First direct access to 2-hydroxybenzophenones via nickel-catalyzed cross-coupling of 2-hydroxybenzaldehydes with aryl iodides

Article abstract of DOI:10.1039/c5ra18890c

An efficient, inexpensive and reusable NiCl₂·6H₂O/n-Bu₄NBr catalytic system is described for the direct C-H arylation of 2-hydroxybenzaldehydes with aryl iodides for the first time.

Full text of DOI:10.1039/c5ra18890c

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DOI: 10.1039/C5RA18890C
Journal Name
COMMUNICATION
First Direct Access to 2-Hydroxybenzophenones via Nickel-
Catalyzed Cross-Coupling of 2-Hydroxybenzaldehydes with Aryl
Iodides
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
DOI: 10.1039/x0xx00000x
N. Nowrouzi, M. Zarei and F. Roozbin
www.rsc.org/
An efficient, inexpensive and reusable NiCl .6H O/n-Bu NBr and flexible synthetic methods of this structural moiety. Generally,
2
2
4
catalytic system is described for the direct C-H arylation of 2- reports on the direct access to 2-hydroxybenzophenones from 2-
hydroxybenzaldehydes with aryl iodides for the first time.
hydroxyarylaldehydes via metal-catalyzed cross-coupling reactions
are very rare in the literature. The first palladium-catalyzed reaction
of 2-hydroxybenzaldehyde and its derivatives with aryl iodides via
cleavage of the aldehyde C-H bond to obtain the corresponding
Aryl ketones are valuable building blocks in both chemistry and
biology that have been widely used in the pharmaceutical,
fragrance, dye, agrochemical, and functional material industries as
8
ketones has been reported by Miura in 1996. This transformation
1
well as in organic synthesis.
gives good yields for many substrates using a catalyst system of
o
Friedel-Crafts acylation in the presence of Lewis acids is one of the
most useful synthetic methods for the preparation of aromatic
ketones, although the reaction sometimes fails with electron-
deficient arenes and generally yields the desired products as
PdCl /LiCl in the presence of Na CO as base in DMF at 100 C under
2
2
3
nitrogen. Several years later, effort has been directed towards the
preparation of 2-hydroxybenzophenones using iodonium salts as
9
analogues of aryl iodides. These salts were used into the reaction
isomeric mixtures. In addition, it requires the use of
a
with salicylaldehyde in the presence of PdCl2 and LiCl as a co-
catalyst in DMF to achieve corresponding ketones. In 2010, Xu
reported an efficient system for the direct arylation of 2-
hydroxybenzaldehydes with arylboronic acids via ligand-free
2
stoichiometric amount of Lewis acid. Oxidation of secondary
alcohols is another common method to access ketones. This
protocol often requires the use of a stoichiometric amount of
oxidant and is commonly limited by poor functional group
10
palladium catalysis. However, the boronic acids are comparably
expensive and not so widely available. Most recently, we have
reported an efficient method for the palladium-catalyzed cross-
coupling reaction of aryl bromides and iodides with 2-
3
tolerance. The reactions of stoichiometric organometallic
compounds with carboxylic acid derivatives are also popular and
4
well-known for the preparation of ketones. However, the poor
functional group tolerance, strict handling requirement of the
organometallic reagents and overaddition (resulting in the
formation of tertiary alcohol products) limits their applications and
thus there is a need for milder, cleaner and catalytic alternatives.
During the last decade, transition-metal catalyzed cross-coupling
reactions have emerged as powerful methods in synthetic
chemistry. Among many methods, direct C–H bond arylation of
aldehydes and their derivatives to give aryl ketones has attracted a
hydroxybenzaldehydes in H O to access 2-hydroxybenzophenones
without the need for any co-catalyst and ligand.
2
11
Whiles palladium based complexes are the most common catalysts
for the coupling reactions, efforts have been made to replace
palladium with less expensive metals. Among the inexpensive
transition metals, Ni appears the most promising for the
replacement of Pd because it is active for coupling reactions and
about 500 times cheaper than palladium.
