Ind. Eng. Chem. Res.

2010, 49, 4607–4613 4607

Hydroxylation of Phenol by Hydrogen Peroxide Catalyzed by Copper(II) and

Iron(III) Complexes: The Structure of the Ligand and the Selectivity of
ortho-Hydroxylation
Edward A. Karakhanov,* Anton L. Maximov, Yulia S. Kardasheva, Vitaliy A. Skorkin,
Sergey V. Kardashev, Ekaterina A. Ivanova,† Elena Lurie-Luke, Jeffrey A. Seeley, and
Scott L. Cron
Department of Chemistry, Moscow State UniVersity, Moscow, 119991, Russia

A number of complexes of copper(II) and iron(III) with different N,N and N,O ligands were tested as catalysts
for the hydroxylation of phenol to dihydroxybenzene by hydrogen peroxide for the purpose of achieving a
high catechol selectivity. Cu(II) complexes were demonstrated to give a high selectivity on catechol. The
best selectivity was found for Cu(II) complex with 2,6-dihydroxypiridine. The best conditions for the selective
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formation of catechol were the reaction time of 15 min and a ratio of 2,6-dihydroxypiridine to copper greater
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than 3 (65 °C). The concentration of phenol and the reaction time had a dramatic influence on the catechol
yield and selectivity for most selective catalysts. At high concentrations and reaction times, both the catechol
yield and selectivity decreased, with tars being formed.

Introduction conversions were not more than 25% on the basis of phenol.
The amount of tars and byproduct was 10-20%. The lowest
Catechol is widely used in industry as an important inter- byproduct formation has been achieved using ketone peroxides
mediate in manufacturing pesticides and medicines and can also (Table 1).
be used to produce perfumes (e.g., piperonal), dyes, photosensi- The key problem of using transition metal catalytic systems
tive material, special inks, antioxidants and polymerization deals with side reactions, especially when a high space time
inhibitors, fungicides, light stabilizers, anticorrosive agents, and yield is achieved.8 Due to the complexity of the whole process,
promoters. Catechol is used in the manufacture of the artificial numerous reaction schemes have been found in the literature.9
flavors vanillin and ethyl vanillin. The world’s first fully In all reviewed literature, two types of byproduct, quinones and
synthetic “marine fragrance” Heliofresh, used in many popular macromolecular tars, were formed (Figure 1).10-16
perfumes as a trendy aroma, was successfully derived from The overoxidation problem is solved, in industry, by using
catechol. Catechol is also used in the manufacture of the high phenol/hydrogen peroxide ratios along with high concen-
insecticides carbofuran and propoxur. The pharmaceuticals used trations of phenol. Because the catechol and o-quinone formed
in the treatment of Parkinson’s disease and hypertension, L-dopa are more easily oxidized than phenol, the reaction is carried
and methyl L-dopa, are manufactured from catechol. The world out in a large excess of phenol. Thus, phenol/hydrogen peroxide
production of catechol is more than 30 000 t.1 molar ratios range from 2 to 20. The rate of the formation of
The current manufacturing process of catechol with hydro- catechol should be high enough to achieve high conversion of
quinone involves a direct hydroxylation of phenol with perox- hydrogen peroxide in a short time to avoid overoxidation of
ides. Only the Brichima process in Italy2 has used heavy metal catechol. A lower ratio leads to a higher conversion rate;
compounds (e.g., small quantities of ferrocene and/or cobalt however, if the conversion of phenol in such conditions is too
salts) as a catalyst (phenol reacts with 60% aqueous hydrogen high, then dihydroxybenzene will be further oxidized to produce
peroxide at 40 °C). Catechol and hydroquinone are produced acids and polymer tars and the selectivity of the reaction will
in the ratio of 1.5-4.1. The other methods include the reaction be reduced.8 Therefore, under a high ratio of phenol/oxidant,
of phenol with 70% hydrogen peroxide or performic acid in phenol has an inhibition effect. The lower the conversion of
the presence of phosphoric acid and catalytic amounts of phenol, the better the selectivity of the reaction to dihydroxy-
perchloric acid at 90 °C (Rhone-Poulenc),3 hydroxylation of benzene. From the industrial point of view, it is preferable to
phenol with ketone peroxides (R-hydroxy hydroperoxides) have a high degree of conversion in order to keep the space
formed in situ from a ketone and hydrogen peroxide in the time yield high. As mentioned above, a conversion should be
presence of an acid catalyst (ratio phenol/hydrogen peroxide
20) (Ube, Rhone-Poulenc),4 and hydroxylation of phenol by Table 1. Comparison of the Phenol Hydroxylation Processes6-8
hydrogen peroxide using TS-1 zeolite heterogeneous catalyst Rhone-Poulenc
(Enichem).5 In all reported data for industrial production,6 the HC(O)OOH+ Ube industries
process and HClO4, Brichima Enichem Rhone-Poulenc
phenol concentration was high (more than 30%), phenol catalyst H3PO4 Fe(II)/Co(II) TS-1 ketone + acid
selectivity was less than 90% (for catalysis by transition metals
not more than 85%), and hydrogen peroxide selectivity was phenol/H2O2 20 3-10 4-10 20
ratio
60-90% (lower for transition metal compound catalysts that % phenol 5 10 25 4-4.5
deals with decomposition of hydrogen peroxide). Phenol conversion
% phenol 90 80 88 90-95
selectivity
* To whom correspondence should be addressed. Tel.: +74959395377. % H2O2 70 50-75 70 80-90
Fax: +7-495- 932-8846. E-mail: kar@petrol.chem.msu.ru. based yield
†
The Procter & Gamble Company. % tar 10 20 12 5-10

