Methyltrioxorhenium-catalyzed oxidation of aromatic aldoximes

Article abstract of DOI:10.1055/s-2004-829088

The first catalytic oxidation of aryl oximes to nitro compounds by means of methyltrioxorhenium and urea hydroperoxide is reported. The formation of carbamates, probably occurring through formation of nitrile oxide intermediates, has been observed from 2,6-disubstituted aryl oximes.

Full text of DOI:10.1055/s-2004-829088

LETTER
1553
Methyltrioxorhenium-Catalyzed Oxidation of Aromatic Aldoximes
M
ethyltrioxor
r
henium-
C
a
atalyzed O
n
xidation of
A
c
r
omatic
A
e
ldoximes sca Cardona,*a Gianluca Soldaini,a Andrea Goti*a,b
a
Dipartimento di Chimica Organica ‘Ugo Schiff’, Università di Firenze, via della Lastruccia 13, Sesto Fiorentino, Firenze 50019, Italy
Associated with ICCOM-CNR, Firenze, Italy
b
Fax +39(055)4573531; E-mail: andrea.goti@unifi.it
Received 11 January 2004
Dedicated to Prof. Francesco De Sarlo on the occasion of his 65th birthday.
sodium perborate8c or oxone,8d or non commercial oxi-
Abstract: The first catalytic oxidation of aryl oximes to nitro com-
pounds by means of methyltrioxorhenium and urea hydroperoxide
is reported. The formation of carbamates, probably occurring
through formation of nitrile oxide intermediates, has been observed
from 2,6-disubstituted aryl oximes.
dants, such as a Mo(VI) oxodiperoxo complex,8e stoichio-
metrically.
Apart from the methods employing halogens or halo de-
rivatives, where formation of nitrile oxides occurs by
dehydrohalogenation of an intermediate hydroximoyl ha-
lide,7 the reported examples of direct oxidation of oximes
to nitrile oxides are even more rare and limited in scope.9
Indeed, only the use of lead tetraacetate,9a active manga-
nese dioxide,9b potassium ferricyanide,9c and ceric ammo-
nium nitrate9d have been reported for this transformation
and are not of general use.
Key words: catalysis, urea hydrogen peroxide, nitro compounds,
carbamates, nitrile oxides
Methyltrioxorhenium (MTO)1 has emerged in the past de-
cade as a useful and versatile catalyst for the oxidation of
several organic compounds, including alkenes, alkynes,
arenes, phenols, ketones, sulfides, phosphines, anilines,
amines and hydroxylamines, with the use of aqueous hy-
drogen peroxide or the complex urea hydrogen peroxide
(UHP) as the usual stoichiometric oxidant.2 More recent-
ly, we have employed the MTO/UHP system for the un-
precedented catalytic hydroxyglycosylation of glycals in
ionic liquids in a domino fashion.3
Importantly, no catalytic procedure for the oxidation of
oximes, either to the corresponding nitro compounds or
nitrile oxides, has been reported so far. Albeit oximes
have been previously reported as the final products of the
MTO-catalyzed oxidation of primary amines,10 we felt
that under proper conditions the oxidation might proceed
farther. In this Letter we report the results of the MTO-
catalyzed oxidation of aryl oximes to the corresponding
aryl nitromethanes and the unexpected results obtained
with 2,6-disubstituted aryl oximes.
During our ongoing research on oxidation of nitrogen
containing compounds with MTO/UHP4 or different oxi-
dants,5 we became interested in the oxidation of oximes.
In principle, oximes 1 may undergo oxidation either to ni-
tro compounds 2 by an oxygenation reaction or to nitrile
oxides 3 by a formal dehydrogenation (Scheme 1). Both
nitro derivatives6 and nitrile oxides7 are very useful inter-
mediates in organic synthesis and oximes, being readily
available from the corresponding aldehydes, may be con-
venient precursors to these classes of compounds.
The results of the oxidation of benzaldehyde oxime, p-
anisaldehyde oxime, 2-nitrobenzaldehyde oxime and 2-
naphthaldeyde oxime employing catalytic methyltrioxo-
rhenium (2–10 mol%) in the presence of 3 equivalents of
UHP at room temperature in MeOH or acetonitrile as sol-
vents are reported in Table 1.11
In all these cases, the reaction furnished the corresponding
aryl nitromethane, identified by comparison with litera-
ture data, as the main compound, together with unidenti-
R
R
CH2NO2
2
OH
[O]
N
_
1
+
R
fied by-products, which were evidenced by TLC and H
1
C
N
O
-H2O
3
NMR of the crude reaction mixture. The extent of conver-
sion of the substrate, and the yield of the nitro compound,
depend on the oxime employed. In particular, electron do-
nating groups at the ortho- and para-positions favor the
N-oxidation and excellent conversions are obtained (e.g.
