Catalytic oxidative synthesis of nitriles directly from primary alcohols and ammonia

Full text of DOI:10.1002/anie.200900418

Communications
DOI: 10.1002/anie.200900418
Heterogeneous Catalysis
Catalytic Oxidative Synthesis of Nitriles Directly from Primary
Alcohols and Ammonia**
Takamichi Oishi, Kazuya Yamaguchi, and Noritaka Mizuno*
Nitriles are a very important class of compounds in chemistry
as well as biology, and they are widely used in the production
of pharmaceuticals, agricultural chemicals, and fine chem-
lack of toxic waste (theoretically, only water is formed as a by-
product [Eq. (1)].
[
1]
icals. Aromatic nitriles can be synthesized by the Sandmeyer
reaction and gas-phase ammoxidation in laboratories and
We have recently reported the efficient aerobic oxidative
[
1]
[6a,b]
[6a,c]
industry, respectively. The nucleophilic substitution of alkyl
halides with a stoichiometric amount of hazardous inorganic
cyanides is a general procedure for the synthesis of alkylni-
triles and is frequently accompanied by the elimination of
hydrogen halides especially in the case of bulky alkyl
dehydrogenation of alcohols
and amines,
and the
[
6d]
catalytic oxygenation of amines to amides catalyzed by an
easily prepared supported ruthenium hydroxide catalyst,
Ru(OH) /Al O . During the course of our investigations, we
x
2
3
discovered that the liquid-phase aerobic oxidative synthesis of
nitriles directly from alcohols and ammonia can be realized in
[
1]
halides. Unsaturated nitriles can be synthesized by the
Wittig reaction of the corresponding aldehydes with cya-
[7]
the presence of the supported ruthenium hydroxide catalyst.
[1]
noalkyl phosphates. The above antiquated procedures often
produce large amounts of inorganic salts as waste, which is not
Various kinds of aromatic and heteroaromatic primary
alcohols can be converted into the corresponding nitriles in
high to excellent yields, and the observed catalysis is hetero-
[2]
desirable from the standpoint of green chemistry. Therefore,
the development of new environmentally friendly procedures
is very important. The transition-metal-catalyzed dehydration
of aldoximes or amides under neutral conditions is a good
[
8]
geneous.
Initially, various kinds of supported metal hydroxide
catalysts and ruthenium-based catalysts were applied to the
transformation of 2-naphthalenemethanol (1a) into 2-naph-
thonitrile (2a) in a solution of ammonia in THF (0.45m, NH3/
1a = 1.8) using air as an oxidant (Table 1). Among various
catalysts examined, Ru(OH) /Al O showed the highest
[
3]
candidate for green nitrile synthesis. Recently, excellent
[3]
examples for the catalytic dehydration have been reported.
An alternative approach to the synthesis of nitriles is the
[
4,5]
oxidative reaction directly from alcohols and ammonia.
x
2
3
The direct synthesis is very difficult, and reported procedures
require the use of stoichiometric amounts of reactive oxidants
catalytic activity and selectivity (Table 1, entry 1). Ruthenium
complexes such as [Ru(acac) ], [RuCl (PPh ) ], [{RuCl (p-
3
2
3
3
2
[
4a,b]
and reagents such as I ,
1,3-diiodo-5,5-dimethylhydantoin
cymene)} ], and [Ru (CO) ] were not effective for the
2 3 12
2
[
4a,c]
[4d]
[4e]
(
DIH),
NiSO /K S O /NaOH,
MnO /MgSO ,
and
present transformation (Table 1, entries 10–13). Similarly,
heterogeneous ruthenium catalysts such as Ru/C (Ru metal
4
2
2
8
2
4f]
4
[
(
Bu N) S O /Cu(HCO ) /Ni(HCO ) /KOH.
