Nickel/zinc-mediated alkyl carbon-oxygen bond cleavage of alkyl aryl ethers

Article abstract of DOI:10.1081/SCC-100103322

Alkyl carbon-oxygen bonds of alkyl aryl ethers bearing suitable coordination sites were efficiently cleaved by treatment with nickel(II) chloride and zinc in p-xylene under neutral conditions.

Full text of DOI:10.1081/SCC-100103322

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NICKEL/ZINC-MEDIATED ALKYL
CARBON-OXYGEN BOND
CLEAVAGE OF ALKYL ARYL
ETHERS
a
a
Katsuya Maeyama , Masato Kobayashi
&
b
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: 09 Nov 2006.
To cite this article: Katsuya Maeyama , Masato Kobayashi & Noriyuki Yonezawa
2001) NICKEL/ZINC-MEDIATED ALKYL CARBON-OXYGEN BOND CLEAVAGE OF ALKYL
(
ARYL ETHERS, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:6, 869-875, DOI: 10.1081/
SCC-100103322
To link to this article: http://dx.doi.org/10.1081/SCC-100103322
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SYNTHETIC COMMUNICATIONS, 31(6), 869–875 (2001)
NICKEL/ZINC-MEDIATED ALKYL
CARBON-OXYGEN BOND CLEAVAGE OF
ALKYL ARYL ETHERS
Katsuya Maeyama, Masato Kobayashi, and Noriyuki
Yonezawa*
Department of Organic and Polymer Materials Chemistry,
Tokyo University of Agriculture and Technology,
Koganei, Tokyo, 184-8588, Japan
ABSTRACT
Alkyl carbon-oxygen bonds of alkyl aryl ethers bearing
suitable coordination sites were efficiently cleaved by treat-
ment with nickel(II) chloride and zinc in p-xylene under
neutral conditions.
1
There are many reagents for cleavage of sp carbon-oxygen bond in
,2
3
3
alkyl ethers, such as HBr/AcOH and BBr . However, almost all of these
4,5
3
reagents are rather violent, so the application to alkyl aryl ethers having
other functionalities is often troublesome. The development of milder
reagents for this purpose is considered to be helpful for the syntheses of
6
organic materials and natural products. Herein, we report that a mixture of
NiCl and Zn is a useful reagent for the cleavage of alkyl aryl ethers where a
coordination site is located at a suitable position.
2
To estimate the feasibility for carbon-oxygen bond cleavage by the
oxidative addition to low-valent transition metals, we attempted the reac-
tion of anisole or 2-methoxynaphthalene with palladium(0) or nickel(0)
*
Corresponding author.
8
69
Copyright & 2001by Marcel Dekker, Inc.
www.dekker.com

8
70
MAEYAMA, KOBAYASHI, AND YONEZAWA
reagent. However, only recovery of the starting materials was confirmed in
these reactions. Then, we planned to cleave alkyl aryl ether by the assist of a
coordination site to low-valent metals in the same molecule, which might
enable metal reagents to approach to the carbon-oxygen bond like ortho-
7
–10
palladation of aromatic compounds.
a, which has a 2-pyridyl group at o-position to methoxy group.
When substrate 2a was treated with 1.0 equiv. of NiCl and 3.0 equiv.
At first, we chose anisole derivative
1
1
2
2
3
of zinc powder in THF under reflux, the sp carbon-oxygen bond cleavage
of alkyl aryl ethers proceeded to give phenol derivative 3a in 5% yield. The
conversion of this dealkylation raised when solvents with high boiling points
were used. Aromatic solvents were found to be suitable for this reaction.
Particularly when p-xylene was used as the solvent, cleavage proceeded to
give phenol derivative 3a under reflux in an almost quantitative yield.
0
Scheme 1. Reaction of 2-(2 -pyridyl)anisole (2a) with Ni/Zn reagent.
Next, we investigated the effect on the alkyl substituents under the
optimized conditions for the reaction in p-xylene. The results are shown
in Table 1. The reactions of aryl ethyl ether 2b and aryl isopropyl ether 2c
proceeded as well to give the dealkylated product 3a in good yields (Runs 2
and 3). However, when phenyl ether 2d was allowed to react under the same
conditions, no reaction proceeded only to recover substrate 2d (Run 4). It is
3
found that application of this method is limited to the cleavage of the sp
carbon-oxygen bond in alkyl aryl ethers.