4-methoxy benzaldehyde oxime, entry 8 vs. 2, Table 1),
while electron withdrawing groups at the same positions
slow down the oxidation reaction (e.g. 2-nitrobenzalde-
hyde oxime, entry 9 vs. 2, Table 1), as expected on the ba-
sis of their influence on the electron density at the nitrogen
atom. It is worth noting that the oxime derived from benz-
aldehyde is oxidized quite satisfactorily with this mild
procedure (75% conversion, 50% isolated yield, entry 6,
Table 1) if compared with most of the previously reported
Scheme 1
A few procedures for the oxidation of oximes to nitro
compounds have already been reported.8 Unfortunately,
they are affected by some limitations, which make their
use unpractical. Indeed, they employ large excess of
strong oxidants such as peroxytrifluoroacetic acid,8a UHP
in combination with trifluoroacetic anhydride (TFAA),8b
SYNLETT 2004, No. 9, pp 1553–1556
Advanced online publication: 29.06.2004
DOI: 10.1055/s-2004-829088; Art ID: D00904ST
2
2.
0
7.
2
0
0
4
© Georg Thieme Verlag Stuttgart · New York

1554
F. Cardona et al.
LETTER
N
OH
R1
methods. For example, 20 equivalents of UHP were nec-
essary to furnish phenylnitromethane in 60% yield with
the UHP/TFAA method.8b
R
H
N
R
OR3
MTO (2–4 mol%)
UHP (3 equiv)
R3-OH, r.t.
O
Attempts to react an aliphatic oxime, namely heptalde-
hyde oxime, under the same conditions furnished a com-
plex mixture of products.
R2
R1
R2
a7 R = R1 = Cl, R2 = H, R3 = Me 64%
8 R = R1 = Cl, R2 = H, R3 = Et 72%
9 R = R1 = Cl, R2 = H, R3 = i-Pr 35%
10 R = R1 = Cl, R2 = H, R3 = Bn 44%
11 R = R1 = R2 = R3= Me 36%
4 R = R1 = Cl, R2 = H
5 R = R1 = R2 = Me
6 R = H, R1 = R2 = Cl
Table 1 Oxidation of Oximes to Nitro Compounds
cat. MTO
UHP (3 equiv)
12 R = H, R1 = R2 = Cl, R3 = Me 10%
ArCH=NOH
ArCH2NO2
MeOH, r.t.
Scheme 2
Entry Ar
MTO
(mol%) (d)
Time
Conversion Yield
(%)a
(%)b
35
44
–
the oxidation in methanol of 2,6-dichlorobenzaldehyde
oxime.
1
2
C6H5
2
4
4
4
4
5
50
Albeit the mechanism of the oxidation reaction has not
been studied in detail, formation of carbamates 7–12
probably comes from nucleophilic attack of the alcohol on
an isocyanate, which, in turn, is suggestive of the interme-
diate formation of nitrile oxides. Indeed, the rearrange-
ment of nitrile oxides to the corresponding isocyanates is
a well known reaction, although it usually requires high
temperatures to occur and, to the best of our knowledge, it
has never been reported under as mild conditions as those
used in this case. Proof of the occurrence of a nitrile oxide
intermediate has been collected by formation of the isox-
azolidine adducts 16, 17 and 18, 1912,15 (Scheme 4) when
the reaction was performed in the presence of good dipo-
larophiles such as N-phenylmaleimide (14) and dimethyl
maleate (15).16
C6H5
8
65
3
C6H5
5
15c
31d
44e
75
4
C6H5
5
–
5
C6H5
4
–
6
C6H5
10
2
6
50
46
44
14
35
n.c.
7
p-MeOC6H4
p-MeOC6H4
o-O2NC6H4
o-O2NC6H4
2-Naphthyl
6
100
100
20
8
4
2
9
4
6
10
11
10
2
6
60
3.5
25
a Calculated by integration of the 1H NMR spectra in the crude mix-
tures.
