The mechanism of the heterogeneous catalytic monooxidation of thiophene derivatives at the S position by hydrogen peroxide

Article abstract of DOI:10.1134/S0036024409110119

A biomimetic catalytic reaction system for hetero-oriented monooxidation of heteroaromatic compounds was developed experimentally. The system consisted of two interacting synchronous reactions of the decomposition of H ₂O₂ and substr

Full text of DOI:10.1134/S0036024409110119

ISSN 0036ꢀ0244, Russian Journal of Physical Chemistry A, 2009, Vol. 83, No. 11, pp. 1873–1878. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © I.T. Nagieva, 2009, published in Zhurnal Fizicheskoi Khimii, 2009, Vol. 83, No. 11, pp. 2062–2067.
CHEMICAL KINETICS
AND CATALYSIS
The Mechanism of the Heterogeneous Catalytic Monooxidation
of Thiophene Derivatives at the S Position by Hydrogen Peroxide
I. T. Nagieva
Baku State University, Baku, Azerbaijan
eꢀmail: inara10@yahoo.com
Received October 24, 2008
Abstract—A biomimetic catalytic reaction system for heteroꢀoriented monooxidation of heteroaromatic
compounds was developed experimentally. The system consisted of two interacting synchronous reactions of
the decomposition of H O and substrate oxidation. The problem related to the preparation, isolation, and
2
2
identification of thiophene derivative Sꢀmonoxides was solved.
DOI: 10.1134/S0036024409110119
INTRODUCTION
the family of thiophene oxides, such as thiopheneꢀ1ꢀ
dioxide and its derivatives, have been studied in much
detail [1]. 1ꢀDioxide, which is easy to synthesize folꢀ
lowing known procedures, likely passes the stage of
formation and accumulation of Sꢀmonoxide in the
system. For this reason, the problem of the synthesis of
Heterocyclic compounds containing N, O, and
S atoms in rings hold an exceedingly important posiꢀ
tion in living nature. They occur in alkaloids, antibiotꢀ
ics, natural pigments, vitamins, nucleic acids, proꢀ
teins, etc. Among these compounds, fiveꢀ and sixꢀ
membered heteroaromatic compounds are of special
1
ꢀmonoxide should likely be solved using nontradiꢀ
tional oxidation methods such as the conjugated oxiꢀ
dation of substrates by hydrogen peroxide in the presꢀ
ence of catalytic biological simulators which model
the mechanism of monoxygenase reactions that occur
in living systems.
importance. They are as a rule divided into
fiveꢀmembered rings with one heteroatom) and
ꢀdeficient (sixꢀmembered rings). Thiophene and its
derivatives are ꢀexcessive heterorings with proꢀ
π
ꢀexcessive
(
π
π
nounced aromatic properties. They are active in elecꢀ
trophilic substitution reactions.
It follows that the development of theoretical and
experimental methods for the monooxidation of hetꢀ
eroatomic compounds with hydrogen peroxide is of
considerable interest, because these reactions give
Thiophene and its derivatives are comparatively
stable toward the action of oxidizers. However, H O2
in an acid medium or peracids oxidize them to sulfoxꢀ
ides (which were not isolated in the free state) or sulꢀ
fones. Both these products are typical diene systems.
2
valuable intermediate products with
tional groups.
S
O funcꢀ
The purpose of this work was the development of a
Acyclic sulfoxides are well known. 2,5ꢀDimethylꢀ reaction system for heteroꢀoriented monooxidation of
ꢀexcessive compound (fiveꢀmemꢀ
sulfoxide and petroleum acyclic sulfoxides prepared by a heteroaromatic
π
the oxidation of sulfurꢀcontaining oil components are bered 3,4ꢀdibromoꢀ2,5ꢀdimethylthiophene) consistꢀ
of the greatest importance. Among heterocyclic ing of two interacting synchronous reactions of H O
2
2
thiophene oxides (tetrahydrothiopheneꢀ1,1ꢀdioxide), decomposition and substrate oxidation.
sulfolane and sulfolenes (dihydrothiopheneꢀ1,1ꢀdioxꢀ
ide) are well known. Sulfolane has low toxicity, and its
alkylꢀsubstituted derivatives are reagents for the
extraction of aromatic compounds (benzene, toluene,
and cumene) from oil etc.
Many thiophene derivatives, in particular, Sꢀdisulꢀ
fides, are used as medicines, and the possibility of the
preparation of a new oxidized thiophene form such as
Sꢀmonoxide can offer promise for the synthesis of a
new class of drugs.
