Perrhenic acid-catalyzed dehydration from primary amides, aldoximes, N-monoacylureas, and α-substituted ketoximes to nitrile compounds

Article abstract of DOI:10.1246/bcsj.80.400

The dehydration reaction of primary amides is one of the most fundamental methods for the synthesis of nitriles, and the development of environmentally benign catalytic reaction processes is needed. We surveyed a variety of metal catalysts and found that perrhenic acid was extremely effective for the dehydration of not only primary amides but also aldoximes. Typically, 1 mol % of perrhenic acid gave the corresponding nitriles from amides or aldoximes under azeotropic reflux conditions with the removal of water in toluene or mesitylene. In addition, perrhenic acid is an extremely efficient catalyst for the Beckmann fragmentation of α-substituted ketoximes to functionalized nitriles. This new catalytic system can be applied to the gram-scale synthesis of nitriles without further modifications.

Full text of DOI:10.1246/bcsj.80.400

400 Bull. Chem. Soc. Jpn. Vol. 80, No. 2, 400–406 (2007)
Ó 2007 The Chemical Society of Japan
Perrhenic Acid-Catalyzed Dehydration from Primary Amides,
Aldoximes, N-Monoacylureas, and ꢀ-Substituted
Ketoximes to Nitrile Compounds
ꢀ1
ꢀ2
Yoshiro Furuya,1 Kazuaki Ishihara, and Hisashi Yamamoto
1Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603
2Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, IL 60637, U.S.A.
Received August 3, 2006; E-mail: ishihara@cc.nagoya-u.ac.jp
The dehydration reaction of primary amides is one of the most fundamental methods for the synthesis of nitriles,
and the development of environmentally benign catalytic reaction processes is needed. We surveyed a variety of metal
catalysts and found that perrhenic acid was extremely effective for the dehydration of not only primary amides but also
aldoximes. Typically, 1 mol % of perrhenic acid gave the corresponding nitriles from amides or aldoximes under azeo-
tropic reflux conditions with the removal of water in toluene or mesitylene. In addition, perrhenic acid is an extremely
efficient catalyst for the Beckmann fragmentation of ꢀ-substituted ketoximes to functionalized nitriles. This new cata-
lytic system can be applied to the gram-scale synthesis of nitriles without further modifications.
The synthetic importance of the dehydration of primary
Table 1. Dehydration of 4-Phenylbutyramide (1a) Cata-
aliphatic and aromatic amides to their corresponding nitriles
lyzed by Metal Compounds
has been thoroughly documented.1,2 Most classical methods
catalyst (10 mol%)
require the use of stoichiometric or excess amounts of highly
Ph
CONH2
reactive dehydrating reagents and harsh conditions in acidic
or basic media, or involve tedious workup procedures. More
recently, several methods for the dehydration of primary
amides under milder conditions have been developed.3 In
1990, Watanabe et al.3a found that dichlorotris(triphenylphos-
phine)ruthenium (1 mol %) catalyzes the dehydration of pri-
mary amides in the presence of urea derivatives (1 equiv) in
diglyme at 180 ꢁC. In 1996, Mioskowski et al.3b developed
the paraformaldehyde-catalyzed (490 mol %) water-transfer re-
action of primary amides in a formic acid/acetonitrile mixture.
In 1999, Bose and Jayalakshmi3c,d reported the first catalytic
dehydration of primary amides in the absence of any additives
except for a catalyst. Unfortunately, this method requires a
large amount of highly toxic dibutyltin oxide (25–35 mol %3c
or 37 mol %3d) as a catalyst.
In our continuous studies on the development of various
catalytic dehydration reactions in the absence of any additives
except for catalyst, such as direct amide condensation,4 direct
ester condensation,5 and the dehydration of alcohols,6 we were
interested in nitrile synthesis by catalytic dehydration reac-
tions. We describe here perrhenic acid as an extremely active
catalyst not only for dehydration reaction of primary amides
and aldoximes but also for the Beckmann fragmentation of
ꢀ-substituted ketoximes to synthesize various nitrile com-
pounds.7
toluene (2 mL)
azeotropic reflux, 16 h
1a (0.5 mmol)
H
N
+
CN
Ph
Ph
Ph
O
O
2a
3
Entry
Catalyst
1a/2a/3
1
2
3
4
5
6
7
8
9
10
11
12
13
(Me3SiO)ReO3
a)
15:82:3
19:78:3
62:32:6
77:23:0
82:12:0
81:14:5
81:11:8
89:11:0
99:1:0
100:0:0
100:0:0
100:0:0
100:0:0
(HO)ReO3
(ReO3)2O
Zr(OiPr)4
Hf(OtBu)4
WOCl3
MoO2Cl2
Ti(OiPr)4
Bu2SnO
VO(OiPr)3
ReO3
ReO2
[RuCl2(p-cymene)]2
a) A 65–70 wt % solution of perrhenic acid (9–10 mol %) in
water.
