Phospho sulfonic acid as an efficient and recyclable solid acid catalyst for the solvent-free preparation of acylals

Article abstract of DOI:10.1016/j.tetlet.2014.07.115

Phospho sulfonic acid (PSA) acts as a highly effective and reusable catalyst for the chemo-selective protection of aldehydes with acetic anhydride under solvent-free conditions. The desirable features of this new catalytic methodology include its sustaina

Full text of DOI:10.1016/j.tetlet.2014.07.115

Tetrahedron Letters 55 (2014) 5373–5376
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Phospho sulfonic acid as an efficient and recyclable solid acid
catalyst for the solvent-free preparation of acylals
⇑
Reddi Mohan Naidu Kalla, Huiju Park, Trinh Thi Kim Hoang, Il Kim
BK21 PLUS Center for Advanced Chemical Technology, Department of Polymer Science and Engineering, Pusan National University, Busan 609-735, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Phospho sulfonic acid (PSA) acts as a highly effective and reusable catalyst for the chemo-selective
protection of aldehydes with acetic anhydride under solvent-free conditions. The desirable features of
this new catalytic methodology include its sustainability, effectiveness in the absence of solvent, a facile
work-up procedure, and economic viability. PSA is fully characterized by Fourier transform infrared spec-
troscopy, wide-angle X-ray scattering analysis, and scanning electron microscopy with energy dispersive
X-ray spectroscopy. The catalyst can be reused several times without significant loss of activity. In
addition, no chromatographic separations are needed to obtain the desired products.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 26 May 2014
Revised 21 July 2014
Accepted 28 July 2014
Available online 8 August 2014
Keywords:
Acylal
Solid acid catalysis
Phospho sulfonic acid
Solvent-free method
Introduction
ment of alternate milder and environmentally sustainable proce-
dures for the preparation of acylals.
The protection of carbonyl group is an important step for a
number of synthetic protocols. Reagents commonly used for pro-
tecting carbonyl groups include 2-mercaptoethanol,1 ethane
dithiol,2 trialkyl orthoformate,3 acetic anhydride,4 and alcohols.5
Among these reagents, acetic anhydride is widely used for its
robustness under neutral, basic, or acidic conditions. Acylals serve
as important precursors for asymmetric allylic alkylation reac-
tions,6 drug synthesis,7 and syntheses of 1-acetoxydienes and
2,2-dichlorovinylacetates (used for Diels–Alder reactions).8,9
Furthermore, acylals may also be used as cross-linking agents for
cellulose in cotton.10 The preparation of acylals is of growing inter-
est given their wide range of applications. Direct methods for
preparing acylals include condensations of carbonyl compounds
with acetic anhydride in the presence of protic acids,11–13 or Lewis
acids14–19 Moreover, reusable heterogeneous catalysts, including
Keggin heteropolyacids,20 solid silica sulfuric acid,21 and nano-
ordered MCM-41-SO3H22 have also been reported. The majority
of Lewis acids are highly moisture sensitive; therefore, they are
required in excess quantities. Because of this, the reaction progress
is not satisfactory and byproducts are formed. Moreover, though
other methods show varying degrees of success, they have limita-
tions such as prolonged reaction times, low yields, requirement of
excess reagents or catalysts, use of toxic solvents, and laborious
work-up procedures. Therefore, there is a need for the develop-
Solid acids are emerging materials for the development of sim-
ple and environment friendly synthetic processes. Recently, most
of these reactions were carried out using protic or Lewis acids.
However, the use of these materials may contribute to environ-
mental pollution. To overcome this problem, recoverable, solid
acids have been developed to catalyze a variety of reactions. Solid
acid catalysis plays a key role in controlling environmental pollu-
tion by reducing the release of waste while strengthening eco-
nomic development of the chemical industry.23 Catalysts are
simply removed from the reaction mixture by filtration or centrifu-
gation without the need for neutralization, thereby enabling more
eco-friendly processes. Phospho sulfonic acid (PSA) is a non-vola-
tile, non-corrosive, recyclable, and eco-friendly solid acid catalyst.
It has been used for the synthesis of indazolo [1,2-b]-phthalazine-
triones and bis-(4-hydroxycoumarin-3-yl)methanes.24,25
The recent development of neat (solvent-free) reactions based
on novel, simple, and efficient synthetic approaches holds great
promise for chemists. In addition, eco-friendly, less laborious
methodologies for the synthesis of various organic compounds
(i.e., heterocyclic and non-heterocyclic compounds) are also being
developed. The most important goals of ‘green chemistry’ include
avoidance of toxic reagents, organic solvents and the reduction of
costs associated with organic synthesis. For these reasons, and
because of our continued interest in the development of efficient,
economical, and new methodologies,26–29 we here in report, the
use of PSA as an environmentally benign and recyclable solid acid
catalyst for the high-yielding, solvent-free synthesis of acylals
(Scheme 1).
⇑
Corresponding author.
http://dx.doi.org/10.1016/j.tetlet.2014.07.115
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

