Microwave assisted oxidative coupling of thiols to symmetrical disulfides with tripropylammonium fluorochromate(VI) (TPAFC)

Article abstract of DOI:10.4314/bcse.v26i1.16

Tripropylammonium fluorochromate(VI) (TPAFC) is an efficient and novel reagent, which can be prepared easily and oxidizes thiols to the corresponding disulfides, quickly. The reactions are performed cleanly and are controlled to stop at the disulfide stage, without over-oxidation or side products. Coupling of thiols to their corresponding disulfides, was studied in solution at room temperature and under conditions using a minimal amount of solvent under microwave irradiation. The easy procedure, simple work-up, short reaction times, and excellent yields are other advantages of this reagent.

Full text of DOI:10.4314/bcse.v26i1.16

Bull. Chem. Soc. Ethiop. 2012, 26(1), 139-144.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v26i1.16
ISSN 1011-3924
 2012 Chemical Society of Ethiopia
SHORT COMMUNICATION
MICROWAVE ASSISTED OXIDATIVE COUPLING OF THIOLS TO
SYMMETRICAL DISULFIDES WITH TRIPROPYLAMMONIUM
FLUOROCHROMATE(VI) (TPAFC)
Mohammad Kazem Mohammadi1* and Shahriare Ghammamy2
1Faculty of Science, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran
2Department of Chemistry, Faculty of Science, Imam Khomeini International University,
Qazvin, Iran
(Received August 3, 2010; revised October 24, 2011)
ABSTRACT. Tripropylammonium fluorochromate(VI) (TPAFC) is an efficient and novel reagent, which can
be prepared easily and oxidizes thiols to the corresponding disulfides, quickly. The reactions are performed
cleanly and are controlled to stop at the disulfide stage, without over-oxidation or side products. Coupling of
thiols to their corresponding disulfides, was studied in solution at room temperature and under conditions using a
minimal amount of solvent under microwave irradiation. The easy procedure, simple work-up, short reaction
times, and excellent yields are other advantages of this reagent.
KEY WORDS: Thiol, Oxidation, Coupling, Disulfide, Tripropylammonium fluorochromate, Microwave
irradiation
INTRODUCTION
Many sulfur-oxidizing reagents have been developed in recent years with some success [1].
Disulfides constitute one of the most important organic sulfur containing classes of compounds
possessing an unique exclusive chemistry both in biochemistry [2] and in synthetic organic
chemistry[3]. Also, disulfides are key intermediates in a wide variety of organic synthetic routes
[4-6]. Sweetening of catalyst poisoning thiols to disulfides of low volatility in the oil industry
[7-8] and also the industrial applications of disulfides in the vulcanization of rubbers and
elastomers led us to investigate a new reagent for the oxidation of thiols to the corresponding
disulfides.
Many stoichiometric reagents like manganese dioxide [9], dichromates [10], halosilane-
chromium trioxide [11], diethyl azodicarboxylate [12], nickel peroxide [13], chromium peroxide
[14], diaryl telluroxide [15], tetrabutylammonium ceric(IV) nitrate [16], sodium perborate [17],
silver trifluoromethane sulphonate [18] and permanganate [19] have been developed for this
transformation. These reagents suffer from either one or more of the following disadvantages:
availability of the reagent, cumbersome work-up procedure, high cost of the reagent, over
oxidation or oxidation of other functional groups in the presence of the thiol group. As a result,
there is still a need for the development of general and efficient new reagents to synthesize
disulfides from the corresponding thiols under mild reaction conditions. These reactions should
not only be interesting from an ecological viewpoint, but also should offer considerable
synthetic advantages in terms of the yield, selectivity and simplicity of the reaction procedure.
Microwave synthesis is a relatively new technique which has been found to provide such
advantages for a number of other chemical reactions. Acceleration of organic reactions by
microwave irradiation has been noted. Overall, in many cases, microwave techniques have been
found to be more effective than a conventionally conducted thermal heating of reactions [20].
__________
*Corresponding author. E-mail: mohammadi@iauahvaz.ac.ir

140
Mohammad Kazem Mohammadi et al.
In a number of applications, reactions under microwave conditions have provided pure
products in high yield [21]. Against this background, we wish to report that tripropylammonium
fluorochromate (TPAFC) is able to oxidize thiols to their disulfides efficiently under various
reaction conditions. In the following, examples of the oxidative coupling of thiols under
solvent-free reactions under microwave irradiation are described. Comparisons with
conventional heating methods, realized either in an oil or sand bath at the same temperature
used for the microwave experiments will be given where available.
