Chemoselective and ligand-free synthesis of diaryl ethers in aqueous medium using recyclable alumina-supported nickel nanoparticles

Article abstract of DOI:10.1016/j.tetlet.2014.10.144

An economical and eco-compatible ligand-free protocol for the synthesis of diaryl ethers has been developed using easily accessible alumina-supported nickel nanoparticles as a stable recyclable heterogeneous catalyst in aqueous medium along with a surfactant (SDS) and a mild base (K₂CO₃). Various sensitive functional groups like allyl, alkoxycarbonyl, formyl, oxo, chloro, bromo, amine and nitro were tolerated in the aforesaid method. Excellent chemoselectivity was demonstrated through competition experiments.

Full text of DOI:10.1016/j.tetlet.2014.10.144

Accepted Manuscript
Chemoselective and ligand-free synthesis of diaryl ethers in aqueous medium
using recyclable alumina-supported nickel nanoparticles
Avishek Ghatak, Sagar Khan, Rimi Roy, Sanjay Bhar
PII:
S0040-4039(14)01862-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.10.144
TETL 45373
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Accepted Date:
14 October 2014
29 October 2014
Please cite this article as: Ghatak, A., Khan, S., Roy, R., Bhar, S., Chemoselective and ligand-free synthesis of diaryl
ethers in aqueous medium using recyclable alumina-supported nickel nanoparticles, Tetrahedron Letters (2014),
doi: http://dx.doi.org/10.1016/j.tetlet.2014.10.144
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Chemoselective and ligand-free synthesis of
diaryl ethers in aqueous medium using
recyclable alumina-supported nickel
nanoparticles
Leave this area blank for abstract info.
Avishek Ghatak, Sagar Khan, Rimi Roy and Sanjay Bhar
Department of Chemistry, Organic Chemistry Section, Jadavpur University, Kolkata-700 032, India.
G1
G1
Ni- alumina (6 mol%)
H2O
G2
G2
X
+
K2CO3 (1eq.)
SDS (8 mol%), 800C
OH
Y
2
O
3
Y
1
X= I, Br, Cl; Y= CH, N
G1= H, 2-Me, 4-Me, 3,4-Me2, 4-Br, 4-Cl, 4-NO2, 2-NH2, 2-(CH2-CH=CH2), 4-CO2Me, 4-CHO
G2= H, 4-NO2, 4-COMe, 4-Me, 4-OMe, 3-CH2OH

1
Tetrahedron Letters
journal homepage: www.els evier.com
Chemoselective and ligand-free synthesis of diaryl ethers in aqueous medium
using recyclable alumina-supported nickel nanoparticles
Avishek Ghataka, Sagar Khana, Rimi Roya and Sanjay Bhara,*
a Department of Chemistry, Organic Chemistry Section, Jadavpur University, Kolkata-700 032, India.
ARTICLE INFO
ABSTRACT
Article history:
Received
An economical and eco-compatible ligand-free protocol for the synthesis of diaryl ethers has
been developed using easily accessible alumina-supported nickel nanoparticles as a stable
recyclable heterogeneous catalyst in aqueous medium along with a surfactant (SDS) and a mild
base (K2CO3). Various sensitive functional groups like allyl, alkoxycarbonyl, formyl, oxo,
chloro, bromo, amine and nitro were tolerated in the aforesaid method. Excellent
chemoselectivity was demonstrated through competition experiments.
Received in revised form
Accepted
Available online
Keywords:
Supported nickel nanoparticles
Diaryl ether
2009 Elsevier Ltd. All rights reserved.
Recyclable catalyst
Chemoselectivity
C-O Ullmann coupling
1. Introduction
One protocol for palladium catalysed arylation in water26 has
The diaryl ether linkage is common and valuable structural
motif used in the synthesis of numerous biologically active
natural products, pharmaceutical compounds and polymers in
material science industry.1 Substituted diphenyl ethers occur in
antibiotics such as vacomycine family2 and in alkaloid3 as well as
in thyroxines.4 Besides biphenyl ether derivatives, substituted 2-
aryloxypyridines are used as glucagon receptor antagonists,5
been recently reported. The major drawbacks associated with this
process are again the use of exotic and costly palladium catalyst
and limited substrate scope. Therefore, development of an
efficient, eco-compatible and economically viable method for
Ullmann coupling reaction remains a formidable challenge to the
synthetic organic chemists till date.
