Reduction of nitrosobenzenes to azoarenes with SmI2

Article abstract of DOI:10.3184/030823410X12706553325118

A novel method was developed to synthesise azoarenes from nitrosobenzenes under mild conditions. Samarium (II) iodine was used to achieve the N-N coupling. The method also provides evidence for the proposed mechanism involved in the reduction of nitro compounds to the amines with SmI₂.

Full text of DOI:10.3184/030823410X12706553325118

214 RESEARCH PAPER
APRIL, 214–215
JOURNAL OF CHEMICAL RESEARCH 2010
Reduction of nitrosobenzenes to azoarenes with SmI2
Wei Yea, Wenbo Dinga, Zhang Hub, Yongping Yua and Hongbin Zoua,c*
aCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P. R. China
bCollege of Science, Guangdong Ocean University, Zhanjiang 524088, P. R. China
cState key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, P. R. China
A novel method was developed to synthesise azoarenes from nitrosobenzenes under mild conditions. Samarium (II)
iodine was used to achieve the N–N coupling. The method also provides evidence for the proposed mechanism
involved in the reduction of nitro compounds to the amines with SmI2.
Keywords: nitrosobenzene, azoarenes, SmI2
The versatile electron donor, samarium (II) iodide (SmI2),
which is easily prepared by a radical reaction,1 has been exten-
sively used in organic synthesis over the last decade especially
as a coupling agent.2–4 SmI2 can also be employed as a reduc-
ing agent in the conversion of nitro compounds to the corre-
sponding amines. It was previously found that the reduction of
nitro groups with SmI2 may yield intermediates between nitro
groups and amines such as hydroxylamines,5 hydrazines,6
azoarenes,7 or azoxyarenes.8 The stepwise organic trans-
formation of a nitro group to an amine was postulated to
proceed by the mechanism shown in Scheme 1 with the forma-
tion of a samarium-containing product, typically written as
“I SmOSmI2”.9,10 To date there is no direct evidence for the
pr2oposed mechanism nor intermediates.
Scheme 2
contributed significantly to the reductive efficiency of SmI .
The results shown here also provide support for the propose2d
mechanism of the reduction of aromatic nitro compounds
with SmI2 through the reductive intermediate azoarenes as
previously postulated.
Experimental
Nitrosobenzene, the intermediate shown in Scheme 1, has a
highly reactive nitroso group and can be found as a reactive
intermediate in biological systems and organic syntheses. To
further illustrate the proposed reduction process and mecha-
nism we describe here a novel reduction of nitrosobenzenes to
azoarenes by SmI2. These are proposed to be the reactive pre-
cursor of the amines in the conversion of nitro group to amine
with SmI2 (Scheme 2). The nitrosobenzenes were easily pre-
pared from corresponding amines by using molybdenum oxide
(MoO3)11 The different substituted nitroso compounds were
reduced with SmI in THF to afford azoarenes (Table 1).
The amount of2SmI used in the reaction should be exact,
since a larger excess2 of SmI , for example 4 equiv, will
automatically transform the nitr2osobenzenes to amines while
insufficient SmI2 will leave the nitrosobenzenes unaltered.
The results presented in Table 1, although in moderate yield,
indicate that the reduction of nitrosobenzenes with the correct
equivalent of SmI2 could be used as a route to synthesise
azoarenes. The nitrosobenzenes with strong electron-donating
substituents on the aromatic ring gave relatively higher yields
than the electron-withdrawing substituted ones. Specifically a
nitrosobenzene with a strong electron-withdrawing trifluoro-
methyl group was not converted to the corresponding azoarene
with SmI2.
Melting points were determined with a Perkin-Taike X-4 apparatus
and then corrected. H NMR spectra were recorded using a Varian
1
INOVA 400 spectrometer with TMS as an internal standard and
CDCl3 as solvent. TLC was performed on silica gel (GF254). Column
chromatography was carried out on silica gel H (10–40 μm). The
silica gel GF254 and silica gel H were purchased from Qingdao Marine
Chemical Factory, China.
Preparation of b1–9; general procedure
I2 (4.4 mmol) was added to Sm (4.4 mmol) in anhydrous THF_
(15 mL) and stirred at room temperature under inert atmosphere to
prepare SmI2. When the colour of the reaction mixture turned from
