Cupric chloride-catalyzed synthesis of symmetrical azo compounds from primary aromatic amines

Article abstract of DOI:10.1080/00397910902774034

Symmetrical azo compounds were synthesized from primary aromatic amines using n-BuMgBr as a base, oxygen as an oxidant, and CuCl2 as a catalyst.

Full text of DOI:10.1080/00397910902774034

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Cupric Chloride–Catalyzed
Synthesis of Symmetrical Azo
Compounds from Primary
Aromatic Amines
Ming Zhang a , Rongli Zhang a , Ai-Qin Zhang b ,
Xinfei Li a & Haihua Liang a
a College of Chemistry, Jiangxi Normal University
(Yaohu Campus), Nanchang, Jiangxi, China
b Department of Environmental and Chemical
Engineering, Nanchang Institute of Aeronautical
Technology, Nanchang, Jiangxi, China
Published online: 04 Sep 2009.
To cite this article: Ming Zhang , Rongli Zhang , Ai-Qin Zhang , Xinfei Li & Haihua
Liang (2009) Cupric Chloride–Catalyzed Synthesis of Symmetrical Azo Compounds
from Primary Aromatic Amines, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:19, 3428-3435, DOI:
10.1080/00397910902774034
To link to this article: http://dx.doi.org/10.1080/00397910902774034
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Synthetic Communications1, 39: 3428–3435, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902774034
Cupric Chloride–Catalyzed Synthesis of
Symmetrical Azo Compounds from
Primary Aromatic Amines
Ming Zhang,1 Rongli Zhang,1 Ai-Qin Zhang,2 Xinfei Li,1 and
Haihua Liang1
1College of Chemistry, Jiangxi Normal University (Yaohu Campus),
Nanchang, Jiangxi, China
2Department of Environmental and Chemical Engineering, Nanchang
Institute of Aeronautical Technology, Nanchang, Jiangxi, China
Abstract: Symmetrical azo compounds were synthesized from primary
aromatic amines using n-BuMgBr as a base, oxygen as an oxidant, and CuCl2
as a catalyst.
Keywords: Amines, azo compounds, copper, Grignard reactions, oxidations
INTRODUCTION
Azo compounds are useful compounds because of their applications in
optical materials, molecular devices, and theoretical studies,[1] so synthesis
of azo compounds is a worthwhile investigation. Symmetrical azo com-
pounds can be synthesized from primary aromatic amines by lead tetra-
acetate,[2a] potassium permanganate,[2a–c] potassium ferricyanide,[2d,3]
sodium hypobromide,[2a] chromic acid anhydride,[2a] manganese dioxi-
de,[2a] lead peroxide,[2a] and cetyltrimethylammonium dichromate.[2b]
Recently, four-electron oxidative formation of aryl diazenes using a
tantalum redox-active ligand complex was reported.[2] Galvinoxyl[4a] or
Received September 9, 2008.
Address correspondence to Ming Zhang, College of Chemistry, Jiangxi
Normal University, Yaohu Campus, 99 Ziyangdadao, Nanchang, Jiangxi
330022, China. E-mail: zmchem@163.com
3428