These results, together with failed attempts to trap a nitrile
oxide intermediate performing the reaction with 4-meth-
oxy benzaldehyde oxime in the presence of maleimide 14,
from which only the corresponding aryl nitromethane was
recovered, suggest that two different reaction pathways
are involved in the MTO-catalyzed oxidation of aryl
oximes. When no substituent is present at the ortho-posi-
tions, an initial N-oxidation takes place, leading directly
to the aci-form of the nitro compounds. In this case, the re-
activity follows the trend expected on the basis of elec-
tronic effects, with electron donating groups favoring N-
oxidation and electron withdrawing ones slowing it down.
On the contrary, when the aryl oxime is substituted at po-
sitions 2 and 6, carbamates are formed. Electronic effects
do not seem to play a role in this reaction, suggesting a
lack of conjugation in the starting oxime. Apparently, af-
ter the initial oxidation, loss of a molecule of water is
highly favored in this case, furnishing a nitrile oxide inter-
mediate, which rearranges to the isocyanate precursor of
b Isolated yields after purification by flash column chromatography.
c MeCN used as solvent.
d A 1:1 mixture of MeCN and MeOH used as solvents.
e 6 Equiv of UHP employed.
With 2,6-dichlorobenzaldehyde oxime (4), 2,4,6-trimeth-
yl benzaldehyde oxime (5) and 2,4-dichlorobenzaldehyde
oxime (6) a different result was obtained (Scheme 2): the
unexpected carbamates 7–12 were formed,12,13 depending
on the alcohol used as solvent, employing 2–4 mol% of
MTO and 3 equiv of UHP.11 The reaction did not proceed
at all in non-nucleophilic solvents such as CH2Cl2, MeCN
or ionic liquids {[BMIM]BF4}, leaving the starting mate-
rial unaltered. Experimental evidence for the formation of
the carbamates 7–12 was obtained from the 13C NMR
spectra, which showed diagnostic signals at d = 153–155
ppm for the quaternary C=O and from the observation of
1
broad singlets at d = 6.00–6.37 ppm in the H NMR
spectra, characteristic of the exchanging N-H protons of
carbamates.
NH2
Cl
H
Cl
Cl
N
OMe
The ultimate proof derived from an independent synthesis
(Scheme 3) of carbamate 7 according to the method re-
ported by Knölker14 starting from 2,6-dichloroaniline
(13). The product showed physical and spectroscopic
properties identical to those of the product obtained from
1. (Boc)2O, DMAP, CH3CN, r.t.
2. MeOH (1.2 equiv), 82 °C
O
Cl
13
7
Scheme 3
Synlett 2004, No. 9, 1553–1556 © Thieme Stuttgart · New York

LETTER
Methyltrioxorhenium-Catalyzed Oxidation of Aromatic Aldoximes
1555
N
(6) (a) The Chemistry of Amino, Nitroso, and Nitro Compounds
and their Derivatives; Patai, S., Ed.; Wiley: Ney York,
1982. (b) Nitro Compounds: Recent Advances in Synthesis
and Chemistry; Feuer, H.; Nielsen, A. T., Eds.; VCH: New
York, 1990.
OH
R
R
O
CO2Me
R1
4 or 5
(7) (a) Jäger, V.; Colinas, P. A. Nitrile Oxides, In The Chemistry
of Heterocyclic Compounds, Vol. 59; Padwa, A.; Pearson,
W. H., Eds.; John Wiley and Sons: New York, 2002.
(b) Torssell, K. B. G. Nitrile Oxides, Nitrones, and
Nitronates in Organic Synthesis; VCH: Weinheim, 1988.
(8) (a) Emmons, W. D.; Pagano, A. S. J. Am. Chem. Soc. 1957,
77, 4557. (b) Ballini, R.; Marcantoni, E.; Petrini, M.
Tetrahedron Lett. 1992, 33, 4835. (c) Olah, G. A.; Ramajah,
P.; Lee, C.-S.; Prakash, G. K. S. Synlett 1992, 337.
(d) Bose, D. S.; Vanajatha, G. Synth. Commun. 1998, 28,
4531. (e) Ballistreri, F. P.; Barbuzzi, E.; Tomaselli, G. A.;
Toscano, R. M. Synlett 1996, 1093.
N
Ph
CO2Me
R1
14
R1
15
O
O
R
R
R
R
CO2Me
N
O
N Ph
N
O
CO2Me
O
16 R = Cl, R1 = H
17 R = R1 = Me
18 R = Cl, R1 = H
19 R = R1 = Me
(9) (a) Just, G.; Dahl, K. Tetrahedron 1968, 24, 5251.
