Green and mild laccase-catalyzed aerobic oxidative coupling of benzenediol derivatives with various sodium benzenesulfinates

Article abstract of DOI:10.1016/j.tetlet.2016.11.119

The oxidative coupling reaction between hydroquinone or catechols and various sodium benzenesulfinates was investigated using the laccase from Trametes versicolor, in the presence of O₂in a phosphate buffer solution at room temperature to afford sulfonyl benzenediols in 75–95% yield.

Full text of DOI:10.1016/j.tetlet.2016.11.119

Accepted Manuscript
Green and mild laccase-catalyzed aerobic oxidative coupling of benzenediol
derivatives with various sodium benzenesulfinates
Davood Habibi, Abdollah Rahimi, Amin Rostami, Sirvan Moradi
PII:
S0040-4039(16)31610-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.11.119
TETL 48405
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
26 September 2016
21 November 2016
28 November 2016
Please cite this article as: Habibi, D., Rahimi, A., Rostami, A., Moradi, S., Green and mild laccase-catalyzed aerobic
oxidative coupling of benzenediol derivatives with various sodium benzenesulfinates, Tetrahedron Letters (2016),
doi: http://dx.doi.org/10.1016/j.tetlet.2016.11.119
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Green and mild laccase-catalyzed aerobic oxidative coupling of benzenediol
derivatives with various sodium benzenesulfinates
Davood Habibi,a,* Abdollah Rahimi, a Amin Rostamib,* and Sirvan Moradib
aDepartment of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
bDepartment of Chemistry, Faculty of Sciences, University of Kurdistan, Sanandaj 6617715143, Iran
Corresponding author email: davood.habibi@gmail.com
Abstract
The oxidative coupling reaction between hydroquinone or catechols and various sodium
benzenesulfinates was investigated using the laccase from Trametes versicolor, in the presence of O2 in a
phosphate buffer solution at room temperature to afford sulfonyl benzenediols in 75-95% yield.
Keywords: Laccase enzyme, catechol, sodium benzenesulfinates, O2, phosphate buffer solution, oxidative coupling,
sulfonyl benzenediols
Introduction
The laccase (benzenediol: oxygen oxidoreductase, EC 1.10.3.2), is a well-known multicopper catalyst for the
oxidative coupling reaction of diverse compounds to form various C-C, C-N or C-O bonds.1-4
Laccases are interesting eco-friendly enzymes since they use air and produce water as the only by-product.
Additionally, they work under mild conditions and have been used in industry,5-7 as well as for a range of organic
transformations.8-10 Different laccases have been studied which exhibit a wide temperature and pH range (usually
pH 4-6),11-13 and are stable in various organic solvents.14,15 The relevant mechanism has been comprehensively
discussed in the literature.16,17
Laccases are also used as catalysts for the synthesis of dyes, cosmetics and pharmaceutically active
compounds.18-22 For example, Wellington and co-workers reported a direct laccase-mediated synthesis of
compounds with anticancer activity,23,24 while Beifuss and co-workers used laccases for various oxidation reactions
to yield carpanones and benzopyrans, as well as for sesamol trimerisation.25,26
Sulfones are ubiquitous in medicinal chemistry,27 and agrochemicals targets.28 Diaryl sulfones are also
important synthons, and are broadly applied in organic chemistry because of their industrial applications.29 Aryl
sulfones are useful building blocks which are found in many drugs, such as the antibacterial Dapsone,30
Laropiprant,31 a prostaglandin D2 antagonist, or the COX-2 inhibitor Vioxx.32 Recently, diaryl sulfones have been
shown to inhibit HIV-1 reverse transcriptase, as well as possess antitumor and antifungal activities.33
Although the preparation of sulfonyl benzenediol derivatives via the oxidative coupling reaction between
benzenediols and sodium sulfinate using potassium ferricyanide as an oxidant34 and electrochemical methods have
been reported,35-37 these methods suffer from some problems in that potassium ferricyanide is a toxic oxidant, and
there are some disadvantages with organic electrochemical processing.38
1

