204 Synthetic Routes toN-Nitro
C ONO 2CH 3CH 3NC80 °CR^1 R^2 NH R^1 R^2 NNO 2R^1 = H, R^2 = n-Pr (50 %)
R^1 = H, R^2 = i-Bu (54 %)
R^1 = Me, R^2 = Me (76 %)
R^1 = Et, R^2 = Et (60 %)
R^1 = n-Pr, R^2 = n-Pr (42 %)Figure 5.22amines (55–80 % yield) and primary amines (50–60 % yield).^38 In these reactions an excess
of the amine is heated with acetone cyanohydrin nitrate at 80◦C, neat in the case of liquid
secondary amines, or in acetonitrile or THF in the case of primary amines or those that are
solids at the reaction temperature.
Acetone cyanohydrin nitrate will not nitrate amines with branching on the carbonαto
the nitrate group. For these substrates the use of ethyl nitrate and lithium bases is favoured.
α-Aminonitriles are frequently observed as impurities under the reaction conditions because
of the slow decomposition of acetone cyanohydrin nitrate to hydrogen cyanide and acetone.
The need for an excess of amine during these reactions is wasteful and only practical if this
component is cheap and widely available. Other cyanohydrin nitrates are less efficientN-
nitrating agents.^38
5.3.2.4 Dinitrogen pentoxide
The first use of dinitrogen pentoxide as anN-nitrating agent appears to have been for the
conversion of aromatic amines to arylnitramines.^39 Difficulties in preparing pure dinitrogen
pentoxide meant that reactions with aliphatic amines were not properly examined for another
60 years.
CCl 4
2 R^1 R^2 NH+N 2 O 5 R^1 R^2 NNO 2 +R^1 R^2 NH. HNO 3 (Eq. 5.9)- 30 °C
Figure 5.23Emmons and co-workers^40 prepared a series of aliphatic secondary nitramines by treating
amines with a solution of dinitrogen pentoxide in carbon tetrachloride at− 30 ◦C (Equation 5.9).
The amine component needs to be in excess of two equivalents relative to the dinitrogen
pentoxide if high yields of nitramine are to be attained. This is wasteful because at least half
the amine remains unreacted. However, yields are high and there is no reason why the amine
cannot be recovered as the nitrate salt. The method is particularly useful for the nitration of
hindered secondary amines substrates such as those with branching on theαcarbon.
The reaction of dinitrogen pentoxide with primary aliphatic nitramines and amines leads
to deamination and the formation of a nitrate ester as the major product. Consequently,
dinitrogen pentoxide cannot be used for the synthesis of primary nitramines. In contrast, both
primary and secondary arylamines undergo efficientN-nitration with dinitrogen pentoxide in
chlorinated solvents.^41