Heteropoly acids as heterogeneous catalysts for thioacetalization and transthioacetalization reactions

Article abstract of DOI:10.1055/s-2002-19300

Heteropoly acids are effective solid catalysts for the thioacetalization of carbonyl compounds. Tungstophosphoric acid (H₃PW₁₂O₄₀), was found to be an effective and a highly selective catalyst for the thioacetalization of aldehydes, ketones and for the transthioacetalization of acetals, acylals and O,S-acetals which proceeded in excellent yields in the absence of solvent. The catalyst has also been successfully applied to the chemoselective conversion of α- or β-diketones and a β-keto ester into the corresponding dithioacetals. Sterically hindered carbonyl compounds such as camphor and benzophenone were also converted to their corresponding thioacetals in refluxing petroleum ether in 89-94percent yields. Surprisingly, anthrone was reduced to anthracene in 91percent yield.

Full text of DOI:10.1055/s-2002-19300

PAPER
59
Heteropoly Acids as Heterogeneous Catalysts for Thioacetalization and
Transthioacetalization Reactions
Heteropoly Acids
a
a
s
Catalyst
b
in Thioaceta
l
ization
b
s
Firouzabadi,* Nasser Iranpoor,* Kamal Amani
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
E-mail: firouzabadi@chem.susc.ac.ir
Received 25 July 2001; revised 9 October 2001
transthioacetalization reactions in the presence and ab-
sence of solvents26–28 and we also have used tungstophos-
phoric acid as an efficient catalyst for the oxidation of
anilines to their nitro compounds in aqueous micellar me-
Abstract: Heteropoly acids are effective solid catalysts for the thio-
acetalization of carbonyl compounds. Tungstophosphoric acid
(H3PW12O40), was found to be an effective and a highly selective
catalyst for the thioacetalization of aldehydes, ketones and for the
transthioacetalization of acetals, acylals and O,S-acetals which pro- dia with sodium perborate.29 Solvent-free reactions have
ceeded in excellent yields in the absence of solvent. The catalyst has
attracted the attention of chemists due to their environ-
also been successfully applied to the chemoselective conversion of
mental and economical advantages and due to their sim-
- or -diketones and a -keto ester into the corresponding dithio-
plicity in process and handling.30 Along this line, we now
acetals. Sterically hindered carbonyl compounds such as camphor
report that tungstophosphoric acid, in the solid state, could
and benzophenone were also converted to their corresponding thio-
acetals in refluxing petroleum ether in 89–94% yields. Surprisingly,
anthrone was reduced to anthracene in 91% yield.
be used as an efficient catalyst for thioacetalization and
transthioacetalization reactions in organic synthesis.
Key words: carbonyl compounds, tungstophosphoric acid, het-
eropoly acids, thioacetalizations, transthioacetalizations
In this paper we describe the dithioacetalization of carbo-
nyl compounds using HPAs or their salts as catalysts. The
results of our studies show that H3PW12O40,
(NH4)2HPW12O40, Cs2.5H0.5PW12O40, and H4SiW12O40 are
very efficient catalysts for dithioacetalization reactions
under solvent-free conditions. In Table 1, we have com-
pared the catalytic activities of H3PW12O40,
(NH4)2HPW12O40, Cs2.5H0.5PW12O40 and H4SiW12O40
with TfOH, CH3SO3H and H2SO4 for a dithioacetalization
reaction. As it is evident from the results summarized in
Table 1, HPAs and their salts are very effective catalyst
for this purpose.
