Tributylammonium halochromates/silica gel: Simple reagents for oxidative coupling of thiols to symmetrical disulfides

Article abstract of DOI:10.1002/cjoc.201090363

New orange solid tributylammonium halochromates, (C₄H ₉)₃N⁺CrO₃X^-, TBAXC (X=F, Cl) are easily synthesized by the reaction of tributylammonium fluoride and chloride with CrO₃ in a 1:1 molar ratio in the presence of HF and HCl. Tributylammonium halochromates(VI) are versatile reagent for the effective and selective oxidation of organic substrates. Silica gel supported TBAFC and TBACC are versatile reagents for the effective and selective oxidation of organic substrates, in particular, thiols, under mild conditions. Considerable improvements are observed in the presence of the absorbent, making the work-up much more convenient. New orange solid tributylammonium halochromates, (C ₄H₉)₃N⁺CrO₃X ^-, TBAXC (X=F, Cl) are easily synthesized by the reaction of tributylammonium fluoride and chloride with CrO₃ in a 1:1 molar ratio in the presence of HF and HCl. Tributylammonium halochromates(VI) are versatile reagent for the effective and selective oxidation of organic substrates. Copyright

Full text of DOI:10.1002/cjoc.201090363

FULL PAPER
Tributylammonium Halochromates/silica Gel: Simple Reagents
for Oxidative Coupling of Thiols to Symmetrical Disulfides
Mohammadi, Mohammad Kazem*,a
Ghammamy, Shahriareb
Zarrinabadi, Sorousha
Farjam, Mohammad Hosseinc
Sabayan, Behrangd
a Faculty of Science, Islamic Azad University, Ahvaz Branch, Ahvaz, 61349-68875, Iran
b Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin, PO Box 288, Iran
c Department of Chemistry, Islamic Azad University, Firouzabad Branch, Firouzabad, Iran
d Department of Chemistry, Islamic Azad University, Shiraz Branch, Shiraz, Iran
New orange solid tributylammonium halochromates, (C4H9)3N＋CrO3X－, TBAXC (X＝ F, Cl) are easily synthe-
sized by the reaction of tributylammonium fluoride and chloride with CrO3 in a 1∶ 1 molar ratio in the presence of
HF and HCl. Tributylammonium halochromates(VI) are versatile reagent for the effective and selective oxidation of
organic substrates. Silica gel supported TBAFC and TBACC are versatile reagents for the effective and selective
oxidation of organic substrates, in particular, thiols, under mild conditions. Considerable improvements are ob-
served in the presence of the absorbent, making the work-up much more convenient.
Keywords tributylammonium halochromates, solid-phase synthesis, oxidation, silica gel, thiol, disulfide
Introduction
bromochromate (Scheme 1).17 With the belief that, these
reagents may have oxidative properties and could be
used for oxidation of organic substrates.
Disulfides are one of the most important organic
sulfur compounds possessing an exclusive chemistry
both in biochemistry and in synthetic area.1 Disulfides
are also key intermediates in a wide variety of organic
synthetic processes. Sweetening of catalyst poisons
thiols to low volatile disulfides in oil industries and in-
dustrial applications of disulfides in vulcanization of
rubbers and elastomers led us to investigate the intro-
duction and applications of new member of this cate-
gory of reagents in oxidation of thiols to the corre-
sponding disulfides.2
The main type of these reactions is the oxidation of
thiols in the presence of manganese dioxide,3 dichro-
mates,4 borohydride exchange resin,5 DMSO/alumina
reagent,6 CBr4/solid K2CO3/18-crown-6/benzene7 and
NaIO3/alumina8 and tetramethylammonium fluoro-
chromate.9
However, some of the reported reagents suffer from
disadvantages such as instability, hygroscopicity, low
selectivity, long reaction time, difficulty of preparation
and need for a large excess of the reagent. Thus a milder,
more selective and inexpensive reagent is still in demand.