amide (1a) in toluene at azeotropic reflux with the removal
of water (Dean–Stark apparatus) for 16 h (Table 1). Commer-
cially available trimethylsilylperrhenate8 was the most effec-
tive catalyst for this reaction (Table 1, Entry 1), and a 65–
70 wt % aqueous solution of perrhenic acid and anhydrous rhe-
nium(VII) oxide exhibited higher catalytic activities than other
metal compounds (Table 1, Entries 2 and 3), whereas rhe-
Results and Discussion
Dehydration Reaction of Primary Amides. We first in-
vestigated the catalytic activities (10 mol %) of various metal
salts, metal alkoxides, metal oxides, and organometallic com-
pounds that promote the model reaction of 4-phenylbutyr-
Published on the web February 13, 2007; doi:10.1246/bcsj.80.400

Y. Furuya et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 2 (2007)
401
Table 2. Solvent Effect on the Dehydration of 4-Phenyl-
butyramide (1a) Catalyzed by Aqueous Perrhenic Acid
Table 3. Dehydration Reaction of Primary Amides Cata-
lyzed by Aqueous Perrhenic Acid
aqueous (HO)ReO3
aqueous (HO)ReO3
(0.9−1 mol%)
(9−10 mol%)
RCONH2
RCN
+
2a
3
1a
(0.5 mmol)
mesitylene (2 mL)
azeotropic reflux, 1 day
solvent (2 mL)
azeotropic reflux, 5 h
1
2
(1 mmol)
2/%a)
Entry
Solvent
t/ꢁCa)
1a/2a/3
Entry
Primary amides
1
2
3
4
5
6
7
8
Mesitylene
Anisole
o-Xylene
PhCl
Toluene
Heptane
EtCN
175
165
155
140
125
110
110
110
2:96:2
11:85:4
7:91:2
9:89:2
62:36:2
98:2:0
95:5:0
91:9:0
Ph
CONH2
1
2
2a, 91
1a
CONH2
2b, 54 (81b))
8
1b
1c
3
2c, 79c)
CONH2
Dioxane
a) Bath temperature.
CONH2
4
5
6
2d, 84
2e, 64
nium(VI) and rhenium(IV) oxides were inert (Table 1, Entries
11 and 12). Since trimethylsilylperrhenate and rhenium(VII)
oxide are very moisture-sensitive and highly expensive, we
chose aqueous perrhenic acid (which is easy to handle and less
expensive than trimethylsilylperrhenate) as a practical dehy-
dration catalyst. Interestingly, dibutyltin oxide was almost
inert under the same conditions (Table 1, Entry 9).3c,d
1d
Ph
CONH2
1e
MeO
2f, 91
CONH2
CONH2
We next investigated the solvent effect on the dehydration
reaction of 1a catalyzed by aqueous perrhenic acid (9–
10 mol %) under azeotropic reflux conditions (Table 2). The
yield of the corresponding nitrile 2a was increased in the order
toluene < chlorobenzene < o-xylene < mesitylene (Table 2,
Entries 1 and 3–5). Anisole was also a good solvent, but its po-
larity slightly lowered the catalytic activity of perrhenic acid
(Table 2, Entry 2). The dehydration of 1a occurred smoothly
only at temperatures above 125 ꢁC. The addition of molecular
sieves to the reaction mixture disturbed the dehydration.
To explore the generality and scope of the above perrhenic
acid-catalyzed dehydration reaction, various structurally di-
verse primary amides were examined (Table 3). The use of
perrhenic acid (1 mol %) under azeotropic reflux conditions
in mesitylene was adequate for dehydrating not only aliphatic
amides but also aromatic amides. The catalyst could be quan-
titatively recovered from the reaction mixture by the distilla-
tion of products and solvents. For example, the catalyst was
reused for the dehydration of o-toluamide (1g) more than three
times with no loss of catalytic activity (Table 3, Entry 7).
This reusability of perrhenic acid is synthetically equal to
>300 of TON. The reaction was successful for sterically con-
gested amides such as 1-adamantanecarboxamide (1d) and 1g
(Table 3, Entries 4 and 7). The reaction of 2-ethylhexanamide
(1c) was carried out in toluene in the presence of trimethyl-
silylperrhenate because the boiling point of the corresponding
nitrile 2c is close to that of mesitylene (Table 3, Entry 3). Ani-
sole was effective as a solvent for the reaction of a less soluble
amide such as 1-naphthalenecarboxamide (1h) in mesitylene
(Table 3, Entry 8).
