Palladium-catalyzed amination of aromatic halides in water-containing solvent systems: A two-phase protocol

Article abstract of DOI:10.1039/a803819h

The use of the six-fold sulfonated ligand BINAS-6 1 permits the Pd⁰-catalyzed amination of aromatic halides in water containing single- or two-phase systems.

Full text of DOI:10.1039/a803819h

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Palladium-catalyzed amination of aromatic halides in water-containing solvent
systems: a two-phase protocol
Guido Wüllner, Helge Jänsch, Sven Kannenberg, Frank Schubert and Gernot Boche*†
Fachbereich Chemie, Philipps-Universität, Marburg, D-35032, Germany
The use of the six-fold sulfonated ligand BINAS-6 1 permits
Me
the Pd0-catalyzed amination of aromatic halides in water
3a: R = Me
3b: R = H
Br
RHN
+
containing single- or two-phase systems.
O
2
3a,b
Following the initial investigations of Kosugi et al.,1 both
Buchwald2 and Hartwig3 and their co-workers have developed
in recent years a new methodology for the amination of
aromatic halides and triflates (ArX: X = Cl, Br, I, OSO2CF3)
with amines RR1NH to yield aromatic amines of the type
ArNRR1.4 ArX and RR1NH were reacted with (di)phosphine-
complexed palladium [Pd0L, 1–5 mol%] and sodium tert-
butoxide (1.4 equiv.) in PhMe at 80–100°C under homogeneous
reaction conditions [eqn. (1)].
solv. A: H2O–MeOH (1:3)
solv. B: H2O–MeOH (1:6)
solv. C: H2O–MeOH–PhMe (1:2:2)
solv. D: H2O
BINAS-6 1
NaOH
solvent A–E
75–110 °C
(2)
solv. E: H2O–butan-2-ol (3:2)
Me
O
4a: R = Me
4b: R = H
N
R
4a,b
Pd0L, NaOBut
ArX
+
HNRR1
ArNRR 1
R1 = aryl
(1)
toluene, 80–100 °C
R = H, alkyl, aryl
(36%) of 4a [eqn. (2); Table 1, entry 3]. The use of emulsifying
agents like tetradecyltrimethylammoniumbromide did not in-
crease the yield of 4a, but resulted in considerable problems
during product recovery. With only water as the solvent (solvent
D) 4a was obtained in 36% yield [eqn. (2); Table 1, entry 4].
Butan-2-ol and water form a biphasic system with good
miscibility of the two solvents. Thus in the reaction of 2 with 3b
in the presence of Pd0–1 and water–butan-2-ol (3 : 2, solvent E)
the product 4b was obtained in 89% yield [eqn. (2); Table 1,
entry 5]. NaOH was found to give the best results as compared
to other group I hydroxides. The catalyst Pd0–1 remains in the
aqueous phase while the products can be collected conveniently
by separation of the organic layer. Only small amounts of
X = Cl, Br, I, OSO2CF3
Under such conditions reapplication of the Pd0 catalyst would
be difficult as is reuse of the relatively expensive (di)phosphine
ligand L. In contrast, by using a two-phase protocol, the
separation of products (and unreacted starting material) from
