Selective reduction of nitro-compounds to primary amines by nickel-catalyzed hydrosilylative reduction

Article abstract of DOI:10.1039/c5ra17731f

Ni(acac)₂ and PMHS were found to be an excellent catalytic system for the chemoselective transfer hydrogenation of nitro-compounds to primary amines. Under mild conditions a series of nitro-compounds containing a variety of sensitive functional groups including aldehydes, esters, cyano, and nitrine were reduced to their corresponding amines in good to excellent yields with no byproduct.

Full text of DOI:10.1039/c5ra17731f

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: X. Wang, Z. Quan
and S. Sun, RSC Adv., 2015, DOI: 10.1039/C5RA17731F.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 5
RSC Advances
View Article Online
DOI: 10.1039/C5RA17731F
Selective Reduction of Nitro-Compounds to Primary Amines by Nickel-Catalyzed
Hydrosilylative reduction
Shuai Sun, Zheng-Jun Quan, and Xi-Cun Wang
Unprecedentedly high
Chemoselectivity: The
tolerance of many kinds of
functional groups such as
aryl-chloride, aryl-bromide,
alkene, alkynyl, ester, ether,
oxhydryl, carboxylic acid,
cyanogroup, nitrine, carbonyl,
acyl, thioether and some
heterocycle groups was studied
for the reduction of
nitro-compounds.

Please do not adjust margins
RSC Advances
Page 2 of 5
View Article Online
DOI: 10.1039/C5RA17731F
Journal Name
COMMUNICATION
Selective Reduction of Nitro-Compounds to Primary Amines by
Nickel-Catalyzed Hydrosilylative reduction
Received 00th January 20xx,
Accepted 00th January 20xx
Shuai Sun,a Zhengjun Quan*a, and Xicun Wang*a
DOI: 10.1039/x0xx00000x
www.rsc.org/catalysis
Ni(acac)2 and PMHS were found to be excellent catalytic system demonstrated harmful since they generate a dangerous and toxic
for the chemoselective transfer hydrogenation of nitro- SiH4 gas. As a consequence, siloxanes having Si-O-Si bridge are
compounds to primary amines. Under mild conditions. A series of considered as being a good alternative to silanes. Indeed, PMHS
nitro-compounds containing a variety of sensitive functional (polymethylhydrosiloxane),
a 40 units polymer, and TMDS
groups including aldehydes, esters, cyano, and nitrine were (tetramethyldisiloxane) are safer since they are not known to
reduced to their corresponding amines in good to excellent yields release this dangerous gas. Besides, Nagashima has reported that
with no byproduct.
siloxanes having Si-O-Si bridge like PMHS and TMDS could show
greater efficiency with their “dual Si-H effect”, in which two
proximate Si-H groups cooperatively could accelerate the reaction.9
When associated with different metals, silanes and siloxanes can
selectively reduce many reducible functional groups including nitro
group. For example, Fernandes has reported a catalytic systems
PhMe2SiH/ReIO2(PPh3)2 (5 mol %) and PhMe2SiH/ReOCl3(PPh3)2 (5
mol %) selectively reduced a series of aromatic nitro-compounds at
refluxing temperature.10 Lykakis has described a nitro-reduction
method using Au nanoparticles catalysts with silanes at low catalyst
loading (0.5-1 mol %).11 Lemaire has also reported a hydrosilation
system using iron catalysts. Although iron is a good alternative to
noble metals, the chemoselectivity was not very good, and the
tedious reaction time (24-48 h) was hard to accept.12 Herein, we
reported a convenient and efficient reduction of nitro-compounds
with PMHS. After the exploratory study on the choice of the metal
catalysts, nickel emerged as an ideal candidate. And we also tried
many kinds of substrates with different functional groups to prove
its chemoselectivity (scheme 1).
