Nafion supported molybdenum oxychloride: Recyclable catalyst for one-pot synthesis of nitrones via direct condensation/oxidation of primary amines and aldehydes using UHP as oxidant

Article abstract of DOI:10.1039/b914402a

Immobilization of molybdenum(vi) oxychloride to the surface of perfluorinated ion-exchange polymer "Nafion"via an ion exchange method was carried out for the first time. The prepared Nafion immobilized molybdenum(vi) oxychloride catalyst was used for the direct synthesis of nitrones via one-pot condensation/oxidation of primary amines with aldehydes using solid urea-hydrogen peroxide (UHP) as oxidant under very mild reaction conditions. The developed polymer immobilized catalyst showed better activity than its analogous homogeneous catalyst with the added benefits of facile recovery and recyclability of the catalyst without leaching and loss in catalytic activity.

Full text of DOI:10.1039/b914402a

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Nafion supported molybdenum oxychloride: Recyclable catalyst for one-pot
synthesis of nitrones via direct condensation/oxidation of primary amines
and aldehydes using UHP as oxidant
Bhawan Singh, Suman L. Jain,* Praveen K. Khatri and Bir Sain*
Received 20th July 2009, Accepted 25th September 2009
First published as an Advance Article on the web 7th October 2009
DOI: 10.1039/b914402a
Immobilization of molybdenum(VI) oxychloride to the
surface of perfluorinated ion-exchange polymer “Nafion”
via an ion exchange method was carried out for the first
time. The prepared Nafion immobilized molybdenum(VI)
oxychloride catalyst was used for the direct synthesis of
nitrones via one-pot condensation/oxidation of primary
amines with aldehydes using solid urea-hydrogen peroxide
(UHP) as oxidant under very mild reaction conditions.
The developed polymer immobilized catalyst showed better
activity than its analogous homogeneous catalyst with the
added benefits of facile recovery and recyclability of the
catalyst without leaching and loss in catalytic activity.
of the catalyst. In recent decades, considerable attention has
been devoted to the immobilization of homogeneous transition
metal complexes onto solid supports9 due to the added benefits
of increased catalyst stability, catalyst recycling, and ease of
product separation. In this regard, transition metal complexes
have widely been supported on silica and other inorganic oxides,
in clays, in siloxanes, exchanged into ion-exchange resins and
attached to polystyrene and other organic polymers through
covalent bonding to the ligands in the metal complexes.9,10
Nafion, a perfluorinated ion exchange polymer developed by
Dupont has many practical applications in catalysis. Owing to
the presence of a strongly electron withdrawing fluorocarbon
backbone, the sulfonic acid sites within Nafion are quite strong.
This has led to the use of Nafion as a solid acid catalyst
for a variety of organic reactions such as alkylation, esterifi-
cation, acylation, olefin oligomerization, and isomerization,11
whereas catalytic active site modified Nafion resins for synthetic
applications have seldom been reported.12 Oxo-molybdenum
complexes are versatile catalysts and have extensively been used
as homogeneous catalysts for the oxidation of organic substrates.
Heterogenization of molybdenum catalysts is an emerging area
of current research interest and a variety of supports, such as
mesoporous materials, polymers and ionic liquids, have hitherto
been used for this purpose.13 In the present study, we have
used Nafion NR-50 ion-exchange resin as a support for the
immobilization of an oxo-molybdenum compound. To the best
of our knowledge this is the first report on the immobilization of
a molybdenum catalyst to Nafion support. The heterogenization
of MoOCl4 to the Nafion support was carried out, as shown in
Scheme 1. Immobilization of Mo catalyst to the polymer support
was confirmed by IR spectroscopy as it showed clear bands of
Nitrones are valuable synthones in the realm of organic synthesis
which are extensively used in the synthesis of biologically active
compounds,1 as spin trap reagents,2 as therapeutic agents3 and
also behave like 1,3-dipoles in cycloaddition reactions.4 Two
main synthetic methods commonly used for the preparation
of nitrones are: i) condensation of carbonyl compounds with
N-monosubstituted hydroxylamines,5 ii) the oxidation of sec-
ondary amines or hydroxylamines.6 However both methods have
certain drawbacks; the condensation method is limited due to
the limited accessibility of the precursors (e.g. hydroxylamines)
and it is difficult to apply it to the preparation of non-conjugated
cyclic nitrones and bulky group containing ketonitrones. How-
ever, the direct oxidation of secondary amines, although a
straightforward approach for the preparation of nitrones, is less
favorable in the case of secondary amines bearing two different
groups due to the formation of two possible isomeric products.