10.1021/ie902040m  2010 American Chemical Society

Published on Web 04/23/2010
4608 Ind. Eng. Chem. Res., Vol. 49, No. 10, 2010
Figure 1. Phenol oxidation pathways.
preferably 5-30% through-put desirable catechol out. On the
basis of this, we considered that a low ratio of phenol/hydrogen
peroxide (greater or equal to 2) is preferable. The experiments’
design described in this article was based on this assumption.
The most common oxidizing agents used in phenol hydroxy-
lation are hydrogen peroxide, H202, and alkyl hydroperoxides.9e,17
Organic peroxides are more potent oxidizing agents than
hydrogen peroxide; however, they are not environmentally
friendly; can be explosive, corrosive, and toxic; and present
extreme fire hazards. Many organic peroxides give off flam-
mable vapors when decomposing. Further, because they are such
strong oxidizing agents, combustible materials contaminated
with residual organic peroxides can catch fire very easily and
burn very intensely.18 The drawback of hydrogen peroxide is
its low selectivity. Hydroxylation of aromatic compounds by
H202 either through electrophilic (H2O2/acid/ketone)19 or free
radical processes (Fenton’s 4 or Udenfriend’s s reagent)20 is
usually not selective because of the further oxidation of the
phenol ring due to the introduction of the activating OH group.
This leads to formation of a mixture of acids and polymeric
compounds.9e The reaction yields hydroquinione and catechol.
The main challenge of catechol production by hydroxylation is
a low selectivity toward catechol. The industrial catalysts give
selectivity on catechol from 50 to 70%.
On the basis of the above, the main drawbacks of these
methods are the formation of high quantities of hydroquinone
and o-quinone as byproducts and low yields on H2O2.21 In spite
of a wide number of metal complexes that were tested as
hydroxylation catalysts, only very few investigations have
looked into the impact of ligand structure on selectivity for
phenol’s oxidation. This publication deals with the hydroxylation
of phenol to catechol, catalyzed by copper and iron complexes
with some commercially available or easily synthesized enamine
ligands (N,N and N,O ligands), and the study of ligands structure
influence on ortho-selectivity in hydroxylation.
2. Experimental Section
2.1. Ligands 1-12. Ligands 1-12 were of commercially
available reagent-grade quality. The purification of solvents was
done according to literature procedures.22
2.2. Ligands 1s-9s. The ligands 1s-9s were synthesized
according to the published procedures.23 About 10 mmol of the
corresponding diamine dissolved in 8 mL of dry methanol was
added into solution of 4 mmol of corresponding aldehyde
dissolved in dry methanol. The mixture was allowed to stir at
room temperature for 2 h. For compounds 1s-4s and 9s, the
crude yellow precipitate was filtered and washed with 2-3 mL
of cold methanol. The product was recrystallized from dichlo-
romethane. The yields were from 89 to 96%. For compounds
5s-8s, the solvent was removed by evaporation. The remaining
yellow oil was washed by diethyl ether repeatedly, and the
precipitate was recrystalized from chloroform/hexane. The yields
were from 80 to 85%
2.3. NMR and ESI Measurements. The 1H NMR measure-
ments were recorded on a Bruker DXP 300 AVANCE spec-
trometer. Element analyses were performed on a Carlo Erba
Element Analyzer (type 1106). ESI-MS spectra were studied
using an Agilent 1100 SL Ion trap mass-spectrometer.
2.4. Hydroxylation of Phenol. A total of 4 mL of solution
of catalyst (Cu(SO4)2 · 5H2O or Fe(NO3)3 · 9H2O and ligand) was
added to 1 mL of solution of a corresponding quantity of phenol
in water. To the reaction mixture kept under the corresponding
temperature was added 1 mL of hydrogen peroxide solution.
The concentration of hydrogen peroxide changed in such way
as to achieve the desired molar ratio of phenol to H2O2. After
the desired time, the reaction mixture was homogenized by
acetone and analyzed by HPLC with UV and MS detectors
(Agilent 1100 SL Ion trap). The quantities of phenol, catechol,
and hydroquinone were determined using anisol as an internal
standard.