Therefore, if
4
2
2
8
2
2
2 2
3
+
the catalytic oxidative synthesis of nitriles directly from
alcohols and ammonia using molecular oxygen (or air) as the
sole oxidant could be realized, it would be a desirable
transformation because of its high atom efficiency and the
on activated carbon), RuHAP (Ru -exchanged hydroxyapa-
[
9]
tite), and RuO anhydrous (bulk oxide) did not show high
2
catalytic activity (Table 1, entries 6–8). Among the catalysts
examined, only Ru(OH) /Al O gave the desired nitrile 2a in
x
2
3
high yield. Under the present conditions, no reaction pro-
ceeded in the absence of the catalyst (Table 1, entry 15), or in
the presence of just Al O (Table 1, entry 14) or the catalyst
2
3
[
*] T. Oishi, Dr. K. Yamaguchi, Prof. Dr. N. Mizuno
Department of Applied Chemistry, School of Engineering
The University of Tokyo
precursor of RuCl ·nH O (Table 1, entry 9).
3
2
To verify whether the observed catalysis is derived from
solid Ru(OH) /Al O or leached ruthenium species, the
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
x
2
3
transformation of 1a into 2a was carried out under the
Fax: (+81)3-5841-7220
E-mail: tmizuno@mail.ecc.u-tokyo.ac.jp
conditions described in Table 1 and the Ru(OH) /Al O
x
2
3
Dr. K. Yamaguchi, Prof. Dr. N. Mizuno
Core Research for Evolutional Science and Technology (CREST)
catalyst was removed from the reaction mixture by filtration
at approximately 30% conversion of 1a. After removal of the
Ru(OH) /Al O catalyst, a solution of ammonia in THF
(
Japan) Science and Technology Agency
-1-8 Honcho, Kawaguchi, Saitama, 332-0012 (Japan)
**] This work was supported in part by the Global COE Program
Chemistry Innovation through Cooperation of Science and Engi-
neering), the Core Research for Evolutional Science and Technology
x
2
3
4
(1 mL, 0.45m) was added to the filtrate and the solution was
[
again heated at 1208C under 6 atmospheres of air. In this case,
no reaction proceeded. It was confirmed by inductively
coupled plasma atomic emission spectroscopy (ICP-AES)
that no ruthenium was in the filtrate (below 0.03%). All these
facts rule out any contribution to the observed catalysis from
ruthenium species that leached into the reaction solution, and
(
(
(
CREST) program of the Japan Science and Technology Agency
JST), and Grants-in-Aid for Scientific Research from Ministry of
Education, Culture, Sports, Science and Technology.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200900418.
[10]
the observed catalysis is intrinsically heterogeneous.
6
286
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 6286 –6288

Angewandte
Chemie
Table 1: Transformation of 2-naphthalenemethanol (1a) into 2-naphtho-
nitrile (2a).
Table 2: Scope of the Ru(OH) /Al O -catalyzed transformation of pri-
mary alcohols into nitriles.
x
2
t [h]
3
3
[
a]
[a]
[
b]
Entry
Substrate
Product
Yield [%]
1
1a
1b
1c
2a 96 (91)
[
b]
Entry
Catalyst
Yield [%]
2
a
3a
2
3
5
5
2b 72
2c 80
1
2
3
4
5
6
7
8
9
Ru(OH) /Al O
3
74
10
n.d.
n.d.
n.d.
22
17
29
1
5
2
30
11
n.d.
n.d.
n.d.
4
x
2
Au(OH) /Al O
x
2
3
Pd(OH) /Al O
x
2
3
Pt(OH) /Al O
3
x
2
Rh(OH) /Al O
3
x
2
4
1d
5
2d 85
Ru/C
RuHAP
4
RuO anhydrous
n.d.
n.d.
n.d.
2
2
5
6
7
1e
1 f
1g
5
5
6
2e 83
RuCl ·nH O
3
2
10
11
12
13
14
15
[Ru(acac)3]
[RuCl (PPh ) ]
2
3 3
2 f 92 (82)
2g 82
[{RuCl (p-cymene)} ]
2
6
3
2
n.d.
2
2
[Ru (CO) ]
n.d.
n.d.
n.d.
3
12
[
c]
2
Al O3
none
[
0
1
a] Reaction conditions: 1a (0.5 mmol), catalyst (metal: 0.05 mmol),
8
9
1h
1i
5
5
2h 82
2i 76
.45m solution of ammonia in THF (2 mL, NH /1a=1.8), air (6 atm),
3
1
208C, 1 h. [b] Yields were determined by GC and H NMR analyses.
n.d.=not detected (<1%). [c] 200 mg. acac=acetylacetonate.