5
lot of attention. However, in some of these transformations the
Despite the fact that various nickel-catalyzed systems are available
12
existence of a hydroxyl group in the substrates led to main
impediment. The prevalence of ortho-hydroxyl-substituted diaryl
in the literature for the synthesis of aryl ketones, to the best of
our knowledge there is no literature precedent for the use of nickel
for the preparation of 2-hydroxybenzophenones using 2-
hydroxybenzaldehydes. Herein we wish to report a direct synthesis
of 2-hydroxybenzophenones by the nickel-catalyzed coupling of 2-
hydroxybenzaldehydes with aryl halides via an oxidative addition
and reductive elimination strategy in a one-pot manner.
6
ketones in a large number of biologically active compounds, in
7
perfumery, pharmaceutical industries and also natural products,
has resulted in a continued demand for the development of general
a.
Department of Chemistry, Faculty of Sciences, Persian Gulf University,
We began our study by examining the cross-coupling between
iodobenzene (1.0 mmol) and 2-hydroxybenzaldehyde (1.0 mmol)
Bushehr,75169, Iran. E-mail: nowrouzi@pgu.ac.ir.
†
Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
using 50 mol% NiCl
.6H
2
O as catalyst in ethylene glycol (2 mL) at
2
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Journal Name
o
Table 1. Effect of different reaction parameters onVitehweArtcicoleuOpnlilninge
1
20 C in the presence of NaOH (2.0 mmol) as base to furnish the
reaction of iodobenzene (1.0 mmol) and salicylaldehyde (1.0 mmol).
DOI: 10.1039/C5RA18890C
corresponding diaryl ketone. Table 1 provides information on the
impact of various reaction parameters on the efficiency of this
process. Surprisingly, we discovered that even without any reducing
agent and ligand, the reaction proceeded smoothly, affording the
coupling product after 24 h, albeit in low yield (Table 1, entry 1).
This promising result encouraged us to do further optimization with
NiCl .6H O as the catalyst precursor to improve the yield of the
O
NiCl .6H O
2
2
CHO
OH
I
Solvent
+
Base
OH
Temperature
Additive
2
2
Catalyst
(mol%)
o
Time Yield
Entry
1
a
Base
Solvent/ C
b
product. Solvent screening showed that no product could be
detected when the reaction was carried out in ethanol, dioxane,
and H O at reflux (Table 1, entries 2-4). Also, no desired product
(h)
(%)
Ethylene glycol
50
NaOH
24
40
2
120
o
was obtained in PEG at 120 C (Table 1, entry 5). Therefore, the
2
3
4
5
50
50
50
50
NaOH
NaOH
NaOH
NaOH
EtOH/reflux
24
24
24
24
-
-
-
-
subsequent reactions were performed in ethylene glycol which
possesses negligible vapor pressure, is thermally stable and
inexpensive. We surveyed several different organic and inorganic
bases for the coupling reaction, and NaOH was found to give the
best results (Table 1, entry 1). Absence of base, or changing the
base to Na CO , Bu N and DABCO did not yield the target product at
all (entries 6-9). In a further attempt to improve the yield of aryl
ketone, the use of 2.0 mmol of iodobenzene was explored (Table 1,
entry 10). Gratifyingly, this change afforded higher yield of the
product (from 40% to 75%). No further yield improvement was
achieved using greater amounts of iodobenzene (Table 1, entry 11).
It was interesting to find that the significant improvement in the
reaction time and the yield of 2-hydroxybenzophenone was
observed following the addition of 0.5 mmol tetrabutylammonium
bromide to the reaction mixture (Table 1, entry 12). The role of
TBAB in this reaction is critical. It is noteworthy that the presence of
TBAB as an additive not only makes the catalytic system stable by
preventing undesired agglomeration and deactivation by forming a
monomolecular layer around the metal core, but also acts as
reducing agent for the generation of Ni(0). Next, the reaction was
carried out with different amounts of NiCl .6H O (30, 40, 60 mol%).
