Remarkably efficient oxidative coupling of N,N-dialkylarylamines in water mediated by cerium(IV) ammonium nitrate

Article abstract of DOI:10.1016/j.tetlet.2005.03.173

A highly effective, economical, and environmentally friendly method using of CAN as oxidant and water as solvent for oxidative coupling of N,N-dialkylarylamines was reported.

Full text of DOI:10.1016/j.tetlet.2005.03.173

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3909–3911
Remarkably efficient oxidative coupling of N,N-dialkylarylamines
in water mediated by cerium(IV) ammonium nitrate
Chanjuan Xi,* Yanfeng Jiang and Xianghua Yang
Key Laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education),
Department of Chemistry, Tsinghua University, Beijing 100084, China
Received 12 January 2005; revised 18 March 2005; accepted 23 March 2005
Available online 12 April 2005
Abstract—A highly effective, economical, and environmentally friendly method using of CAN as oxidant and water as solvent for
oxidative coupling of N,N-dialkylarylamines was reported.
Ó 2005 Elsevier Ltd. All rights reserved.
N,N,N0,N0-tetraalkylbenzidine derivatives have received
growing interest in their tunable electric conductivity,
which admits to diverse applications such as organic
light-emitting diodes,1 organic field-effect transistors,2
organic solar cells,3 and organic photoconductors.4 Oxi-
dative coupling of aniline derivatives provides an effi-
cient access to benzidine derivatives. Although several
methods for the coupling reaction have been reported,
most of them are low yielding processes.5–7 Recently,
TiCl4-mediated oxidative coupling appeared to be the
most practical method for benzidines,8 despite the
requirement of a large excess of starting anilines and uti-
lization of dichloromethane as solvent. More recently,
an alternative coupling of N,N-dialkylanilines in higher
yield has been developed by using organic oxidant such
as 1,8-bis(diphenyl-methylium)-naphthalenediyl dica-
tions.9 However, to get such organic oxidant could be
troublesome.
Cerium(IV) ammonium nitrate (CAN) has emerged as a
versatile one-electron oxidant for carbon–carbon bond
formation reactions.11 The advantages of good solubil-
ity in water, low cost, low toxicity, commercial avail-
able, easy handling, and profound reactivity give rise
to the possibility for development of more practical
reactions in aqueous medium. To the best of our knowl-
edge, CAN-mediated oxidative coupling of aniline
derivatives is rather rare.12 Herein, we would like to
report a remarkable efficient coupling of N,N-dialkyl-
aniline in water mediated by CAN (Scheme 1).
R1
R2
R1
R1
R2
CAN
H2O
N
N
N
R2
R
R
R
Scheme 1.
In light of the current interest to develop more efficient
and environmentally friendly methods for chemical syn-
theses, the use of water as the solvent clearly has both
economical and environmental advantages because it is
inexpensive, abundant, nontoxic, and readily separated
from organic compounds.10 Accordingly, it is highly
desirable to develop a direct oxidative coupling of
aniline derivatives in water by using a readily available,
water-soluble oxidant.
CAN is well known as one electron-transfer oxidant and
theoretically one equivalent of CAN is required for
mediating this coupling reaction. At first, we tested the
coupling of N,N-diethylaniline 1a in water using 1 equiv
of CAN. However, nearly half of the N,N-dialkylaniline
remained after quenched by an aqueous solution of
K2CO3. When the amount of CAN was increased to
1.5 equiv, some N,N-diethylaniline still remained even
after two days. The best yield of the coupling product
was obtained when the N,N-diethylaniline:CAN was
1:2 ratio at room temperature for 2 h (Scheme 2).13
N,N,N0,N0-Tetraethylbenzidine 2a was obtained in 81%
isolated yield with excellent regioselectivity. It is
noteworthy that neither product nor remaining
*
Corresponding author. Tel.: +86 10 62782695; fax: +86 10
62618239; e-mail: cjxi@tsinghua.edu.cn
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.173

