Oxidation of sulfides with hydrogen peroxide catalyzed by vitamin B 2 derivatives

Article abstract of DOI:10.1080/00397911.2013.767912

5-Ethyl-3-methyl-2′,4′:3′,5′-di-O- methylenedioxyriboflavinium perchlorate (1, DMRFlEt⁺ClO₄ ^-), derived readily from commercially available vitamin B₂ (riboflavin), exhibits high catalytic activity for the oxidation of organic sulfides with hydrogen peroxide. The reaction provides an efficient and selective method for the oxidative transformation of organic sulfides to the corresponding sulfoxides under mild conditions.

Full text of DOI:10.1080/00397911.2013.767912

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Oxidation of Sulfides with Hydrogen Peroxide
Catalyzed by Vitamin B2 Derivatives
Yasushi Imada a b , Masamitsu Takagishi a , Naruyoshi Komiya a & Takeshi Naota a
a Department of Chemistry, Graduate School of Engineering Science , Osaka University ,
Toyonaka , Osaka , Japan
b Department of Chemical Science and Technology , Institute of Technology and Science, The
University of Tokushima , Tokushima , Japan
Accepted author version posted online: 18 Jun 2013.
To cite this article: Synthetic Communications (2013): Oxidation of Sulfides with Hydrogen Peroxide Catalyzed by Vitamin B2
Derivatives, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
DOI: 10.1080/00397911.2013.767912
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Oxidation of Sulfides with Hydrogen Peroxide Catalyzed by Vitamin B2 Derivatives
Yasushi Imada1,2, Masamitsu Takagishi1, Naruyoshi Komiya1, Takeshi Naota1
1Department of Chemistry, Graduate School of Engineering Science, Osaka University,
Toyonaka, Osaka, Japan, 2Department of Chemical Science and Technology, Institute of
Technology and Science, The University of Tokushima, Tokushima, Japan
Address Correspondence to Yasushi Imada, Department of Chemical Science and
Technology, Institute of Technology and Science, The University of Tokushima,
Minamijosanjima, Tokushima 770-8506, Japan Tel.: +81-88-656-7407; E-mail:
imada@chem.tokushima-u.ac.jp
Takeshi Naota, Department of Chemistry, Graduate School of Engineering Science,
Osaka University, Machikaneyama, Toyonaka, Osaka 560-8531, Japan Tel.:
+81-6-6850-6220; Fax: +81-6-6850-6222; E-mail: naota@chem.es.osaka-u.ac.jp
Abstract
5-Ethyl-3-methyl-2’,4’:3’,5’-di-O-methylenedioxyriboflavinium perchlorate (1,
–
DMRFlEt+ClO4 ), derived readily from commercially available vitamin B2 (riboflavin),
exhibits high catalytic activity for the oxidation of organic sulfides with hydrogen
peroxide. The reaction provides an efficient and selective method for the oxidative
transformation of organic sulfides to the corresponding sulfoxides under mild conditions.
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[Supplementary materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications® for the following free supplemental resource(s): Full
experimental and spectral details.]
