Dimethylglyoxime as an efficient ligand for copper-catalyzed hydroxylation of aryl halides

Article abstract of DOI:10.1007/s12039-017-1416-x

The CuI/dimethylglyoxime (CuI/DMG) catalyzed direct hydroxylation of aryl iodides with CsOH takes place at 120°C in a mixed solvent system (DMSO–H ₂O ,1:1), afforded the corresponding phenols in good to excellent yield. Aryl bromides are found to be less reactive than aryl iodides under these reaction conditions. Graphical Abstract: SYNOPSIS. (CuI/DMG) catalyzed synthesis of phenol from aryl iodide and aryl bromide in presence of mixed solvents (H ₂O : DMSO) is reported in this paper. This protocol is general, economical, easy and convenient for transformation of aryl iodides and bromides to substituted phenols under mild reaction conditions. [Figure not available: see fulltext.].

Full text of DOI:10.1007/s12039-017-1416-x

J. Chem. Sci. (2018) 130:13
© Indian Academy of Sciences
https://doi.org/10.1007/s12039-017-1416-x
REGULAR ARTICLE
Dimethylglyoxime as an efficient ligand for copper-catalyzed
hydroxylation of aryl halides
∗
SURESH S SHENDAGE
Department of Chemistry, KET’S Vinayak Ganesh Vaze College of Arts, Science and Commerce,
Mithagar Road, Mulund (E), Mumbai, Maharashtra 400 081, India
E-mail: sureshsshendage@gmail.com
MS received 21 September 2017; revised 1 December 2017; accepted 9 December 2017
Abstract. The CuI/dimethylglyoxime (CuI/DMG) catalyzed direct hydroxylation of aryl iodides with CsOH
◦
takes place at 120 C in a mixed solvent system (DMSO–H2O,1:1), afforded the corresponding phenols in good
to excellent yield. Aryl bromides are found to be less reactive than aryl iodides under these reaction conditions.
Keywords. Aryl halide; C-O coupling; dimethyl glyoxime; hydroxylation; phenol.
3
1
. Introduction
iodides using CuI and either 1, 3-diketone or 1, 10-
12
phenanthroline in aqueous DMSO can be used for
synthesis of phenols. In addition to this several other lig-
ands such as lithium pipecolinate, tetrabutylammonium
hydroxide pentahydrate, 8-hydroxyquinoline-N-oxide
Phenols play key role in production of natural products,
pharmaceutical and medicinal compounds, as well as in
polymers and other materials. These days, about more
than 90% of the world’s phenol requirement is satisfied
by the Hock process, which entail the peroxidation of
cumene, itself obtained from benzene propylation.
The conventional methods used in synthesis of phe-
nols are nucleophilic aromatic substitution of activated
arylhalides, benzyneprocedure, andcopper-mediated
transformation of arene diazonium salts. Recently, var-
ious efficient palladium/phosphine-catalyzed protocols
have been developed for the formation of phenols.
11,13–15
and D-glucose
were used, which shows that lig-
ands play important role in the activity of catalyst.
However, in spite of these advancements, there is a need
for economical and easily available ligands which have
general applicability. Copper catalyzed route is essential
from an industrial perspective, owing to the availability
1
–4
5
6
7
16,17
of reagents, low cost and low toxicity.
This paper reports a simple, practical and efficient
copper-catalyzed synthesis of substituted phenols from
aryl halides by using dimethyl glycoxime (Butane-2, 3-
dione dioxime) as an inexpensive, simple, and efficient
ligand in presence of CsOH base. Thus, dimethylgly-
oxime has drawn considerable interest from both the
chemical and biological sciences. The oxime group
8
,9
However, less expensive copper (I) salt as catalyst would
be most attractive option for economic benefits and
low toxicity issues. The usage of a cheaper system
facilitates the hydroxylation1
0,11
of aryl halides have
turn out to be an important objective. In organic syn-
thesis the development of a mild, general and highly
efficient method for the preparation of phenols is a
challenging task. At present the availability of start-
ing materials and the direct nucleophilic substitution of
a halogen atom in aryl halides are interesting strate-
gies for the preparation of substituted phenols. These
days copper-catalyzed hydroxylation of aryl halides has
gained considerable attention. In the past it was reported
that direct crosscoupling of hydroxide salts and aryl
(
>C=N–OH), which perhaps considered to be derived
from oxy-imine, is amphoteric since it contains slightly
basic nitrogen and mildly acidic hydroxyl groups.18
2
. Experimental
All reagents were commercially purchased and used without
further purification. The reation products were identified by
comparing observed and reported H-NMR spectra and melt-
ing point. HNMRspectra were recorded ona Bruker AC-400
(400 MHz) spectrometer with TMS as an internal Standard.
1
1
*
For correspondence
Electronic supplementary material: The online version of this article (https://doi.org/10.1007/s12039-017-1416-x) contains
supplementary material, which is available to authorized users.

