Rhenium-catalyzed highly efficient oxidations of tertiary nitrogen compounds to N-oxides using sodium percarbonate as oxygen source

Article abstract of DOI:10.1055/s-2006-951487

Sodium percarbonate was found to be an ideal and efficient oxygen source for the oxidation of tertiary nitrogen compounds to N-oxides in excellent yields in presence of various rhenium-based catalysts under mild reaction conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-951487

LETTER
2661
Rhenium-Catalyzed Highly Efficient Oxidations of Tertiary Nitrogen
Compounds to N-Oxides Using Sodium Percarbonate as Oxygen Source
R
henium-Cata
u
lyzed Oxida
m
T
ertiar
y
N
it
a
roge
n
Com
n
pounds to
N
-Oxide
L
s
. Jain, Jomy K. Joseph, Bir Sain*
Chemical and Biotechnology Division, Indian Institute of Petroleum, Dehradun 248005, India
Fax +91(135)2660202; E-mail: birsain@iip.res.in
Received 28 March 2006
R
R
Abstract: Sodium percarbonate was found to be an ideal and effi-
R
Re catalyst, SPC
MeCN, 50 °C
R
R
R
cient oxygen source for the oxidation of tertiary nitrogen com-
pounds to N-oxides in excellent yields in presence of various
rhenium-based catalysts under mild reaction conditions.
R
R
N
N
O
,
,
N
N
O
Re catalyst = MTO, Re2O7, HReO4
Key words: rhenium, solid oxidants, sodium percarbonate, oxida-
tion, N-oxides
Scheme 1
The results are summarized in Table 1. Among the vari-
ous catalysts studied, methyltrioxorhenium was found to
be the most competent for this transformation. To evalu-
ate the effect of catalyst, blank oxidation of 4-picoline
with sodium percarbonate was also carried out under
similar reaction conditions in the absence of catalyst. The
reaction was found to be very slow and afforded a poor
yield of the corresponding N-oxide (Table 1, entry 1). In
order to compare the effectiveness of this solid oxidant,
we also studied the oxidation of 4-picoline using aqueous
hydrogen peroxide as oxidant in place of SPC in the
presence of various Re catalysts under similar reaction
conditions as shown in Table 1 (entries 2–4). All the reac-
tions were found to be slow and afforded poor yields of
the N-oxide, confirming the deactivation of Re catalyst
due to the presence of water
The development of metal-catalyzed green and environ-
mentally benign synthetic methodologies using hydrogen
peroxide and molecular oxygen as oxidants is an area of
tremendous importance.1 Rhenium-based systems, owing
to their unique properties such as higher oxidation ability,
versatility and non-productive decomposition of hydro-
gen peroxide have attracted particular attention in recent
years in various oxidation reactions. Methyltrioxorheni-
um (MTO) first reported by Herrmann et al.2 due to its
ease of synthesis, commercial availability and stability in
air has proven to be an exceptionally versatile oxygen
transfer catalyst for various oxygenation reactions with
aqueous hydrogen peroxide in both organic and aqueous
solvents. The major drawback of this efficient system is
the limited stability of MTO due to its decomposition in
water. Solid peroxy compounds such as sodium perborate
(SPB) and sodium percarbonate (SPC) owing to their ease
of synthesis, safe handling and storage stability have
proven to be safe alternatives of dangerous anhydrous
hydrogen peroxide.3 However, potential of these solid
oxidants in MTO-catalyzed oxidation reactions has
remained largely unexplored and to the best of our knowl-
edge there is only one literature report on the use of sodi-
um percarbonate as oxygen source for the epoxidation of
alkenes using MTO as catalyst.4 In continuation to our
studies on the development of green synthetic methods5
herein we wish to report an efficient and simple method-
ology for the oxidation of tertiary nitrogen compounds us-
ing sodium percarbonate as solid oxidant6 in presence of
various rhenium-based catalysts such as MTO, Re2O7 and
HReO4 under very mild reaction conditions (Scheme 1).
