Reaction with nitrous acid. Diazotization

Primary amino groups attached to azole rings react normally with nitrous acid to give diazonium compounds via primary nitroso compounds. However, the azole series shows two special 

Attempted diazotization in dilute acid sometimes yields primary nitroso compounds. Reactions of 3- and 5-amino-1,2,4-thiadiazoles with sodium nitrite and acid give primary nitrosamines (e.g. 589 — 590) (65AHC(5)119) which can be related to the secondary nitrosamines (591) prepared in the normal way. 1-Substituted 5-aminotetrazoles with nitrous acid give stable primary nitrosamines (592). Primary nitrosamines have been isolated in the imidazole series. 

Diazotization of aminoazoles with free cyclic NH groups can give diazo anhydrides which show many of the normal reactions of diazoniums (67AHC(8)l). In the pyrazole series these diazo anhydrides (e.g. 593) are particularly stable. 

Diazotetrazole (594) has been prepared on pyrolysis it yields carbon atoms and nitrogen 

Pyridine-2- and -4-diazonium ions are far less stable than benzenediazonium cations. Azole-diazonium salts generally show intermediate stability provided diazotization is carried out in concentrated acid, many of the usual diazonium reactions succeed. Indeed, azolediazonium salts are often very reactive in coupling reactions. 

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Butler recently reviewed the diazotization of heterocyclic amines (317). Reactions with nitrous acid yield in most cases N-exocyclic compounds. Since tertiary amines are usually regarded as inen to nitrosation, this... 

Amino derivatives of 1,2,3- and 1,2,4-triazoles are useful precursors to the corresponding nitro-substituted triazoles. 3-Amino-1,2,4-triazole (98) undergoes diazotization on reaction with nitrous acid the resulting diazonium salt (110) can react with a range of nucleophiles, including an aqueous solution of sodium nitrite which yields 3-nitro-1,2,4-triazole (111). Diazotization of 3,5-diamino-l,2,4-triazole (112), followed by heating with an aqueous solution of sodium nitrite, yields 3,5-dinitro-1,2,4-triazole (113). ... 

One of the most versatile classes of intermediates for the synthesis of other aromatic compounds are the aryl diazonium ions formed by diazotization of anilines in acidic solution." Unlike aliphatic diazonium ions, which decompose very rapidly to molecular nitrogen and the aliphatic carbonium ion, aryl diazonium ions have sufficient stability to permit controlled reactions, and in some cases salts of the diazonium ions can be isolated. The usual procedure for nitrosation involves reaction with nitrous acid in aqueous solution ... 

The most important reaction of primary aromatic amines is diazotization, i.e. their reaction with nitrous acid with the formation of diazonium salts which can be coupled with phenols or with aromatic amines to give intensely colored azo dyes... 

In this section, we will consider reactions of amino acids other than those leading to peptide formation—that is much the most significant process and will be covered in the next section. Many of the other reactions are simply those you would expect for primary amines, or carboxylic acids. The amino groups can be acylated by acid chlorides or anhydrides (Figure 22.24). Reaction with nitrous acid leads to diazotization the reaction in Figure 22.25 goes with a double inversion of configuration, via an unstable a-lactone. The product is obtained in better than 95 % enantiomer excess. 

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 treatment of 3-amino-1,2,4-triazine 2-oxides 1 or 3-amino-1,2,4-benzotri-azine 1-oxides 29 with nitrous acid proceeds as a diazotization reaction, but the diazo compounds have never been isolated owing to the easy displacement of the di-azo group with nucleophiles. Thus the reaction of 3-amino-1,2,4-triazine 2-oxides 1 with sodium nitrite in hydrochloric or hydrobromic acids leads to the corresponding 3-halogen-1,2,4-tiiazine 2-oxides 119 or 3-bromo-l,2,4-benzotriazine 1-oxides 120 (77JOC546, 82JOC3886). 

The reaction of nitrous acid with the amino group of the /3-amino alcohol—e.g. 1-aminomethyl-cyclopentanol 1—leads to formation of the nitrosamine 4, from which, through protonation and subsequent loss of water, a diazonium ion species 5 is formed " —similar to a diazotization reaction ... 

Arylamines are converted by diazotization with nitrous acid into arenediazonium salts, ArN2+ X-. The diazonio group can then be replaced by many other substituents in the Sandmeyer reaction to give a wide variety of substituted aromatic compounds. Aryl chlorides, bromides, iodides, and nitriles can be prepared from arenediazonium salts, as can arenes and phenols. In addition to their reactivity toward substitution reactions, diazonium salts undergo coupling with phenols and arylamines to give brightly colored azo dyes. 

For aromatic amines, the reaction is very general. Halogen, nitro, alkyl, aldehyde, sulfonic acid, and so on, groups do not interfere. Since aliphatic amines do not react with nitrous acid below a pH of 3, it is even possible, by working at a pH of 1, to diazotize an aromatic amine without disturbing an aliphatic amino group in the same molecule. ... 

Rearrangements Involving Diazonium Ions. Aminomethyl carbinols yield ketones when treated with nitrous acid. The reaction proceeds by formation and rearrangement of diazonium ions. The diazotization reaction generates the same type of (J-hydroxycarbocalion that is involved in the pinacol rearrangement. 

Treatment of 36 with nitrous acid in dilute acetic acid gives a mixture of anthranilazide (37) and 3-amino-1,2,3-benzotriazin-4(3/f)-one (10, R = NH2). When the same reaction is carried out in dilute hydrochloric acid, the sole product formed initially with one mole equivalent of nitrous acid is 10, R = NHj, but this readily reacts further to give 10, R = Diazotization of acetophenone anthranylhydrazone followed by mild acid hydrolysis is a superior route to 10, R = NHj, and gives a much purer product. l,2,3-Benzotriazine-4(3/0-thione (39, R = H) and the 3-substituted derivatives (39) are readily available by diazotization of thioanthranilamide (38, R = H) and its derivatives. ... 

Parnell has reexamined the reaction of anthraniionitrile with ammonia, found that o-aminobenzamidine can in fact be prepared relatively easily, and shown that it is converted into 56, R = H, on diazotization." Reaction of 57 under the same conditions gives 58. Treatment of A,A -diaryl-o-aminobenzamidines (59) with nitrous acid... 

The reaction of aminoguanidine with nitrous acid in the presence of an excess of acetic acid gives also l,3-ditetrazyltriazine(IX).It is possible that 5-aminotetrazole first arises, which then undergoes diazotization and the diazo compound thus formed couples with the remaining aminotetrazole ... 

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