214 Synthetic Routes toN-Nitro
the breakage of the amide bond in path A, whereas rupture of either of the other two C–N
bonds in path B leads to a secondary nitramide (78). Examples exist of both types of reaction,
but generally speaking, the secondary nitramine is the observed product from the nitrolysis of
N, N-disubstituted amides.
5.6.1.1 Nitrolysis with acidic reagents
Acidic reagents composed of nitric acid and its mixtures are by far the most important
reagents used in nitrolysis reactions. Early work by Robson and Reinhart^93 ,^94 showed that
N, N-disubstituted amides in the form of formamides, acetamides and sulfonamides containing
straight chain alkyl groups in association with the acyl group undergo efficient nitrolysis to
the corresponding secondary nitramines when treated with a solution of fuming nitric acid in
trifluoroacetic anhydride. The use of nitric acid in acetic anhydride is generally less efficient,
although good yields of nitramine product can be attained for some substrates.^93 ,^94 A number
of important observations were made: (1) alkyl groups with branching on theαcarbon lead to
greatly reduced yields, (2) substrates containing electronegative substituents next to the acyl
group give a greatly reduced yield of nitramine product due to a reduction in electron density at
the acyl nitrogen and (3)N, N-dialkylureas andN, N-dialkylcarbamates are found to be poor sub-
strates for nitrolysis with acid anhydride–nitric acid mixtures. WhileN, N-dialkylacetamides
undergo facile nitrolysis with nitric acid–acid anhydride mixtures, the correspondingN-alkyl-
N, N-diacylamines are inert to nitrolysis under these conditions, a consequence of the further
reduction in electron density at the acyl nitrogen.^95
O 2 NNO 2NO 2
4
(HMX)NNNNH 2 C CH 2H 2 C CH 2AcAcRRNNNNH 2 C CH 2H 2 C CH 2NO 279, R = Ac (79 %)
80, R = NO 2 (98 %)N 2 O 5 , HNO 3Figure 5.42The nitrolysis ofN, N-disubstituted amides is one of the key tools for the synthesis of
nitramine containing energetic materials. The present synthesis of the high performance ex-
plosive HMX is via the nitrolysis of hexamine (Section 5.15). This is an inefficient reaction
requiring large amounts of expensive acetic anhydride. An alternative route to HMX (4) is
via the nitrolysis of either 1,3,5,7-tetraacetyl-1,3,5,7-tetraazacyclooctane (79) (79 %) or 1,5-
dinitro-3,7-diacetyl-1,3,5,7-tetraazacyclooctane (80) (98 %) with dinitrogen pentoxide in ab-
solute nitric acid.^96 These reactions are discussed in more detail in Section 5.15.
Nitrolysis reactions employing 1,3,5-trisubstituted-1,3,5-triazacyclohexanes have been ex-
plored as alternative routes to RDX.^30 ,^97 Some of the results are illustrated in Table 5.4 and
show the difference in the efficiency of the three nitrolysis agents used, namely, absolute nitric
acid, phosphorus pentoxide–nitric acid and trifluoroacetic anhydride–nitric acid. The acetamide
derivative (81) (TRAT) undergoes incomplete nitrolysis on treatment with absolute nitric acid
and trifluoroacetic anhydride–nitric acid to give a crude product containing some 1-acetyl-3,5-
dinitro-1,3,5-triazacyclohexane (TAX) (82) (Table 5.4, Entry 1); the latter can be preferentially
formed in 93 % by suitably modifying the reaction conditions.^97 Interestingly, the nitrolysis of