To generalize the method, a variety of tertiary nitrogen
compounds was subjected to the oxidation using substrate
(10 mmol) with a catalytic amount of methyltrioxorheni-
um (1 mol%) and sodium percarbonate (20 mmol) in the
presence of acetic acid (20 mol%) in acetonitrile at 50 °C
Table 1 Comparison of Results of Rhenium-Catalyzed Oxidation
of 4-Picoline with Sodium Percarbonate/Hydrogen Peroxide
Oxidantsa
Entry Catalyst Sodium percarbonate 30% H2O2
Reaction Yield (%)b Reaction Yield (%)b
time (h)
time (h)
1c
2
–
8
30
92
85
90
8
Trace
90
To evaluate the efficiency of various rhenium-based cata-
lysts we carried out the oxidation of 4-picoline (10 mmol)
with sodium percarbonate (20 mmol) in the presence of
acetic acid (20 mol%) and Re catalyst (1 mol%) at 50 °C.
MTO
Re2O7
HReO4
1.5
3.5
3
2.5
4.5
30
4
2.0
5.0
50
a Reaction conditions: 4-picoline (10 mmol), oxidant (20 mmol),
AcOH (20 mol%), catalyst (1 mol%), MeCN (3 mL) at 50 °C.
b Isolated yields.
SYNLETT 2006, No. 16, pp 2661–2663
Advanced online publication: 22.09.2006
DOI: 10.1055/s-2006-951487; Art ID: D08906ST
© Georg Thieme Verlag Stuttgart · New York
0
4
.1
0
.2
0
0
6
c Experiment carried out in the absence of Re catalyst.

2662
S. L. Jain et al.
LETTER
under nitrogen atmosphere.7 All the substrates were selec-
tively converted into the corresponding N-oxides and the
results are presented in Table 2. In general triethylamine
and substituted anilines were found to be most reactive
(Table 2, entry 9–11) while among the various pyridines
studied, those substituted with electron-donating groups
were found to be more reactive and required shorter reac-
tion times for their oxidation (Table 2, entry 3, 4 and 7).
The presence of acetic acid was found to be essential for
these reactions and in its absence reactions were found to
be very slow and gave very poor yields of the oxidized
products, probably due to the fact that presence of acid
may help in releasing the hydrogen peroxide from both
sodium percarbonate and sodium perborate reagents. The
use of triflouroacetic acid in place of acetic acid also
yielded comparable results while the use of inorganic
acids such as hydrochloric acid and sulfuric acid gave no
oxidation. It was also observed that the addition of acetic
acid in one portion gave poor yields of the products while
its dropwise addition gave better yields of the oxidized
products. The reaction mixture of substrate, MTO and so-
dium percarbonate in acetonitrile upon addition of acetic
acid gave vibrant yellow color indicating the formation of
activated peroxo species during the reaction, while the
disappearance of the yellow color indicates the comple-
tion of the reaction. To compare the efficiency of both
solid oxidants, we carried out the oxidation of pyridine
with SPB instead of SPC in presence of catalytic amount
of MTO under similar reaction conditions. Neither the
yellow color of the reaction mixture upon addition of
acetic acid nor the oxidation was observed as shown in
Table 2 (entry 2).
Table 2 Methyltrioxorhenium-Catalyzed Oxidation of Tertiary
Nitrogen Compounds Using SPC as Oxygen Sourcea (continued)
Entry Substrate
Product
Time Yield
(h)
(%)b,c
5
4.0
75
CN
CN
N
O
N
6
6.5
70
O
C
O
C
NH2
NH2
N
N
N
O
7
8
9
2.75
8.5
90
55
92
Me
Me
N
O
N
N
O
1.25
Et
O
Et
Et
Et
Et
N
N
10
1.0
94
O
Me
Et
Me
N
N
Table 2 Methyltrioxorhenium-Catalyzed Oxidation of Tertiary
Nitrogen Compounds Using SPC as Oxygen Sourcea
Entry Substrate
Product
Time Yield
(h)
(%)b,c
11
1.0
95
Et3N
Et3N
O
1
2.5
90
a Reaction conditions: substrate (10 mmol), MTO (1 mol%), SPC
(20 mmol), AcOH (20 mol%), acetonitrile (3 mL), at 50 °C under
nitrogen atmosphere.