Formation of nitrones through N-alkyaltion of aldoximes with
a,b-unsaturated carbonyl compounds and their use as 1,3-
dipoles for intermolecular cycloaddition reactions has also been
reported in the literature.7 Recently, Goti et al.8 reported an
efficient one-pot synthesis of nitrones from primary amines
and aldehydes using methyltrioxorhenium as catalyst. This
method is particularly advantageous from the economic as
well as green chemistry viewpoints as it involves a single step
synthesis without isolation of any intermediate, which helps in
saving time and energy as well as reducing waste production.
However, the major drawbacks of this method are its expensive
nature, tedious synthesis and particularly the non-recyclability
=
n Mo O (at n 951, very sharp). The metal loading onto the
polymer was calculated by TGA analysis and was found to be
2.6% (0.18 mmol g-1).†
Process Engineering Applied Chemistry and Biotechnology Division,
Indian Institute of Petroleum, Dehradun, India 248005.
E-mail: suman@iip.res.in, birsain@iip.res.in
Scheme 1 Immobilization of MoOCl4 to the Nafion support.
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Table 1 One-pot oxidative synthesis of nitrones 2 from aldehyde 3 and amine 4a
Entry
Aldehyde 3
Amine 4
4 [eq]
Nitrone 2
t/h
Yieldb(%)
1
2
3
4
5
6
7
8
3a: R1 = Ph
4a: R2 = PhCH2
1.0
1.2
1.5
2.0
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
2a: R1 = Ph; R2 = PhCH2
2a
4.0
4.0
6.0
8.0
4.0
4.0
4.5
5.0
5.5
4.5
4.5
5.0
5.5
6.5
7.0
7.0
5.0
6.0
3.5
3.5
5.0
75
78
50
3a: R1 = Ph
4a: R2 = PhCH2
3a: R1 = Ph
4a: R2 = PhCH2
2a
3a: R1 = Ph
4a: R2 = PhCH2
2a
2a
—
c
3a: R1 = Ph
4a: R2 = PhCH2
65d
80
68
70
64
70
71
64
65
56
70
68
65
58
74
72
3a: R1 = Ph
4a: R2 = PhCH2
2a: R1 = Ph; R2 = PhCH2
2b: R1 = Ph; R2 = nBu
2b: R1 = Ph; R2 = nBu
2c: R1 = Ph; R2 = tBu
3a
4b: R2 = nBu
3a
4b: R2 = nBu
9
3a
4c: R2 = tBu
10
11
12
13
14
15
16
17
18
19
20
21
3b: R1 = 4-MeOC6H4
4a
4a
4b
4b
4c
4a
4a
4b
4c
4a
4a
4a
2d: R1 = 4-MeOC6H4; R2 = PhCH2
2d: R1 = 4-MeOC6H4; R2 = PhCH2
2e: R1 = 4-MeOC6H4; R2 = nBu
2e: R1 = 4-MeOC6H4; R2 = nBu
2f: R1 = 4-MeOC6H4; R2 = tBu
1: R1 = 4-NO2C6H4; R2 = PhCH2
2g: R1 = 4-NO2C6H4; R2 = PhCH2
2h: R1 = 4-NO2C6H4; R2 = nBu
2i: R1 = 4-NO2C6H4; R2 = tBu
2j: R1 = 2-furyl; R2 = PhCH2
2j: R1 = 2-furyl; R2 = PhCH2
R1 = CH3(CH2)2CH2 R2 = PhCH2
3b: R1 = 4-MeOC6H4
3b
3b
3b
3c: R1 = 4-O2N–C6H4
3c: R1 = 4-O2N–C6H4
3c
3c
3d: R1 = 2-furyl
3d: R1 = 2-furyl
3e: R1 = CH3(CH2)2CH2
e
—
a Reaction conditions: Aldehyde (1 mmol), amine (1.2 mmol), catalyst (2 mol%), UHP (3 eq.), MeOH (3 ml) at room temp. b Isolated yields. c Intricate
mixture obtained. d Using homogeneous MoOCl4 as catalyst. e Intricate mixture obtained.