1f
2g, >99 (1st run)
7d)
2g, >99 (2nd run)
2g, >99 (3rd run)
1g
8
2h, 93e)
CONH2
1h
a) Isolated yield. b) (Me3SiO)ReO3 (1 mol %) was used as
a catalyst. The reaction time was prolonged to 2 days. c)
(Me3SiO)ReO3 (10 mol %) was used as a catalyst in toluene
in place of mesitylene. d) Perrhenic acid (1 mol %) was reused.
e) Anisole was used in place of mesitylene.
acylureas to nitriles might proceed in the presence of perrhenic
acid. In fact, N-(4-phenylbutyryl)urea was transformed to ni-
trile 2a via primary amide 1a as an intermediate by heating
in mesitylene at azeotropic reflux in the presence of 10 mol %
of perrhenic acid (Eq. 1).
O
O
HOReO3 (10 mol%)
N
H
NH2
2a
ð1Þ
mesitylene (4mL)
azeotropic reflux, 20 h
Ph
(1 mmol)
84% yield
Furthermore, we succeeded in a one-pot synthesis of nitriles
from the corresponding carboxylic acids and urea in the pres-
ence of a catalytic amount of 3,5-bis(trifluoromethyl)phenyl-
boronic acid and perrhenic acid. Thus, 2a and 2g were ob-
tained in good yields (Eqs. 2 and 3). This means that we can
use urea as a synthetic equivalent of ammonia.
Recently, we reported the catalytic synthesis of N-acylureas
through the direct condensation of carboxylic acids with ureas
using 3,5-bis(trifluoromethyl)phenylboronic acid as a cata-
lyst.4c We envisaged that a fragmentation reaction of N-mono-

402 Bull. Chem. Soc. Jpn. Vol. 80, No. 2 (2007)
Perrhenic Acid-Catalyzed Dehydration
Table 4. Catalytic Dehydration of Aldoximes to Nitriles
HOReO3 (10 mol%)
3,5-(CF3)2C6H3B(OH)2
aqueous (HO)ReO3
OH
HO
(0.9−1 mol%)
(10 mol%)
N
N
CO2H
or
RCN
(H2N)2C=O (3 equiv)
mesitylene (8 mL)
ð2Þ
ð3Þ
toluene (2 mL)
azeotropic reflux, 1 h
R
R
2a
2
syn - 4
anti - 4
Ph
(2 mmol)
azeotropic reflux, 20 h
(1 mmol)
83% yield
Entry
1
Aldoxime (syn/anti)
2/%a)
HOReO3 (10 mol%)
3,5-(CF3)2C6H3B(OH)2
(10 mol%)
n-C10H21CH=NOH
4a (0:100)
2i, >99b)
CO2H
cyclo-C6H11CH=NOH
4b (63:37)
2
3
2j, 91
(H2N)2C=O (3 equiv)
2d
C8H15
NOH
mesitylene (8 mL)
azeotropic reflux, 20 h
2k, 91c)
4c (97:3)
(2 mmol)
76% yield
NOH
Dehydration Reaction of Aldoximes.
Dehydration of
aldoximes with an appropriate dehydrating agent is an alterna-
tive method for the synthesis of nitriles.9 Recently, Yang and
Chang reported that the catalytic dehydration of aldoximes can
be promoted efficiently with [RuCl2(p-cymene)]2 (3 mol %).9a
However, this reaction requires molecular sieves (2 wt equiv)
to increase the reaction rate. According to our comparative ex-
periment in Table 1, Entry 13, [RuCl2(p-cymene)]2 was inert
for the dehydration of primary amides. Furthermore, in 1993,
Narasaka et al. reported that Bu4NReO4 is a good catalyst
for the dehydration of aldoximes to nitriles in the presence
of TfOH.10 Although they gave an example of the dehydration
of aldoximes, the yield of the obtained nitrile is not satisfacto-
ry. In their catalytic system, TfOH is necessary as a co-catalyst
to activate Bu4NReO4, and therefore it is not suitable for acid-
sensitive substrates. Thus, we interested in the catalytic activ-
ity and scope of perrhenic acid for the dehydration of aldo-
ximes to nitriles.