Solutions to these problems lead to the development of a
good number of other oxidants, such as pyridinium
chlorochromate,10 pyridinium fluorochromate,11 quino-
linium dichromate,12 2,2'-bipyridinium chlorochromate,13
quinolinium chlorochromate14 and isoquinolinium
fluorochromate.15 We synthesized tetramethylammo-
nium fluorochromate16 and cetyltrimethylammonium
Scheme 1
This manuscript introduces tributylammonium
fluorochromate(VI) (TBAFC) and tributylammonium
chlrochromate(VI) (TBACC) absorbed on silica gel, as
new reagents with improved work-up efficiency and
durability, for the oxidation of thiols to disulfides.
Experimental
Material and instruments
CrO3 (Merck, p.a.) was used without further purifi-
cation. Silica gel Aldrich, 150 mesh and merck Tlc
plates were used. Solvents were purified by standard
methods. Infrared spectra were recorded as KBr disks on
a Shimadzu model 420 spectrophotometer. The UV/Vis
measurements were made on an Uvicon model 922
1
spectrometer. H and 13C NMR were carried out on a
Bruker AVANCE DRX 500 spectrometer at 500, 125
and 470.66 MHz, respectively using SiMe4 as internal
*
E-mail: mohammadi@iauahvaz.ac.ir; Tel.: 0098-6113348345
Received September 28, 2009; revised May 26, 2010; accepted June 11, 2010.
Chin. J. Chem. 2010, 28, 2199— 2203
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2199

Mohammadi et al.
FULL PAPER
stamdarcl. Chromium was estimated iodometrically. In
the case of the reduced product of the oxidant, chro-
mium was determined after oxidizing with acidic per-
oxodisulfate (K2S2O8) solution. The percent composi-
tion of carbon, hydrogen and nitrogen were obtained
from the Microanalytical Laboratories of the Depart-
ment of Chemistry, OIRC, Tehran.
pressure dropping funnel was used. The cold solution of
TBAFC or TBACC, prepared by complete solving of
TEAXC (X＝F, 0.2 mol, 44.2 g; X＝Cl, 0.2 mol, 47.4 g)
in CH2Cl2 (10 mL) was stirred with silica gel (Aldrich,
150 mesh, 60 g) over a period of 30 min at room tem-
perature. 30 min Evaporation of the solvent under low
pressure vacuum affords orange-red slurry, tributylam-
monium halochromates/silica gel, which is completely
dried on the surface of highly dried day plate in the air.
Tributylammonium － fluorochromate
(C4H9)3NH＋[CrO3F]
(TBAFC),
Typical procedure for oxidation coupling of ben-
zenethiol with tributylammonium halochromates/
silica gel
A sample of chromium(VI) oxide, CrO3 (1 g, 0.01
mol) and of 40% hydrofluoric acid (0.9 mL, 0.02 mol)
were added to 20 mL of water in a 100 mL polyethylene
beaker with stirring. After 5 min, the homogeneous so-
lution was cooled to ca. 0—2 ℃. To the resultant clear
orange solution, tributylamine (0.235 mL, 0.01 mmol)
was added drop wise with stirring over a period of 0.5 h
and stirring was continued for 0.5 h at －4 ℃. The
precipitated yellowish-orange solid was isolated by fil-
tration on a polyethylene funnel, washed with petroleum
ether (60 mL×3) and dried in vacuum for 2 h at room
temperature. Yield 84%, m.p. 134 ℃, Anal. calcd for
C12H28CrFNO3: C 47.20, H 9.24, N 4.58; found C 46.92,
A suspension of benzenethiol (1f) (0.110 g, 0.001
mol), TBAFC (0.221 g, 0.001 mol) and 0.2 g wet SiO2
(50%, w) in CH2Cl2 (10 mL) was stirred magnetically at
room temperature. The completion of the reaction was
followed by TLC using ether/petroleum ether (V∶V＝
60∶40) as eluant. After its completion, the mixture was
stirred in EtOH/CHCl3 (V∶V＝1∶3) solution for
separating products from the solid support. This mixture
allowed to stand for 1 h and then filtered, to give a clear
solution. The solution was evaporated and the residual
product purified by distillation, recrystallization or col-
umn chromatography to give 1,2-diphenyldisulfane (2f)
in 79% yield in 123 min. m.p. 57—58 ℃ (Lit.18 58—
60 ℃).