Figure 2. Commercially available ligands 1-12.
3. Results and Discussion
3.1. Ligand Selection. A number of different types of ligands
have been examined to identify a ligand that would provide the
highest selectivity. In this article, we focus on metal complexes
with N,O ligands and O,O ligands with aromatic fragments
(Figure 2), taking inspiration from enzymes, recognized as active
and selective oxidation catalysts, wherein the copper or iron
coordinates to a number of N (e.g., from histidine) and O (e.g.,
carboxyls and hydroxyl groups) atoms.
A number of ligands (1-7) were used without any modifica-
tion (Figure 2). These ligands are the simplest models of such
catalysts and provide the possibility to elucidate the impact of
catalyst selectivity as a function of coordination environment.
In a number of works, it has been demonstrated that complexes
of iron and copper containing N,N (e.g., dipyridil, N,N-bis[2-
(2-pyridyl)-amin) or N,O ligands (salen type and bis(2-hydroxy-
benzyl)ethylenediamine type) have been active in hydroxylation
of aromatic compounds by oxygen or hydrogen peroxide. These
ligands form the (µ-ν2:ν2-peroxo)dicopper(II) complexes or
high valence iron complexes that prove to be active toward
selective hydroxylation of phenol.24 It has been shown that
copper ions can increase the selectivity of hydroxylation,25 and
in most cases, substituted phenols have been used as the
substrates in such studies. The orientation of donor atoms in
ligands 1-11 promotes the formation of chelates and prevents
the oxidation of phenol catalized by noncoordinated ions. The
aromatic fragment of ligands can enhance the oxidation and
the reduction of the metal ion in the catalytic cycle. The ligands
(5-12) that contain a hydroxyl or an amino group linked with
an aromatic fragment can induce oxidation by scavenging free
radicals and forming semiquinone-like particles.26 The charge
transfer from the ligand to the metal ion could increase the
catalytic activity.27
The synthetic Schiff-base ligands containing N,N- and N,O-
chelate fragments are a family of attractive oxidation catalysts
for a variety of organic substrates due to their cheap and easy
synthesis as well as chemical and thermal stability.23 These
ligands widely vary in their structures, flexibility, electronic
nature, and the presence of additional donor atoms besides imino
nitrogen. Further tuning of their coordination characteristics can
be achieved by varying the nature of the aromatic fragment
Ind. Eng. Chem. Res., Vol. 49, No. 10, 2010 4609
Figure 3. Synthesis of enamyne type ligands.
Table 2. Hydroxylation of Phenol in Homogeneous System
Catalyzed by Cu(II) and Fe(III) Complexesa
copper complexes iron complexes
selectivity conversion phenol selectivity conversion phenol
on catechol to dihydroxybenzene on catechol to dihydroxybenzene
ligand [%] based on H2O2 [%] [%] based on H2O2 [%]
1 94 3 82 50
2 91 4 68 19
3 90 2 65 16
4 87 4 72 19
5 <1 71 28
6 95 9 73 21
7 89 3 67 18
8 91 2 64 15
a
Reaction conditions: 45°C, 30 min, [Cu] ) 0.002 M, [PhOH]/[Cu]
) 70, [PhOH]/[H2O2] ) 2, [ligand]/[Cu] ) 1 or [ligand]/[Fe] ) 2.
(phenolyc, pyridine, imidazol-based fragments), the linkage size,
and the position of substituents. A wide variety of ligand types
are obtained via the one-step Schiff base condensation of
corresponding amines and aldehydes (Figure 3). The ligands
1s-9s are characterized by 1H NMR and 13C -NMR spectros-
copy and ESI-MS spectrometry.
The copper(II) and iron(III) complexes were prepared in situ
for the investigation of hydroxylation of phenol. These ligand
complexes were tested at three temperatures to determine the
best lead candidates. Hydroxylation of phenol was carried out
in water using an excess of phenol. The primary products
determined were catechol, hydroquinone, and benzoquinone.
The conversion of phenol on the basis of H2O2 was estimated
as moles of reacted phenol per mole of H2O2; the conversion
of phenol to dyhydroxybenzene on the basis of H2O2, as moles
of dihydroxybenzene formed per mole of H2O2; the selectivity
on dihydroxybenzenes, as moles of dihydroxybenzene formed
per mole of reacted phenol; and the selectivity on catechol, as
moles of catechol formed per mole of dihydroxybenzene formed.
The selectivity was determined as a function of temperature,
oxidant conversion, and solvent and metal complex concentration.
3.2. Phenol Oxidation in Homogeneous Conditions:
Copper and Iron Complexes. Catechol formation and phenol
conversion catalyzed by the copper compared to iron systems
based on ligands 1-8 are listed in Table 2. The highest
conversion of phenol was 50% on the basis of hydrogen
peroxide, and a catechol selectivity of 84% was found for a
complex of iron with phenantroline. The data correlated with
the experiments presented by Liu et al.,28 where good selectivity
4610 Ind. Eng. Chem. Res., Vol. 49, No. 10, 2010