1
0
1j
1k
1l
7
7
6
2j 80
2k 67
2l 81
Next, the scope of the present Ru(OH) /Al O -catalyzed
x
2
3
reaction with regard to various kinds of structurally diverse
primary alcohols was examined. Ru(OH) /Al O showed high
11
x
2
3
catalytic activities for the transformation of benzylic, allylic,
and heteroatom-containing alcohols, as summarized in
Table 2. The transformation of benzylic alcohols 1a–1g,
which contain electron-donating as well as electron-with-
drawing substituents, efficiently proceeded to afford the
corresponding aromatic nitriles in high yields (Table 2,
entries 1–7). In the transformation of allylic alcohols 1h and
12
[
c]
13
1m 12
2m 65
[
0
a] Reaction conditions: primary alcohol (0.5 mmol), catalyst (Ru:
.05 mmol), 0.45m THF solution of ammonia (2 mL, NH /alcohol=
3
1
i, the corresponding unsaturated nitriles could be obtained
1.8), air (6 atm), 1208C. [b] Yields were determined by GC and
H NMR analyses (also see Table S1 in the Supporting Information).
Values in the parentheses are the yields of the isolated products.
1
without isomerization, hydrogenation, and hydration of the
double bonds (Table 2, entries 8 and 9). Also, heteroatom-
containing alcohols 1j–1m were converted into the corre-
sponding nitriles in high yields (Table 2, entries 10–13).
Additionally, the present Ru(OH) /Al O catalyst could be
[c] 1308C.
x
2
3
employed for the one-pot synthesis of amides through the
oxidative synthesis of nitriles from alcohols and ammonia and
[11]
the subsequent hydration of the nitriles formed.
example, the corresponding amide 4b could be obtained in
0% yield for the transformation of 1b under the conditions
For
Scheme 1. One-pot synthesis of benzamide. Reaction conditions:
a) alcohol (0.5 mmol), catalyst (Ru: 0.05 mmol), 0.45m solution of
7
ammonia in THF (2 mL, NH /alcohol=1.8), air (6 atm), 1208C, 5 h;
3
described in Scheme 1. After the reaction was completed, the
Ru(OH) /Al O catalyst could easily be retrieved from the
b) addition of water (2 mL), Ar (5 atm), 1508C, 24 h.
x
2
3
reaction mixture by filtration (or centrifugation). In the
recycling experiment using the retrieved catalyst, an 81%
yield of 2a was obtained from the transformation of 1a by
using the reaction conditions described in Table 2.
containing, and aliphatic aldehydes in the presence of
ammonia and air (Table 3). Thus, the present Ru(OH)x/
Al O -catalyzed transformation possibly proceeds through
2
3
three sequential reactions, that is, the aerobic oxidative
[
6a,b]
The reaction profile for the transformation of 1a into 2a
showed that the corresponding aldehyde 3a was initially
produced, followed by the formation of 2a. In addition,
Ru(OH) /Al O showed high catalytic performance for the
dehydrogenation of alcohols to aldehydes,
condensation of the aldehydes and ammonia into imines,
and the aerobic oxidative dehydrogenation of the imines to
the dehydrative
[12]
[
6b,c]
produce the corresponding nitriles.
A possible reaction
x
2
3
oxidative transformation of various kinds of structurally
diverse aldehydes including benzylic, allylic, heteroatom-
mechanism for the present transformation is given in
Scheme S1 in the Supporting Information.
Angew. Chem. Int. Ed. 2009, 48, 6286 –6288
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 6287

Communications
Table 3: Scope of the Ru(OH) /Al O -catalyzed transformation of alde-
hydes into nitriles.