the catalyst and subsequent reapplication of the catalyst in
further reactions is made facile.5 For this reason there is
increasing interest in two-phase catalysis both in the labo-
ratory6,7 and for industrial applications.8 Here we report on a
two-phase protocol of the aforementioned Pd0-catalyzed amina-
tion reaction.
The ligand used here is the six-fold sulfonated
2,2A-bis(diphenylphosphinomethyl)-1,1A-binaphthyl 1 (BINAS-
6) dissolved in water.9
Table 1 Pd0–1 catalysed aminations of ArX in water-containing solvent
systems. All reactions were carried out under argon with degassed solvents
and starting materials. 1 was applied in an aqueous solution (140 mmol l21).
Physical and spectroscopic data of the products were consistent with those
reported previously in the literature.
NaO3S
Ar
P
Ar
Ar =
Ar
Reaction
Solvent time/h
Yield
Product (%)
P
Entrya
Halide
Amine
SO3Na
Ar
1
2
3
4
5
6
7
2
2
2
2
2
5
5
3a
3b
3a
3a
3b
3b
3c
A
B
C
D
E
E
E
2
3
32
25
6
4a
4b
4a
4a
4b
6a
6b
88
91
36
36
89
81
71
NaO3S
1
The reaction of 4-bromoacetophenone
2
with
N-methylaniline 3a in water–MeOH (1:3; solvent A) using
NaOH as the base and the aforementioned catalyst Pd0–1
afforded 1-[4-(N-methylanilino)phenyl]ethan-1-one 4a in 88%
yield [eqn. (2); Table 1, entry 1].
6
8
a Details of entries 1–7. 1: 160 mmol 1, 20 mmol Pd(OAc)2, 3 ml MeOH, 1
mmol ArX, 1.3 mmol amine, 1.3 mmol NaOH, 75 °C; products were
extracted with Et2O. 2: 70 mmol 1, 9 mmol Pd(OAc)2, 6 ml MeOH, 1 mmol
ArX, 1.3 mmol amine, 1.4 mmol NaOH, 75 °C; products were extracted
with Et2O. 3: 840 mmol 1, 100 mmol Pd(OAc)2, 12 ml MeOH, 12 ml PhMe,
6 ml water, 2 mmol ArX, 2.4 mmol amine, 2.8 mmol NaOH, 70 °C;
products were collected by separation of the organic layer. 4: 840 mmol 1,
100 mmol Pd(OAc)2, 12 ml water, 2 mmol ArX, 2.4 mmol amine, 2.8 mmol
NaOH, 90 °C; products were extracted with Et2O. 5–7: 80 mmol 1, 11 mmol
Pd(OAc)2, 3 ml water, 2 ml butan-2-ol, 1 mmol ArX, 1.3 mmol amine, 1.3
mmol NaOH, 110 °C; products were collected by separation of the organic
layer.
Reacting 2 with 3b in the presence of Pd0–1 and NaOH as the
base in water–MeOH (1 : 6; solvent B) resulted in the formation
of 1-(4-anilinophenyl)ethan-1-one 4b in 91% yield [eqn. (2);
Table 1, entry 2]. The Pd0–1 catalyst, which is dissolved in the
aqueous phase, can be reused after separation of the products.
The reaction was repeated under similar conditions. The
following yields were achieved: second reaction 85% 4b, (5 h);
third reaction 53% 4b, (7 h); fourth reaction 36% 4b, (7 h).
The use of a two-phase H2O–MeOH–PhMe system (1:2:2;
solvent C) in the reaction of 2 with 3a afforded only low yields
Chem. Commun., 1998
1509

