Nickel/zinc-mediated synthesis of aromatic nitriles from aromatic oxime ethers

Article abstract of DOI:10.1081/SCC-120005932

Treatment of o-alkoxybenzaldoxime ethers 3 with an equimolar amount of NiCl₂ and 3 equimolar amounts of Zn gave o-alkoxybenzonitriles 4 in good yields. It is suggested that the reaction proceed via coordination of the ether oxygen atom of alkyl

Full text of DOI:10.1081/SCC-120005932

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NICKEL/ZINC-MEDIATED SYNTHESIS OF AROMATIC
NITRILES FROM AROMATIC OXIME ETHERS
a
a
a
b
Katsuya Maeyama , Masato Kobayashi , Hiroshi Kato & Noriyuki Yonezawa*
a
Department of Organic and Polymer Materials Chemistry , Tokyo University of Agriculture
and Technology , Koganei, Tokyo, 184-8588, Japan
b
Department of Organic and Polymer Materials Chemistry , Tokyo University of Agriculture
and Technology , Koganei, Tokyo, 184-8588, Japan
Published online: 16 Aug 2006.
To cite this article: Katsuya Maeyama , Masato Kobayashi , Hiroshi Kato & Noriyuki Yonezawa* (2002) NICKEL/ZINC-MEDIATED
SYNTHESIS OF AROMATIC NITRILES FROM AROMATIC OXIME ETHERS, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 32:16, 2519-2525, DOI: 10.1081/SCC-120005932
To link to this article: http://dx.doi.org/10.1081/SCC-120005932
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 16, pp. 2519–2525, 2002
NICKEL/ZINC-MEDIATED SYNTHESIS
OF AROMATIC NITRILES FROM
AROMATIC OXIME ETHERS
Katsuya Maeyama, Masato Kobayashi,
Hiroshi Kato, and Noriyuki Yonezawa*
Department of Organic and Polymer Materials
Chemistry, Tokyo University of Agriculture and
Technology, Koganei, Tokyo, 184-8588, Japan
ABSTRACT
Treatment of o-alkoxybenzaldoxime ethers 3 with an equi-
molar amount of NiCl2 and 3 equimolar amounts of Zn
gave o-alkoxybenzonitriles 4 in good yields. It is suggested
that the reaction proceed via coordination of the ether
oxygen atom of alkyl ether moiety to low-valent metal species.
Key Words: Aromatic oxime ether; Aromatic nitriles;
Nickel/zinc reagent
Nitriles are the useful synthetic intermediates applicable to transfor-
mation to various organic compounds such as amines, ketones, and hetero-
cycles. In general, nitriles have been synthesized via substitution reaction
[
1]
of alkyl halides with metal cyanide, reaction of diazonium salts with
[2]
copper cyanide, and dehydration of primary amides or aldoximes.
*
Corresponding author. E-mail: yonezawa@cc.tuat.ac.jp
519
2
DOI: 10.1081/SCC-120005932
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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2
520
MAEYAMA ET AL.
However, metal cyanide has high toxicity and is troublesome to be handled.
Dehydration of primary amides or aldoxime generally requires acidic
[
3]
[4]
or SOCl2. Basic reagents such as
n-BuLi are also available for the synthesis of nitriles from aldoximes or
dehydrating reagent such as P O
2
5
[5]
aldoxime ethers. A few papers have been reported on synthesis of nitriles
0
from aldoximes using DCC or 1,1 -carbonyldiimidazole under neutral con-
[6]
ditions. Previously, we reported NiCl /Zn-mediated alkyl carbon–oxygen
2
[
7]
bond cleavage of alkyl aryl ethers (Scheme 1). This reaction proceeds by
coordination of nitrogen atom on the pyridine ring to low-valent nickel
species. The results prompted us to extend the reaction to other conversions.
We planned the synthesis of nitriles utilizing activation of aldoxime
derivatives by low-valent metal species.
0
Scheme 1. Reaction of 2-(2 -pyridyl)anisole (1) with Ni/Zn reagent.
Scheme 2. Reaction of ethyl (E)-o-anisaldehyde O-ethyloxime (3a) with Ni/Zn
reagent.
Herein we would like to report that a mixture of NiCl and Zn is a
2
useful reagent for the conversion of aldoxime ethers to the corresponding
nitriles on condition that a coordination site is located at a suitable
position in the aldoxime ether molecules (Scheme 2).
When (E)-o-methoxybenzaldehyde O-ethyloxime (3a) was treated
with an equimolar amount of NiCl and 3 equimolar amounts of zinc
2
powder in p-xylene under reflux, o-methoxybenzonitrile (4a) was obtained
in a 71% yield. To estimate the feasibility for this transformation, we
attempted the reaction of benzaldoxime ethyl ether (3b) with NiCl /Zn
2
reagent. However, only recovery of the starting material was confirmed.

