Amines with nitrous acid

R—N=N Aryl diazonium 10ns are formed by treatment of primary aromatic amines with nitrous acid They are ex tremely useful in the preparation of aryl halides phenols and aryl cyanides... 

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. 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. 

Up to this point no evidence was forthcoming that any oneoffthe fenchenes prepared was pure, as the optical rotation of nearly every specimen was different. Wallach i has, however, more recently prepared fenchene by treating fenchyl-amine with nitrous acid. The resulting terpenes were separated by fractional distillation into two main portions, one of which had the following characters —... 

Probably the best leaving group is N2 from the species RN2 , which can be generated in several ways, of which the two most important are the treatment of primary amines with nitrous acid (see p. 816 for this reaction)... 

Nitrosamines are readily produced from the reaction of amines with nitrous acid, i.e., acidified nitrite (3), and are also produced vivo when amines and nitrite are administered, as reflected by tumor induction [reviewed in (3)], and the in vivo appearance of nitrosamines (2> ) Challis and Kyrtopoulos (5) showed that gaseous NO2 reacts directly with amines in neutral or alkaline aqueous solutions to produce nitrosamines and nitramines. The kinetics of the extremely rapid reaction of... 

Undoubtedly the most significant discovery in colour chemistry in the post-Mauveine period was due to the work of Peter Griess, which provided the foundation for the development of the chemistry of azo dyes and pigments. In 1858, Griess demonstrated that the treatment of an aromatic amine with nitrous acid gave rise to an unstable salt (a dia-zonium salt) which could be used to prepare highly coloured compounds. 

Reaction of amines with nitrous acids Primary Secondary Primary RNH2 + HONCM>N2 + other products Secondary R2NH + HONO—>R2N—NO... 

The unexpected feature of the reaction of the primary aromatic amines with nitrous acid is that the diazo-compound, which is doubtless formed at low temperatures according to the scheme so far used, undergoes rearrangement by the acid present in the solution, and forms... 

Nitrosamines, which are the amides of nitrous acid, are more stable and are derived from secondary amines with nitrous acid. iV-nitrosamides are substances which have a carbonyl group attached to a nitrogen-bearing NO group, e.g. iV-nitrosamides, iV-nitrosocarbamates and /V-nitrosoLireas see Figure 10. 

Demjanov rearrangement org chem A structural rearrangement that accompanies treatment of certain primary aliphatic amines with nitrous acid the amine will undergo a ring contraction or expansion. dem ya-nof re-3 ran -m3nt) denaturant chem An inert, bad-tasting, or poisonous chemical substance added to a product such as ethyl alcohol to make it unfit for human consumption. de na-chs rsnt ... 

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 Primary Aromatic Amines with Nitrous Acids. 

In the reaction of amines with nitrous acid, one would expect the primary reaction to be the formation of an alkylammonium nitrite salt. Despite a few observations on the formation of such salts in the late nineteenth and early twentieth centuries, the formation of such salts was largely ignored until quite... 

On treatment of certain other tertiary aromatic amines with nitrous acid, it has been found that either C-nitroso compounds, nuclear nitro compounds, or jV-nitrosoamines are formed with loss of an alkyl group. In the case of the nitrodimethylanilines, the latter two types of reaction may occur. The formation of nitro-jV-nitrosomethylanilines predominate at room temperature, whereas the formation of polynitro compounds predominates at more elevated temperatures. The formation of nitrosoamines from iVW-dimethylanilines appears to be particularly favored when both ortho positions are occupied by nitro groups, although /V-nitroso compounds were also obtainable from other nitrodimethylanilines. The product of the reaction, of course, is an /V-nitroso secondary amine. 

Since the neutralization reaction of an amine with nitrous acid may be presumed to be instantaneous while the nitrosation of an amine proceeds at a slower rate, further investigations would be of interest to elucidate the problem of whether nitrite salt formation is a necessary preliminary step to the formation of iV-nitrosoamines or whether the covalent product forms independently. In the latter case, there would be competitive reactions of significantly different reaction rates and mechanisms. The yield of A-nitrosoamines may be influenced by the extent to which the more water-soluble nitrite salts may be present in the course of a preparation. 

The best known example of the treatment of a primary aliphatic amine with nitrous acid involves the reaction of esters of glycine hydrochloride with sodium nitrite to form esters of diazoacetic acid. This reaction is carried out at low temperatures and under such reaction conditions that any IV-nitroso primary amine which might have been formed is immediately converted to the diazoacetate [15, 16]. Treatment of 1-methyl-2,2,2-trifluoroethylamine hydrochloride, another primary amine, with sodium nitrite in an aqueous system also evidently leads to the corresponding diazoalkane [17]. 

The treatment of aliphatic amines with nitrous acid is not a useful method for the preparation of olefins any more than it is for the preparation of alcohols (p. 355), though some olefin is usually formed in such reactions. 

Clearly, the plethora of products to be expected, particularly those resulting from rearrangement (see Exercise 23-31), prevents the reaction of the simple primary amines with nitrous acid from having any substantial synthetic utility. 

Exercise 23-29 Predict the products expected from the reactions of the following amines with nitrous acid (prepared from NaN02 + HCI in aqueous solution) ... 

Primary amines react with nitrous acid to yield a diazonium salt, which is highly unstable and degradates into a carbocation that is capable of reaction with any nucleophile in solution. Therefore, reacting primary amines with nitrous acid leads to a mixture of alcohol, alkenes, and alkyl halides. 

The nitrosation of primary aromatic amines with nitrous acid (generated in situ from sodium nitrite and a strong acid, such as hydrochloric acid, sulfuric acid, or HBF4) leads to diazonium salts, which can be isolated if the counterion is non-nucleophilic. 

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