Efficient hydration of nitriles promoted by simple amorphous manganese oxide using reduced amounts of water

Article abstract of DOI:10.1246/cl.2012.574

Hydration of various kinds of nitriles could efficiently be promoted by amorphous MnO2 using reduced amounts of water (2 equiv or less), giving the corresponding primary amides in moderate to high yields. The observed catalysis was truly heterogeneous, and the retrieved MnO2 could be reused without an appreciable loss of its high catalytic performance.

Full text of DOI:10.1246/cl.2012.574

doi:10.1246/cl.2012.574
574
Published on the web May 12, 2012
Efficient Hydration of Nitriles Promoted by Simple Amorphous Manganese Oxide
Using Reduced Amounts of Water
Kazuya Yamaguchi, Ye Wang, Hiroaki Kobayashi, and Noritaka Mizuno*
Department of Applied Chemistry, School of Engineering, The University of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656
(Received February 14, 2012; CL-120126; E-mail: tmizuno@mail.ecc.u-tokyo.ac.jp)
Table 1. Hydration of benzonitrile (1a) to benzamide (2a)a
Hydration of various kinds of nitriles could efficiently be
promoted by amorphous MnO2 using reduced amounts of water
(2 equiv or less), giving the corresponding primary amides in
moderate to high yields. The observed catalysis was truly
heterogeneous, and the retrieved MnO2 could be reused without
an appreciable loss of its high catalytic performance.
Entry
Catalyst
Solvent
Yield/%
1
2b
3
4c
5
Amorphous MnO2
Amorphous MnO2
OMS-2
¢-MnO2
KMnO4
MnSO4¢H2O
Co3O4
CeO2
KF/Al2O3
Ru(OH)x/Al2O3
RuHAP
Amorphous MnO2
Amorphous MnO2
Amorphous MnO2
Amorphous MnO2
Amorphous MnO2
None
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
n-Heptane
Toluene
62
64
27
42
<1
<1
3
<1
<1
<1
<1
58
48
13
1
6
7
Primary amides are one of the most important chemicals that
have widely been utilized as important synthons, producing
engineering plastics, detergents, lubricants, pharmaceuticals,
agricultural chemicals, and specialty chemicals.1 Instead of
antiquated procedures using activated carboxylic acid deriva-
tives, the development of efficient synthetic routes to primary
amides using various kinds of starting materials is a very
important subject in modern organic synthesis. Several green
catalytic procedures starting from nitriles (hydration),2,3 aldox-
imes (rearrangement),4 primary alcohols (oxidative amidation
with aqueous ammonia),5 and primary amines (oxygenation)6
have been developed. Very recently, we have successfully
developed two new green synthetic routes to primary amides
from (i) primary alcohols and aqueous ammonia5 and (ii)
primary amines6a via catalytic relay reactions in the presence of
manganese-based oxide octahedral molecular sieves (OMS-2,
KMn8O16). One of the most important findings in these studies is
that OMS-2 can efficiently catalyze hydration of nitriles (the
final step of the above relay reactions).5,6a
8c
9c
10
11c
12
13
14
15
16d
17
DMF
Ethanol
Solvent-free
1,4-Dioxane
94
<1
aReaction conditions: 1a (0.5 mmol), catalyst (50 mg), water
(2 equiv with respect to 1a), solvent (2 mL), 140 °C (bath
temp), under Ar, 30 min. Yields were determined by GC using
naphthalene as an internal standard. Water (1 equiv). Com-
mercially available (see the Supporting Information13). 1 h.
b
c
d
Hydration of nitriles is an important reaction to produce
primary amides in academic as well as industrial laboratories.
Many efficient procedures using homogeneous transition-metal-
based complexes2 and microorganisms for enzymatic hydration7
have been developed, while these systems have disadvantages,
i.e., difficulty in catalyst/product separation and necessity of
special handling of metal complexes and microorganisms in
some cases. Alternatively, several supported catalysts, e.g.,
MnO2/SiO2,3a KF/Al2O3,3b Na/FAP (FAP: fluoroapatite),3c
AgHAP (HAP: hydroxyapatite),3d RuHAP,3e and Ru(OH)x/
Al2O3,3f have been developed. Several simple metal oxides have
been reported to be active for hydration of nitriles. For example,
MnO2 is known to be effective for limited substrates, e.g., 3-
We demonstrate herein that simple amorphous MnO2 (with
a relatively large BET surface area, 304 m2 g¹1)8 can promote
hydration of various kinds of nitriles using reduced amounts of
water and that the activity is much higher than those of several
previously reported heterogeneous catalysts including OMS-2
(Table 1).3 The present procedures have the following signifi-
cant advantages in comparison with previously reported sys-
tems; (i) various structurally diverse nitriles including aromatic,
heteroaromatic, unsaturated, and aliphatic compounds can be
converted (even under solvent-free conditions), (ii) the amount
of water can be much reduced (2 equiv or less), (iii) no ligands
or additives are necessary, (iv) catalyst separation and product
isolation are very easy, (v) gram-scale hydration is also effective,
(vi) MnO2 is easily prepared (commercially available) and rather
inexpensive in comparison with precious-metal-based catalysts,
and/or (vii) MnO2 can be reused without an appreciable loss of
its high catalytic performance.