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NITRILES FROM OXIME ETHERS
2521
Scheme 3. Reaction of benzaldoxime ethyl ether derivatives with Ni/Zn reagent.
This fact means the methoxy group would promote this transformation.
Then, we next attempted the reaction of aldoxime ether 3c with methoxy
group at p-position. However, the transformation did not proceed and the
starting material was recovered. On the basis of these results, we were con-
vincedthatthereactionproceedsbytheassistofthecoordinationoftheoxygen
atom on aryl methyl ether moiety to low-valent metal species (Scheme 3).
Then we examined the effects of the kind of metal reagents and
reaction conditions. Table 1shows the results.
When the reaction was carried out in the presence of NiCl /Zn,
2
Ni(acac) /Zn, or Ni(cod) , the desired product was obtained in moderated
2
2
yields (Runs 1–3). However, the yield was lowered when the reaction was
undertaken in the presence of an equimolar amount of PPh (Run 4).
3
Addition of an extra ligand was proved to interfere with the reaction. These
results demonstrate that low-valent metal species takes part in the reaction.
The reaction of aldoxime ether 3a with FeCl /Zn system gave no
3
nitrile compound. Instead, only o-anisaldehyde was obtained which was
probably produced via hydrolysis of aldoxime ether 3a. Accordingly, it
has become apparent that NiCl /Zn, Ni(acac) /Zn, or Ni(cod) is suitable
2
2
2
for this transformation.
The reaction of aldoxime ether 3a with FeCl /Zn system gave no
3
nitrile compound. Instead, only o-anisaldehyde was obtained which was
probably produced via hydrolysis of aldoxime ether 3a. Accordingly, it
has become apparent that NiCl /Zn, Ni(acac) /Zn, or Ni(cod) is suitable
2
2
2
for this transformation.
Then we examined the effect on the substituents (R , R ) on the
1
2
two kinds of ether bonds in the reaction with NiCl /Zn. The results are
2
shown in Table 2. In the reaction of aldoxime ethers 3a,d,e, the desired
product was obtained in moderated yields (Runs 1–3). However, when

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522
MAEYAMA ET AL.
Table 1. Reaction of Aromatic Aldoxime Ether 3a
Run
Metal Reagents
Additive
Yield (%)
1
2
3
4
5
NiCl
2
/Zn
Ni(acac) /Zn
none
none
71
72
55
43
2
Ni(cod)
NiCl /Zn
FeCl /Zn
2
none
a
2
PPh
3
none
b
0
3
Reaction conditions: substrate, 0.3 mmol; nickel or iron reagent, 0.3 mmol; Zn,
0
.9 mmol (except for Run 3); p-xylene, 1mL.
PPh (0.3 mmol) was added.
o-Anisaldehyde was obtained in a ca. 40% yield.
a
3
b
isopropyl ether 3f was employed for this reaction, the yield was greatly
lowered (Run 4). It is due to the difficulty of coordination or interaction
of the sterically hindered oxygen atom to the metal center.
This result demonstrates that the coordination or the related inter-
action of the oxygen atom of the aryl methyl ether moiety is essential for
this reaction. There are two plausible pathways; one is oxidative addition of
nickel(0) reagent generated in situ to nitrogen–oxygen bond followed by
b-elimination to produce nitriles and H–Ni–OR. In this pathway,
however, the nitrogen–oxygen bond and aryl alkyl ether oxygen atom are
suspected to be too apart to coordinate to one metal center at the same time.
The other pathway is as follows: (1) coordination of aryl alkyl ether oxygen
atom to low-valent metal species, (2) its oxidative addition to imino carbon–
hydrogen bond situated in the neighborhood of the coordination site, and (3)
b-elimination to produce nitriles and H–Ni–OR. At present, however, we
have not made the reaction mechanism clear yet.
In conclusion, we realized the effective conversion of alkyl aromatic
aldoxime ethers, which have a coordination site on the benzene ring, to
aromatic nitriles in the presence of Ni/Zn reagent.
EXPERIMENTAL
1
13
H and C NMR spectra were recorded on a JEOL JNM-A500
1
13
H; 500 MHz, C; 125 MHz) spectrometer or a JEOL FX-200 ( H;
1
(