(b) Kiegiel, J.; Popławska, M.; Jóźwik, J.; Kosior, M.;
Jurczak, J. Tetrahedron Lett. 1999, 40, 5605. (c) Gagneux,
A. R.; Meier, R. Helv. Chim. Acta 1970, 53, 1883.
(d) Giurg, M.; Młochowski, M. Pol. J. Chem. 1997, 71,
1093.
Scheme 4 Reaction conditions: MTO (4 mol%), UHP (3 equiv), 14
or 15 (1.5 equiv), MeOH, r.t.; 16: 17 h, 82%; 17: 27 h, 50%; 18: 24 h,
46%; 19: 4 d, 44%.
the carbamate. When only one ortho-substituent is present
the two pathways are in competition, as demonstrated by
2,4-dichlorobenzaldehyde oxime (6), which gave the car-
bamate 12 in a poor 10% yield (Scheme 2), together with
traces of the nitro compound, detected by 1H NMR in the
crude reaction mixture.
(10) Yamazaki, S. Bull. Chem. Soc. Jpn. 1997, 70, 877.
(11) Typical Procedure for the Oxidation of Oximes: A 10 mL
reaction flask was charged sequentially with MTO (0.02–
0.04 mmol), MeOH (2 mL), and UHP (3 mmol). The stirred
solution became yellow due to the formation of peroxy
species and after 5 min the oxime (1 mmol) was added. The
reaction mixture was stirred at r.t. for the time reported in
Table 1. The solvent was evaporated, the crude reaction
mixture was added with CH2Cl2 and the undissolved urea
was filtered off. The pure products were collected by
chromatography on silica gel using the appropriate eluent.
(12) All new compounds gave satisfactory analytical and
spectroscopic data.
In conclusion, the first catalyzed oxidation of oximes has
been reported. The reaction gives the corresponding aryl
nitromethanes from aryl oximes without substituents at C-
2 and C-6. The peculiar formation of aryl carbamates
when the starting oxime is ortho-disubstituted is also re-
ported. Isoxazolidines, deriving from intermediate nitrile
oxides, have been obtained in this case by addition of re-
active dipolarophiles.
(13) Selected data for carbamates:
8: Rf = 0.17 (petroleum ether–Et2O 6:1). Pale yellow solid;
mp 118–120 °C. IR (CDCl3): 3421, 2984, 2934, 1730, 1497,
1227 cm–1. 1H NMR (200 MHz, CDCl3): d = 7.39–7.34 (m,
2 H, ArH), 7.20–7.11 (m, 1 H, ArH), 6.26 (br s, 1 H, NH),
4.24 (q, 2 H, J = 7.0 Hz, OCH2), 1.30 (t, 3 H, J = 7.0 Hz,
CH2CH3). 13C NMR (50 MHz, CDCl3): d = 153.8, 133.8,
132.0, 128.4, 128.2, 62.0, 14.4. MS: m/z (%) = 233 (4) [M+
– 1], 200(13), 198 (47), 176 (32), 173 (40), 163 (54), 161
(100). Anal. Calcd for C9H9Cl2NO2: C, 46.18; H, 3.88; N,
5.98. Found: C, 46.48; H, 3.84; N, 5.76.
11: Rf = 0.20 (petroleum ether–Et2O 4:1). White solid; mp
107–109 °C. IR (CDCl3): 3427, 3314, 2956, 2922, 2861,
1726, 1500, 1450, 1355, 1225 cm–1. 1H NMR (200 MHz,
CDCl3): d = 6.90 (m, 2 H, ArH), 6.11 (br s, 1 H, NH), 3.76
(br s, 3 H, OCH3), 2.28 (s, 3 H), 2.22 (s, 6 H). 13C NMR (50
MHz, CDCl3): d = 155.1, 136.8, 135.6, 130.9, 128.8, 52.4,
20.8, 18.1. MS: m/z (%) = 193 (91) [M+], 162 (34), 160 (45),
146 (27), 135 (80), 132 (100), 119 (23), 91 (51). Anal. Calcd
for C11H15NO2: C, 68.37; H, 7.82; N, 7.25. Found: C, 68.76;
H, 7.85; N, 7.72.
Acknowledgment
This work has been supported by CNR-Agenzia 2000 Progetto Gio-
vani. We thank Maurizio Passaponti for Technnical Support.
