Silica-supported phosphorus pentoxide: A reusable catalyst for S,S-acetalization of carbonyl groups under ambient conditions

Article abstract of DOI:10.1080/17415993.2010.542155

Phosphorus pentoxide supported on silica gel (P₂O ₅/SiO₂) efficiently acts as a highly active and reusable catalyst for cyclic and non-cyclic S,S-acetalization of a variety of carbonyl compounds under mild, solvent-free an

Full text of DOI:10.1080/17415993.2010.542155

Journal of Sulfur Chemistry
Vol. 32, No. 1, February 2011, 85–91
Silica-supported phosphorus pentoxide: a reusable catalyst for
S,S-acetalization of carbonyl groups under ambient conditions
Hamid Reza Shaterian*, Kobra Azizi and Nafiseh Fahimi
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, PO Box 98135-674,
Zahedan, Iran
(Received 4 September 2010; final version received 18 November 2010)
Phosphorus pentoxide supported on silica gel (P2O5/SiO2) efficiently acts as a highly active and reusable
catalyst for cyclic and non-cyclic S,S-acetalization of a variety of carbonyl compounds under mild, solvent-
free and ambient conditions. This method offers significant advantages such as high conversion, clean
work-up, short reaction times and simplicity in operation.
R1
R2
S
HSCH2(CH2)nCH2SH
n
S
R1
R2
P2O5/SiO2 (catalyst, 5 mg)
n=0,1
or
O
or
H2O
Solvent-free, room temperature
2R3SH
SR3
R1
R3=Alkyl, Aryl
R2
SR3
Keywords: P2O5/SiO2; S,S-acetal; solvent-free; heterogeneous catalyst; aldehydes; ketones
1. Introduction
The protection of aldehydes and ketones to cyclic and non-cyclic S,S-acetals is a common and
interesting method in organic chemistry such as multi-steps synthesis of poly-functional complex
molecules (1). S,S-Acetals are quite stable under basic and acidic conditions (2). The S,S-acetals
are also utilized as masked acyl anions (3) or masked methylene functions in carbon–carbon bond-
forming reactions (4). Generally, they are prepared by condensation of carbonyl compounds with
thiols or dithiols using strong Brønsted and Lewis acid catalysts such as HCl (5), BF3·OEt2(6),
AlCl3 (7), TiCl4 (8), Mg(OTf)3 (9) and LaCl3 (10). There is still a need to develop a simple
and efficient method for S,S-acetalization of carbonyl groups and chemoselective protection of
aldehydes and ketones.
*Corresponding author. Email: hrshaterian@chem.usb.ac.ir
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2010.542155
http://www.informaworld.com