endothelial
antagonists,6,7
anti-hypercholesteremic,
anti-
Organic reactions using heterogeneous catalysts are extremely
important to develop sustainable chemical processes due to cost-
effectiveness, better selectivity and operational simplicity. Owing
to their inherent and well-established advantages, nanocatalysis
bears significant potential in the development of innovative
systems with improved activity and selectivity in different
chemical transformations. There are only a few reports27 of
alumina-supported nickel nanoparticles (hereafter to be called as
Ni-alumina) used mainly for C-N bond formation reactions. In
this connection, we report herein a mild, ligand-free, more eco-
compatible and efficient protocol for the C-O arylation with
broader substrate scope using Ni-alumina as an easily accessible
and heterogeneous reusable nanocatalyst.
hyperlipoproteinemic and anti-hyperglycaemic agents8 and
herbicides.9,10
The most straightforward way to synthesise diaryl ethers is
either palladium or copper catalysed coupling reaction between
aryl halides and phenols. The harsh conditions of classical
Ullmann synthesis have limitations due to involvement of
stoichiometric amounts of copper reagents with some extra
ligands,11-20 requirement of high temperatures along with long
reaction time,11,13-20-22 and use of moisture sensitive, costly
base11,13-16,18,19,22 as well as employment of inert atmosphere.11-
13,15,16,18,21-24
For this reason, immense efforts have been spent in
past few years for the discovery of more attractive and utilitarian
arylation methods. However, palladium-based protocols,
although successful to some extent, have some inherent
limitations such as moisture sensitivity, prohibitive cost of metal
catalysts, non-commercial sophisticated phosphorated ligands,
environmental toxicity and limited substrate scope.25
2. Results and discussion
Ni-alumina was prepared as a grey easy flowing powder by
reduction of nickel chloride hexahydrate adsorbed on neutral
alumina with methanolic solution of sodium borohydride and
subsequent repeated washings with distilled water and methanol
to make it free from the by-products, namely, sodium chloride
and boric acid. Ni-alumina (Figure 1) has been found to be stable
in air and moisture and retains its activity for months.
∗ Corresponding author. Tel.: +918697179547; fax: +91-33-
24137902; e-mail: sanjaybharin@yahoo.com,
sanjay_bhar@chemistry.jdvu.ac.in

2
Tetrahedron Letters
When an equimolecular mixture of iodobenzene and p-
The remarkable recyclability of this nanocatalyst prompted us to
undertake comparative studies between a) neutral alumina, b)
freshly prepared Ni-alumina and c) recycled Ni-alumina (after
seven runs) to get some idea about their morphological features.
For this purpose, scanning electron microscopic images were
recorded and presented in Figures 2a-2c. From the comparison of
SEM images of neutral alumina and freshly prepared Ni-alumina,
a clear change of morphology was noted; the roughness of the
surface was increased and thoroughly distributed over the entire
area of the support. It was also maintained in the recycled
catalyst. The phenomenal catalytic activity of Ni-alumina
nanocatalyst might be ascribed to this widely distributed
roughness of the catalyst surface, which provided greater surface
area with proper chemical polarization towards the substrates to
accomplish facile intermolecular coupling.
cresol in water was heated at 800C in the presence of Ni-alumina
under ambient atmosphere, 1-methyl-4-phenoxybenzene was
obtained (Scheme 1). The reaction was carried out with different
bases, solvents and varying amounts of catalyst to obtain the
optimum condition. The results are summarised in Table 1.
Ni-alumina,
solvent
I
OH
O
+
additive, base
800C-1000C
Me
Me
Scheme 1: Reaction of p-cresol with iodobenzene with Ni-alumina
Table1. Ni-Alumina catalysed O-arylation of p-cresol with
iodobenzene-optimisation of reaction conditions.
