Efficient Mo(VI)-catalyzed hydration of nitrile with acetaldoxime

Article abstract of DOI:10.1080/00397911.2013.806668

A method for the selective hydration of nitrile to amide by employing commercially available acetaldoxime and inexpensive oxometallate such as molybdate, vanadate, and tungstate in environmentally friendly water is described. Under this protocol, nitriles including aromatic nitriles, heterocyclic nitriles, and aliphatic nitriles were converted into the corresponding amides in good to excellent yields.

Full text of DOI:10.1080/00397911.2013.806668

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Efficient Mo(VI)-Catalyzed Hydration of
Nitrile with Acetaldoxime
a
a
a
Xiaoyun Ma , Ying He & Ming Lu
a
Chemical Engineering College , Nanjing University of Science and
Technology , Nanjing , China
Published online: 27 Dec 2013.
To cite this article: Xiaoyun Ma , Ying He & Ming Lu (2014) Efficient Mo(VI)-Catalyzed Hydration
of Nitrile with Acetaldoxime, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 44:4, 474-480, DOI: 10.1080/00397911.2013.806668
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Synthetic Communications , 44: 474–480, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.806668
EFFICIENT Mo(VI)-CATALYZED HYDRATION OF
NITRILE WITH ACETALDOXIME
Xiaoyun Ma, Ying He, and Ming Lu
Chemical Engineering College, Nanjing University of Science and
Technology, Nanjing, China
GRAPHICAL ABSTRACT
Abstract A method for the selective hydration of nitrile to amide by employing
commercially available acetaldoxime and inexpensive oxometallate such as molybdate,
vanadate, and tungstate in environmentally friendly water is described. Under this protocol,
nitriles including aromatic nitriles, heterocyclic nitriles, and aliphatic nitriles were converted
into the corresponding amides in good to excellent yields.
[Supplementary materials are available for this article. Go to the publisher’s online
1
edition of Synthetic Communications for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Acetaldoxime; amide; hydration; nitrile; sodium molybdate(VI) dihydrate
INTRODUCTION
Hydration of nitriles to the corresponding amides is an important
[
1]
transformation from both academic and industrial points of view. Classically the
reaction was carried out in the presence of a strong acid or base catalyst, methods
which usually cause overhydrolysis of the amides into the corresponding carboxylic
[
2]
acids, a faster reaction specially under basic conditions. To overcome the
[
limitation, several protocols using enzymes, hydroxylamine derivatives, hetero-
3]
[4]
[5]
geneous catalysts, and homogeneous catalysts based on transition metals such as
[
6]
[7]
[8]
[9]
[10]
[11]
rhodium, ruthenium, palladium, cobalt, molybdenum,
gold
platinum,
have been developed for selective conversion of nitriles to amides. In
addition, the hydration of nitriles promoted by the combination of oxime and metal
and
[
12]
[
13]
[14]
[15]
compounds, such as RhCl(PPh ) , Pd(OAc)2, and InCl3 etc. have also been
3
3
reported. Recently, the study on efficient, cheaper, and environmentally friendly
Received December 18, 2012.
Address correspondence to Ming Lu, Chemical Engineering College, Nanjing University of Science
and Technology, Nanjing 210094, China. E-mail: lumingnjust@163.com
4
74