As it was shown in entries 13-15 of Table 1, at 120 C, 40 mol% of
the catalyst was sufficient to catalyze the reaction efficiently; in this
case, the corresponding product was obtained in 94% yield within 2
h (Table 1, Entry 14). As expected, no product could be detected in
the absence of nickel catalyst (Table 1, entry 16). A temperature of
Dioxane/reflux
H O/reflux
2
PEG/120
Ethylene glycol
6
7
8
50
50
50
50
50
50
50
60
40
30
-
-
24
24
24
24
24
24
2
-
1
20
Ethylene glycol
20
Ethylene glycol
20
Ethylene glycol
20
Ethylene glycol
20
2
3
3
Na CO
-
2
3
1
Bu
3
N
-
1
9
DABCO
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
-
1
c
10
75
75
94
93
94
75
-
1
d
Ethylene glycol
120
Ethylene glycol
TBAB/120
Ethylene glycol
TBAB/120
Ethylene glycol
TBAB/120
Ethylene glycol
TBAB/120
Ethylene glycol
TBAB/120
Ethylene glycol
TBAB/100
11
c
c
c
c
c
c
12
13
14
2
13
2
2
2
o
15
16
9
24
24
17
40
70
1
20 °C was the optimal temperature for this reaction. Decreasing
the reaction temperature caused a decrease in the yield of desired
product (Table 1, entry 17) and higher temperature (Table 1, entry
c
c
Ethylene glycol
TBAB/140
120/TBAB
1
8
9
40
40
40
NaOH
NaOH
NaOH
2
24
2
94
trace
93
1
1
8) did not improve the conversion and yield. Next, the model
c,d
Ethylene glycol
20
reaction was carried out in the absence of ethylene glycol. The
result indicated that the existence of ethylene glycol is necessary in
this transformation (Table 1, entry 19). Finally, we decided to re-
examine the coupling reaction of iodobenzene and salicylaldehyde
TBAB/120
a
b
c
NiCl
2
.6H
2
O ≥98% purity was used. Isolated yield. 2.0 mmol iodobenzene
d
d
was used. 3.0 mmol iodobenzene was used. NiCl
2
≥99.99% purity was
used.
using NiCl with a purity of ≥99.99% instead of nickel salt with a
purity of ≥98% under our optimized reaction conditions to confirm
that the reaction was not catalyzed by a trace metal contaminant.
2
Under the obtained optimized conditions; NiCl .6H O (40 mol%),
2
2
aryl halide (2.0 mmol), 2-hydroxybenzaldehyde (1.0 mmol), NaOH
2.0 mmol) and tetrabutylammonium bromide (0.5 mmol) in
(
As shown in Table 1, entry 20, the use of NiCl with a purity of
2
o
ethylene glycol (2 mL) at 120 C, the substrate scope of the direct
arylation of 2-hydroxybenzaldehydes was explored. As shown by
the results in Table 2, this cross coupling is efficiently applicable to a
wide range of aryl iodides. The coupling reaction with electron-
neutral, electron-rich and electron-poor aryl iodides were carried
≥99.99% did not led to lower yield than the same reaction with
nickel salt of lower purity. This observation indicated that the
presence of trace amounts of metal impurities in the commercially
available nickel catalyst were not capable of catalyzing the coupling
reactions.
o
out successfully at 120 C to generate the corresponding products
in good to excellent yields. The influence of steric effects was
2
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studied by introduction of an alkyl substituent into the ortho-
position of the halobenzene ring. As shown by the data in entry 4 of
Table 2, a substituent such as methyl at the ortho position had
steric effect and in this case, no desired product was obtained even
after prolonged reaction time. We then studied the applicability of
this catalytic system for the reaction of aryl bromides. For this
purpose, reaction of bromobenzene with salicylaldehyde under the
optimal conditions was studied. The data presented in entry 12 of
Table 2 show that, the reaction did not proceed at all and starting
material was isolated intact after appropriate reaction time.