Entry
Catalyst
(mol %)
Base
Solvent
Additive
(mol %)
Yield
(%)
1
2
3
4
5
6
7
8
9
4
4
KOH
K2CO3
K2CO3
K2CO3
K2CO3
KOH
H2O
H2O
-
trace
15
72
-
4
H2O
H2O
SDS (4%)
SDS (8%)
SDS (8%)
-
6
89
90
10
6
H2O
DMSO
DMSO
DMSO
DMSO-
H2O(1:1)
DMF
53
61
40
46
6
6
KOH
K2CO3
K2CO3
SDS (8%)
SDS (8%)
-
6
10
11
6
6
K2CO3
Et3N
SDS (8%)
SDS (8%)
37
trace
Figure 2a. SEM image of neutral Alumina
DMSO
There was negligible reaction in the presence of KOH (entry 1),
the unreacted substrates were isolated intact. When a milder base
K2CO3 was used in place of KOH, the extent of conversion was
increased to 15% (entry 2). On addition of a surfactant (4 mol%
SDS), the yield of the reaction was dramatically increased to 72%
(entry 3). Further increase of SDS (8 mol %) and amount of
catalyst (6 mol %) led to an increment of the yield to 89% (entry
4). With further increase of catalyst amount (10 mol %), the yield
of the reaction remained more or less same (entry 5). As evident
from Table.1, water and K2CO3 have come out as most suitable
medium or base respectively for the said protocol. Changing the
solvent from water to other protic polar solvents like DMF or
DMSO, the yield of the reaction was decreased (entries 6-10). It
is very important to note that in contrast to most of the methods
involving metal nanocatalysts, no inert atmosphere is required for
the reaction described in Scheme 1. The aforesaid Ullmann
coupling reaction did neither occur with neutral alumina alone
nor with nickel nanopowder without support or nickel chloride
supported on neutral alumina.The importance of alumina-
supported nickel nanocatalyst in terms of its stability and
catalytic activity was thereby firmly established. Ethyl acetate (an
eco compatible solvent) was added to the reaction mixture to
dissolve the products after completion of each reaction and the
catalyst was isolated through filtration. It was washed repeatedly
with EtOAc followed by water, dried at 1300C for one hour and
used for the next reaction. It was successfully recycled with little
variation of yield (Figure 1).
Figure 2b. SEM image of Ni-alumina before reaction
Figure 2c. SEM image of Ni-alumina after reaction
Transmission electron microscopic (TEM) image of the Ni-
alumina support was recorded and presented in Figure 3.
According to these images, the dimension of encapsulated Ni
nanoparticles was 50‒100 nm. The nickel nanoparticles seemed
to be highly stabilized through encapsulation inside pores of
neutral alumina which is responsible for the recyclability and
catalytic efficiency of Ni-alumina support.
80
60
40
20
0
1
2
3
4
5
6
7
Number of Reactions
Figure 1. Recycling of Ni-alumina using 1a (2 mmol), 2a (2 mmol)
and catalyst (6mol %) at 800C for 8 hours in water; % of yield was
isolated yield.
Figure 3. TEM image of Ni-alumina

3
The EDAX spectra of the freshly prepared Ni-alumina (Figure
4a) and recycled Ni-alumina (Figure 4b) along with the
comparative profile of the atom composition (Table 2) provided a
further guidance to substantiate the efficacy and recyclability of
the present alumina-supported nickel nanocatalyst.
no necessity of maintaining inert atmosphere during the
reaction in spite of using zero-valent metal nanocatalyst and (h)
simple work up procedure with high product yield and purity.
Therefore, the present protocol comes out with greater
advantages compared to many literature reports in terms of cost,
procedural simplicity, eco-compatibility, catalytic activity and
recycling of renewable resource.
Inspired with the aforesaid findings and intending to extend
the applicability of this newly developed methodology, we
carried out systematic investigations on Ullmann coupling of
differently substituted phenols 1 with various aryl halides 2 using
Ni-alumina (6 mol%) as the air and moisture tolerant supported
nanocatalyst in the presence of K2CO3 and SDS in water at 80oC
(Scheme 2) to check the substrate scope and tolerance of various
functional groups. The results are shown in Table 3.
Figure 4a. EDAX spectra of Ni-alumina (freshly prepared)
G1
G1
G2
G2 Ni- alumina (6 mol%)
H2O, K2CO3 (1eq.)