Catalytic activity
yield of the desired product, whereas aliphatic aldehydes showed
limitations and yielded an intricate mixture of the products
(Table 1, entry 21). The addition of a slight excess (1.2 equiv.)
of amine in comparison to the aldehyde (1 mmol) improved the
yield of the nitrone; however, the use of greater excess (1.5 mmol,
2 mmol) of amine adversely affected the reaction and no nitrone
formation was occurred even after prolongedreactiontime, these
results are presented in Table 1, entry 1–4. We also compare the
catalytic efficiency of Nafion immobilized MoOCl4 1 with its
homogeneous analogues MoOCl4 (Table 1, entry 5). The Nafion
immobilized catalyst was found to be better and afforded better
yield of the desired product than its homogeneous analogues
with the added benefits of having facile recovery and recycling
ability of the polymer immobilized catalyst. These facts establish
the superiority of the heterogenized catalyst over homogeneous
ones.
We also studied the reaction of benzaldehyde and benzylamine
in the absence of the molybdenum catalyst under the described
reaction conditions. The reaction afforded the corresponding
imine (easily detectable by TLC) as the only product at the end
of the reaction without undergoing further oxidation to nitrone.
Also, the use of aq. hydrogen peroxide as oxidant in the absence
of Mo-catalyst, afforded the corresponding imine only, albeit
in lower yield without any formation of the nitrone. The use of
aq. H2O2 as oxidant in the presence of the Nafion supported
molybdenum catalyst afforded the nitrone; however, the yield of
the product was found to be lower, along with the formation
of a mixture of many side products. Similarly, the use of other
solid peroxy compounds, such as sodium perborate and sodium
percarbonate, in place of urea-hydrogen peroxide although gave
the corresponding nitrone selectively but afforded poor yields
The catalytic activity of the prepared Nafion immobilized
MoOCl4 was studied for the direct synthesis of nitrones from
the one-pot condensation/oxidation of primary amines and
aldehydes using solid UHP as oxidant under mild reaction
conditions (Scheme 2).
Scheme 2 One-pot synthesis of nitrones 2.
The present method has the added benefits of easy handling,
facile recovery and reusability of the catalyst without loss
in catalytic activity and importantly, no metal leaching was
observed during this course. The protocol developed for the
one-pot synthesis of nitrones consists of the addition of solid
UHP and Nafion-Mo catalyst 1 (2 mol%, 0.11 g) into the
stirred mixture of aldehyde and primary amine in methanol.
Anhydrous sodium sulfate was added in order to facilitate
the reaction and the resulting mixture was stirred at room
temperature. After completion of the reaction (as analyzed by
TLC), the polymer beads were easily separated via decantation,
washed with methanol, dried and reused for subsequent runs.
Evaporation of the solvent under reduced pressure followed
by the usual work-up of the resulting residue gave nitrones in
good yields. The results for the one-pot condensation/oxidation
of a variety of primary amines and aldehydes to nitrones are
summarized in Table 1. Among the various aldehydes studied,
aromatic aldehydes were found to be more efficient in terms of
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Table 2 Results of recycling experimentsa
Conclusions
Run
Aldehyde
Amine
t/h
Yieldb(%)
In summary, we demonstrated for the first time the use of
Nafion-NR-50 (commercially available) polymer resin as a solid
support for the immobilization of molybdenum oxychloride.
The immobilization could be achieved in a very simple manner
and the resulting Nafion immobilized MoOCl4 was found to
be an efficient catalyst for the direct synthesis of nitrones in
good yields via one pot condensation/oxidation of primary
amines with aldehydes using solid UHP as oxidant under mild
reaction conditions. The key advantages, like the direct one step
synthesis of nitrones without isolation of any intermediate, green
synthesis, facile recovery and recycling ability of the catalyst
without loss in catalytic activity and leaching of metal, make the
present method superior and more advantageous than existing
methods.
1
2
3
4
5
6
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzylamine
Benzylamine
Benzylamine
Benzylamine
Benzylamine
Benzylamine
4
4
4
4
4
4
78
78
78
76
77
77
a Reaction conditions as described in text. b Isolated yields
under similar reaction conditions. These results established the
superiority of the urea-hydrogen peroxide adduct over other
peroxy compounds/hydrogen peroxide.
We also performed the reactions via first formation of imine
(easily detectable by TLC) by the reaction of aldehyde (1 mmol)
and amine (1.2 mmol) before adding the catalyst and oxidant
under otherwise similar reaction conditions. It is worthy to
mention that in both cases, i.e. when adding all the substrates,
UHP and catalyst in the beginning or by the preformed
formation of imine by the condensation of aldehyde and amine
followed by the addition of UHP and catalyst into the reaction
mixture, nitrones were obtained as the only product at the end
of the reaction and the reaction times and yields of the products
remained almost the same (Table 1, entries 2 vs. 6, 7 vs. 8, 10 vs.
