Nitrous acid, in diazotization

Urea reacts with nitrous acid to yield carbon dioxide and nitrogen this is a useful way to destroy excess nitrous acid in diazotizations. 

The reagent is used to destroy excess nitrous acid in diazotizations. 

The behavior of aminopyrazole 88 (R = 4-NO2—C6H4) under these conditions was quite different diazotization using nitrous acid in concentrated hydrochloric acid afforded an alkynylpyrazole diazonium chloride, which did not participate in the Richter reaction, probably due to the electron-withdrawing effect of the nitro group. Instead, after neutralization of the hydrochloric acid with sodium hydrogen... 

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. ... 

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 ... 

Aryl fluorides also may be prepared from arenamines by way of dia-zonium salts if the procedure is slightly modified. The amine is diazotized with nitrous acid in the usual way then fluoroboric acid or afluoroborate salt is added, which usually causes precipitation of a sparingly soluble diazonium fluoroborate. The salt is collected and thoroughly dried, then carefully heated to the decomposition point—the products being an aryl fluoride, nitrogen, and boron trifluoride ... 

None of the methods mentioned gives satisfactory diazotization of 1,2- and 2,1-aminonaphthols or their sulfonic acid and other derivatives, all of which are readily oxidized to quinones by nitrous acid in acid solution. Diazotization of these compounds can be carried out successfully by using just enough acid to make the aminonaphthol salt, or, in the case of the sulfo derivatives, to make the compound containing one free sulfo group, and treating with nitrite in the presence of one equivalent of a zinc salt or a small amount of a copper salt. If a copper salt is used, the copper must be removed when diazotization is complete, but the presence of zinc in a diazo solution usually does no harm. 

The foimation of aromatic diazonium salts from aromatic primary amines is one of the oldest synthetic procedures in organic chemistry. Methods based on nitrosation of amine with nitrous acid in aqueous solution are die best known, but diere are variants which are of particular use widi weakly basic amines and for the isolation of diazonium salts fiom nonaqueous media. General reviews include a book by Saunders and AUen and a survey of preparative methods by Schank. There ate 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 common procedure for diazotization by means of nitrous acid in aqueous solutions is illustrated by the synthesis of benzenediazonium chloride, o-, m-, and p-methylbenzenediazonium sulfates, and/S-naph-thalenediazonium chloride. ... 

Diazotization of 2-aminopyrazine with nitrous acid in dilute or concentrated sulfuric acid gave 2 hydroxypyrazine (to 67% yield) (86, 477, 720, 818). Many such conversions have been described, mostly using nitrosylsulfuric acid in concentrated sulfuric acid solution. Preparations of hydroxypyrazines from the aminopyrazines are summarized as follows 2-hydroxy-3-methylpyrazine (sodium nitrite in concentrated sulfuric acid-acetic acid) (681), 2Jiydroxy-3,5-dimethylpyrazine (aqueous nitrous acid, then at 60°) (524), 3-hydroxy-2,5-dimethylpyrazine (477), 2,5-diethyl-3-hydroxypyrazine (aqueous nitrous acid) (478), 2-hydroxy-6-phenyl-pyrazine (365a), 24iydroxy-3,5-diphenylpyrazine (nitrous acid in N hydrochloric acid) (524), 3-hydroxy-2,5-diphenylpyrazine (282), 2-s-butyl-3-hydroxy-5-isobutyl-pyrazine (93), 5TS-butyl-3 hydroxy-2-isobutylpyrazine (92, 536), 2,5-di-s-butyl-3-hydroxypyrazine (89, 720), 3-hydroxy-2-isobutyl-5-isopropylpyrazine (103, 525), 2,3-dihydroxypyrazine (from 2 amino-3-hydroxypyrazine) (757, 1055) and its... 