4
2l, 91d),e)
4d (100:0)
o-(MeO)C6H4CH=NOH 4e
(100:0)
m-(MeO)C6H4CH=NOH 4f
(100:0)
p-(MeO)C6H4CH=NOH 4g
(100:0)
5
6
7
2m, 94b)
2n, 86b)
2f, 97b)
O
O
NOH
8
9
2o, 95b)
4h (100:0)
O
NOH
O
2p, 99b)
The dehydration reaction was examined with various struc-
turally diverse aldoximes in the presence of aqueous perrhenic
acid (1 mol %) under azeotropic reflux conditions in toluene or
mesitylene (Table 4). The reaction was complete in less than
1 h for all aliphatic and aromatic substrates, except nicotin-
aldoxime (4l), and the corresponding nitriles were isolated in
good to excellent yields. Sterically congested aldoximes such
as cyclohexanecarbaldoxime (4b) (Table 4, Entry 2), o-me-
thoxybenzaldoxime (4e) (Table 4, Entry 5), ꢀ-naphthalenecarb-
aldoxime (4j) (Table 4, Entry 10), and mesitylenecarbaldo-
xime (4k) (Table 4, Entry 11) were more reactive than less
hindered aldoximes such as undecanaldoxime (4a) (Table 4,
Entry 1), and m- and p-methoxybenzaldoximes (4f and 4g re-
spectively) (Table 4, Entries 6 and 7): the former were dehy-
drated at reflux in toluene, whereas the latter were dehydrated
at reflux in mesitylene. trans-2-Undecenaldoxime (4c) and
all-trans-retinaldoxime (4d)9a were readily converted into their
corresponding nitriles in high yield with partial inversion of
the double bond (Table 4, Entries 3 and 4). The present meth-
od was useful for acid-sensitive substrates such as 2,3-(meth-
ylenedioxy)benzaldoxime (4h) and 3,4-(methylenedioxy)benz-
aldoxime (4i) (Table 4, Entries 8 and 9). Furthermore, per-
rhenic acid could be used as a dehydration catalyst in the pres-
ence of basic nitrogen-containing compounds: aldoxime 4l was
smoothly dehydrated with the catalyst system to give pyridine-
4i (100:0)
10
11
12
1-NapCH=NOH 4j (100:0)
2,4,6-Me3C6H2CH=NOH 4k
(100:0)
2h, 98
2q, >99
2r, 84b),f)
3-Pyridylch=NOH 4l (100:0)
a) Isolated yield. b) Mesitylene was used in place of toluene.
c) The E=Z ratio of the product was 92:8. d) o-Xylene was
used in place of toluene. The reaction time was prolonged
to 2 h. e) The isolated product was >98% all-trans. f) The
reaction time was prolonged to 3 h.
3-carbonitrile (2r) in 84% yield (Table 4, Entry 12).
Application of the Dehydration Reaction to a Large-
Scale Process. The applicability of the present protocol to
a large-scale process was investigated. Complete dehydration
of amide 1g (100 mmol) and aldoxime 4e (40 mmol) was ob-
served in the presence of aqueous perrhenic acid (<1 mol %),
and the corresponding nitriles (2g and 2m) were isolated in
high yield (Eqs. 4 and 5).
(HO)ReO3
(0.45−0.5 mol%)
ð4Þ
1g
2g
mesitylene (40 mL)
(100 mmol)
97% yield
azeotropic reflux, 1 day

Y. Furuya et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 2 (2007)
403
amides should give the corresponding imides 3. Therefore, the
oxophilicity of rhenium(VII) oxo complexes is a significant
factor in obtaining nitriles as major products.13,14 The high re-
activity of sterically congested aldoximes and the low reactiv-
ity of less hindered aldoximes can be explained through B and
B0, which is generated from a syn isomer of aldoximes. syn/
anti Isomerization of aldoximes is known to occur under ther-
mal or acidic conditions.15 Therefore, the reactivity of aldo-
ximes for this dehydration may depend on their syn/anti
equilibrium under these reaction conditions. In the case of
Beckmann fragmentation, the reaction mechanism could be
explained by the idea that an oxygen atom on rhenium attacks
the cationic carbon atom at the ꢀ-position of ketoximes instead
of the proton in transition states B and B0. It is not clear why
trimethylsilylperrhenate is more active than perrhenic acid
(HO)ReO3
(0.9−1.0 mol%)
ð5Þ
4e
2m
toluene (20 mL)
azeotropic reflux, 4.5 h
(40 mmol)
91% yield
The Beckmann Fragmentation of ꢀ-Substituted Keto-
ximes. The Beckmann fragmentation of ꢀ-substituted cyclic
ketoximes is a powerful tool for the synthesis of functionalized
nitriles.11 However, most of the examples reported to date re-
quire the use of stoichiometric dehydrating or acidic reagents,
and only a few reports have referred to the catalytic reaction.12
For example, in 1983, Nishiyama, Itoh, and co-workers found
that a catalytic amount of trimethylsilyl trifluoromethanesul-
fonate (Me3SiOTf) promotes the Beckmann fragmentation
of ꢁ-trimethylsilylketoxime acetates to unsaturated nitriles.12a
The substrates of this catalytic system are limited to ꢁ-trialkyl-
silylated ketoximes because the silyl cation is required for
regeneration of the catalyst. Since the activation step of frag-
mentation is the same as in the dehydration of aldoximes,
we expected that perrhenic acid might effectively promote
the fragmentaion of ketoximes bearing an electron-donating
group at the ꢀ-position.