N
N
O
b Isolated yields; purity >99% as determined by GC.
c All the products were characterized via their physical (mp) and
spectral (IR and 1H NMR) data.8
2d
8.0
1.5
–
d Experiment carried out using SPB as oxidant in place of SPC.
N
N
O
The effect of various solvents was studied by carrying out
the oxidation of 4-picoline under similar reaction condi-
tions using different solvents such as acetonitrile, di-
chloroethane, toluene and ethanol. Among the various
solvents studied acetonitrile and dichloroethane were
found to be the good solvents for this transformation.
3
4
92
Me
N
Me
N
O
A plausible mechanism of these reactions may involve the
formation of active peroxo species of rhenium by the re-
action with sodium percarbonate in the presence of acetic
acid as shown in the Scheme 2. The subsequent oxygen
transfer from these reactive peroxo species to tertiary
nitrogen compound yields the corresponding N-oxide.
2.5
89
N
N
O
Me
Me
Synlett 2006, No. 16, 2661–2663 © Thieme Stuttgart · New York

LETTER
Rhenium-Catalyzed Oxidations of Tertiary Nitrogen Compounds to N-Oxides
2663
(6) The use of SPC as oxidant with water donor for oxidation of
tertiary nitrogen compounds to N-oxides has been reported:
(a) Rosenau, T.; Potthast, A.; Kosma, P. Synlett 1999, 1972.
(b) Rosenau, T.; Hofinger, A.; Potthast, A.; Kosma, P. Org.
Lett. 2004, 541.
O
Re
R
R
R
O
N
N
H2O
(7) Typical Experimental Procedure: To a stirred solution of
4-picoline (10 mmol, 0.93 g), in MeCN (3 mL) were added
SPC (3.12 g, 20 mmol) and MTO (25 mg, 1 mol%) and the
mixture was heated to 50 °C under nitrogen atmosphere.
AcOH (20 mol%) was added dropwise over a period of 15
min at 50 °C to this vigorously stirred solution. A vibrant
yellow color appeared in the reaction mixture upon addition
of AcOH. The progress of the reaction was monitored by
TLC (SiO2). After completion, the solvent was evaporated
and the residue was dissolved in CH2Cl2. The organic layer
was washed with water (2 ×) and dried over anhyd Na2SO4.
The solvent was evaporated under reduced pressure and the
residue thus obtained was purified by passing through a short
silica gel column using EtOAc–hexane (4:6) as eluent.
Evaporation of the solvent under reduced pressure yielded
pure 4-picoline N-oxide (1.02 g, 92%); mp 180–181 °C (Lit.9
182 °C). IR: 3033, 1470, 1250, 1176 cm–1. 1H NMR: d = 2.39
(s, 3 H), 7.10–7.22 (d, 2 H), 8.09–8.20 (d, 2 H).
R
R
O
H2O2
R
Re
O
Re=O: MTO, Re2O7, HReO4
AcOH + SPC
Scheme 2
In summary sodium percarbonate was found to be an
efficient and versatile oxygen source for the oxidation of
tertiary nitrogen compounds to N-oxides using various
rhenium-based compounds as catalysts under mild reac-
tion conditions. The safe and ease of handling of the SPC
in place of anhydrous hydrogen peroxide, controlled re-
lease of the hydrogen peroxide, easy workup and better
yields of the products makes this a facile and valuable
protocol for the oxidation of tertiary amines.
(8) Product Characterization Data.
Pyridine N-Oxide (Table 2, entry 1): mp 60–61 °C (Lit.9
62–63 °C). IR: 3076, 1388, 1265, 1176 cm–1. 1H NMR: d =
7.42–7.45 (m, 3 H), 8.25–8.40 (m, 2 H).
2-Picoline N-Oxide (Table 2, entry 4): Hygroscopic oil. IR:
3030, 1482, 1252, 1190 cm–1. 1H NMR: d = 2.42 (s, 3 H),
7.10–7.19 (m, 3 H), 8.10–8.23 (m, 1 H).
Acknowledgment
We are grateful to the Director of IIP for his kind permission to
publish these results. Suman L. Jain and Jomy K. Joseph are thank-
ful to CSIR, New Delhi for the award of Research Fellowships.