EXPERIMENTAL
Materials and instruments. CrO3 (Merck, P.A.) was used without further purification. Solvents
were purified by standard methods. Infrared spectra were recorded as KBr disks on a Shimadzu
model 420 spectrophotometer. The UV/Visible measurements were made on an Uvicon model
922 spectrometer.1H and 13C NMR spectra were recorded on a Bruker spectrometer at 300 MHz.
All the chemical shifts are quoted in ppm using the high-frequency positive convention. 1H and
13C NMR spectra were referenced to external SiMe4. Chromium was analyzed iodometrically. In
the case of the reduced product of the oxidant, chromium was determined after oxidation with
an acidic peroxodisulfate (K2S2O8) solution. The percent composition of carbon, hydrogen and
nitrogen were obtained from the micro analytical laboratories, Department of Chemistry, OIRC,
Tehran. Melting points were measured on an Electrothermal 9100 melting point apparatus. The
authors used a Microsynth Millstone laboratory microwave oven. Experiments were carried out
in a closed vessel multi-mode Microsynth Milstone laboratory microwave oven using a 400
Watts Westpoint microwave operating at 3.67 GHz. All experiments had good reproducibility as
ascertained by repetition of the experiments under the same conditions.
Preparation of tripropylammonium fluorochromate (TPAFC). A sample of chromium(VI) oxide
(CrO3, 15 g, 150 mmol) and 40% hydrofluoric acid (11.3 mL, 225 mmol) was added to water
(20 mL) in a 100 mL polyethylene beaker under stirring. After 5-7 min, the homogeneous
solution was cooled to ca. 1-2 °C, and distilled tripropylamine (28.3 mL, 150 mmol) was added
in small portions to this solution with stirring over a period of 0.5 h at 0 °C.
The precipitated orange solid was isolated by filtration on a polyethylene funnel, and
washed with petroleum ether (3 × 60 mL) and dried in vacuo for 2 h at room temperature. Yield:
37.5 g (95%); m.p. 142 °C. C9H22CrFNO3: calc. C, 41.05; H, 8.35; N, 5.31. Found: C, 41.19; H,
8.43; N, 5.43. IR (KBr): 904 cm-1 ν1(A1) or ν(CrO3) that shows as ν(Cr-O), 647 cm-1 ν 2(A1) or
ν(Cr-F), 949 cm-1 ν4(E) or ν(CrO3) that shows as ν(Cr-O). Electronic absorption at 248 nm,
corresponding to 1a2→9e (ε = 140 M-1 cm-1); 348 nm to 8e→9e (ε = 667 M-1 cm-1); and 278 nm
1
to 12a1→9e (ε = 1287 M-1 cm-1). H-NMR (300 MHz, CD3CN): δ = 3.23 (t, 6 H, 3 CH2), 1.97
(m, 6 H, 3 CH2), 0.91 (t, 9H, CH3). 13C-NMR (300 MHZ, CD3CN): δ 11.45, 20.25, 55.26.
HRMS Calcd 263.1035 for C9H22CrFNO3. Found 260.1038. (Scheme 1).
H
N
CrO
3
N
CrOF
3
HF40%
Scheme 1
1
IR, UV, 13C NMR, and H NMR were all consistent with the TPAFC structure. The above
procedure can be scaled up to larger quantities, if desired. Molar conductance (ΛM, 25 °C) of
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141
0.001 M solutions of TPAFC in water was 125 Ω-1 cm2 mol-1. The pH of 0.01 M solution of
TPAFC in water was 3.3.
General procedure for the oxidative coupling of thiols in dichloromethane. To a stirred solution
of 4-methylthiophenol (0.248 g, 2 mmol) in dichloromethane (5 mL), TPAFC (0.263 g, 1 mmol)
was added, and the mixture was stirred at room temperature for 67 min. A solid was formed and
treated with a 1:1 mixture of ether and water (2 mL). The reaction mixture was extracted with
ether (3 × 10 mL). The organic layers were combined and dried over anhydrous MgSO4.
Evaporation of the solvent followed by column chromatography (EtOAc/hexane as eluent)
afforded the pure disulfide 2 g in 77 % (0.207 g) yield, which was characterized by NMR and
IR spectrum. m.p. 45 °C (Lit. [22] m.p. 45-46 °C) (Scheme 2).