3j
3k
cyanopyridine, in water.3g-3i Very recently, CeO2 and Co3O4
have been reported to be active, though their applicabilities were
quite limited; for example, CeO2 for only 2-cyanopyridine and
2-furancarbonitrile derivatives3j and Co3O4 for only aromatic
nitriles.3k In most of the reported heterogeneous systems, the
hydration has typically been carried out in water (using large
excess of water (reactant)),3 which produces large amounts of
waste water containing organic contamination. Therefore, it is
desirable to reduce the amounts of water to (near) stoichiometric
amounts with respect to nitriles.
Initially, various kinds of catalysts including previously
reported ones were applied to the hydration of benzonitrile (1a)
to benzamide (2a) using “2 equiv of water” with respect to 1a in
1,4-dioxane (Table 1).9 Among catalysts examined, only man-
ganese-based oxides such as amorphous MnO2, OMS-2, and
¢-MnO2 gave significant yields of 2a (27-62% yields). For
Chem. Lett. 2012, 41, 574-576
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

575
a
Table 2. Hydration of various nitriles with amorphous MnO2
example, when the hydration of 1a was carried out with
amorphous MnO2 at 140 °C (bath temp), 62% yield of 2a was
obtained in 30 min. Notably, the hydration efficiently proceeded
even with “1 equiv of water.” The catalytic activity of
amorphous MnO2 was higher than those of OMS-25,6a and ¢-
MnO2. KMnO4 and MnSO4¢H2O (precursors of amorphous
Entry
Substrate
Product
Time
/ h
Yield
/ %
O
1
1a
1a
1a
2a
2a
2a
1
1
3
87 (94d)
88 (93d)
80
CN
2b
3c
NH2
8
MnO2 ) were not effective for the hydration, suggesting that
O
CN
soluble manganese species are not the active species for the
present hydration. Previously reported heterogeneous catalysts
such as Co3O4,3k CeO2,3j KF/Al2O3,3b Ru(OH)x/Al2O3,3f and
RuHAP3e did not work well under the conditions described in
Table 1 using only “2 equiv of water.” 1,4-Dioxane, n-heptane,
and toluene were good solvents for the hydration, giving 62-
48% yields of 2a. On the other hand, highly polar solvents such
as DMF and ethanol were poor solvents. It is emphasized that
the hydration also efficiently proceeded even under solvent-free
conditions (Entry 16 in Table 1).
NH2
4
1b
2b
1
13
O
CN
CN
NH2
5
1c
1c
2c
2c
1
1
82
83
6b
O
NH2
7
1d
2d
1
80
O
MeO
CN
CN
MeO
8
1e
2e
1
94 (93d)
NH2
NH2
O
O
Next, the scope of the present MnO2-catalyzed system with
regard to various kinds of structurally diverse nitriles was
examined. Amorphous MnO2 showed high catalytic activities
for hydration of aromatic, heteroaromatic, unsaturated, and
aliphatic nitriles, giving the corresponding amides in moderate
to high yields (except for 1b) using only 2 equiv of water
(Table 2). Hydration of benzonitrile derivatives 1a and 1c-1i,
which contain electron-donating as well as electron-withdrawing
substituents at m- and p-positions, efficiently proceeded to give
the corresponding benzamide derivatives in high yields. In the
hydration of o-, m-, and p-tolunitriles (1b-1d), the reaction rate
of o-tolunitrile (1b) was much smaller than those of m- and p-
derivatives 1c and 1d, and the steric effect was very significant.
This observation suggests the coordination of nitriles on the
surface of MnO2. A similar steric effect has been reported for
Ru(OH)x/Al2O3-catalyzed hydration.3f Hydration of heteroaro-
matic nitriles such as pyridine (1j) and thiophene (1k) carbon-
itriles efficiently proceeded to afford the corresponding hetero-
aromatic amides in high yields. An unsaturated nitrile (1l) gave
the corresponding unsaturated amide. The hydration of a less
reactive aliphatic nitrile 1m also proceeded to afford the
corresponding aliphatic amide, though the yield was moderate.