The protection of carbonyl groups as acetals or thioacetals
is often necessary during the synthesis of multi-functional
complex molecules1 and natural products.2 Generally,
thioacetals have been prepared by the condensation of car-
bonyl compounds and thiols catalyzed with protic acids,3,4
solid acids,5,6 (such as HY or H-mordenite Zeolite,
Nafion-H, Amberlyst-15), Lewis acids7–9 or solid sup-
ports.10,11 Transthioacetalization of acetals has also been
conducted in the presence of BF3 OEt2,12 i-
Bu2AlS(CH2)2SAl(i-Bu)2,13 CoCl2 Me3SiCl14 and natural
kaolinitic clay.15 In recent years, catalytic properties of
solid heteropoly compounds, in particular their acidic
properties, have been the subjects of reviews.16,17 Het-
eropoly acids (HPAs) in solution are stronger than the
usual mineral acids such as H2SO4, HCl, HNO3, etc.18 Sol-
id HPAs also are stronger than conventional solid acids
such as SiO2/Al2O3, H3PO4/SiO2, and HX or HY zeo-
lites.19 HPAs with the Keggin structure constitute the
most extensively studied and important class of polyoxo-
metalates.20–22
We therefore chose the most effective catalyst
H3PW12O40, for the protection of other carbonyl com-
Table 1 Thioacetalization of Benzaldehyde with Propane-1,3-dithi-
ol in the Presence of Heteropoly Acids (HPAs), Some of Their Salts
and Other Strong Protic Acids in Solventless Systems
Entry Catalyst
Substrate/
Thiol/Cat.
Time
(min)
GC Yield
(%)
1
2
H3PW12O40
1:1.2:0.005
1:1.2:0.002
1:1.2:0.001
1:1.2:0.001
1:1.2:0.001
1:1.2:0.001
<1
2
98
98
H3PW12O40
In the past two decades, the broad utility of HPAs as acid
and oxidation catalysts in solution as well as in the solid
state for various industrial processes has been demonstrat-
ed for a wide variety of synthetically useful transforma-
tions of organic substrates.23,24 Kinetic studies of liquid-
phase acetal formation catalyzed by Keggin-type het-
eropoly acids are also reported.25 Recently we have intro-
duced new catalysts for thioacetalization and
3
H3PW12O40
2.5
3.5
18
98
4
H3PW12O40 nH2O
(NH4)2HPW12O40
Cs2.5H0.5PW12O40
>98
98
5
6
50
97
7
H4SiW12O40 nH2O 1:1.2:0.001
120
60
96
8
TfOH
1:1.2:0.003
1:1.2:0.003
1:1.2:0.0015
30
Synthesis 2002, No. 1, 28 12 2001. Article Identifier:
1437-210X,E;2002,0,01,0059,0062,ftx,en;T06601SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
9
CH3SO3H
H2SO4
60
24
10
120
20

60
H. Firouzabadi et al.
PAPER
pounds. Various types of aromatic and aliphatic aldehydes presented results show that aliphatic and aromatic alde-
were cleanly and rapidly converted to their corresponding hydes were protected more quickly than aromatic or hin-
dithioacetals in excellent yields in the presence of a 1.2 dered ketones. It was also observed that
fold molar excess of thiol or dithiol and 0.001 mmol transthioacetalization of acetals, ketals, O,S-acetals and
(0.003 equiv) of tungstophosphoric acid at room tempera- acylals was achieved efficiently with catalytic amounts of
ture (Scheme 1, Table 2, entries 1–8).
tungstophosphoric acid to afford the corresponding S,S-
acetals in excellent yields under solvent–free conditions
(Table 2, entries 14 20). Protection of carbonyl groups of
hindered ketones such as (+)-camphor and benzophenone
is a very difficult process and is usually accompanied with
low yields of the products and requires long reaction
times. In the absence of solvent, thioacetalization of these
sterically hindered ketones proceeded in 30% and 50%
yields, respectively after 24 hours at room temperature.
However, this reaction in refluxing petroleum ether (bp
60–80 °C) proceeded efficiently and gave the desired
products in 89% and 94% yields, respectively. Thioacetal-
ization of anthrone with propane-1,3-dithiol in boiling pe-
troleum ether (bp 60–80 °C) gave anthracene in 91% yield
instead of producing the 1,3-dithiane (Scheme 2).