Table 5. Beckmann Fragmentation of ꢀ-Substituted Ketoximes
NOH
CN OH
aqueous (HO)ReO3 (0.45−0.5 mol%)
X
C
C
C
C X
toluene (4 mL)
azeotropic reflux, 30 min
5 (2 mmol)
6
The Beckmann fragmentation of several ketoximes was ex-
amined in the presence of 0.5 mol % of perrhenic acid under
azeotropic reflux in toluene for 30 min (Table 5). As a result,
the corresponding nitriles were obtained in excellent yield with-
out any other side products. The use of [RuCl2(p-cymene)]2,9a
Bu2SnO,3c,d and Me3SiOTf12a instead of perrhenic acid as a
catalyst showed no activity for the Beckmann fragmentation
of 5a.
Consideration of the Reaction Mechanism for the Dehy-
dration of Primary Amides and Aldoximes Catalyzed by
Perrhenic Acid. Based on the reactivities of primary amides
and aldoximes in perrhenic acid-catalyzed dehydrations, we
propose the mechanism shown in Scheme 1. The reaction of
the substrates and perrhenic acid leads to six-membered cyclic
transition states A and B (upon dehydration) or to the analo-
gous transition states A0 and B0 (without dehydration).3c,d De-
hydration of primary amides and aldoximes to produce nitriles
should be promoted by the selective coordination of rhe-
nium(VII) oxo complexes with their oxygen atoms. In contrast,
coordination of the catalyst with the nitrogen atom of primary
Isolated
yield/%
Entry
Ketoxime
Product
OH
N
OHC
O
1a)
5a
5b
6a
6b
97
CN
CN
OMe
2
>99
MeO
N
OH
OH
OHC
CN
3
4
5c
6c
>99
N
N
OH
HO2C
CN
O
5d
6d
93
OH
a) [RuCl2(p-cymene)]2,9a Bu2SnO,3c,d and Me3SiOTf12a were
inert.
OH
O
O
HO
O
O
O
H
(HO)ReO3
−(HO)ReO3
O
Re
N
Re
RCN
RCN
O
O
or
or
R
R
NH2
(−H2O for A)
(−H2O for A')
H
R
R
N
A
A'
OH
O
O
HO
O
O
OH
N
Re
Re
−(HO)ReO3
(HO)ReO3
O
O
O
N
H
(−H2O for A')
N
H
(−H2O for A)
H
R
R
B'
syn-anti
isomerization
B
Scheme 1. Proposed mechanism for the dehydration of primary amides and aldoximes to form nitriles.

404 Bull. Chem. Soc. Jpn. Vol. 80, No. 2 (2007)
Perrhenic Acid-Catalyzed Dehydration
pound was prepared by known method.9a IR (KBr) 3264, 2986,
2908, 2785, 1498, 1463, 1309, 1253, 1222, 1201, 1082, 1028, 968,
and rhenium(VII) oxide. Pure perrhenic acid has not been
isolated because it exists preferentially as a dimeric species
O3ReOReO3 under anhydrous conditions,16 whereas trimethyl-
silylperrhenate is monomeric. Therefore, monomeric rhe-
nium(VII) oxo species may be more active than dimeric or oli-
gomeric complexes.
927 cmꢂ1 1H NMR (300 MHz, CDCl3) ꢂ 9.15 (s, 1H), 8.14 (s,
;
1H), 6.96–6.83 (m, 3H), 6.07 (s, 2H); 13C NMR (75 MHz, CDCl3)
ꢂ 148.0, 146.0, 145.1, 121.8, 121.1, 114.5, 109.5, 101.5; HRMS
(FAB) calcd for C8H7NO3 [ðM þ HÞþ] 166.0504, found 166.0500.
General Procedure for the Dehydration of Primary Amides
and Aldoximes (Tables 3 and 4). A solution of primary amides
(1 mmol) or aldoximes (1 mmol), perrhenic acid (65–70 wt % solu-
tion in water, 0.009–0.010 mmol, 0.9–1.0 mol %), and solvent
(2 mL) was heated at azeotropic reflux with the removal of water.
