The MTO-catalyzed oxidative conversion of N,N-dimethylhydrazones to nitriles

Article abstract of DOI:10.1039/a802723d

Methyltrioxorhenium catalyzes the fast and efficient oxidation of aldehyde N,N-dimethylhydrazones to the corresponding nitriles in high yield.

Full text of DOI:10.1039/a802723d

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The MTO-catalyzed oxidative conversion of N,N-dimethylhydrazones to
nitriles
Sasˆa Stankovic´ and James H. Espenson*†
Ames Laboratory and Department of Chemistry, Iowa State University, Ames, Iowa, 50011, USA,
Methyltrioxorhenium catalyzes the fast and efficient oxida-
tion of aldehyde N,N-dimethylhydrazones to the corre-
sponding nitriles in high yield.
ylamines are known to undergo oxidation to nitrones with
H2O2–MTO.7 No attempts were made to detect either dime-
thylhydroxylamine or its oxidation product.
N,N-Dialkylhydrazones are versatile and useful intermedi-
ates in organic synthesis, especially in carbon–carbon bond
forming11 reactions, which has led to considerable interest in
the development of mild methods for their transformation into
nitriles. Non-oxidative procedures via N,N,N-trimethylhydra-
zonium salts or directly, in hyperbasic media,12,13 have been
used, but they require high temperatures and strong bases.
Several mild oxidative procedures for the use of hydrogen
peroxide, using 3-chloroperbenzoic acid and magnesium mo-
noperoxyphthalate, have been reported.10,14,15 These reactions,
however, are rather slow; for example, the 3-chloroperbenzoic
acid reactions require several hours.
N,N-Dimethylhydrazones derived from aldehydes (1) can be
oxidatively transformed into nitriles (2) using hydrogen per-
oxide as the oxidizing agent and methyltrioxorhenium
(CH3ReO3, abbreviated as MTO) as the catalyst, usually at the
1% level, as shown in eqn. (1). Ten specific examples are
H
Me
N
cat. MTO
H2O2
R
C
N
(1)
R
N
Me
1
2
presented in Table 1.
Hydrogen peroxide is a desirable reagent on several counts.
Selenium dioxide and 2-nitrobenzeneselenic acid catalyze its
reactions, giving good yields of nitriles from aromatic and
MTO is a well established catalyst for oxidations utilizing
hydrogen peroxide,1,2 including oxidations of various nitrogen-
containing compounds.3–7 The reactions were best carried out in
acetonitrile–acetic acid–pyridine solvent, 94.5 : 5 : 0.5. The use
of acetic acid was mandatory since the hydrazones are
sufficiently basic to deactivate MTO to the inactive perrhenate.8
Without pyridine, however, the reaction was accompanied by
5–10% hydrolysis to the parent aldehyde. Hydrolysis can
effectively be suppressed by a small amount of pyridine, to
reduce the Lewis acidity of MTO and its peroxo adducts. This
procedure prevents the hydrolysis of epoxides formed by the
oxidation of alkenes by MTO–hydrogen peroxide.9 Pyridine
also accelerates the formation of the catalytically active
peroxorhenium complexes as in eqn. (2).
Table 1 Preparation of nitriles from aldehyde N,N-dimethylhydrazonesa
Entry
1
Hydrazone
Product
Yieldb (%)
N
N
88
CN
CN
N
2
3
90
N
N
N
N
92
CN
O
CH3
Re
CH3
Re
N
O
O
H3C
H2O2
H2O
H2O2
O
O
O
O
CN
4
5
95
93
(2)
Re
O
O
O
O
O
OH2
CN
A
B
N
N
Under the described conditions the hydrazones 1 were
completely transformed into the corresponding nitriles after
several minutes as indicated by GC–MS analysis. The reaction
is quite general: N,N-dimethylhydrazones of aliphatic, un-
saturated, aromatic and heterocyclic aldehydes were success-
fully oxidized to the corresponding nitriles. Other present
oxidizable functionalities did not interfere (see Table 1, entry 8
where the hydrazone was oxidized without the pyridine N-oxide
being formed). In this particular example pyridine was not used,
since the starting hydrazone itself functions in this regard. Also
in entry 10, as expected, the double bond was not epoxidized
during the reaction, indicating far greater reactivity of the
hydrazone moiety compared to the double bond.
N
N
NC
CN
6
94
N
N
N
N
93
7
8
CN
O
O
N
N
92c
N
CN
N
CN
N
N
9
94
91
The oxidation of 1 presumably goes through the oxide 2,
which undergoes a Cope-type elimination10 to yield the nitrile 3
and dimethylhydroxylamine 4, eqn. (3). N,N-Dialkylhydrox-
CN
N
N
10
OH
H
Me
N
H
O–
cat. MTO
H2O2
Me
Me
a With 10 m
M substrate, 300 mM H2O2, 25 mM pyridine and 1 mM MTO in
acetonitrile, acetic acid, pyridine (94.5:5:0.5) for 15 min. Isolated yield.
c Without pyridine.
+N
+
Me
R
C
N
N
(3)
b
Me
R
N
Me
R
N
1
3
4
Chem. Commun., 1998
1579