The use of inorganic biological simulators [1] for
the monooxidation of heteroatomic substances in the
hetero position opens up new possibilities in fine
organic synthesis. This approach can be used to preꢀ
EXPERIMENTAL
Gasꢀphase free radical chain oxidation with hydroꢀ
gen peroxide is fairly successfully used to prepare
pare
S
O monoxides by the chemical conjugation
Nꢀmonoxide of 4ꢀvinylpyridine
omatic compound [2].
π
ꢀdeficient heteroarꢀ
mechanism without resort to complex technology. The
questions of the synthesis and identification of
thiopheneꢀ1ꢀmonoxide are still open in the chemistry
All attempts to use this variant of synchronous oxiꢀ
of thiophene, whereas more accessible compounds of dation with hydrogen peroxide for the preparation of
1873

1874
NAGIEVA
Sꢀmonoxides of thiophene derivatives as
π
ꢀexcessive a static system for a long time. We synthesized biomiꢀ
heteroaromatic compounds were, however, unsucꢀ metics of two types, which only differed in the valence
cessful. Under the conditions similar to those of the state of the iron ion. They were tested in synchronous
gas phase Nꢀoxidation of 4ꢀvinylpyridine with hydroꢀ oxidation of simple thiophene derivatives for the prepꢀ
gen peroxide, almost no Sꢀoxidation was observed; aration of thiopheneꢀ1ꢀmonoxide derivatives.
small amounts (~4%) of 3,4ꢀdimethylꢀ2,5ꢀdibroꢀ
The synthesis of catalytic biomimetics was perꢀ
mothiophene underwent oxidative destruction, and
formed as follows. NH OH was added to an aqueous
4
the decomposition of H O predominantly occurred
2
2
solution of Fe (SO ) (to prepare active centers conꢀ
2
4 3
in the reaction system.
We believe that ꢀdeficient heteroaromatic comꢀ The solution was filtered, and the precipitate was
pounds, such as pyridines, easily participate in various washed with hot water. The precipitate was then disꢀ
free radical reactions, whereas ꢀexcessive thiophenes solved in an aqueous solution of EDTA. The adsorpꢀ
3+
taining Fe ions) to completely precipitate Fe(OH)3
.
π
π
are stable toward free radical attacks. Bearing this in tion of this solution was performed by depositing it on
2+
mind, we changed our approach to performing synꢀ alumina. Catalysts with Fe in active centers was preꢀ
chronous oxidation by hydrogen peroxide from free pared by adding an aqueous solution of EDTA to an
radical to biomimetic catalytic. We had to synthesize a aqueous solution of FeSO4. The complex obtained was
biomimetic catalyst on which an oxidative intermediꢀ deposited on Al O3. The monosodium salt of the
2
3+
ate would form (as a result of the catalytic decomposiꢀ EDTA Fe complex was adsorbed from an aqueous
tion of H O ) with “active oxygen” electrophilic in solution on a certain amount of Al O3. Alumina was
2
2
2
character, because thiophenes, which are ꢀexcessive used in the neutral or basic form.
π
heteroaromatic compounds, easily participate in elecꢀ
trophilic interactions.
The experimental unit was a threeꢀneck flask with
a backflow condenser and a tap for gaseous products.
The flask was connected with a gasometer by a rubber
hose. A thermometer and a pipe for taking liquid samꢀ
ples were placed inside the flask. The unit was also
equipped with a stirrer and furnace for heating it.
In recent years, a new area of catalysis has been
intensely explored. This is the creation of newꢀgenerꢀ
ation catalysts, soꢀcalled biomimetics, which model
separate enzyme functions in usual chemical systems.
They differ by the method of synthesis of mimetics
themselves, their functions, and types of modeled bioꢀ
chemical oxidation reactions. One of successful oxiꢀ
The products were identified and quantitatively
estimated using gasꢀliquid and liquid chromatography,
1
3+
chromatoꢀmass spectrometry, and H NMR spectrosꢀ
dation models is РРFe OH (iron protoporphin)
deposited on alumina, which models catalase, peroxꢀ
ide, and monooxygenase reactions [3].
copy.
The substrates were thiophene derivatives 3,4ꢀ
A method for the perfection of these systems is the dibromothiophene, 2,5ꢀdimethylthiophene, and 3,4ꢀ
modification of the organic ligand of the redox center dibromoꢀ2,5ꢀdimethylthiophene. We used acetone,
or its replacement by simpler and more accessible methanol, and dichloromethane as solvents and
organic ligands with similar action. This was perꢀ hydrogen peroxide of “reaktivnyi” (reactive) grade as
3
+
formed for the РРFe OH/Al O biomimetic, in a solvent.