Table 3. Hydroxylation of Phenol Using Cu(II) and Fe(III) Complexes with Ligand 1s-9sa
copper complexes iron complexes
selectivity selectivity on total conversion selectivity on selectivity on total conversion
PhOH/ on catechol dihydroxybenzenes based on H2O2 catechol dihydroxybenzenes based on H2O2
ligand H2O2 T [°C] [%] [%] [%] PhOH/H2O2 T [°C] [%] [%] [%]
1s 1 65 90 2.6 3 1 65 72 35 60
2s 1 45 90 80 3 1 45 73 51 54
2s 1 65 84 80 5 1 65 71 60 55
2s 1 85 80 28 72 1 85 71 51 70
2s 2 85 82 22 36 1
2s 4 85 85 13 14 1
3s 1 65 81 15 10 1 65 70 57 71
4s 1 65 89 32 21 1 65 69 54 74
4sb 1 65 87 51 35 1 65 <1
5s 1 65 90 20 25 1 65 <1
6s 1 65 82 80 15 1 65 <1
7s 1 65 61 50 95 1 65 <1
8s 1 65 78 58 60 1 65 <1
9s 1 65 66 65 5 1 65 68 51 12
a
Reaction conditions: 30 min, [Cu] ) 0.002M, [PhOH]/[Cu] ) 70, [PhOH]/[H2O2] ) 2, [Ligand]/[Cu] ) 2, [Ligand]/[Cu] ) 4. b
Reaction time 5
min.