Lett. 2001, 42, 4127; d) M. B. Smith, J. March, Marchꢀs Advanced
Organic Chemistry: Reactions, Mechanisms, and Structure, 6th
ed., Wiley, Hoboken, NJ, 2007.
x
2
t [h]
3
3
[
a]
[
b]
Entry
Substrate
Product
Yield [%]
2a 93
[
2] a) P. T. Anastas, J. C. Warner, Green Chemistry: Theory and
Practice, Oxford University Press, London, 1998; b) R. A.
Sheldon, Green Chem. 2000, 2, G1; c) P. T. Anastas, L. B.
Bartlett, M. M. Kirchhoff, T. C. Williamson, Catal. Today 2000,
1
3a
3e
5
5, 11.
3] a) K. Ishihara, Y. Furuya, H. Yamamoto, Angew. Chem. 2002,
14, 3109; Angew. Chem. Int. Ed. 2002, 41, 2983; b) P. Yan, P.
Batamack, G. K. S. Prakash, G. A. Olah, Catal. Lett. 2005, 101,
41; c) S. H. Yang, S. Chang, Org. Lett. 2001, 3, 4209; d) E. Choi,
2
5
2e 85
[
1
3
4
5
3 f
3h
3l
5
5
6
2 f 90
2h 82
2l 76
1
C. Lee, Y. Na, S. Chang, Org. Lett. 2002, 4, 2369; e) K.
Yamaguchi, H. Fujiwara, Y. Ogasawara, M. Kotani, N. Mizuno,
Angew. Chem. 2007, 119, 3996; Angew. Chem. Int. Ed. 2007, 46,
3922.
[
4] a) S. Iida, H. Togo, Tetrahedron 2007, 63, 8274; b) N. Mori, H.
Togo, Synlett 2005, 1456; c) S. Iida, H. Tago, Synlett 2007, 407;
d) S. Yamazaki, Y. Yamazaki, Chem. Lett. 1990, 571; e) G. D.
McAllister, C. D. Wilfred, R. J. K. Taylor, Synlett 2002, 1291;
f) F.-E. Chen, Y.-Y. Li, H.-Q. Jia, Synthesis 2002, 1804.
[
[
c]
c]
6
7
CH (CH ) CHO 3n 16
CH (CH ) CN
CH (CH ) CN
3 2 8
2n 71
2o 81
3
2
6
3
2 6
CH (CH ) CHO 3o 16
3
2
8
[
a] Reaction conditions: aldehyde (0.5 mmol), catalyst (Ru: 0.05 mmol),
0
.45m THF solution of ammonia (2 mL, NH /aldehyde=1.8), air
3
1
[5] Very recently, excellent examples for the homogeneous tran-
(
(
6 atm), 1208C. [b] Yields were determined by GC and H NMR analyses
also see Table S2 in the Supporting Information). [c] 1308C.
[
5a]
sition-metal-catalyzed direct synthesis of amines
and ami-
[
5b]
des from alcohols using gaseous ammonia (typically 7.5 atm)
and liquid ammonia, respectively, have been reported: a) C.
Gunanathan, D. Milstein, Angew. Chem. 2008, 120, 8789; Angew.
Chem. Int. Ed. 2008, 47, 8661; b) T. Zweifel, J.-V. Naubron, H.
Grꢀtzmacher, Angew. Chem. 2009, 121, 567; Angew. Chem. Int.
Ed. 2009, 48, 559.
In conclusion, Ru(OH) /Al O served as an efficient
x
2
3
heterogeneous catalyst for the aerobic oxidative synthesis of
nitriles directly from alcohols (or aldehydes) and ammonia.
Furthermore, the one-pot synthesis of amides could also be
realized. The observed catalysis was truly heterogeneous. The
results demonstrated herein will open up a new avenue for the
green nitrile synthesis, which avoids the use of the conven-
tional hazardous reagents, such as inorganic cyanides, in
stoichiometric amounts.
[
6] a) K. Yamaguchi, N. Mizuno, Angew. Chem. 2002, 114, 4720;
Angew. Chem. Int. Ed. 2002, 41, 4538; b) K. Yamaguchi, N.
Mizuno, Chem. Eur. J. 2003, 9, 4353; c) K. Yamaguchi, N.
Mizuno, Angew. Chem. 2003, 115, 1518; Angew. Chem. Int. Ed.