Attempts to find reaction conditions that enabled the conversion of
bromobenzene to product, such as increasing the concentration of
bromobenzene or the addition of more nickel catalyst during the
View Article Online
19
10
DOI: 10.1039/C5RA18890C
24
70
9
11
24
75
12
13
14
24
24
24
-
-
-
reaction, failed. Also, the addition of PPh which is often necessary
for the Pd-catalyzed coupling reactions, did not improve the
conversion and yield of the coupling product.
3
a
Reaction conditions: Iodobenzene (2.0 mmol), 2-hydroxybenzaldehyde (1.0
mmol), NiCl .6H O (40 mol%), n-Bu NBr (0.5 mmol), NaOH (2.0 mmol) in 2
2
2
4
mL ethylene glycol at 120 °C.
b
Isolated yield.
Table 2. Nickel-catalyzed cross-coupling of 2-hydroxybenzaldehydes
a
with aryl iodides.
To explore the reaction mechanism, the following control
experiments were performed under the standard reaction
conditions. Coupling of p-hydroxybenzaldehyde with iodobenzene
gave no desired 4-hydroxybenzophenone (Table 2, entry 13).
Furthermore, the reaction of benzaldehyde with iodobenzene
under the optimal conditions yielded no benzophenone (Table 2,
entry 14). These results suggested that the phenolic function at the
ortho-position of the formyl group is essential for successful
performance of the reaction.
In order to gain insight about the reducing property of ethylene
glycol and tetrabutylammonium bromide, we probed the ultraviolet
(UV) spectrum of Ni(II) in the presence of TBAB and ethylene glycol
separately. The UV spectra of these solutions are shown in Figure 1.
The peak at around 400 and 700 nm of curve A shows the presence
b
Time
Yield
(%)
Entry
1
Aldehyde
ArX
ref
(
h)
9
2
94
1
4
2
3
8
90
of Ni(II) species. Curves B and C belong to the solution of NiCl .6H O
2 2
in ethylene glycol and TBAB respectively. The disappearance of the
peaks related to Ni(II) at 400 and 700 nm, confirms that Ni(II) has
been reduced to the Ni(0) species in the presence of ethylene glycol
9
16
48
83
20-22
and TBAB (Figure 1).
4
5
-
1
5
24
18
60
78
80
1
6
6
7
8
9
16
20
17
8
88
89
1
8
6
Figure 1. UV spectra of the nickel catalyst. (A) NiCl
2 2 2
.6H O in H O. (B)
NiCl .6H O in ethylene glycol. (C) NiCl .6H O in TBAB.
2
2
2
2
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10
7
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DOI: 10.1039/C5RA18890C
1
According to the above results, a proposed mechanism for the aryl
ketone formation is shown in Scheme 1. Step 1 involves an
oxidative addition in which Ni(0) inserts into the aryl halide bond.
The formed nickel(II) species subsequently reacts with
salicylaldehyde to give aryl(aryloxy)nickel intermediate I. Insertion
of the aryl to the carbonyl group gives intermediate II, which then
gives intermediate III via a β-hydride elimination process. Finally,
the subsequent reductive elimination from III, yields 2-
hydroxybenzophenone and also regenerates the nickel(0) catalyst.
a
Isolated yield.
In summary, We have reported the first Ni(0) catalytic method for
the efficient cross-coupling reaction of aryl iodides with 2-
hydroxybenzaldehydes in the presence of n-Bu NBr in ethylene
glycol to access 2-hydroxybenzophenones. The absence of ligand,
co-catalyst and external reducing agent in the catalytic system
together with its recyclability are considered as other advantages of
this system.
4
Acknowledgments
We thank the Persian Gulf University Research Council and
Iran National Science Foundation (INSF-Grant number of
9
2012390) for support of this study.
