1,2-Eliminations in a novel reductive coupling of nitroarenes to give azoxy arenes by sodium bis(trimethylsilyl)amide

Article abstract of DOI:10.1021/ol050924x

(Chemical Equation Presented) Symmetric azoxy arenes were successfully prepared in one step from 2 equiv of the corresponding nitroarenes by use of sodium bis-(trimethylsilyl)amide as the deoxygenating agents in THF at 150°C in a sealed tube.

Full text of DOI:10.1021/ol050924x

ORGANIC
LETTERS
2005
Vol. 7, No. 15
3211-3214
1,2-Eliminations in a Novel Reductive
Coupling of Nitroarenes to Give Azoxy
Arenes by Sodium
Bis(trimethylsilyl)amide
Jih Ru Hwu,* Asish R. Das, Chia Wei Yang, Jiann-Jyh Huang, and Ming-Hua Hsu
Organosilicon and Synthesis Laboratory, Department of Chemistry, National Tsing
Hua UniVersity, Hsinchu, Taiwan 30013, Republic of China
jrhwu@mx.nthu.edu.tw
Received April 26, 2005
ABSTRACT
Symmetric azoxy arenes were successfully prepared in one step from 2 equiv of the corresponding nitroarenes by use of sodium bis-
(trimethylsilyl)amide as the deoxygenating agents in THF at 150 C in a sealed tube.
°
Sodium bis(trimethylsily)amide often acts as a strong base
in organic transformations.1-6 Because of its nucleophilicity,
this commercially available reagent is also used to provide
for addition of a nitrogen atom to organic compounds.7-9
Transformation of aromatic esters to nitriles in one flask
represents a recent application of sodium bis(trimethylsily)-
amide.7 Moreover, this silicon-containing reagent exhibits a
selective monodemethylating ability in dimemthoxy aromatic
compounds.10 Thus, it can be applied as an efficient
deprotecting agent. In our investigation of new applications
of silicon-containing compounds, we considered the potential
deoxygenation ability of sodium bis(trimethylsily)amide.
Consequently, an unprecedented deoxygenation reaction was
developed for the conversion of nitroarenes to azoxy
compounds by use of sodium bis(trimethylsily)amide. The
reaction mechanism is intriguing since it may invole three
sequential 1,2-eliminations.
(1) Paquette, L. A. In Encyclopedia of Reagents for Organic Synthesis;
Wiley: Chichester, UK, 1995; pp 4564-4566.
(2) Chow, S.; Wen, K.; Sanghvi, Y. S.; Theodorakis, E. A. Bioorg. Med.
Chem. Lett. 2003, 13, 1631-1634.
(3) Bargiggia, F.; Piva, O. Tetrahedron: Asymmetry 2003, 14, 1819-
1827.
(4) Pe´rard-Viret, J.; Prange´, T.; Tomas, A.; Royer, J. Tetrahedron 2002,
58, 5103-5108.
(5) Palomo, C.; Aizpurua, J. M.; Oiarbide, M.; Garc´ıa, J. M.; Gonza´lez,
A.; Odriozola, I.; Linden, A. Tetrahedron Lett. 2001, 42, 4829-4831.
(6) de Parrodi, C. A.; Clara-Sosa, A.; Pe´rez, L.; Quintero, L.; Maran˜o´n,
V.; Toscano, R. A.; Avin˜a, J. A.; Rojas-Lima, S.; Juaristi, E. Tetrahedron:
Asymmetry 2001, 12, 69-79.
(7) Hwu, J. R.; Hsu, C. H.; Wong, F. F.; Chung, C.-S.; Hakimelahi, G.
H. Synthesis 1998, 329-332.
(8) Bestmann, H. J.; Wo¨lfel, G.; Mederer, K. Synthesis 1987, 848-850.
(9) Bestmann, H. J.; Wo¨lfel, G. Chem. Ber. 1984, 117, 1250.
Current interest in azoxy compounds is increasing dra-
matically because of their physiological activities and ap-
(10) Hwu, J. R.; Wong, F. F.; Huang, J.-J.; Tsay, S.-C. J. Org. Chem.
1997, 62, 4097-4104.
10.1021/ol050924x CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/21/2005