86 H.R. Shaterian et al.
R1
R2
S
n
HSCH2(CH2)nCH2SH
S
P2O5/SiO2 (catalyst, 5 mg)
R1
R2
n=0,1
or
O
or
H2O
Solvent-free, room temerature
2R3SH
SR3
R1
R2
R3=Alkyl, Aryl
SR3
Scheme 1. The S,S-acetalization reaction of carbonyl compounds in the presence of silica
supported P2O5 as catalyst under solvent-free and ambient conditions.
Phosphorus pentoxide is a white, flammable, dangerous, corrosive to metal and extremely
deliquescent compound (11a). It reacts vigorously with water and water-containing substances,
liberates much heat and may even cause fire (11). Phosphorus pentoxide-methanesulfonic acid
was used for the first time as a convenient alternative to polyphosphoric acid (PPA) by Eaton
et al. to escape the difficulties encountered with PPA (12). Then, P2O5 supported on SiO2 as
an inexpensive, heterogeneous stable, free flowing and white powder was prepared (13). This
heterogeneous catalyst has been used in several organic reactions such as Fries rearrangement (14),
nitration of aromatic compounds (15), Beckmann or Schmidt rearrangements (16), preparation
of bisindolylmethanes (17), synthesis of N-sulfonyl imines (18) and Ritter reaction (19). In
continuationofourresearchontheapplicationofheterogeneouscatalystsinorganicreactions(20),
we have employed silica supported P2O5 in S,S-acetalization of carbonyl compounds (Scheme 1).
2. Results and discussion
Initially, a systematic study was carried out for catalytic evaluation of P2O5/SiO2 for S,S-
acetalization of benzaldehyde (1 mmol) with benzyl thiol (2.2 mmol) under various conditions.
The reaction is best carried out at ambient temperature under neat conditions. Next, we optimized
the quantity of the catalyst for this reaction. It was observed that the use of just 5 mg (6.5 w/w%)
(18) is sufficient to push the reaction forward immediately (Table 1, Entry 3). Larger amounts of
the catalyst did not improve the results (Table 1, Entries 1 and 2). Using 2 mg of the catalyst, the
reaction take place within 2 min with 90% yield.
To explore the scope and limitations of this new protocol, a range of aromatic and aliphatic
aldehydes and ketones with various substitution patterns were reacted with (a): 1,3-propanedithiol;
(b): 1,2-ethanedithiol; (c): benzyl thiol; (d): ethyl thiol under the optimized conditions. As can
be seen from Table 2, most of the substrates gave good to excellent yields of the corresponding
cyclic and non-cyclic S,S-thioacetals immediately. Not only aldehydes but also ketones reacted
immediately using P2O5/SiO2 (5 mg) as the catalyst under solvent-free conditions at ambient
temperature, and the desired product was obtained in satisfactory yields.
Table 1. Optimization of S,S-acetalization conditions in the model reaction
of benzaldehyde and benzyl thiol in the presence of P2O5/SiO2 as the catalyst
under solvent-free conditions at ambient temperature.
Entry
Catalyst (mg)
Time (min)
Yield (%)a
1
2
3
4
15
10
5
Immediately
Immediately
Immediately
2 min
95
96
98
90
2
Note: aYield refer to isolated pure products.

Journal of Sulfur Chemistry 87
Table 2. Immediate S,S-acetalization of various aldehydes and ketones in the presence of P2O5/SiO2 (5 mg) as the
catalyst under solvent-free conditions at ambient temperature.
Aldehydes
Entry and ketones
Thiols or Yield
dithiols (%)a
Aldehydes
and ketones
Thiols or Yield
dithiols (%)a
Refb
Entry
17
Refb
1
a
b
c
d
94
96
98
92
(21–25)
a
b
c
d
91
88
93
87
(21)
2
a
b
c
d
92
89
86
95
(21–25)
18
a
b
c
d
90
95
98
93
(21, 22, 24, 25)
3
4
5
a
b
c
d
88
93
94
91
(21, 23)
(21–25)
(21, 22)
19
20
21
a
b
c
d
92
94
93
91
(21)
(21)
a
b
c
d
93
91
93
87
a
b
c
d
88
96
89
97
a
b
c
d
98
92
90
88
a
b
c
d
93
86
89
95
(21, 25)
6
7
a
b
c
d
95
86
96
93
(21, 23, 25)
(21–24)
22
23
a
b
c
d
93
86
92
93
(24)
a
b
c
d
92
94
89
94
a
b
c
d
87
97
91
94
(22, 25)
8
9
a
b
c
d
93
90
97
92
(22, 23)
(22, 23)
(22)
24
25
26
a
b
c
d
86
93
95
87
(21)
(22, 25)
(24)
a
b
c
d
91
97
93
90
a
b
c
d
93
92
88
91
10
a
b
c
d
92
91
97
93
a
b
c
d
94
98
87
96
11
a
b
c
d
93
95
91
98
(22)
27
a
b
c
d
86
92
97
90
(25)
12
13
a
b
c
d
92
94
94
92
(22)
(22)
28
29
a
b
c
d
87
94
92
91
(26)
(26)
a
b
c
d
95
89
91
93
a
b
c
d
95
96
93
94
(Continued)

