Selective synthesis of N-Alkyl hydroxylamines by hydrogenation of nitroalkanes using supported palladium catalysts

Article abstract of DOI:10.1002/cssc.201000137

The selective hydrogenation of nitroalkanes to the corresponding N-alkyl hydroxylamines is achieved at room temperature with excellent yields (up to 98 %), by using common supported palladium catalysts. The reaction temperature is key to the highly selective formation of the hydroxylamines, which proceeds smoothly in a H₂ atmosphere without additives. The catalyst can be recycled up to five times.

Full text of DOI:10.1002/cssc.201000137

DOI: 10.1002/cssc.201000137
Selective Synthesis of N-Alkyl Hydroxylamines by Hydrogenation of
Nitroalkanes using Supported Palladium Catalysts
Yasumasa Takenaka,*[a] Takahiro Kiyosu,[b] Jun-Chul Choi,[a] Toshiyasu Sakakura,[a] and Hiroyuki Yasuda*[a]
Organic hydroxylamines are useful compounds in a wide range
of applications, including intermediates in the synthesis of bio-
logically active substances,[1] reagents for organic synthesis,[2]
raw materials for polymerization inhibitors,[3] and release
agents for photoresists.[4] A number of different synthetic
routes to hydroxylamines have been reported. Examples in-
clude the alkylation of hydroxylamines;[5] the stoichiometric
(with zinc, tin, samarium diiodide, boron hydrides, silicon hy-
drides, or hydrazine),[6] electrochemical,[7] and electron-transfer
reduction of nitro compounds;[8] and biosynthesis by using
bakers’ yeast.[9] However, these processes are not necessarily
environmentally benign and cost-efficient. In addition, some of
these routes have disadvantages when they are scaled up and/
or applied industrially. Thus, the development of methods that
are more efficient, greener, and more practical is desirable.
Because H2 is a clean and relatively cheap reductant, the se-
lective catalytic hydrogenation of nitro compounds is an ideal
process for the production of hydroxylamines. Although sever-
al groups have reported the synthesis of N-aryl hydroxylamines
through the hydrogenation of nitroaromatics,[10] the yields and
selectivities were insufficient because suppressing overhydro-
genation was difficult. We have recently reported that by using
supported platinum catalysts and small amounts of additives,
N-aryl hydroxylamines can be successfully produced in high
yields (up to 99%) under atmospheric pressure and tempera-
ture.[11] Unfortunately, this method cannot be applied to the
synthesis of aliphatic hydroxylamines. More recently, Lu et al.
have reported that N-aryl hydroxylamines can be selectively
formed via additive-free hydrogenation in THF using carbon-
supported platinum colloid catalysts.[12] However, the sub-
strates for this reaction were limited to aromatic nitro com-
pounds with an electron-withdrawing substituent, such as o-,
m-, p-dinitrobenzene and 1-(4-nitrophenyl)ethanone.
quire the separation of these additives and/or the purification
of the hydroxylamines. Herein, we report that by using sup-
ported palladium catalysts, genuine N-alkyl hydroxylamines (R-
NHOH) can be obtained in high yields (up to 98%) through hy-
drogenation of nitroalkanes (R-NO2) without the need for selec-
tivity-improving additives.
Adding small amounts of dimethyl sulfoxide (DMSO) and
amines, which serve as inhibitor and promoter, respectively, to
the reaction mixture during the selective hydrogenation of ni-
troaromatics over supported platinum catalysts such as Pt/SiO2
realizes the fast and highly selective formation of the corre-
sponding N-aryl hydroxylamines.[11] In contrast, a Pd/SiO2 cata-
lyst was found to be nonselective for the hydrogenation of ni-
trobenzene, even in the presence of DMSO and amine; the
major product was aniline.[11] Thus, we initially attempted the
hydrogenation of 1-nitrohexane (nHex-NO2) by using a com-
mercial Pt/SiO2 catalyst. The hydrogenation in isopropyl alcohol
(IPA) under a H2 pressure of 1 bar at room temperature exclu-
sively afforded 1-hexylamine (nHex-NH2) (Table 1, entry 1). How-
n
ever, in the case of Hex-NO2, adding DMSO and triethylamine
was ineffective for the selective formation of N-hexyl hydroxyl-
amine (nHex-NHOH). On the other hand, when Pt/SiO2 was re-
n
placed with a commercial Pd/SiO2 catalyst, Hex-NO2 was selec-
tively and smoothly hydrogenated to give nHex-NHOH in a
high yield (90%) without additives. Likewise, the two types of
palladium on silica (Pd/SIO-1 and Pd/SIO-2) catalysts prepared
in this study as well as commercial Pd/C and Pd/Al2O3 catalysts
n
n
afforded Hex-NHOH in excellent yields (up to 96%). Hex-NO2
was also hydrogenated selectively by using palladium acetate
as a homogeneous catalyst, but palladium acetate formed pal-
Table 1. Selective hydrogenation of 1-nitrohexane
For aliphatic nitro compounds, some patents have claimed
that for the hydrogenation of nitroalkanes over supported palla-
dium catalysts, the addition of oxalic acid,[13a] sulfuric acid,[13b,c,e]
metal cations such as iron, nickel, and cobalt ions,[13d] or ethyle-
nediaminetetraacetic acid (EDTA)[13f] effectively increases the
yield of N-alkyl hydroxylamines. However, these processes re-
Entry
Catalyst
t
[h]
Conv.[b]
[%]
Yield 1[b]
[%]
Yield 2[b]
[%]
Select.[b]
[%]
1
Pt/SiO2
Pt/SiO2
Pt/SiO2
Pd/SiO2
Pd/SIO-1
Pd/SIO-2
Pd/SIO-2
Pd/C
6
24
24
2
92
0
0
90
>99
64
>99
>99
>99
33
0
0
0
90
94
62
92
0
0
0
0
0
2[c]
3[d]
4
trace
>99
94
97
96
94
94
94
[a] Dr. Y. Takenaka, Dr. J.-C. Choi, Prof. T. Sakakura, Prof. H. Yasuda
National Institute of Advanced Industrial Science and Technology (AIST)
Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565 (Japan)
Fax: (+81)29-861-4580
5
6
7
8
9
10[f]
2
1
2
2
2
2
6
2
4
6
6
2
96 (95[e]
94
)
E-mail: takenaka-yasumasa@aist.go.jp
Pd/Al2O3
Pd(OAc)2
94
31
h.yasuda@aist.go.jp
[b] T. Kiyosu
[a] 2 mmol nHex-NO2, 20 mg catalyst, 2 mL catalyst. [b] Determined by
1H NMR with 1,3,5-trimethyl benzene as an internal standard. [c] 0.030 mL
DMSO. [d] 0.030 mL DMSO, 0.010 mL triethylamine. [e] Isolated yield.
[f] 0.5 mol% Pd(OAc)2.
Wako Pure Chemical Industries, Ltd.
1633 Matoba, Kawagoe, Saitama 350-1101 (Japan)
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cssc.201000137.
1166
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ChemSusChem 2010, 3, 1166 – 1168

