Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

SYNTHESIS OF NITRONES 131
Treated with m-CPBA as an oxidant, spontaneous rearrangement of oxaziridines
derived from 2H -imidazole -1-oxide (9), pyrroline (10), and N -adamantylphenylimine
(11) into nitrones is observed, either upon heating or treatment with
acids. Substituted N -benzylidene-tert-butylamines are oxidized by m-CPBA into
oxaziridines, which can easily be isomerized into nitrones, with electron-donor
substituents facilitating this process (12–14). Peracid oxidation of the corresponding
imines gives N-arylbenzoquinonimine-N -oxides (15). Oxidation of imines (2)
and (4) resulting from the interaction between amino acid (1) and its tripeptide
(3), upon treatment with benzaldehyde and m-CPBA, gives the corresponding
oxaziridines (5) and (7), which can be isomerized into stable nitrones (6) and (8)
(Scheme 2.3) (16).
It is noteworthy that quick and effective formation of diaryl nitrones can
be achieved through oxidation of diaryl imines with Oxone (potassium peroxymonosulfate)
in such media as aqueous solution of NaHCO3 in acetonitrile or
acetone. When oxidized under such conditions, dialkyl or monoaryl imines give
oxaziridines (17). Oxidation of 3,4-dihydroisoquinoline (9) with Oxone initially
leads to the formation of oxaziridine (10) which is easily transformed into the corresponding
3,4-dihydroisoquinoline N -oxide (11) upon treatment with catalytic
amounts of p-toluenesulfonic acid (Scheme 2.4) (18).
Oxidation of N-alkyl imines with dimethyldioxirane (DMD) in a solution
of dichloromethane-acetone gives nitrones without the apparent formation of
oxaziridines (13). Under the conditions of phase transfer, imines can be oxidized
into nitrones upon treatment with permanganate ion MnO4 − (19).
Also, nitrones can be formed by photochemical oxidation (λ350 nm) of
aldimines in acetonitrile, in the presence of O2 over a TiO2 suspension (20, 21).
Air oxidation of imines into oxaziridines with their subsequent transformation
into nitrones, using cobalt catalysts, provides good yields. Utilization of molecular
oxygen in the oxidation process seems highly promising due to its cost-effectiveness,
availability, and the possibility of industrial application (22).
EfÞcient oxidation of imines into nitrones can be achieved by using methyl
(trißuoromethyl)dioxirane as an oxidant. This method provides enantiopure
nitrones derived from 2H -pyrrole 1-oxide (23, 24).
Diaryl diselenides and benzisoselenazole-3(2H )-ones are used as efÞcient catalysts
in the process of imine oxidation with hydrogen peroxide and tert-butylhydroperoxide
(25).
2.2.1.2. Oxidation of Amines Oxidation of primary amines is often viewed as a
particularly convenient way to prepare hydroxylamines. However, their direct oxidation
usually leads to complex mixtures containing nitroso and nitro compounds
and oximes. However, oxidation to nitrones can be performed after their conversion
into secondary amines or imines. Sometimes, oxidation of secondary amines
rather than direct imine oxidation seems to provide a more useful and convenient
way of producing nitrones. In many cases, imines are Þrst reduced to secondary
amines which are then treated with oxidants (26). This approach is used as a basis
for a one-pot synthesis of asymmetrical acyclic nitrones starting from aromatic
aldehydes (Scheme 2.5) (27a) and 3,4-dihydroisoquinoline-2-oxides (27b).