yellow to dark blue, the nitrosobenzenes a1–9 (2.2 mmol) in anhy-
drous THF was added to it and stirred until the colour changed from
dark blue to yellow. The reaction was quenched by addition of dilute
HCl (5%) until the yellow solid disappeared. It was evaporated under
reduced pressure to remove THF and the remaining mixture was
extracted with EtOAc. The organic extract was washed with saturated
aqueous NaHCO3, aqueous Na2S2O4 (5%), and then brine and dried
over anhydrous Na2SO4 overnight. Evaporation of the extract under
reduced pressure afforded the crude product which was purified by
column chromatography to afford the corresponding azobenzenes
b1–9. The physical and spectra data of the compounds b1–9 are as
follows.
b1: M.p. 67–70°C (lit.12 66–68 °C). 1H NMR: δ 7.38 (m, 2H, H4,4′),
8.16 (m, 4H, H3,3′,5,5′), 8.30 (d, 4H, H2,2′,6,6′, J = 7.2 Hz); ESI: m/z =
183.2 (M+H+).
In conclusion, we have utilised SmI2 as a reducing agent
for the conversion of nitrosobenzenes to azoarenes which had
not been reported previously. It was found that the electron
donating properties of the substituent on the aromatic ring
b2: M.p. 142–145 °C (lit.13 145–146 °C). 1H NMR: δ 2.43 (s, 6H,
CH3), 7.31 (d, 4H, H3,3′,5,5′, J = 8.0 Hz), 7.81 (d, 4H, H2,2′,6,6′, J = 8.0
Hz); ESI: m/z=211.3 (M+H+).
Scheme 1
* Correspondent. E-mail: zouhb@zju.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2010 215
Table 1 Reduction of aromatic nitroso compounds with SmI2
Entry
Nitrosobenzenes (a1–10)
Azoarenes (b1–10)
Yield /%a
70
1
2
3
4
5
6
7
8
9
45
50
55
40
50
40
25
30
0
10
a Isolated yield.
b3: M.p. 54–57 °C (lit.13 55 °C). 1H NMR: δ 2.74 (s, 6H, CH3), 7.25
(m, 2H, H4,4′), 7.46 (m, 4H, H3,3′,5,5′), 7.62 (d, 2H, H6,6′, J = 6.8 Hz); ESI:
m/z=211.3(M+H+).
Received 18 January 2010; accepted 11 March 2010
Paper 100961 doi: 10.3184/030823410X12706553325118
Published online: 28 April 2010
b4: M.p. 54–57 °C (lit.13 54–55 °C). 1H NMR: δ 2.46 (s, 6H, CH ),
7.29 (d, 2H, H4,4′, J = 7.2 Hz), 7.40 (m, 2H, H5,5′), 7.72 (m, 4H, H2,2′,6,63′);
ESI: m/z=211.3(M+H+).
References
b5: M.p. 160–164 °C (lit.14 160–161 °C). 1H NMR: δ 3.88 (s, 6H,
OCH3), 7.00 (d, 4H, H3,3′,5,5′, J = 7.2 Hz), 7.88 (d, 4H, H2,2′,6,6′, J = 7.2
Hz); ESI: m/z=243.3(M+H+).
1
P. Girard, J.L. Namy and H.B. Kagan, J. Am. Chem. Soc., 1980, 102,
2693.
2
3
4
5
Z. Petr and S. Bhavdeep, Chem. Rev., 1994, 94, 1621.
H.B. Kagan, Tetrahedron, 2003, 59, 10351.
K. Alain and L. Anne-Marie, Chem. Rev., 1999, 99, 745.
H. Feuer, R.S. Bartlett, B.F. Vincent and R.S. Anderson, J. Org. Chem.,
1965, 30, 2880.
b6: M.p. 184–188 °C (lit.13 185–187 °C). 1H NMR: δ 8.18 (d, 4H,
H3,3′,5,5′, J = 7.2 Hz), 8.28 (d, 4H, H2,2′,6,6′, J = 7.2 Hz); ESI: m/z=
252.1(M+H+).
b7: M.p. 201–204 °C (lit.15 203–204 °C). 1H NMR: δ 7.67 (d, 4H,
H3,3′,5,5′, J = 7.2 Hz), 7.81 (d, 4H, H2,2′,6,6′, J = 7.2 Hz); ESI: m/z=
341.0(M+H+).
6
7
G.A. Olah, J. Am. Chem. Soc., 1959, 81, 3165.
R.O. Hutchins, D.W. Lamson, L. Rua, C. Milewski and B. Maryanoff,
J. Org. Chem., 1971, 36, 803.
1
b8: M.p. 101–104 °C (lit.16 101 °C). H NMR: δ 7.19 (m, 4H,
H3,3′,5,5′), 7.92 (dd, 4H, H2,2′,6,6′, J1 = 4.0 Hz, J2 = 7.2 Hz); ESI: m/z=
219.2(M+H+).
8
9
K. Ohe, S. Uemura, N. Sugita, H. Masuda and T. Taga, J. Org. Chem.,
1989, 54, 4169.
B.H. Kim, S.K. Kim,Y.S. Lee,Y.M. Jun,W. Baik and B.M. Lee, Tetrahedron
Lett., 1997, 38, 8303.
b9: M.p. 100–103 °C (lit.13 100–101 °C). 1H NMR: δ 7.46 (m, 4H,
H4,4′,6,6′), 7.83 (m, 2H, H5,5′), 7.90 (s, 2H, H2,2′); ESI: m/z=
252.1(M+H+).
10 E.D. Brady, D.L. Clark, D.W. Keogh, B.L. Scott and J.G. Watkin, J. Am.
Chem. Soc., 2002, 124, 7007.
11 A. Defoin, Synthesis, 2004, 5, 706.
12 F. Saeid, Acta Chim. Slov., 2007, 54, 647.
13 H.M. Nanjundaswamy, J. Chem. Res. (S), 2005, 12, 772.
14 P. Hanson, A.B. Taylor, P.H. Walton andA. W. Timms, Org. Biomol. Chem.,
2007, 5, 679.
15 C. Nallaiah and J.A. Strickson, Tetrahedron, 1986, 42, 4083.
16 G.G. Furin, J. Fluorine Chem., 1985, 28, 1.
This research work was funded by National Science and
Technology Major Project “Key New Drug Creation and
Manufacturing Program” of China (No. 2009ZX09501-010),
the National Natural Sciences Foundation of China (No
20802066), the State Key Laboratory of Drug Research (No.
SIMM0901KF-06) and the Department of Education of
Zhejiang Province Foundation (No. Y200805312).

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.