HYDRATION OF NITRILE
475
16]
[
catalysts for functional group transformation has become a research hotspot.
During our recent studies of conversion of nitrile to amide, we disclosed an efficient
method for the preparation of amides from nitriles by employing acetaldoxime and
bivalent metal salt such as copper oxide (CuO) and nickel(II) chloride hexahydrate
[
17]
(
NiCl Á 6H O) in water. Under this protocol, nitriles were selectively converted to
2
2
amides in excellent yields, and nitriles having electron-withdrawing groups could be
converted into the corresponding amides in good to excellent yields at room tem-
perature. Heterocyclic nitriles with a lone heteroatom pair positioned ortho to the
nitrile group could be hydrated at refluxing temperature in the absence of acetaldox-
ime. In the continuation of our study on inexpensive catalysts for the hydration of
nitriles, we found that some oxometallates also showed good catalytic activity for
hydration of various nitriles.
In this article, the catalytic activity of various oxometallate such as molybdate,
vanadate, and tungstate for hydration of nitriles has been investigated. Sodium mol-
ybdate showed the greatest catalytic activity and it was used as catalyst for hydration
of various nitriles.
RESULTS AND DISCUSSION
As shown in Table 1, we found that all the metal salts displayed catalytic
properties in the hydration of benzonitrile to benzamide with the aid of acetaldox-
ime. Use of sodium molybdate(VI) dihydrate (Na MoO Á 2H O) alone at room tem-
2
4
2
perature resulted in no product (Table 1, entry 1) and a trace amount of benzamide
was detected after 24 h at reflux temperature (Table 1, entry 2). No benzamide was
obtained in the presence of Na MoO Á 2H O and acetaldoxime at room temperature
2
4
2
(Table 1, entry 3); however, benzamide was obtained in 76% yield when the tempera-
ture was raised to reflux (Table 1, entry 4). Therefore, we concluded that the reaction
temperature had a significantly effect on the reaction rate and the product yield.
a
Table 1. Screen of reaction conditions
b
Entry
Conditions
Yield (%)
1
2
3
4
5
6
7
8
Na
Na
Na
Na
2
2
2
2
MoO
MoO
MoO
MoO
4
4
4
4
Á 2H
Á 2H
Á 2H
Á 2H
2
2
2
2
O (0.1 equiv), H
O (0.1 equiv), H
2
O, rt, 24 h
0
Trace
0
2
O, reflux, 24 h
O (0.1 equiv), acetaldoxime (1.0 equiv), H
O (0.1 equiv), acetaldoxime (1.0 equiv), H
2
O, rt, 24 h
2
O, reflux, 24 h
76
70
NaVO
3
Á 2H
WO
PO
MoO
2
O (0.1 equiv), acetaldoxime (1.0 equiv), H
O (0.1 equiv), acetaldoxime (1.0 equiv), H
Á 12WO Á 18H O (0.1 equiv), acetaldoxime (1.0 equiv), H
Á 2H O (0.1 equiv), acetaldoxime (3.0 equiv), H O, reflux, 12 h
2
O, reflux, 24 h
O, reflux, 24 h
O, reflux, 24 h
Na
Na
Na
2
3
2
4
Á 2H
2
2
38
13
4
3
2
2
4
2
2
90
a
Reaction conditions: benzonitrile (2 mmol), H
Isolated yield.
2
O (10 mL).
b

476
X. MA, Y. HE, AND M. LU
Sodium metavanadate(V) dihydrate (NaVO Á 2H O) exhibited a low catalytic
3
2
activity as compared to Na MoO Á 2H O (Table 1, entry 5). In the cases of sodium
2
4
2
tungstate(VI) dihydrate (Na WO Á 2H O) and sodium phosphotungstate octadeca-
2
4
2
hydrate (Na PO Á 12WO Á 18H O), benzamide was obtained in poor yield (Table 1,
3
4
3
2
entries 6 and 7). When we increased the amounts of acetaldoxime to 3 equiv, the
reaction time was reduced from 24 h to 12 h and the yield was increased (Table 1,
entry 8). It should be noted that no benzoic acid was detected in the reaction mixture
at high temperatures.
On the basis of these results, we can conclude that using Na MoO Á 2H O and
2
4
2
acetaldoxime at refluxing temperature is the optimality conditions for nitrile
hydration. This protocol of hydration was subsequently applied to various aromatic
nitriles, aliphatic nitriles, and heterocyclic nitriles. As shown in Table 2, various
nitriles including aromatic nitriles having electron-donating or electron-withdrawing
substituents (Table 2, entries 1–4), heterocyclic nitriles (Table 2, entries 5–9), and ali-
phatic nitriles (Table 2, entries 10–12) were converted into the corresponding amides
in good to excellent yields. Substrates bearing electron-donating groups (Table 2,
entries 1 and 2) renders the nitrile carbon less electrophilic to nucleophilic attack
by acetaldoxime and exhibited relatively lower conversions. In addition, 4 mol equiv
of acetaldoxime was used in these cases. In contrast, the hydration of nitriles with an
electron-withdrawing group proceeded more effectively (Table 2, entries 3–7 and 9).
For example, nicotinonitrile was converted to the corresponding amide with com-
plete conversion after a relatively short reaction time of 5 h and 2 mol equiv of acet-
aldoxime was used in this case. It is worth noting that the nitrile hydration was
affected by steric factors. By-products are generated in the hydartion of nitriles bear-
ing a group positioned ortho to the nitrile group. For example, compared with iso-
nicotinamide, the yield of picolinamide is relatively lower due to a lone pair at the
ortho position (Table 2, entry 5). Similarly, 3-methylpicolinonitrile showed low reac-
tivity due to the methyl group at the ortho position (Table 2, entry 8). In addition,
the water solubility of the nitriles also affect the hydration reaction and the
hydration of poorly water-soluble nitriles required a long reaction time. For
example, the hydration of isonicotinonitrile proceeded fast compared with the
hydration of 4-nitrobenzonitrile (Table 2, entries 4 and 7). In the case of aliphatic
nitriles the hydration process was similar to aromatic nitriles; aliphatic nitriles
(Table 2, entries 10–12) were smoothly hydrated to give the corresponding amides
in good yields under the employed reaction conditions.
Nitrile with strong electron-withdrawing substituent can be hydrated at room
temperature. As shown in Scheme 1, isonicotinonitrile was converted into isonicoti-
namide in the presence of Na MoO Á 2H O and acetaldoxime. Actually, the
2
4
2
hydration of isonicotinonitrile to isonicotinamide did not proceed at all with either
Na MoO Á 2H O or acetaldoxime taken alone at room temperature. Therefore, we
2
4
2
are certain that Na MoO Á 2H O is a catalyst in this case. Noteworthy, the
2
4
2
oxometalates are readily prone to hydrolysis in aqueous solution under the high-
temperature condition and form their poly-condensed types called polyoxometalates
[18]
according to the literature.
Under our protocol for the hydraton of various
nitriles, the reactions were carried out in water at high temperature, so we thought
that the polyoxometalate generated and acted as a catalyst in the reaction. Accord-
[
17]
[13–15]
ing to our previous metal-catalyzed hydration papers
and other literature,