H 9.64, N 5.20. IR (KBr): 914 [ν (A1) or ν(CrO3)], 634
1
－1
[ν (A1) or ν(Cr-F)], 950 [ν (E) or ν(CrO3)] cm . Elec-
2
4
－ 1
tronic absorption at 22321 cm , corre－sponding to
－1
－1
1
1
1A2→1E (ε＝177 L•mol •cm ); 28735 m to E→1E
－1
－1
－1
1
(ε＝701 L•mol － •cm － ) and 35971 cm to A1→1E
For other thiols (1a—1e, 1g—1h), these procedures
were the same as above. The same procedure was ap-
plied for coupling of benzenethiol to 1,2-diphenyldi-
sulfane with TBACC and the above procedure could be
achieved for large scales, without any problems.
(ε＝1314 L•mol •cm ). UV/Visible, 13C NMR and 1H
NMR, were all consistent with the TBAFC structure.
The above procedure can be scaled up to－larger quanti-
1
1
1
ties, if desired. The pH of 0.01 mol•L solution of
1,2-Diisopropyldisulfane (2a)18 1H NMR (CDCl3,
300 MHz) δ: 2.71 (d, J＝7.0 Hz, 2H), 1.55 (d, J＝8.0
Hz, 12H); 13C NMR (CDCl3, 300 MHz) δ: 38.50 (d),
24.21 (q); IR (KBr) ν: 3000—2900 (C—H, aliph,
strech), 1400—1350 (C—H, aliph bend), 1200—1100
TBAFC in water was 3.15 (Scheme 1).
Tributylammonium
chlrochromate
(TBACC),
(C4H9)3NH＋[CrO3Cl]－
Chromium(VI) oxide (1.0 g, 0.01 mol) was dissolved
－1
＋
－1
in water in a beaker and 6 mol•L hydrochloric acid
(C—S, strech) cm ; HRMS calcd for C6H14S2 (M )
(0.251 mL, 0.015 mol) was added under stirring at 0 ℃.
To the resultant orange solution, tributylamine (0.235
mL, 0.01 mmol) was added dropwise under stirring over
a period of 0.5 h and the stirring was continued for 0.5 h
at －4 ℃. The precipitated orange solid was isolated
by filtration, washed with petroleum ether 60 mL×3)
and dried under vacuum for 2 h at room temperature.
Yield 71%, m.p. 126 ℃. Anal. calcd for C12H28ClCrNO3:
C 44.79, H 8.70, N 4.35; found C 44.59, H 8.81, N 4.38.
IR (KBr): 898 [v1(A1) or v(CrO3)], 436 [v2(A1) or v(Cr—
150.4125, found 150.4117.
1,2-Dipentyldisulfane (2b)18 1H NMR (CDCl3,
300 MHz) δ: 2.50 (t, J＝7.4 Hz, 4H) ,1.62 (m, 4H), 1.25
(m, 4H) 1.33 (m, 4H), 0.85 (t, J＝10.0 Hz, 6H); 13C
NMR (CDCl3, 300 MHz) δ: 36.35, 33.13, 31.27, 23.53,
14.50; IR (KBr) ν: 2980—2900 (C—H, aliph, strech)
－1
1200—1150＋(C—S, strech) cm ; HRMS calcd for
C10H22S2 (M ) 206.8542, found 206.1654.
1,2-Dioctyldisulfane (2c)18 1H NMR (CDCl3, 300
MHz) δ: 2.61 (t, J＝7.9 Hz, 4H ) ,1.52 (m, 4H), 1.26 (m,
18H), 94 (t, J＝7.7 Hz, 6H); 13C NMR (CDCl3, 300
MHz) δ: 33.66, 32.56, 31.43, 31.35, 31.22, 27.03, 23.51,
15.02; IR (KBr) ν: 2940—2900 (C—H, aliph, strech)
－1
1
Cl)], 940 [v4(E) or v(CrO3)] cm . UV/Visible and H
NMR were all consistent with the TBACC structure.
