Nitrosamine rearrangement

As a first example we may take the nitrosamine rearrangement, as given by the equation... 

A secondary arenamine behaves like a secondary alkanatnine in reacting with nitrous acid to give an Af-nitrosamine. However, when treated with an acid the IV-nitrosamine rearranges ... 

The most ancient classification considers whether a certain compound class or chemical scaffold is being formed with success under given reaction conditions -often described by the name of the chemist who discovered or made major contributions to this reactions. Between 700 and 900 such named reactions are known [1]. This classification is mostly product based, but can be connected in certain cases to specific starting materials, e.g. the nitrosamine rearrangement. 

FISCHER - HEPP Nitrosamine Rearrangements Rearrangement o( N-nitroso to C-nitroso denvatives... 

The reaction occurs with technical material only, and, once formulated, the nitrosamine content is not altered as a function of time at ambient formulation temperatures. This intra-molecular rearrangement requires careful attenticn to conditions in the formulation of dinitroaniline herbicides. 

The rearrangement of aromatic nitrosamines to be discussed later is also of this type, e.g. 

Secondary amines such as methylaniline and diphenylamine also form nitrosamines very rapidly. By means of gaseous hydrochloric acid in anhydrous solvents they undergo rearrangement to the isomeric p-nitroso-bases. 

It has been found that, though stable to light in neutral solution, N-nitrosamines can rearrange to the corresponding amidox-imes (U,26,2T) in acid solution other products can also be formed... 

The very unstable hydroxy nitrosamine then loses formaldehyde to form the primary alkynitrosamine, which rapidly rearranges to the alkyl diazonium ion. The latter, being a powerful electrophile, alkylates various cellular nucleophiles, including the nucleic acids. 

The nitrosamines are neutral oily liquids of little importance in themselves. This reaction, however, serves to separate secondary bases from mixtures of primary, secondary and tertiary. The aromatic nitrosamines undergo an interesting rearrangement when heated with alcoholic hydrochloric acid (B., 20, 1247), the nitroso group migrating to a position in the nucleus, forming p-nitroso compounds. 

Aromatic A-nitrosamines on treatment with acid can undergo the well-known Fisher-Hepp rearrangement (32). For example, A-nitroso-A-methylaniline (NMA) on treatment with concentrated HC1 in ethanol rearranges to A-methyl-4-nitrosoaniline. It has been mentioned that A-nitrosamines are slowly denitrosated by treatment, especially on heating, with inorganic acids. Such denitrosation, however, proceeds smoothly and much faster in anhydrous medium, e.g., upon treatment with HBr in glacial acetic acid (35). Analysis of the resulting secondary amines or the nitrous acid provides the basis for several analytical methods to be discussed later. 

Primary and secondary aliphatic nitroso compounds, with an a-hydrogen, are unstable and readily rearrange to or exist as the more stable tautomeric oximes. Therefore, these nitroso compounds can be understood to be hydrogenated in the form of the oximes. On the other hand, tertiary and aromatic nitroso compounds as well as (V-nitrosamines may be hydrogenated as the compounds with a true nitroso group. 

When the electron-deficient atom is the nitrogen atom of nitrous acid or nitrosyl chloride, the products will depend on whether the amine is a primary or secondary amine. Primary aliphatic amines give rise to dia-zonium salts (RNj X) which readily decompose, sometimes with rearrangement. Aromatic diazonium salts (ArNj X ) are very important in aromatic transformations, and are discussed later. Secondary amines, on the other hand, give rise to nitrosamines... 

Nitrosamine and para Nitroso Methyl Aniline.—The reaction with nitrous acid is characteristic of secondary amines and yields phenyl methyl nitrosamine, the nitroso group entering the amino radical. This, however, undergoes rearrangement with the transference of the nitroso group to the ring yielding a nitroso benzene compound. 

The nitroso substitution products of secondary amines, e.g. monomethyl aniline, CcHb—NH(CHs), are formed by a rearrangement of the nitrosamine which itself is formed by the direct action of nitrous acid on the secondary amine (p. 547). 

The rearrangement occurs also when nitro benzene is electrolytically reduced by immersing the cathode in nitro benzene and sulphuric acid and the anode in sulphuric acid. Phenyl hydroxyl amine is first produced and by the above rearrangement is converted into para amino phenol. This rearrangement is analogous to the one occurring when phenyl methyl nitrosamine goes over to para-nitroso methyl aniline (P- S59)-... 

Fischer-Hepp rearrangement. Rearrangement of secondary aromatic nitrosamines to p-nitro-soarylamines. 

Tert-Amines - sec-amines.1 When a tertiary amine in pyridine is shaken with 2-nitropropane and CuCl under oxygen, it is converted into a nitrosamine (5), which can be isolated in yields of 15-65% and then reduced to a secondary amine. The reaction proceeds through oxidation to an amine oxide (2) with conversion of (1) into 2-nitro-2-propanol (3). This decomposes into acetone and nitrous acid. The nitrous acid traps the secondary amine formed from the amine oxide (2) after rearrangement to the carbinolamine (4). It is noteworthy that even... 

Properties and reactions of nitramines Secondary nitramines are neutral, primary nitramines form salts with bases, but an excess of alkali often causes decomposition to the carbonyl compound, nitrogen, and water. Secondary nitramines and aqueous alkali afford nitrous acid, aldehyde, and primary amine. Acids decompose primary aliphatic nitramines with formation of nitrous oxide in a reaction that has not yet been clarified thus these compounds cannot be hydrolysed by acid to amines in the same way as nitrosamines, although, like the latter, they can be reduced to hydrazines. Primary and secondary aromatic nitramines readily rearrange to C-nitroarylamines in acid solution. Most nitramines decompose explosively when heated, but the lower aliphatic secondary nitramines can be distilled in a vacuum. 

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