The first example of catalytic N-oxidation of tertiary amines by tungstate-exchanged Mg-Al layered double hydroxide in water: A green protocol

Article abstract of DOI:10.1039/b104754j

A green process, using a recyclable tungstate-exchanged Mg-A1 layered double hydroxide (LDH-WO₄^2-) heterogenised catalyst and aqueous H₂O₂ oxidant in water, leads to N-oxidation of aliphatic tert-amines to amine N-oxides in quantitative yields, at a high rate at room temperature.

Full text of DOI:10.1039/b104754j

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The first example of catalytic N-oxidation of tertiary amines by
tungstate-exchanged Mg–Al layered double hydroxide in water: a
green protocol†
B. M. Choudary,* B. Bharathi, Ch. Venkat Reddy, M. Lakshmi Kantam and K. V. Raghavan
Indian Institute of Chemical Technology, Hyderabad-500007, India. E-mail: choudary@iict.ap.nic.in
Received (in Cambridge, UK) 31st May 2001, Accepted 23rd July 2001
First published as an Advance Article on the web 28th August 2001
A green process, using a recyclable tungstate-exchanged
vanadate, respectively. The Mg–Al LDH (3+1) tungstate (cat 1)
22
9c
Mg–Al layered double hydroxide (LDH-WO
4
) hetero-
was prepared according to the reported procedure. 1 g of Mg–
genised catalyst and aqueous H
2
O
2
oxidant in water, leads to
Al–Cl LDH was stirred in 100 ml of an aqueous solution of 1.87
mM (0.616 g) sodium tungstate at 293 K for 24 h. The solid
catalyst was filtered off, washed with deionised and decarbon-
ated water and lyophilized to dryness. Similarly, the Mg–Al
LDH molybdate (cat 2) and Mg–Al LDH vanadate (cat 3) were
N-oxidation of aliphatic tert-amines to amine N-oxides in
quantitative yields, at a high rate at room temperature.
Aliphatic tert-amine N-oxides are essential and major compo-
nents for ubiquitously used materials such as hair conditioners,
shampoos, toothpaste, laundry detergent powders, fabric soften-
ers, toilet soaps and cosmetics as well as in biomedical
applications.1 Amine oxides are compounds of increasing
interest as potential cytoximes which are hypoxia-selective for
prepared. The preparation of LDH-{PO
was carried out according to the literature procedure. To a
solution of 0.46 mmol of isolated (NBun
){PO [WO(O } in
acetone (3 ml) was added 1 ml of H [35% (w/w) aqueous
4 2 4
[WO(O )] } (cat 4)
10
4
4
2 2 4
) ]
2 2
O
solution] and 1 g of Mg–Al–Cl LDH and the mixture was stirred
for 16 h at room temperature. The obtained material (cat 4) was
treated consecutively with water–acetone (1+1) and acetone.
All these catalysts were well characterised by powder-XRD,
2
the treatment of solid tumors. These N-oxides are also used as
stoichiometric oxidants to accomplish catalytic cycles in
important reactions such as osmium catalysed dihydroxylation
of olefins,3 ruthenium catalysed oxidation of alcohols and
a,b
3c
TGA–DTA and chemical analysis. The X-ray powder diffrac-
3d
22
Mn–salen catalysed epoxidation of olefins. Amine N-oxides
tion patterns of the LDH and LDH-WO
4
(cat 1), LDH-
22
2
are currently prepared via a non-catalytic oxidation of tert-
MoO
4
(cat 2), LDH-VO
3
(cat 3), LDH-{PO
4
[WO(O )] }
2 4
amines with H
2
O
2
in a slow reaction.3
a,4
Other oxidants
(cat 4) scarcely differ in the range 2q = 3–65°. These data
clearly indicate that the above anions are not intercalated but lie
on edge-on positions of LDH in the solid catalyst. Chemical
analysis of the catalysts revealed the tungstate (%) content in cat
1 as 11% and cat 4 as 21% while the molybdate content in cat
2 was 9.9%, and vanadate content in cat 3 was 7.8%. The
thermogravimetric profiles and the relative derivative curves
(TGA and DTA) for the tungstate, molybdate and vanadate
exchanged LDH catalysts cat 1–4 show two stages of weight
loss associated with two endotherms characteristic of LDHs.
These results provide evidence that there is no structural
disorder after the ion-exchange.
employed to hasten the oxidation of tert-amines include
5a
5b
peracids, magnesium monophthalate, 2-sulfonyloxaziridi-
5c
5d
5e
nes, a-azohydroperoxides and dioxiranes, which are not
only expensive, but also generate large amounts of effluent
during the reaction. The biomimetic oxidation of tert-amines is
2 2
induced by 4a-hydroperoxyflavin in the presence of H O as
6
oxidant. This forms the sole example of a catalytic reaction to
the best of our knowledge. There is a strong need to develop a
7
‘
greener technology’ with higher throughput, and in order to
conform to the above, we accordingly designed and developed
an eco-compatible process utilising a recyclable heterogeneous
catalyst in aqueous medium. We report here, an efficient and
heterogeneous tungstate-exchanged layered double hydroxide
The exchanged LDH catalysts (cat 1–4) and their homoge-
neous analogues were evaluated in oxidation of aliphatic tert-
2
2
catalyst (LDH-WO
4
), for the oxidation of aliphatic tert-
as oxidant
2 2
amines with H O in order to identify the best catalysts (Table
amines in water as solvent using aqueous H
2
O
2
1). The tert-amine is oxidised with aqueous hydrogen peroxide
(30% w/w) using water as a solvent in the presence of catalyst
at room temperature under continuous stirring, while monitor-
ing the progress of the reaction by TLC. The order of activity of
which leads to excellent yields for the first time (Scheme 1).
8
Layered double hydroxides (LDHs) have recently received
9
II
much attention. LDHs consist of alternating cationic M 12x
-
III
x+
n2
M
x
(OH)
2
and anionic A ·zH
2
O layers. The positively
II
III
charged layers contain edge-shared metal M and M hydrox-
n2
Table 1 Catalytic N-oxidation of N-methylmorpholine to N-methylmorpho-
line N-oxide catalysed using various metal ion-exchanged LDH catalysts
and their homogeneous analogues
ide octahedra, with charges neutralized by A
interlayer spacings or at edges of the lamellae. Small hexagonal
LDH crystals of composition Mg12xAl (OH) Cl ·2H O were
located in
x
2
x
2
9a
synthesized following existing procedures (here x = 0.25).
The anionic species tungstate, molybdate and vanadate were
exchanged with LDH-Cl to give LDH tungstate, molybdate and
c
Entry
1
Catalyst
Time/h
Yield (%)
LDH-WO422 (cat 1)
Procedure I
Procedure IIb
LDH-MoO
LDH-VO
LDH-{PO
a
1.0
1.0
3.5
3.5
3.5
3.5
3.5
3.5
24.0
96
96
90
40
40
75
15
48
25
2
3
4
5
6
7
8
a
4
22(cat 2)
2
3
(cat 3)
4
2 4
[WO(O )] } (cat 4)
Na
NaVO
Na MoO
None
2
WO
4
3
2
4
Scheme 1 Oxidation of tert-amines to amine N-oxides catalysed by
tungstate-exchanged Mg–Al LDH.
2 mmol of substrate, 200 mg of catalyst, 10 ml of water and 6 mmol of aq.
H O (30% w/w). 6 mg of dodecylbenzenesulfonic acid sodium salt added
2 2
b
c
as surfactant. Isolated yield.
†
IICT Communication No: 4804.
1736
Chem. Commun., 2001, 1736–1737
DOI: 10.1039/b104754j
This journal is © The Royal Society of Chemistry 2001