Amines are useful intermediates in the preparation of dyes,
pharmaceuticals, and agricultural chemicals and can be easily
obtained by the reduction of aromatic nitro-compounds.1 Among
the numerous available methodologies, reductions via
hydrogenation with noble metal-based catalysts (Pd,2 Ru,3 Pt,4 etc.),
hydrazine hydrate/catalysts (Co,5 Fe,6 etc.), methanol/catalysts (Pd,7
Zn,8 etc.) or under transfer hydrogenation conditions are largely
employed (Scheme 1). However, these conventional methods for
nitro reduction not only involve environmentally harmful
stoichiometric reducing agents and stringent conditions such as
high pressure and temperature but also may suffer from the use of
hazardous reagents (e.g., hydrazine). Significantly, most of these
methods lack the desired chemoselectivity over other functional
groups that are often present in the substrates such as alkene,
halide and nitrile. In addition, reduction of nitro-compounds often
stops at an intermediate stage, yielding hydroxylamine, hydrazines,
and azoarenes. Due to the high importance of selective reduction of
nitro-compounds, the search for alternative efficient and highly
chemo- and regioselective methods remains an important target in
organic synthesis.
Over the last decades, silanes have appeared to be new potential
reducing agents because of their special advantages (mild
conditions, high chemoselectivity and easy workup) when
associated with metals. Unfortunately, several silanes have been
a.Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of
Education, China. Gansu Key Laboratory of Polymer Materials, College of
Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou,
Gansu 730070, P. R. China.
Scheme 1. Different Processes for the Reduction of Nitro-Compounds
Initially, we studied the reduction of the test substrate
nitrobenzene 1a catalyzed by metal catalysts in the presence of
PMHS as the reductant in DMF at 100 °C for 12 h (Table 1). Among
E-mail: quanzhengjun@hotmail.com, wangxicun@nwnu.edu.cn
†Electronic
Supplementary
Information
(ESI)
available.
See
DOI:
10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

PPlelaesaeseddoonnoot tadadjujuststmmaragrigninss
Page 3 of 5
RSC Advances
COMMUNICATION
Journal Name
10
Ni(acac)2
PMHS
(1.5)
DMF
100
12View Ar7ti2cle Online
the tested metal catalysts, the active catalysts were Fe(acac)3 and
Ni(acac)2, however, no reaction was found with Zn(OAc)2, NiCl2,
NiCl2(PPh3)2, FeCl3 or Fe(OAc)2 (Table 1, entries 1-7). Other silanes
were examined in combination with PMHS but resulted in lower
yields of the reduction product 2a. TMDS as an “dual Si-H effect”
siloxane was tested with Ni(acac)2, but the reaction occurred with
lower yield of 2a (Table 1, entry 8). Besides, the inefficiency of
EtO3SiH (single “Si-H”) was proved when it was used as the
reductant in this reaction (Table 1, entry 9).
DOI: 10.1039/C5RA17731F
11
12
Ni(acac)2
Ni(acac)2
PMHS (2)
DMF
DMF
100
100
12
3
72
71
PMHS
(1.5)
13
14
15
16
17
-
PMHS
(1.5)
DMF
100
60
3
3
3
3
3
3
3
3
3
3
3
N.R.
32
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
PMHS
(1.5)
methano
l
We then tried to control reaction time and the amount of PMHS
in order to find out the best reaction condition. Interestingly, by
adjusting the amount of PMHS to 1.5 and 2 equiv, respectively, full
conversion of nitrobenzene 1a was achieved affording aniline 2a in
both 72% yield (Table 1, entries 10 and 11). Decreasing the reaction
time markedly to 3 h, the yield could still be 71% (Table 1, entry 12).
As expected, in the absence of any metal-catalyst, none 2a was
formed (Table 1, entry 13).
PMHS
(1.5)
ethanol
THF
60
36
PMHS
(1.5)
60
46
PMHS
(1.5)
CH2Cl2
CHCl3
40
< 20
< 20
48
In consideration of the importance and influence of solvents and
temperature, the searches for the appropriate solvent and 18
temperature were also summarized (Table 1, entries 14-23). When
the reaction was conducted in MeOH, EtOH, toluene, CHCl3, CH2Cl2,
PMHS
(1.5)
40
19
PMHS
(1.5)
toluene
xylene
DMSO
dioxane
dioxane
100
100
100
100
80
THF or DMSO, xylene at refluxing or 100 °C led to lower reactivity
(Table 1, entries 14-21). Gratefully, by using dioxane, full conversion
of 1a was achieved affording 2a in 84% or 81% yield at 100 or 80 °C,
respectively (Table 1, entries 22 and 23).
