Nitration of Primary Amines to

Form Primary Nitramines (Review)

Daniel c
M Ateer, Jean-François Pons, Ian Wilson, Hamish Cavaye

Introduction
The synthesis of primary nitramines is a much neglected area of energetic materials chemistry. This is due to the limited use of primary nitramines in explosive
compounds and the apparent difficulty in their synthesis. The difficulty faced in the formation of nitramines from their corresponding amines is linked to several
hurdles. Firstly, most nitration reactions occur in acidic media which quickly forms an unreactive ammonium salt. A second difficulty lies in the instability of
primary aliphatic nitramines under acidic conditions (Figure 1). Alternative routes are generally multistep approaches which are often long and inefficient.

Figure 1

Traditional Acidic Route

• Original preparations of primary nitramines
were from the nitramide analogues.
• The nitramide could be formed by nitration of
an amide with mixed acid or concentrated
HNO3.
• The nitramide was then hydrolysed to form the
primary nitramine.
• The route from the primary amine to the
nitramine was often a minimum of 3 steps as Figure 2
observed in the routes to methylnitramine
(Figure 2).
• Single step syntheses of primary nitramines
from the corresponding amine with nitric acid
have been reported for only those amines
bonded directly to an aromatic ring (Figure 3). Figure 3
Alternative Nitrating Agents
• There are a wide variety of alternative nitrating agents which are summarised in Figure 4 and Table 1.
• N2O5 has been reported to convert primary amines to nitrate esters rather than nitramines, however it is highly
successful in forming the secondary nitramine from the corresponding amine yielding 97% of the nitramine
when reacted with diisobutylamine.
• N2O4 has been reported to be of limited use in forming primary nitramines directly from the primary amine. It
has been successfully used to produce secondary nitramines in a highly chemoselective reaction which may
produce a high yield of either nitrosamine or nitramine depending on the reaction temperature.
• NO2BF4 presents a commercially available source of the nitronium ion and has been reported to successfully
produce n-butyl nitrate in limited yields from n-butylamine. NO2BF4 is unfortunately an expensive reagent
Figure 4 (£137 per 25 g from Sigma Aldrich UK) and thus is not a practical solution for multi-gram synthesis.
O
n-BuLi then Cl O
NO2BF4 N2O5 N2O4 NC ONO2 F3C ONO 2
EtONO2 N
N NO 2

Primary amine - - 53% 35-58% 50-55% - -

Secondary amine 54% 81-97% 97% - 42-76% 58-75% 28-90%
Cyclic amine 72% 64-91% - - 60-81% 72-100% 82-82%
Table 1
Activating/Protecting Group
• Nitrodesilylation and nitrodestannylation have been reported as successful methods in forming the secondary nitramine but not the primary (Figure 5).
Nitrodephosphorylation has also been reported and was used to produce N,N-dimethylnitramine from hexamethylphosphoramide with a substantial (12%)
proportion of the crude yield being identified as the carcinogen, N,N-dimethylnitrosamine.
• Chlorine mediated nitrations of primary amines have been reported as progressing via the chloramine intermediate which is susceptible to nitration with
traditional reagents (Figure 6) and may be dechlorinated using base to yield the primary nitramine in 45% yield.

Figure 5

Figure 6

Conclusion
• This review highlights the difficulties encountered when preparing aliphatic nitramines and in particular targeting primary aliphatic nitramines.
• There are very few direct methods to nitrate a primary aliphatic amine and fewer still which may be readily implemented on a large, multi-gram scale (only a
small set of conditions has been described for secondary amines). It would therefore be of great interest to develop a new methodology to fill the knowledge-
gap regarding primary nitramine production and thus pave the way for further research into this much neglected family of energetic materials.

www.cranfield.ac.uk Centre for Defence Chemistry, Cranfield University,

Defence Academy of the United Kingdom, Shrivenham, SN6 8LA UK
*Refer to full paper for references d.mcateer@cranfield.ac.uk