88 H.R. Shaterian et al.
Table 2. Continued.
Aldehydes
Thiols or Yield
dithiols
Aldehydes
and ketones
Thiols or Yield
dithiols
Entry
and ketones
(%)a
Refb
Entry
30
(%)a
Refb
14
a
b
c
d
95
85
96
93
(23)
a
b
c
d
94
90
89
92
(26)
15
16
a
b
c
d
88
96
90
89
(23)
31
32
a
b
c
d
93
93
90
89
(26)
(21)
a
b
c
d
94
92
93
87
(21, 22, 24, 25)
a
b
c
d
96
98
92
95
Notes: a: 1,3-Propanedithiol; b: 1,2-ethanedithiol; c: benzyl thiol; d: ethyl thiol.
aYields refer to the pure isolated products. The structure all known products were confirmed by comparison of their spectral data (FT-IR,
NMR) with those of known samples (21–26). bLiterature references for known products.
R1
C O
R2
R1
R2
S
S
–H
H
P2O5/SiO2
(P2O5/SiO2)
R1
R2
R1
S
C O
R2
S
HSCH2CH2SH
–H2O
H
(P2O5/SiO2)
R1
R2
O
SCH2CH2SH
Scheme 2. The suggested mechanism for the conversion of carbonyl compounds to their
corresponding 1,3-dithiolanes using 1,2-ethandithiol in the presence of P2O5/SiO2 as catalyst.
According to the literature survey (23) and our results, we suggest the following mecha-
nism for the conversion of carbonyl compounds to their corresponding 1,3-dithiolanes using
1,2-ethandithiol in the presence of P2O5/SiO2 as catalyst (Scheme 2).
In order to explore the ability of P2O5/SiO2 act as a selective catalyst, we carried out a com-
petitive S,S-acetalization reaction using an equimolar mixture of benzaldehyde (1.0 mmol) and
4-phenylbutan-2-one or acetophenone (1.0 mmol) with 1,2-ethanedithiol (1 mmol) (Scheme 3).
Employing this catalytic system, the highly selective conversion of benzaldehyde to 2-phenyl-1,3-
dithiolane was observed, whereas ketones were intact. These observations show that the presented
method is potentially applicable for the chemoselective conversion of aldehydes to corresponding
S,S-acetals in the presence of ketone functions in multi-functional molecules.

Journal of Sulfur Chemistry 89
S
S
O
100%
S
H
Catalyst (5 mg)
1,2-ethanedithiol (1mmol)
+
+
r.t.
immediately
O
S
0%
Ph
CH3
Ph
CH3
O
S
100%
0%
H
S
Catalyst (5 mg)
1,2-ethanedithiol (1mmol)
+
+
r.t.
S
O
immediately
S
CH3
CH3
Scheme3. ChemoselectiveconversionofaldehydestocorrespondingS,S-acetalsinthepresence
of ketones.
100
98
96
95
94
100
90
80
70
60
50
92
92
92
90
88
Product
yield %
40
30
20
10
Catalyst
yield %
0
1
2
3
4
5
6
7
Number of runs
Figure 1. Recycling of the catalyst.
We also investigated the recycling of the catalyst under solvent-free conditions using a model
reaction of benzaldehyde (2 mmol) and 1,2-ethanedithiol (2.2 mmol) solvent-free at ambient tem-
perature (Table 2, Entry 1b). After completion of reaction as checked by TLC, it was diluted
with n-hexane and the catalyst was filtered off .The catalyst was washed twice (2 × 5 ml) with
n-hexane. The recovered catalyst was dried in vacuum and was used for the subsequent cat-
alytic runs. The catalytic system worked well up to five catalytic runs without loss its activities
(Figure 1). Thus, this solid heterogeneous acidic catalyst is safe, easy to handle, environmentally
benign, presents fewer disposal problems and is stable in reaction media. It has the advantage