+
SDS (8 mol%), 800C
X
OH
Y
O
Y
1
2
3
Scheme 2: Ullmann coupling between substituted phenols with aryl
and heteroaryl halides.
As shown in Table 3, a wide variety of the substrates
underwent C-O coupling reaction in the presence of Ni-alumina
suspended in aqueous medium containing K2CO3 as a mild base
and SDS as a surfactant without any requirement of any
additional ligand to afford the diaryl ethers 3 in good yield. In
general, aryl iodides were found to be most effective but aryl
bromides as well as low cost, readily available and industrially
viable aryl chlorides also came out as efficient enough to provide
the products in good yield (entries 1 and 4). Phenol itself reacted
with iodobenzene, bromobenzene and chlorobenzene to produce
diphenyl ether in good yield in each case (entry 3). Sterically
congested phenols bearing alkyl substituent at the o-position also
reacted smoothly with iodobenzene, bromobenzene and
chlorobenzene (entry 2). Interestingly, the halogen substituents in
phenols 1e and 1f remained totally unaffected under the present
condition (entries 5 and 6) and afforded 3e and 3f respectively. 4-
Nitrophenol 1g, often found sluggish in various reported
protocols12-14,17-24,25a,26,28 for Ullmann coupling, reacts well with
2a in the present Ni-alumina catalysed protocol (entry 7) to
furnish the product 3g in 70%(X=I) and 69%(X=Br) yield.
Figure 4b. EDAX spectra of Ni-alumina (recycled 7 times)
Table 2: Comparative Profile of Atom Composition
Support
Ni-alumina
(freshly prepared)
Element
O K
Weight%
51.93
44.75
3.32
Atomic%
65.42
33.44
1.14
Total
100.0
Al K
Ni K
O K
Ni-alumina
(recycled 7 times)
54.31
42.66
3.03
67.52
31.45
1.03
100.0
Al K
Ni K
As evident from Table 2, there was extremely marginal loss of
Ni metal from the supported catalyst during the reaction. This
was also confirmed from the atomic absorption spectroscopic
analysis of the leftover reaction medium which was found to
contain 0.935 ppm of nickel after the reaction. The occurrence of
such a small amount of nickel in the reaction medium was due to
its leaching from the supported catalyst which came out to be
0.34% with respect to the nickel nanoparticles supported on
alumina. So it can be concluded that in Ni- alumina, Ni atom
remains encapsulated and firmly immobilized on the alumina
support. Probably this is the reason why alumina-supported
nickel nanoparticles are highly stable in air and resistant to
oxidation which permits them to be used under normal
atmospheric condition without any aid of inert environment. It is
extremely important to note the excellent recyclability of the
present catalyst where after the 7th run the product yield of the
reaction between p-cresol and iodobenzene varies a little (Figure
2). This demonstrates the superiority and catalytic efficiency of
Ni-alumina for Ullmann reaction in comparison to the many
recently reported protocols, for example, Pd catalyst grafted on
graphene oxide.25a The present catalyst is prepared very easily
using inexpensive compounds and it is highly stable in air and
moisture. No inert atmosphere is required during the reaction.
Table 3: Ni-Alumina catalysed O-arylation of different
phenols with haloaromatics under optimised reaction
conditions.