13
Page 2 of 4
J. Chem. Sci. (2018) 130:13
OH
I
96% (Table 1, entry 6) yield of the corresponding prod-
uct higher than ligand L3 (85%) (Table 1, entry 3).
Hence the ligand L6 was identified as a competent
ligand, whereas ligands L1(2,2-Bipyridine), L2(1,10-
CuI (10mol%), Ligand (20mol%)
Base (3 equiv.),Solvent
o
1
20 C, 10 h
Phenanthroline),
and L5 (2,2 ,2 ,2 -(ethane-1,2-diylbis(azanetriyl)tetra-
acetic acid) afforded lower yield (Table 1, entries 1, 2, 4
L4[N-(2-cyanophenyl)benzamide]
ꢀ
ꢀꢀ ꢀꢀꢀ
Scheme 1. Copper catalyzed Hydroxylation of Aryl
Halides.
&
5) . In the absence of ligand, controlled experiments
were carried out in order to check whether reaction pro-
.1 General procedure for the synthesis of substituted ceeds in absence of ligand or not. It was found that only
2
phenols
15% yield of the desired product was obtained without
the aid of the ligand (Table 1, entry 16).
The appropriate aryl halide (1 mmol), CsOH (3 mmol), and
H2O (1 mL) were added over 0.1 h, to a stirred solution
of CuI (19.0 mg, 10 mol%) and Dimethylglyoxime (L6;
2
3.2 mg, 20 mol%) in DMSO (1 mL), and the reaction
N
N
◦
N
N
mixture was stirred at 120 C (aryl iodides) or (aryl bro-
mides). The progress of the reaction was monitored by TLC
L1
L2
(EtOAc–hexane). The reaction mixture was then cooled to
room temperature and acidified with 0.5 M HCl (0.5 mL).
The resulting mixture was extracted with EtOAc (3×10 mL)
and dried (Na2SO4). Evaporation of the solvent gave a residue
that was purified by column chromatography.
N
NH
N
CN
L3
O
L4
O
3
. Results and Discussion
HO
O
N
OH
HO
N
Initially, the reaction conditions were optimized using
iodobenzeneasamodelsubstrateandusingdifferentlig-
ands, bases, copper salts and solvents (Table 1, entries
HO
N
OH
N
O
OH
L6
1
(
–16). Among several ligands briefly screened, L6
dimethylglyoxime) and L3 (N, N, N, N-Tetramethyl-
ethane-1,2-diamine) are effective. The ligand L6 gave
O
L5
Table 1. Optimization of Hydroxylation of Aryl Halidesa.
b
Sr. no Ligand Solvent [2ml]
Base [Cu] salts Yield (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
L1
L2
L3
L4
L5
L6
L6
L6
L6
L6
DMSO/H2O 1:1 CsOH
DMSO/H2O 1:1 CsOH
DMSO/H2O 1:1 CsOH
DMSO/H2O 1:1 CsOH
DMSO/H2O 1:1 CsOH
DMSO/H2O 1:1 CsOH
DMSO/H2O 1:1 KOH
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuCl
72
76
85
66
35
96
82
20
NMP
DMF/H2O 1:1 CsOH
H2O CsOH
CsOH
No Reaction
0
1
2
3
4
5
6
05
32
30
62
42
50
15
L6 1,4-dioxane/H2O CsOH
L6
L6
L6
L6
—
DMSO
CsOH
DMSO/H2O 1:1 CsOH
DMSO/H2O 1:1 CsOH CuSO4
DMSO/H2O 1:1 CsOH Cu(OAc)2
DMSO/H2O 1:1 CsOH
CuI
a
Iodobenzene (1 mmol), Ligand (20 mol%), CuI (10 mol%).
Isolated yield.
b