Scheme 1
Aliphatic ketones were also converted to the correspond-
ing dithioketals in excellent isolated yields (Table 2, en-
tries 9,10). However, aromatic ketones required
prolonged reaction times even in the presence of 0.02–
0.05 mmol of the catalyst (Table 2, entries 11,12). The
Table 2 Thioacetalization of Carbonyl Compounds, Acetals, Ketals, O,S-Acetals and Acylals with Tungstophosphoric Acid (H3PW12O40)
R1
R2
H
X
R
Substrate/Thiols/Cat.
1:1.2:0.001
1:1.2:0.01
1:1.2:0.01
1:1.2:0.001
1:1.2:0.001
1:1.2:0.001
1:1.2:0.001
1:1.2:0.001
1:1.5:0.001
1:1.2:0.001
1:1.5:0.02
1:1.7:0.05
1:2:0.2
Time (min)
Yielda (%)
98
Ref.
3,5,9,15
Ph
O
(CH2)3
Ph
2.5
10
25
1
28
Ph
H
O
97
3
Ph
H
O
Bu
97
10,15
10,15
28
p-MeOC6H4
p-ClC6H4
o-ClC6H4
C5H11
H
O
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)2
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)3
99
H
O
30
50
3
95
H
O
97
31
H
O
89
32
PhCH=CH
PhCH2
H
O
2
91
28
Me
O
10
4
96
9,15
5,9,15
5,9,15
3,15
3,5,9,15
3,5,9,15
28
-(CH2)5-
O
98
Ph
Me
Ph
O
70
40
24c
5
98
Ph
O
94b
89b
98
(+)-camphor
Ph
O
H
H
H
H
(OMe)2
O(CH2)3O
O(CH2)3O
O(CH2)3S
O(CH2)3O
O(CH2)3O
(OAc)2
1:1.2:0.004
1:1.2:0.004
1:1.2:0.01
1:1.2:0.01
1:2:0.01
Ph
5
94
o-ClC6H4
p-MeC6H4
50
8
94
28
96
9,15
5,9,15
28
-(CH2)5-
10
2c
4
89
Ph
Me
H
1:1.2:0.02
1:1.2:0.01
94
p-MeC6H4
98
a
In refluxing petrolrum ether (bp 60-80 °C).
b The products were purified by column chromatography on silica gel (60–230 Mesh, EtOAc–petroleum ether 9:1).
c Reaction time in hours.
Synthesis 2002, No. 1, 59–62 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Scheme 2
Heteropoly Acids as Catalyst in Thioacetalizations
61
Solvent-Free Thioacetalization and Transdithioacetalization of
Carbonyl Compounds; General Procedure
Aldehydes or ketones (5 mmol), dithiol (6–7.5 mmol) and tungsto-
phosphoric acid (0.015–0.288 g, 0.005–0.1 mmol) were mixed and
the resulting mixture was magnetically stirred at r.t. After comple-
tion of the reaction (controlled by TLC or GC) the reaction was
quenched with 20% aq solution of Na2CO3 (5 mL), and the mixture
was continuously extracted with CH2Cl2 (10 mL) in a micro contin-
uos extractor (in order to minimize the amount of the required sol-
vent). The organic layer was isolated, and washed with H2O (2 10
mL) and dried (Na2SO4). Evaporation of the solvent gave almost
pure products. Further purification was performed by column chro-
matography on silica gel (60–230 mesh) using petroleum ether–
EtOAc (9:1) as eluent to afford the desired pure products in good to
excellent yields (Table 2). Crystalline unknown compounds 2,8
(Scheme 3) were recrystallized from hexane for further purification.
In order to show the chemoselectivity of the method for
the protection of different carbonyl groups we performed
a number of competitive reactions that demonstrate the
high selectivity of the method (Scheme 3).33
In conclusion, a wide range of aldehydes, ketones, - or -
diketones and a -keto ester could be transferred to the
corresponding 1,3-dithiolane and 1,3-dithianes in good to
excellent yields by the described method. Selectivity of
the method is very promising and discriminates between
Thioacetalization of Sterically Hindered Ketones in Petroleum
different CO functionalities. The catalytic activities of the Ether; General Procedure
Ketones (5 mmol), dithiol (8.5–10 mmol) and tungstophosphoric
heteropoly acids were much higher than those of conven-
tional acid catalysts such as sulfuric acid, methanesulfonic
acid and triflic acid.