References
(1) Beattie, G.; Jones, P. J. Inorg. Chem. 1979, 18, 2318.
(2) For reviews, see: (a) Herrmann, W. A.; Kühn, F. E. Acc.
Chem. Res. 1997, 30, 169. (b) Owens, G. S.; Arias, J.; Abu-
Omar, M. M. Catal. Today 2000, 55, 317. (c) Kühn, F. E.;
Herrmann, W. A. Chemtracts 2001, 14, 59.
(3) Soldaini, G.; Cardona, F.; Goti, A. Tetrahedron Lett. 2003,
44, 5589.
(4) (a) Goti, A.; Nannelli, L. Tetrahedron Lett. 1996, 37, 6025.
(b) Goti, A.; Cardona, F.; Soldaini, G. Org. Synth. 2004, 81,
in press.
(5) (a) Goti, A.; Romani, M. Tetrahedron Lett. 1994, 35, 6567.
(b) Goti, A.; De Sarlo, F.; Romani, M. Tetrahedron Lett.
1994, 35, 6571. (c) Cicchi, S.; Cardona, F.; Brandi, A.;
Corsi, M.; Goti, A. Tetrahedron Lett. 1999, 40, 1989.
(d) Cicchi, S.; Corsi, M.; Goti, A. J. Org. Chem. 1999, 64,
7243. (e) Cicchi, S.; Marradi, M.; Goti, A.; Brandi, A.
Tetrahedron Lett. 2001, 42, 6503.
(14) Knölker, H.-J.; Braxmeier, T. Tetrahedron Lett. 1996, 37,
5861.
(15) Selected data for cycloadducts:
16: White solid; mp 207–209 °C (CH3OH). IR (CDCl3):
3072, 2975, 1732, 1562, 1499, 1433, 1377, 1192 cm–1. 1H
NMR (200 MHz, CDCl3): d = 7.48–7.26 (m, 8 H, ArH), 5.73
(d, 1 H, J = 9.3 Hz, H-6a), 4.91 (d, 1 H, J = 9.3 Hz, H-3a).
13C NMR (50 MHz, CDCl3): d = 171.1, 168.9, 150.0, 135.2,
132.1, 130.8, 129.4, 129.2, 128.4, 126.0, 125.3, 80.0, 56.7.
MS: m/z (%) = 361 (10) [M+], 360 (27) [M+ – 1], 212 (51),
Synlett 2004, No. 9, 1553–1556 © Thieme Stuttgart · New York

1556
F. Cardona et al.
LETTER
Anal. Calcd for C16H19NO5: C, 62.94; H, 6.27; N, 4.59.
173 (50), 119 (100), 91 (7). Anal. Calcd for C17H10Cl2N2O3:
C, 56.53; H, 2.79; N, 7.76. Found: C, 56.37; H, 2.64; N, 8.00.
19: Rf = 0.19 (petroleum ether–Et2O 5:1). White solid; mp
129–130 °C. IR (CDCl3): 2956, 1743, 1437, 1310, 1269,
1225 cm–1. 1H NMR (200 MHz, CDCl3): d = 6.87 (m, 2 H,
ArH), 5.58 (d, 1 H, J = 6.6 Hz, H-5), 4.70 (d, 1 H, J = 6.6 Hz,
H-4), 3.85 (s, 3 H, OCH3), 3.60 (s, 3 H, OCH3), 2.27 (s, 3 H),
2.18 (s, 6 H). 13C NMR (50 MHz, CDCl3): d = 169.3, 167.2,
153.5, 139.2, 136.9, 128.5, 123.3, 80.7, 59.7, 53.1, 53.0,
21.1, 19.6. MS: m/z (%) = 306 (1) [M+], 305 (5) [M+ – 1],
246 (32), 219 (25), 214 (10), 186 (61), 158 (29), 57 (100).
Found: C, 62.58; H, 6.02; N, 4.40.
(16) Typical Procedure for the Synthesis of Cycloadducts: To
a stirred solution of MTO (0.04 mmol) in MeOH (2 mL) was
added UHP (3 mmol), the dipolarophile (1.5 mmol) and the
oxime (1 mmol). The reaction mixture was stirred at r.t. until
no more oxime was detected by TLC. The solvent was
evaporated, the crude mixture was added with CH2Cl2 and
the undissolved urea was filtered off. The residue was
purified by chromatography on silica gel to afford the pure
products.
Synlett 2004, No. 9, 1553–1556 © Thieme Stuttgart · New York