Nitrous acid tertiary amines

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... 

The nitrosating agent most often used is nitrous acid itself. Phenols are usually dissolved in sodium hydroxide solution, aqueous sodium nitrite solution is added, and nitrous acid is developed by dropping in a dilute mineral acid. Tertiary amines are dissolved in an excess of mineral acid, and the calculated amount of sodium nitrite solution is dropped in. The reaction temperature should not exceed 10°. 

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

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. 

With nitrous acid, primary amines are diazotised (equation 58), secondary amines undergo iV nitrosation (section II.C.2.e), and tertiary aliphatic or alicyclic amines fail to react while tertiary aromatic amines may undergo C-nitrosation. 

Nitrous acid does not react with aliphatic tertiary amines, such as triethyl-amine, (CaHj)aN, nor does it usually react with aromatic tertiary amines such as triphenylamine, (CaHj)aN, which contain three aryl groups. 

If, however, a tertiary amine has two alkyl groups and also an aryl group having the para position unsubstituted, then the action of nitrous acid is to insert the nitroso group directly into this para position. Dimethylaniline, for example, when treated with nitrous acid readily gives p-nitrosodimethyl-... 

Tertiary amines containing one alkyl and two aryl groups, such as mono-I ncthyldiphenyhiniir.e, Cl l3(C, l l.diX , arc rarely encountered and arc unimportant. They usually react with nitrous acid with the insertion of a nitroso group into only one of the two available para positions monomethyl-diphenylamine thus gives monomethyl-mono - pnitroso-diphenylamine. Cl hj(C.ill .)N C l 1 jXO, or V-nicthyl-p-nitrosodiphcnylaniine. 

They are readily hydrolysed by boiling dilute hydrochloric acid and the original amine can be recovered by neutralisation with alkali and steam distillation. Primary aliphatic amines liberate nitrogen with nitrous acid whilst tertiary amines are unaffected. 

Secondary and tertiary amines are not generally prepared in the laboratory. On the technical scale methylaniline is prepared by heating a mixture of aniline hydrochloride (55 parts) and methyl alcohol (16 parts) at 120° in an autoclave. For dimethylaniline, aniline and methyl alcohol are mixed in the proportion of 80 78, 8 parts of concentrated sulphuric acid are added and the mixture heated in an autoclave at 230-235° and a pressure of 25-30 atmospheres. Ethyl- and diethyl-anihne are prepared similarly. One method of isolating pure methyl- or ethyl-aniline from the commercial product consists in converting it into the Y-nitroso derivative with nitrous acid, followed by reduction of the nitroso compound with tin and hydrochloric acid ... 

Tertiary aliphatic - aromatic amines, unlike those of the aliphatic series, react with nitrous acid with the formation of G-nitroso compounds the nitroso group enters almost exclusively in the para position if available, otherwise in the ortho position. Thus dimethylaniline yields />-nitrosodiniethylaniline ... 

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... 

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. ... 

Nitrosodimethylaniline.—It is a peculiarity of the tertiary aromatic amines, which distinguish them fiom the corresponding aliphatic compounds, that they arc capable of reacting with nitrous acid. Here the nitroso-group replaces hydrogen in the para-position to the dimethylamino-group. 

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. " ... 

When secondary amines are treated with nitrous acid, N-nitroso compounds (also called nitrosamines) are formed. The reaction can be accomplished with dialkyl-, diaryl-, or alkylarylamines, and even with mono-N-substituted amides RCONHR -I-HONO RCON(NO)R. Tertiary amines have also been N-nitrosated, but in these cases one group cleaves, so that the product is the nitroso derivative of a secondary amine.The group that cleaves appears as an aldehyde or... 

The evidence for this mechanism includes the facts that nitrous oxide is a product (formed by 2 HNO —y H2O + N2O) and that quinuclidine, where the nitrogen is at a bridgehead, and therefore caruiot give elimination, does not react. Tertiary amines have also been converted to nitrosamines with nitric acid in Ac20 and with... 

Secondary and tertiary amines react with nitrous acid in a different manner. 

Tertiary amines. Tertiary amine type compounds, react with nitrous acid to yield secondary-amine type N-nitroso compounds. The myth that tertiary amines do not nitrosate to yield N-nitroso compounds, is a remarkable feat of misinformation that has persisted for over 100 years (23, 24, 25). 

The reaction of tertiary amine oxides with nitrous acid has also been shown to produce N-nitroso compounds. The mechanism for the amine oxides is similar to that for the tertiary amines (26). 

As a result of our previous work on the scope and mechanism of tertiary amine nitrosation (X), we became interested in the behavior of N-alkylaziridines toward nitrous acid. Possible modes of reaction are illustrated in Scheme 1. The operation of either path A or C would be consistent with our previous studies of oxidative dealkylation of tertiary amines (1 ), while pathway B would be akin to the observed cheleotropic transformation of N-nitroso-aziridines (2). 

In Table 1 is a list of the environmental secondary and tertiary amines which have been tested by feeding to rats together with nitrite. Of these, several react very readily with nitrite in acid solution, but some, for example phenmetrazine (2 , 27), give rise to a noncarcinogenic N-nitroso derivative. On the other hand, aminopyrine reacts extremely readily with nitrous acid, although it is a tertiary amine, and forms the potent carcinogen nitrosodimethylamine in high yield (28, ). The other amines vary considerably in the extent to which they form N-nitroso derivatives by reaction with nitrous acid, especially at the relatively low concentrations which model human exposure more closely... 

Chemists have long been aware that amines can react with various nitrosating agents, under a variety of conditions, to form a wide array of N-nitroso derivatives (1 ). It was generally assumed that only secondary amines can effectively form stable N-nitrosamines. However, it has now become apparent that primary and tertiary amines, as well as tetraalkylammonium salts, can all form N-nitroso derivatives under the appropriate reaction conditions (2-10). It has also become apparent that there are several mechanisms possible for the formation of the most common N-nitroso derivatives. Thus, in addition to the more customary reaction of an amine with nitrous acid, N-nitroso derivatives can also form via the reaction of an amine with NO (NO2, N2O3, N2O4) ( ). Amines can also be transnitrosated with already formed N-N-nitroso or C-nitro compounds via a transnitrosation reaction, they can be converted into their N-nitroso derivatives ). 

Treatment of Tertiary Aromatic Amines with Nitrous Acids. 

In the aliphatic series, primary amines are deaminated by nitrous acid, secondary aliphatic amines are A-nitrosated, while tertiary aliphatic amines form salts in the acidic medium followed by secondary reactions such as dealkylation [1, 21a, b]. 

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