plications to liquid crystals.11-13 They are also utilized as
DNA cleavers, polymerization inhibitors, stabilizers, dyes,
and analytical reagents.14 Azoxy compounds can be prepared
from amines,14,15 hydroxylamines,16,17 nitrosohydroxylamine
ammonium salts,18 and azo,19,20 nitro,21-23 and nitroso
compounds.24,25 Those methods often require reducing agents,
oxidizing agents, or UV light.
In the newly developed method, we treated a THF solution
of a nitroarene with 1.0 equiv of NaN(SiMe3)2 in a sealed
tube at 150 °C for 12 h. After normal workup and purification
with silica gel column chromatography, the desired azoxy
arene was often isolated in solid form (see Scheme 1 and
Table 1. Transformations of Nitroarenes to the Corresponding
Azoxy Arenes by Use of NaN(SiMe3)2 (1.0 equiv) in THF at
150 °C
nitroarene
X
Y
azoxy producta
yield (%)
1a
1b
1c
1d
1e
1f
1g
1h
1ib
H
OMe
H
OMe
OEt
SMe
H
H
H
OMe
OMe
H
2a
2b
2c
2d
2e
2f
2g
2h
2I
21
45
40
51
42
46
25
22
>20
H
NMe2
-OCH2CH2O-
-O(CH2CH2O)4-
a Compounds 2a-g were reported previously;21b our spectroscopic data
are consistent with those in the literature. b Use of DMEU as the cosolvent
and 2.5 equiv of NaN(SiMe3)2 for 48 h.
Scheme 1
significant amount. In a control experiment, we performed
the reaction involving 1b in THF at reflux (∼65 °C) under
an N2 atmosphere. The desired product 2b was produced in
32% yield (versus 45% in Table 1). Moreover, the same
reaction did not proceed at room temperature.
In addition to the intermolecular couplings, we found that
cyclization took place on 2,2′-dinitrobiphenyl (3) under the
same thermal conditions (Scheme 1). It gave the intramo-
lecular coupling product 4 in 20% yield.
The azoxy arenes 2a-i and 4 were fully characterized by
spectroscopic methods. For example, compound 2d possessed
characteristic resonance at δ 150.23 ppm for the aromatic
13C-N+(O-)dN and at δ 148.26 ppm for the aromatic 13C-
NdN+(O-). Its IR absorptions showed peaks at 1455 cm-1
for antisymmetric stretching and at 1278 cm-1 for symmetric
stretching of the N+(O-)dN- functional group. The exact
masses for these zwitterionic type compounds were obtained
by mass spectrometer.
A plausible pathway for the conversion of nitroarenes 5
to symmetric azoxy arenes 13 is shown in Scheme 2, which
accounts for our original design. The lack of acidic protons
in nitroarenes 5 allows them to undergo nucleophilic attack
by NaN(SiMe3)2 to give adducts 6. We supposed that the
first intramolecular 1,2-elimination took place at the Si-
N-N+-O- moiety of 6 to give azoxysilanes 7 and Me3-
SiO-. This is analogous to Kru¨ger’s26 report on a deoxy-
Table 1). Among various solvents, including THF, p-dioxane,
