Novel CuI/tributyl phosphine catalyst system for amination of aryl chlorides

Article abstract of DOI:10.1039/b308034j

A simple and efficient methodology for the synthesis of triarylamines from aryl chlorides in a single step has been demonstrated using a novel Cul/ tributyl phosphine catalyst system with high activity and selectivity (80-87% yield).

Full text of DOI:10.1039/b308034j

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Retraction
Novel CuI/tributyl phosphine catalyst system for amination of aryl
chlorides
Nandkumar M. Patil, Ashutosh A. Kelkar, Zahid Nabi and Raghunath
V. Chaudhari
Chem. Commun., 2003, 2460 (DOI: 10.1039/b308034j). Retraction
published 27th September 2004
We, the named authors, hereby wholly retract this Chemical Communication.
Signed: Nandkumar M. Patil, Ashutosh A. Kelkar, Zahid Nabi and Raghunath
V. Chaudhar, Pune, India, September 2004.
Retraction endorsed by Sarah Thomas, Managing Editor

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Novel CuI/tributyl phosphine catalyst system for amination of aryl
chlorides†
Nandkumar M. Patil, Ashutosh A. Kelkar, Zahid Nabi and Raghunath V. Chaudhari*
Homogeneous Catalysis Division, National Chemical Laboratory, Pune-411008, India.
E-mail: rvc@ems.ncl.res.in; Tel: +91-20-5893260
Received (in Cambridge, UK) 15th July 2003, Accepted 18th August 2003
First published as an Advance Article on the web 26th August 2003
A simple and efficient methodology for the synthesis of
triarylamines from aryl chlorides in a single step has been
demonstrated using a novel CuI/tributyl phosphine catalyst
system with high activity and selectivity (80–87% yield).
chemical synthesis. Arylamines have also been employed as
ligands for transition metals, and in the design of conducting
polymers and other electronically interesting materials.6
Recently, milder Ullmann type methodologies for the N-
arylation of anilines,9 imidazoles,10a,b amides11 and nitrogen
heterocycles12 have been developed. However, most of the
work has been carried out using aryl iodides as reactants. Aryl
chlorides are the most attractive aryl halides for synthetic
applications on an industrial scale, because they are inexpensive
and readily available in bulk quantities. However, there is only
one report on the amination of aryl chlorides using copper
catalyst with poor results (49% yield of triarylamine in 36 h).9
Thus, there is a need to develop an improved catalyst system for
copper catalyzed amination of aryl chlorides.
Our efforts have been directed towards the development of an
improved and single step catalytic system for copper catalyzed
amination of aryl chlorides. We wish to report here for the first
time, the use of monodentate phosphine ligands in the activation
of aryl chlorides with high activity and selectivity. Aryl
chlorides are usually inert and the order of reactivity, ArI >
ArBr > ArCl is consistent with the Ar–X bond strength.2
Experimentally found bond dissociation energies for phenyl
halide at 298 K for Cl, Br and I are 96, 81 and 65 Kcal mol21
respectively.13 Also it is known that a metal center coordinated
by electron-rich phosphine ligands can effectively activate C–
Cl bonds of aryl chlorides.13,14
Arylamines are prevalent in compounds with end use in
biological, pharmaceutical and novel materials.1–3 Their wide-
spread importance has led to the development of many synthetic
methods for the formation of aryl–nitrogen bonds.4 Amongst
them, the classical copper-mediated Ullmann coupling and the
recently developed palladium(0) catalyzed aryl couplings are
the more commonly used methods.5a–d Although, the Pd-
