Chemoselective reduction of halo-nitro aromatic compounds by β- cyclodextrin-modified transition metal catalysts in a biphasic system

Article abstract of DOI:10.1055/s-1999-3568

Transition metal complexes of a water-soluble β-cyclodextrin modified diphosphine can be used in the biphasic (H₂O/organic) hydrogenation of halo- nitro aromatic compounds. The platinum complex is the most active and selective, resulting in the chemoselective formation of halo-aniline derivatives.

Full text of DOI:10.1055/s-1999-3568

SHORT PAPER
1555
Chemoselective Reduction of Halo-Nitro Aromatic Compounds by
b-Cyclodextrin-Modified Transition Metal Catalysts in a Biphasic System
Manfred T. Reetz,* Christoph Frömbgen
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim/Ruhr, Germany
Fax:+49(208)3062985; E-mail: reetz@mpi-muelheim.mpg.de
Received 8 March 1999
phase. Following hydrogenation (20 bar H2), the organic
phase was analyzed by gas chromatography. Although
complete optimization was not strived for, the results
summarized in the Table show some clear trends. In all
cases chemoselectivity in favor of halo-amines 4, 8 or 10
was observed (Scheme 2), but the degree of selectivity
varied. The ruthenium and palladium catalysts are least
suitable (Table, Entries 9 and 10). In contrast, Rh, Ir, Pt,
Ni and Co show better performance, the platinum system
appearing to be optimal since it is very active and also
highly chemoselective (Table, Entry 5). Upon reusing the
aqueous phase in the Pt-catalyzed reduction of substrate
3a, essentially the same result was obtained (Table, Entry
6).
Abstract: Transition metal complexes of a water-soluble b-cyclo-
dextrin modified diphosphine can be used in the biphasic (H2O/or-
ganic) hydrogenation of halo-nitro aromatic compounds. The
platinum complex is the most active and selective, resulting in the
chemoselective formation of halo-aniline derivatives.
Key words: b-cyclodextrin modified diphosphine, phase transfer
catalysis, catalytic reduction, supramolecular catalysis, transition
metals
We have recently shown that b-cyclodextrin-modified
diphosphines of the type 1 are excellent water-soluble
ligands for Rh-catalyzed hydrogenation and hydroformy-
lation of olefins in two-phase systems (aqueous/organic
phases).1 The underlying concept is based on the well-
known propensity of b-cyclodextrin (b-CD) to bind re-
versibly organic compounds in the hydrophobic inner
cavity,2 aromatic compounds often being the preferred
substrates. Host/guest phenomena also form the basis of
phase transfer catalytic properties of b-CD.2,3 In the case
of water-soluble transition metal complexes 2, the revers-
ible formation of host/guest supramolecules not only
makes phase transfer catalysis in a biphasic system4 pos-
sible, it also sets up an entropically favorable transition
metal catalyzed process such as hydrogenation or hydro-
formylation.1 In this publication we demonstrate that tran-
sition metal complexes 2 derived from the ligand 1
(Scheme 1) are efficient supramolecular catalysts in the
biphasic reduction of halo-nitro-aromatics with chemose-
lective formation of the corresponding aromatic amines.
NO2
NH2
NO2
NH2
a)
+
+
Cl
Cl
3a ortho
b meta
c para
4
5
6
NO2
NH2
a)
+
4
+
5 + 6
Cl
Cl
Cl
Cl
7
8
NO2
NH2
a)
PPh2
PPh2
PPh2
PPh2
+
5
+
6
MLn
N
N
Br
Br
9
10
1
2
Reagents and conditions: a) Ligand 1/metal salt/H2 (20 bar); see Table
Scheme 2
Scheme 1
Thus, this new aqueous catalyst system constitutes an al-
ternative to previous methods for the chemoselective con-
version of halo-nitro aromatic substrates.5-9 In most of the
processes problems occur concerning catalyst-product
separation, the low activity of the catalyst or its selectivi-
ty. This usually leads to incomplete conversion of the
starting materials or substantial amounts of dehalogenated
All reactions were performed in an in situ manner, i.e., the
ligand 11 was dissolved in a small amount of methanol and
treated with the equivalent amount of a transition metal
salt, the catalyst then being added to the biphasic system
consisting of the halo-nitro aromatic compound 3, 7 or 9
dissolved in toluene as one phase and water as the second
Synthesis 1999, No. 9, 1555–1557 ISSN 0039-7881 © Thieme Stuttgart · New York