Notes and references
1
(a) Y. Shen and C. F. Chen, Chem. Rev. 2012, 112, 1463; (b) Y.
B. Wu, Z. Y. Ni, Q. W. Shi, M. Dong, H. Kiyota, Y. C. Gu and B.
Cong, Chem. Rev. 2012, 112, 5967; (c) B. Skillinghaug, C.
Skold, J. Rydfjord, F. Svensson, M. Behrends, J. Savmarker, P.
J. R. Sjoberg and M. Larhed, J. Org. Chem. 2014, 79, 12018;
(
d) X. Jia, S. Zhang, W. Wang, F. Luo and J. Cheng, Org. Lett.
009, 11, 3120; (e) K. R. Romines, G. A. Freeman, L. T.
2
Schaller, J. R. Cowan, S. S. Gonzales, J. H. Tidwell, C. W.
Andrews, D. K. Stammers, R. J. Hazen, R. G. Ferris, S. A. Short,
J. H. Chan and L. R. Boone, J. Med. Chem. 2006, 49, 727; (f) S.
Rahimipour, C. Palivan, F. Barbosa, I. Bilkis, Y. Koch, L.
Weiner, M. Fridkin, Y. Mazur and G. J. Gescheidt, J. Am.
Chem. Soc. 2003, 125, 1376; (g) S. Baggett, E. P. Mazzola and
E. J. Kennelly, Stud. Nat. Prod. Chem. 2005, 32, 721.
2
3
(a) G. A. Olah, Friedel-Crafts Chemistry, Wiley, New York,
Scheme 1. A possible mechanism for the cross-coupling of aryl
iodides with 2-hydroxybenzaldehydes.
1
973; (b) G. Sartori and R. Maggi, in: Advances in Friedel-
Crafts Acylation Reactions: Catalytic and Green Process, CRC
Press, Florida, 2010.
The reusability of catalyst is the major area of interest due to
environmental and economic concerns. One of the significant
advantages of the use of ammonium salts as reaction medium is
possibility of catalyst recycling. Regarding this property of
ammonium salts, the recyclability of the catalytic system was also
examined in the reaction of iodobenzene with salicylaldehyde. After
initial experimentation, the reaction mixture was extracted with
(a) G. Tojo and M. Fernandez, Oxidation of Alcohols to
Aldehyde and Ketones: A Guide to Current Common Practice,
Springer, 2006; (b) M. Hudlicky, In Oxidations in Organic
Chemistry, ACS Monograph 186, American Chemical Society:
Washington, DC, 1990.
4
5
(a) J. March, Advanced Organic Chemistry, Wiley, New York,
3
1
rd edn, 1985, pp. 433 and 824; (b) R. K. Dieter, Tetrahedron,
999, 55, 4177.
diethyl ether, and the obtained Ni(0)/n-Bu NBr/ethylene glycol was
(a) L. Yang, T. Zeng, Q. Shuai, X. Guo and C. J. Li, Chem.
Commun. 2011, 47, 2161; (b) J. Karthikeyan, K. Parthasarathy
and C. H. Cheng, Chem. Commun. 2011, 47, 10461; (c) B. K.
Dey, J. Dutta, M. G. B. Drew and S. Bhattacharya, J.
Organomet. Chem. 2014, 750, 176; (d) H. Rao, L. Yang, Q.
Shuai and C. J. Li, Adv. Synth. Catal. 2011, 353, 1701; (e) J. Y.
Chen, S. C. Chen, Y. J. Tang, C. Y. Mou and F. Y. Tsai, J. Mol.
Catal. A: Chem. 2009, 307, 88; (f) T. W. Lyons and M. S.
Sanford, Chem. Rev. 2010, 110, 1147; (g) M. Pucheault, S.