Entry
Substrate
Aryl
Product
Time(hr)/
Yield (%)a
Halide
O
OH
8/89(X=I)
8/85(X=Br)
1
X
3a
1a
9/80(X=Cl)
2a
8/85(X=I)
8/80(X=Br)
O
OH
X
2
3
9/78(X=Cl)
3b
2a
1b
OH
O
9/84(X=I)
9/83(X=Br)
X
X
3c
10/80(X=Cl)
2a
2a
1c
Therefore, the present method using Ni-alumina as
a
heterogeneous nanocatalyst bears the advantages like (a) the use
of water as the most eco-compatible reaction medium, (b)
marginally small leaching of nickel during the reaction, (c) easy
recovery of the catalyst simply by filtration, (d) excellent
recyclability of the catalyst, (e) no requirement of any extra
ligand during the reaction, (f) mildly basic reaction medium, (g)
OH
8/83(X=I)
8/82(X=Br)
O
4
5
3d
9/79(X=Cl)
1d
OH
O
8/78(X=I)
8/74(X=Br)
Br
Br
3e
1e

4
Tetrahedron Letters
isomerise to the more conjugated vinyl moiety under basic
condition) located at the close proximity of the reactive OH
group remained unaffected in 3i under the present reaction (entry
10). Hydrolysable functional groups like methoxycarbonyl also
survived in the present protocol (entry 11) to give the product 3j
without any transesterification. Formyl group, which is highly
susceptible to aerial oxidation and highly responsive towards
reductive transformations, was also tolerated in the
corresponding product 3k during the aforesaid reaction (entry
12). Reactions with 2c (having ketomethyl group at the p-
position with respect to bromine), are sometimes problematic11
with some Pd-mediated procedures. In the present case 2c reacts
smoothly with 1a to give the product 3l in 77% yield (entry 13)
keeping the ketomethyl moiety unaffected. Haloarenes 2d and 2e
with electron donating substituents (which are less susceptible to
nucleophilic attack) required a little higher temperature (1000C)
and longer reaction time (10 hours) to react with 1a and yielded
3m and 3n with 76% and 78% respectively. The present method
was extended to the reactions of 2-halopyridines and with
phenols bearing chloro and methyl groups as the substituents,
where the corresponding 2-aryloxypyridines were produced in
quite good yield (entries 16-19). As before, the reactions went
fine with both 2-bromo- as well as 2-chloropyridines. 3-
Chloropyridine, which is generally less responsive towards
nucleophilic substitution, also reacted well with phenol and o-
cresol under the present condition and afforded the corresponding
3-aryloxypyridines in good yield (entries 20-21). It is important
to note that 3-aryloxypyridines and their N-oxides demonstrate
diverse pharmacological properties. They inhibit gastric secretion
without anticholinergic, ganglionic or adrenergic blocking
activity,29a rectify cognitive dysfunction29b and act as
anticonvulsant agent.29c
OH
O
8/74(X=I)
9/72(X=Br)
X
6
7
8
Cl
Cl
3f
1f
2a
OH
O
11/70(X=I)
X
I
O2N
12/69(X=Br)
1g
NO2
3g
2a
OH
O
11b/72
NO2
O2N
3g
1c
2b
OH
NH2
O
X
9
9/79(X=I)
NH2
OH
1h
9/76(X=Br)
3h
2a
2a
X
O
10
11
11/78(X=I)
12/75(X=Br)
1i
3i
OH
O
11/76(X=I)
X
MeOC
O
CO2Me
12/73(X=Br)
3j
1j
2a
2a
OH
O
12/74(X=I)
X
12
13
14
15
16
12/69(X=Br)
OHC
CHO
3k
1k
OH
Br
O
11b/77
10b/76
10b/78
3l
O
1a
2c
O
O
I
OH
3m
O
2d
1a
I
OH
Interestingly, n-hexyl alcohol, benzyl alcohol and cinnamyl
alcohol did not undergo any C-O coupling with iodobenzene
under the present reaction condition. Therefore the present Ni-
alumina catalysed protocol can be used for chemoselective
Ullmann coupling between phenol and halobenzene in the
presence of alcoholic OH. This is an additional and extremely
important attribute of the present protocol in contrast to many
reported methods21 where such a chemoselectivity was not
observed. Intermolecular competition reaction of an
equimolecular mixture of p-cresol and benzyl alcohol with excess
iodobenzene under optimised condition (Scheme 3) yielded the
corresponding diaryl ether from p-cresol exclusively where
benzyl alcohol totally remained unaffected.
MeO
MeO
3n
1a
2e
OH
OH
O
N
X
9/83(X=Br)
9/81(X=Cl)
N
N
2f
2f
2f
1b
1a
3o
O
N
X
17
18
9/84(X=Br)
9/80(X=Cl)
3p
OH
OH
O
N
X
10/81(X=Br)
11/77(X=Cl)
N
N
3q
1c
O
19
20
21
11/74(X=Br)
11/70(X=Cl)
N
X
Cl
Cl
3r
OH
OH
2f
N
1f
OH
I
Ni- alumina (6 mol%)
H2O, K2CO3 (1eq.)