3910
C. Xi et al. / Tetrahedron Letters 46 (2005) 3909–3911
of N,N-dibutylaniline 1f in 5 min and it made further
Et
Et
Et
Et
Et
Et
2 eq. CAN
N
N
N
stirring become impossible. The scope of this method
could be extended to the substituted N,N-dialkylaniline.
When ortho-methyl substituted N,N-diethylaniline 1h
was treated, para-coupled benzidine was exclusively
formed in good yield (Table 1, entry 9), while N-dealkyl-
ation reaction occurred in the reported method using
TiCl4.8 The reaction of diethyl-naphthalen-1-yl-amine
1i also gave naphthidines 2i in good yields.
H2O, r.t., 2h
Scheme 2.
N,N-diethylaniline was observed without quenching the
reaction mixture with aq K2CO3 solution. This pheno-
menon implies that product and starting material
coordinate to CAN. In other words, 2 equiv of CAN
is required to achieve the reaction.
A mechanistic rationale for this coupling reaction is pre-
sented in Scheme 3. Firstly, the N,N-dialkylaniline 1 is
coordinated to CAN to form complex 3, which under-
goes oxidative electron transfer with second CAN to
afford the radical cation 4. Secondly, the radical cation 4
directly dimerizes to give diiminium ions intermediate 5,
which is converted to dimer 6 after deprotonation.
Finally, product 2 forms after the workup procedure.
This is consistent with the fact that 2 equiv of CAN is
required for efficient reaction. It is noteworthy that no
other reduction product was observed from radical cat-
ion 4 abstracting H from water in the experiment, so we
The transformation was found to be general for various
aniline derivatives under the optimized condition. Rep-
resentative examples are shown in Table 1. In most
cases, the reaction gave high regioselectivity to para-
coupled bisaniline with exceptions of entries 2 and 4.
In the cases of entry 2 and entry 4, small amount of
ortho–para-coupled bisanilines was isolated in 10% and
6% yields, respectively. The use of N,N-dibutylaniline
1f diminished the yield of product 2f. In this case, the
reaction gave a polymer-like mixture after the addition
Table 1. The reaction of N,N-dialkylarylamines with CAN in watera
Entry
Substrate
Time (h)
Productb
Yield (%)c
81
Et
Et
Et
N
Et
Et
1
2
N
2a
N
1a
1b
1c
1d
Et
Me
Me
N
Me
Me
N
Me
2
3
4
5
6
7
8
2
81
71
78
85
53
72
73
N
2b
2c
2d
Me
Me
Me
N
Et
Me
N
Et
2
N
Et
Me
Me
N
Bu
Me
N
Bu
2
N
Bu
i-Pr
i-Pr
N
Bu
i-Pr
2
N
N
2e
1e
Bu
Bu
Bu
Bu
Bu
N
Bu
Bu
0.25
2
N
N
N
2f
1f
Bu
N
N
2g
1g
Me
Me
Me
Et
Et
Et
N
Et
Et
2
N
1h
N
2h
2i
Et
Et
Et
Et
N
Et
Et
Et
9
2
62
N
N
1i
a Conditions: N,N-dialkylarylamines (1 equiv), CAN (2 equiv), room temperature.
b The products were identified using 1H NMR, 13C NMR, mass spectra analysis, and comparison with reported data.
c Isolated yield.

