chlorobenzene or 2-chlorotoluene with 10 equivalents of
lithium amide in dioxane at 110 1C gave the corresponding
triaryl amine as the major product (Scheme 1). Reducing the
temperature to 80 1C slightly improved the yield of aniline but
triphenylamine and diphenylamine were still obtained in
excess. Apparently, the desired aniline product is readily
deprotonated by the base which generates a strong nucleophile
that reenters the catalytic cycle to produce considerable
amounts of diaryl and triaryl amines.
(i) S. Liu, J. P. C. Pestano and C. Wolf, Synthesis, 2007,
519–3527; (j) B. P. Fors, P. Krattiger, E. Strieter and
S. L. Buchwald, Org. Lett., 2008, 10, 3505–3508; (k) D. S. Surry
and S. L. Buchwald, Angew. Chem., Int. Ed., 2008, 47, 6338–6361;
(l) Q. Shen, T. Ogata and J. F. Hartwig, J. Am. Chem. Soc., 2008,
130, 6586–6596.
3
2
3
X. Gao, H. Fu, R. Qiao, Y. Jiang and Y. Zhao, J. Org. Chem.,
2
008, 73, 6864–6866.
(a) S. Lee, M. Jorgensen and J. F. Hartwig, Org. Lett., 2001, 3,
2729–2732; (b) X. H. Huang and S. L. Buchwald, Org. Lett., 2001,
3
1
, 3417–3419; (c) D.-Y. Lee and J. F. Hartwig, Org. Lett., 2005, 7,
169–1172.
Yadav et al. showed that primary and secondary amines as
well as amides undergo C–N bond formation with aryl halides
when catalytic amounts of activated copper are employed
4
C.-Z. Tao, J. Li, Y. Fu, L. Liu and Q.-X. Guo, Tetrahedron Lett.,
008, 49, 70–75.
2
5 (a) J. P. Wolfe, J. Ahman, J. P. Sadighi, R. A. Singer and
S. L. Buchwald, Tetrahedron Lett., 1997, 38, 6367–6370;
1
6
under microwave irradiation. We therefore decided to avoid
the use of base and explored the feasibility of the microwave-
assisted reaction of aryl chlorides with ammonia in aqueous
solution. Using essentially the same conditions as described
above for the reaction between aqueous ammonia and aryl
bromides and iodides, we found that chlorobenzene affords
aniline in 93% yield upon heating to 110 1C in a microwave
oven for 10 hours (Table 2, entry 1). The scope of this copper-
catalyzed reaction has been further tested using a wide range
of aryl chlorides carrying electron-donating or withdrawing
groups. The corresponding anilines were formed in 79–89%
yield with excellent monoarylation versus diarylation selectivity
(
(
b) C. L. Cioffi, M. L. Berlin and J. Herr, Synlett, 2004, 841–845;
c) G. A. Grasa, M. S. Viciu, J. Huang and S. P. Nolan, J. Org.
Chem., 2001, 66, 7729–7737.
6 S. Jaime-Figueroa, Y. Liu, J. M. Muchowski and D. G. Putman,
Tetrahedron Lett., 1998, 39, 1313–1316.
7
(a) J. Yin and S. L. Buchwald, Org. Lett., 2000, 2, 1101–1104;
b) A. A. Trabanco, J. A. Vega and M. A. Fernandez, J. Org.
Chem., 2007, 72, 8146–8148.
(
8
9
X. Liu, M. Barry and H.-R. Tsou, Tetrahedron Lett., 2007, 48,
409–8412.
8
(a) F. Lang, D. Zewge, I. N. Houpis and R. P. Volante, Tetra-
hedron Lett., 2001, 42, 3251–3254; (b) H. Zhai, H. Lin, X. Lu and
X.-H. Xia, Chem. Lett., 2006, 1358–1359; (c) Q. Shen and
J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 10028–10029;
(
d) D. S. Surry and S. L. Buchwald, J. Am. Chem. Soc., 2007,
29, 10354–10355.