DMF, and HMPA, we found that the use of THF or a mixture
of THF/HMPA gave the best results. The coupling reaction
required 12 h for completion. A shorter reaction time led to
a lower yield for the desired azoxy arenes, yet a longer time
gave over-reduced azo compounds as the byproducts in a
(11) Ikeda, T.; Tsutumi, O. Science 1995, 268, 1873-1875.
(12) Campbell, D.; Dix, L. R.; Rostron, P. Dyes Pigm. 1995, 29, 77-
83.
(13) For books, see (a) Gilchrist, T. L. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol.
7, p 735. (b) Rosenblatt, D. H.; Burrows, E. P. In The Chemistry of Amino,
Nitroso and Nitro Compounds and their DeriVatiVes; Patai, S., Ed.; Wiley:
Chichester, 1982; p 1085.
(14) Waghmode, S. B.; Sabne, S. M.; Sivasanker, S. Green Chem. 2001,
3, 285-288.
(22) For representative reports involing metal-reducing agents, see: (a)
Hou, Z.; Fujiwara, Y.; Taniguchi, H. J. Org. Chem. 1988, 53, 3118-3120.
(b) McKillop, A.; Raphael, R. A.; Taylor, E. C. J. Org. Chem. 1970, 35,
1670-1672. (c) Olah, G.; Pavlath, A.; Kuhn, I. Acta Chim. Acad. Sci. Hung.
1955, 7, 71-84.
(23) For reports involing hydride reducing agents, see: (a) Dewar, M.
J. S.; Goldberg, R. S. Tetrahedron Lett. 1966, 2717-2720. (b) Shine, H.
J.; Mallory, H. E. J. Org. Chem. 1962, 27, 2390-2391. (c) Weill, C. E.;
Panson, G. S. J. Org. Chem. 1956, 21, 803.
(24) For reviews and books, see: (a) Wang, P. G.; Xian, M.; Tang, X.;
Wu, X.; Wen, Z.; Cai, T.; Janczuk, A. J. Chem. ReV. 2002, 102, 1091-
1134. (b) Hrabie, J. A.; Keefer, L. K. Chem. ReV. 2002, 102, 1135-1154.
(c) Timberlake, J. W.; Stowell, J. C. In The Chemistry of the Hydrazo,
Azo, and Azoxy Groups; Patai, S., Ed.; Wiley: New York, 1975; pp 96-
101.
(15) Sakaue, S.; Tsubakino, T.; Nishiyama, Y.; Ishii, Y. J. Org. Chem.
1993, 58, 3633-3638.
(16) Pizzolatti, M. G.; Yunes, R. A. J. Chem. Soc., Perkin Trans. 2 1990,
759-764.
(17) Becker, A. R.; Sternson, L. A. J. Org. Chem. 1980, 45, 1708-
1710.
(18) Hwu, J. R.; Yau, C. S.; Tsay, S.-C.; Ho, T.-I. Tetrahedron Lett.
1997, 38, 9001-9004.
(19) Nakata, M.; Kawazoe, S.; Tamai, T.; Tatsuta, K. Tetrahedron Lett.
1993, 34, 6095-6098.
(20) Newbold, B. T. J. Org. Chem. 1962, 27, 3919-3923.
(21) For recent reports on the conversion of nitroarenes to azoxyarenes,
see: (a) Siemeling, U.; Tu¨rk, T.; Vorfeld, U.; Fink, H. Monatsh. Chem.
2003, 134, 419-423. (b) Wada, S.; Urano, M.; Suzuki, H. J. Org. Chem.
2002, 67, 8254-8257. (c) Luboch, E.; Kravtsov, V. Ch.; Konitz, A. J.
Supramol. Chem. 2001, 1, 101-110.
(25) Cardellini, L.; Greci, L.; Stipa, P.; Rizzoli, C.; Sgarabotto, P.;
Ugozzoli, F. J. Chem. Soc., Perkin Trans. 2 1990, 1929-1934.
3212
Org. Lett., Vol. 7, No. 15, 2005