Moreover, under the solvent-free conditions, the hydration of
various kinds of nitriles also efficiently proceeded even in the
case of “solid substrates” such as 1g and 1h10 (see values in the
parentheses in Table 2).
9
1f
1f
2f
2f
1
1
86
90
10b
MeO
Cl
MeO
Cl
CN
CN
CN
NH2
NH2
NH2
11
1g
1g
2g
2g
1
1
97 (>99d)
97
12b
O
O
13
1h
1h
2h
2h
1
1
99 (>99d)
99
14b
O2N
O2N
15
1i
2i
3
96
O
O
N
CN
CN
16
1j
1j
2j
2j
1
1
>99 (99d)
>99
N
NH2
17b
18
1k
2k
1
96
NH2
O
S
S
CN
19
1l
1l
2l
2l
2
2
93 (96d)
95
NH2
20b
O
21e
12
54
CN
NH2
1m
2m
aReaction conditions: substrate (0.5 mmol), MnO2 (50 mg),
water (2 equiv with respect to substrates), 1,4-dioxane (2 mL),
140 °C (bath temp), under Ar. Yields were determined by GC
b
The gram-scale hydration was also effective; the hydration
of 1g (1.03 g) efficiently proceeded without any decrease in the
performance in comparison with the small-scale transformation
in Table 2, and 2g was produced in 94% yield (by GC). MnO2
was separated by filtration and washed with ethanol and acetone.
Evaporation of the combined filtrate gave a crude product
followed by rinsing with n-hexane (ca. 10 mL), giving 1.07 g of
2g (92% isolated yield, >99% purity by GC and NMR) (eq 1).
using naphthalene or biphenyl as an internal standard. Reuse
experiments. cMnO2 (10 mg). dUnder the solvent-free con-
e
ditions. MnO2 (100 mg), 150 °C (bath temp).
filtration at 50-60% conversion of 1a. Then, the filtrate was
again heated at 140 °C. In this case, no further production of 2a
was observed. It was confirmed by ICP-AES analysis that no
manganese species was detected in the filtrate. All these facts
can rule out any contribution to the observed catalysis from
manganese species that leached into the reaction solution,
and the observed catalysis is intrinsically heterogeneous.11 In
addition, the retrieved MnO2 catalyst9 could be reused without
an appreciable loss of high catalytic performance for various
nitriles (Entries 2, 6, 10, 12, 14, 17, and 20 in Table 2).
O
CN
MnO2 (750 mg)
NH2
ð1Þ
+
H2O
(2 equiv)
1,4-dioxane (30 mL)
140 °C, 1 h, Ar
Cl
1g (1.03 g)
Cl
2g (1.07 g, 92% yield)
In order to verify whether the observed catalysis is derived
from solid amorphous MnO2 or leached manganese species, the
hydration of 1a was carried out under the conditions described in
Table 1, and MnO2 was removed from the reaction mixture by
The catalytic activities of amorphous MnO2 for the hydra-
tion of p-substituted benzonitrile derivatives increased in the
Chem. Lett. 2012, 41, 574-576
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

576
0.8
0.6
References and Notes
1
a) C. E. Mabermann, in Encyclopedia of Chemical Technology, ed. by
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Uguen, Tetrahedron Lett. 1994, 35, 1401. b) C. G. Rao, Synth.
Commun. 1982, 12, 177. c) A. Solhy, A. Smahi, H. El. Badaoui, B.
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p-NO2
0.4
p-Cl
0.2
p-Me
ρ = +0.60
2
3
p-H
0
−0.2
−0.4
p-OMe
−0.4 −0.2
0
0.2
0.4
0.6
0.8
1
σp
Figure 1. Hammett plot for competitive hydration of benzoni-
trile (1a) and p-substituted benzonitrile derivatives 1d, 1f, 1g,
and 1h. Reaction conditions: 1a (0.25 mmol), p-substituted
benzonitrile (0.25 mmol), amorphous MnO2 (50 mg), water
(2 equiv with respect to substrates), 1,4-dioxane (2 mL), 140 °C
(bath temp), under Ar.
order of 1f (0.80) < 1d (0.87) < 1a (1.00) < 1g (1.57) < 1h
(3.29), where the values in the parentheses are the relative rates
and the rate for 1a is taken as a unity. The slope of the linear line
in Figure 1 gave the Hammett µ value of +0.60. The positive
value of the Hammett µ can be interpreted the formation of a
negatively charged transition state. A very similar Hammett µ
value of +0.58 has been reported for the CeO2-catalyzed
hydration of substituted 2-cyanopyridine derivatives, where
the activation (polarization) of water on the surface of CeO2
followed by nucleophilic attack of OH¤¹ species to a nitrile
carbon is proposed.3j In the same way, the present MnO2-
catalyzed hydration would proceed through the above-men-
tioned reaction mechanism.