In this study, we report the application of laccase (from Trametes versicolor, which is commerically available)
for the synthesis of sulfonyl benzenediol derivatives in good to high yields via the oxidative coupling reaction
between benzenediols and sodium sulfinate, using O2 as an oxidant and a phosphate buffer solution as solvent at
room temperature (Fig. 1).
Results and Discussion
The laccase catalyzed oxidation of model compound 2b was studied in aqueous media and a range of organic
solvents (Table 1), which showed that the phosphate buffer solution (pH = 5.0, 0.1 M) was optimal (Entry 3). No
reaction took place in DMF and DMSO, probably due to laccase denaturation (Entries 8-9). In water, ethanol and a
water/ethanol solution (1:1) the reaction proceeded with moderate yields (38-50%, Entries 5-7).
Table 1. Solvent optimization for the synthesis of sulfonyl benzene diol 3ea
Entry
1
Solvent
Yield (%)b
phosphate buffer solution (0.1 M, pH = 7.0) 75
phosphate buffer solution (0.1 M, pH = 6.0) 50
phosphate buffer solution (0.1 M, pH = 5.0) >99%
2
3
4
5
6
7
acetate buffer solution (0.1 M, pH = 5.0)
70
38
45
50
H2O
EtOH
H2O/EtOH (1:1)
8
9
DMF
-
-
DMSO
aReaction conditions: Laccase (75.5 mg), 1b (1 mmol), 2b (1 mmol), solvent (15 mL), O2, r.t., 18 h; bGC yield.
The effect of laccase concentration on the reaction rate was next investigated (Table 2). It was found that the
rate of formation improved with increased catalyst concentration. A blank reaction was carried out to evaluate the
catalytic efficiency of laccase where no product formation occurred even after 18 h (Entry 5). The optimal enzyme
concentration was found to be 40 U (Entry 4), and therefore was selected as a standard concentration in all further
reactions.
Table 2. Optimization of the laccase concentration for the synthesis of sulfonyl benzenediol 3ea
2

Entry Concentration of enzyme (U) Yield (%)b
1
2
3
4
5
20
30
40
30
70
>99%
>99%
-
60
No Laccase
aReaction conditions: Laccase (75.5 mg), 1b (1 mmol), 2b (1 mmol), phosphate buffer solution (0.1 M, 15 mL, pH =
5.0), O2, r.t., 18 h; bGC yield.
Additionally, the effect of reaction temperature was investigated by various temperatures ranging from 4 to
50 ᵒC; the optimum temperature was found to be room temperature.
Hence, with respect to the optimized conditions, the reaction between hydroquinone or catechol derivatives
with sodium benzenesulfinates were carried out by laccase (from Trametes versicolor; 40 U, 75.5 mg) in the
presence of O2 in a phosphate buffer solution (0.1 M, 15 mL, pH = 5.0) at room temperature (Fig. 1).
Table 3. Synthesis of different sulfonyl benzenediola
Figure 1. Synthesis of sulfonyl benzenediol derivatives
Sodium
sulfinate
Entry
1
Benzenediol
Product
Time (h) Yield (%)b
20
22
75
87
2
3
4
5
24
20
18
90
79
90
3

6
7
8
20
21
23
90
87
89
9
24
18
16
19
92
90
95
92
10
11
12
aReaction conditions: Laccase (75.5 mg), 1 (1 mmol), 2 and 4 (1 mmol), phosphate buffer solution (0.1 M, 15 mL,
pH = 5.0), O2, r.t., 18 h. bIsolated yield.
A probable mechanism for this reaction which includes oxidation of benzenediols to the corresponding
diketone and subsequent reaction of the electron deficient site with sodium benzenesulfinates is suggested in
Figure 2. The selectivity of these transformations may be understood in such a way that the initial 1,4-addition
exclusively occurs at the more electrophilic C-5 carbon atom of the corresponding o-benzoquinones,39 followed by
reduction of one molecule of oxygen to two molecules of water. The existence of a methyl or a methoxy group at
the C-3 position (2b and 2c) could potentially cause the corresponding Michael acceptors (2b’ and 2c’) to undergo
attack by the sodium benzenesulfinates at the C-4 and/or the C-5 positions to yield two product types. However,
according to thin layer chromatography (TLC) and 1H NMR results, we suggest that o-quinones 2b’ and 2c’ are only
attacked at the C-5 position by sodium benzenesulfinates, leading to the formation of the products 3b, 3c, 3e, 3f,
3h and 3i, respectively. 40
4

Figure 2. Suggested mechanism for the synthesis of sulfonyl benzenediols
3. Conclusion
In conclusion, we present a simple and efficient approach for the synthesis of several sulfonyl benzenediols
using the laccase catalyzed aerobic oxidative coupling of catechols or hydroquinone with sodium benzenesulfinate
derivatives. The reaction can be performed under mild conditions using O2 as an oxidant and proceeds at room
temperature in a phosphate buffer solution at pH=5.0. The easy work-up procedure makes this methodology a
valid contribution to existing processes in the field of enzymatic catalysis.
Acknowledgements
The authors gratefully acknowledge financial support from the Bu-Ali Sina University, Hamedan 6517838683, Iran.
Supplementary data
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/.......
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Highlights
1. Application of an eco-friendly catalyst (Laccase).
2. Application of an environmentally friendly solvent.
3. Application of a green oxidant (O2).
4. Working at ambient temperature.
5. Simple experimental methods and easy work-up procedure.
8

Green and mild laccase-catalyzed aerobic oxidative coupling of benzenediol
derivatives with various sodium benzenesulfinates
Davood Habibi*, Abdollah Rahimi, Amin Rostami*, and Sirvan Moradi
9