Cupric Chloride–Catalyzed Synthesis
3429
2,4,6-tri-tert-butylphenol[4b] was used as phase-transfer catalyst to prepare
symmetrical azo compounds from primary amines; the oxidant potassium
ferricyanide was stoichiometric. The manganese(III) complex of 5,10,15,
20-tetrakis(4-aminophenyl)porphyrin covalently bound to cross-linked
chloromethylated polystyrene was used as catalyst for oxidation of
primary aromatic amines to corresponding azo compounds; the oxidant
sodium periodate was stoichiometric.[5] Cupric chloride was used as cata-
lyst to prepare symmetrical azo compounds from primary aromatic
amines using air as oxidant; althogh this system is environmentally benign
and safe, yields are poor.[6] Although synthesis of symmetrical azo com-
pounds from primary aromatic amines is well established, there are many
drawbacks in literature methods, such as stoichiometric amounts of
oxidants,[2,3,5] expensive or toxic oxidants,[2a–c,4] poor yields,[2a,6] and long
reaction time.[2d] Herein we report an efficient method for synthesis of
symmetrical azo compounds from primary aromatic amines catalyzed
by cupric chloride using oxygen as an oxidant.
RESULTS AND DISCUSSION
Several reaction systems were investigated in the synthesis of azo
benzene: various copper or iron compounds were used as oxidants,
and K2CO3, Et3N, or n-BuMgBr were used as bases. The results are
listed in Table 1. It is efficient when the base is n-BuMgBr (2 equiv)
and oxidant is CuCl2 (2 equiv); the isolated yield is 95% in this case
(entry 9, Table 1). It is successful when a catalytic amount of CuCl2
(0.1 mmol, 10 mol%) is used and oxygen is used as an oxidant; the iso-
lated yield is 93% in this case (entry 10, Table 1). Because the CuCl2 is
toxic and O2 is cheap and nontoxic, the method in entry 10 (Table 1) is
better than that in entry 9 (Table 1) in view of economic effects and
environmental protection.
To explore the scope of the method using oxygen as an oxidant,
n-BuMgBr as a base, and CuCl2 as a catalyst, more primary aromatic
amines were used as substrates. The results are listed in Table 2. When
substituents are in the meta- or para-position to the amino group, the
yields are 87–92% (entries 2–4, Table 2). When substituents are in ortho-
position to the amino group, the yields are 82–85% (entries 5–7, Table 2).
It shows that steric hindrance of primary aromatic amines has an effect
on the formation of azo compounds.
When the substrate was m-nitroaniline, the product (2-n-butyl-
3-nitroaniline, 9) of nucleophilic substitution was obtained in 14% yield
(Scheme 1), and no corresponding azo compound (8) was found.

3430
M. Zhang et al.
Table 1. Optimization of reaction systems in the synthesis of azobenzene
Reaction Isolated
time
(h)
yield
(%)
Entry
1
Catalyst
—
Oxidant
Base
2 mmol
Fe(acac)3
2 mmol
Fe(acac)3
2 mmol
3 mmol Et3N
72
72
24
0a
Tracea
0a
2
3
—
—
2 mmol n-BuMgBr
2.5 mmol
K2CO3
Cu(OAc)2 ꢀ
H2O
4
5
—
—
2 mmol
Cu(acac)2
2 mmol
Cu(acac)2
2 mmol CuCl2
2 mmol CuCl2 3 mmol Et3N
2 mmol CuCl2 2.5 mmol K2CO3
2 mmol CuCl2 2 mmol n-BuMgBr
2 mmol n-BuMgBr
72
72
76a
0a
—
—
6
7
8
9
10
—
—
—
—
72
72
72
5
0a
Tracea
Tracea
95a
0.1 mmol
CuCl2 (10 mol%)
O2
2 mmol n-BuMgBr
24
93
aReaction conditions: Aniline (1 mmol) was added to a solution of a base
in THF (8 mL). After stirring for 1=2 h, an oxidant was added to the reaction
mixture, which was stirred at room temperature for the specified time.
The yields by this present method are much greater than that by the
literature method[5] in which CuCl was used as catalyst and air was used
as oxidant (Table 3).
A possible mechanism is postulated as follows: n-BuMgBr acts as a
base, oxygen acts as an oxidant, and CuCl2 acts as a catalyst. The
mechanism involves free radicals (Scheme 2). 1,2-Bis(3-nitrophenyl)
diazene (8) could not be obtained from 3-nitroaniline; the possible reason
was that the free radical could be captured by a nitro group.[7] This
phenomenon is the same as that observed in the literature.[4b]
In conclusion, an efficient reaction system using n-BuMgBr as a base,
oxygen as an oxidant, and CuCl2 as a catalyst is reported for the synthesis
of symmetrical azo compounds from primary aromatic amines.

Cupric Chloride–Catalyzed Synthesis
3431
Table 2. Synthesis of azo compounds catalyzed by CuCl2
Isolated
yield (%)
Entry Substrate
1
Product
Mp (lit. mp)
93
68–69 (67–68)[4]
2
3
4
89
92
87
102–104 (99)[4]
144–145 (144–145)[2b]
153–154 (160)[2b]
5
6
83
85
129–130 (136)[4]
53–54 (54)[4]
7
82
150–151 (143–145)[4]
8
9
0
—
14
56–57