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the LDH exchanged catalysts is: cat 1 > cat 2 > cat 3 = cat 4
2
2
and thus LDH-WO
4
(cat 1) is inferred to be the best catalyst
in the oxidation of tert-amines. The heterogeneous catalysts
provide superior performance over their homogeneous counter-
parts. The efficacy in increasing the rate of N-oxidation is
22
evident from Table 1, in which LDH-WO
4
affords 96%
conversion in 1 h cf. 25% in 24 h in the absence of a catalyst.
In an effort to understand the scope of the reaction, several
other amines having different R groups attached to the tertiary
nitrogen atom were subjected for oxidation using the best
Scheme 2 Plausible catalytic cycle for the N-oxidation of tert-amines to
amine N-oxides by tungstate-exchanged Mg–Al LDH.
2
2
catalytic LDH–WO
4
2 2
–H O system to give excellent yields
and  100% selectivity (Table 2). No other by-products were
observed in these reactions. Water proved to be the best solvent
in terms of activity in the N-oxidation of tert-amines. When the
dodecylbenzenesulfonic acid sodium salt is employed as an
additive, the rate of the N-oxidation reaction is increased 2–3
fold except in the case of N-methylmorpholine (Table 2). This
may be due to the high hydrophilicity of the latter, when
compared with other tert-amines used. The present N-oxidation
reaction takes place under liquid–solid–liquid triphasic condi-
tions, comprising of organic tert-amine, solid catalyst and
aqueous phase. We assumed that the main role of the surfactant
is to increase the contact area of the interface between the
aqueous and organic phases and to enhance the transfer of the
lipophilic amine from the organic to the aqueous phase. The
amine N-oxides thus obtained are useful additives for the
11,12
surfactants,
for example, the product in Table 2, entry 18 is
1a
sold under the trade name Barlox 10S. The benzylic amine N-
oxides (Table 2, entries 14, 16 and 21) serve as substrates.
13
Furthermore cat 1 can be reused for six cycles (see Table 2,
entry 23) without loss of activity and selectivity. The reaction
did not proceed when conducted with the resulting filtrate after
separation of the solid catalyst from the previous batch. This
indicates that the active ingredient has not leached out of the
solid catalyst during the reaction.
A plausible catalytic cycle in the oxidation of amines to
amine oxides as described in Scheme 2 involves formation of
peroxotungstate, IV on interaction of tungstate LDH III with
2
2
(cat 1)a
9c
Table 2 Oxidation of tert-amines catalysed by LDH-WO
4
hydrogen peroxide II. A shift of lmax 250 (LDH III) to 325
nm (IV) according to UV-DRS confirms the formation of
peroxotungstate species. The peroxotungstate IV species trans-
fers its electrophilic oxygen to an amine VI forming the amine
N-oxide V with regeneration of the active catalyst III.
In conclusion, the present process represents the sole
example for synthesis of N-oxides wherein the heterogenised
tungstate-based Mg–Al LDH is used as a catalyst. The potential
for its commercial application is strengthened by the high
throughput of the product, lower process inventories and use of
an aqueous phase reaction system.
Yieldb
(%)
Entry Tertiary amine
9
Procedure Amine oxide
Time/h
I
II
1.0
1.0
96
96
10
1
1
1
2
I
II
3.0
1.5
96
96
B. B. and Ch. V. R. thank CSIR, India for SRF.
13
I
3.0
94
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1
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96
95
5
2
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97
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2
9
0
I
II
2.5
1.0
95
95
2
2
1
2
I
II
1.5
1.0
95
96
6
7
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2
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I
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3.5
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95(94)c
95
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2
5
6
I
II
3.0
1.0
96
95
1
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1
Chem. Commun., 2001, 1736–1737
1737