J. Chem. Sci. (2018) 130:13
Page 3 of 4 13
Table 2. Copper(I)-Catalyzed Hydroxylation of Aryl
Iodides and Bromides .
Among the bases, potassium hydroxide and cesium
hydroxide, the latter provided the best results (Table 1,
a
entries 6 & 7). A 1:1 mixture of DMSO/H O was found
2
to be the suitable solvent for this reaction. Solvents such
as NMP, water, DMF/H O (1:1) and 1,4-dioxane/H O
2
2
(
Table 1, entries 8–12) were found to be less effec-
tive, providing the desired product in less than 32%.
In addition, other copper salts such as CuCl, CuSO and
4
Cu(OAc) were poorer. The optimum temperature was
2
◦
1
20 C (Scheme 1).
The scope of the CuI/DMG catalyzed synthesis of
phenols was then investigated under above optimized
conditions. Irrespective of the aryl iodides as electron-
rich, electron-poor, or sterically bulky, all of them
afforded good to excellent yields (Table 2, entries 1–
1
1) of the corresponding products in presence of CsOH
in DMSO/H O (1:1). The hydroxylation of iodoben-
2
zene went on smoothly in high yields (96%) (Table 2,
entry 6). In case of the activated aryl iodides, such
as Nitro, carbonyl (Table 2, entries 3 & 4) the reac-
tions proceeded in 7 h providing the products in 94
&
95% yield. In addition to this, high yields observed
in the reaction of 4-methoxyphenyl, 4-butoxyphenyl
and 4-t-butylphenyl (Table 2, entries 6, 7 and 10).
Furthermore, 2-Iodonaphthalene gave 90% yield in
1
2 h. However, chloro substituted iodobenzene pro-
vided 89% yield of the corresponding product (Table 2,
entry 2).
The reaction conditions were further investigated
for the hydroxylation of the less reactive aryl bro-
mides, most of the aryl bromides were smoothly
converted into the corresponding phenols (Table 2,
entries 1–8). Bromobenzene underwent hydroxylation
to give the phenol with 85% yield, but required 17
h (Table 2, entry 1). However, the CuI/DMG sys-
tem were able to tolerate some functional groups such
as t-butyl, carbonyl, methyl, t-butoxide, nitro, and
methoxy groups but showed lower yield of the corre-
sponding products, compared to aryl iodides (Table 2,
entries 3–7 and 10). Moreover, 2-bromonaphathalene
afforded 80% yield in 20 h (Table 2, entry11). This
protocol has advantages such as short reaction time
and low reaction temperature over earlier reported
methods.
4
. Conclusion
This paper reports use of dimethylglyoxime (L6) as a
simple, efficient and economical ligand for the direct
copper-catalyzed synthesis of phenols. This protocol
tolerates various substituted and unsubstituted aryl
iodides and aryl bromides. The present protocol could
a
Reaction conditions: Aryl iodide (1 mmol), CuI (10 mol%),
DMG(L6;20mol%), CsOH(3equivalent), DMSO/H2O(1:1;
2
◦
b
mL), 120 C. Isolated yield.

13
Page 4 of 4
J. Chem. Sci. (2018) 130:13
be used for synthesis of various substituted phenols. In
general, the lower cost of copper and the use of readily
available ligands offer undisputable advantages over the
expensive metal/ligand systems. The reported protocol
will attract much attention in research because of their
wide applications in pharmaceuticals, polymers and nat-
ural products.
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Supplementary Information (SI)
1HNMR, 13C NMR and GC-MS spectral data for compounds
dealt in this article can be accessed at www.ias.ac.in/chemsci.
1
Acknowledgements
1
The author is thankful to KET’S V. G. Vaze College for finan-
cial support. The author is also thankful SAIF, IIT Mumbai
for Mass and Instrumentation department Solapur University,
1
13
Solapur for H NMR and C NMR analysis.
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