In the hydration of 1a with amorphous MnO2, the reaction
rate with D2O12 was almost the same as that with H2O, and no
kinetic isotope effect was observed (kH/kD = 0.96). As men-
tioned above, the reaction rate was almost independent of water
concentrations (Entries 1 and 2 in Table 1). Taking all the above-
mentioned results into account, the nucleophilic attack of OH¤¹
species to a nitrile carbon is likely included in the rate-limiting
step for the present MnO2-catalyzed hydration.
4
a) H. Fujiwara, Y. Ogasawara, K. Yamaguchi, N. Mizuno, Angew.
Chem., Int. Ed. 2007, 46, 5202. b) N. A. Owston, A. J. Parker, J. M. J.
Williams, Org. Lett. 2007, 9, 73. c) H. Fujiwara, Y. Ogasawara, M.
Kotani, K. Yamaguchi, N. Mizuno, Chem.®Asian J. 2008, 3, 1715.
d) M. Kim, J. Lee, H.-Y. Lee, S. Chang, Adv. Synth. Catal. 2009, 351,
1807.
5
6
K. Yamaguchi, H. Kobayashi, T. Oishi, N. Mizuno, Angew. Chem.,
Int. Ed. 2012, 51, 544.
a) Y. Wang, H. Kobayashi, K. Yamaguchi, N. Mizuno, Chem.
Commun. 2012, 48, 2642. b) J. W. Kim, K. Yamaguchi, N. Mizuno,
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7
8
K. Ingvosersen, J. Kamphuis, in Enzyme Catalysis in Organic
Synthesis:
A Comprehensive Handbook, ed. by K. Drauz, H.
Waldmann, VCH, Weinheim, 1995, Vol. 1, pp. 365-392.
Amorphous MnO2 was prepared as follows: MnSO4¢H2O (8.8 g) was
dissolved in deionized water (30 mL). To this solution, a solution
consisting of KMnO4 (5.89 g) in deionized water (100 mL) was added
dropwise under continuous stirring. The resulting mixture was stirred
at room temperature for 10 min. Then, the solid was filtered off,
washed with deionized water (ca. 4 L), and dried in an oven at 150 °C
for 12 h, affording 5.0 g of amorphous MnO2 as a dark brown powder
(BET surface area: 304 m2 g¹1).
In summary, simple amorphous MnO2 could act as an
efficient, reusable heterogeneous catalyst for hydration of
various kinds of structurally diverse nitriles including aromatic,
heteroaromatic, unsaturated, and aliphatic ones even in the
presence of reduced amounts of water (2 equiv or less) in 1,4-
dioxane or even under solvent-free conditions. Though MnO2
is known to be effective for hydration of limited nitriles in
water,3g-3i the above-demonstrated high performance and use-
fulness of amorphous MnO2 are previously unknown and new
findings.
9
Procedure for nitrile hydration: Amorphous MnO2 (50-100 mg), 1,4-
dioxane (2 mL) (or solvent-free), nitrile (0.5 mmol), and water
(1-2 equiv) were placed in a Teflon vessel with a magnetic stirring
bar. The Teflon vessel was attached inside an autoclave, and the
reaction was carried out at 140-150 °C (bath temp) in 3 atm of Ar.
After the hydration was completed, MnO2 was separated by filtration
(>95% catalyst recovery, BET surface area of retrieved MnO2:
197 m2 g¹1) and washed with ethanol and acetone. The product was
isolated by evaporation of volatiles (combined filtrate), followed by
rinse with n-hexane. The retrieved MnO2 was washed with water and
then dried at 150 °C under air atmosphere for 1 h just before using for
the reuse experiment.
10 The melting points of 1g and 1h are 91.5 and 145.5 °C, respectively.
11 R. A. Sheldon, M. Wallau, I. W. C. E. Arends, U. Schuchardt, Acc.
Chem. Res. 1998, 31, 485.
12 For the hydration with D2O, MnO2 was pretreated with D2O before
the reaction. See the Supporting Information for details.13
13 Supporting Information is available electronically on the CSJ-Journal
Web site, http://www.csj.jp/journals/chem-lett/index.html.
This work was supported in part by the Global COE
Program (Chemistry Innovation through Cooperation of Science
and Engineering), Japan Chemical Innovation Institute (JCII),
and Grants-in-Aid for Scientific Researches from Ministry of
Education, Culture, Sports, Science and Technology.
Chem. Lett. 2012, 41, 574-576
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/