Direct transformation of benzilic amines to carbonyls using polyacrylamide-bound tungstate under phase-transfer catalysis conditions

Article abstract of DOI:10.1016/j.tetlet.2007.04.071

A recyclable catalytic system under heterogeneous phase-transfer catalysis conditions was designed by using polyacrylamide-bound tungstate. A convenient method for the oxidative direct transformation of benzilic amines to carbonyls with hydrogen peroxide was then developed.

Full text of DOI:10.1016/j.tetlet.2007.04.071

Tetrahedron Letters 48 (2007) 4239–4242
Direct transformation of benzilic amines to carbonyls
using polyacrylamide-bound tungstate under
phase-transfer catalysis conditions
Hiromi Hamamoto, Yachiyo Suzuki, Hideyo Takahashi and Shiro Ikegami*
School of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 229-0195, Japan
Received 7 March 2007; revised 5 April 2007; accepted 13 April 2007
Available online 20 April 2007
Abstract—A recyclable catalytic system under heterogeneous phase-transfer catalysis conditions was designed by using polyacryl-
amide-bound tungstate. A convenient method for the oxidative direct transformation of benzilic amines to carbonyls with hydrogen
peroxide was then developed.
Ó 2007 Elsevier Ltd. All rights reserved.
Solid-phase catalysts offer a number of important
advantages over their homogeneous counterparts.
The chemical transformation of amino groups to car-
1
,2
5
bonyl ones is sometimes utilized in organic synthesis.
6
For example, their separation from reaction products
is easy and their subsequent recycling steps have the
potential for green chemical processes. Despite these
advantages, solid-phase catalysts show low reactivity
due to weak affinity between the substrate and catalyst
under heterogeneous conditions. Therefore, the creation
of efficient reaction systems utilizing solid-phase cata-
lysts is recognized as an important topic in the current
organic synthesis.
Some metal oxidizing reagents such as KMnO ,
4
7
8
9
10
K FeO , Pb(OAc) , NiO , and HgO–I
have been
2
4
4
2
2
used to convert amines to carbonyl compounds through
imines. However, these processes require stoichiometric
or large amounts of poisonous late transition metals.
Although multi-step process using a strong base such
as n-butyllithium or DBU to generate imines from
amines and subsequent hydrolysis could provide an
alternative, examples of the simple and convenient
1
1–13
transformation methods are still limited.
Recently, the use of an amphiphatic solid-phase catalyst
under a phase-transfer condition or an aqueous system
is regarded as a potential strategy to form highly reac-
In the course of our research on the creation of a new
solid-phase catalyst, utilization of poly(N-isopropyl-
acrylamide) (PNIPAAm) polymers as a catalyst sup-
ported material was found to be useful in the
development of recyclable reaction systems and some
efficient schemes under organic solvent free conditions
3
,4
tive catalytic systems.
Since an amphiphatic-mole-
cular mediated reaction in water often causes
difficulties in the removal of surfactants and the clean-
up of the used water, the utilization of a recyclable
solid-phase type catalyst may take a lot of advantages
when isolating product from solution and removing sur-
factants that cause environmental pollution in many
cases.
1
4–16
were reported.
This work focuses much attention
on the use of PNIPAAm-based catalyst under phase-
transfer conditions and provided a novel oxidation sys-
tem for the direct transformation of benzilic amines to
carbonyls.
Previously, we have investigated the self-assembled pro-
cess between PNIPAAm-based polymer ligands and an
1
4,15
inorganic species.
This process afforded a networked
Keywords: Phase-transfer catalysis; Oxidation; Supported catalysts;
Benzilic amines; Green chemistry.
supramolecular complex where the polymers are cross-
linked together by the inorganic species. Thus the ob-
tained complex with phosphotungstate (1) was insoluble
*
Corresponding author. Tel./fax: +81 42 685 3729; e-mail: somc@
pharm.teikyo-u.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.04.071