5374
R.M.N. Kalla et al. / Tetrahedron Letters 55 (2014) 5373–5376
Figure 1. FT-IR spectra of (a) DHAMP and (b) PSA.
Scheme 1. PSA-catalyzed synthesis of acylals.
Results and discussion
Synthesis and characterization of PSA
A 25 mL reaction flask was equipped with a constant-pressure
dropping funnel. The gas outlet was connected to a vacuum system
through an alkali solution trap. Diammonium hydrogen phosphate
(DHAMP; 7.5 mmol) was added to the flask, and chlorosulfonic
acid (22.5 mmol) in CH2Cl2 (10 mL) was added drop-wise over a
period of 15 min at room temperature. After the addition, the mix-
ture was stirred for 2 h, and the residual HCl was eliminated by
suction. The mixture was then washed with CH2Cl2, and was
obtained as a solid, white powder (Scheme 2). The characterization
of the new PSA is described below.
To evaluate the extent to which the sulfonic acid group was
incorporated onto DHAMP, Fourier transform infrared (FT-IR) spec-
tra of the individual DHAMP and PSA samples were compared
(Fig. 1). The FT-IR spectrum of DHAMP shows the P@O stretching
frequency at 1034 cmÀ1 while that of PSA shows the analogous fre-
quency at 1032 cmÀ1. The sharp peak at 3246 cmÀ1 corresponds to
the OAH stretch of the SO3H group. The O@S@O asymmetric and
symmetric stretching peaks at 1232 and 1102 cmÀ1, respectively,
and the SAO stretching peak at 767 cmÀ1 precisely confirmed the
presence of the SO3 group linkage. Furthermore, there are no peaks
at 1232 and 1102 cmÀ1 in the spectrum of DHAMP, indicating that
sulfonation has occurred to produce PSA.
The X-ray powder diffraction (XRD) analysis shows that the dif-
fraction pattern of the DHAMP (Fig. 2a) is completely different
from that of PSA (Fig. 2b) as a result of sulfonation within the for-
mer. The diffraction pattern showed peaks characteristic of PSA,
demonstrating good crystallinity. Moreover, the peaks at
2h = 25°–28° are characteristic of the SO3 group, confirming that
PSA contains the SO3 functionality. In addition, there are no peaks
beyond 28° in Figure 2b, providing further evidence of sulfonation.
The scanning electron microscopy (SEM) image of DHAMP (see
Fig. S1 in Supporting information) exhibits an irregular morphol-
ogy, bearing regions of both high and low surface areas, while that
of PSA shows a regular, cubic shape. The sulfonation was also con-
Figure 2. XRD patterns of (a) DHAMP and (b) PSA.
firmed by energy dispersive X-ray (EDX) analysis (inset in Fig. S1),
which showed the presence of both sulfur and phosphorus.
PSA-catalyzed synthesis of acylals
To standardize the conditions, a model reaction using benzalde-
hyde and acetic anhydride was carried out using different cata-
lysts, and the results are presented in Table 1. The preliminary
experiment was performed neat in the absence of catalyst at room
temperature for 24 h; no product was formed (entry 1). A number
of trials using ZrOCl2, ZrOCl2–SiO2, BF3ÁSiO2, ClSO3H, KHSO4, or
oxone as catalysts gave relatively low product yields (entries 2–
6). The reaction performed with DHAMP proved unproductive
Table 1
Synthesis of
1 using a variety of catalysts in the absence of solvent at room
temperaturea
Entry
Catalyst
Catalyst amount (mol %)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
Catalyst free
ZrOCl2
ZrOCl2ÁSiO2
BF3ÁSiO2
KHSO4
Oxone
ClSO3H
(NH4)2HPO4
PSA
PSA
PSA
PSA
PSA
—
5
5
5
5
5
1
5
1
1.5
2
2.5
3
24
1
0.3
0.4
2
nrc
65
78
80
58
62
75
nrc
85
90
94
99
99
2
0.1
12
0.1
0.1
0.1
0.1
0.1
9
10
11
12
13
a
Reaction conditions:30 benzaldehyde = 1 mmol, acetic anhydride = 1 mmol, and
PSA = 2.5 mol %.
b
Isolated yield measured gravimetrically.
No reaction.
c
Scheme 2. Preparation of the solid acid PSA.