Darses and J. P. Genet, J. Am. Chem. Soc. 2004, 126, 15356;
4
subjected to a second run of the reaction by charging with the same
substrates (iodobenzene and salicylaldehyde). As shown in Table 3,
quantitative conversion to the corresponding product was observed
for three runs. From the fourth run, loss of the activity of the
system was observed.
Table 3. Recycling of the catalyst for the coupling reaction of
iodobenzene with salicylaldehyde.
(i) Y. Fu, Y. Yang, H. M. Hügel, Z. Du, K. Wang, D. Huanga and
Y. Hu, Org. Biomol. Chem. 2013, 11, 4429; (j) C. Qin, J. Chen,
H. Wu, J. Cheng, Q. Zhang, B. Zuo, W. Su and J. Ding,
Tetrahedron Lett. 2008, 49, 1884; (k) J. R. Schmink and S. W.
Krska, J. Am. Chem. Soc. 2011, 133, 19574.
(a) G. Tang, Z. Nikolovska-Coleska, S. Qiu, C. Yang, J. Guo and
S. Wang, J. Med. Chem. 2008, 51, 717; (b) S. Zhong, X. Chen,
X. Zhu, B. Dziegielewska, K. E. Bachman, T. Ellenberger, J. D.
Ballin, G. M. Wilson, A. E. Tomkinson and A. D. Jr. MacKerell,
Cycle
Time (h)
Yield % a
1
2
3
2
3
94
91
86
6
5.5
4
| J. Name., 2012, 00, 1-3
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Please do not adjust margins

Page 5 of 6
Please Rd So Cn oA tda vd aj un sc te ms argins
Journal Name
COMMUNICATION
J. Med. Chem. 2008, 51, 4553; (c) T. J. Crisman, M. T. Sisay
and J. Bajorath, J. Chem. Inf. Model. 2008, 48, 1955.
(a) A. Krick, S. Kehraus, C. Gerhuser, K. Klimo, M. Nieger, A.
Maier, H. H. Fiebig, I. Atodiresei, G. Raabe, J. Fleischhauer
and G. M. Knig, J. Nat. Prod. 2007, 70, 353; (b) Y. Deng, Y. W.
Chin, H. Chai, W. J. Keller and A. D. Kinghorn, J. Nat. Prod.
View Article Online
DOI: 10.1039/C5RA18890C
7
2
007, 70, 2049; (c) C. Zhang, J. G. Ondeyka, K. B. Herath, Z.
Guan, J. Collado, G. Platas, F. Pelaez, P. S. Leavitt, A. Gurnett,
B. Nare, P. Liberator and S. B. Singh, J. Nat. Prod. 2005, 68
6
1
,
,
11; (d) J. Li, Y. Jiang and P. F. Tu, J. Nat. Prod. 2005, 68
802; (e) M. Pecchio, P. N. Sols, J. L. Lpez-Prez, Y. Vsquez, N.
Rodrguez, D. Olmedo, M. Correa, A. S. Feliciano and M. P.
Gupta, J. Nat. Prod. 2006, 69, 410.
8
T. Satoh, T. Itaya, M. Miura and M. Nomura, Chem. Lett.
1
996, 823.
9
1
M. Xia and Z. Chen, Synth. Commun. 2000, 30, 531.
0 F. Weng, C. Wang and B. Xu, Tetrahedron Lett. 2010, 51
2
,
593.
1
1
1 N. Nowrouzi, S. Motevalli and D. Tarokh, J. Mol. Catal. A:
Chem. 2015, 396, 224.
2 (a) L. J. Gu, C. Jin and H. T. Zhang, Chem. Eur. J. 2015, 21
,
8
741; (b) S. H. Kim and R. D. Rieke, Tetrahedron Lett. 2011,
, 1523; (c) Y. C. Wong, K. Parthasarathy and C. H. Cheng,
5
2
Org. Lett. 2010, 12, 1736; (d) F. Wu, W. Lu, Q. Qian, Q. Ren
and H. Gong, Org. Lett. 2012, 14, 3044; (e) N. Iranpoor, H.