catalyzed C–N coupling has recently become the most im-
portant method for laboratory scale synthesis of substituted aryl
amines, the copper mediated coupling is still the reaction of
choice for large and industrial-scale production of these
compounds6,7 as shown in Scheme 1.
One of the earliest applications of triaryl amines was in the
production of brightly colored synthetic dyes, introduced in the
late nineteenth century.8 High purity triarylamines find applica-
tions in xerographic photoreceptors,6 as constituents of non-
linear optical chromophores useful in the design of integrated
electro-optic switches and modulators. Arylamines have a large
number of other applications and are thus attractive targets for
We investigated amination of iodobenzene using CuI as a
catalyst and o-tolyl phosphine and tributyl phosphine as ligands
(Table 1; entries 4 and 9). High activity and selectivity for
amination of iodobenzene was observed even at a CuI : ligand
ratio of 1 : 1 for both the ligands. This is in sharp contrast to no
activity with PPh3 as a ligand at CuI : PPh3 ratio of 1 : 110a and
poor activity at higher ratios (Table 1 entries 1–3),15 clearly
showing the influence of the nature of ligand on catalytic
activity. Best results were obtained at a CuI : ligand ratio of 1 :
2 (Table 1; entries 5 and 10). Both the ligands were tested for
catalytic activity using bromobenzene and chlorobenzene as
Scheme 1
† Electronic supplementary information (ESI) available: experimental and
analytical details (G.C. and NMR analysis). See http://www.rsc.org/
suppdata/cc/b3/b308034j/
Table 1 Copper catalysed amination reaction using different monodentate phosphine ligands
Product yield (%)
CuI : Ligand
Ratio
Reaction
time/h
Conv. of
aniline (%)
Entry
Ligand
X
1
2
1a
2a
3a
4
5
6
7b
8b
9
10
11
12b
13b
PPh3
PPh3
PPh3
1 : 1
1 : 2
1 : 3
1 : 1
1 : 2
1 : 3
1 : 2
1 : 2
1 : 1
1 : 2
1 : 3
1 : 2
1 : 2
3.5
3.5
3.5
3.5
3.5
I
I
I
I
I
I
Br
Cl
I
I
I
Br
Cl
12
62
73
89
95
94
81
58
91
100
95
100
99
0
0
15
19
80
87
83
58
41
80
93
88
92
87
17
25
5
5
6
12
8
6
2
2
(o-tol)3P
(o-tol)3P
(o-tol)3P
(o-tol)3P
(o-tol)3P
P(Bu)3
P(Bu)3
P(Bu)3
P(Bu)3
P(Bu)3
3.5
10.5
10.5
3.5
3.5
3.5
10.5
10.5
1
1
Reaction conditions: aryl halide: 16.48 mmol; aniline: 7.85 mmol; CuI: 0.28 mmol; toluene: 23 ml; temperature: 110 °C; a = literature reports see ref. 15;
b
= 135 °C.
2460
CHEM. COMMUN., 2003, 2460–2461
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reactants. Interestingly in both the cases good activity was
observed (Table 1; entries 7,8 and 12,13). It may be noted that
the results obtained with tributyl phosphine as a ligand are better
than the previous reports (bromobenzene: 92% yield in 10.5 h at
135 °C as compared to 73% by Gujadhur et al.9 and
chlorobenzene: 87% yield in 10.5 h at 135 °C compared to 49%
in 36 h at 110 °C by Gujadhur et al.9). Better results obtained
with tributyl phosphine as a ligand may be due to electron rich
nature of PBu3 (Compare entries 7 and 8 with 12 and 13 of
Table 1). This is the first report on the amination of aryl
chlorides using CuI as a catalyst and a monodentate phosphine
as ligand.
A number of bases were screened with CuI as a catalyst,
aniline, chlorobenzene as reactants and tributylphosphine as a
ligand. Of all the bases, KOtBu gave best results (87% yield of
triphenylamine, Table 1; entry 13). Very poor results were
obtained with NaOtBu and reaction did not proceed with other
bases.
(85–87%) while lower yield ( ~ 80%) was obtained with a CH3
group at ortho positions. However, with electron deficient