1556
M. T. Reetz, C. Frömbgen
SHORT PAPER
by-products or toxic azo compounds. The liberation of un- It is environmentally benign because water is the solvent
desired halogen acid (HX) causes sever corrosion of and the only by-product. The two-phase system offers
equipment, and its neutralization generates undesired simple product-catalyst separation and recycling for batch
amounts of inorganic salts or contaminated wastewaters.6 as well as continuously fed flow processes and in some
In the case of heterogeneous catalysts like Raney nickel or cases conversion can take place without any organic sol-
noble metals on inert supports in fluid phases additional vent under very mild reaction conditions (Table, Entries 4
problems arise from the separation of the finely dispersed and 16).
catalyst by filtration and from the removal of the solvent.7
In addition usually high temperatures and/or hydrogen
Our system also appears to be superior to the use of water-
soluble Pt- and Rh-complexes of tris(m-sulfonatophe-
pressure for fast and complete conversion have to be ap-
nyl)phosphine trisodium salt (tppts),10 a catalyst system
plied. To overcome the problem of dehalogenation nu-
well known in the biphasic hydroformylation of pro-
merous methods have been employed, including
pene.4e,11 For example, under comparable conditions the
modification or deactivation of the catalysts by appropri-
reaction of substrate 3c is catalyzed by (COD)PtCl2/
10 tppts to afford 95% of 4c and 4% of 6, and
Rh(COD)2[BF4]/10 tppts leads to 89% of 4c and 10% of 6
which means that selectivity is only 95 and 90%, respec-
ate additives.8 Although gas phase reduction of halo-nitro
aromatic compounds with modified heterogeneous cata-
lysts is very selective, this cannot be applied to sensitive
fine chemicals that are subject to decomposition.5b
tively. The unacceptably low-degree of chemoselectivity
Chemical reducing agents like Fe/FeCl2 in acidic aqueous in the case of the Rh-tppts-system10 was reported previ-
solution, (poly)sulfides, sulfites or SO2 suffer from a lack ously in the patent literature.7 In contrast, our method
of chemoselectivity.5b Other methods like the reduction based on Pt/1 is highly chemoselective and also allows for
under water gas shift conditions (CO/H2O) by the aid of a simple separation and re-use of the catalyst containing
homogeneous noble metal catalysts9 or the electrochemi- aqueous phase without significant loss of activity.
cal reduction5b in general suffer from low activity, al-
though good selectivities (> 99%) towards functional
groups have been reported in some cases.
In summary, the water-soluble PtCl2 complex of the b-
CD-modified diphosphine 1 is an excellent catalyst in the
biphasic hydrogenation of halo-nitro aromatic com-
Reduction in an aqueous two-phase system with molecu- pounds, the corresponding halo-aniline derivatives being
lar hydrogen as described in this paper is a desirable goal. formed chemoselectively. Accordingly, 1/PtCl2 acts as a
Table Hydrogenation of Compounds 3, 7 and 9 Catalyzed by Transition Metal Salts in the Presence of the Equivalent Amount of Ligand 1 in
Aqueous/Organic Two-Phase Systemsa
Entry
Substrate
Transition Metal
Salt
Temp.
(°C)
Time
(h)
Main Productb
(%)
Side Product
(%)
Selectivity
(%)
TONc
TOFd
(h–1)
1
2
3
4
5
6
7
8
3a
3a
3a
3ae
3a
3af
3b
3c
3cg
3c
3c
3c
3c
3c
7
[Rh(COD)2]BF4
[Rh(COD)2]BF4
[Rh(COD)2]BF4
[Rh(COD)2]BF4
(COD)PtCl2