4240
H. Hamamoto et al. / Tetrahedron Letters 48 (2007) 4239–4242
Temperature-
Quaternary
NH2
R1 R2
NHOH
R1 R2
NO2
R1 R2
[
O]
NO
R1 R2
[O]
Catalyst unit
[O]
responsive unit ammonium unit
2
CH2 CH 12 CH2 CH 1
C O
NH
C O
NH
3
PW12O40
n
R1
R2
O
N N
R2
R1
OH
R1
R2
O
N N
R2
R1
O
R1 R2
[O]
N
R1 R2
O
(
C12H25) NMe2
3n
3
1
Scheme 2. Possible reaction formation mechanism for 3.
3
4
À
Scheme 1. Networked PNIPAAm À PW12
O
complex (1).
0
production of undesired side products and excess
amounts of organic solvents were required for the
Table 1. Direct catalytic transformation of 1-phenethylamine (2a) into
acetophenone (3a) with hydrogen peroxide
2
1
extractive workup process (entries 3 and 4). In addi-
tion, the reaction under organic solvent free condition
was also ineffective and undesired side products were
obtained again (entry 5). On the other hand, carbonyl
product 3a was not obtained when the reaction was car-
ried out using sodium tungstate in the presence of sur-
factants (entry 6). The higher yield of the desired
carbonyl product obtained utilizing easily recyclable
heterogeneous catalyst 1 under phase-transfer condition
is noteworthy and temperature dependent nature which
would cause strong affinity for the organic substrate at
high temperature might play an important role in the
activation.
NH2
O
catalyst (0.01 mol eq)
CH3
CH3
3
0 % aq H O (5 mol eq)
2 2
6
0 °C, 6 h
2a
3a
a
b
Entry
Catalyst
Solvent
Yield (%)
c
1
2
3
4
5
6
1
Toluene
Toluene
92
1 (2nd use)
90
80
81
50
d
1
1
1
3
CH CN
d
t-BuOH
—
Toluene
e
f
Na2WO4
Trace
a
b
c
d
e
f
The oxidation hardly proceeded in the absence of catalyst.
Yield of isolated product.
The oxime was obtained in 25% yield at 0 °C.
Compound 1 was soluble in MeCN or tert-butyl alcohol at 60 °C.
Scheme 2 depicts a plausible reaction pathway. The oxy-
genation of primary amines possessing an a-C–H bond
generally produces hydroxylamines initially, which is
subsequently oxidized to nitroso compounds. The unsta-
ble nitroso compounds transform to oxime by tautomer-
ization or to the nitrosodimer by dimerization. Some of
the nitroso compounds react with hydroxylamines to
form azoxy compounds. Further oxidation of oxime
produces carbonyl compounds. In the 1-catalyzed oxi-
dation of 2a under phase-transfer condition, carbonyl
product 3a was the only significant product (Table 1,
entry 1). On the other hand, loss of the selectivity was
observed under the homogeneous condition (entries 3
and 4) or the organic solvent free condition (entry 5),
and the mixture of oxime, nitroso dimer, and azoxy
compound was mainly obtained when the oxidation
was carried out using sodium tungstate (entry 6).
3 8 17 3 4 2 2 3
Additive: [CH (n- H ) N]ÆHSO and NH CH PO H.
The oxime was obtained in 25% yield at 0 °C.
in water and worked as an efficient oxidation catalyst
under organic solvent free conditions in water (Scheme
1
). In addition, the application of the unique potentiality
1
7
of poly(N-isopropylacrylamide) (PNIPAAm), which
undergoes thermally reversible changes between hydro-
philic and hydrophobic states, brought valuable catalyst
recycling strategies via the thermo-regulated formation
of stable emulsion species. To exploit the utility of
PNIPAAm-based catalyst in the creation of a new
solid-phase catalysis, the potentiality of PNIPAAm-
bound phosphotungstate under phase-transfer condi-
tions was explored in the oxidative transformation of
benzilic amines to carbonyls with hydrogen peroxide.
1
6
The scope of this oxidation system was studied further
2
2
with various benzilic amines (2). Oxidation proceeded
efficiently to give the corresponding carbonyl products
(
3) under phase-transfer systems (Table 2, entries 1–5).
When the reaction was performed on the toluene–aque-
ous hydrogen peroxide system in the presence of catalyst
In addition, oxidation of oximes also afforded the corre-
sponding carbonyl products (3) (Table 2, entries 6 and
7).
1
8–20
1
,
1-phenylethylamine (2a) was smoothly converted
to acetophenone (3a) (Table 1, entry 1). In addition the
catalyst could be recovered by simple filtration and
reused without significant loss of activity (entry 2). The
We have devised a novel catalytic heterogeneous oxida-
tion system utilizing PNIPAAm-based tungsten catalyst
with hydrogen peroxide and demonstrated its efficiency
in the oxidative direct transformation of benzilic amines
to carbonyls. The reaction driving under the heteroge-
neous phase-transfer conditions led to an acceleration
of the reactivity and ease in catalyst recycling in the oxi-
dation. The results described here will enhance the mul-
3
1
P NMR spectrum of recovered 1 was unchanged rela-
tive to that of 1 before the reaction and no other species
1
5b,20
was evident.
Alternatively, the reactions were also
carried out under homogeneous systems by using polar
organic solvent such as MeCN or tert-butyl alcohol,
but slight lower yields were exerted attributable to the