20
21
22
23
a
PMHS
(1.5)
54
PMHS
(1.5)
68
Table 1. Screening of the Conditions for the Catalyzed Reduction of
Nitrobenzene to Anilinea
PMHS
(1.5)
84
PMHS
(1.5)
81
b
Reaction conditions: nitrobenzene (1.0 mmol), solvent (3 mL). Isolated
c
yield (all of the products were purified by column chromatography). No
Entr
y
Catalyst (10 Reductant
Solvent
Temp.
°C
Time
(h)
Yieldb
(%)
reaction.
mol/%)
(equiv.)
After these studies on the nitrobenzene 1a, the best conditions
(Table 1, entry 23) were applied on different nitro-compounds
(Scheme 2). As depicted in Scheme 2, the reduction of aromatic
nitro-compounds was selective and efficient. When nitroarenes
were substituted with bromine or chlorine (Scheme 2, 2b-2e), no
dehalogenated product was observed in comparison to
hydrogenation in classical conditions with palladium on charcoal.13
Moreover, when it with other functionalities such as ether (Scheme
2, 2n and 2o), hydroxy (Scheme 2, 2j and 2k), carboxylic group
(Scheme 2, 2i and 2m), alkenyl (Scheme 2, 2s), amide (Scheme 2, 2t)
or disulfide (Scheme 2, 2u), the reaction showed high selectivity and
only the nitro group was reduced to the corresponding amines in
moderate yield with no byproduct.
1
2
3
4
5
6
7
8
FeCl3
PMHS (1)
PMHS (1)
PMHS (1)
PMHS (1)
PMHS (1)
PMHS (1)
PMHS (1)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
100
100
100
100
100
100
100
100
12
12
12
12
12
12
12
3
N.R.c
N.R.
48
Fe(OAc)2
Fe(acac)3
Zn(OAc)2
NiCl2
N.R.
N.R.
N.R.
65
NiCl2(PPh3)2
Ni(acac)2
Ni(acac)2
TMDS
(1.5)
66
12
10
Although Fe(acac)3 and ReIO2(PPh3)2 have been proved as
effective catalysts, the chemoselectivity of carbonyl group did not
realize. To our surprise, herein, we found the atalytic system from
9
Ni(acac)2
EtO3SiH (3) DMF
100
3
trace
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 4 of 5
COMMUNICATION
Journal Name
Ni(acac)2 and PMHS is
a
more efficient catalysts with high different functionalized DHPMs were reduced undeVrietwhAerticoleptOinmlinael
DOI: 10.1039/C5RA17731F
chemoselectivity of several kinds of functional groups besides reaction conditions. According to this work, the tolerance of
carbonyl group (Scheme 2, 2r). Nevertheless the reaction time was thiocarbonyl, cyano, ester, ether, nitrine, and heterocycle groups
very important for the reduction of p-nitrobenzaldehyde, or it would such as morpholine, pyrimidone was very fine.
form a series of amines in extending time.
According to the high utility of this protocol as mentioned above,
we considered applying it to the reduction of nitroalkene derivatives.
Thankfully, it could be reduced to the corresponding enamines with
no byproduct (Scheme 2, 2v-2z). In this way, strong reducing agents,
noble catalysts and tedious procedures were avoided as well, and it
might be a good alternative to some non-reducing methods such as
the dehydration of hydroxylamines.
After that, we were interested to test the reduction with two
nitro groups. In the case of the 1,4-dinitrobenzene, only one nitro
was reduced to amine with 1.2 eq PMHS in 3 h (Scheme 2, 2p). If
the amount of PMHS was elevated to 4 equivalent, diamine was
obtained in 83% yield within 5 h (Scheme 2, 2q). However, we could
only obtain the double nitro reduced product when uses 1,2-bis(4-
nitrophenyl)disulfane and 1-nitro-3-(2-nitrovinyl)benzene as
substrates, no matter how much the reductant was used (Scheme 2,
2u and 2z).
Scheme 3. Chemoselective reduction of DHPMs with PMHS catalyzed by Ni(acac)2
Conclusions
In summary, we have demonstrated that the catalytic system
PMHS/Ni(acac)2 is an efficient and convenient protocol for the
reduction of nitro-compounds. Compared with the conventional
methods, this reduction protocol provides an unprecedentedly high
chemoselectivity toward aryl-chloride, aryl-bromide, alkene, alkynyl,
ester, ether, oxhydryl, carboxylic acid, cyanogroup, nitrine, carbonyl,
acyl, thioether and some heterocycle groups. Besides, no reduction
byproduct was detected during the reaction process.