KEYWORDS: Organocatalysis; H2O2 Oxidation, Sulfides, Sulfoxides
INTRODUCTION
Organocatalytic oxidative transformation of sulfides has been extensively studied as a
typical environmentally benign process that can be substituted for conventional methods
using stoichiometric and catalytic amounts of transition metal complexes.[1,2] Various
organic compounds including acridinium perchlorate,[3] N-hydroxyphthalimide,[4]
fructose-derived ketone,[5] N,N’’-bis[3,5-bis(trifluoromethyl)phenyl]thiourea,[6]
N-formyl-L-proline,[7] pyrazinium tetrafluoroborate,[8] phosphoric acids,[9] and
flavins[10,11] have been reported as efficient organocatalysts that catalyze the oxidative
transformation of sulfides with peroxides[5-9,11a,b,d,f-j] and molecular oxygen.[3,4,11c,e]
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Scheme 1 shows the redox cycle for the catalytic oxidative transformation of organic
substrates (S) with synthetic flavins.[10] Reaction of the flavin catalyst (Flox) with
reductants (AH2) gives reduced flavin (Flred), which undergoes O2 incorporation to afford
4a-hydroperoxyflavin (FlOOH). Oxygen transfer and subsequent dehydration from
4a-hydroxyflavin (FlOH) affords the sulfoxide product (SO) and Flox to complete the
catalytic cycle. The active FlOOH species can also be generated by a shunt process of
direct transfer from Flox upon treatment with hydrogen peroxide instead of the combined
use of reductants and molecular oxygen. This catalytic process provides a green and
sustainable method for the oxygenation of a variety of organic substrates such as
sulfides,[11] amines,[11a,12] and ketones,[13] using a catalytic amount of
isoalloxazine,[11a,b,d,f,g,13] and alloxazine derivatives.[11d,e,h-j,12]
We have reported that aerobic Baeyer-Villiger oxidation of cyclic ketones proceeds
efficiently under an O2 atmosphere (1 atm) with synthetic flavin catalysts.[13c] In this
reaction, 5-ethyl-3-methyl-2’,4’:3’,5’-di-O-methylenedioxyriboflavinium perchlorate (1,
DMRFlEt+ClO4 ), derived readily from vitamin B2 (riboflavin), exhibited the highest
–
catalytic activity among the various catalysts examined. In this paper, we describe that
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flavin 1 acts as a highly efficient and robust organocatalyst for the oxidation of organic
sulfides with hydrogen peroxide to afford the corresponding sulfoxides selectively under
mild conditions (Scheme 2).
RESULTS AND DISCUSSION
The catalytic activity of representative flavin compounds (1 mol%) was examined for the
oxidation of dibutyl sulfide (1.0 mmol) with 30% hydrogen peroxide (1.0 mmol) in
MeOH (1 mL) at 25 °C. Figure 1 shows the time dependence for the yield of dibutyl
–
sulfoxide in reactions with DMRFlEt+ClO4 (1), 5-ethylriboflavinium perchlorate (2), and
5-ethyllumiflavinium perchlorate (3) catalysts (Scheme 3). Flavin 1 can be readily
obtained from vitamin B2, an inexpensive mass-produced material, by a conventional
process, as depicted in Scheme 4. Yields of the product sulfoxide were determined
periodically using gas-liquid chromatography (GLC) analysis with an internal standard.
Oxidation with riboflavinium catalyst 2 was significantly slowed down after stirring for 1
h and finally afforded the product in 84% yield, although the initial reaction with 2 was
faster than that with the lumiflavinium catalyst 3.[11a] A contrasting reaction profile has
been observed for the reaction with catalyst 1, where the reaction undergoes acceleration
after a specific induction period of approximate 30 min to exhibit the best quantitative
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result for the formation of the product after 240 min. The results indicate that catalyst 1
is inexpensive, readily available, robust, and a sufficiently effective organocatalyst for the
oxidation of sulfides with hydrogen peroxide, while some flavin catalysts are degraded
after extended reaction times.
Representative results for the oxidation of organic sulfides are summarized in Table 1.
A variety of aliphatic (entries 1–4) and aromatic (entries 5–10) sulfides were converted to
the corresponding sulfoxides with high efficiency when the reaction was performed in
MeOH or CH2Cl2 with flavin 1 catalyst (2 mol%) and 1.5 equiv of a 30% aqueous
solution of hydrogen peroxide at ambient temperature. In all cases, the reaction affords
the sulfoxides exclusively without the formation of sulfones as the corresponding
overoxidation products. Catalyst 1 is highly soluble in water, and the reaction proceeds
quantitatively and selectively; therefore, the product sulfoxides can be obtained
conveniently with a simple evaporation-extraction process. Bulky sulfides such as
diphenyl sulfide (entry 11) also react smoothly under the present conditions. Olefin and
ester moieties are tolerated by the reaction (entries 4 and 5). Aromatic sulfides bearing
various substituents are quantitatively converted into the corresponding sulfoxides,
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irrespective of the type of substituents (entries 6–9), although electron-donating groups
accelerate the reaction (entry 7).[11e]
CONCLUSION
–
In summary, the highly available flavin compound, DMRFlEt+ClO4 1 acts as a robust
and efficient organocatalyst for the monooxygenation of sulfides. This method provides
an environmentally benign and convenient method for the synthesis of various organic
sulfoxides under mild conditions. Efforts are currently underway to investigate the full
scope of the reaction and to apply this organocatalyst to other systems.