Firouzabadi and E. Etemadi Davan, J. Organomet. Chem.
2
015, 794, 282.
1
1
3 M. T. Reetz and J. G. de Vries, Chem. Commun. 2004, 1559.
4 C. Bandyopadhyay, K. R. Sur and H. K. Das, J. Chem. Res.
Miniprint, 1999, 2561.
1
5 (a) T. Das, A. Chakraborty and A. Sarkar, Tetrahedron Lett.
2
1
014, 55, 7198; (b) D. J. Chen and Z. C. Chen, Synlett 2000,
175.
1
1
6 S. K. Chittimalla, T. C. Chang, T. C. Liu, H. P. Hsieh and C. C.
Liao, Tetrahedron 2008, 64, 2586.
7 O. Kysel, R. Zahradník and B. Pakula, Collection of
Czechoslovak Chem. Commun. 1970, 35, 3020.
1
1
8 C. Zhou and R. C. Larock, J. Org. Chem. 2006, 71, 3551.
9 A. R. Katritzky, K. N. B. Le and P. P. Mohapatra, Synthesis
2
007, 3141.
0 N. Iranpoor, H. Firouzabadi, Kh. Rajabi Moghadam and S.
Motavalli, RSC Adv. 2014, , 55732.
2
4
2
2
1 N. Nowrouzi and M. Zarei, Tetrahedron 2015, 71, 7847.
2 S. V. Kryatov, B. S. Mohanraj, V. V. Tarasov, O. P. Kryatova, E.
V. Rybak-Akimova, B. Nuthakki, J. F. Rusling, R. J. Staples, A.
Y. Nazarenko, Inorg. Chem. 2002, 41, 923.
2
3
General Procedure: A mixture of tetrabutylammonium
bromide (0.5 mmol, 0.16 g), aryl iodide (2.0 mmol), 2-
hydroxybenzaldehyde (1.0 mmol), NiCl .6H O (0.4 mmol,
2
2
0
.114 g) and NaOH (2.0 mmol, 0.08 g) were added to a flask
containing 2 mL of ethylene glycol. The mixture was heated
o
in an oil bath at 120 C with stirring and the reaction was
followed by TLC analysis. When the reaction was completed,
the solution was allowed to cool to room temperature and
the product was extracted with diethyl ether (3×3 mL). The
organic layer was dried over anhydrous Na SO and purified
2
4
by column chromatography over silica gel using n-
hexane/ethyl acetate (5:1) as eluent to afford the highly pure
product (Table 2).
9
2
-Hydroxybenzophenone (Table 2, Entry 1) [117-99-7]: IR
-
1 1
(
KBr): 3500, 1728 cm . H-NMR (250 MHz, CDCl ) δ (ppm):
3
1
1.96 (s, 1H, OH), 7.62-7.40 (m, 7H, Ar), 7.02-6.98 (m, 1H,
13
Ar), 6.83-6.77 (m, 2H, Ar). C-NMR (62.9 MHz, CDCl ) δ
3
(
ppm): 200.01, 158.02, 140.77, 133.85, 133.76, 132.95,
32.04, 127.96, 127.46, 120.01 (overlap, two peaks). Anal.
Calcd for C H O : C, 78.77; H, 5.09. Found: C, 78.37; H,
1
13 10 2
4
.96.
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RSC Advances
Page 6 of 6
View Article Online
DOI: 10.1039/C5RA18890C
First Direct Access to 2-Hydroxybenzophenones via Nickel-
Catalyzed Cross-Coupling of 2-Hydroxybenzaldehydes with
Aryl Iodides
*
Najmeh Nowrouzi, Marjan Zarei and Fatemeh Roozbin
The Nickel-catalyzed cross-coupling of 2-hydroxybenzaldehydes with aryl iodides
proceeds in ethylene glycol to give the corresponding 2-hydroxybenzophenones.