. 

The wide utility of aryl diazonium ions as synthetic intermediates results from the excellence of N2 as a leaving group. There are several general mechanisms by which substitution can occur. One involves unimolecular thermal decomposition of the diazonium ion, followed by capture of the resulting aryl cation by a nucleophile. The phenyl cation is very unstable (see Part A, Section 3.4.1.1) and therefore highly unselective.86 Either the solvent or an anion can act as the nucleophile. 

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... 

As Schaffer has found 2.4.6-triphenyl-X -phosphorin 22 and other 2.4.6-tri-substituted X -phosphorins react smoothly with aryl diazonium salts in benzene. Nitrogen develops and the aryl residue bonds with the phosphorus. In presence of alcohols as nucleophiles, l-alkoxy-l-aryl-2.4.6-triphenyl-X -phosphorins 100 can be isolated. The aryl diazonium-tetrafluoroborate without any nucleophile in DMOE yields l-aiyl-l-fluoro-2.4.6-triphenyl-X -phosphorin 70i. As with other oxidants like halogen or mercury-Il-acetate, we suppose that in the first step triphenyl-X -phosphorin radical cation is formed. This could be shown by ESR spectroscopy. The next step may be a radical-radical addition to the X -phosphorin cation or a nucleophileradical addition respectively ... 

Because aryl diazonium salts are reasonably stable, other nucleophiles may be introduced to capture the aryl cation when the diazonium salt is heated. Among these, iodide ion is important as it allows the preparation of aryl iodides in good yield. These compounds are not so easy to make by electrophilic substitution (Chapter 22) as aryl chlorides or bromides because iodine is not reactive enough to attack benzene rings. Aryl iodides are useful in the more modern palladium chemistry of the Heck reaction, which you will meet in Chapter 48. 

Revision of nucleophilic aromatic substitution (p. 597) with diazonium salts and contrasting cations... 

Aryl diazonium salts react with a wide range of nucleophiles, Nu, to give substitution yielding Ar-Nu. Although the reaction is usually written as involving a phenyl cation, in a number of cases, a phenyl radical is the more likely intermediate. 

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