TPAFC
H3C
S-H
H3C
s-s
CH3
r.t. / mw
Scheme 2
4,4-Ditolyl disulfide (2g). IR (KBr) cm-1 3200-2100 C-H (Ar . stretch), 3000-2900 C-H (aliph.,
stretch) 1480-1400 C-H (Ar, bend), 1200-1100 C-S (stretch). 1H NMR (300 MHz, CDCl3) δ
7.5 (d, 4 H), 7.2 (d, 4H), 2.5 (s, 6H). 13C NMR (300 MHz, CDCl3) δ 126.21 (S), 130.42 (d),
127.3 (d), 124.85 (s), 21.17 (q). HRMS calcd 246.05423 for C14H14S2. Found 246.05425.
General procedure for the preparation of silica gel supported TPFAC reagent. A 500 mL
suction flask equipped with a constant pressure dropping funnel was used. The cold solution of
TPAFC, prepared by completely dissolving of TPAFC (X = F, 0.2 mol, 52.6 g) in CH2Cl2 (10
mL), was stirred with silica gel (Aldrich, 150 mesh, 60 g) over a period of 30 min at room
temperature. 30 min evaporation of the solvent under high vacuum affords an orange-red slurry
of tripropylammonium fluorochromate/silica gel, which is completely dried in 70 oC for 2 h.
Typical procedure for oxidative coupling of thiophenol with tripropyl ammonium
fluorochromate/silica gel under microwave irradiation
Preparation of diphenyl disulfide (2f). A suspension of thiophenol (1f) (0.110 g, 0.001 mol),
TPAFC (0.263 g, 0.001 mol) and 1 g wet SiO2 (50%, w) acetonitrile (2 mL) (for better
absorbing the microwave irradiation) was completely mixed and the mixture was irritated in a
microwave oven at 2.45 GHz (800 W). The completion of the reaction was followed by TLC
using ether/petroleum ether (V:V = 60:40) as eluent. After completion, the mixture was stirred
in a EtOH/CHCl3 (V:V = 1:3) solution for separating products from the solid support. This
mixture was allowed to stand for 1 h and then filtered, to give a clear solution. The solvent was
evaporated and the residual product purified by column chromatography (EtOAc/hexane as
o
eluent) to give diphenyl disulfide (2f) in 92% yield in 8 min, m.p. 57-58 C (Lit. [23] 58-60 oC)
(Scheme 2).
The above procedure could be carried out in larger scale, without any problems.
Characteristic data for disulfides
Diisopropyl disulfide (2a). IR (KBr) cm-1 3000-2900 C-H (aliph., stretch), 1400-1350
C-H (aliph., bend), 1200-1100 C-S (stretch). 1H NMR (300 MHz, CDCl3) δ 2.7 (m, 2H ), 1.5
(d, 12H). 13C NMR (300 MHz, CDCl3 ) δ 38.5 (d), 24.65 (q). HRMS calcd 150.0571 for
C6H14S2. Found 150.0569.
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Mohammad Kazem Mohammadi et al.
Di-n-pentyl disulfide (2b). IR (KBr) cm-1 3000-2900 C-H (aliph., stretch), 1200-1100 C-S
(stretch ). 1H NMR (300 MHz, CDCl3) δ 2.5 (t, 4 H), 1.6 (m, 4H), 1.25 (m, 4H), 1.3 (m, 4H), 1.2
(t, 6H). 13C NMR (300 MHz, CDCl3) δ 36.53, 33.78, 31.13, 23.55, 14.50. HRMS calcd
206.1281 for C10H22S2. Found 206.1283.
Di-n-octyl disulfide (2c). IR (KBr) cm-1 3000-2900 C-H (aliph., stretch), 1200-1100 C-S
(stretch). 1H NMR (300 MHz, CDCl3) δ 2.6 (t, 4 H), 1.5 (m, 4H), 1.3 (m, 18H) 1.2 (t, 6H). 13
C
NMR (300 MHz, CDCl3) δ 33.66, 32.5, 31.43, 31.35, 31.22, 27.03, 23.5, 15.02. HRMS calcd
290.2142 for C16H34 S2. Found 290.2146 .
Dicyclohexyl disulfide (2d). IR (KBr) cm-1 3000-2900 C-H (aliph., stretch), 1200-1100 C-S
(stretch). 1H NMR (300 MHz, CDCl3) δ 2.5 (m, 2 H), 1.65 (dt, 8H), 1.4 (m, 12H). 13C NMR
(300 MHz, CDCl3) δ 52.56, 34.52, 26.59, 25.38. HRMS calcd 230.1235 for C12H22S2. Found
230.1232.