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NITRILES FROM OXIME ETHERS
Table 2. Reaction of Aromatic Aldoxime Ethers 3
2523
1
2
Run
Substrate
R
R
Yield (%)
1
2
3
4
3a
3d
3e
3f
Et
Me
Et
Me
Me
Et
71
43
68
20
Et
i-Pr
Reaction conditions: substrate, 0.3 mmol; nickel chloride, 0.3 mmol; Zn, 0.9 mmol;
p-xylene, 1mL.
1
13
2
00 MHz) spectrometer using Me Si ( H, ꢀ 0.00) and CDCl ( C, ꢀ 77.0) as
4 3
internal standards. IR spectra were recorded on a JEOL FTIR-5300 spec-
trometer. Aldoxime ethers 3 were prepared according to a conventional
ꢀ
procedure. Ni(acac) and FeCl were dried at 150 C under reduced pressure
3
2
before use. Ni(cod) was purchased and used without any purification.
2
ꢀ
NiCl was dried at 150 C in vacuo for 3 h and immediately used for the
2
reaction. p-Xylene was distilled from CaH just before use. Zinc powder
2
was activated according to the following method. Acetic acid (200 mL)
was added to zinc powder (40 g), and the mixture was stirred overnight.
After acetic acid was removed by decantation, the residual mixture was
[
8]
washed with ether for three times, and dried under reduced pressure.
E)-o-Anisaldehyde O-ethyloxime (3a) IR (neat) 2976, 2839, 1607,
(
À1
1
1
489, 1464, 1439, 1252, 1055, 1028 cm ; H NMR ꢀ (CDCl ) 1.32 (3H, t,
3
J ¼ 6.7 Hz), 3.83 (3H, s), 4.22 (2H, q, J ¼ 6.7 Hz), 6.88 (1H, d, J ¼ 7.5 Hz),
6
8
1
7
.94 (1H, t, J ¼ 7.5 Hz), 7.31( 1H , t, J ¼ 7.5 Hz), 7.79 (1H, d, J ¼ 7.5 Hz),
1
3
.48 (1H, s) ppm; C NMR ꢀ (CDCl ) 14.6, 55.5, 69.6, 111.0, 120.7, 121.0,
3
26.3, 130.9, 144.5, 157.5 ppm. Anal. Calcd. for C H NO : C, 67.00%; H,
13
1
0
2
.32%; N, 7.82%. Found: C, 67.22%; H, 7.60%; N, 7.57%.
(
[
E)-o-Anisaldehyde O-methyloxime (3d) IR (neat) 2937, 1607, 1489,
5]
À1
1
1
6
7
ꢀ
466, 1254, 1055, 754 cm ; H NMR ꢀ (CDCl ) 3.84 (3H, s), 3.97 (3H, s),
3
.88 (1H, d, J ¼ 7.6 Hz), 6.95 (1H, t, J ¼ 7.6 Hz), 7.34 (1H, dt, J ¼ 2.0,
1
3
.6 Hz), 7.78 (1H, dd, J ¼ 2.0, 7.6 Hz), 8.46 (1H, s) ppm; C NMR
(CDCl ) 61.8, 62.4, 110.0, 120.7, 120.8, 126.4, 131.1, 144.8, 157.5 ppm.
3
Anal. Calcd. for C H NO : C, 65.42%; H, 6.71%; N, 8.48%. Found:
9
11
2
C, 65.29%; H, 6.59%; N, 8.28%.