After several hours, the mixture was cooled to ambient tempera-
ture and saturated aqueous NaHCO3 was added. The organic layer
was extracted with ethyl acetate and dried over anhydrous
MgSO4, filtered, and concentrated under vacuum. The crude prod-
uct was purified by flash column chromatography on silica gel.
Procedure for Preparation of N-Carbamoyl-4-phenylbutan-
amide. A mixture of 4-phenylbutanoic acid (131 mg, 2 mmol),
urea (132 mg, 2.2 mmol), and 3,5-bis(trifluoromethyl)phenylbo-
ronic acid (25.8 mg, 0.1 mmol) in toluene (10 mL) was heated at
azeotropic reflux with removal of water. After reaction completed,
the resulting mixture was cooled to ambient temperature and
washed with saturated aqueous ammonium chloride and satulated
aqueous NaHCO3, and the product was extracted with ethyl ace-
tate. The combined organic layers were dried over anhydrous
MgSO4, The solvent was evaporated, and the residue was purified
by flash column chromatography on silica gel to give pure product
in 92% yield. IR(KBr) 3378, 3327, 3229, 1655, 1418, 1183, 1095,
Conclusion
We have reported here several noteworthy features of new
catalysts for the dehydration not only of primary amides and
aldoximes but also of N-monoacylureas. Furthermore, we have
also demonstrated that rhenium(VII) oxo complexes efficiently
catalyze the Beckmann fragmentation of ꢀ-substituted keto-
ximes. These reactions proceed under acidic but nearly neutral
conditions, and the catalyst is recoverable and reusable. This
protocol can be readily applied to large-scale processes with
high efficiency and selectivity, making it an economical and
environmentally benign process for the preparation of nitriles.
Experimental
General. Infrared (IR) spectra were recorded on a JASCO
FT/IR-460 plus spectrometer. 1H NMR spectra were measured
on a Varian Gemini-2000 spectrometer (300 MHz). Tetramethyl-
silane was used as an internal standard (ꢂ 0.00 ppm). 13C NMR
spectra were measured on a Varian Gemini-2000 spectrometer
(75 MHz). Chemical shifts were recorded in ppm from the solvent
resonance (CDCl3 at 77.0 ppm). High-resolution mass spectral
analysis (HRMS) was performed at the Chemical Instrument
Room, Research Center for Material Science, Nagoya University.
Microanalyses were performed at the Chemical Instrument Room,
Research Center for Material Science, Nagoya University. For
preparative column chromatography, Merck silica gel 60 (0.040–
0.063 mm) was used. Unless otherwise noted, materials were ob-
tained from commercial suppliers and used without further purifi-
cation. Trimethylsilylperrhenate was purchased from Gelest-
Azmax. Perrhenic acid (65–70% in water, 99.999+%) and rhe-
nium(VII) oxide were purchased from Aldrich. Primary amides
1a–1h are commercially available. The following obtained nitriles
are commercially available: 2a–2j, 2m, 2n, and 2p–2r. The fol-
lowing obtained nitriles are known compounds: 2k,17 2l,9a and
2o.18 Aldoximes 4b, 4c, 4e–4g, and 4i–4l are commercially avail-
able. Aldoxime 4d was prepared by the known method.9a The fol-
lowing aldoxime is a known compound: 4a.19 Ketoximes 5c and
5d are commercially available. Ketoxime 5a is a known com-
pound.20 The following obtained nitriles are known compounds:
6a,21 6c,22 and 6d.23
696 cmꢂ1 1H NMR (300 MHz, THF-d8) ꢂ 9.68 (s, 1H), 7.98 (s,
;
1H), 7.26–7.11 (m, 5H), 6.70 (s, 1H), 2.63 (t, J ¼ 7:5 Hz, 2H),
2.29 (t, J ¼ 7:5 Hz, 2H), 1.92 (quintet, J ¼ 7:5 Hz, 2H); 13C NMR
(75 MHz, THF-d8) ꢂ 175.0, 155.4, 142.6, 129.2, 129.1, 126.6,
36.4, 35.9, 27.3; HRMS (FAB) calcd for C11H15N2O2 [ðM þ
HÞþ] 168.1025, found 168.1013.
Procedure for Dehydration of N-Carbamoyl-4-phenylbu-
tanamide. A mixture of N-carbamoyl-4-phenylbutanamide, per-
rhenic acid (65–70 wt % solution in water, 0.09–0.10 mmol, 9.0–
10 mol %), and mesitylene (4 mL) was heated at azeotropic reflux
with the removal of water. After 20 h, the mixture was cooled to
ambient temperature and saturated aqueous NaHCO3 was added.