In addition, the high stability of Ni(acac)2 and PMHS toward air
and moisture makes the reaction be conducted under air
atmosphere. Other outstanding advantages of this protocol include
the use of PMHS, given that PMHS is produced as a byproduct in
silicone industry on a large scale. Ni(acac)2 is commercially available
and the reaction only requires a couple of hours to go to
completion, and all of these features make this newly developed
conditions attractive for synthetic chemists.
Scheme 2. Chemoselective Reduction of Nitro-Compounds with PMHS Catalyzed
by Ni(acac)2
Based on the wide ranging biological activity of 3,4-
dihydropyrimidinones and its utilization as an important precursor
in the synthesis of pyrimidine bases,14 as well as our continuous
interest in the synthesis of novel pyrimidine derivatives,15 we would
like to further explore this protocol to the reduction of the
Acknowledgements
We are thankful for the financial support from the NSFC (Nos.
derivatives of 3,4-dihydropyrimidin-2(1H)-one (DHPM) (Scheme 3). 21362032, 21362031 and 21562036), and Gansu Provincial
It was also efficiency (higher isolate yield in 6 hours), and high Department of Finance.
chemoselectivity of several functional groups performed
unexpectedly. As depicted in Scheme 3, only the nitro group in
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

PPlelaesaeseddoonnoot tadadjujuststmmaragrigninss
Page 5 of 5
RSC Advances
COMMUNICATION
Journal Name
27 X. H. Li, Y. Y. Cai, L. H. Gong, W. Fu, K. X. Wang, H. VLi.ewBaAort,icXle.OWnlienie,
J. S. Chen, Chem. Eur. J., 2014, 20, 16732.DOI: 10.1039/C5RA17731F
28 C. H. Tang, L. He, Y. M. Liu, Y. Cao, H. Y. He, K. N. Fan, Chem. Eur.
J., 2011, 17, 7172.
29 R. G. Noronha, C. C. Romao, A. C. Fernandes, Org. Lett., 2005, 7,
5087.
30 S. Das, D. Addis, S. Zhou, K. Junge, M. Beller, J. Am. Chem. Soc.,
2010, 132, 1770.
31 S. Park, M. Brookhart, J. Am. Chem. Soc., 2012, 134, 640.
Notes and references
1
(a) J. S. M. Samec, J.-E. Backvall, P. G. Andersson, P. Brandt,
Chem. Soc. Rev., 2006, 35, 237; (b) A. M. Tafesh, J. Weiguny,
Chem. Rev., 1996, 96, 2035; (c) K. J. Nomura, Mol. Catal. A:
Chem., 1998, 130, 1; (d) L. He, L. C. Wang, H. Sun, J. Ni, Y. Cao, H.
Y. He, K. N. Fan, Angew. Chem., Int. Ed., 2009, 48, 9538; (e) N.
Zhang, Y. J. Xu, Chem. Mater., 2013, 25, 1979; (f) Y. Zhang, N.
Zhang, Z. R. Tang, Y. J. Xu, ACS Sustainable Chem. Eng., 2013, 1,
1258.
2
3
X. Y. Pan, Y. J. Xu, ACS Appl. Mater. Interfaces., 2014, 6, 1879.
P. Tomkins, E. Gebauer-Henke, W. Leitner, T. E. Muller, ACS
Catal., 2015, 5, 203.
4
5
M. J. Climent, A. Corma, S. Iborra, L. Martí, ACS Catal., 2015, 5,
157.
R. K. Rai, A. Mahata, S. Mukhopadhyay, S. Gupta, P. Z. Li, K. T.
Nguyen, Y. L. Zhao, B. Pathak, S. K. Singh, Inorg. Chem., 2014, 53,
2904.
6
7
D. Cantillo, M. M. Moghaddam, C. O. Kappe, J. Org. Chem., 2013,
78, 4530.
N. Arai, N. Onodera, A. Dekita, J. Hori, T. Ohkuma, Tetrahedron
Lett., 2015, 56, 3913.