If the base is slightly soluble in acid, as in the case of those arylamines which have very feeble basic properties, a large excess of acid is used, or a suspension of the finely divided base is diazo-tized. The base dissolves as fast as that portion which is in solution is diazotized. The aminosulfonic and aminocarboxylic acids are diazotized by first dissolving in alkali to form the sodium salt and then adding the calculated amount of nitrite. The mixture is cooled and added slowly to a solution of acid. The end of all diazotizations is recognized by the presence of,free nitrous acid in the solution. As a test of this, a drop of the solution of the diazonium salt placed on starch-iodide paper produces a dark blue stain immediately, due to the oxidation of iodide by nitrous acid to iodine and action of the latter on starch. 

Diazotization of cyclopropylamines in the presence of a chloride source is also a useful method for the preparation of some chlorocyclopropanes. When 1-aminocyclopropanecarboxylic acid was treated with nitrous acid in the presence of potassium chloride, 1-chlorocyclopropanecarb-oxylic acid (9) was isolated in 75% yield. Similarly, a modified Sandmeyer reaction of 7-ami-nocyclopropanoacenaphthylene (10) yielded 7-chlorocyclopropanoacenaphthylene (11). ... 

Diazotization of 1-aminocyclopropanecarboxylic acid with nitrous acid in the presence of lithium bromide gave 1-bromocyclopropanecarboxylic acid (16) in 75% yield. ... 

Treatment of aminopurine nucleosides with nitrous acid in aqueous solution normally results in replacement of the amino group by a hydroxyl group thus, inosine is prepared from adenosine. Although this process is undoubtedly a diazotization, the intermediate diazonium salt must have... 

Having understood the various steps that are involved in the diazotization process, one may define it as— A chemical interaction whereby an aromatic primary amine, having amino (-NH ) function directly attached to the nucleus, upon treatment with nitrous acid in cold (0— 5°C) yield diazonium salts. ... 

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 ... 

In some cases the hydroxypyridine was a byproduct in the preparation of a halogenopyridine. t From reaction of the nitramino compoimd with nitrous acid, t Diazotization was carried out in 60 per cent hydrofluoric acid. 

Several color reactions can be used to detect nitramines reaction with aromatic amines in acetic acid (71), reaction with ferrous sulfate in sulfuric acid (72,73), diazotization with nitrous acid in 50% acetic acid, and coupling with a suitable component (74) (for aromatic nitramines) ... 

Aromatic diazonium salts are generally prepared by diazotization of aromatic amines in aqueous systems with nitrous acid. In non-aqueous systems, diazotizations have been carried out with isoamyl nitrite. 

It is prepared by an intramolecular transformation of diazoaminobenzene in the presence of aniline hydrochloride, or in one stage by diazotizing a solution of aniline and aniline hydrochloride with an insufficient amount of nitrous acid. 

The most important reaction of the diazonium salts is the condensation with phenols or aromatic amines to form the intensely coloured azo compounds. The phenol or amine is called the secondary component, and the process of coupling with a diazonium salt is the basis of manufacture of all the azo dyestuffs. The entering azo group goes into the p-position of the benzene ring if this is free, otherwise it takes up the o-position, e.g. diazotized aniline coupled with phenol gives benzeneazophenol. When only half a molecular proportion of nitrous acid is used in the diazotization of an aromatic amine a diazo-amino compound is formed. 

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... 

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 reactivity of the amino groups at the pteridine nucleus depends very much upon their position. All amino groups form part of amidine or guanidine systems and therefore do not behave like benzenoid amino functions which can usually be diazotized. The 4-, 6-and 7-amino groups are in general subject to hydrolysis by acid and alkali, whereas the 2-amino group is more stable under these conditions but is often more susceptible to removal by nitrous acid. 

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. 432->433) (65AHC(5)n9) which can be related to the secondary nitrosamines (434) prepared in the normal way. 1-Substituted 5-aminotetrazoles with nitrous acid give stable primary nitrosamines (435). Primary nitrosamines have been isolated in the imidazole series. 

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