90 H.R. Shaterian et al.
of being easily removed from the organic product by simple filtration and also this reagent has
improved storage stability in moisture in comparison to P2O5, which is very sensitive to moisture
and also it showed much more reactivity than unsupported P2O5 (27).
3. Conclusion
In summary, we have developed a simple and efficient method for the S,S-acetalization of carbonyl
compounds using a catalytic amount of silica supported phosphorus pentoxide immediately under
solvent-free conditions at ambient temperature. The catalyst can be recovered and reused for
several times. This catalytic reaction show several advantages such as requirement of very low
amount of catalyst, high yields, cost-effective, highly efficient, chemoselective, convenient and
mild reaction conditions.
4. Experimental
All reagents were purchased from Merck and Aldrich and used without further purification.
P2O5/SiO2 was prepared according to the reported procedure (18). All yields refer to isolated
products after purification. Products were characterized by comparison with authentic samples
and by spectroscopy data (FT-IR, NMR spectra). The NMR spectra were recorded on a Bruker
Avance 300 MHz instrument. The spectra were measured in CDCl3 relative to TMS (0.00 ppm).
FT-IR spectra were recorded on a Perkin-Elmer 781 spectrophotometer. TLC was performed on
Silica-gel polygram SIL G/UV 254 plates.
4.1. S,S-Thioacetalization of carbonyl compounds (general procedure)
Amixtureofcarbonylcompounds(2 mmol), dithiol(2.2 mmol)orthiol(4.4 mmol)andP2O5/SiO2
(5 mg) was stirred at ambient temperature. After completion of reaction as checked by TLC, it
was diluted with n-hexane and the catalyst was filtered off. The filtrate solution (50 ml) was
washed with aqueous 10% NaOH (2 × 10 ml) solution and then dried over anhydrous Na2SO4.
The solvent was evaporated by rotary evaporator and the crude product was purified through a
column of silica gel (n-hexane:EtOAc, 80:20) to obtain the pure product. All the products were
characterized by comparison of their spectroscopic and physical data with the authentic samples
(21–26).
4.2. Spectral data of two representative products
4.2.1. S,S-Acetals of 28a
FT-IR (KBr, cm−1): 2925, 2925, 1675, 1415, 1232, 1158, 925, 800. 1H NMR (CDCl3, 300 MHz):
δ (ppm): 8.25 (d, 2H, J = 8.31 Hz), 7.88 (d, 2H, J = 8.25 Hz), 7.81 (d, 2H, J = 6.60 Hz), 5.76
(s, 2H), 3.15 (t, 4H, J = 5.56 Hz), 2.26–2.23 (m, 4H), 2.11–2.04 (m, 4H).
4.2.2. S,S-Acetals of 29a
FT-IR (KBr, cm−1): 2925, 1662, 1492, 1363, 1274, 1205, 1125, 983, 912, 855. 1H NMR (CDCl3,
300 MHz): δ (ppm): 9.42 (s, 1H), 8.25–8.21 (m, 1H), 8.18–8.14 (m, 1H), 7.92–7.84 (m, 2H), 3.24
(t, 2H, J = 9.64 Hz), 3.20 (d, 1H, J = 6.44 Hz), 2.86–2.77 (m, 2H), 2.20–2.08 (m, 2H).