The organic layer was extracted with ethyl acetate and dried over
anhydrous MgSO4, filtered, and concentrated under vacuum. The
crude product was purified by flash column chromatography on
silica gel to give 1a in 84% yield.
Procedure for One-Pot Synthesis of Nitriles from Carboxyl-
ic Acids and Ureas. A mixture of carboxylic acid, urea (46.0 mg,
6 mmol), 3,5-bis(trifluoromethyl)phenylboronic acid (51.6 mg, 0.2
mmol, 10 mol %), perrhenic acid (65–70 wt % solution in water,
0.09–0.10 mmol, 9.0–10 mol %), and mesitylene (8 mL) was heat-
ed at azeotropic reflux with the removal of water. After 1 day, the
mixture was cooled to ambient temperature and saturated aqueous
NaHCO3 was added. The organic layer was extracted with ethyl
acetate and dried over anhydrous MgSO4, filtered, and concentrat-
ed under vacuum. The crude product was purified by flash column
chromatography on silica gel to give pure product.
Procedure for Preparation of 1-Methoxybicyclo[2.2.2]oct-5-
en-2-one Oxime (5b). To a mixture of 1-methoxybicyclo[2.2.2]-
oct-5-en-2-one24 (2.0 g, 13.2 mmol) and hydroxylamine hydro-
chloride (2.12 g, 30.3 mmol) in 18 mL of methanol, 9 mL of aque-
ous solution of sodium acetate trihydrate (4.53 g, 33.0 mmol) was
adde at rt. The mixture was then refluxed until all starting material
consumed. The reaction mixture was poured into saturated aque-
(E)-Undec-2-enal Oxime (4c). This compound was prepared
by known method9a and obtained in a syn/anti mixture (The ratio
1
of syn/anti was 97/3 determined by H NMR spectra.). IR (neat)
3205, 3067, 2925, 2855, 1649, 1465, 1336, 1117, 976 cmꢂ1
;
1H NMR (300 MHz, CDCl3) for syn-4c ꢂ 7.73 (d, J ¼ 9:0 Hz,
1H), 7.59 (brs, 1H), 6.16–5.99 (m, 2H), 2.16 (q, J ¼ 6:9 Hz, 2H),
1.44–1.27 (m, 12H), 0.88 (t, J ¼ 6:6 Hz, 3H); for anti-4c ꢂ 7.04
(d, J ¼ 9:3 Hz, 1H), 6.72 (dd, J ¼ 9:6, 15.6 Hz, 1H), 6.12 (dt,
J ¼ 6:9, 15.6 Hz, 1H), 2.19 (q, J ¼ 7:2 Hz, 2H), 1.44–1.27 (m,
12H), 0.88 (t, J ¼ 6:4 Hz, 3H); 13C NMR (125 MHz, CDCl3) for
syn-4c ꢂ 151.7, 142.8, 123.6, 32.7, 31.8, 29.3, 29.2, 29.1, 28.6,
22.6, 14.0; for anti-4c ꢂ 148.7, 144.2, 118.6, 32.8, 31.7, 29.3,
29.1 (2C), 28.5, 22.6, 14.0; HRMS (FAB) calcd for C11H21NO
[ðM þ HÞþ] 184.1701, found 184.1700.
2,3-Methylenedioxybenzaldehyde Oxime (4h). This com-

Y. Furuya et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 2 (2007)
405
ous NaHCO3, the organic layer was extracted with ethyl acetate
and washed with brine. Drying of combined extracts over MgSO4,
followed by evaporative concentration, and flash chromatography
on silica gel gave the pure 5b in 36% yield. IR (KBr) 3230,
6
a) K. Ishihara, H. Kurihara, H. Yamamoto, Synlett 1997,
597. b) S. Saito, T. Nagahara, H. Yamamoto, Synlett 2001, 1690.
Part of this work has been published as a preliminary
7
communication: K. Ishihara, Y. Furuya, H. Yamamoto, Angew.
Chem., Int. Ed. 2002, 41, 2983.