2
3
3
+
which the iron ion (Fe ) was coordinated with ethylꢀ
enediaminotetraacetic acid (EDTA) rather than proꢀ
toporphin [4]. The selection of EDTA as an organic
ligand was not fortuitous. For instance, the broadly
known Hamilton and Udenfried oxidative systems
contain diꢀ and trivalent iron linked with EDTA. An
analysis of the mechanism of enzymatic reactions with
the participation of hydrogen peroxide (catalase and
peroxidases) excluded reactions with radical chain
mechanisms, which have nothing in common with
enzymatic oxidation.
In all experiments, a substrate (0.1 g) dissolved in
one of the solvents was loaded into the static reactor,
and Perhydrol was added in the amount corresponding
to the S (substrate) : H O2(Perhydrol) = 1 : 1.5 or 2.0
2
ratio. This reaction mixture was heated to 50–55°С
,
the catalyst (0.1–0.15 g) was added to it, and the magꢀ
netic stirrer was switched on. At the first stage, the
reaction continued for ~5 h. After this, a sample was
taken and analyzed. The gasometer was used to moniꢀ
tor the rate of oxygen release. In ~5 h, the intensity of
oxygen release sharply decreased, which was evidence
In enzymatic catalysis, we observe concerted parꢀ of a low concentration of H O2. During this time, the
2
ticipation of catalytic redox and acidꢀbase centers in catalyst became active in the main. Product yields
selective oxidation. A new inorganic biomimetic (catꢀ were easy to determine from the mass spectra. Next,
alyst) should contain acidꢀbase and redox catalytic H O2 in an amount 10 times larger than its initial
2
centers on the one hand and be able to perform oxidaꢀ amount was added to the system to create the most
tion by the mechanism of coherentꢀsynchronous reacꢀ favorable conditions for conjugated oxidation. The
tions on the other. In addition, in liquid phase oxidaꢀ reaction continued for more than a day. Samples for
tion with hydrogen peroxide, EDTA is much more staꢀ analyses were taken systematically to draw concluꢀ
ble to the destructive action of the oxidizer compared sions about the depth of transformations. The intenꢀ
with porphin. This allows oxidation to be performed in sity of oxygen release was monitored using the gasoꢀ
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THE MECHANISM OF THE HETEROGENEOUS CATALYTIC MONOOXIDATION
1875
meter; the results were evidence of the presence of of unsaturated bonds in oxidation and the influence of
H O and catalyst activity.
substituents on the predominant direction of the reacꢀ
tion toward the formation of 1ꢀmonoxide. It is shown
below that both factors strongly influence the formaꢀ
tion of 1ꢀmonoxide and the rate of its formation. Oxiꢀ
dation was performed under the conditions described
above using three different solvents; qualitatively difꢀ
2
2
After twofold separation on a liquid chromatoꢀ
graph, the supposed basic product 3,4ꢀdibromoꢀ2,5ꢀ
dimethylthiopheneꢀ1ꢀmonoxide was isolated from
reaction products. This allowed us to record the 1
Н
NMR spectrum of 1ꢀmonoxidedimethylthiophene for
the first time; its mass spectrum contained an ion with
m/e = 44 (the C–S fragment), which was more intense
than all the other ions and could probably be used as a
characteristic mass for the identification of thiopheneꢀ
ferent results were obtained. The use of CH Cl did
2
2
not lead to a noticeable change in the substrate,
because the presence of water (aqueous solution of
hydrogen peroxide) contributed to reaction mixture
layering with the formation of three phases that did not
mix. Two of these were liquid and one solid (catalytic).
Such a system had low efficiency. We used acetone and
methanol as solvents which formed a homogeneous
mixture with the substrate and water.
1
ꢀmonoxide and its derivatives. Note that the ion with
the mass 44 for thiophene and its derivatives, including
thiopheneꢀ1ꢀdioxide, does not have the intensity
characteristic of monoxides. The reaction was considꢀ
ered complete when the release of molecular oxygen
ceased. The heterogeneous catalyst was easy to sepaꢀ
rate from the liquid reaction mixture (which was its
obvious advantage). It was tested for activity in the
A fairly noticeable selective oxidation of the subꢀ
strate with hydrogen peroxide is observed when aceꢀ
tone is used as a solvent. The yield of the product with
the mass number 283 then reaches ~25 wt %. The
compound (mass number 284) has the structural forꢀ
mula
decomposition of H O2. Every time, it exhibited high
2
activity and could be repeatedly used in the oxidation
of the substrate. We performed control experiments
with pure solvents (without substrates) to check their
stability to oxidation with hydrogen peroxide under
catalysis conditions.
