MTO catalyzed oxidation of aldehyde N,N-dimethylhydrazones with hydrogen
peroxide: high yield formation of nitriles and N-methylene-N-methyl N-oxide
Henri Rudler*† and Bernard Denise
Laboratoire de Synthe`se Organique et Organome´tallique, UMR 7311, Universite´ Pierre et Marie Curie, Tour 44-45, 4 Place
Jussieu, 75252 Paris Cedex 5, France
N,N-Dimethylhydrazones of aldehydes react with hydrogen
peroxide at 250 °C in the presence of catalytic amounts of
methyltrioxorhenium (MTO) to give in high yield the
corresponding
N-oxide.
nitriles
and
N-methylene-N-methyl
Scheme 3
The transformation of aldehydes into nitriles is an important
process in organic synthesis.1,2 Several procedures are available
for that purpose and very recently the oxidative conversion of
N,N-dimethylhydrazones of aldehydes using dimethyldioxirane
has been described.3 Such a transformation has also been
achieved by the use of peracids.4 Both methods suffer from
serious drawbacks: they both use stoichiometric amounts of
oxidants which are either expensive (low yield formation of
dimethyldioxirane from potassium peroxysulfate) and/or are
waste-forming processes (acids from peracids). The use of
hydrogen peroxide alone2 or associated with a catalyst (either
phosphomolybdic acid or sodium tungstate)5 has also draw-
backs: in the first case satisfactory yields were observed only in
the case of hydrazones derived from aromatic aldehydes,
whereas in the second case side reactions took place.
are also catalytically converted into nitrones by the same system
(Scheme 4).13,14 Taken together, these two reactions would
imply the formation of nitriles and N-methylene-N-methyl
N-oxide from N,N-dimethylhydrazones of aldehydes. This
indeed turned out to be the case (Scheme 5).
Scheme 4
During our search for new applications of MTO6 in organic
synthesis, mainly based on the analogy which exists between
dimethyldioxirane and the peroxo derivatives obtained upon
oxidation of MTO with hydrogen peroxide (e.g. the epoxidation
of olefins, Scheme 1),7–11 we surmised that this system might be
a good and efficient candidate for the catalytic transformation of
N,N-dimethylhydrazones of aldehydes into nitriles.
Scheme 5
Thus, an ethanolic solution of the N,N-dimethylhydrazone of
heptanal15 (0.45 g, 2 ml of EtOH) was added dropwise to a
yellow solution of MTO and H2O2 (1.5%, 2 equiv. of 35%
H2O2) in EtOH at 250 °C. The solution was then allowed to
warm to room temperature over 1 h. Evaporation of most of the
solvent followed by the addition of water and extraction with
Et2O gave, after evaporation of the organic solvent, the
expected nitrile (0.29 g, 90%). The aqueous layer was also
evaporated in vacuo to give an oily yellow liquid, which was
also soluble in CH2Cl2. The mass spectrum of this product
Scheme 1
1
confirmed the molecular formula C2H5NO (m/z 59). The H
Indeed, the mechanism which was suggested for the
oxidative cleavage of dimethylhydrazones involved an electro-
philic oxygen transfer from dioxirane to the terminal nitrogen
atom leading to an N-oxide.3 An intramolecular elimination of
dimethylhydroxylamine was then supposed to lead to the nitrile
(Scheme 2).
NMR spectrum disclosed two signals: a singlet at d 3.60 for the
NMe group and an AB system for two hydrogens at d 6.67. The
13C NMR spectrum confirmed the presence of a methyl and a
methylene group (DEPT experiment), respectively, at d 132.5
and 50.85.11
An NMR experiment with stoichiometric amounts of pre-
formed MTO diperoxide9 and the N,N-dimethylhydrazone of
benzaldehyde clearly demonstrated the formation of the
expected nitrone. It appears therefore that the transformation of
the hydrazones into a mixture of nitriles and nitrone 3‡ via
dimethylhydroxylamine requires indeed 2 equiv. of H2O2.
Similar results, shown in Table 1, were observed under the
same experimental conditions, starting from a series of
hydrazones, and giving high yields of the expected nitriles.
Interestingly, epoxidation of the carbon–carbon double bonds
of the hydrazones 4–7 was not observed under these precise
reaction conditions. However, addition of an excess of H2O2
(3–4 equiv.) led, in the case of 6, to the expected epoxy-nitrile
It is known that MTO catalyzes the oxidation of tertiary
amines to N-oxides (Scheme 3).12 Moreover, hydroxylamines
Scheme 2
Chem. Commun., 1998
2145
Rudler, Henri