ladium black during the reaction, resulting in giving nHex-
NHOH in a low yield (31%; Table 1, entry 10).
primary R-NO2 compounds such as nitroethane and 1-nitropro-
pane were hydrogenated using the Pd/SIO-2 catalyst into the
corresponding R-NHOH compounds in yields greater than 90%
(Table 4, entries 1 and 2). Sterically hindered R-NO2 substrates
such as 2-nitropropane (nitro-iso-propane), nitro-cyclo-pentane,
and 2-methyl-2-nitropropane (nitro-tert-butane) were also hy-
drogenated selectively to the corresponding R-NHOH ana-
logues, but a longer reaction time was necessary.
We then investigated the reaction conditions using the Pd/
SIO-2 catalyst. The hydrogenation proceeded significantly
faster when the H2 pressure was increased to 2 bar, while a
high nHex-NHOH selectivity was maintained (97%; Table 2,
entry 1). Further increasing the H2 pressure slightly decreased
the selectivity (87%). On the other hand, when the reaction
temperature was increased from room temperature to 508C,
n
the rate of hydrogenation of Hex-NO2 increased, but further
hydrogenation of nHex-NHOH was accelerated, which de-
creased the nHex-NHOH yield to 49% (Table 2, entry 3). Sherwin
et al. performed the hydrogenation of 2-nitropropane with Pd/
Al2O3 catalysts under hydrogen pressures of 2–5 bar at 50–
708C in the absence of a promoter (i.e., EDTA), and reported a
medium N-isopropyl hydroxylamine selectivity (56–89%),[13f]
consistent with our results. Hence, these observations demon-
strate that controlling the reaction temperature is key to ach-
Table 4. Selective hydrogenation of nitroalkanes
[b]
Entry
R
t
Conv.[b] Yield R-NHOH[b] Yield R-NH2
Select.[b]
[%]
[h] [%]
[%]
[%]
1
2
3
4
5
Et
1-Pr
2-Pr
2
2
2
>99
>99
98
91
97
98
98
89
9
3
91
97
>99
98
trace
cyclo-Pen 12 >99
tert-Bu 30 98
2
9
n
ieving a high selectivity in the formation of Hex-NHOH.
91
[a] 2 mmol R-NO2, 20 mg Pd/SIO-2, 2 mL IPA. [b] Determined by 1H NMR
with 1,3,5-trimethyl benzene as an internal standard.
Table 2. Effect of reaction conditions.[a]
Entry
P
T
t
Conv.[b] Yield 1[b] Yield 2[b] Select.[b]
Finally, we investigated the recyclability of the Pd/SIO-2 cata-
[bar] [8C] [min] [%]
[%]
[%]
[%]
n
lyst in the selective hydrogenation of Hex-NO2. After each run,
1
2
3
2
5
1
RT
RT
50
30
24
30
97
88
83
94 (90[c])
77
3
11
34
97
87
59
the catalyst was separated by filtration, washed with IPA, dried
in vacuum at room temperature, and pretreated in a H2 stream
at 2008C for 1 h. The catalyst was then reused in a subsequent
run. By using this process, the recovered catalyst could be re-
49
[a] 2 mmol nHex-NO2, 20 mg Pd/SIO-2, 2 mL IPA. [b] Determined by
1H NMR with 1,3,5-trimethyl benzene as an internal standard. [c] Isolated
yield.
n
cycled at least five times without a loss in the yield of Hex-
NHOH (Table 5). When comparing the catalytic activity of the
Pd/SIO-2 in the sixth recycling experiment to that of the fresh
Pd/SIO-2, no significant deactivation can be observed (Table 5,
entry 7 vs. Table 1, entry 6). In addition, when ICP–AES meas-
urements of the filtrates obtained from the runs in entries 1