Table 4. Hydroxylation of Phenol in Homogeneous Conditions with

was demonstrated for an iron(II)/phenantroline complex (70% 2,6-Dihydroxypiridine Analogsa
selectivity and 12% conversion for 3 h under a ratio [PhOH]/
overall conversion
[H2O2] ) 2). The main drawback of iron systems was a high selectivity on of phenol based
rate of byproduct formation. The overall selectivity on dihy- ratio ligand/ catechol ratio catechol/ on H2O2 tars
droxybenzene was not more than 40% for 45 min and not more ligand Cu(II) [%] hydroquinone [%] [%]
than 30% for 2 h for all complexes. An excess amount of 6 1 95 16 9 <1
hydrogen peroxide was needed to improve the oxidation versus 6 3 93 15 30 1
byproduct formed within the first 5 min of the reaction. The 9 1 50 1 50 <1
9 2 50 1 32 <1
overall selectivity on catechol was poor. The main byproducts 9 4 50 1 34 <1
were polymeric tars. In most cases, tars and their structures are 10 1 66 2.5 26 7
not directly detectable, and the presence of tars in the reaction 10 2 68 3.2 25 10.5
10 4 72 4 21 10
mixture was identified by mass balance and by the quantity of 11 1 48 1.1 38 8
the brown precipitate that was formed during the reaction. 11 2 48 1.16 42 10
Cu(II) complexes demonstrated a lower activity in hydroxy- 11 4 54 1.4 42 7
12 1 56 4.2 22 30
lation. The results obtained indicate that the Cu(II) complexes 12 2 82 16 15 12
with ligands 1-4 and 6-8 are able to mediate the regiospecific 12 4 74 4 <1
ortho-hydroxylation of phenol in the presence of hydrogen a
Reaction conditions: PhOH/H2O2 ) 2, 65°C, 30 min.
peroxide. A low quantity of tars and quinones was formed. The
system with 2,6-dihydroxypiridine was the most active (the Table 5. Hydroxylation of Phenol in Homogeneous Conditions with
conversion was 9% with high selectivity on catechol). 2,6-Dihydroxypiridinea

