Oxidative coupling reaction of N,N-dialkylanilines with cerium(IV) ammonium nitrate in the solid state

Article abstract of DOI:10.1080/00397910600781067

Oxidative coupling reactions of N,N-dialkylanilines with cerium(IV) ammonium nitrate can be achieved by grinding at room temperature in the absence of solvents. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600781067

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Oxidative Coupling Reaction of
N,N‐Dialkylanilines with Cerium(IV)
Ammonium Nitrate in the Solid State
Xianghua Yang a , Chanjuan Xi a & Yanfeng Jiang a
a Key Laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology
(Ministry of Education), Department of Chemistry , Tsinghua University ,
Beijing, China
Published online: 27 Oct 2006.
To cite this article: Xianghua Yang , Chanjuan Xi & Yanfeng Jiang (2006) Oxidative Coupling Reaction of
N,N‐Dialkylanilines with Cerium(IV) Ammonium Nitrate in the Solid State, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:17, 2413-2419, DOI:
10.1080/00397910600781067
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Synthetic Communicationsw, 36: 2413–2419, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600781067
Oxidative Coupling Reaction of
N,N-Dialkylanilines with Cerium(IV)
Ammonium Nitrate in the Solid State
Xianghua Yang, Chanjuan Xi, and Yanfeng Jiang
Key Laboratory for Bioorganic Phosphorus Chemistry and Chemical
Biology (Ministry of Education), Department of Chemistry,
Tsinghua University, Beijing, China
Abstract: Oxidative coupling reactions of N,N-dialkylanilines with cerium(IV)
ammonium nitrate can be achieved by grinding at room temperature in the absence
of solvents.
Keywords: Grinding, N,N-dialkylarylamine, oxidative coupling, solid state
N,N,N0,N0-Tetraalkylbenzidine derivatives have received much attention for
their tunable electric conductivity, which has the potential to be utilized
in industrial fields such as organic light-emitting diodes,[1] organic field-
effect transistors,[2] organic solar cells,[3] and organic photoconductors.[4]
Oxidative coupling of N,N-dialkylanilines provides an efficient access to
such products, but most known methods for such reactions are either low
yielding[5–7] or not very regioselective. Some newly reported methods seem
to be more practical, such as TiCl4-mediated oxidative coupling[8] and 1,8-
bis(diphenylmethylium)naphthalenediyl dications,[9] but the former requires
a large excess of substrates and dichloromethane as solvent and the organic
oxidant for the latter is troublesome to get.
With increasing public concern about environmental degradation, one of
the challenges for chemists is to come up with new approaches that are less
Received in R.O.C. January 16, 2006
Address correspondence to Chanjuan Xi, Key Laboratory for Bioorganic Phos-
phorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry, Tsinghua University, Beijing 100084, China. E-mail: cjxi@tsinghua.edu.cn
2413

2414
X. Yang, C. Xi, and Y. Jiang
hazardous to human health and the environment.[10] The solvents used in
organic synthesis are high on the list of environmental pollutants, because
they are employed in large amounts and usually are volatile liquids. To be
environmentally friendly, we are interested in seeking new processes
involving solvent-free reactions for organic reactions, although the solvent-
free method has been utilized in a wide range of reactions recently.[11–14]
In our previous work, we developed a cerium(IV) ammonium nitrate
(CAN)-mediated oxidative coupling of N,N-dialkylanilines using water as
solvent,[15] which was efficient, economical, and environmentally friendly.
During the course of our study, we found oxidative coupling reactions of
N,N-dialkylanilines with CAN can be achieved by grinding at room tempera-
ture in the absence of solvents.
By milling constantly with a mortar and pestle, this method was found to
be significantly faster than traditional methods based on solvent[12–14] and
much easier to carry out. When N,N-dialkylanilines were tried with this
method (Scheme 1), similar conclusions, such as faster proceeding, easier
handling, and higher regioselectivity, were demonstrated by our study.
At the very beginning, experiments were made to test the proper
amount of CAN, and in accordance with the aqueous system we
reported,[15] 2 equiv of CAN seems to be the most proper (Table 1).
When 1 equiv of CAN was added to 1 mmol of substrate and ground con-
stantly with a mortar and pestle for 15 min, most substrate still remained.
When the amount of CAN changed from 2 equiv to 5 equiv, only the
yield mildly differed. When N,N-diethylaniline 1a was used in these
testing reactions, para-position coupling happened and N,N,N0,N0-tetraethyl-
benzidine 2a was the main isolated product in 58% yield with excellent
regioselectivity.
The ratio of 1 : 2 of substrate to CAN for oxidative p,p-coupling was
found to be general for other N,N-dialkylanilines, and some examples are
shown in Table 2. In most cases, the reaction gave high regioselectivity for
p,p-coupling products, with the only exception of 3,5-dimethyl-N,N-diethyla-
niline 1d, which gave o,p-coupled product 2d in 80% yield. 1-Phenylpiperi-
dine 1j showed low yield of 2j in 28% probably because the ring on the N
atom make the proceeding of the reaction harder. Reactions of other substrates
were similar to 1a.
As for the mechanism of this reaction, we hold the radical cation
procedure, which we reported in our previous work,[15] as presented in
Scheme 2. First, the N,N-dialkylaniline 1 is coordinated to CAN to form
Scheme 1.