O
+
+
+
Cl
Cl
O
OH
Me
SDS (8 mol%), 800C
Me
10/75
10/78
N
3s
2g
2g
1c
Scheme 3: Intermolecular competition experiment to demonstrate
chemoselectivity.
O
OH
N
N
3t
1b
Similar chemoselectivity has been elegantly demonstrated
when phenol reacted with 3-bromobenzyl alcohol under identical
condition and afforded 3-phenoxybenzyl alcohol exclusively with
84% isolated yield (Scheme 4) without the self coupled product
of 3-bromobenzyl alcohol. It is important to note that 3-
phenoxybenzyl alcohol serves as one of the structural subunits of
an important pyrethroid insecticide, namely, permethrin. So the
present alumina-supported nickel nanometal-mediated protocol
for chemoselective C-O arylation provides a utilitarian arsenal to
the synthetic methodology. The wider applicability of the present
protocol is demonstrated by another important feature of the
aforesaid reaction where m-substituted aryl halide smoothly
underwent C-O arylation with phenol which are often difficult to
perform according to some earlier reports.25a
a) Yield of isolated products, fully characterized spectroscopically. b) Reactions
were carried out at 100oC.
Among halonitroarenes, 4-iodonitrobenzene 2b is least
reactive towards aromatic nucleophilic substitution. But this
compound, in the present case, underwent efficient coupling with
1c (entry 8) to give 3g in 72% yield. This is not commonly
observed in some literature reports.28 Excellent chemoselectivity
was observed with 2-aminophenol 1h, where the phenolic-OH
group reacted exclusively with 2a leaving behind the nearby
more nucleophilic NH2 group intact (entry 9) in the product 3h.
1
This was confirmed by H-NMR where a broad peak at î 3.81
specific for free amine was observed. This phenomenon is
relatively rare so far as the previous reports15,19,20,22,28 are
concerned. Highly vulnerable allylic moiety (susceptible to

OH
OH
Ni- alumina (6 mol%)
H2O, K2CO3 (1eq.)
5
OH
References and notes
+
SDS (8 mol%), 800C
1. (a) Boeger, D. L.; Patane, M. A.; Zhou, J. J. Am. Chem. Soc. 1994, 116,
8544; (b) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108,
3054; (c) Lindley, J. Tetrahedron 1984, 40, 1433; (d) Monnier, F.;
Br
O
1c
2h
3u
Scheme 4: Chemoselective arylation of phenolic-OH in the presence
of alcoholic-OH.
Taillefer, M. Angew. Chem. 2008, 120, 3140; Angew. Chem. Int. Ed. 2008,
47, 3096 ; (e) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003,
42, 5400; (f) Beletskaya, I.; Cheprakov, A. CoordChem. Rev. 2004, 248,
2337.
The aforesaid protocol was applied for the synthesis of
immensely important aryl and heteroaryl naphthyl ethers
(Scheme 5) using coupling reaction between 1- and 2-naphthols
with halobenzenes and 2-halopyridines (Table 4) where the
similar trend was also observed in terms of reaction efficiency
2. (a) Williams, J. C. D. H. Acc. Chem. Rex. 1984, 17, 364; (b) Barna, J.;
Williams, D. H. Annu. Rev. Microbiol. 1984, 38, 339; (c) Nicolaou, K. C.;
Natarajan, S; Li, H.; Jain, N. F.; Hughes, R. M.; Solomon,E;
Ramanjulu, J. M.; Boddy, C. N. C.; Takayanagi, M. Angew. Chem. 1998,
110, 2872; Angew. Chem. Int. Ed.1998, 37, 2708; (b) Evans, D. A.;
Dinsmore. C. J.; Watson. P. S.; Wood.;M. R.; Richardson.T. I.;Trotter B.
W.; Katz, J. L. Angew. Chem. 1998, 110, 2868; Angew. Chem. Int. Ed.
1998, 37, 2704.
and product yield.
Ni- alumina (6mol%)
H2O, K2CO3 (1eq.)