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524
MAEYAMA ET AL.
(
607, 1489, 1454, 1250, 1053 cm
E)-o-Ethoxybenzaldehyde O-ethyloxime (3e) IR (neat) 2980, 2934,
À1
1
1
;
H NMR ꢀ (CDCl ) 1.34 (3H, t,
3
J ¼ 7.0 Hz), 1.42 (3H, t, J ¼ 7.0 Hz), 4.05 (2H, q, J ¼ 7.0 Hz), 4.23 (2H, q,
J ¼ 7.0 Hz), 6.93 (1H, d, J ¼ 7.2 Hz), 6.99 (1H, t, J ¼ 7.2 Hz), 7.37 (1H,
dt, J ¼ 2.0, 7.2 Hz), 7.86 (1H, dd, J ¼ 2.0, 7.2 Hz), 8.48 (1H, s) ppm;
1
3
C NMR ꢀ (CDCl ) 14.6, 14.8, 63.9, 69.6, 112.0, 120.6, 121.0, 126.2,
3
1
30.7, 144.6, 156.9 ppm. Anal. Calcd. for C H NO : C, 68.35%; H,
1
1
15
2
7
.83%; N, 7.25%. Found: C, 68.65%; H, 7.89%; N, 7.17%.
E)-o-Isopropoxybenzaldehyde O-ethyloxime (3f): IR (neat) 2978, 2932,
(
À1
1
1
607, 1485, 1246, 1055 cm ; H NMR ꢀ (CDCl ) 1.32–1.34 (9H, m), 4.22
3
(
2H, q, J ¼ 7.0 Hz), 4.56 (1H, sept, J ¼ 6.0 Hz), 6.88 (1H, d, J ¼ 7.5 Hz), 6.91
(
1H, t, J ¼ 7.5 Hz), 7.29 (1H, dt, J ¼ 1.5, 7.5 Hz), 7.80 (1H, dd, J ¼ 1.5,
1
3
7
.5 Hz), 8.48 (1H, s) ppm; C NMR ꢀ (CDCl ) 14.6, 22.0, 69.6, 70.7,
3
113.8, 120.6, 122.0, 126.3, 130.7, 144.8, 155.9 ppm. Anal. Calcd. for
C H NO : C, 69.52%; H, 8.27%; N, 6.76%. Found: C, 69.63%; H,
1
2
17
2
8
.40%; N, 6.47%.
Typical reaction procedure: reaction of (E)-o-Anisaldehyde O-ethyl-
oxime (3a) with Ni/Zn reagent: A mixture of nickel(II) chloride (39 mg,
.30 mmol), zinc powder (59 mg, 0.90 mmol), and (E)-o-anisaldehyde
0
O-ethyloxime (3a) (56 mg, 0.30 mmol) was stirred in p-xylene (1mL) under
reflux for 1day under nitrogen atmosphere. The resulting solution
was quenched by addition of water (20 mL). The aqueous solution thus
obtained was extracted with ethyl acetate (15 mL) for three times. The
combined extracts were washed with brine and dried over with MgSO4
overnight. After removal of solvents, the residue was separated by prepara-
tive TLC (Wakogel B-5F) with n-hexane/ethyl acetate (9 : 1) to give o-meth-
oxybenzonitrile (4a) (28 mg) in a 71% yield.
ACKNOWLEDGMENT
This work was supported by Mitsubishi Chemical Corporation
Fund and the Ministry of Education, Culture, Sports, Science, and
Technology of Japan.
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(
b) Mowry, D.T.; Butler, J.M. Org. Synth., Coll. Vol. IV, 1963, 486.

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NITRILES FROM OXIME ETHERS
2525
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8
3
Received in Japan July 2, 2001

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