Oxidative Coupling Reaction of N,N-Dialkylanilines
2415
Table 1. Effect of amount of CAN on the oxidative coupling
reaction of N,N-dialkylaniline
Entry
CAN (eq)
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
9
1
1
2
2
2
2
3
4
5
5
15
5
Trace
Trace
Trace
35
10
15
20
15
15
15
58
58
46
42
44
aIsolated yield based on the amount of N,N-dialkylaniline.
complex 3, which undergoes oxidative electron transfer with second CAN to
afford the radical cation 4. Second, the radical cation 4 directly dimerizes to
give diiminium ions intermediate 5, which is converted to dimer 6 after depro-
tonation. Finally, product 2 forms after the workup procedure.
In conclusion, we have found a highly regioselective, fast, and environ-
mentally friendly oxidative coupling reaction of N,N-dialkylanilines with
cerium(IV) ammonium nitrate (CAN) in the absence of solvent.
EXPERIMENTAL
Representative Procedure
N,N-Diethylaniline 1a (1 mmol, 159 mL) and CAN (2 eq, 1.096 g) were mixed
together in a mortar, and the mixture was constantly milled with a pestle. Ten
to fifteen minutes later, the reaction mixture was quenched with an aqueous
solution of K2CO3, followed by extraction of the organic phase with ethyl
acetate. Then the solvent was evaporated under reduced pressure, and the
residue was purified by chromatography on neutral Al2O3 column using
1:100 EtOAc/petroleum mixture as eluent.
1
Structures of the final products were comfirmed by H NMR (300 MHz)
and 13C NMR (300 MHz) in deuterated chloroform. Chemical shifts (d) are
reported in parts per million (ppm) relative to tetramethylsilane. Proton and
carbon spectra were typically obtained at room temperature. ESI-MS data
were used to strengthen our results.

2416
X. Yang, C. Xi, and Y. Jiang
Table 2. Oxidative coupling of N,N-dialkylanilines with CAN in solid state
Yield
(%)a
Entry
1
Substrate
Product
1a
1b
2a
2b
58
2
3
78
1c
2c
48
80
4
1d
2d
5
6
1e
1f
1g
1h
1i
2e
2f
2g
2h
2i
77
54
43
49
46
28b
7
8
9
10
1j
2j
aIsolated yield based on substrate.
bSubstrate 1j remained.
Data
N,N,N0,N0-Tetraethylbiphenyl-4,40-diamine (2a):[8] yellow solid (58%).
1H NMR (CDCl3) d 7.40 (d, J ¼ 8.6 Hz, 4H), 6.72 (d, J ¼ 8.6 Hz, 4H), 3.35

Oxidative Coupling Reaction of N,N-Dialkylanilines
2417
Scheme 2.
(q, J ¼ 6.9 Hz, 8H), 1.17 (t, J ¼ 6.9 Hz, 12H); 13C NMR (CDCl3) d 146.4,
128.9, 127.2, 112.3, 44.5, 12.8. ESI-MS: 297 (M þ Hþ).
N,N,N0,N0-Tetraethyl-2,20-dimethylbiphenyl-4,40-diamine (2b): light yellow
1
liquid (78%). H NMR (CDCl3) d 6.87 (d, J ¼ 8.3 Hz, 2H), 6.46 (m, 4H),
3.26 (q, J ¼ 7.2 Hz, 8H), 1.98 (s, 6H), 1.09 (t, J ¼ 7.2 Hz, 12H); 13C NMR
(CDCl3) d 146.8, 137.4, 131.2, 129.5, 112.9, 109.2, 44.4, 20.9, 12.9. ESI-
MS: 325 (M þ Hþ). HRMS: calcd. for C22H32N2 324.2565; found 324.2568.
N,N,N0,N0-Tetraethyl-3,30-dimethylbiphenyl-4,40-diamine (2c): light yellow
liquid (48%). 1H NMR (CDCl3) d 7.40 (m, 4H), 7.08 (d, J ¼ 8.3 Hz,
2H), 3.02 (q, J ¼ 7.2 Hz, 8H), 2.35 (s, 6H), 1.00 (t, J ¼ 7.2 Hz, 12H); 13C
NMR (CDCl3) d 148.8, 135.9, 135.4, 129.4, 124.5, 122.4, 47.7, 18.7, 12.7.
ESI-MS: 325 (M þ Hþ). HRMS: calcd. for C22H32N2 324.2565; found
324.2563.
N,N,N0,N0-Tetraethyl-20,4,6,60-tetramethylbiphenyl-2,40-diamine
(2d):
1
colorless liquid (80%). H NMR (CDCl3) d 6.46 (s, H), 6.31 (s, 3H), 3.31
(m, 8H), 2.26 (s, 9H), 1.89 (s, 3H), 1.15 (m, 12H); 13C NMR (CDCl3) d
148.0, 146.5, 138.7, 137.1, 128.4, 117.5, 111.1, 109.8, 44.3, 44.2, 21.9,
20.8, 12.9, 12.7. ESI-MS: 353 (M þ Hþ). HRMS: calcd. for C24H36N2
352.2878; found 352.2875.
N,N0-Diethyl-N,N0-diisopropylbiphenyl-4,40-diamine (2e): colorless liquid
1
(77%). H NMR (CDCl3) d 7.20 (m, 4H), 6.72 (m, 4H), 4.02 (m, 2H), 3.22
(m, 4H), 1.15 (m, 18H); 13C NMR (CDCl3) d 148.6, 129.2, 115.8, 112.9,