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product ( < 5%) remain in the aqueous phase. In this solvent
system the catalyst can be reused as well.
lorganische Chemie) and the Fonds der Chemischen Industrie
for financial support, and Dr H. Bahrmann, Celanese GmbH,
Werk Ruhrchemie, for BINAS-6 1 as well as helpful discus-
sions. The Degussa AG provided us with Pd(OAc)2.
Reacting 1-chloroanthraquinone 5 with aniline 3b in the
presence of Pd0–1 and NaOH in water–butan-2-ol (3 : 2)
allowed amination of 5, affording 1-anilinoanthraquinone 6a in
81% yield [eqn. (3); Table 1, entry 6]. The use of o-toluidine 3c
under similar conditions gave 1-(o-toluidino)anthraquinone 6b
in 71% yield [eqn. (3); Table 1, entry 7].
Notes and References
† E-mail: boche@ps1515.chemie.uni-marburg.de
1 M. Kosugi, M. Kameyama and T. Migita, Chem. Lett., 1983, 927; M.
Kosugi, M. Kameyama and T. Migita, Nippon Kagaku Kaishi, 1985, 3
547.
O
Cl
R
2 A. S. Guram, R. A. Rennels and S. L. Buchwald, Angew. Chem., 1995,
107, 1456; Angew. Chem., Int. Ed. Engl., 1995, 34, 1348; J. P. Wolfe,
R. A. Rennels and S. L. Buchwald, Tetrahedron, 1996, 52, 7525; J. P.
Wolfe, S. Wagaw and S. L. Buchwald, J. Am. Chem. Soc., 1996, 118,
7215; S. Wagaw and S. L. Buchwald, J. Org. Chem., 1996, 61, 7240;
palladium-catalyzed aminations of triflate-arenes J. P. Wolfe and S. L.
Buchwald, J. Org. Chem., 1996, 61, 1133; J. P. Wolfe and S. L.
Buchwald, J. Org. Chem., 1997, 62, 1264.
3b: R = H
3c: R = Me
+
H2N
3b,c
O
Pd0/BINAS-6 1
5
(3)
NaOH
H2O–butan-2-ol
3 J. Louie and J. F. Hartwig, Tetrahedron Lett., 1995, 36, 3609; M. S.
Driver and J. F. Hartwig, J. Am. Chem. Soc., 1996, 118, 7217; J. Louie,
M. S. Driver and B. C. Hamann and J. F. Hartwig, J. Org. Chem., 1997,
62, 1268.
4 See also M. Beller, T. M. Riermeier, C.-P. Reisinger and W. A.
Herrmann, Tetrahedron Lett., 1997, 38, 2073; N. P. Reddy and M.
Tanaka, Tetrahedron Lett., 1997, 38, 4807.
O
R
6a: R = anilino
6b: R = o-toluidino
O
5 B. Cornils, Angew. Chem., 1995, 107, 1709; Angew. Chem., Int. Ed.
Engl., 1995, 34, 1575.
6a,b
6 W. A. Herrmann and C. W. Kohlpaintner, Angew. Chem., 1993, 105,
1588; Angew. Chem., Int. Ed. Engl., 1993, 32, 1524; P. Kalck and F.
Monteil, Adv. Org. Chem., 1992, 34, 219.
7 T. Prinz, W. Keim and B. Drießen-Hölscher, Angew. Chem., 1996, 108,
1835; Angew. Chem., Int. Ed. Engl., 1996, 35, 1708.
8 W. Keim, Chem Ing. Tech., 1984, 56, 850; G. Mercier and P. Chabardes,
Pure Appl. Chem., 1994, 66, 1509; Y. Tokitoh, N. Yoshimura, T.
Higashi, K. Mino and M. Murasawa, EP 436226, 1991; Chem. Abstr.,
1991, 115, 158508z; A. Behr and W. Keim, Arab. J. Sci. Eng., 1985, 10,
377.
9 H. Bahrmann, K. Bergrath, H.-J. Kleiner, P. Lappe, C. Naumann, D.
Peters and D. Regnat, J. Organomet. Chem., 1996, 520, 97.
10 H. S. Bien, J. Stawitz and K. Wunderlich, Ullmann’s Encyclopedia of
Industrial Chemistry, VCH, Weinheim, 1985, vol. A2, p. 355.
In conclusion, it has been demonstrated that the Pd0-
catalyzed amination of aromatic halides with amines can be
performed by means of a two-phase protocol with NaOH
instead of the expensive NaOBut as the base. Further advan-
tages are the facile catalyst/product separation and the reusabil-
ity of the water-soluble Pd0/BINAS-6 catalyst. The catalyst
system is also suitable for the preparation of substituted
anthraquinones, which are important in dye stuff production.10
Further work is being conducted to optimise the reaction
conditions and to perform selective single amination reactions
of dichloro-substituted anthraquinones.
We are grateful to the Deutsche Forschungsgemeinschaft
(Sonderforschungsbereich 260 and Graduiertenkolleg Metal-
Received in Liverpool, UK, 20th May 1998; 8/03819H
1510
Chem. Commun., 1998