Diazonium ions nucleophilic substitution reactions

Nucleophilic substitution reactions that occur imder conditions of amine diazotization often have significantly different stereochemisby, as compared with that in halide or sulfonate solvolysis. Diazotization generates an alkyl diazonium ion, which rapidly decomposes to a carbocation, molecular nitrogen, and water ... 

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 ... 

Nucleophilic substitution reactions may involve several different combinations of charged and uncharged species as reactants. The equations in Scheme 4.1 illustrate the four most common charge types. The most common reactants are neutral halides or sulfonates, as illustrated in Parts A and B of the scheme. These compounds can react with either neutral or anionic nucleophiles. When the nucleophile is the solvent, as in Entries 2 and 3, the reaction is called a solvolysis. Reactions with anionic nucleophiles, as in Entries 4 to 6, are used to introduce a variety of substituents such as cyanide and azide. Entries 7 and 10 show reactions that involve sulfonium ions, in which a neutral sulfide is the leaving group. Entry 8 involves generation of the diphenylmethyl diazonium ion by protonation of diphenyldiazomethane. In this reaction, the leaving... 

Nevertheless, several kinetic studies have shown that certain nucleophilic substitution reactions of aryl diazonium ions are first order and independent of the concentration of the nucleophilic species. Solvent effects, isotope effects, and substituent effects are also in agreement with a rate-determining unimolecular decomposition of the aryl diazonium ion. In other reactions, an adduct of the nucleophile and diazonium ion is a distinct intermediate. Substitution results when nitrogen is eliminated from the adduct. Finally, substitution can occur via radical... 

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 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). 

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. 

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. 

The diazonium group can be replaced by a number of groups.222 Some of these are nucleophilic substitutions, with SnI mechanisms (p. 644), but others are free-radical reactions and are treated in Chapter 14. The solvent in all these reactions is usually water. With other solvents it has beeen shown that the SnI mechanism is favored by solvents of low nucleo-philicity, while those of high nucleophilicity favor free-radical mechanisms.222 (For formation of diazonium ions, see 2-49.) The N2 group can be replaced by Cl, Br. and CN, by a nucleophilic mechanism (see OS IV, 182). but the Sandmeyer reaction is much more useful (4-25 and 4-28). As mentioned on p. 651 it must be kept in mind that the N2 group can activate the removal of another group on the ring. 

The occurrence of some substitution in the deamination of 2-amino-2-deoxy-/3-D-mannopyranosides131 152 (72), and its absence in the reaction of the a-D-pyranoside150 69, must be due to the steric effect of the axial anomeric substituent which (in the a-D-pyran-oside) hinders the approach of the nucleophile (water) to either the C-2 carbonium ion or to C-2 of the diazonium ion. The glucose and glucitol tentatively detected as minor products in the deamination of 72 (R = D-glucose residue and R = D-glucitol residue) presumably arose by way of a hydride shift of H-l to C-2. 2-Deoxy-D-glucono-1,5-lactone (75) was not detected, as it would probably have. o,... 

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 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. 

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