－1
Electronic absorption at 21881 cm , corresponding to
－
－1
－1
1A2→1E (ε＝336 L•mol •cm ); 28089 cm 1 to 1E→1E
－1
1150—1100＋(C—S, strech) cm ; HRMS calcd for
－1
－1
－1
1
(ε＝891 L•mol •cm ) and 34965 cm to A2→1A1
C16H34S2 (M ) 290.1213 found 290.3564.
－1
－1
－
(ε＝1178 L•mol •cm ). The pH of 0.01 mol•L 1 solu-
1,2-Dicyclohexyl disulfane (2d)18
1H NMR
tion of TBACC in water was 2.9.
(CDCl3, 300 MHz) δ: 2.5 (m, 2H), 1.65 (dt, J＝7.0 Hz,
8H), 1.43 (m, 12H); 13C NMR (CDCl3, 300 MHz) δ:
52.56, 34.52, 26.59, 25.38; IR (KBr) ν: 2970—290－20
General procedure for preparation of silica gel sup-
ported reagents
1
(C—H, aliph, strech), 1200—1100 (C—S, strech) cm ;
A 500 mL suction flask equipped with a constant-
2200
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 2199— 2203

Tributylammonium Halochromates/silica Gel: Simple Reagents for Oxidative Coupling of Thiols
HRMS calcd for C12H22S2 (M ＋ ) 230.2135, found
230.2120.
effective heterogeneous surface area for the oxidation
and at the same time, make the work up much more
convenient. The strong electronic bind between the
oxygen of SiO2 in silica gel solid support and quaternary
ammonium positive charge might occurred and probably
could result in higher absorbent of reagents to solid
support as compared to other similar reagents. The na-
ture of the solvent does not appear to be particularly
critical. Hydrocarbons, benzene, ethers and chlorinated
hydrocarbons are equally effective with combination to
ethanol to separate the product from the solid support.
The practical choice is oriented by the solubility of the
products and the desired reaction temperature. The
chromium(VI) contents could be easily determined io-
dometrically. It is seemed from the Table 1 that TBAFC
was more effective than TBACC for saturated organic
thiols (1a—1d) especially in time of the reaction. This is
probably due to higher electro negativity of fluore atom
in TBAFC than TBACC.16
As may be seen, the method offers a simple, mild
and efficient solid state route for the oxidation of a vari-
ety of thiols to the corresponding disulfides. Notably,
disulfides did not undergo further oxidation to their cor-
responding disulfide S-oxides (thiolsulfinates), disulfide
S-dioxides (thiolsulfonates), and/or sulfonic acids under
the reaction conditions. It must also be noted that no
severe exothermal or other safety problems were ob-
served during the mixing of the starting materials and
the reactions themselves.
It is important to note that most of the previously
reported methods for the oxidation of thiols use synthe-
sized or toxic reagents and/or suffer from other disad-
vantages such as long reaction time and low yields,3-9
but this method uses a readily available reagent and ad-
ditionally offers the advantages of high yields, short
reaction time, no side reactions, mild reaction conditions,
a solid state reaction and simple isolation of the prod-
ucts. Consequently, this methodology should represent a
good addition to list of methods already available for
this purpose.
The IR spectra of TBAFC and TBACC are similar to
that of other fluoro and chlorochromates.19 TBAFC and
TBACC are soluble in water, dimethylformamide, ace-
tonitrile, acetone and dichloromethane, and only spar-
ingly soluble in benzene, carbon tetrachloride, chloro-
form and hexane.
Disulfanyl-acetic acid (2e)18 1H NMR (CDCl3,
300 MHz) δ: 2.27 (s, 4H), 11.58 (s, 2H); 13C NMR
(CDCl3, 300 MHz) δ: 35.28 (t), 179.19 (s); IR (KBr) ν:
3500—3200 (COOH, strech), 3050—2930 (C—H, aliph,
－1
strech), 1150—1100 (C—S, strech) cm ; HRMS calcd
for C4H6 O4S2 (M＋): 182.1478, found 182.3421.
