Amines with nonacidic reagents

Despite the amount of research focused on the iV-nitration of amines with nonacidic reagents, the use of conventional acidic reagents based on nitric acid and acid anhydrides has been far more extensive for the synthesis of energetic materials. 

Other reagents have been used for the direct nitration of amines under nonacidic conditions. Mandel reported the synthesis of methylnitramine, dimethylnitramine and diisopropy-Initramine from the reaction of nitryl fluoride with the parent amine. The presence of an excess of amine appears to be of prime importance given that other reports give the nitrosamine as a major by-product. 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

Direct N-nitration of secondary amines by nitric acid is possible only for weakly basic amines. The more basic amines can be nitrated under neutral conditions with reagents such as dinitrogen pentoxide and nitronium tetrafluoroborate, but nitrosamines are significant by-products. The nitrate ester CF3CMe20N02 has been recommended as a nonacidic nitrating agent for secondary amines which avoids the problem of contamination of the products by )V-nitrosamines piperidine and pyrrolidine were nitrated in yields of 75% and 72%, respectively. Amides and imides are efficiently N-nitrated using ammonium nitrate in trifluoroacetic anhydride. ... 

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