4-Cyanopyridine N-Oxide (Table 2, entry 5): mp 180–182
°C (Lit.9 182–183 °C). IR: 3076, 2247, 1492, 1282, 1176
cm–1. 1H NMR: d = 7.89–8.00 (d, 2 H), 8.42–8.46 (d, 2 H).
Nicotinamide N-Oxide (Table 2, entry 6): mp 289–290 °C
(decomp.). IR: 3350, 3060, 1694, 1450, 1140 cm–1.
1H NMR: d = 7.37–7.45 (m, 2 H), 8.27–8.40 (m, 2 H).
3-Picoline N-Oxide (Table 2, entry 7): Hygroscopic oil. IR:
3030, 1470, 1252, 1162 cm–1. 1H NMR: d = 2.35 (s, 3 H),
7.11–7.21 (m, 2 H), 8.18–8.20 (m, 2 H).
Reference and Notes
(1) (a) Anastas, P. T.; Warner, J. C. Green Chemistry, Theory
and Practice; Oxford University: Oxford, 1998. (b) Eissen,
M.; Metzger, J. O.; Schmidt, E.; Schneidewind, U. Angew.
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Chemistry & Technology; Clark, J.; Macquarrie, D., Eds.;
Blackwell: Oxford, 2002.
(2) For reviews, see: (a) Kühn, F. E.; Scherbaum, A.;
Herrmann, W. A. J. Organomet. Chem. 2004, 689, 4149.
(b) Romao, C. C.; Kuhn, F. E.; Herrmann, W. A. Chem. Rev.
1997, 97, 3197. (c) Espenson, H. Chem. Commun. 1999,
479. (d) Owens, S.; Arias, J.; Abu-Omar, M. M. Catal.
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Quinoline N-Oxide (Table 2, entry 8): mp 50–52 °C (Lit.9
52–53 °C). IR: 3030, 1484, 1298, 1176 cm–1. 1H NMR: d =
7.21–7.35 (m, 4 H), 8.10–8.19 (m, 2 H), 8.40 (m, 1 H).
N,N-Diethylaniline N-Oxide (Table 2, entry 9):
Hygroscopic solid. IR: 3013, 2941, 1369, 1219, 1190 cm–1.
1H NMR: d = 1.2 (t, 6 H), 3.3 (q, 2 H), 6.9 (m, 3 H), 7.3 (m,
2 H).
N,N-Dimethylaniline N-Oxide (Table 2, entry 10):
Hygroscopic solid. IR: 3010, 2941, 1367, 1219, 1175 cm–1.
1H NMR: d = 3.32 (s, 6 H), 7.22–7.28 (m, 3 H), 7.49–7.55
(m, 2 H).
Triethylamine N-Oxide (Table 2, entry 11): Hygroscopic
solid. IR: 2940, 2870, 1470, 1250 cm–1. 1H NMR: d = 1.12
(t, 9 H), 3.30 (q, 6 H).
(3) For reviews, see: (a) McKillop, A.; Sanderson, W. R.
Tetrahedron 1995, 51, 6145. (b) Muzart, J. Synthesis 1995,
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(4) Vaino, A. R. J. Org. Chem. 2000, 65, 4210.
(5) (a) Joseph, J. K.; Jain, S. L.; Sain, B. Eur. J. Org. Chem.
2006, 590. (b) Jain, S. L.; Sain, B. Angew. Chem. Int. Ed.
2003, 42, 1265. (c) Sharma, V. B.; Jain, S. L.; Sain, B.
Tetrahedron Lett. 2003, 44, 383. (d) Jain, S. L.; Sain, B.
Chem. Commun. 2002, 1040. (e) Jain, S. L.; Sain, B. J. Mol.
Catal. 2001, 176, 101. (f) Sharma, V. B.; Jain, S. L.; Sain, B.
Tetrahedron Lett. 2003, 44, 3235. (g) Jain, S. L.; Sain, B.
Appl. Catal. A. Gen. 2006, 301, 259.
(9) Prasad, M. R.; Kamalkar, G.; Madhavi, G.; Kulkarni, S. J.;
Raghavan, K. V. J. Mol. Catal. A: Chem. 2002, 186, 109.
Synlett 2006, No. 16, 2661–2663 © Thieme Stuttgart · New York