Journal of Sulfur Chemistry 91
Acknowledgement
We are thankful to the University of Sistan and Baluchestan Research Council for the partial support of this work.
References
(1) Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis; Wiley: New York, 1999.
(2) Surya, K.D. Tetrahedron Lett. 2004, 45, 1035–1036.
(3) Seebach, D. Angew. Chem., Int. Ed. Engl. 1969, 8, 639–649.
(4) Pettit, G.R.; Van Tamelen, E.E. Org. React. 1962, 12, 356–527.
(5) Ralls, J.W.; Dobson, R.M.; Reigel, B. J. Am. Chem. Soc. 1949, 71, 3320–3325.
(6) Fieser, L.F. J. Am. Chem. Soc. 1954, 76, 1945–1947.
(7) Ong, B.S. Tetrahedron Lett. 1980, 21, 4225–4228.
(8) Kumar, V.; Dey, S. Tetrahedron Lett. 1983, 24, 1289–1292.
(9) Corey, E.J.; Shimoji, K. Tetrahedron Lett. 1983, 24, 169–172.
(10) Garlaschelli, L.; Vidari, G. Tetrahedron Lett. 1990, 31, 5815–5816.
(11) (a) Corbridge, D.E.C. Phosphorus: An Outline of its Chemistry, Biochemistry, and Technology, 5th ed.; Elsevier:
Amsterdam, The Netherlands, 1978; (b) Patnaik, P.A. Comprehensive Guide to the Hazardous Properties of Chemical
Substances; John Wiley & Sons: New York, 2007.
(12) Eaton, P.E.; Carlson, G.R.; Lee, J.T. J. Org. Chem. 1973, 38, 4071–4073.
(13) Eshghi, H.; Rafei, M.; Karimi, M.H. Synth. Commun. 2001, 31, 771–774.
(14) Eshghi, H.; Rafei, M.; Gordi, Z.; Bohloli, M. J. Chem. Res. (S) 2003, 763–764.
(15) Hajipour, A.R.; Ruoho, A.E. Tetrahedron Lett. 2005, 46, 8307–8310.
(16) Eshghi, H.; Hassankhani, A. Synth. Commun. 2006, 36, 2211–2216.
(17) Hasaninejad, A.R.; Zare, A.; Sharghi, H.; Niknam, K.; Shekouhy, M. Arkivoc 2007, 14, 39–50.
(18) Hasaninejad, A.R.; Zare, A.; Sharghi, H.; Shekouhy, M. Arkivoc. 2008, 11, 64–74.
(19) Tamaddon, F.; Khoobi, M.; Keshavarz, E. Tetrahedron Lett. 2007, 48, 3643–3646.
(20) (a) Shaterian, H.R.; Yarahmadi, H. Tetrahedron Lett. 2008, 49, 1297–1300; (b) Shaterian, H.R.; Yarahmadi, H.
Arkivoc 2008, 2, 105–114; (c) Shaterian, H.R.; Ghashang, M.; Hassankhani, A. Dyes Pigm. 2008, 76, 564–568;
(d) Shaterian, H.R.; Hosseinian, A.; Ghashang, M. Synth. Commun. 2008, 38, 4097–4106; (e) Shaterian, H.R.;
Hosseinian, A.; Ghashang, M. Synth. Commun. 2008, 19, 3375–3389.
(21) Shaterian, H.R.; Ahmadian, H.R.; Ghashang, M.; Doostmohammadi, R.;Yarahmadi, H. Phosphorus, Sulfur, Silicon
2008, 183, 1099–1108.
(22) Wu, Y.C.; Zhu, J. J. Org. Chem. 2008, 73, 9522–9524.
(23) Hajipour, A.R.; Azizi, G.; Ruohoa, A.E. Synlett. 2009, 12, 1974–1978.
(24) Gupta, N.; Sonu Kad, G.L.; Singh, J. Catal. Commun. 2007, 8, 1323–1328.
(25) Karimi, B.; Khalkhali, M. J. Mol. Catal. A-Chem. 2007, 271, 75–79.
(26) Goswami, S.; Maity, A.C. Tetrahedron Lett. 2008, 49, 3092–3096.
(27) (a) Tamaddon, F.; Khoobi, M.; Keshavarz, E. Tetrahedron Lett., 2007, 48, 3643; (b) Hasaninejad, A.; Zare, A.;
Sharghi, H.; Shekouhya, M. Arkivoc, 2008, xi, 64–74.

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