100
80
60
60
80
80
60
60
80
80
80
80
80
80
80
80
100
20
20
18
18
18
18
15
15
18
18
25
15
15
15
15
15
24
12
18
65
160
4a (87.9)
4a (92.4)
4a (39.2)
4a (83.7)
4a (98.7)
4a (98.2)
4b (73.7)
4c (88.6)
4c (56.0)
4c (73.8)
4c (97.0)
4c (95.9)
4c (98.1)
4c (99.5)
8 (99.8)
6 (11.9)
6 (7.2)
5 (0.6)/6 (1.3)
5 (0.1)/6 (2.3)
6 (0.5)
6 (1.34)
6 (0.4)
5 (0.2)/6 (0.7)
6 (0.8)
6 (25.8)
6 (3)
6 (3.9)
6 (1.1)
6 (0.5)
88.1
92.7
96.8
97.3
99.5
98.7
99.5
99.2
98.6
73.9
97.3
96.0
98.9
99.5
99.8
99.5
79.0
97.2
97.1
103
103
405
870
103
996
741
888
570
738
103
103
103
103
103
104
103
948
103
38
29
23
48
> 70
66
42
49
23
> 70
> 70
> 70
> 70
> 70
> 30
840
350
(COD)PtCl2
[Rh(COD)2]BF4
[Rh(COD)2]BF4
[(cymol)RuCl2]2
Pd(OAc)2
Ir(COD)2BF4
Ni(COD)2
[Co(NH3)6]Cl2
(COD)PtCl2
(COD)PtCl2
9
10
11
12
13
14
15
16
17
18
19
4/6 (0.2)
4/6 (0.2)
6 (21.0)
6 (2.8)
7e
(COD)PtCl2
[Rh(COD)2]BF4
(COD)PtCl2
8 (99.5)
9
9
9
10 (79.0)
10 (94.8)
10 (97.1)
h
–
–
h
(COD)PtCl2
6 (2.9)
a Toluene and H2O as solvents/20 bar H2, except in the case of entries 4 and 16 where the substrate also served as the organic solvent (no toluene).
b In those cases in which the sum of the yields of main and side products is less than 100%, the reaction was incomplete, i.e., the difference is
the amount of starting material still present.
c Turn over number.
d Turn over frequency.
e No organic solvent used (only substrates and H2O); product was dissolved in toluene for analysis.
f Aqueous phase reused.
g Colloidal Rue is formed.
h Not determined.
Synthesis 1999, No. 9, 1555–1557 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Chemoselective Reduction of Halo-Nitro Aromatic Compounds
(d) Breslow, R. Science 1982, 218, 532.
1557
phase transfer catalyst (probably on the basis of host/guest
phenomena) and as a transition metal catalyst, therefore
constituting an interesting case of supramolecular cataly-
sis.1b,2
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All reactions were carried out using the standard Schlenk technique.
Solvents were dried and distilled under argon, water was degassed
in vacuo in an ultrasonic bath. The substrates were obtained from
Aldrich or Fluka and were used without further purification. The β-
cyclodextrin-phosphine 1 was prepared according to the literature
procedure.1 The products were analyzed with a GC Hewlett Packard
6890 equipped with a HP-5 column.
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release), Wiley-VCH: Weinheim, 1998.
Chemoselective Reduction of Halonitro Compounds 3,7 and 9
Using b-Cyclodextrin-Modified Transition Metal catalysts,
General Procedure
A transition metal salt (5 µmol) was added to the solution of 1
(5.5 µmol) in anhyd (free of O2) MeOH (2 mL). After 15 min the
solvent was evaporated in vacuo and the residue was dissolved in
H2O (10 mL) and transferred into an argon flushed steel autoclave
(100 or 200 mL) equipped with a magnetic stirring bar. Then
NaHCO3 (~ 50 mg) and a solution of the halo-nitrobenzene (5
mmol) in toluene (10 mL) were added. The autoclave was pressur-
ized with H2 (20 bar) and heated to the temperature indicated in the
Table under vigorous stirring. At the end of the reaction samples of
the organic phases were collected and analyzed by GC (Table).
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Article Identifier:
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Synthesis 1999, No. 9, 1555–1557 ISSN 0039-7881 © Thieme Stuttgart · New York