The iron complexes with ligands 1s-4s and 9s catalyzed the overall conversion
selectivity of phenol based
oxidation of phenol with the selectivity on catechol being only [PhOH], time on catechol ratio catechol/ quinones on H2O2
68-73% at a selectivity on dihydroxybenzene of about 60% [M] [min] [%] hydroquinone yield [%]
(Table 3). The complexes with ligands 5s-8s with basic
0.14 30 81 10 11 25
fragments were not active because of the fast formation of iron 0.14 180 66 3 12 35
hydroxide. The Cu complexes with ligand 2s were selective for 0.14b 30 45 14 37 25
catechol formation at low conversion. The complexes with the 0.5 30 81 55 18 21
0.5 180 63 2.5 13 29
other ligands catalyzed fast oxidation of catechol and hydro- 0.9 30 70 4 12 26
quinone, but the ratio of catechol to hydroquinone was high. a
Reaction conditions: 2,6-dihydroxypiridine/Cu(II)/Co(III) )
The maximum conversion was achieved for the ligands obtained 3:1:0.05. PhOH/H2O2 ) 2, 65°C. b Double quantity of catalyst.
with the use of 1,4-diaminobutane (four methylene fragments).
The distance between the coordinating groups appears to be Also, it was found that the activity of Cu(II) catalytic systems
optimal in this case. was optimal at pH 5.5-6. At lower or higher pH ranges, the
The Cu(II) complex with 2,6-dihydroxypiridine was the most activity of the catalyst diminished rapidly.
selective in the hydroxylation of phenol at the ratio ligand/metal Following these results, the catalytic system was modified
) 3 (Table 4). Low selectivity was observed in the case of the from 2,6-dihydroxybenzene by Co(III) (5-10 mol % to Cu(II)),
Cu complexes with analogs of 2,6-dihydroxypiridine (9-10) and also Ar as an inert gas was used. The oxidation data of this
and catechol (11-12). For all the systems, the yield of catalytic system are summarized in Table 5.
overoxidation products was low and near 90% of hydrogen The conversion based on hydrogen peroxide was near 25%,
peroxide converted to dihydroxybenzene. The quantity of tars and overall selectivity on catechol was more than 80% (catechol/
was high only for ligand 12 at a low ratio of Cu(II) to ligand. hydroquinone ratio more than 10) without overoxidation and
However, after 1 h of the reaction, the selectivity for all the with a small quantity of tars. Selectivity on o- and p-
ligands decreased to 60% due to overoxidation. benzoquinones was 11%. When comparing the results obtained
 Ind. Eng. Chem. Res., Vol. 49, No. 10, 2010 4611
a
Table 6. Phenol Oxidation with Catalytic System Cu(II)/2,6-Dihydroxypyridine
selectivity selectivity on conversion phenol
on catechol dihydroxy-benzene to dihydroxy-benzene based
[Cu(II)]/[L] [PhOH]/[Cu(II)] [PhOH]/[H2O2] T [°C] [%] [%] on H2O2 [%]
3 70 1 45 92 99 12
3 50 1 45 92 98 9
3 70 1 65 89 94 23
3 70 2 65 93 98 30
3 70 4 65 91 99 34
3 350 1 65 92 98 24
1 23 1 65 75 87 31
3b 70 1 65 97 98 26
3 70 1 75 71 94 29
a
Reaction conditions: [PhOH] ) 0.2 M, 30 min. b Adding hydrogen peroxide by portion, 30 min.

