Practical copper-catalyzed N-arylation of amines with 20% aqueous solution of n-Bu4NOH

Article abstract of DOI:10.1016/j.cclet.2011.12.015

N-Arylation of a wide variety of amines with phenylboronic acid catalyzed by copper acetate under 20% aqueous solution of n-Bu₄NOH was accomplished in good to excellent yields (up to 92%) and substrate conversions (up to 96%).

Full text of DOI:10.1016/j.cclet.2011.12.015

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 301–304
www.elsevier.com/locate/cclet
Practical copper-catalyzed N-arylation of amines with
20% aqueous solution of n-Bu4NOH
*
Hamidreza Molaei, Mohammad Mehdi Ghanbari
Department of Chemistry, Sarvestan Branch, Islamic Azad University, Sarvestan, Iran
Received 14 October 2011
Available online 24 January 2012
Abstract
N-Arylation of a wide variety of amines with phenylboronic acid catalyzed by copper acetate under 20% aqueous solution of n-
Bu4NOH was accomplished in good to excellent yields (up to 92%) and substrate conversions (up to 96%).
# 2011 Mohammad Mehdi Ghanbari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Copper-catalyzed; N-Arylation; Phenylboronic acid; Amines
Transition-metal-catalyzed C–N bond formation is considered to be an important approach which has wide
applications in the synthesis of many compounds such as drugs and natural products [1]. Among metals that are able to
perform such transformations, copper stands out as a convenient alternative for palladium catalysts, because copper
salts are often cheap and environmental friendly [2]. In the recent years, several reviews have been published showing
some recent progresses of copper-catalyzed coupling reactions [3,4], but different ligands should be applied in most of
these successful examples. And some ligand-free copper-catalyzed N-arylation reactions have been reported [5,6].
Reactions in aqueous media are of great interest for industrial processes for economic and safety reasons. These
procedures have already been applied successfully which replace partially or fully organic solvents by water [7].
Among the different cross-coupling procedures known today, protocols involving boronic acids as coupling partners
are becoming increasingly popular [8]. Because of this fact that most of the boronic acids are air and moisture-stable,
using these reagents is highly attractive [9]. There has been reported N-arylation in aqueous media in the absence of
ligands in which copper acetate and in organic solvent in the present of ligands is used as a catalyst in the microwave
conditions [10]. Another paper has reported previously a method for the construction of C–N bond with n-Bu4NOH as
a base in organic solvent [11]. As part of our current studies on the development of new compounds synthesis [12], we
wish to report N-arylation reaction of the primary and secondary amines with phenyl boronic acid catalyzed by copper
acetate in 20% aqueous solution of n-Bu4NOH at room temperature. Schemes 1 and 2 illustrate the synthesis of these
amines.
In order to optimize the reaction conditions, we chose the reaction of indole with phenyl boronic acid as a model
reaction. As shown in Table 1, different copper sources and bases have been applied for the reaction. No reaction was
* Corresponding author.
E-mail address: m.mehdi.ghanbari@gmail.com (M.M. Ghanbari).
1001-8417/$ – see front matter # 2011 Mohammad Mehdi Ghanbari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.12.015

302
H. Molaei, M.M. Ghanbari / Chinese Chemical Letters 23 (2012) 301–304
Catalyst (20 mol%)
N
Base (2 eq)
B(OH)2
+
20% aq. nBu4NOH, rt
N
H
Scheme 1.
R1
B(OH)2
R1
Cu(OAC)2 (20 mol%)
NH
R2
+
N
nBu4NOH, tBuOK, rt, 22
h
R2
Scheme 2.
Table 1
Evaluation of bases and catalysts.
Entry
Catalyst
base
Isolated yield (%)
a
1
2
Cu(OAC)2
Cu(OAC)2
Cu(OAC)2
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
–
62
76
92
88
82
78
55
47
61
64
51
72
–
b
3
4
Cu(OAC)2H2O
CuSO4
5
6
CuCl2
7
CuI
9
Cu(OAC)2
Cu(OAC)2
Cu(OAC)2
Cu(OAC)2
Cu(OAC)2
–
10
11
12
13
14
NaOH
K2CO3
Et3N
Cs2CO3
t-BuOK
a
10 mol% of the copper acetate was used.
15 mol% of the copper acetate was used.
b
observed without any copper source (Table 1, entry 14). The yields of the product improved when the amount of the
copper increased. The amounts of the byproduct increased when we rose the reaction temperature. We applied these
optimized conditions for the rest of the substrates.
Thus, the reaction of amine and phenylboronic acid in the presence of Cu(OAC)2, n-Bu4NOH and t-BuOK leads to
products in good yields (Scheme 2 and Table 2). The 1H and 13C NMR spectra of the aliphatic and aromatic amines
clearly indicated the formation of them. The structures of these compounds were deduced from their elemental
analyses and their IR, 1H NMR, and 13C NMR spectra. The mass spectra of these compounds displayed molecular ion
peaks at appropriate m/z values. Any product other than these products could not be detected by NMR spectroscopy.
Although we have not yet established the mechanism of this reaction in an experimental manner, a possible
explanation is proposed in Scheme 3.
In summary, we have developed a practical and simple approach for the N-arylations of amines with phenylboronic
acid. The 20% aqueous solution of n-Bu4NOH was used as a base solvent which plays the role of a phase transfer
catalyst (PTC). We believe that the versatility, convenient operation, and environmental friendliness of this procedure
without organic ligand such as diazabutadienes (DABs) make it easily transferable to industrial applications.
Typical experimental procedure: To stirred solution of the round bottomed flask containing the amine (1 mmol),
Cu(OAC)2 (20 mol%), n-Bu4NOH (2 mmol) and t-BuOK (2 mmol) was added phenylboronic acid (1.5 mmol). The
reaction mixture was stand for 22 h the product was filtered and the residue was purified by silica column
chromatography (Merck 230–400 mesh) using n-hexane–AcOEt to afford the N-arylated product.