Disulfanyl-acetic acid (2e). IR (KBr) cm-1 3500-3200 COOH (stretch), 3000-2900 C-H(aliph,
stretch), 1200-1100 C-S (stretch). 1H NMR (300 MHz, CDCl3) δ 2.27 (s, 4H), 11.5 (s, 2H). 13
C
NMR (300 MHz, CDCl3) δ 35.81 (t), 179.91 (s). HRMS calcd 181.9714 for C4H6S2. Found
181.9717.
Diphenyl disulfide (2f). IR (KBr) cm-1 3200-3100 C-H (Ar, stretch), 1200-1150 C-S (stretch). 1H
NMR (300 MHz, CDCl3) δ 7.65 (d, 4 H), 7.25 (m, 6H). 13C NMR (300 MHz, CDCl3) δ 133.21,
131.48, 130.25, 129.53. HRMS calcd 182.0224 for C12H10S2. Found 182.0226.
Dinapth-2-yl disulfide (2h). IR (KBr) cm-1 3200-3100 C-H (Ar, stretch), 1200-1150 C-S
(stretch). 1H NMR (300 MHz, CDCl3) δ 8.1 (s, 2 H), 7.7 (d, 2H), 7.5 (d, 6H) 7.32 (d, 4H). 13
C
NMR (300 MHz, CDCl3) δ 137.76, 137.11, 135.26, 134.52, 131.57, 128.92, 127.08, 126.16,
125.02, 124.87. HRMS calcd 318.0512 for C20H14S2. Found 318.0509.
RESULTS AND DISCUSSION
The oxidative coupling of thiols with the TPFAC reagent was investigated in dichloromethane
at room temperature and under microwave irradiation using a minimal amount of solvent
(acetonitrile). As shown in Table 1, a series of aliphatic and aromatic thiols could be reacted
with 1 molar equivalent of the reagent to afford the corresponding disulfides in excellent yields.
This oxidation could also be performed under microwave conditions with the TPAFC reagent.
The results show that under microwave conditions, reaction times were shorter.
Microwave irradiation in these cases offers some advantages in terms of simplicity of
performance, simple operation, no side product formation, very short reaction time and a wide
range of substrates that could be converted to their corresponding disulfides.
TPAFC is a very versatile oxidant based on quaternary ammonium halochromates. In our
research on oxidation processes, it has been found that TPAFC is an oxidant that is very well
suited for microwave synthesis. As it is an ionic and magnetically retrievable material, it carries
the benefit of an efficient conversion of electromagnetic energy into heat according to the
dielectric heating mechanism (Table 1).
Mineral oxides are often very poor conductors of heat, but behave as very efficient
microwave adsorbents, this resulting in turn in a very rapid and homogeneous heating.
Consequently, they display very strong specific microwave effects, with significant
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143
improvements in temperature homogeneity and heating rates, enabling faster reactions and less
degradation of final products when compared to classical heating.
Table 1. Oxidation coupling of thiols (1a-h) with TPAFC in solution and under microwave irradiation
using a minimal amount of solvent.
In solution
Product
Under microwave
irradiation
Substrate
Time
(min)
Yiel Time
(min)
Yield
(%)
d
(%)
75
S
55
6
85
H
S
S
1 a
2a
54
78
7
85
83
S
4
H
H
S
4
2b
4
S
1b
S
60
50
72
65
10
7
S
7
7
S
2c
1 c
S
H
H
6
5
89
80
S
S
1d
2d
O
O
56
73
72
80
S
O
S
S
OH
OH
1e
OH
2e
8
6
92
84
S
H
S
S
1f
2f
H3
C
S
S
CH3
67
84
77
68
H3C
S
H
1g
1h
2g
S
14
81
H
S
S
2h
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Mohammad Kazem Mohammadi et al.
CONCLUSIONS
In conclusion, it has been found that TPAFC acts as a simple, efficient, and fast oxidizing
reagent in the oxidative coupling of thiols. The easy procedure, simple work-up, the easy
preparation of the reagent, short reaction times, and excellent yields of the products would make
this reagent a useful addition to available oxidants. Also, it should be emphasized that the
reactions can be performed cleanly and can be controlled to stop at the disulfide stage. Over-
oxidation has not been observed, even when the reactions were carried out under different
conditions. In this paper, we reported a procedure where the oxidation is performed in
microwave irradiation, in order to prevent problems connected with conventional heating (cost,
handling, safety, pollution, and decreases in reactivity by dilution of the reactants).
ACKNOWLEDGEMENTS
The authors are grateful to the Imam Khomeini International University research council for the
support of this work and to Mr. K. Ghoddamy and Dr. K. Mahanpoor for their valuable
comments.
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