Br Br
H
S
O
RESULTS AND DISCUSSION
Substrate oxidation is accompanied by solvent oxiꢀ
dation with the formation of hydrogenation and
hydroxylation products, that is, glycols, in fairly large
amounts.
A series of experiments with the catalytic oxidation
of thiophene derivatives to the corresponding 1ꢀmonꢀ
3+
oxide in the presence of the EDTA Fe ОН/Al O
2
3
catalyst was performed with 3,4ꢀdibromoꢀ2,5ꢀdimeꢀ
Generally, the transformations observed in the sysꢀ
thylthiophene. We had to minimize the participation tem can be described by the scheme
Br Br
H
Br Br
S
S
O
H O, Acetone
2
+
H O
2 2
CH CH(OH)–CH OH + CH –CCH (OH)–CHOH–CH
3
3
2
3
3
The formation of glycols from acetone in this reacꢀ tic acid) are observed. This leads us to conclude that
3+
tion can be of interest of its own. Acetone behaves as the H O –H2O–EDTA Fe ОН/Al O3–acetone mixꢀ
2
2
2
an active component of the system and influences the ture has reducing properties thanks to the combined
formation of the oxidation product. This causes the presence of hydrogen peroxide, acetone, and the
necessity to exclude the additional source of active mimetic.
interference into the formation and consumption of
reaction intermediates. If only hydrogen peroxide parꢀ
ticipates in the formation of intermediates, quite
selective and predictable substrate oxidation can be
expected.
Before using methanol as a solvent for the oxidaꢀ
tion of 3,4ꢀdibromoꢀ2,5ꢀdimethylthiophene, we
checked its stability to oxidation in the absence of a
substrate under the conditions similar to those
described above. We found that it was completely
The oxidation of acetone (solvent) itself in the indifferent with respect to oxidation with hydrogen
absence of a substrate is of certain scientific interest. peroxide for a long time, which was evidence of its
For instance, initially, the reaction proceeds with the minimum influence of CH OH on chemical transforꢀ
3
formation of isopropanol, and only small amounts of mations. In addition, the absence of oxidation prodꢀ
destructive oxidation products (acetaldehyde and aceꢀ ucts leads us to conclude that the decomposition of
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1876
NAGIEVA
H O on the mimetic occurs as a heterogeneous cataꢀ
2
2
lytic reaction, that is, there is no ejection of free radiꢀ
cals into solution. Otherwise, free OH radicals,
which are highly reactive particles, would react with
H O
2 2
H O
2
3+
3+
methanol. We used methanol as a solvent to study EDTA Fe OH/Al O
EDTA Fe OOH/Al O
2 3
2
3
the oxidation of 3,4ꢀdibromoꢀ2,5ꢀdimethylthioꢀ
phene with hydrogen peroxide in the presence of
(I)
3+
EDTA Fe ОН/Al O3. We were able to synthesize
2
H O
2 2
2
H O + O2
1
ꢀmonoxide in a fairly simple way according to the
scheme
2
H O = 2H + O (overall reaction
)
2
2
2
2
Br Br
EDTA Fe3+/Al O , MeOH
Br Br
S
2
3
Secondary reaction
+
H O
2 2
S
H O
2
H O
2
2
(1)
Br Br
SO
Br Br
H
H
O
3+
3+
EDTA Fe OH/Al O
EDTA Fe OOH/Al O
2 3
+
+
2
3
SO2
O
(2)
(3)
(II)
Br Br
SO
Br Br
S
(
yield, wt %: 1, 30.0; 2, 16.0; 3, 10.0).
The products were for the first time characterized
Н
by 1
NMR and mass spectrometry. 3,4ꢀDibroꢀ
mothiophene formed in an amount of ~8.0% (36.0%
based on the unreacted initial substance). The mass
spectrum (m/z) of the purified reaction product
Br Br
Br Br
SO
+
H2O =
2
+H O (overall reaction)
2
S
formed from 3,4ꢀdibromoꢀ2,5ꢀdimethylthiophene
over the m/z range 487–509 is shown in Fig. 1a. The
Scheme (I) describes the formation of the intermeꢀ
mass (m/z
) 286 corresponds to the 3,4ꢀdibromoꢀ2,5ꢀ diate product in the conjugation of two reactions.
According to scheme (II), this product induces and
accelerates the secondary reaction synchronized with
the first one.
thiopheneꢀ1ꢀmonoxide molecule, and the intense peak
at m/z = 44, which can be assigned to the C–S fragꢀ
ment, can be used as a characteristic peak for the idenꢀ
tification of thiopheneꢀ1ꢀmonoxide and its derivaꢀ
We studied the influence of the valence state of iron
2+
tives. The 1
using a different catalyst with Fe as the central ion.
