An environmentally friendly oxidation system for the selective oxygenation of aldimines to oxaziridines with anhydrous TBHP and alumina-supported MoO 3 as a recyclable heterogeneous catalyst

Article abstract of DOI:10.1002/ejoc.200600980

A highly efficient and selective protocol for the oxygenation of various aldimines to oxaziridines, which proceeds in excellent yields with enhanced selectivity by using alumina-supported M0O₃ as a recyclable heterogeneous catalyst and anhydrous TBHP as the ultimate oxidant, is described. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200600980

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200600980
An Environmentally Friendly Oxidation System for the Selective Oxygenation
of Aldimines to Oxaziridines with Anhydrous TBHP and Alumina-Supported
MoO3 as a Recyclable Heterogeneous Catalyst
Sweety Singhal,[a] Suman L. Jain,[a] V. V. D. N. Prasad,[a] and Bir Sain*[a]
Keywords: Oxygenation / Supported catalysts / Heterogeneous catalysis / Imines
A highly efficient and selective protocol for the oxygenation
of various aldimines to oxaziridines, which proceeds in excel-
lent yields with enhanced selectivity by using alumina-sup-
ported MoO3 as a recyclable heterogeneous catalyst and an-
hydrous TBHP as the ultimate oxidant, is described.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
transformation as oxaziridines are synthetically important
building blocks that find wide application in asymmetric
synthesis,[3–5] in the preparation of biologically active com-
pounds[6,7] and extensively used as nitrogen[8,9] and oxy-
gen[10,11] transfer reagents in various synthetically impor-
tant reactions. A variety of oxidizing agents such as m-
CPBA,[12–16] Ac2O/H2O2,[17] urea/H2O2,[18] H2O2/ni-
trile,[19,20] tert-amyl hydroperoxide[21] and molecular oxy-
gen[22,23] in the presence of transition metals were used to
accomplish this transformation. However, most of these
methods are associated with drawbacks such as harsh reac-
tion conditions, the use of aldehydes as a sacrificial agent,
the formation of side products, poor yields and difficult
work up procedures, which leaves room to develop an ef-
ficient and simple process for the oxygenation of imines to
oxaziridines. Herein, we wish to reveal, for the first time,
a highly efficient oxidation system for the oxygenation of
aldimines to the corresponding 2-alkyl-3-aryl oxaziridines
in excellent yields by employing alumina-supported MoO3
as a heterogeneous recyclable catalyst and anhydrous TBHP
in toluene[24] as the oxidant without using additional or-
ganic solvent under mild reaction conditions (Scheme 1).
Introduction
The replacement of conventional oxidation methods,
which involve the use of metal oxidants that generate enor-
mous amounts of undesirable waste products, with atom
efficient catalytic processes that use green and inexpensive
oxidants such as O2, H2O2, TBHP, etc., has gained con-
siderable attention in recent years. In particular, hetero-
geneous catalysts are preferred because of their inherent ad-
vantages, which include its ease of use, its ease of separation
from the product, its decreased corrosiveness and its high
atom economy, stability and reusability.[1] In this context,
supported metal catalysts such as metal-containing zeolites
and alumina-supported metal oxides are extensively used in
the development of industrial oxidation processes. However,
the major drawbacks of these catalysts are their low activity,
their tendency to leach metal catalysts from the support
during the reaction and their requirement for high tempera-
tures and pressures. Furthermore, the presence of water in
the system not only facilitates the leaching of the metal cat-
alyst from the support, but it also makes the oxidation reac-
tions less efficient and selective as a result of the formation
of byproducts. These limitations led us to become interested
in the development of environmentally benign oxidation
methodologies that use anhydrous oxidants. Recently,
TBHP in decane was used as an anhydrous oxidant for the
epoxidation of olefins by using immobilized MoVI com-
plexes on functionalized silica as the heterogeneous cata-
lyst.[2] Oxygenation of imines is an important synthetic
Scheme 1.
Results and Discussion
[a] Chemical and Biotechnology Division, Indian Institute of Pe-
troleum,
A 16 wt-% MoO3/Al2O3 catalyst was prepared on a γ-
Al2O3 support (Condea, Germany) [BET surface area:
280 m2 g–1, total pore volume: 0.7 mLg–1, total acidity:
0.31 mmolg–1 (strong)] by an incipient wet impregnation
Mohkampur, Dehradun, 248005 India
Fax: +91-135-2660202
E-mail: birsain@iip.res.in
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2007, 2051–2054
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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S. Singhal, S. L. Jain, V. V. D. N. Prasad, B. Sain
SHORT COMMUNICATION
method with the use of ammonium heptamolybdate Table 1. Oxidation of N-benzylidene-tert-butylamine (1a) with an-
hydrous TBHP by using MoO3/Al2O3 as the catalyst under various
conditions.
[(NH4)6Mo7O24 4H2O] salt. The catalyst was dried at
110 °C (overnight) and finally calcined at 550 °C for six
hours.[25]
Entry
Additional solvent
Oxidant
Temp. Reaction
Yield
[%][a]
[°C]
time [h]
Physicochemical Characterization of the Catalyst: The
Mo content was estimated by ICP-AES and measured as
16%. XRD pattern did not show any characteristic peak
for MoO3, which indicates that MoO3 is finely dispersed
over the Al2O3 surface. This was in agreement with low-
