Amine reaction with nitrous acid

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. 

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. " ... 

The formation of Af-nitrosamines which usually separate as orange-yellow oils or low melting solids indicates the presence of a secondary amine. Confirm the formation of the nitrosamine by the Liebermann nitroso reaction. This consists in warming the nitrosamine with phenol and concentrated sulphuric acid. The sulphuric acid liberates nitrous acid from the nitrosamine, and the nitrous acid reacts with the phenol to form p-nitrosophenol, which then combines with another molecule of phenol to give red indophenol. In alkaline solution the red indophenol yields a blue indophenol anion. 

Reactions with Nitrous Acid.—With nitrous acid (HO—NO) primary amines, due to the presence of two remaining ammonia hydrogen atoms, react with the oxygen of nitrous acid which is linked directly to the nitrogen alone. In the case of the alkyl amines the reaction does not stop here, but the hydroxyl group of the nitrous acid unites with the alkyl radical forming an alcohol and the nitrogen is set free. 

These reactions with nitrous acid should be considered in connection with the discussion of the action of nitrous acid on alkyl amines as given in Part I, p. 60. 

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 —... 

Nitrous acid reacts with all classes of amines. The products that we obtain from these reactions depend on whether the amine is primary, secondary, or tertiary and whether the amine is aliphatic or aromatic. 

When treated with nitrous acid, tertiary aliphatic amines, whether water-soluble or water-insoluble, are protonated to form water-soluble salts. No further reaction occurs beyond salt formation. This reachon is of no practical use. 

Path d) retention of corfguration. Alcohols are formed in low yield in the nitrous acid deamination of amines in acetic acid, and they have been isolated in only a few instances. The alcohol represents the intramolecular product of the deamination and with the exception of the norbomanols, which will be discussed later, they are formed from secondary and tertiary carbinamines with overall retention of configuration (Table 12). The results are so striking and so similar to those of the nitrosoamide decomposition (Tables 6 and 7) that we feel a common reaction mechanism must be involved. Paths (d) and (g) (equation 146) involving predominant collapse on the front side of the cation are proposed for the formation of the alcohoP° -i3i-i °. 

When nihous acid reacts with amines, the products are very useful. We will soon see that these products can be used in a large number of synthetic transformations. So, let s make sure that you are comfortable with the reactions between amines and nitrous acid. 

Nitrous acid reacts with primary aliphatic amines in the presence of mineral acids with the formation of volatQe nitrosamines, which isomerise to stable diazohydroxides. Diazohydroxides are split into nitrogen and a primary alkyl cation, which may partly isomerise to a secondary cation and both cations are eliminated, which yields the corresponding alkene. Substitution reactions then yield primary and secondary alcohols and symmetrical and unsymmetrical secondary amines. I n the presence of hydrohalogen acids, both alkyl... 

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... 

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). ... 

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