acid (0.6–2.88 g, 0.2–1 mmol) and petroleum ether (bp 60–80 °C,
10 mL) were mixed together and refluxed for the appropriate time
(Table 2, entries 12,13 and anthrone). After completion of the reac-
tion (controlled by TLC), the volume of the mixture was reduced to
3 mL and subsequently quenched with 20% aq solution of Na2CO3
(5 mL). The workup of the mixture was performed as mentioned in
the preceding experimental section. The desired products were iso-
lated in high purities and no further purification was necessary.
Tungstophosphoric acid (H3PW12O40 nH2O) was purchased from
Merck and was purified by extraction with Et2O from an aqueous
solution of the acid. After evacuating at 150–300 °C for 1–2 h under
reduced pressure pure H3PW12O40 was obtained.19 Tungstosilicic
acid (H4SiW12O40 nH2O) was purchased from Merck and dehydrat-
ed by evacuating at 150–300 °C. The acidic salts of heteropoly acids
were prepared according to the known procedures.34 The products
were purified by column chromatography and the purity determina-
tion of the products was accomplished by GC on a Shimadzu model
GC-14A instrument or by TLC on silica gel polygram SIL G/UV
254 plates. Mass spectra were run on a Shimadzu GC-Mass-QP
1000 EX at 20 ev. The IR spectra were recorded on a Perkin Elmer
781 spectrophotometer. The NMR spectra were recorded on a Bruk-
er avance DPX 250 MHz spectrometer.
2
White crystals; mp 69–70 °C (uncorrected).
1H NMR (250 MHz, CDCl3): = 1.95 (s, 3 H, CH3), 3.22–3.39 (m,
4 H, SCH2CH2S), 3.76 (s, 2 H, CH2), 7.41–7.96 (m, 5 H, C6H5).
13C NMR (63.9 MHz, CDCl3): = 197.09, 137.19, 133.66, 128.99,
128.40, 62.78, 54.03, 39.82, 32.73.
IR (KBr): 1677 cm–1 (C=O).
Scheme 3
Synthesis 2002, No. 1, 59–62 ISSN 0039-7881 © Thieme Stuttgart · New York

62
H. Firouzabadi et al.
PAPER
(8) Tietze, L. F.; Weigand, B.; Wulff, C. Synthesis 2000, 69.
MS (20 eV): m/z (%) = 238 (M+, 14.6), 179 (9.5), 133 (8.7), 119
(54.1), 105 (100), 77 (54.7), 59 (16.6), 51 (22.6).
(9) Tani, H.; Masumoto, K.; Inamasu, T.; Suzuki, H.
Tetrahedron Lett. 1991, 32, 2039.
Anal. Calcd for C12H14OS2: C, 60.47; H, 5.92. Found: C, 60.41;H,
5.9.
(10) Anand, R. V.; Saravanan, P.; Singh, V. K. Synlett 1999, 415.
(11) Chandrasekhar, S.; Takhi, M.; Reddy, Y. R.; Mohapatra, S.;
Rao, C. R.; Reddy, K. V. Tetrahedron 1997, 53, 14997.
(12) Moss, R. A.; Mallon, C. B. J. Org. Chem. 1975, 40, 1368.
(13) Satoh, T.; Uwaya, S.; Yamakawa, K. Chem. Lett. 1983, 667.
(14) Bellesia, F.; Boni, M.; Ghelf, F.; Pagnoni, U. M.
Tetrahedron 1993, 49, 199.
(15) Jnaneshwara, G. K.; Barhate, N. B.; Sudalai, A.; Deshpande,
V. H.; Gajare, A. S.; Shingare, M. S.; Sukumar, R. J. Chem.
Soc., Perkin Trans.1 1998, 965.
(16) Kozhevnikov, I. V. Chem. Rev. 1998, 98, 171.
(17) Misono, M.; Mizuno, N. Chem. Rev. 1998, 98, 199.
(18) Kozhevnikov, I. V. Russ. Chem. Rev. 1987, 56, 811.