11, 12 vs. 13, 15 vs. 16, 19 vs. 20). These findings clearly indicate
the advantages of performing the two steps in the same reaction
vessel, without additional steps for the isolation of intermediates,
and also it helps in saving time, energy and production of waste.
The presence of anhydrous sodium sulfate was found to be vital,
as its absence led to the formation of nitrones in lower yields.
To check the reusability and recyclability of the catalyst we
have carried out the condensation/oxidation of benzaldehyde
and benzyl amine using solid UHP as oxidant under similar
reaction conditions. After completion of the reaction, the
catalyst was separated by decantation, washed with methanol,
dried and reused as such for subsequent experiments (6 runs),
after adding fresh substrates and oxidant (UHP), under the
described reaction conditions (Table 2). In these experiments,
the reaction times and yield of the nitrone remained the same,
establishing the recyclability and reusability of catalyst without
significant loss in catalytic activity. To check the leaching of
the metal during the experiments, we first stirred the Nafion
immobilized MoOCl4 beads in methanol at room temperature
for 8 h. The polymer beads were separated by filtration and the
filtrate thus obtained was used for the condensation/oxidation
of benzaldehyde and benzyl amine with UHP under similar
reaction conditions. No nitrone formation was observed, even at
a longer reaction time (8 h), establishing that there was no metal
leaching occurring and the reaction is truly heterogeneous in
nature.
Notes and references
† Preparation of catalyst: Commercially available Nafion NR-50 was
taken as a support. Into a stirred mixture of Nafion beads (2 g) in dry
THF (10 ml) was added NaH slowly over 30 min at lower temperature
(5–10 ◦C). After completion of the addition, the mixture was stirred for
3 h at room temperature. A solution of molybdenum(VI) oxychloride
(0.2 g) in dry THF was added drop wise to the stirred mixture of Nafion
in THF. The suspension was further stirred for 3 h under nitrogen
atmosphere at room temperature. The solution became light colored
while Nafion beads became highly colored during this period. The dark
colored polymer beads were easily separated by filtration and washed
thoroughly with THF, MeOH and then dried under vacuum. IR (cm-1):
2355, 1670, 1522, 986, 981, 951. Metal loading was determined by TGA
analysis and was found to be 0.18 mmol g-1 of polymer.
General procedure for the synthesis of nitrones 1 (protocol I): Into a
stirred solution of aldehyde (1 mmol) in MeOH (3 ml) was added
anhydrous Na2SO4, UHP (3 mmol) and Nafion immobilized Mo catalyst
1 (2 mol%, 0.11 g). The resulting solution was cooled to 0 ◦C and
after 5 min the amine (1.2 mmol) was added drop-wise. The reaction
mixture was stirred at room temperature for 4–8 h. After completion
as analyzed by TLC, the catalyst could readily be separated from the
reaction by decantation, washed thoroughly with water, methanol and
dried and reused for subsequent experiments. The filtrate so obtained
was concentrated under reduced pressure. The residue was diluted
with CH2Cl2 and the organic layer was washed with water (3 times),
dried over anhydrous sodium sulfate and concentrated under reduced
pressure to afford crude product, which was purified by flash column
chromatography on silica gel using ethyl acetate–hexane (1 : 9) as eluent.
Results obtained for the one pot condensation/oxidation of a variety of
aldehydes and primary amines to nitrones are summarized in Table 1.
All the products were characterized by comparing their physical and
spectral data to the reported compounds.
General procedure for the synthesis of nitrones via first formation of imine
(Protocol II): Into a 25 ml round bottomed flask, a mixture of aldehyde
(1 mmol) and primary amine (1.2 mmol) in MeOH (3 ml) was stirred
until the formation of imine was completed (as analyzed by TLC). After
completion, UHP (3 mmol) and Nafion immobilized Mo catalyst 1 (2
mol%, 0.11 g) was added into the above mentioned reaction mixture. The
resulting mixture was stirred at room temperature for 4–8 h (completion
of the nitrone formation was analyzed by TLC). At the end of the
reaction, the catalyst was separated by decantation and resulting residue
was subjected to usual workup to crude product, which was purified by
flash column chromatography on silica gel using ethyl acetate–hexane
(1 : 9) as eluent.
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=
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