H. Molaei, M.M. Ghanbari / Chinese Chemical Letters 23 (2012) 301–304
303
Table 2
Copper catalyzed synthesis of arylamines.
Entry
1
Amine
Producta
Yield (%)b
92
Entry
7
Amine
Producta
Yield (%)b
78
2
3
85
81
8
9
61
67
4
5
82
72
10
11
60
75
6
65
a
All the products were characterized on the basis of their IR, 1H NMR and 13C NMR spectral analysis and compared with the literature data [1–7].
Isolated yields.
b
2,4-Dichloro-N-phenylaniline (6): IR (KBr) (nmax/cmÀ1): 3405 (NH), 1494 (C C); Anal. Calcd. (%) for C12H9
Cl2N (238.11): C, 60.53; H, 3.81; N, 5.88. Found: C 60.28; H, 3.78; N, 5.91; 1H NMR (300 MHz, CDCl3): d 5.66 (1H,
s, NH), 6.92–7.97 (8H, m, ArH); 13C NMR (75 MHz, CDCl3): d 120.5 (2 CH), 122.4 (CH), 123.1 (CH), 127.2 (CH),
127.3 (CH), 127.5 (C), 128.8 (C), 129.3 (C), 129.6 (2 CH), 141.0 (C).
1-Phenyl-1H-imidazole (7): IR (KBr) (nmax/cmÀ1): 3408 (NH), 1496 (C C); Anal. Calcd. (%) for C9H8N2
(144.17): C, 74.98; H, 5.59; N, 19.43. Found: C 75.08; H, 5.48; N, 19.51; 1H NMR (300 MHz, CDCl3): d 6.71–7.92
(8H, m, ArH); 13C NMR (75 MHz, CDCl3): d 118.3 (CH), 121.5 (2 CH), 127.5 (CH), 129.9 (2 CH), 130.3 (CH), 135.6
(CH), 136.7 (C).
2-Methyl-1-phenyl-1H-imidazole (8): IR (KBr) (nmax/cmÀ1): 3400 (NH), 1498 (C C); Anal. Calcd. (%) for
C11H13N2 (173.23): C, 76.27; H, 7.56; N, 16.17. Found: C 75.98; H, 7.62; N, 15.98; 1H NMR (300 MHz, CDCl3): d
2.17 (s, 3H, CH3), 7.01–7.48 (m, 7H, ArH); 13C NMR (75 MHz, CDCl3): d 13.4 (CH3), 106.5 (CH), 125.5 (2 CH),
126.4 (CH), 128.6 (CH), 129.4 (2 CH), 137.9 (C), 145.2 (C).
1-Phenyl-1H-pyrrole (10): IR (KBr) (nmax/cmÀ1): 3410 (NH), 1500 (C C); Anal. Calcd. (%) for C10H9N (143.19):
C, 83.88; H, 6.34; N, 9.78. Found: C 84.02; H, 6.28; N, 9.85; 1H NMR (300 MHz, CDCl3): d 6.70–8.22 (9H, m, ArH);
13C NMR (75 MHz, CDCl3): d 110.4 (2 CH), 115.6 (2 CH), 119.3 (2 CH), 125.6 (CH), 129.5 (2 CH), 140.6 (C).
R1
+
N H base
R2
Cu(OAc)2
R1
R1
N
Ph
N
R2
Cu OAc
R2
OH
B
O
C
H +
Ph
O
R1
N
CuII Ph
R2
Scheme 3.