8
9
J. W. Dong, B. Jin, P. P. Sun, Org. Lett., 2014, 16, 4540.
S. Hanada, E. Tsutsumi, Y. Motoyama, H. Nagashima, J. Am.
Chem. Soc., 2009, 131, 15032.
10 R. G. Noronha, C. C. Romao, A. C. Fernandes, J. Org. Chem., 2009,
74, 6960.
11 S. Fountoulaki, V. Daikopoulou, P. L. Gkizis, I. Tamiolakis, G. S.
Armatas, L. N. Lykakis, ACS Catal., 2014, 4, 3504.
12 L. Pehlivan, E. Metay, S. Laval, W. Dayoub, P. Demonchaux, G.
Mignani, M. Lemaire, Tetrahedron., 2011, 67, 1971.
13 A. M. Tafesh, J. Weiguny, Chem. Rev., 1996, 96, 2035.
14 (a) C. O. Kappe, Tetrahedron, 1993, 49, 6937; (b) C. O. Kappe,
Acc. Chem. Res., 2000, 33, 879; (c) C. O. Kappe, Eur. J. Med.
Chem., 2000, 35, 1043. (d) C. O. Kappe, A. Stadler, Org. React.,
2004, 63, 1; (e) D. Dallinger, A. Stadler, C. O. Kappe, Pure Appl.
Chem., 2004, 76, 1017; (f) L. Z. Gong, X. H. Chen, X. Y. Xu,
Chem.-Eur. J., 2007, 13, 8920; (g) M. A. Kolosov, V. D. Orlov, Mol.
Diversity., 2009, 13, 5; (h) Z. J. Quan, Z. Zhang, Y. X. Da, X. C.
Wang, Chin. J. Org. Chem., 2009, 29, 876 (In Chinese).
15 (a) X. C. Wang, Z. J. Quan, J. K. Wang, Z. Zhang, M. G. Wang,
Bioorg. Med. Chem. Lett., 2006, 16, 4592; (b) Z. J. Quan, F. Q.
Jing, Z. Zhang, Y. X. Da, X. C. Wang, Eur. J. Org. Chem., 2013, 31,
7175; (c) Z. J. Quan, Y. Lv, Z. J. Wang, Z. Zhang, Y. X. Da, X. C.
Wang, Tetrahedron Lett., 2013, 54, 1884; (d) Z. J. Quan, Y. Lv, F.
Q. Jing, X. D. Jia, X. C. Wang, Adv. Synth. Catal., 2014, 356, 325;
(e) B. X. Du, Z. J. Quan, Y. X. Da, Z. Zhang, X. C. Wang, Adv. Synth.
Catal., 2015, 357, 1270.
16 M. Igarashi, T. Fuchikami, Tetrahedron Lett., 2001, 42, 1945.
17 J. Pal, C. Mondal, A. K. Sasmal, M. Ganguly, Y. Negishi, T. Pal,
ACS Appl. Mater. Interfaces., 2014, 6, 9173.
18 V. Zimmermann, F. Avemaria, S. Bra, J. Comb. Chem., 2007, 9,
200.
19 A. J. Wang, H. Y. Cheng, B. Liang, N. Q. Ren, D. Cui, N. Lin, B. H.
Kim, K. R. Environ, Sci. Technol., 2011, 45, 10186.
20 J. C. Anderson, A. J. Blake, P. J. Koovits, G. J. Stepney, J. Org.
Chem., 2012, 77, 4711.
21 A. Saha, B. Ranu, J. Org. Chem., 2008, 73, 6867.
22 D. M. Dotzauer, S. Bhattacharjee, Y. Wen, M. L. Bruening,
Langmuir, 2009, 25, 1865.
23 T. Schabel, C. Belger, B. Plietker, Org. Lett., 2013, 15, 2858.
24 R. B. Nasir Baig, R. S. Varma, ACS Sustainable Chem. Eng., 2014,
2, 2155.
25 R. Mallampati, S. Valiyaveettil, ACS Sustainable Chem. Eng.,
2014, 2, 855.
26 J. Kim, C. Park, T. Ok, W. So, M. Jo, M. Seo, Y. Kim, J-H. Sohn, Y.
Park, M. K. Ju, J. Kim, S-J. Han, T-H. Kim, J. Cechetto, J. Namc, P.
Sommer, Z. No, Bioorg. Med. Chem. Lett., 2012, 22, 2119.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Please do not adjust margins