temperature oxygen chemisorption (LTOC) studies, which
indicated the crystallite size of MoO3 to be 16.1 Å with an
equivalent molybdenum surface area of 38.6 m2 g–1, surface
coverage (θ) 9.1%. Temperature programmed reduction
(TPR) studies of the catalyst showed two characteristic
1
2
3
4
5
6
7
acetonitrile
1,2-dichloroethane
anhyd. TBHP
anhyd. TBHP
anhyd. TBHP
anhyd. TBHP
anhyd. TBHP
anhyd. TBHP
70% aq. TBHP
80
80
67
110
room
80
5.5
7.0
10
2.5
6.0
4.5
5.5
50
30
55
96
trace
45
methanol
–
–
–
acetonitrile
80
60
[a] Isolated yields.
peaks first at 500 °C for MoVI to MoIV and second at tron-donating groups on the phenyl ring attached to the C-
900 °C for MoIV to Mo0.[26]
atom of the aldimine were found to be the most reactive
The protocol developed for the oxygenation of various and required shorter reaction times under the described re-
aldimines consists of the addition of anhydrous TBHP in action conditions (Table 2, Compounds 1d–f). Aldimines
toluene to the stirred reaction mixture of the substrate and having electron-withdrawing groups on the phenyl ring were
the 16 wt-% MoO3/Al2O3 catalyst (5 mol-%) at 110 °C with- generally found to be less reactive (Table 2, Com-
out the addition of further organic solvent as the reaction pounds 1g,h) than aldimines derived from benzaldehyde
media under a nitrogen atmosphere. We first selected N- and the corresponding amine (Table 2, Compounds 1a–c,
benzylidene-tert-butylamine as a model substrate and 1i). However, furfurylidine-tert-butylamine was found to be
studied its oxygenation with TBHP using alumina sup- the least reactive and afforded a poor yield of the corre-
ported MoO3 as the catalyst to optimize the reaction condi- sponding oxaziridine under these reaction conditions
tions. The results of these optimization experiments are pre- (Table 2, Compound 1j).
sented in Table 1. The effect of various additional solvents
To compare the efficiency of this method, we performed
such as acetonitrile, dichloroethane and methanol on the the oxygenation of N-benzylidene-tert-butylamine using
oxygenation of N-benzylidene-tert-butylamine under re- commercially available aq. TBHP (70%) in combination
fluxing conditions is shown in Table 1, Entries 1–4. Surpris- with 5 mol-% alumina-supported MoO3 as a catalyst in re-
ingly the reaction was found to be very slow in the presence fluxing acetonitrile. The oxygenation reaction was slow and
of additional solvent and required a longer reaction time proceeded with lower selectivity and afforded an intricate
for completion. In the absence of additional solvent at mixture of products (Table 1, Entry 7). In addition, we did
110 °C, the reaction was complete within 2.5 h and gave observe the leaching of the metal while using aq. TBHP as
maximum yield of the corresponding oxaziridine. In a con- the oxidant. This is probably due to the presence of water,
trolled blank experiment under similar reaction conditions, which facilitates the leaching of metal catalysts from the
the oxygenation of N-benzylidene-tert-butylamine did not support.
proceed in the absence of catalyst. We also performed the
We used anhydrous TBHP in toluene as the oxidant in
oxygenation of N-benzylidene-tert-butylamine using pure these experiments; as a result of the absence of water in the
thermally treated alumina support as the catalyst under system, leaching of the catalyst from the support was not
otherwise similar reaction conditions. The reaction did not expected. We carried out a catalyst-leaching experiment and
proceed, which indicates that molybdenum oxide is the studied the oxygenation of N-benzylidene-tert-butylamime
main promoter for this reaction. Further, the oxygenation under similar reaction conditions. After completion of the
of N-benzylidene-tert-butylamine was found to be highly reaction to 50% conversion, we filtered off the catalyst from
dependant upon the reaction temperature. At room tem- the reaction mixture and continued the reaction as such at
perature, the reaction was very slow (Table 1, Entry 5), the same reaction temperature. The reaction did not pro-
whereas 110 °C was found to be the optimum temperature ceed any further, which confirms that there is no catalyst
for this reaction in terms of reaction time and yield of the leaching during the reaction. Further, it was ascertained by
product.
inductively coupled plasma atomic emission spectroscopy
To generalize the developed protocol, we studied the oxy- (ICP-AES) that the Mo content of the recovered MoO3/
genation of various substituted aldimines and these results Al2O3 catalyst was the same as that of fresh MoO3/Al2O3
are depicted in Table 2. All the aldimines except benzyl- and there was no dissolved molybdate in the filtrate. To
idene-aniline were selectively converted into the corre- check the recyclability and reusability of alumina-supported
sponding oxaziridines without any evidence for the forma- MoO3 with anhydrous TBHP, we carried out the oxygena-
tion of nitrones or other side products. The oxidation of tion of N-benzylidene-tert-butylamine under similar reac-
benzylidene-aniline under these reaction conditions yielded tion conditions. After completion of the reaction, the cata-
benzaldehyde as the sole product (Table 2, Compound 1k). lyst could be separated by filtration and reused as such for
Among the various aldimines studied, those having elec- subsequent oxygenation of N-benzylidene-tert-butylamine
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Eur. J. Org. Chem. 2007, 2051–2054