HYDRATION OF NITRILE
Table 2. Hydration of various nitriles using Na MoO
477
a
2
4
Á 2H
2
O and acetaldoxime
b
Entry
1
Nitrile
Amide
Time (h)
16
Yield (%)
c
73
c
2
3
16
12
83
91
92
4
5
6
7
12
5
d
87
95
95
d
d
c
5
5
8
9
16
77
d
5
86
10
12
89
1
1
1
2
CH
CH
3
(CH
(CH
2
)
10CN
CN
CH
CH
3
(CH
(CH
2
)
10CONH
CONH
2
2
12
12
88
87
3
2
)
6
3
2
)
6
a
Reaction conditions: nitrile (2 mmol), acetaldoxime (6 mmol), Na
2
MoO
4
Á 2H
2 2
O (0.2 mmol), H O
(
10 mL), reflux.
b
Isolated yield.
mmol acetaldoxime was used.
mmol acetaldoxime was used.
c
8
d
4

478
X. MA, Y. HE, AND M. LU
Scheme 1. Hydration of isonicotinonitrile at room temperature.
Scheme 2. Proposed mechanism of nitrile hydration via molybdenum catalyst and acetaldoxime.
the nucleophilic addition of acetaldoxime to nitrile can be carried out only when
coordination of nitrile to the metal catalyst and the catalytic effect of catalyst is
attributed to the coordination of nitrile to metal catalyst. In this article, we thought
that coordination of nitrile to molybdenum (VI) results in an enhanced electrophili-
city of the nitrile carbon, whether Na MoO Á 2H O or polyoxomolybdate. So both
2
4
2
Na MoO Á 2H O and polyoxomolybdates can act as catalyst in the hydration of
2
4
2
nitriles. We thought that the reaction mechanism for nitrile hydration is likely
to be similar to the mechanism reported in the literatures.
[
13–15,17,19]
As shown in
Scheme 2, initially, coordination of benzonitrile to molybdenum(VI) results in an
enhanced electrophilicity of the nitrile carbon, then the nucleophilic addition of
acetaldoxime yields the intermediate I, and the following disruption of the
intermediate I into benzamide and acetonitrile proceeds in a concerted manner.
CONCLUSIONS
In conclusion, we disclosed a method for the hydration of nitrile to amide using
commercially available acetaldoxime and inexpensive oxometallate such as molyb-
date, vanadate, and tungstate in water. The catalytic activities of these oxometallates
were investigated, and molybdate showed the greatest catalytic activity. Sodium
molybdate(VI) dihydrate was used as a catalyst for the hydration of various nitriles
and nitriles including aromatic nitriles, heterocyclic nitriles, and aliphatic nitriles
were converted into the corresponding amides in good to excellent yields.

HYDRATION OF NITRILE
479
EXPERIMENTAL
Melting points were determined on a Thomas Hoover capillary apparatus and
1
were uncorrected. H NMR spectra were recorded on Bruker DPX-400 or DPX-500
spectrometer. Analytical thin-layer chromatography (TLC) was performed on pre-
coated silica gel 60 F254 plates. Yields refer to the isolated yields of the products
after purification by silica-gel column chromatography (300 mesh). All starting che-
micals are commercially available. All the amide products are known compounds
1
and they were characterized by melting point and H NMR spectra.
To a 25 mL round-bottom flask equipped with magnetic stirrer were added
nitrile (2 mmol), acetaldoxime (6 mmol), sodium molybdate(VI) dihydrate (0.2 mmol),
and H O (10 mL). The mixture was heated to reflux for 5–16 h. After cooling to
2
room temperature, the solution was directly evaporated to dryness and the residue
was purified by column chromatography on silica gel (ethyl acetate=n-hexane) to
give the corresponding amide.
ACKNOWLEDGMENT
Financial support from the National Natural Science Foundation of China-
NSAF (Grant No. 11076017) is gratefully acknowledged.
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