1
2970, 1613, 1422, 1112, 1015 cmꢂ1; H NMR (300 MHz, CDCl3)
ꢂ 7.56 (brs, 1H), 6.36 (d, J ¼ 3:6 Hz, 2H), 3.54 (s, 3H), 2.83 (brs,
1H), 2.43 (dd, J ¼ 2:5, 17.8 Hz, 1H), 2.26 (dt, J ¼ 18:0, 3.1 Hz,
1H), 1.90–1.81 (m, 1H), 1.75–1.64 (m, 2H), 1.57–1.50 (m, 1H);
13C NMR (75 MHz, CDCl3) ꢂ 160.2, 134.5, 131.5, 79.2, 52.7,
31.3, 30.0, 29.1, 24.8; HRMS (FAB) calcd for C9H14NO2 [ðM þ
HÞþ] 168.1025, found 168.1013.
8
For isomerization of allylic alcohols or allylic ethers
catalyzed by (R3SiO)ReO3, see: a) S. Bellemin-Laponnaz, H.
Gisie, J. P. Le Ny, J. A. Osborn, Angew. Chem., Int. Ed. Engl.
1997, 36, 976. b) S. Bellemin-Laponmaz, J. P. Le Ny, J. A.
Osborn, Tetrahedron Lett. 2000, 41, 1549. c) C. Morrill, R. H.
Grubbs, J. Am. Chem. Soc. 2005, 127, 2842. d) E. C. Hansen,
D. Lee, J. Am. Chem. Soc. 2006, 128, 8142.
General Procedure for Beckmann Fragmentation of Keto-
ximes (Table 5). A solution of ketoximes (2 mmol), perrhenic
acid (65–70 wt % solution in water, 0.009–0.010 mmol, 0.45–
0.50 mol %), and toluene (4 mL) was heated at azeotropic reflux
with the removal of water for 30 min. The resulting mixture was
purified by flash column chromatography on silica gel to afford
pure products.
9
a) S. H. Yang, S. Chang, Org. Lett. 2001, 3, 4209. b) P.
Yan, P. Batamack, G. K. S. Prakash, G. A. Olah, Catal. Lett.
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K. R. Sabu, Synth. Commun. 1999, 29, 3409. g) G. Sabitha, M.
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Battioni, J.-L. Boucher, D. Mansuy, J. Am. Chem. Soc. 1998,
120, 12524. i) O. Attanasi, P. Palma, F. Serra-Zanetti, Synthesis
1983, 741. j) H. M. Meshram, Synthesis 1992, 943.
10 For a Beckmann rearrangement catalyzed by [Bu4NReO4]
and trifluoromethanesulfonic acid, see: H. Kusama, Y. Yamashita,
K. Narasaka, Bull. Chem. Soc. Jpn. 1995, 68, 373.
11 a) T.-L. Ho, Heterolytic Fragmentation of Organic
Molecules, Wiley, New York, 1992. b) K. Hori, K. Nomura, S.
Mori, E. Yoshii, J. Chem. Soc., Chem. Commun. 1989, 712.
c) P. J. Biju, M. S. Laxmisha, G. S. R. S. Rao, J. Chem. Soc.,
Perkin Trans. 1 2000, 4512.
(4-Oxocyclohex-2-enyl)acetonitrile (6b).
IR(neat) 2954,
2870, 2247, 1682, 1390, 1252 cmꢂ1; H NMR (300 MHz, CDCl3)
ꢂ 6.82 (dt, J ¼ 10:2, 2.4 Hz, 1H), 6.12 (dd, J ¼ 1:9, 10.0 Hz, 1H),
2.93–2.83 (m, 1H), 2.63–2.54 (m, 3H), 2.44 (ddd, J ¼ 5:1, 12.0,
17.1 Hz, 1H), 2.34–2.24 (m, 1H), 1.90 (ddt, J ¼ 10:0, 13.0, 4.5
Hz, 1H); 13C NMR (75 MHz, CDCl3) ꢂ 197.6, 149.1, 130.8,
117.3, 36.1, 32.9, 28.2, 22.5; HRMS (FAB) calcd for C8H10NO
[ðM þ HÞþ] 136.0762, found 136.0762.
1
Financial support for this project was provided by SORST,
JST, the 21st Century COE Program of MEXT. We thank
Mr. Toshikatsu Maki for helpful experiments.
12 a) H. Nishiyama, K. Sakuta, N. Osaka, K. Itoh, Tetra-
hedron Lett. 1983, 24, 4021. b) H. Nishiyama, K. Sakuta, N.
Osaka, H. Arai, M. Matsumoto, K. Itoh, Tetrahedron 1988, 44,
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Tetrahedron Lett. 1991, 32, 5367.
13 For the oxophilicity of rhenium(VII) oxo complexes, see:
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14 For the coordination of N,N-dimethylformamide to rhe-
nium complexes through its oxygen atom, see: a) H.-A. Lehmann,
Ch. R. Ringel, Z. Anorg. Allg. Chem. 1969, 366, 73. b) T.
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