EXPERIMENTAL
NMR spectra were obtained using a Varian Unity-Inova 500 spectrometer (1H, 500 MHz,
13C, 125 MHz). Mass spectra were measured using a Jeol JMS-DX303HF mass
spectrometer. UV spectra were recorded on a Shimadzu MultiSpec-1500 UV-Vis
photodiode array spectrophotometer. IR spectra were recorded on a Bruker EQUINOX
55/s. Cyclic voltammetry potentials were measured on an ALS/chi model 600A
electrochemical analyzer with a standard three-electrode cell that consisted of a 1.6 mm
diameter platinum working electrode, a platinum wire counter electrode, and a Ag/AgCl
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–
reference electrode in CH3CN containing 0.1 M Bu4N+ClO4 at a scan rate of 0.1 V/s
under an argon atmosphere at 25 °C. Melting points were measured in a glass capillary
with a Büchi B-545 melting point apparatus. Riboflavin (vitamin B2) and all sulfides
were commercially available reagents. The flavinium perchlorates 2 and 3 were
obtained according to procedures in the literature.[14]
Preparation Of 3-Methyl-2’,4’:3’,5’-Di-O-Methylenedioxyriboflavin[13c]
A mixture of riboflavin (376 mg, 1.0 mmol), concentrated HCl (600 L), and 37%
aqueous solution of formaldehyde (900 L) was refluxed in a water-bath at 60 °C for 48
h. After evaporation under reduced pressure at 80 °C, K2CO3 (1.38 g, 10 mmol),
dimethylformamide (DMF; 100 mL), and CH3I (0.620 mL, 10 mmol) were added
successively to the resulting crude O-protected riboflavin, and the mixture was stirred for
25 h at room temperature. The reaction mixture was poured into CHCl3 (100 mL) and
washed with water (100 mL × 5). The combined organic layers were dried over MgSO4
and evaporated under reduced pressure. The crude product was purified by column
chromatography (Al2O3, MeOH—CHCl3) to give
3-methyl-2’,4’:3’,5’-di-O-methylenedioxyriboflavin (153 mg, 37%) as a yellow solid:
Mp >300 °C; IR (KBr) 1712, 1658, 1584, 1547, 1350, 1277, 1237, 1078, 1053, 1014, 990,
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980 cm–1; 1H NMR (500 MHz, CDCl3) δ 2.44 (s, 3 H), 2.55 (s, 3 H), 3.52 (s, 3 H),
3.54–3.61 (m, 3 H), 4.17 (dd, J = 7.6, 3.0 Hz, 1 H), 4.27 (ddd, J = 9.1, 9.1, 3.6 Hz, 1 H),
4.62 (d, J = 6.3 Hz, 1 H), 4.69 (d, J = 6.3 Hz, 1 H), 4.91 (d, J = 6.3 Hz, 1 H), 4.84–4.98
(m, 1 H), 5.05 (d, J = 6.3 Hz, 1 H), 5.10 (br, 1 H), 7.56 (s, 1 H), 8.06 (s, 1 H); 13C NMR
(125 MHz, CDCl3) δ 19.4, 21.6, 28.7, 45.2, 68.2, 72.8, 75.0, 77.1, 93.5, 94.1, 116.0,
131.8, 132.6, 134.8, 135.6, 136.5, 147.4, 149.2, 155.7, 160.0. HRMS (FAB) Calcd for
C20H23O6N4 (M+H+): 415.1618. Found: 415.1629.