C. Xi et al. / Tetrahedron Letters 46 (2005) 3909–3911
3911
H. C.; Hu, N.-H. J. Org. Chem. 1999, 64, 670–674; (c)
OꢀBrien, D. F.; Burrows, P. E.; Forrest, S. R.; Koene, B.
E.; Loy, D. E.; Thompson, M. E. Adv. Mater. 1998, 10,
1108–1112.
R1
CAN
R1
CAN
R2
R1
CAN
N
N
N
CAN
R2
R2
R
R
3
1
4
5. (a) Vettorazzi, N.; Fernandez, H.; Silber, J. J.; Sereno, L.
Electrochim. Acta 1990, 35, 1081–1088; (b) Mizoguchi, T.;
Adams, R. N. J. Am. Chem. Soc. 1962, 84, 2058–2061.
6. Carrick, W. L.; Karapinka, G. L.; Kwiatkowski, G. T.
J. Org. Chem. 1969, 34, 2388–2392.
R1
H
+ R1
CAN
N
N
N
CAN
R2
H
R2
5
´
´
7. Lopez-cortes, J. G.; Penieres-Carrillo, G.; Ortega-Alfaro,
´
´
M. C.; Gutierrez-Perez, R.; Toscano, R. A.; Alvarez-
Toledano, C. Can. J. Chem. 2000, 78, 1299–1304.
8. Periasamy, M.; Jayakumar, K. N.; Bharathi, P. J. Org.
Chem. 2000, 65, 3548–3550.
R1
R1
CAN
R2
CAN
R1
N
2H+
OH-
R2
6
9. Saitoh, T.; Yoshida, S.; Ichikawa, J. Org. Lett. 2004, 6,
4563–4565.
R1
N
N
10. (a) Li, C. J.; Chan, T. H. Organic Reactions in Aqueous
Media; John Wiley & Sons: New York, 1997; (b) Anastas,
P. T.; Warner, J. C. Green Chemsitry: Theory and Practice;
Oxford University Press: Oxford, 1998; (c) Lindstro¨m, U.
M. Chem. Rev. 2002, 102, 2751–2772; (d) Lubineau, A;
R2
R2
2
Scheme 3.
´
Auge, J. In Topics in Current Chemistry; Springer: Berlin,
Heidelberg, 1999; Vol. 206, p 1.
excluded the possibility that the radical intermediate 4
abstracts H from water, which would lead to a relatively
unstable ÆOH radical.
11. For reviews on CAN-mediated reactions see: (a) Ho, T. L
Synthesis 1973, 354–374; (b) Ho, T. L. Organic Synthesis
by Oxidation with Metal Compounds; Plenum: New
York, 1986; (c) Imamoto, T. Lanthanide Reagents in
Organic Synthesis; Academic: London, 1994, p 119; (d)
Nair, V.; Mathew, J.; Prabhakaran J. Chem. Soc. Rev.
1997, 127–132; (e) Hwu, J. R.; King, K.-Y. Curr. Sci.
2001, 8, 1043–1053; (f) Nair, V.; Panicker, S. B.; Nair, L.
G.; George, T. G.; Augustine, A. Synlett 2003, 156–165;
(g) Nair, V.; Balagopal, L.; Rajan, R.; Mathew, J. Acc.
Chem. Res. 2004, 37, 21–30.
In summary, a method using CAN as oxidant and water
as solvent for oxidative coupling of N,N-dialkylaryl-
amines was developed. This method has several advant-
ages, including easy handling, high efficiency, low cost,
and friendly to the environment. The synthetic applica-
tions of this reaction are currently under investigation.
12. Galliani, G.; Rindene, B.; Scolastico, C. Synth. Commun.
1975, 5, 319–323.
Acknowledgements
13. Representative procedure for the reaction of N,N-dialkyl-
arylamines. Oxidative coupling of N,N-diethylaniline. In
deionized H2O (3 mL), CAN (1.098 g, 2 mmol) and N,N-
diethylaniline (160 lL, 1 mmol) were added in turn at
room temperature. The reaction mixture was stirred for
2 h. The reaction mixture was quenched by aq K2CO3
solution and the organic residue was extracted with
CH2Cl2. The combined extract was dried over anhydrous
MgSO4. The solvent was removed and the residue was
chromatographed on an Al2O3 gel column. N,N,N0,N0-
Tetraethylbenzidine 2a8 was isolated (120 mg, 81%) as
white solid using 1:50 EtOAc/petroleum mixture as eluent.
1H NMR (CDCl3) d 7.40 (4H, d, J = 8.6 Hz), 6.71 (4H, d,
J = 8.6 Hz), 3.35 (8H, q, J = 7.2 Hz), 1.15 (12H, t,
J = 7.2 Hz); 13C NMR (CDCl3) d 146.2, 128.8, 127.0,
112.1, 44.4, 12.6; ESI-MS: 297(M+H+).
This work was supported by the National Natural
Science Foundation of China (20172032) (20372041).
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