1,2-Diphenyldisulfane (2f)17 1H NMR (CDCl3,
300 MHz) δ: 7.65 (d, J＝10.0 Hz, 4H), 7.25 (m, 6H);
13C NMR (CDCl3, 300 MHz) δ: 133.51, 131.44, 130.20,
129.53; IR (KBr) ν: 3200—3100－(C—H, Ar, strech),
1200—1150 (C—S, strech) cm 1. Anal. calcd for
C12H10S2: C 66.13, H 4.71, S 29.37; found C 66.22, H
4.65, S 29.23.
1,2-Di-p-tolyldisulfane or bis(4-methylphenyl)-
disulfidev (2g) m.p. 42—44 ℃ (Lit.19 43—44 ℃);
1H NMR (CDCl3, 300 MHz) δ: 7.54 (d, J＝10.5 Hz, 4H),
7.29 (d, J＝12.0 Hz, 4H), 2.57 (s, 6H); 13C NMR
(CDCl3, 300 MHz) δ: 126.31 (s), 130.26 (d), 127.12 (d),
124.08 (s), 21.87 (q); IR (KBr) ν: 3200—3100 (C—H,
Ar, strech), 2950—2900 (C—H, aliph, strech), 1480—
1400 (C—H, Ar, bend), 1170—1050 (C—S, strech)
－1
cm . Anal. calcd for C14H14S2: C 68.29, H 5.70, S
26.14; found C 68.46, H 5.60, S 26.23.
1-(n-Naphthalene-3-yl)-2-(naphthalene-6-yl)disulf-
ane (2h) m.p. 140—142 ℃ (Lit.19 142—145 ℃); 1H
NMR (CDCl3, 300 MHz) δ: 8.11 (s, 2H), 7.74 (d, J＝
11.6 Hz, 2H), 7.53 (d, J＝12.7 Hz, 6H) 7.32 (d, J＝14.0
Hz, 4H); 13C NMR (CDCl3, 300 MHz) δ: 137.76, 137.11,
135.26, 134.52, 131.57, 128.92, 127.08, 126.16, 125.02,
124.87; IR (KBr) ν: 3140—3100 (C—H, Ar, strech),
1200—1150 (C—S, strech). Anal. calcd for C20H14S2: C
75.47, H 4.40, S 20.12; found C 75.36, H 4.32, S 20.89.
Results and discussion
Different thiols were subjected to oxidations with
tributylammonium fluorochromate(VI), (TBAFC) and
tributylammonium chlrochromate(VI), (TBACC) ab-
sorbed on silica gel, in dichloromethane (Scheme 2).
Scheme 2
These oxidations take place under mild and com-
pletely heterogeneous conditions giving excellent yields
(Table 1).
Conclusion
New reagents tributylammonium fluorochromate(VI)
(TBAFC) and tributylammonium chlrochromate(VI)
(TBACC) absorbed on silica gel are easily synthesized.
They prove to be low cost, readily available oxidizing
reagents for a variety of aromatic and none aromatic
thiols. Their advantages include higher yields, shorter
reaction time, lower thiol/oxidant molar ratios, and ease
of separation of products. Moreover, during the reaction,
Oxidations may also occur using only TBAFC and
TBACC, in the absence of silica gel, but considerable
improvements were observed in the presence of solid
support. These improvements are in the term of yields,
removing hazardous organic solvents, simplified ma-
nipulation, easily separating the products and especially
in the case of time of the reactions. This implies that the
silica gel may act as a reaction medium, providing an
Chin. J. Chem. 2010, 28, 2199— 2203
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2201

Mohammadi et al.
FULL PAPER
Table 1 Oxidation of thiols (1a— 1h) with TBAFC and TBACC on silica gel
TBAFC
Product
TBACC
Entry
1
Substrate
Time/min
Yield/%
Time/min
Yield/%
115
78
150
77
91
1a
1b
2a
2b
2c
2d
2
3
4
65
68
84
74
90
82
68
91
89
80
1c
1d
1e
152
5
60
88
212
85
2e
2f
6
7
42
28
79
93
38
34
92
89
1f
1g
2g
8
41
81
50
92
1h
2h
the color of the oxidants change from orange to brown,
thus providing a visual means for ascertaining the pro-
gress of the oxidation. This reaction is easily applicable
for producing a minor to large amount of disulfides in
simple and efficient procedure. Because of phase trans-
fer properties of reagents, availability, versatility and
high absorbance on silica gel by quaternary ammonium,
these reagents, are suitable for oxidative coupling of
thiols to disulfides. The mechanism of oxidation is
probably similar to other quaternary ammonium re-
agents.21 Many functional groups are inert towards these
oxidizing agents, including, sulfides and phenols, en-
hancing the usefulness of the oxidants and the oxidation
conditions for the synthesis of highly functionalized
molecules.