304
H. Molaei, M.M. Ghanbari / Chinese Chemical Letters 23 (2012) 301–304
References
[1] (a) I.P. Beletskaya, A.V. Cheprakov, Coord. Chem. Rev. 248 (2337) (2004);
(b) E.M. Beccalli, G. Broggini, M. Martinelli, S. Sottocornola, Chem. Rev. 107 (5318) (2007);
(c) J.P. Corbert, G. Mignani, Chem. Rev. 106 (2006), 2651;
(d) S.V. Ley, A.W. Thomas, Angew. Chem. Int. Ed. 42 (2003) 5400.
[2] (a) K.M. Lakshmi, B. Neelima, R.C. Venkat, et al. J. Mol. Catal. 249 (201) (2006);
(b) G.O. Jones, P. Liu, K.N. Houk, S.L. Buchwald, J. Am. Ceram. Soc. 132 (2010) 6205;
(c) H.H. Chen, H.M. Huang, S.C. Chen, et al. J. Chin. Chem. Soc. 57 (2010) 14;
(d) W. Deng, Y.F. Wang, C. Zhang, et al. Chin. Chem. Lett. 17 (2006) 313;
(e) X.M. Wu, W.Y. Hu, Chin. J. Chem. 29 (2011) 2124.
[3] (a) K. Kunz, U. Scholz, D. Ganzer, Synlett (2003) 2428;
(b) W. Deng, L. Liu, Q.X. Guo, Chin. J. Org. Chem. 24 (2004) 150;
(c) G. Evano, N. Blanchard, T. Toumi, Chem. Rev. 108 (2008) 3054;
(d) F. Monnier, M. Taillefer, Angew. Chem. Int. Ed. 48 (2009) 6954;
(e) D. Ma, Q. Cai, Acc. Chem. Res. 41 (2008) 1450.
[4] (a) C.T. Yang, Y. Fu, Y.B. Huang, et al. Angew. Chem. Int. Ed. 48 (2009) 7398;
(b) E.R. Strieter, B. Bhayana, S.L. Buchwald, J. Am. Ceram. Soc. 131 (2009) 78;
(c) S. Jammi, S. Sakthivel, L. Rout, et al. J. Org. Chem. 74 (2009) 1971.
´
[5] (a) N. Joubert, E. Basle, M. Vaultier, et al. Tetrahedron Lett. 51 (2010) 2994;
(b) B. Weng, HuaLi, J. Appl. Organomet. Chem. 23 (2009) 375;
(c) X. Guo, H. Rao, H. Fu, et al. Adv. Synth. Catal. 348 (2006) 2197;
(d) L. Zhu, L. Cheng, Y. Zhang, et al. J. Org. Chem. 72 (2007) 2737.
[6] (a) K. Okano, H. Tokuyama, T. Fukuyama, Org. Lett. 5 (2003) 4987;
(b) A. Kelka, N.M. Patil, R.V. Chaudhari, Tetrahedron Lett. 43 (2002) 7143;
(c) L.B. Zhu, P. Guo, G.C. Li, et al. J. Org. Chem. 72 (2007) 8535;
(d) L.B. Zhu, G.C. Li, L. Guo, et al. J. Org. Chem. 74 (2009) 2200;
(e) R. Zhu, L. Xing, Adv. Synth. Catal. 350 (2008) 1253;
(f) X. Wang, C. Cheng, D. Su, et al. Adv. Synth. Catal. 349 (2007) 2673.
[7] (a) F. Lang, D. Zewge, I.N. Houpis, R.P. Volante, Tetrahedron Lett. 42 (2001) 3251;
(b) G.E. Job, S.L. Buchwald, Org. Lett. 4 (2002) 3703;
(c) M. Carril, R. SanMartin, E. Dominguez, I. Tellitu, Green Chem. 9 (219) (2007);
(d) D. Ma, C. Xia, Org. Lett. 3 (2001) 2583;
(e) H.H. Rao, H. Fu, Y.Y. Jiang, Y.F. Zhao, J. Org. Chem. 70 (2005) 8107;
(f) L. Liu, M.X. Frohn, N. Dominguez, et al. J. Org. Chem. 70 (2005) 10135;
(g) Z. Lu, R.J. Twieg, S.D. Huang, Tetrahedron Lett. 44 (2003) 6289;
(h) Z. Lu, R.J. Twieg, Tetrahedron Lett. 46 (2005) 2997;
(i) X.H. Zhu, Y. Ma, L. Su, et al. Synthesis (2006) 3955;
(j) M. Carril, R. San Martin, E. Dominguez, Chem. Soc. Rev. 37 (2008) 639;
(k) Y.C. Teo, Adv. Synth. Catal. 351 (2009) 720.
[8] (a) E. Tyrell, P. Brookes, Synthesis (2003) 469;
(b) N. Miyaura, Top. Curr. Chem. 219 (2002) 11.
[9] H. Prokopcov, C. Oliver, A. Kappe, Synth. Catal. 349 (2007) 448.
[10] (a) L.D.S. Yadav, B.S. Yadav, V.K. Rai, Synthesis (2006) 1868;
(b) K. Brajendra, V. Christian, D.R.J. Stevens, et al. Tetrahedron Lett. 50 (2009) 15.
[11] Y.S. Feng, Q.S. Man, P. Pan, et al. Tetrahedron Lett. 50 (2009) 2585.
[12] (a) I. Yavari, M.M. Ghanbari, J. Azizian, F.J. Sheikholeslami, Chem. Res. 35 (2011) 87;
(b) M.M. Ghanbari, Chem. Month 142 (2011) 794;
(c) I. Yavari, M.M. Ghanbari, A.S. Shahvelayati, et al. Phosphorus, Sulfur Silicon Relat. Elem. 185 (2010) 2551;
(d) D. Azarifar, E. Nadimi, M.M. Ghanbari, Chin. Chem. Lett. 22 (2011) 447.