ALKYL CARBON-OXYGEN BOND
Table 1. Cleavage of Alkyl Aryl Ethers
871
Run
Substrate
R
Yield (%)
1
2
3
4
2a
2b
2c
2d
CH
C H
3
97
68
71
2
5
3 7
i-C H
a
C
6
H
5
0
Reaction conditions: Substrate, 0.3 mmol; NiCl , 0.3 mmol; Zn,
2
0
.9 mmol; p-xylene, 1mL, reflux, 3 days.
a
Substrate was recovered.
Furthermore, we studied the effect of the structure and the property of
the coordination site in the substrates. Instead of 2-pyridyl group, we
employed substrates 2e–g, having a nitrogen atom as the coordination site
at o-position to methoxy group. The results of the reaction are shown in
Table 2. Substrate 2e, which has an N-methylimidazoyl group, gave the
corrresponding product (3e) in a moderate yield (Run 2). A small decrease
of the yield is considered to be due to the delicate difference of the coordina-
tion directions of the metal to the nitrogen atom. Similarly, substrate 2f,
having an imino group, produced dealkylated product 3f in a moderate yield
(Run 3). The small decrease of the yield is thought to be caused by the steric
hinderance of the phenyl group bonded to the nitrogen atom. The reaction
of substrate 2g, having an N,N-diethylaminomethyl group where the coor-
3
dination site was connected to the aryl part through the sp carbon, gave
product 3g in a 51% yield (Run 4). The moderate yield is supposed to be due
to the steric hinderance of ethyl groups bonded to the nitrogen atom, and
also attributed to the free rotation of benzylic carbon-nitrogen ꢀ bond.
When substrates with carbonyl parts as the coordination sites were allowed
to react, no reaction proceeded (Runs 5 and 6).
Considering these results, substrate 2a, which has 2-pyridyl group at
o-position to methoxy group, is most suitable to the cleavage of alkyl
aryl ethers.
To examine toleration of other functionalities, we next carried out the
reaction of substrate 2j which has a methoxy and an ethoxycarbonyl group

8
72
MAEYAMA, KOBAYASHI, AND YONEZAWA
Table 2. Reaction of Anisole Derivatives with Coordination Sites
Run
Substrate
L
Yield (%)
1
2
3
4
5
6
2a
2e
2f
2g
2h
2i
2-C
1-Methyl-2-imidazoyl
CH=NC
CH NEt
5
H
4
N
97
68
71
51
6
H
5
2
2
a
CO Et
2
0
a
CONEt
2
0
Reaction conditions: Substrate, 0.3 mmol; NiCl
mmol; p-xylene, 1mL, reflux, 3 days.
Substrate was recovered.
2
, 0.3 mmol; Zn, 0.9
a
at o- and m-positions to 2-pyridyl group, respectively. As a result, the reac-
tion proceeded to produce only dealkylated product 3j in a good yield. Only
3
the sp carbon-oxygen bond was cleaved and the ester part tolerated. In this
way, this reaction takes place under mild conditions, and only the neighbor-
ing ether bond to the coordination site can be cleaved.
Scheme 2. Chemoselective ether cleavage.
In conclusion, the Ni/Zn-mediated dealkylation of alkyl aryl ethers
occurs in existence of a nitrogen coordination site in the same molecule.
Particularly, when 2-pyridyl group locates at the o-position to alkoxy group
on the substrate, reaction proceeds most efficiently. This reaction occurs
without cleavage of coexisting ester parts.
EXPERIMENTAL
1
13
H and C NMR spectra were recorded on a JEOL JNM-A500 ( H;
1
1
00 MHz, C; 125 MHz) spectrometer or a JEOL FX-200 ( H; 200 MHz)
spectrometer using Me Si ( H, ꢁ 0.00) and CDCl ( C, ꢁ 77.0) as internal
3
1
5
1
13
4
3
standards. IR spectra were recorded on a JEOL FTIR-5300 spectrometer.