O-) share a common feature in that a siloxide is excluded
from the Si-X-Y-O- moieties. For X and Y, both of them
are carbon atoms in the Peterson olefination. Nevertheless,
at least one of them is a nitrogen atom in the other three
1,2-eliminations (see Scheme 3).
Scheme 2
At elevated temperature, the second intramolecular 1,2-
elimination may occur to azoxysilanes 7 to give diazonium
arenes 8 and Me3SiO- (see Scheme 2). Reaction of 8 with
the second equivalent of NaN(SiMe3)2 provides triazenes 9,
in which a terminal silyl group can undergo migration to
give the isomers 10.31 Then, Me3SiO-, which is generated
in situ during the conversions of 6 f 7 f 9, attacks the
terminal silyl group in 10 to afford anilides 11 and N2. The
oxidation state of the nitrogen atoms in NaN(SiMe3)2 is thus
increased by two. The reactant NaN(SiMe3)2 in the entire
transformation can be regarded as a reducing agent. In the
next step, the anilides are coupled with the second molecules
of 5 to give the unstable intermediates 12. Finally, the third
intramolecular 1,2-elimination takes place at the Si-N-N+-
O- moiety to generate the target azoxy arenes 13.
In a control experiment for the conversion of 1a f 1b,
we were able to identify N,N-bis(trimethylsilyl)aniline (bp
54 °C) as the byproduct by GC-mass spectroscopic tech-
niques. The N,N-bis(trimethylsilyl)aniline may come from
silylation of the anilide 11 (R ) H). Alternatively, diazonium
arenes 8 could decompose to give N2 and the corresponding
phenylium species. Trapping of this active species with NaN-
(SiMe3)2 in situ could also give N,N-bis(trimethylsilyl)aniline.
A key step for the formation of azoxy arenes 13 is the
coupling of anilides 11 with nitroarenes 5 (see Scheme 2).
We found two factors that retarded the coupling efficiency.
The first factor is the ortho effect. Our experimental results
showed that a nitrobenzene with an -OMe or -OEt at the
ortho position cannot be converted to the corresponding
azoxy arenes. In sharp contrast, nitroarenes with the same
substituents at a meta or para position were dimerized
successfully (see rows 2-5 of Table 1). The second factor
is the electronic effect from an electron-withdrawing sub-
stituent. Placement of a -NO2 group at the para or ortho
position in nitrobenzene made the conversion unfeasible.
These substituents in 11 would deactivate their nucleophi-
licity. On the other hand, substituents with electron-donating
ability (e.g., -OMe, -OEt, -SMe, and -NMe2) promoted
the coupling process.
genating step involving the Si-N-C-O- moiety (Scheme
3). Moreover, a related 1,2-elimination of R-trimethylsilyl
Scheme 3
For the same chemical transformation, the established
methods often give azoxy products in higher yield than those
by our method. However, some of them require a strong
reducing agent such as LiAlH4;23a some of them involve
heterogeneous reaction conditions such as the use of Zn22c
and Bi metals.21
In conclusion, sodium bis(trimethylsily)amide was devel-
oped as a deoxygenating agent for the coupling of nitroarenes
to azoxy arenes. This newly developed reaction proceeded
N-oxide, Si-C-N-O-, has also been developed as the key
step in monodeoxygenations of nitroalkanes, nitrones, and
heterocyclic N-oxides.27,28 These intramolecular 1,2-elimina-
tions and the Peterson olefination29,30 (involving Si-C-C-
(26) Kru¨ger, C.; Rochow, E. G.; Wannagat, U. Chem. Ber. 1963, 96,
2132-2137.
(27) Hwu, J. R.; Tseng, W. N.; Patel, H. V.; Wong, F. F.; Horng, D.-N.;
Liaw, B. R.; Lin, L. C. J. Org. Chem. 1999, 64, 2211-2218.
(28) Hwu, J. R.; Wetzel, J. M. J. Org. Chem. 1985, 50, 400-402.
(29) Hudrlik, P. F.; Gebreselassie, P.; Tafesse, L.; Hudrlik, A. M.
Tetrahedron Lett. 2003, 44, 3409-3412.
(30) van Staden, L. F.; Gravestock, D.; Ager, D. J. Chem. Soc. ReV.
2002, 31, 195-200.
(31) Wiberg, N.; Pracht, H. J. Chem. Ber. 1972, 105, 1377-1387.
Org. Lett., Vol. 7, No. 15, 2005
3213

in a sealed tube at 150 °C. The entire process involved three
deoxygenating steps, during which the silyl groups removed
oxygen atoms from the intermediates through intramolecular
1,2-eliminations.
Supporting Information Available: Synthetic and ex-
perimental procedures, analytical data, and NMR spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. For financial support, we thank the
National Science Council of Republic of China.
OL050924X
3214
Org. Lett., Vol. 7, No. 15, 2005