10 J. Kim and S. Chang, Chem. Commun., 2008, 3052–3054.
1
7
(
entries 2–8).
In summary, we have developed a copper(I)-catalyzed method
1
1
1
1
1 (a) R. Ntaganda, B. Dhudshia, C. L. B. Macdonald and
A. N. Thadani, Chem. Commun., 2008, 6200–6202; (b) N. Xia
and M. Taillefer, Angew. Chem., Int. Ed., 2009, 48, 337–339.
2 A copper-catalyzed method for the amination of arylboronic acids
with ammonia has been recently reported: H. Rao, H. Fu, Y. Jiang
and Y. Zhao, Angew. Chem., Int. Ed., 2009, 48, 1114–1116.
that allows the direct synthesis of a range of primary anilines
from electron-rich and electron-deficient aryl halides using
2
aqueous ammonia. The Cu O-catalyzed reaction eliminates
the need for inert atmosphere, expensive catalysts and ligands,
anhydrous solvents, and base or other additives which greatly
facilitates operation. Excellent yields are obtained with aryl
bromides and iodides and also with aryl chlorides when the
reaction is conducted in the microwave oven.
2
3 Buchwald showed that Cu O catalyzes the amidation of
3
,5-dimethylphenyl iodide with N-methyl formamide: A. Klapars,
X. Huang and S. L. Buchwald, J. Am. Chem. Soc., 2002, 124,
7421–7428.
1
4 C. Couture and A. J. Paine, Can. J. Chem., 1985, 63, 111–120.
5 Selected examples of copper-catalyzed amination of 2-halobenzoic
acids: (a) C. Wolf and X. Mei, J. Am. Chem. Soc., 2003, 125,
10651–10658; (b) M. L. Docampo Palacios and R. F. Pellon
Comdom, Synth. Commun., 2003, 33, 1771–1775; (c) X. Mei and
C. Wolf, J. Org. Chem., 2005, 70, 2299–2305; (d) X. Mei and
C. Wolf, J. Am. Chem. Soc., 2004, 126, 14736–14737; (e) X. Mei
and C. Wolf, Chem. Commun., 2004, 2078–2079.
1
Notes and references
1
Selected examples: (a) J. F. Hartwig, M. Kawatsura, S. I. Hauck,
K. H. Shaughnessy and L. M. Alcazar-Roman, J. Org. Chem.,
1
999, 64, 5575–5580; (b) J. P. Wolfe, H. Tomori, J. P. Sadighi,
J. Yin and S. L. Buchwald, J. Org. Chem., 2000, 65, 1158–1174;
c) F. Y. Kwong, A. Klapars and S. L. Buchwald, Org. Lett., 2002,
(
4
, 581–584; (d) D. Ma, Q. Cai and H. Zhang, Org. Lett., 2003, 5,
16 L. D. S. Yadav, B. S. Yadav and V. K. Rai, Synthesis, 2006,
1868–1872.
2453–2455; (e) Q. Shen, S. Shecar, J. P. Stambuli and
J. F. Hartwig, Angew. Chem., Int. Ed., 2005, 44, 1371–1375;
f) X. Mei, A. T. August and C. Wolf, J. Org. Chem., 2006, 71,
42–149; (g) C. Wolf, S. Liu, X. Mei, A. T. August and
17 The use of microwave irradiation is essential to the reaction of aryl
chlorides. Conventional heating of a mixture of chlorobenzene,
(
1
2 2
ammonia and Cu O (5 mol%) in NMP–H O to 160 1C for 36 h did
M. D. Casimir, J. Org. Chem., 2006, 71, 3270–3273; (h) X. Xie,
T. Y. Zhang and Z. Zhang, J. Org. Chem., 2006, 71, 6522–6529;
not show any sign of conversion. Due to increasing pressure, we
were not able to use microwave irradiation above 110 1C.
This journal is ꢀc The Royal Society of Chemistry 2009
Chem. Commun., 2009, 3035–3037 | 3037