lamic Azad University, Ahvaz Branch.
References
1
Capozzi, G.; Modena, G. The Chemistry of Thiol Group in
Chemistry of Functional Groups, Part 1, Ed.: Patai, S.,
Wiley, New York, 1974, p. 785.
2
Holbrook, D. L. Handbook of Petroleum Refining Processes,
Ed.: Meyers, R. A., McGraw Hill, New York, 1996, Chap.
11.3.
3
4
Papadopoulos, E. P.; Jarrar, A.; Issidoides, C. H. J. Org.
Chem. 1966, 31, 615.
Lopez, C.; Conzales Cossio, A.; Palomo, C. Synth. Commun.
1985, 15, 1197.
5
6
Choi, J.; Yoon, N. M. J. Org. Chem. 1995, 60(11), 3266.
Hirano, M.; Yakabe, S.; Monobe, H.; Marimoto, T. J. Chem.
Res., Synop. 1998, 472.
Acknowledgements
7
Abele, E.; Abele, R.; Lukevics, E. J. Chem. Res., Synop.
1999, 624.
The author thanks valuable help and support of Is-
2202
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 2199— 2203

Tributylammonium Halochromates/silica Gel: Simple Reagents for Oxidative Coupling of Thiols
8
9
Hirano, M.; Yakabe, S.; Ando, K.; Morimoto, T. J. Chem.
Res., Synop. 1998, 816.
Imanieh, H.; Ghamami, S.; Mohammadi, M. K.; Jangjoo, A.
Russ. J. Gen. Chem. 2007, 77(2), 282.
dron Lett. 2003, 44(24), 4555.
17 Ghammamy, S.; Eimanieh, H.; Mohammady, M. K. Synth.
Commun. 2007, 37, 599.
18 Aldrich Catalog Handbook of Fine Chemicals, 1996— 1997,
p. 1159.
19 Montazerozohori, M.; Joohari, S.; Karami, B.; Haghighat, N.
Molecules 2007, 12, 694.
10 Corey, E. J.; Boger, D. L. Tetrahedron Lett. 1978, 28, 2461.
11 Bhattacharjee, M. N.; Chauduri, M. K.; Dasgupta, H. S.
Synthesis 1982, 588.
12 Chaubey, G. S.; Das, S. M.; Mahanti, K. Croatica Chem.
Acta 2003, 76(4), 287.
13 Guziec, F. S.; Luzzio, F. A. Synthesis 1980, 691.
14 Jeyanthi, G.; Vijayakumar, F. G.; Elango, K. P. J. Serb.
Chem. Soc. 2002, 67(12), 803.
20 Nakamoto, K. Part II, Inorganic Compounds, Infrared and
Raman Spectra of Inorganic and Coordination Compounds,
Vol. 1, 3rd ed., John Wiley & Sons, New York, 1978, pp.
140— 150.
21 Walters, M. A.; Chaparro, J.; Siddiqui, T. F.; Williams, U,
C.; Rheingold, A. L. Inorg. Chim. Acta 2006, 359, 3996.
22 Patel, S.; Mishra, B. K. Tetrahedron 2007, 63, 4367.
15 Srinivasan, R.; Stanley, P.; Balasubramanian, K. Synth.
Commun. 1997, 27(12), 2057.
16 Mahjoub, A. R.; Ghammami, S.; Kassaee, M. Z. Tetrahe-
(E0909284 Zhao, C.; Zheng, G.)
Chin. J. Chem. 2010, 28, 2199— 2203
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2203