and 6 in Table 5 indicated that the palladium content was
below the detection limit (0.01 ppm). These results demon-
strate that Pd/SIO-2 is a sufficiently stable heterogeneous cata-
lyst for the selective hydrogenation of R-NO2.
We then examined the effect of solvent. Table 3 compares
n
the reaction times required for the conversion of Hex-NO2 to
exceed 95%. Alcoholic solvents such as IPA and ethanol pro-
n
duced Hex-NHOH in high yields within a short reaction time
(105 min) (Table 3, entries 1 and 2). Although employing low-
polarity solvents such as toluene or dichloromethane required
n
somewhat longer reaction times, Hex-NHOH was produced se-
lectively.
In summary, we have developed a highly efficient synthetic
method for preparing R-NHOH by selectively hydrogenation of
Table 3. Effect of solvent.[a]
Entry
Solvent
t
Conv.[b]
[%]
Yield 1[b]
[%]]
Yield 2[b]
[%]
Select.[b]
[%]
Table 5. Catalyst recycling in the selective hydrogenation of 1-nitrohexa-
ne.[a]
[min]
1
2
3
4
5
6
IPA
EtOH
Et2O
THF
Toluene
CH2Cl2
105
105
135
210
210
240
98
95
99
99
99
98
95
93
96
95
95
92
3
2
3
4
4
6
97
98
97
96
96
94
Entry
Catalyst
t
[h]
Conv.[b]
[%]
Yield 1[b]
Yield 2[b]
[%]
Select.[b]
[%]
[%]]
1c]
2
3
4
Pd/SIO-2
2
2
2
2
2
2
1
>99
>99
>99
>99
>99
>99
59
96
98
98
97
98
98
58
4
2
2
3
2
2
1
96
98
98
97
98
98
98
1
2
3
4
st reuse
nd reuse
rd reuse
th reuse
[a] 2 mmol nHex-NO2, 20 mg Pd/SIO-2, 2mL solvent. [b] Determined by
1H NMR with 1,3,5-trimethyl benzene as an internal standard.
5
6[c]
7
5th reuse
th reuse
6
1
The synthesis of R-NHOH through selective hydrogenation
using palladium on silica catalysts is applicable to various R-
[a] 2 mmol nHex-NO2, 20 mg catalyst, 2 mL IPA. [b] Determined by HNMR
with 1,3,5-trimethyl benzene as an internal standard. [c] The palladium
content of the filtrates was measured by ICP–AES.
n
NO2 substrates, as summarized in Table 4. Similar to Hex-NO2,
ChemSusChem 2010, 3, 1166 – 1168
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemsuschem.org
1167

R-NO2 with supported palladium catalysts. This method has
the following advantageous and attractive aspects: (1) the se-
lective hydrogenation proceeds efficiently under an atmos-
pheric pressure of H2 at room temperature and does not re-
quire additives; (2) the hydrogenation method can be applied
to a wide range of R-NO2 substrates, and organic solvents; and
(3) the palladium on silica catalyst can be recycled at least five
times. The presented synthetic procedure towards R-NHOH
can be considered green and practical.
for Functional Materials” Project of the New Energy and Industrial
Technology Development Organization (NEDO), Japan.
Keywords: amines · heterogeneous catalysis · hydrogenation ·
nitrogen · palladium
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1
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Acknowledgements
Received: May 11, 2010
Revised: June 14, 2010
Published online on August 16, 2010
This research was financially supported by the of “Development
of Microspace and Nanospace Reaction Environment Technology
1168
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 2010, 3, 1166 – 1168