at 65 °C, after 30 min or 3 h of reaction, overoxidation to

benzoquinone and a change in selectivity was observed. The
quantity of catechol and o-quinone increased slowly versus the
quantity of hydroquinone. The hydrogen peroxide consumption
was low (the products’ yields were not more than 30% over
3 h).
3.3. Reaction Conditions. The best catalyst for hydroxyla-
tion of phenol to catechol in the terms of optimal efficiency
and selectivity was copper complexed with ligand 6 (2,6-
dihydroxybenzene). In order to acquire suitable reaction condi-
tions for maximum transformation of phenol, the catalysts were
studied in detail by considering the following reaction param-
eters: the effect of the phenol/H2O2 concentration ratio, the effect
of ligand concentration, and the effect of temperature (Table
6).
The optimal temperature for hydroxylation of phenol with
Cu(II)/2,6-dihydroxypyridine was 65 °C. A conversion of more
than 24% was achieved under a ratio of [PhOH]/[H2O2] ) 1
with a selectivity on catechol of more than 89%. On the basis
of our observations, at a lower phenol/H2O2 ratio, the conversion
of phenol was higher, and the same was noted for the selectivity
for dihydroxybenzene and catechol. Using three different
amounts of phenol for a fixed amount of hydrogen peroxide
and catalyst (phenol/H2O2 ) 4, 1, 0.5), the percentage of phenol
conversion was around 34%, with the lowest H2O2 concentration
(i.e., 4:1 phenol/H2O2 ratio) yielding high selectivity for catechol
(93%). Two other concentrations (1:1 and 1:2 4-phenol/H2O2
ratios) gave comparable results of about 23-30% conversion
and a selectivity for catechol of 89-93%. The catalytic system
gave high selectivity on ortho-hydroxylation at a high phenol/
hydrogen peroxide ratio. Additional oxidant gave the best
selectivity on catechol with a phenol conversion of 26%. The
main byproduct is the benzoquinone, and only traces of
hydroquinone are formed.
The data on the kinetics of the reaction catalyzed by the
Cu(II)/2,6-dihydroxypyridine complex are presented in the
Figure 4. The selectivity was poor after 1 h of the reaction.
The predominant feature of the reaction was the existence of
an induction period, followed by an autocatalysis. Catechol,
hydroquionone, and detectable amounts of p- and o-benzo-
quinones were formed at the start of the reaction, and the
catechol partly oxidized after 25-30 min, forming higher
quantities of quinones and acids. When the reaction was
conducted under Ar, the quantity of quinones decreased. Also,
the selectivity was lower under a high concentration of phenol
in water (0.9 M). The conversion was 27% with a selectivity
lower than 70% for 30 min.
In all cases, the overoxidation of the catechol and hydro-
quinone proceeded under a higher concentration of phenol and
longer reaction times. The dihydroxybenzenes oxidized rapidly
to benzoquinones, o-hydroxy-p-benzosemiquinone and hy-
Figure 4. Oxidation of phenol by H2O2 using catalytic system 2,6-
dihydroxypyridine/Cu(II). Reaction conditions: [Cu] ) 0.002 M, [PhOH]/
[Cu] ) 70, [PhOH]/[H2O2] ) 1, 75 °C.
droxyl-p-benzoquinone. All these products were detected by
ESI-MS. Subsequently, the ring breaks down, forming low
molecular weight carboxylic acids (<C6). The hydrogen atom
abstraction from the benzylic position induces the benzylic
ligand hydroxylation, and hydrogen atom abstraction from the
phenol group leads to phenol polymerization.
We investigated reaction mixtures in situ by ESI-MS under
a high concentration of phenol (0.9M) and under different
reaction times. The study has indicated that, after mixing the
solution of copper complex and phenol from mononuclear
complex copper with 2,6-dihydroxypyridine (m/z 284), the
binuclear complex with the ligand and phenol was formed (m/z
457). The concentration of this species decreases within 10 min
of hydrogen peroxide addition. After this time, the complex with
catechol is detected as the main species (m/z 421) in the sample.
It is very likely that the orthohydroxylation proceeds inside the
coordination sphere of the binuclear complex Cu(II)/2,6-
dihydroxypiridine/phenol. The selective formation of one of the
products can be affected when the orientation of the substrate
is fixed by coordination of its hydroxyl group on the metal
center, as was shown for Cu-dinuclear enzymes.25 The catalytic
overoxidation of catechols by copper(II) complexes occurred
through the formation of a dicopper-catechol complex, a
precursor to the qionones and acids.
It is likely that the drop in selectivity is due to the formation
of the catechol complex with copper (formation constant more
than 1014 for Cu(Cat) and 1023 for Cu(Cat)211). The letter
demonstrated a low selectivity in the hydroxylation of phenol
and high activity in overoxidation. To verify this, the kinetics
of phenol hydroxylation catalyzed by a Cu(II)/catechol complex
4612 Ind. Eng. Chem. Res., Vol. 49, No. 10, 2010

Figure 5. Oxidation of phenol by H2O2 using the catalytic system catechol/

Cu(II). [Cu] ) 0.002 M, [PhOH]/[Cu] ) 70, [PhOH]/[H2O2] ) 1, 75 °C.