OH
+
SDS (8 mol%), 800C
X
Y
O
Y
3. (a) Gozler, B.; Shamma, M. ibid. 1984, 47, 753; (b) Schiff, P. L. J. Nat.
Prod. 1983, 46, 1
4. E. C. Jorgensen in 'Burger's Medicinal Chemistry,' ed. M. E. Wolff, John
Wiley & Sons, New York, 1981, 4th edn., part 111, 103.
5. W. R. Schoen, G. H. Ladouceur, J. H. Cook, T. G. Lease, D. J. Wolanin,
R. H. Kramss, D. L. Hertzog and M. H. Osterhout, U.S., 2001, US
6218431 B1 20010417
6. M. Takahashi, K. Sakurai, S. Niwa and S. Oono, Molecular Modeling and
Prediction of Bioactivity, Proceedings of the European Symposium on
Quantitative Structure-Activity Relationships: Molecular Modeling and
Prediction of Bioactivity, 12th, Copenhagen, Denmark, Aug 23e28, 1998,
2000,416e417.
Scheme 5: Ullmann coupling between substituted naphthols with
aryl and heteroaryl halides.
Table 4:
Entry
Substrate
2-naphthol(1l)
2-naphthol(1l)
X
I
Y
Time(hr)
Product/Yield
(%)a
1.
CH
CH
8
8
3v/87
2.
Br
3v/84
3v/80
7. K. Sakurai, S. Niwa, S. Oono and H. Uchita , Jpn. Kokai Tokkyo Koho,
1998, JP 10029979 A 19980203.
3.
Cl
CH
9
2-naphthol(1l)
8. G. Schmidt, R. Angerbauer, A. Brandes, M. Muller-Gliemann, H.
Bischoff, D. Schmidt, S., Wohlfeil , W. R. Schoen, G. H. Ladouceur
and, J. H. Cook , II. PCT Int. Appl., 1998, WO 9804528 A2 19980205.
9. M. Myazaki, M. Matsuzawa, K. Toyabe and M. Hirata, Jpn. Kokai
Tokkyo Koho, 1994, JP 06041116 A 19940215.
4.
5.
I
CH
CH
8
8
3w/84
3w/81
1-naphthol(1m)
1-naphthol(1m)
Br
6.
7.
8.
Cl
Br
Cl
CH
N
8
3w/78
3x/80
3x/76
1-naphthol(1m)
2-naphthol(1l)
2-naphthol(1l)
10. M. Miyazaki, M. Matsuzawa, K. Toriyabe and M. Hirata, PCT Int.
Appl., 1992, WO 9217468 A1 19921015.
10
10
11. Zhang, Q.; Wang, D.; Wang, X.; Ding, K. J. Org. Chem. 2009, 74,
7187.
12. Otto, N.; Opatz, T. Beilstein J. Org. Chem. 2012, 8, 1105.
13. Altman, R. A.; Shafir, A.; Choi, A.; Lichtor P. A; Buchwald, S. L. J.
Org. Chem. 2008, 73, 284.
N
a Yield of isolated products, fully characterized spectroscopically.
14. Ma, D.; Cai, Q. Org. Lett. 2003, 5, 3799.
15. Cristau, H. J.; Cellier, P. P; Hamada, S.; Spindler, J. F.; Taillefer, M.
Org. Lett. 2004, 6, 913
3. Conclusion
16. Zhou , Q.; Zhang , B.; Du, T.; Gu, H.; Ye, Y.; Jiang, H.; Chen, R.
Tetrahedron 2013, 69, 327
A cost-effective, operationally simple and eco-friendly
protocol for the O-arylation of phenols with aryl halides under
ambient atmosphere in aqueous medium has been developed
using alumina-supported nickel nanoparticles as an efficient,
recyclable and stable heterogeneous catalyst. The reactions
neither necessitate any ligand nor any inert environment. The
present protocol for Ullmann coupling is highly chemoselective
where more nucleophilc aromatic NH2 and alcoholic OH groups
remain unaffected. Chemically susceptible motifs like allyl,
alkoxycarbonyl, formyl, oxo and nitro are well tolerated during
the reaction. Thus the present study has developed a green
method for chemoselective Ullmann coupling under aqueous
medium using easily accessible, economically viable, highly
stable and recyclable supported metal nanocatalyst with greater
merits and wider applicability compared to many earlier reports.