2003, 42, 1480; d) J. W. Kim, K. Yamaguchi, N. Mizuno, Angew.
Chem. 2008, 120, 9389; Angew. Chem. Int. Ed. 2008, 47, 9249;
e) K. Yamaguchi, T. Koike, J. W. Kim, Y. Ogasawara, N. Mizuno,
Chem. Eur. J. 2008, 14, 11480.
[
7] The gas-phase ammoxidations of small alcohols (reaction
temperature ꢀ 3508C) have been reported: a) B. M. Reddy, B.
Manohar, J. Chem. Soc. Chem. Commun. 1993, 234; b) S. J.
Kulkarni, R. R. Rao, M. Subrahmanyam, A. V. R. Rao, J. Chem.
Soc. Chem. Commun. 1994, 237.
Experimental Section
General procedure: An alcohol (or an aldehyde) (0.5 mmol),
Ru(OH) /Al O (Ru: 0.05 mmol), and a solution of ammonia in
x
2
3
THF (2 mL, 0.45m, NH /substrate = 1.8) were placed in a Teflon
3
vessel with a magnetic stir bar. The Teflon vessel was placed inside an
autoclave, and the reaction was carried out at 120–1308C (bath
temperature) under 6 atm of air. The reaction rates were not affected
by stirring rates ranging from 500 to 1000 rpm. After the reaction was
completed, the used Ru(OH) /Al O catalyst was removed by
[8] The development of easily recovered and recycled heteroge-
neous catalysts, especially for oxidation reactions, has received
interest and can solve the problems associated with the
homogeneous systems: a) R. A. Sheldon, H. van Bekkum,
Fine Chemical through Heterogeneous Catalysis, Wiley, Wein-
heim, 2001; b) G. Centi, F. Cavani, F. Trifiro, Selective Oxidation
by Heterogeneous Catalysis, Kluwer, New York, 2001; c) I. V.
Kozhevnikov, NATO Science Series, II: Mathematics, Physics and
Chemistry, Kluwer, New York, 2003, pp. 351 – 380; d) B. Warren,
S. T. Oyama, Heterogeneous Hydrocarbon Oxidation, ACS,
Washington, DC, 1996; e) A. Bhan, E. Iglesia, Acc. Chem. Res.
2008, 41, 559.
x
2
3
filtration (or centrifugation), washed with acetone, an aqueous
solution of NaOH (0.1m), and water, and then dried in vacuo prior
to being recycled. The product nitrile was isolated after purification
using silica gel column chromatography (diethyl ether). The products
were confirmed by the comparison of their GC retention times, GC
1
13
mass spectra, and H and C NMR spectra with those of authentic
samples.
[
9] K. Yamaguchi, K. Mori, T. Mizugaki, K. Ebitani, K. Kaneda, J.
Am. Chem. Soc. 2000, 122, 7144.
Received: January 22, 2009
Published online: March 30, 2009
[
[
[
10] R. A. Sheldon, M. Wallau, I. W. C. E. Arends, U. Schuchardt,
Acc. Chem. Res. 1998, 31, 485.
11] K. Yamaguchi, M. Matsushita, N. Mizuno, Angew. Chem. 2004,
116, 1602; Angew. Chem. Int. Ed. 2004, 43, 1576.
Keywords: alcohols · ammonia · heterogeneous catalysis ·
.
nitriles · ruthenium
12] During the transformation of 1a into 2a, the corresponding
imine of 2-naphthalenemethanimine could be detected by GC–
+
MS (MS (EI): m/z (%): 156 (12), 155 (100) [M ], 154 (92), 153
[
1] a) A. J. Fatiadi in Preparation and Synthetic Applications of
Cyano Compounds (Eds.: S. Patai, Z. Rappaport), Wiley, New
York, 1983; b) J. S. Miller, J. L. Manson, Acc. Chem. Res. 2001,
(18), 128 (32), 127 (44), 126 (18), 77 (18)) albeit in an only small
amount (below 1% yield).
34, 563; c) P. Magnus, D. A. Scott, M. R. Fielding, Tetrahedron
6
288 www.angewandte.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 6286 –6288