(19) Misono, M.; Misono, N.; Katamura, K.; Kasai, A.; Konishi,
Y.; Sakata, K.; Okuhara, T.; Yoneda, Y. Bull. Chem. Soc.
Jpn. 1982, 55, 400.
(20) Essayem, N.; Coudurier, G.; Fournier, M.; Vedrine, J. C.
Catal. Lett. 1995, 34, 223; and references cited therein.
(21) Misono, M.; Soeda, H.; Okuhara, T. Chem. Lett. 1994, 909.
(22) Misono, M.; Okuhara, T.; Nishimora, T.; Watanabe, H. J.
Mol. Catal. 1992, 74, 247.
8
White crystals; mp 68–70 °C (uncorrected).
1H NMR (250 MHz, CDCl3): = 0.86 (s, 3 H, CH3), 0.93 (s, 3 H,
CH3), 0.98 (s, 3 H, CH3), 1.55–1.67 (m, 2 H, 6-H), 1.76–1.87 (m, 1
H, 7-Hendo), 1.90–2.04(m, 1 H, 7-Hexo), 2.28–2.30 (m, 1 H, 3-H),
3.19–3.49 (m, 4 H, SCH2CH2S).
13C NMR (63.9 MHz, CDCl3): = 218.03, 69.88, 60.60, 56.06,
46.75, 41.47, 37.73, 30.95, 28.25, 22.62, 20.37, 10.47.
IR (KBr): 1738 cm–1 (C=O).
MS (20 eV): m/z (%) = 242 (M+, 10.8), 214 (20.7), 186 (24.6), 131
(100), 83 (11.5), 71 (26.4), 57 (44.6), 41 (49.2).
Anal. Calcd C12H18OS2: C, 59.46; H, 7.48. Found: C, 59.42; H,
7.47.
Acknowledgment
We appreciate partial support of Shiraz University Research
Council.
(23) Kozhevnikov, I. V. Chem. Rev. 1998, 98, 171; and
references 2–16 cited therein.
(24) Misono, M.; Nojiri, N. Appl. Catal. 1990, 64, 1.
(25) Sato, S.; Sagara, K.; Furuta, H.; Nozaki, F. J. Mol. Catal. A
1996, 114, 209.
References
(26) Firouzabadi, H.; Iranpoor, N.; Karimi, B.; Hazarkhani, H.
Synlett 2000, 263.
(27) Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synlett 1999, 319.
(28) Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synthesis 1999, 58.
(29) Firouzabadi, H.; Iranpoor, N.; Amani, K. Green Chem.
2001, 3, 131.
(30) Toda, F.; Tanaka, K. Chem. Rev. 2000, 100, 1025.
(31) Burczyk, B.; Kortylewicz, Z. Synthesis 1982, 831.
(32) Saraswathy, V. G.; Sankararaman, S. J. Org. Chem. 1994,
52, 4665.
(33) Ong, B. S. Tetrahedron Lett. 1980, 21, 4225.
(34) Okuhara, T.; Nishimura, T.; Watanabe, H.; Misono, M. J.
Mol. Catal. 1992, 74, 247.
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1991, 2nd ed. Chap. 4, 178–
207.
(2) Smith, A. B.; Condon, S. M.; McCauley, J. A. Acc. Chem.
Res. 1998, 31, 35.
(3) Ku, B.; Oh, Y. Synth. Commun. 1989, 19, 433.
(4) Page, P. C. B.; Prodger, J. C.; Westwood, D. Tetrahedron
1993, 49, 10355.
(5) Kumar, P.; Reddy, R. S.; Singh, A. P.; Pandey, B. Synthesis
1993, 67.
(6) Taleiwa, J.; Horiuchi, H.; Vemura, S. J. Org. Chem. 1995,
60, 4039.
(7) Muthusamy, S.; Babu, S. A.; Gunanathan, C. Tetrahedron
Lett. 2001, 42, 359.
Synthesis 2002, No. 1, 59–62 ISSN 0039-7881 © Thieme Stuttgart · New York