Preparation Of 5-Ethyl-3-Methyl-2’,4’:3’,5’-Di-O-Methylenedioxyriboflavinium
Perchlorate (1)[13c]
Acetaldehyde (2.20 g, 50 mmol) was added dropwise to a mixture of
3-methyl-2’,4’:3’,5’-di-O-methylenedioxyriboflavin (207 mg, 0.50 mmol), NaBH3CN
(314 mg, 5.0 mmol), Na2S2O4 (348 mg, 2.0 mmol), and acetic acid (150 L) in DMF (12
mL), and the mixture was stirred at 60 °C for 2 h. After the resulting mixture was
dissolved in CHCl3 (100 mL), the organic layer was washed successively with brine (30
mL) and saturated Na2S2O4 aqueous solution (50 mL), dried over Mg2SO4, and
evaporated under reduced pressure. An aqueous solution of 4 M HClO4 (6.0 mL),
NaNO2 (138 mg, 2.0 mmol), and NaClO4 (306 mg, 2.5 mmol) were added successively to
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the resulting residue with stirring at 0 °C. After stirring at room temperature for 1 h, the
resulting purple precipitate was filtered, washed successively with water (5 mL × 2),
diethyl ether (5 mL × 3), and CHCl3 (5 mL × 3), and dried under reduced pressure to give
1 (172 mg, 63%) as a purple powder: Mp 206–208 °C; UV ( max, nm, CH3CN) 418 ( =
8420 M–1 cm–1), 559 ( = 6590 M–1 cm–1); IR (KBr) 1710, 1650, 1600, 1560, 1460, 1440,
–
1360, 1180, 1120, 1100 cm–1; CV (CH3CN, Bu4N+ClO4 ): E°’ = 322, –364 mV
(Ag/AgCl); HRMS (FAB) Calcd for C22H28O6N4 (M–ClO4+H+): 444.2009. Found:
444.1976.
Flavin-Catalyzed Oxidation Of Sulfides With Hydrogen Peroxide
A typical procedure for the monooxygenation of sulfides with hydrogen peroxide in the
presence of flavin catalysts is exemplified by the reaction of dibutyl sulfide with catalyst
1. A 30% aqueous solution of hydrogen peroxide (2.0 mL, 1.1 equiv) was added
dropwise to a stirred mixture of dibutyl sulfide (146 mg, 1.0 mmol) and 1 (5.4 mg, 0.01
mmol) in MeOH (1 mL). After the mixture was stirred at ambient temperature for 5 h,
the reaction was quenched by the addition of a saturated Na2SO3 aqueous solution (1 mL)
to decompose the remaining hydrogen peroxide. The reaction mixture was extracted
with CH2Cl2 (1 mL × 2), dried over MgSO4, and evaporated under reduced pressure to
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afford dibutyl sulfoxide[15] (159 mg, 98%) as a colorless solid: Mp 32–34 °C (lit[16]
33–35 °C); IR (KBr) 2958, 2927, 2874, 1654, 1464, 1409, 1382, 1026 cm–1; 1H NMR
(CDCl3, 500 MHz) δ 0.97 (t, J = 7.3 Hz, 6 H), 1.41–1.58 (m, 4 H), 1.72–1.79 (m, 4 H),
2.63 (ddd, J = 13.0, 8.7, 7.5 Hz, 2 H), 2.69 (ddd, J = 13.0, 8.5, 6.2 Hz, 2 H); 13C NMR
(CDCl3, 125 MHz) δ 13.6, 22.0, 24.6, 51.8. HRMS (EI) Calcd for C8H18SO (M+):
162.1078. Found 162.1053.
Supplementary Information
General experimental details and physical and spectral data of sulfoxides are included in
the Supplementary Information, which can be found via “Supplementary” section of this
article’s Web page.
ACKNOWLEDGEMENTS
This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology of Japan.
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Table 1. Oxidation of Sulfides with Catalyst 1.a
Entry Sulfide
Product
Time
(h)
5
Yield (%)b
1
2
98c
83d
92
12
5
3
O
S
O
S
CH3
4
8
98
O
O
O
CH3
5
6
7
8
6
91
96
98
96
92
96d
12
6
34
51
14
O
S
S
CH3
9
O2N
CH3
O2N
10
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55
94
aThe reaction of sulfide (1 mmol) was carried out in MeOH (1 mL) in the presence of 1
(0.02 mmol), and a 30% aqueous solution of H2O2 (1.5 mmol) at ambient temperature.
bIsolated yield. c1 (0.01 mmol), 30% H2O2 aqueous solution (1.1 mmol). dCH2Cl2 (1
mL) was used instead of MeOH.
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Scheme 1. Redox process for catalytic oxidative transformation with synthetic flavins.
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Scheme 2.
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Scheme 3.
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Scheme 4. Synthesis of 1
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Figure 1. Reaction profiles for the oxidative transformation of dibutyl sulfide to dibutyl
sulfoxide upon treatment with a 30% aqueous solution of H2O2 (1.1 equiv) in the
presence of flavin catalysts (1 mol%) in MeOH at 25 °C. Flavin catalysts; ○: 1; ●:2; ▲:
3.
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