ALKYL CARBON-OXYGEN BOND
873
0
11,12
Synthesis of 2-(2 -pyridyl)anisole (2a)
A hexane solution of n-butyllithium (11 mL, 1.5 M, 16.5 mmol) was
added dropwise to a freshly distilled THF solution (23 mL) of 2-bromo-
ꢁ
anisole (1) (2.81g, 15 mmol) at ꢀ78 C under nitrogen atomosphere. After
stirring for 0.5 h, a THF solution (45 mL) of anhydrous zinc chloride (6.33 g,
46.5 mmol) was added, resulting in the formation of heavy white precipi-
tates. The mixture was gradually warmed to room temperature over
0
0
1
.5 h, then treated with tetrakis (triphenylphosphine)palladium (0.87 g,
.75 mmol), followed by the addition of 2-bromopyridine (3.08 mg,
8 mmol). The reaction mixture was heated under reflux for 1.5 h. Cool
water was added and the mixture was extracted with dichloromethane
50 mL) three times. The combined extracts were washed with brine, dried
over sodium sulfate, and evaporated. The residue was purified by chromato-
(
graphy on silica gel (Merck Silica gel 60, 0.063–0.200 mm) with n-hexane/
0
ethyl acetate (3:1) to give 2-(2 -pyridyl)anisole (4.38 g, 8.7 mmol, 58%) as a
yellow oil: IR (KBr) 3055, 3005, 2835, 1601, 1583, 1494, 1259, 1242,
ꢀ
1 1
7
(
54 cm ; H NMR ꢁ (CDCl ) 4.07 (3H, s), 6.97 (1H, d, J ¼ 8.0 Hz), 7.07
3
1H, t, J ¼ 7.2 Hz), 7.17 (1H, t, J ¼ 7.2 Hz), 7.66 (1H, t, J ¼ 8.0 Hz), 7.76
1H, dd, J ¼ 2.0, 8.0 Hz), 7.79 (1H, d, J ¼ 8.0 Hz), 8.68 (1H, d, J ¼ 4.8 Hz)
(
ppm;
1
3
C NMR ꢁ (CDCl ) 55.4, 111.2, 120.1, 125.0, 129.0, 131.0, 135.5,
3
1
49.2, 156.0, 156.8 ppm.
0
Typical Reaction Procedure: Reaction of 2-(2 -Pyridyl)anisole (2a)
with Ni/Zn Reagent
1
A mixture of nickel(II) chloride (39 mg, 0.30 mmol), zinc powder
(59 mg, 0.90 mmol), and 2-(2 -pyridyl)anisole (2a) (56 mg, 0.30 mmol) was
stirred in p-xylene (1mL) are under reflux for 3 days under nitrogen atmos-
phere. The resulting solution was quenched by the addition of water
3
14
0
(20 mL). The aqueous solution thus obtained was extracted with ethyl acet-
ate three times. The combined extracts were washed with brine and dried
over with MgSO . After removal of solvents, the residue was purified by
4
preparative TLC (Wakogel B-5F) with n-hexane/ethyl acetate (3:1) to give
0
2
-(2 -pyridyl)phenol (3a) (47 mg, 0.29 mmol) in 97% yield.
0
12
2
-(2 -Pyridyl)phenol (3a)
ꢀ
1
IR (KBr) 3055, 2569, 1593, 1562, 1502, 1269, 754 cm ; H NMR
1
ꢁ
7
(CDCl ) 4.47 (1H, br), 7.93 (1H, t, J ¼ 8.6 Hz), 7.07 (1H, d, J ¼ 9.4 Hz),
3
.20–7.40 (2H, m), 7.70–7.90 (3H, m), 8.50 (1H, d, J ¼ 5.0 Hz) ppm;

8
74
MAEYAMA, KOBAYASHI, AND YONEZAWA
1
3
C NMR ꢁ (CDCl ) 118.2, 118.5, 118.5, 118.7, 121.2, 125.9, 131.2, 137.5,
3
1
45.4, 157.4 ppm.
1
5
2
-(1-Methyl-2-imidazoyl)phenol (3e)
ꢀ
1
IR (KBr) 2924, 2364, 1608, 1469, 1377, 1292, 1145, 750 cm
;
1
H NMR ꢁ (CDCl ) 3.90 (3H, s), 6.84–6.89 (2H, m), 7.08–7.13 (2H, m),
3
1
3
7
1
.24 (1H, s), 7.55 (1H, dd, J ¼ 1.0, 8.0 Hz) ppm; C NMR ꢁ (CDCl ) 36.3,
3
13.8, 117.7, 118.3, 122.6, 125.3, 125.4, 130.0, 145.6, 157.8 ppm.
1
6
(
2-Hydroxybenzylidene)aniline (3f)
ꢀ
1
IR (KBr) 3055, 2883, 1616, 1589, 1572, 1483, 1400, 1277, 756 cm
;
1
H NMR ꢁ (CDCl ) 6.97 (1H, t, J ¼ 8.3 Hz), 7.01(1H, t, J ¼ 8.3 Hz),
3
1
3
7
.20–7.50 (4H, m), 8.60 (1H, s), 13.30 (1H, s) ppm; C NMR ꢁ (CDCl )
3
1
17.2, 119.0, 119.2, 121.1, 126.9, 132.2, 133.1, 148.5, 161.1, 162.6 ppm.
0
Ethyl 4-hydroxy-3-(2 -pyridyl)benzoate (3j)
ꢀ
1
IR (KBr) 3003, 2986, 2912, 1707, 1597, 1496, 1284, 765 cm
;
1
H NMR ꢁ (CDCl ) 1.40 (3H, t, J ¼ 6.7 Hz), 4.37 (2H, q, J ¼ 6.7 Hz), 5.11
3
(
1H, br), 7.02 (1H, d, J ¼ 8.6 Hz), 7.27 (1H, t, J ¼ 6.0 Hz), 7.86 (1H, dd,
J ¼ 2.2, 8.0 Hz), 7.97 (1H, dd, J ¼ 2.2, 8.6 Hz), 8.02 (1H, d, J ¼ 8.0 Hz), 8.48
1
3
(
1H, d, J ¼ 6.0 Hz), 8.54 (1H, d, J ¼ 2.2 Hz) ppm; C NMR ꢁ (CDCl ) 14.3,
3
6
1
0.6, 118.0, 118.3, 119.1, 120.7, 121.9, 128.3, 132.5, 137.9, 145.4, 156.8,
64.1, 166.2 ppm.
ACKNOWLEDGMENTS
This work was supported by the Ministry of Education, Science,
Sports, and Culture of Japan.
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1
2
. Bhatt, M.V.; Kulkarni, S.U. Synthesis 1983, 249.

ALKYL CARBON-OXYGEN BOND
875
3
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1
4
5
2
6
4
3
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Received in Japan April 10, 2000