Nitrous acid, reaction 4-amines

Some of the most important reactions of amines are brought about by nitrous acid (HONO). The character of the products depends very much on whether the amine is primary, secondary, or tertiary. In fact, nitrous acid is a useful reagent to determine whether a particular amine is primary, secondary, or tertiary. With primary amines nitrous acid results in evolution of nitrogen gas with secondary amines insoluble yellow liquids or solid 7V-nitroso compounds, R2N—N=0, separate tertiary alkanamines dissolve in and react with nitrous acid solutions without evolution of nitrogen, usually to give complex products ... 

The reaction which takes place between dimethylamine and nitrous acid is of importance, as it is an example of a general reaction used to distinguish secondary amines from the other classes of amines. Nitrous acid reacts with dimethylamine and forms a substance which belongs to the class known as nitroso compounds —... 

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. 

Aromatic primary amines differ markedly from aliphatic amines in their reaction with nitrous acid. Thus a cold aqueous solution of mono thylamine hydrochloride reacts with nitrous acid to give mainly the corresponding primary alcohol ... 

Diazonium salts couple readily with aromatic primary amines, giving diazoamino compounds. If for instance an aqueous solution of aniline sulphate is diazotised with a deficiency of nitrous acid, only part of it is converted into benzenediazonium sulphate and the latter then couples with the unchanged aniline to give diazoaminobenzene. The reaction is carried out at the opti-CeHsNHj.HjSO + HONO = CbHsNjHSO, + zHaO... 

The Reaction has the following limitations (i) a compound that can liberate nitrous acid in acid solution is required (e.g., a metallic nitrite or a nitroso-amine, p. 204). (2) Nitrophenols and />-substituted phenols do not give the test. (3) Among the dihydroxyphenols. only resorcinol gives a satisfactory positive test. 

Primary aromatic amines differ from primary aliphatic amines in their reaction with nitrous acid. Whereas the latter yield the corresponding alcohols (RNHj — ROH) without formation of intermediate products see Section 111,123, test (i), primary aromatic amines 3neld diazonium salts. Thus aniline gives phcnyldiazonium chloride (sometimes termed benzene-diazonium chloride) CjHbNj- +C1 the exact mode of formation is not known, but a possible route is through the phenjdnitrosoammonium ion tlius ... 

The experimental conditions necessary for the preparation of a solution of a diazonium salt, diazotisation of a primary amine, are as follows. The amine is dissolved in a suitable volume of water containing 2 5-3 equivalents of hydrochloric acid (or of sulphuric acid) by the application of heat if necessary, and the solution is cooled in ice when the amine hydrochloride (or sulphate) usually crystallises. The temperature is maintained at 0-5°, an aqueous solution of sodium nitrite is added portion-wise until, after allowing 3-4 minutes for reaction, the solution gives an immediate positive test for excess of nitrous acid with an external indicator—moist potassium iodide - starch paper f ... 

Some reference to the use of nitrous acid merits mention here. Primary aromatic amines yield diazonium compounds, which may be coupled with phenols to yield highly-coloured azo dyes (see Section IV,100,(iii)). Secondary aromatic amines afford nitroso compounds, which give Liebermann a nitroso reaction Section IV,100,(v). Tertiary aromatic amines, of the type of dimethylaniline, yield p-nitroso derivatives see Section IV,100,(vii). ... 

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... 

Nitrosation (Section 22 15) The reaction of a substance usu ally an amine with nitrous acid Pnmary amines yield dia zonium 10ns secondary amines yield N nitroso amines Tertiary aromatic amines undergo nitrosation of their aro matic ring... 

Synthesis. The classic laboratory synthesis of /V-nitrosamines is the reaction of a secondary amine with acidic nitrite [14797-65-0] at ca pH 3. The primary nitrosating intermediate is N2O2 arising from nitrous acid [7782-77-6] (48). 

Cycloaliphatic amines are strong bases with chemistry similar to that of simpler primary, secondary, or tertiary amines. Upon reaction with nitrous acid,... 

Reaction with Nitrous Acid. Primary, secondary, and tertiary aromatic amines react with nitrous acid to form a variety of products. Primary aromatic amines form diazonium salts. ... 

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. 

If primary or secondary amines are used, A/-substituted amides are formed. This reaction is called aminolysis. Hydra2ines yield the corresponding hydra2ides, which can then be treated with nitrous acid to form the a2ides used in the Curtius rearrangement. Hydroxylamines give hydroxamic acids. 

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

Oresol,—This reaction resembles that of nitrous acid on an aliphatic primary amine but the liquid requires to be warmed. 

Aniline 77 was converted into its diazonium salt with nitrous acid and this was followed by reduction with stannous chloride to afford the corresponding arylhydrazine 78. Condensation of 78 with 3-cyanopropanal dimethylacetal 79 gave the arylhydrazone 80. Treatment of 80 with PPE resulted in cyclization to indole 81. The nitrile group was then reduced to the primary amine by catalytic hydrogenation. Reaction of the amine with excess formalin and sodium borohydride resulted in Imitrex (82). 

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