Secondary amines nitrations, nitric acid

There is as yet no evidence that in the presence of sulphuric acid secondary amines lose nitric acid which would be capable of nitrating phenol. Attack by concentrated sulphuric acid, presumbaly loosens the linkage between the nitrogen atoms, leading to the expulsion of the nitronium ion NOf, which is a nitrating agent. 

Direct N-nitration of secondary amines by nitric acid is possible only for weakly basic amines. The more basic amines can be nitrated under neutral conditions widi reagents such as dinitrogen pentoxide and nitronium tetrafluoroborate, but nitrosamines are significant by-products. The nitrate ester CF3CMe20N02 has been recommended as a nonacidic nitrating agent for secondary amines which avoids the problem of contamination of the products by A(-nitrosamines piperidine and pyrrolidine were nitrated in yields of 75% and 72%, respectively. Amides and imides are efficiendy N-nitrated using ammonium nitrate in trifluoroacetic anhydride. ... 

The instability of primary nitramines in acidic solution means that the nitration of the parent amine with nitric acid or its mixtures is not a feasible route to these compounds. The hydrolysis of secondary nitramides is probably the single most important route to primary nitramines. Accordingly, primary nitramines are often prepared by an indirect four step route (1) acylation of a primary amine to an amide, (2) A-nitration to a secondary nitramide, (3) hydrolysis or ammonolysis with aqueous base and (4) subsequent acidification to release the free nitramine (Equation 5.17). Substrates used in these reactions include sulfonamides, carbamates (urethanes), ureas and carboxylic acid amides like acetamides and formamides etc. The nitration of amides and related compounds has been discussed in Section 5.5. 

The direct nitration of a primary amine to a nitramine with nitric acid or mixtures containing nitric acid is not possible due to the instability of the tautomeric isonitramine in strongly acidic solution (Equation 5.1). Secondary amines are far more stable under strongly acidic conditions and some of these can undergo electrophilic nitration with nitric acid in a dehydrating medium like acetic anhydride. 

The role of dialkylchloramines as intermediates in the chloride-catalyzed nitration of secondary amines is discussed in Section 5.3.1. Wright and co-workers" studied this reaction further and prepared a number of dialkylchloramines by treating secondary amines with aqueous hypochlorous acid (Equation 5.12). Treatment of these dialkylchloramines with nitric acid in acetic anhydride forms the corresponding secondary nitramine, a result consistent with the chloride-catalyzed nitration of amines." ... 

Solutions of dinitrogen pentoxide in aprotic solvents like methylene chloride, chloroform and carbon tetrachloride are efficient reagents for the iV-nitration of secondary amines. These reactions, known as nucleophilic nitrations , need excess amine present to react with the nitric acid formed during the reaction. Such nitrations are useful for the synthesis of secondary... 

In some more complex cases, secondary amines can be nitrated with nitrating mixtures. Diethanolnitramine dinitrate (DINA), for example, can be prepared by the action on diethanolamine of a mixture of nitric acid, nitric anhydride and zinc chloride (this is dealt with in more detail on p. 10). 

At present there are four good methods for preparing secondary nitramines. They are the oxidation of nitrosamines by peroxytrifluoro-acetic acid (5), the chloride-ion catalyzed direct nitration of amines (3), the nitrolysis of dialkylamides with nitric acid (16), and the alkaline nitration of amines with acetone cyanohydrin nitrate (6). We have found that treating two equivalents of several secondary aliphatic amines... 

Nitration of Heteroatoms. Secondary amines and primary and secondary amides can be converted to A -nitro compounds by direct nitration with nitric acid. 46 Although most primary amines cannot be nitrated directly, it is possible to obtain primary nitramines by nitration of the corresponding dichloroamines (eq 9). Treatment of pyrrolidone with nitric acid and acetic acid in the presence of copper provides lV-nitroso-2-pyrrolidone in 70% yield note that this transformation represents A -nitrosation. 

---