2418
X. Yang, C. Xi, and Y. Jiang
48.2, 38.0, 20.1, 15.1. ESI-MS: 325 (M þ Hþ). HRMS: calcd. for C22H32N2
324.2565; found 324.2566.
N,N0-Dibutyl-N,N0-diisopropylbiphenyl-4,40-diamine (2f):[16] yellow solid
1
(54%). H NMR (CDCl3) d 7.34 (d, J ¼ 8.9 Hz, 4H), 6.68 (d, J ¼ 8.9 Hz,
4H), 3.98 (m, 2H), 3.04 (m, 4H), 1.49 (m, 4H), 1.32 (m, 4H), 1.27
(m, 12H), 0.88 (m, 6H); 13C NMR (CDCl3) d 146.6, 128.5, 126.3, 112.8,
18.0, 43.2, 31.0, 19.9, 19.5, 13.4. ESI-MS: 381 (M þ Hþ).
N,N,N0,N0-Tetramethylbiphenyl-4,40-diamine (2 g):[8] yellow solid (43%).
1H NMR (CDCl3): d 7.45 (d, J ¼ 8.4 Hz, 4H), 6.80 (d, J ¼ 8.4 Hz, 4H),
2.97 (s, 12H); 13C NMR (CDCl3): d 149.4, 130.0, 127.0, 113.2, 40.8. ESI-
MS: 241 (M þ Hþ).
N,N0-Dibutyl-N,N0-dimethylbiphenyl-4,40-diamine (2 h):[16] yellow solid
1
(49%). H NMR (CDCl3): d 7.42 (d, J ¼ 8.9 Hz, 4 H), 6.72 (d, J ¼ 8.9 Hz,
4 H), 3.30 (br, 4 H), 2.93 (s, 6 H), 1.52–1.58 (m, 4 H), 1.29–1.38 (m, 4 H),
0.94 (t, J ¼ 7.2 Hz, 6 H). 13C NMR (CDCl3): d 147.8, 129.1, 126.9, 112.4,
52.6, 38.4, 28.9, 20.4, 14.0. ESI-MS: 325 (M þ Hþ).
N,N0-Diethyl-N,N0-dimethylbiphenyl-4,40-diamine (2i):[8] yellow solid
(46%). 1H NMR (CDCl3): d 7.61 (m, 4H), 6.92 (m, 4H), 3.58
(q, J ¼ 7.2 Hz, 4H), 3.06 (s, 6H), 1.27 (t, J ¼ 7.2 Hz, 6H); 13C NMR
(CDCl3): d 147.8, 129.49, 127.1, 112.9, 47.0, 37.6, 11.4. ESI-MS: 269
(M þ Hþ).
4,40-Di(piperidin-1-yl)biphenyl (2j):[8] yellow solid (28%). 1H NMR
(CDCl3): d 7.51 (m, 4H), 7.13 (m, 4H), 3.24 (s, 8H), 1.70 (m, 12H); 13C
NMR (CDCl3): d 150.8, 132.0, 127.0, 116.8, 50.8, 25.9, 24.4. ESI-MS: 321
(M þ Hþ).
ACKNOWLEDGMENTS
This work was supported by the National Natural Science Foundation of
China (20572058, 20372041) and Beijing Department of Education
(XK100030514).
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