3432
M. Zhang et al.
Scheme 1. Nucleophilic substitution of m-nitroaniline.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
1H NMR was measured on a Bruker 400-MHz spectrometer with
tetramethylsilane (TMS) as internal standard. Infrared (IR) spectra were
measured on a Nicolet Magna-IR550 spectrometer. Microanalyses were
performed with a PE 2400 elemental analyzer. Tetrahydrofuran (THF)
was distilled from Na=benzophenone immediately prior to use.
General Procedure for Catalyzed Synthesis of Symmetrical
Azo Compounds
An amine (1 mmol) was added to a solution of 2 mmol n-BuMgBr in dry
THF (8 mL). After stirring for 1=2 h, the catalyst CuCl2 (0.1 mmol,
10 mmol%) was added to the reaction mixture. Dry O2 was bubled into
the reaction mixture; the rate of bubling was faster for the first 30 min,
then it was very slow. The mixture was stirred at room temperature for
24 h under an atmosphere of O2. Then a little amount of silica gel was
added, and the resulting mixture was evaporated to dryness. Purification
was done by column chromatography on silica gel to give the product
Table 3. Comparison of yields with literature method
Yield by present
method (%)
Yield by literature
method (%)[5]
Product
1
3
4
5
7
93
92
87
83
82
33
85
71
8
46

Cupric Chloride–Catalyzed Synthesis
3433
Scheme 2. Mechanism for catalyzed synthesis of azo compounds.
(ethyl acetate=petroleum ether 30–60ꢁC as eluent solvent (1:9 for
products 1–6, 1:3 for products 7 and 9).
Data
1,2-Bis(3-chlorophenyl)diazene (2)
1
Orange red solid. H NMR (CDCl3, 400 MHz): 7.47 (m, 4H), 7.84 (m,
2H), 7.90 (s, 2H). IR (KBr, cmꢂ1): 3072, 1585, 1569, 1464, 1417, 1201,
1067, 887, 793, 684. Elemental analysis: calcd. C, 57.37%; H, 3.19%; N,
11.16%; found C, 57.51%; H, 3.12%; N, 11.28%.
1,2-Bis(4-methoxyphenyl)diazene (4)
Yellow solid. 1H NMR (CDCl3, 400 MHz): 3.89 (s, 3H), 7.0 (dd,
J1 ¼ 2 Hz, J2 ¼ 4.8 Hz, 2H), 7.88 (dd, J1 ¼ 2 Hz, J2 ¼ 4.8 Hz, 2H). IR
(KBr, cmꢂ1): 3018, 2929, 1600, 1579, 1498, 1458, 1440, 1245, 1145,
1024, 843. Elemental analysis: calcd. C, 69.42%; H, 5.79%; N, 11.57%;
found C, 69.22%; H, 6.02%; N, 11.45%.
1,2-Bis(2-chlorophenyl)diazene (5)
1
Orange red solid. H NMR (CDCl3, 400 MHz): 7.36 (m, 2H), 7.44 (m,
2H), 7.56 (m, 2H), 7.78 (m, 2H). IR (KBr, cmꢂ1): 3087, 1582, 1466,

3434
M. Zhang et al.
1442, 1254, 1060, 764, 726. Elemental analysis: calcd. C, 57.37%; H,
3.19%; N, 11.16%; found C, 57.58%; H, 3.33%; N, 10.92%.
1,2-Bis(2-methoxyphenyl)diazene (7)
1
Orange red solid. H NMR (CDCl3, 400 MHz): 4.02 (s, 6H), 7.00 (t,
J ¼ 8 Hz, 2H), 7.06 (d, J ¼ 8.4 Hz, 2H), 7.42 (m, 2H), 7.64 (m, 2H). IR
(KBr, cmꢂ1): 3003, 2946, 1593, 1489, 1470, 1437, 1280, 1251, 1159,
765. Elemental analysis: calcd. C, 69.42%; H, 5.79%; N, 11.57%; found
C, 69.54%; H, 5.91%; N, 11.49%.
2-n-Butyl-3-nitroaniline (9)
1
Brown solid. H NMR (CDCl3, 400 MHz): 0.97 (t, J ¼ 7.2 Hz, 3H), 1.43
(m, 2H), 1.63 (m, 2H), 2.55 (t, J ¼ 7.6 Hz, 2H), 4.00 (s, 2H), 7.14 (d,
J ¼ 8 Hz, 1H), 7.50 (d, J ¼ 2 Hz, 1H), 7.57 (m, 1H). IR (KBr, cmꢂ1):
3486, 3394, 2956, 2928, 2870, 1633, 1511, 1464, 1437, 1346, 1289, 1278,
1106, 950, 874, 818, 737. Elemental analysis: calcd. C, 61.86%; H,
7.22%; N, 14.43%; found C, 62.07%; H, 7.35%; N, 14.19%.
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