–NO2 groups in para positions very poor results were obtained
(Table 2, entries 11–14). Results obtained with the CuI/PBu3
catalyst system for chlorobenzene and aniline as reactants
(80–87% yield) in 10.5 h, show significant improvement over
literature reports (49% yield in 36 h).9 Improved results
obtained are mainly due to combination of electronic as well as
steric effects of tributylphosphine. Further work is necessary to
understand the exact role of ligands.
In summary we have demonstrated for the first time a high
yield of triaryl amines (80–87%) using the CuI/PBu3 catalyst
system. Further work on understanding the role of ligands is in
progress in our laboratory.
N.M.P. thanks the Council of Scientific and Industrial
Research, New Delhi, India for financial assistance for this
work.
Thus, CuI/PBu3 catalyst system with KOtBu as a base was
found to be the best system for amination of aryl chlorides. In
order to check the tolerance of substituents a few substituted
chlorobenzenes, bromobenzenes and aniline derivatives were
screened using the CuI/PBu3 catalyst system and KOtBu as a
base (See Table 2). A marginal increase in yield was observed
with electron donating –OCH3 groups at para positions
Notes and references
1 J. P. Wolfe, S. Wagaw, J. F. Marcoux and S. L. Buchwald, Acc. Chem.
Res., 1998, 31, 805–818.
2 J. F. Hartwig, Angew. Chem., Int. Ed. Engl., 1998, 37, 2046–2067.
3 M. Beller, C. Breindl, T. H. Riermeier and A. Tillack, J. Org. Chem.,
2001, 66, 1403–1412.
4 M. S. Driver and J. F. Hartwig, J. Am. Chem. Soc., 1997, 119,
8232–8245.
Table 2 Copper catalysed amination reactions involving substituted aryl
chlorides and bromides using tributylphosphine as a ligand
5 (a) J. Lindley, Tetrahedron, 1984, 40, 1433–1456; (b) Y. Hong, C. H.
Senanayake, T. Xiang, C. P. Vandenbossche, G. J. Tanoury, R. P.
Bakale and S. A. Wald, Tetrahedron Lett., 1998, 39, 3121–3124; (c) J.
P. Wolfe, H. Tomori, J. P. Sadighi, J. J. Yin and S. L. Buchwald, J. Org.
Chem., 2000, 65, 1158–1174; (d) A. H. Lewin, M. J. Zovko, M. J.
Rosewater and T. Cohen, J. Chem. Soc., Chem. Commun., 1967, 80.
6 H. B Goodbrand and N-X. Hu, J. Org. Chem., 1999, 64, 670–674.
7 P. J. Fagan, E. Hauptman, R. Shapiro and A. J. Casalnuovo, J. Am..
Chem. Soc., 2000, 122, 5043–5051.
8 B. H. Yang and S. L. Buchwald, J. Organomet. Chem., 1999, 576,
125–146.
9 R. K. Gujadhur, C. G. Bates and D. Venkataraman, Org. Lett., 2001, 3,
4315–4317.
10 (a) R. K. Gujadhur, D. Venkataraman and T. J. Kintigh, Tetrahedron
Lett., 2001, 42, 4791–4793; (b) R. Gujadhur and D. Venkataraman,
Synth. Commun., 2001, 31, 139–153.
11 A. Kiyomori, J. F. Marcoux and S. L. Buchwald, Tetrahedron Lett.,
1999, 40, 2657–2660.
12 M. Wolter, A. Klapars and S. L. Buchwald, Org. Lett., 2001, 3,
3803–3805.
13 V. V. Grushin and H. Alper, Chem. Rev., 1994, 94, 1047–1062.
14 A. F. Littke and G. C. Fu, Angew. Chem., Int. Ed. Engl., 2002, 41,
4176–4211.
Product
yield (%)*
Conv. of
aryl
Entry
X
R
RA
amines (%)
1
2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Cl
Cl
Cl
H
H
H
H
100
94
96
100
98
94
100
97
100
100
62
82
84
80
87
85
80
86
82
85
87
35
31
41
29
2
5
4
3
3
3
2
2
5
2
p-OMe
o-CH3
p-OMe
H
H
H
p-OMe
p-OMe
o-CH3
p-OMe
o-CH3
H
p-OMe
p-NO2
p-NO2
H
H
p-OMe
p-OMe
H
H
p-NO2
p-NO2
11
9
10
8
55
59
52
p-NO2
Reaction conditions: aryl halide: 16.48 mmol; aryl amine: 7.85 mmol; CuI:
0.28 mmol; tributylphosphine: 0.56 mmol; toluene: 23 ml; time 10.5 h;
temperature: 135 °C; * = isolated yields
15 A. A. Kelkar, N. M. Patil and R. V. Chaudhari, Tetrahedron Lett., 2002,
43, 7143–7146.
CHEM. COMMUN., 2003, 2460–2461
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