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unsaturated N,N-dimethylhydrazones, but hours, even days, are
required. Moreover, these catalysts give poor results with
aliphatic N,N-dimethylhydrazones which are largely hydro-
lyzed. Phosphomolybdic acid, H3PO4·12MoO3·12H2O, per-
forms better with aliphatic hydrazones but it gives by-products
such as the corresponding acids. Compared to these catalysts,
MTO is clearly superior. MTO also catalyzes the oxidative
cleavage of ketone hydrazones to the parent carbonyl com-
pounds; these reactions are now being investigated.
Notes and References
† E-mail: espenson@ameslab.gov
1 W. A. Herrmann and F. E. Kühn, Acc. Chem. Res., 1997, 30, 169.
2 J. H. Espenson and M. M. Abu-Omar, Adv. Chem. Ser., 1997, 253,
99.
3 S. Yamazaki, Bull. Chem. Soc. Jpn., 1997, 70, 877.
4 R. W. Murray, K. Iyanar, J. Chen and J. T. Wearing, Tetrahedron Lett.,
1996, 37, 805.
5 R. W. Murray, K. Iyanar, J. Chen and J. T. Wearing, J. Org. Chem.,
1996, 61, 8009.
6 A. Goti and L. Nanneli, Tetrahedron Lett., 1996, 37, 6025.
7 T. H. Zauche and J. H. Espenson, Inorg. Chem., 1997, 36, 5257.
8 M. M. Abu-Omar, P. J. Hansen and J. H. Espenson, J. Am. Chem. Soc.,
1996, 118, 4966.
9 J. Rudolph, K. L. Reddy, J. P. Chiang and K. B. Sharpless, J. Am. Chem.
Soc., 1997, 119, 6189.
10 R. Fernandez, C. Gasch, J. Lassaletta, J. Llera and J. Vazquez,
Tetrahedron Lett., 1993, 34, 141.
11 E. J. Corey and D. Enders, Chem. Ber., 1978, 111, 1337, 1362.
12 R. F. Smith and R. E. J. Walker, Org. Chem., 1962, 27, 4372.
13 T. Cuvigny, J. F. Le Borgne, M. Larcheveque and H. Normant,
Synthesis, 1977, 237.
14 S. B. Said, J. Skarzewski and J. Mlochowski, Synthesis, 1989, 223.
15 J. Mlochowski, K. Kloc and E. Kubicz, J. Prakt. Chem., 1994, 336,
467.
A typical experimental procedure is as follows: 1 (100 mmol)
was added to a rapidly stirred solution of MTO (1 m
hydrogen peroxide (0.3 , added as 30% solution in water),
pyridine (25 m ) in 100 ml of acetonitrile containing 5 vol%
M),
M
M
HOAc. After 15 min, most of the acetonitrile was removed by
rotary evaporation, and the residue poured into 300 ml of diethyl
ether, washed successively with 0.1
M
HCl and saturated
sodium hydrogen carbonate. (In the case of 4-cyanopyridine,
entry 8, the ether solution was washed only once with saturated
sodium hydrogen carbonate.) The ethereal solution was then
dried over anhydrous sodium sulfate, and the product obtained
after evaporation. The crude nitriles were purified by column
chromatography (n-hexane–acetone).
This research was supported by the US Department of
Energy, Office of Basic Energy Sciences, Division of Chemical
Sciences under contract W-7405-Eng-82.
Received in Bloomington, IN, USA, 14th April 1998; 8/02723D
1580
Chem. Commun., 1998