17. Cheng, A. Y.; Hsieh, J. C. Tetrahedron Lett. 2012, 53, 71
18. Yang, S.; Wu, C.; Zhou, H.; Yang, Y.; Zhao, Y.; Wang, C.; Yang W.;
Xu, J. Adv. Synth. Catal
19. Benyahya, S.; Monnier, F.; Man, M. W. C.; Bied, C.; Ouazzani
Taillefer, M. Green Chem. 2009 11, 1121
20. Qu, X.; Li, T.; Zhu, Y.; Sun, P.; Yang H.; Mao, J. Org. Biomol. Chem.
2011 , 5043
. 2013, 355, 53
b
, F.
,
,
9
21. Niu, J.; Zhou, H.; Li, Z.; Xu, J.; Hu, S. J. Org. Chem. 2008, 73, 7814
22. Wang, M.; Yuan, B.; Ma, T.; Jiang, H.; Li, Y. RSC Adv. 2012, 2, 5528
23. Zhang, J.; Zhang, Z.; Wang, Y.; Zheng X.; Wang, Z. Eur. J. Org.
Chem. 2008, 5112.
24. Swapna, K.; Murthy, S. N.; Jyothi M. T.; Nageswar, Y. V. D. Org.
Biomol. Chem., 2011, 9, 5978–5988
25. (a) Joshi, H.; Sharma, K. N.; Sharma, A. K.; Prakash O.; Singh, A. K.
Chem. Commun. 2013, 49, 7483; (b) Burgos, C. H.; Barder, T. E.;
Huang, X.; Buchwald, S. L. Angew. Chem., Int. Ed. 2006, 45, 4321; (c)
Acknowledgments
Prim, D.; Campagne, J. M.; Joseph, D.; Andrioletti, B. Tetrahedron
2002, 58, 2041; (d) Kataoka, N.; Shelby, Q.; Stambuli, J. P.; Hartwig,
J. F. J. Org. Chem. 2002, 67, 5553.
A. G. and R. R. thank CSIR, New Delhi, Government of India
for senior research fellowships. S. K. thanks UGC, New Delhi,
Government of India for senior research fellowship. The
aforesaid investigation has enjoyed financial support from the
Council of Scientific and Industrial Research, New Delhi,
Government of India (CSIR Grant No. 01(2383)/10/EMR-II) and
DST-PURSE-programme at Jadavpur University which are also
acknowledged. The authors also gratefully put on record the
instrumental assistance received from the DST-FIST programme
at Jadavpur University. Thanks to Mr. J. Poddar of Jadavpur
University and Mr. N. Dutta of Indian Association for the
Cultivation of Science for necessary assistance.
26. Zolfigol, M. A.; Khakyzadeh, V.; Zare, A. R. M.; Rostami, A.; Zare, A.;
Iranpoor, N.; Beyzavi M. H.; Luque, R. Green Chem. 2013, 15, 2132.
27. (a) Shimizu, K.; Imaiida, N.; Kon, K.; Siddiki S. M. A. H.; Satsuma,
A. ACS Catal. 2013, 3, 998; (b) Shimizu, K.; Kon, K.; Onodera, W.;
Yamazaki, H.; Kondo, J. ACS Catal. 2013, 3, 112.
28. Agawane, S. M.; Nagarkar, J. M. Tetrahedron Lett. 2011, 52, 5220.
29. (a) Butler, D. E.; Bass, P.; Nordin, I. C.; Hauck Jr., F. P.; L’Italien, Y. J.
J. Med. Chem. 1971, 14, 575-579; (b) Butler, D. E.; Poschel, B. P. H.;
Marriott, J. G.; J. Med. Chem. 1981, 24, 346-350; (c) Pavia, M. R.;
Taylor, C. P.; Hersheneon, F. M.; Lobbestael, S. J.; Butler, D. E.
J. Med. Chem. 1988, 31, 841-847.
Supplementary Material
General experimental procedure and the characterization data of
the final compounds are available as supporting information.