Nitrite, sodium reaction with aryl diazonium salts

Nitrous acid (3), which is generated from sodium nitrite and aqueous acid, undergoes dehydration under the acidic conditions to form nitrosyl cation 4. Reaction of 4 with the aryl amine eventually affords the aryl diazonium salt after tautomerization and dehydration. The addition of fluoroboric acid sets the stage for the second step leading to aryl fluoride. 

Generation of an aryl radical and an aryl cation from a diazonium salt are easy processes. Both species are very reactive and are readily trapped by a wide variety of nucleophiles. Conversion of an amino group into a nitro group involves reaction of a diazonium fluoroborate with aqueous sodium nitrite solution in the presence of copper powder (Scheme 8.22). 

Treatment of diazonium salts with cuprous, Cu(I), salts generates aryl halides. When 398 reacts with CuCl (cuprous chloride) or CuBr (cuprous bromide), the products are chlorobenzene or bromobenzene via what is probably a radical reaction.29l jhis conversion is known as the Sandmeyer reaction. 2 The use of copper powder rather than cuprous salts for this transformation is often called the Gattermann reaction. 93,292b,c Aryl iodides are also produced from diazonium salts by reaction with potassium iodide (KI) but the actual reactive species may be l3-.294,295 Treatment of aniline derivative 403 with sodium nitrite and HCl followed by treatment with KI, for example, gave a 89% yield of 404.Aryl nitriles are generated under Sandmeyer conditions using cuprous cyanide (CuCN), as in the conversion of 405 to benzonitrile derivative 407 via diazonium chloride, 406. 

Aryl halides are frequently prepared from the corresponding aryldiazonium salts by diazotation procedures. However, diazonium salts can be subjected directly to very mild Heck arylation conditions, which deliver coupled products (entry 19). Preferably, the reaction is executed in nonaqueous solvents such as acetonitrile, acetone, or methylene chloride with sodium acetate as base and with palladiumbis(dibenzylideneacetone) as catalyst. Alternatively, a combination of the amine and f-butyl nitrite, in a mixture of acetic acid and monochloroacetic acid, can provide the desired product directly, which makes the isolation of a diazonium salt unnecessary (entry 20). " It is also possible to use aromatic acid anhydrides as oxidative addition precursors (entry 21). Clearly, anhydrides are very interesting starting materials for a number of Heck reactions due to price and absence of halide salt formation. 

The successful synthesis of these compounds showed the feasibility of using the carbodiimidazole coupling reaction in the formation of aryl-azido ATP analogs. For the general synthesis of the arylazidocarboxylic acids, 4-fluoro-3-nitroaniline is first diazotized in a concentrated hydrochloric acid medium in the presence of sodium nitrite [Eq. (2)]. The diazonium salt is subsequently treated with sodium azide, which results in the formation of a light-sensitive 4-fluoro-3-nitrophenyl azide (IV) [Eq. (3) ]. The structure of (IV) has been confirmed by its melting point of 52°-52.5° (recrystallized from petroleum ether) its NMR spectrum, 7.47 ppm (2 protons), 7.78 ppm (1 proton) and its mass spectrum, m/e 182. 

The Schiemann reaction is the most common method for the introduction of fluorine onto an aromatic ring. It is carried out by treatment of a primary aromatic amine with sodium nitrite in aqueous HCl followed by addition of HBF or NaBF. The diazonium fluoroborate salt precipitates and is collected and dried. Heating the dry salt brings about its decomposition to an aryl fluoride, nitrogen, and boron trifluoride. The Schiemann reaction is also thought to involve an aryl cation intermediate. 

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