H. Hamamoto et al. / Tetrahedron Letters 48 (2007) 4239–4242
4241
a
Table 2. Oxidation of benzylamines (2) and oximes (4) catalyzed by 1
Angew. Chem. 2001, 113, 670–701; (d) Kobayashi, S.;
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b
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Product
Yield (%)
3
NH2
O
1
993; (b) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-
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CH3
CH3
1
80
(
2b
3a
Newman, R., Eds.; Blackie Achademic and Professional:
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NH2
O
4
. (a) Regen, S. L. Angew. Chem., Int. Ed. Engl. 1979, 18,
2
3
4
5
6
7
89
93
69
78
91
80
4
21–492; (b) Freedman, H. H. Pure. Appl. Chem. 1986, 58,
2
c
3c
857–868; (c) Benaglia, M.; Puglisi, A.; Cozzi, F. Chem.
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. Davis, L.; Metzler, D. E. In The Enzymes; 3rd ed.
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. (a) Rawalay, S. S.; Schechter, H. J. Org. Chem. 1967, 32,
NH2
O
5
6
2
d
3d
3
129–3131; (b) Noureldin, N. A.; Bellegarde, J. W.
Synthesis 1999, 939–942.
7. Audette, R. J.; Quail, J. W.; Smith, P. J. Tetrahedron Lett.
971, 12, 279–282.
8. Stephens, F. F.; Bower, J. D. J. Chem. Soc. 1949, 2971–
2972.
O
NH2
H
H
1
2e
3e
O
NH2
9. Nakagawa, K.; Onoue, H.; Sugita, J. Chem. Pharm. Bull.
1964, 12, 1135–1138.
H C
3
H C
2f
3
1
0. Orito, K.; Hatakeyama, T.; Takeo, M.; Uchiito, S.;
Tokuda, M.; Suginome, H. Tetrahedron 1998, 54, 8403–
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f
OH
O
N
8
410.
11. (a) Chen, H. G.; Knochel, P. Tetrahedron Lett. 1988, 29,
701–6702; (b) Buckley, T. F.; Rapoport, H. J. Am. Chem.
CH3
CH3
6
3a
4
a
Soc. 1982, 104, 4446–4450; (c) Matuo, J.; Kawana, A.;
Fukuda, Y.; Mukaiyama, T. Chem. Lett. 2001, 712–713.
2. Miyazawa, A.; Tanaka, K.; Sakakura, T.; Tashiro, M.;
Tashiro, H.; Prakash, G. K. S.; Olah, G. A. Chem.
Commun. 2005, 2104–2106.
OH
O
H
N
1
H
H C
3
H C
3
3f
4
f
1
3. (a) Hoffman, R. V. J. Am. Chem. Soc. 1976, 98, 6702–
6704; (b) Lee, G. A.; Freedman, H. H. Tetrahedron Lett.
a
Condition: 1 (0.01 mol equiv), 30% aq H
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2 2
O (5 mol equiv), toluene,
1
976, 17, 1641–1644; (c) Hu, Y.; Hu, H. Synth. Commun.
6
b
1992, 22, 1491–1496.
Yield of isolated product.
1
1
4. (a) Yamada, Y. M. A.; Takeda, K.; Takahashi, H.;
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4
018.
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Acknowledgments
This work was partially supported by a Grant-in-Aid of
the Ministry of Education, Culture, Sports, Science, and
Technology, Japan. We thank Ms. J. Shimode and Ms.
A. Tonoki (Teikyo University) for performing spectro-
scopic measurements.
16. Hamamoto, H.; Suzuki, Y.; Yamada, Y. M. A.; Tabata,
H.; Takahashi, H.; Ikegami, S. Angew. Chem., Int. Ed.
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1
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1
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8. Poly(N-isopropylacrylamide) (PNIPAAm) based tungsten
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1
5b
References and notes
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9. A typical experimental procedure for the direct transforma-
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1
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(
4
benzilic amine 2 (4 mmol) and 30% aq H
2 2
O (1.9 ml,
20 mmol) in toluene (or C CF , 10 ml) was heated to
H
6
5
3
4
(
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recovered 1 was washed with Et O and distilled water,
2
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recovered 1 was reused for subsequent catalytic experi-
ments. The aqueous phase was extracted two times with
4
662; (c) Kirschning, A.; Monenschein, H.; Wittenberg, R.

4242
H. Hamamoto et al. / Tetrahedron Letters 48 (2007) 4239–4242
O (10 ml) and the combined organic extracts were
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washed with brine. The organic phase was then dried over
MgSO4 and concentrated under reduced pressure. The
products were purified by column chromatography with
silica gel and the isolated yields were determined. All
carbonyl products (3) were commercially available and
corresponded.
2
0. (a) Ishii, Y.; Yamawaki, K.; Ura, T.; Yamada, H.;
Yoshida, T.; Ogawa, M. J. Org. Chem. 1988, 53, 3587–
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1
991, 56, 5924–5931; (c) Aubry, C.; Chottard, G.; Platzer,
compound
PhCH CH
dimmer 36%, azoxy 19%).
was
obtained
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C.; Ledon, H. Inorg. Chem. 1991, 30, 4409–4415; (d)
2
2
NH
2
; carbonyl 26%, oxime < 5%, nitroso