Н
NMR spectrum of 3,4ꢀdibromoꢀ2,5ꢀ
The oxidation of 3,4ꢀdibromoꢀ2,5ꢀdimethylꢀthiophene
dimethylthiopheneꢀ1ꢀmonoxide is shown in Fig. 1b.
2+
in the H O –H O–СН3OH–EDTA Fe OH/Al O
2
2
2
2
3
The chemical shift value observed for 3,4ꢀdibromoꢀ system was performed under identical conditions. The
activity of this system in oxidation was found to be very
low. The total yield of the products with the mass
numbers 299 and 301, which we assigned to the
2
,5ꢀdimethylthiopheneꢀ1ꢀmonoxide (1.7 ppm) is situꢀ
ated behind the chemical shifts of 3,4ꢀdibromoꢀ2,5ꢀ
dimethylthiophene (2.38 ppm) and 3,4ꢀdibromoꢀ2,5ꢀ
dimethylthiopheneꢀ1ꢀdioxide (2.19 ppm). As regards
compounds 2 and 3, their identification was mainly
based on the mass spectra and, with 3, liquid chromaꢀ
tography. Of course, the identification of 2 on the
basis of its mass spectrum only is not very reliable.
Br Br
H
compound (molecular weight 300) and
SO
O
the compound with molecular weight 302 was less than
1
%. It follows that the valence state of iron in the
active catalyst center predetermines oxidation results.
It was no less important to determine the influꢀ
ence of the character and number of thiophene subꢀ
stituents on its oxidation. Vigorous reaction of H O
As in similar oxidative systems, the oxidation of the
substrate in the system under consideration follows a
synchronous mechanism. Accordingly, the mechaꢀ
nism of the reaction can be described by the following
2
2
decomposition was only observed in the system
2+
H O –H O–СН OH–EDTA Fe OH/Al O3–3,4ꢀ
2
2
2
3
2
schemes taking into account the overall transformaꢀ dibromothiophene under identical conditions. Transꢀ
tions in the system:
formations of 2,5ꢀdimethylthiophene were characterꢀ
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THE MECHANISM OF THE HETEROGENEOUS CATALYTIC MONOOXIDATION
1877
Fig. 1. (a) Mass spectrum and (b) 1
Н NMR spectrum of 3,4ꢀdibromoꢀ2,5ꢀdimethylthiopheneꢀ1ꢀmonoxide.
ized by a high percentage of its participation in the
reaction, but the main products had the masses 154, ents substantially influence the qualitative and quantiꢀ
22, and 279, which was evidence of its deeper oxidaꢀ tative characteristics of biomimetic oxidation with
tion. hydrogen peroxide, which shows that we correctly
It follows that the nature and number of substituꢀ
2
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1878
NAGIEVA
selected 3,4ꢀdibromoꢀ2,5ꢀdimethylthiophene as the
principal substrate.
REFERENCES
1
. T. M. Nagiev, Interaction of Sinchronous Reactions in
Chemistry and Biology (ELM, Baku, 2001) [in Russian].
The highꢀefficiency reaction system developed in
this work offers a solution to the problem of the prepꢀ
aration, isolation, and identification of thiophene
Sꢀmonoxide derivatives. This reaction system consistꢀ
ing of two coherent synchronous reactions of the
decomposition of H O and heteroꢀoriented monooxꢀ
2. A. M. Magerramov, I. T. Nagieva, M. A. Allakhverdiyev,
in Proc. of the 2nd Eur. Catalysis Symp., Sept. 23–26,
2
001, Pisa, Italy (2001), p. 41.
3
. A. M. Magerramov, I. T. Nagieva, M. A. Allakhverdiyev,
in Proc. of the 16th Intern. Kongress of Chem. and Proꢀ
cess Eng., Aug. 22–26, 2004, Prague, Czech Republic
(2004), P1.40.
2
2
idation of heteroaromatic compounds allowed us to
effectively perform liquidꢀphase monooxidation of
thiophene and its derivatives as
π
ꢀexcessive heteroaroꢀ
4
. A. M. Magerramov, I. T. Nagieva, and M. A. Allakhverꢀ
diuev, in Proc. of the 19th Intern. Congress on Chemistry,
Kushadasy, Turkey (2005), OGPꢀ103.
matic compounds in the presence of a heterogeneous
3+
biomimetic catalyst (EDTA, Fe OH/Al O3).
2
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