Direct nitration of amines 203Bamberger^34 improved upon the method of Angeli^32 by using alkali metal alkoxides as bases
rather than the alkali metal. However, this method is still a low yielding route to nitramines
and is a consequence of nitrate esters functioning more like alkylating agents than nitrating
agents. This problem is largely overcome by using lithium bases, which react irreversibly with
the amine to form the conjugate base (Equation 5.7). Both butyl lithium and phenyl lithium are
commonly used as bases in these reactions and, in some reactions, nitrate esters other than ethyl
nitrate are used. The reaction of a series of primary amines with butyl lithium in the presence
of ethyl nitrate at− 78 ◦C in diethyl ether or hexane solvents has been used to prepare primary
nitramines in moderate to good yield, including: methylnitramine (35 %),iso-propylnitramine
(58 %),n-butylnitramine (49 %),sec-butylnitramine (45 %) andtert-butylnitramine (37 %).^35
This procedure also works well for the synthesis of nitramines from secondary amine substrates.
EtMgBr n-BuONO 2
R^1 R^2 NH R^1 R^2 N MgBr R^1 R^2 NNO 2 (Eq. 5.8)Figure 5.21More recently, Polish chemists^36 have reported a synthesis of both aryl and aliphatic sec-
ondary nitramines by treating amine substrates with ethyl magnesium bromide followed by
reaction withn-butyl nitrate (Equation 5.8). This method, which uses nonpolar solvents like
hexane or benzene, has been used to synthesize aliphatic secondary nitramines, andN-nitro-
N-methylanilines which otherwise undergo facile Bamberger rearrangement in the presence
of acid. The direct nitration ofN-unsubstituted arylamines usually requires the presence of an
electron-withdrawing group. Reactions are retarded and yields are low for sterically hindered
amines.
Despite the moderate to good yields obtained for a range of primary and secondary
nitramines, the above methods have not found wide use. Their use in organic synthesis is
severely limited by the incompatibility of many functional groups in the presence of strong
bases. This is particularly relevant to the synthesis of explosive materials, where nitrate ester
andC-nitro functionality are incompatible with strong bases.
5.3.2.2 Electron-deficient nitrate esters
Ordinarily, alkyl nitrate esters will not nitrate amines under neutral conditions. However,
Schmitt, Bedford and Bottaro^37 have reported the use of some novel electron-deficient ni-
trate esters for the directN-nitration of secondary amines. The most useful of these is 2-
(trifluoromethyl)-2-propyl nitrate, which nitrates a range of aliphatic secondary amines to the
corresponding nitramines in good to excellent yields. Nitrosamine formation is insignificant in
these reactions. 2-(Trifluoromethyl)-2-propyl nitrate cannot be used for the nitration of primary
amines, or secondary amines containing ethylenediamine functionality like that in piperazine.
Its use is limited with highly hindered amines or amines of diminished nucleophilicity due to
inductive or steric effects.
5.3.2.3 Cyanohydrin nitrates
Acetone cyanohydrin nitrate, a reagent prepared by treating acetone cyanohydrin with nitric
acid–acetic anhydride, has been used for theN-nitration of aliphatic and alicyclic secondary