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

[O]
SYNTHESIS OF NITRONES 143
N H
N
H
N
OH
O
O− 2 2
+
+
N H
OH
HA NR
N HA
Scheme 2.17
calcoaceticus NCIMB 9871 (CHMO) (EC 1.14.13.22) has been reported (97, 98).
The reaction is of limited synthetic value; however, it has become a subject of
considerable mechanistic interest.
2.2.1.3. Oxidation of Hydroxylamines The mildest oxidation method of nitrone
formation seems to be via oxidation of the corresponding hydroxylamines (HA)
containing one or more protons at α-C. In this reaction, air, H2O2, m-CPBA,
oxides of different metals (MnO2, PbO2, HgO, Ni2O3, etc.) can be used as oxidants.
The resulting nitroxyl radicals (NR) undergo a disproportionation reaction
(Scheme 2.17), and with an excess of the oxidant, give nitrones (N) astheÞnal
reaction products (99, 100).
In electrochemical oxidation of 1-hydroxy-3-imidazoline-3-oxides containing
one to four H atoms at α-C, one observes in ESR-spectra not only triplet splitting
of the nucleus 14 N of the nitroxyl group (aN 15-16 G) but also splitting of
the neighboring protons (aH 18-20 G), with multiplets corresponding to their
number (from doublet to quintet) (101). Unlike spatially hindered hydroxylamines
which show reversibility in electrochemical oxidation, hydroxylamines with H at
α-C are oxidized irreversibly. Oxidation of hydroxylamines with nitroxyl radical
proceeds easily and with quantitative yields (102). In the oxidation of asymmetric
polyßuorinated hydroxylamines with MnO2, isomeric polyßuorinated nitrones
have been obtained (103).
Study of the kinetics of the oxidation of asymmetric secondary hydroxylamines
to nitrones with H2O2, catalyzed by methylrhenium trioxide, has led
to the elucidation of the mechanism of the reaction (104). Full transformation
of N,N -disubstituted hydroxylamines into nitrones upon treatment with H2O2
occurs on using polymeric heterogeneous catalysts such as polymer-supported
methylrhenium trioxide systems (105).
In the mechanism study of N-benzyl-N -alkyl hydroxylamines, regarding oxidation
with HgO and p-benzoquinone, it has been proposed on the basis of
intra- and intermolecular kinetic isotope effects that, initially, there takes place
a one-electron transfer from a nitrogen atom to the oxidant, with a subsequent
proton abstraction (106–108).
Oxidation of cyclic and acyclic hydroxylamines with yellow mercuric oxide
appears to proceed with high regioselectivity (109–115). Regioselectivity is
determined by the electronic nature of the substituents (116). The oxidative
regioselectivity of MnO2 is comparable to that of HgO, but due to its lower
toxicity, it has been proposed to use MnO2 rather than HgO (Table 2.2) (117).