Nitrosation primary aromatic amines

Typical nitrosating agents are sodium nitrite with mineral acids or pentyl nitrite with mineral acids. A relatively new reagent, nitrosylsulfuric acid, has been used to nitrosate primary aromatic amines. 

Dyes. Sodium nitrite is a convenient source of nitrous acid in the nitrosation and diatozation of aromatic amines. When primary aromatic amines react with nitrous acid, the intermediate diamine salts are produced which, on coupling to amines, phenols, naphthols, and other compounds, form the important azo dyes (qv). The color center of the dye or pigment is the -N=N- group and attached groups modify the color. Many dyes and pigments (qv) have been manufactured with shades of the entire color spectmm. 

Synthesis. Almost without exception, azo dyes ate made by diazotization of a primary aromatic amine followed by coupling of the resultant diazonium salt with an electron-rich nucleophile. The diazotization reaction is carried out by treating the primary aromatic amine with nitrous acid, normally generated in situ with hydrochloric acid and sodium nitrite. The nitrous acid nitrosates the amine to generate the N-nitroso compound, which tautomerizes to the diazo hydroxide. 

The nitrosation of primary aromatic amines 1 with nitrous acid 2 and a subsequent dehydration step lead to the formation of diazonium ions 3. The unstable nitrous acid can for example be prepared by reaction of sodium nitrite with aqueous hydrochloric acid. 

This type of scheme for the nitrosation of primary aromatic amines was first used by Ridd in 1959. The comparison of the present scheme with that from 1959 demonstrates how much more diversified the knowledge on diazotization mechanisms has become in three decades. 

Ring nitrosation with nitrous acid is normally carried out only with active substrates such as amines and phenols. However, primary aromatic amines give diazonium ions (12-47) when treated with nitrous acid, " and secondary amines tend to give N-nitroso rather than C-nitroso compounds (12-49) hence this reaction is normally limited to phenols and tertiary aromatic amines. Nevertheless secondary aromatic amines can be C-nitrosated in two ways. The N-nitroso compound first obtained can be isomerized to a C-nitroso compound (11-32), or it can be treated with another mole of nitrous acid to give an N,C-dinitroso compound. Also, a successful nitrosation of anisole has been reported, where the solvent was CF3COOH—CH2CI2. " ... 

Diazotization is the reaction of a primary aromatic amine with a nitrosating agent, such as sodium nitrite or, to a lesser extent, with nitrosylsulfuric acid N0S04H, nitrous gases, or organic nitrites in an aqueous acidic solution at a temperature between 0 and 5°C, converting the amine to its diazonium salt ... 

Contrary to earlier assumptions, the aryl ammonium ion is not able to undergo diazotization since the crucial step in the diazotization mechanism is the electrophilic nitrosation of the free amino group in the free-base primary aromatic amine 12 ... 

Because primary aromatic amines are weaker bases/nucleophiles than aliphatic (due to interaction of the electron pair on N with the n orbital system of the aromatic nucleus), a fairly powerful nitrosating agent is required, and the reaction is thus carried out at relatively high acidity. Sufficient equilibrium concentration of unprotonated... 

Nitrobenzene chloride, sulfonylperoxy radical reactions, 1035, 1036 2-Nitrobenzenesulfinylperoxy intermediate, superoxide reactions, 1034 Nitrogen-containing compound oxidation bis(trimethylsilyl) peroxide reactions, 802-3, 804 dioxiranes, 1151-5 primary aromatic amines, 1151 A-oxidation, 531-8, 539 Nitrohpids, hpid hydroperoxides, 952-4 Nitronate ions, dioxirane oxidation, 1152-3 Nitrosation, malondialdehyde, 667 Nitroso compounds, spin trapping, 664 Nitrotyrosine, peroxynitiite determination, 740-1... 

Tertiary aromatic amines may be nitrosated directly with nitrous acid, whereas primary aromatic amines normally are diazotized under these conditions. Some phenols may also be nitrosated under conditions similar to those used for the nitrosation of tertiary amines. 

The primary aromatic amines which will be preferentially nitrosated rather than diazotized are those which do not bear strongly electron-withdrawing substituents and are capable of coupling with diazonium salts to give azo dyes. 

The nitrosation of primary aromatic amines with nitrous acid (generated in situ from sodium nitrite and a strong acid, such as hydrochloric acid, sulfuric acid, or HBF4) leads to diazonium salts, which can be isolated if the counterion is non-nucleophilic. 

Griess diazo reaction. Formation of aromatic diazonium salts from primary aromatic amines and nitrous acid or other nitrosating agents. 

Secondary aliphatic amines form stable N-nitrosoamines, however, and therefore, their investigation will be discussed briefly in this section, although N-nitroso derivatives of secondary aliphatic amines do not fall within the scope of this book. We will see that kinetics and mechanisms of nitrosation of secondary amines display many similarities with the diazotization of primary aromatic amines. 

Nitrosation (Section 22.15) The reaction of a substance, usually an amine, with nitrous acid. Primary amines yield dia-zonium ions secondary amines yield A-nitroso amines. Tertiary aromatic amines undergo nitrosation of their aromatic ring. 

Although Eqs. (7)- 10) may be valid for a wide range of aromatic amines treated in the usual manner in a mineral acid medium with sodium nitrite, direct nuclear nitrosation of certain primary and secondary aromatic amines was found possible when nitrosylsulfuric acid in concentrated sulfuric acid was used as the nitrosation agent [22]. 

Amines and amides can be N-nirra/erf549 with nitric acid,55" N205,551 or N02, 552 and aromatic amines can be converted to triazenes with diazonium salts. Aliphatic primary amines can also be converted to triazenes if the diazonium salts contain electron-withdrawing groups.555 C-Nitrosation is discussed at 1-3 and 2-8. 

The fonnation of aromatic diazonium salts from aromatic primary amines is one of the oldest synthetic procedures in organic chemistry. Methods based on nitrosation of die amine with nitrous acid in aqueous solution are the best known, but there are variants which are of particular use with weakly basic amines and for the isolation of diazonium salts from nonaqueous media. General reviews include a book by Saunders and Allen and a survey of preparative methods by Schank. There are also reviews on the diazotization of heteroaromatic primary amines and on the diazotization of weakly basic amines in strongly acidic media. The diazotization process (Scheme 11) goes by way of a primary nitrosamine. 

The reaction of aromatic amines with nitrous acid is of considerable importance and the formation of diazonium salts from the primary amines is discussed in detail in Section 8.6. Reaction of nitrous acid with secondary amines does not give diazonium salts, but results instead in A -nitrosation. Tertiary amines such as A, A -dimethylaniline do not N-nitrosate, but undergo electrophilic substitution by the nitrosonium cation (NO ) to give A, A -dimethyl-4-nitrosoaniline (Scheme 8.8). 

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