Selective Oxygenation of Aldimines to Oxaziridines
SHORT COMMUNICATION
Table 2. MoO3/Al2O3 catalyzed oxidation of aldimines with anhydrous TBHP in toluene.[a]
[a] Reaction conditions: substrate (10 mmol), TBHP in toluene (20 mmol), 16 wt-% MoO3/Al2O3 (5 mol%) at 110 °C under a nitrogen
atmosphere without adding further solvent. [b] Isolated yields.
(for three runs) after adding fresh substrate and oxidant the catalyst during the reaction established the merits of
(anhydrous TBHP in toluene) under similar reaction condi- this developed protocol over previously known methods.
tions. In these experiments, reaction times and yields of the
The exact mechanism of the reaction is not clear at this
oxaziridine remained almost the same as those reported in stage. The reaction probably involves the Mo-catalyzed oxy-
Table 3.
gen transfer from TBHP to substrate promoted by the sup-
port.
Table 3. Results of the reusability study of alumina-supported
MoO3.
Conclusions
Entry
Substrate
Run
Yield[a]
In summary, we have developed a new and highly ef-
ficient methodology for the selective oxygenation of various
aldimines to the corresponding oxaziridines in excellent
yields using catalytic amounts of 16 wt% MoO3/Al2O3 as
a catalyst and anhydrous TBHP as the oxidant. The key
1
2
3
1a
1a
1a
1
2
3
96
94
94
[a] Isolated yield.
The use of anhydrous TBHP as a clean and more selec- advantages of this developed protocol are: (1) the use of
tive oxidant, the recyclability/reusability of the catalyst with anhydrous TBHP as the oxidant provides a nearly water-
consistent reactivity and no leaching of the Mo species from free atmosphere, which makes the reactions more selective
Eur. J. Org. Chem. 2007, 2051–2054
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2053

S. Singhal, S. L. Jain, V. V. D. N. Prasad, B. Sain
SHORT COMMUNICATION
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towards the oxaziridines rather than ring-opening products,
(2) the supported MoO3/Al2O3 catalyst can be recycled and
reused without loss of activity and (3) no leaching of the
Mo species from the catalyst during the reaction is ob-
served. Easy work up, high yields of the products, recycl-
ability of catalyst and mild reaction conditions make this
method an improved, clean and environmentally acceptable
synthetic tool for the oxygenation of imines to oxaziridines.
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Experimental Section
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General Experimental Procedure: A 33% anhydrous TBHP solution
in toluene (20 mmol) was added dropwise to a stirred mixture of
aldimine (10 mmol) and 16 wt-% MoO3/Al2O3 (5 mol%) at 110 °C
under a nitrogen atmosphere without the addition of further sol-
vent. The progress of the reaction was monitored by TLC (SiO2).
After completion, the reaction mixture was cooled to room tem-
perature and diluted with ethyl acetate. The catalyst was separated
by filtration through a Buchner funnel and reused as such for sub-
sequent experiments. The filtrate obtained was washed with water
(6ϫ). The organic layer was dried with anhydrous Na2SO4, and the
solvent was removed under reduced pressure. The crude product
was purified by passage through a short column of silica gel (ethyl
acetate/hexane, 4:6). The yields and reaction times of the oxazirid-
ines are presented in Table 2.
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Supporting Information (see footnote on the first page of this arti-
cle): Preparation of the catalyst and product characterization data.
Acknowledgments
[23] L. Martiny, K. A. Jorgensen, J. Chem. Soc., Perkin Trans. 1
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We are thankful to the Director, IIP for his kind permission to
publish these results. S. S. and S. L. J. are thankful to CSIR, New
Delhi for Research Fellowships. We are very grateful to the catalyst
preparation laboratory of this institute who provided help in the
characterization of the catalyst.
[24] Anhydrous TBHP in toluene was prepared according to the
literature procedure.[27] The strength of the solution was ana-
lyzed by sodium thiosulfate/KI method and was found to be
33%.
[25] B. M. Reddy, E. P. Reddy, S. T. Srinivas, J. Catal. 1992, 136,
50.
[26] Other physicochemical characteristics of the catalyst deter-
mined by N2 adsorption–desorption isotherm at liquid nitro-
gen temperature (–195 °C) were: SBET: 248.9 m2 g–1, micro-
pore area: 15.1 m2 g–1, external surface area: 233.8 m2 g–1, total
pore volume: 0.394 mLg–1, pore size distribution [Å (%)]: Ͻ10
(15.14), 10–20 (8.04), 20–100 (48.85), 100–200 (25.71), 200–500
(1.49), Ͼ500 (0.77).
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Received: November 9, 2006
Published Online: March 13, 2007
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