Chloride-catalyzed nitration, amines

Wright illustrated the effectiveness of chloride-catalyzed nitration for a number of amines of different basicity. Wright showed that weakly basic amines like iminodiacetonitrile and its dimethyl and tetramethyl derivatives are all nitrated in high yield with nitric acid-acetic anhydride mixtures in the absence of chloride ion. In contrast, the slightly more basic 3,3 -iminodipropionitrile is not appreciably nitrated with acetic anhydride-nitric acid, but the inclusion of a catalytic amount of the hydrochloride salt of the amine base generates the corresponding nitramine in 71 % yield. ... 

The founder of the chloride-catalyzed nitration of amines, G. F. Wright, has extensively reviewed chloride-catalyzed nitration. " Even 50 years later, the importance and success of this method as a route to nitramines is illustrated by the number of examples which can be found in the literature. 

Acetic anhydride-nitric acid mixtures are extensively used for chloride-catalyzed nitrations. Other nitrating agents have been used and involve similar sources of electropositive chlorine for intermediate chloramine formation. 4,10-Dinitro-4,10-diaza-2,6,8,12-tetraoxaisowurtzitane (TEX) (40), an insensitive high performance explosive (VOD 8665 m/s, d = 1.99 g/cm ), is synthesized by treating the dihydrochloride salt of the corresponding amine (39) with strong mixed acid. ... 

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." ... 

In view of the highly carcinogenic nature of many nitrosamines any experiments involving their isolation must be discouraged, and for this reason, this section has only been written for completeness. This high toxicity is unfortunate because the preparation of nitrosamines from the parent amines is often facile and they provide a route to highly pure nitramines. Other equally useful methods for the synthesis of nitramines, such as the chloride-catalyzed nitration of secondary amines, also suffer from the formation of nitrosamines in appreciable amounts and must also be viewed with caution. 

May be catalyzed with amine hydrochloride, magnesium chloride, zinc nitrate or any of the standard organic and inorganic accelerators. 

If nitration under acidic conditions could only be used for the nitration of the weakest of amine bases its use for the synthesis of secondary nitramines would be severely limited. An important discovery by Wright and co-workers " found that the nitrations of the more basic amines are strongly catalyzed by chloride ion. This is explained by the fact that chloride ion, in the form of anhydrous zinc chloride, the hydrochloride salt of the amine, or dissolved gaseous hydrogen chloride, is a source of electropositive chlorine under the oxidizing conditions of nitration and this can react with the free amine to form an intermediate chloramine. The corresponding chloramines are readily nitrated with the loss of electropositive chlorine and the formation of the secondary nitramine in a catalytic cycle (Equations 5.2, 5.3 and 5.4). The mechanism of this reaction is proposed to involve chlorine acetate as the source of electropositive chlorine but other species may play a role. The success of the reaction appears to be due to the chloramines being weaker bases than the parent amines. 

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... 

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