reason for ortho-hydroxylation being the predominant pathway

in this type of catalyst.
were studied (Figure 5). The selectivity on catechol was lower
than in the case of the complex with 2,6-hydroxypyridine. 4. Conclusions
Catechol and hydroquinone were obtained with a ratio of around
3:1. The yield of dihydroxybenzenes reached only 13%, and The results obtained indicated the copper(II) complexes are
selectivity on dihydroxybenzenes was less than 40%. Polymeric able to mediate the region-specific ortho-hydroxylation of phenol
tars and quinones were formed. Copper-mediated overoxidation in the presence of hydrogen peroxide under homogeneous
is supposed to proceed through the formation of Cu(II) conditions. The iron complexes did not catalyze selective
catecholate complexes, then Cu(I) semiquinone complexes and hydroxylation to the ortho isomer. Although for the copper
further oxidation of the ligand by hydrogen peroxide, oxygen, complexes the conversion of phenol was lower than that of the
or Cu(II) ion12 iron complexes, the selectivity to catechol was high. The yields
The activity of the catalyst based on 2,6-dihydroxypyridine of products based on H2O2 after 30 min of the reaction varied
compared with some literature results on phenol hydroxylation between 2 and 9% for commercially available ligands. The
catalysts is presented in Table 7.29-33 The former demonstrates selectivity on dihydroxybenzene was more than 95%, and the
a higher time-space yield than the most selective catalyst selectivity on catechol was more than 85%. The Cu(II)
([Ni{MeBzo2[14]aneN4}]Cl2) without CH3CN as a cosolvent. complexes with enamine ligands were shown to provide good
It should be emphasized that it is a commercially available catechol selectivity for ligands 1s-6s with a high rate of tar
ligand in comparison with the ligand used for the synthesis of formation.
a Ni-containing catalyst. Complexes of Cu with 2,6-dihydroxypyridine gave the best
The orientation of phenol in the intermediate complex, at results. The overall selectivity on catechol was more than 90%
which it is the ortho position that is the most favorable for without overoxidation (30 min). The optimal reaction time for
hydroxylation, appears to be important for selectivity. Such most selective catalysts was 15 min; the optimal temperature
restricting of the approach of phenol toward the complex may was 65 °C. The selectivity on dyhydroxybenzene was lower at
occur when dimeric particles with copper and peroxide are higher temperatures and higher at low conversions. High
formed as in tirosinase.34 We suppose that the selective catalysts selectivity could be achieved at a phenol/H2O2 ratio of more
were dimeric Cu(II) complexes that were formed in water than 2. The selectivity decreased to 60% after 1 h of the reaction
solutions under pH 5.3-7.5 with such tridentant ligands as 1,6- because of overoxidation due to the formation of a copper-
dihydroxypyridine.11 The first copper atom coordinates with the catechol complex.
oxygen atom of phenol and activates the substrate. The second One of the possible ways to overcome this problem could be
atom activates hydrogen peroxide. This could be a plausible to choose a ligand with a very high stability constant to copper
Table 7. Phenol Hydroxylation Catalyzed by Different Catalytic Systems
conversion phenol
selectivity on to dihydroxy-benzene based
catalyst solvent [PhOH] [PhOH]/[H2O2] time, min T [°C] catechol [%] on H2O2[%] ref
Cu(II)/2,6-dihydroxypyridine water 0.2 1 30 65 89 23
water 0.2 2 30 65 93 30
[Ni{Me4Bzo2[14]aneN4}]Cl2 water 5 1 360 80 85 15 29
CH3CN/water 5 1 360 80 89 40
CH3CN/water 5 2 360 80 92 8
CuCl2 + H4SiW12O40 water 1.2 1 270 70 64 39 30
CuUSY water 0.3 1 120 60 60 9 (tars) 31
CuHbeta water 0.3 1 120 60 18 35(tars) 31
[Cu(Mebzlh)]-Y CH3CN/water 1.05 0.1 360 80 71 52 32
poly-[Fe(C10H7 2-NdCHC6H4 4-O)3] CH3CN/water 5 1 360 50 84 17 33

versus catechol. The design of better catalysts could be obtained
by the modification of copper-based catalytic systems through
the combination of electronic and coordination properties of the
ligand with molecular recognition abilities, characteristic for
such molecules as cyclodextrines.
Supporting Information Available: Spectral data on ligands
1s-9s. This information is available free of charge via the
Internet at http://pubs.acs.org/.
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ReceiVed for reView December 23, 2009
ReVised manuscript receiVed April 1, 2010
Accepted April 11, 2010
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