R.M.N. Kalla et al. / Tetrahedron Letters 55 (2014) 5373–5376
5375
Table 2
(entry 8). We then turned our attention toward the solid acid PSA
catalyst (entry 9), which was highly efficient, furnishing the
desired acylals product 1 in good yield. In order to compare the
effectiveness of the solvent-free system with those that use sol-
vents, the model reaction was re-examined with PSA in different
solvents (Table 2). When the reaction was performed in protic sol-
vents such as EtOH, MeOH, or H2O, the reactions proceeded slowly
and resulted in reduced product yields (Table 2, entries 2–4). How-
ever, in the case of aprotic solvents, such as CH2Cl2, CH3CN, CHCl3,
and THF, the reactions proceeded faster and resulted in higher
product yields.
Effects of various solvents on the yield of model reactiona
Entry
Solvent
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
Solvent-free
EtOH
MeOH
H2O
CH2Cl2
CH3CN
CHCl3
THF
6
60
80
90
50
45
50
35
99
65
60
55
85
88
91
90
a
Reaction conditions: benzaldehyde = 1 mmol, acetic anhydride = 1 mmol, and
To determine the optimum loading of PSA catalyst, the model
reaction was carried out neat using 1, 1.5, 2, 2.5, and 3 mol % PSA
at room temperature, affording product yields of 85%, 90%, 94%,
99%, and 99%, respectively. Increasing the amount of catalyst
beyond 2.5% had no apparent effect on the product yield.
PSA = 2.5 mol % at room temperature.
Table 3
Solvent-free PSA-catalyzed acetylation of various aldehydes with acetic anhydride at
With optimal conditions identified (Table 1, entry 12), we
sought to establish the generality of this methodology by perform-
ing reactions of other aldehydes with acetic anhydride neat in the
presence of 2.5 mol % PSA; the results are summarized in the
Table 3. All of the reactions proceeded smoothly resulting in good
product yields. Use of aliphatic aldehydes, as well as aromatic or
heterocyclic aldehydes containing either electron-donating or
withdrawing substituents, gave rise to the desired products.
The advantages of PSA were compared with those of other
reported homogeneous and heterogeneous catalysts for the acyla-
tion of aldehydes, and the results are represented in Table 4. In
2012, Tourani22 reported the synthesis of acylals by using MCM-
41-SO3H, wherein the heterogeneous catalyst loading was high
and the yield of the product was low compared to those in the case
of PSA. Recently, Zong et al.31 reported the use of PEG–SO3H acid
catalyst for the preparation of acylals. This method relies on the
use of PEG–SO3H (a biodegradable catalyst), and the reaction times
and product yields are low. Jin et al.32 reported using NH2SO3H as a
catalyst for the synthesis of acylals, which required reaction times
of almost 60 min and gave product yields of 90%. Compared to the
above-mentioned acid catalysts, the novel PSA described herein is
superior for the high-yielding synthesis of acylals, since it does not
require harsh reaction conditions, additional energy input (i.e.,
microwave or ultrasonication), nor laborious work-up procedures;
the full comparison is summarized in Table 4.
room temperaturea
Compound
R in R–CHO
Yield (%)
Time (min)
Mp (°C)
1
2
3
4
5
6
7
8
C6H5
2-Cl-C6H4
2-Br-C6H4
3-Br-C6H4
98
99
99
98
99
97
94
95
94
94
95
97
98
96
94
93
5
4
4
5
4
6
10
8
10
8
7
43–44
56–57
78–79
81–82
95–96
124–125
63–65
80–82
93–95
93–94
101–103
92–94
51–52
50–52
Oil
4-Br-C6H4
4-NO2-C6H4
4-Me-C6H4
4-OMe-C6H4
3,5-OMe-C6H3
4-OH-C6H4
2-OH-C6H4
2-OH-5-Br-C6H3
2-Furfural(C4H3O)
5-Me-2-Furfural(C4H2O)
CH(CH3)2
9
10
11
12
13
14
15
16
5
6
8
9
C5H13
10
Oil
a
Reaction conditions: benzaldehyde = 1 mmol, acetic anhydride = 1 mmol, and
PSA = 2.5 mol %.
Table 4
Comparison of various catalysts used for the synthesis of acylal 1a
Entry Catalyst (mg)
Solvent Time (min) Yield (%) Ref.
According to the obtained results, the following reaction mech-
anism is proposed for protection of aldehydes with acetic anhy-
dride in the presence of PSA (Scheme 3).22 Initially the
benzaldehyde reacts with acidic hydrogen from PSA to form a ben-
zylideneoxonium ion which reacts with acetic anhydride to form
an oxonium ion intermediate. This intermediate rearranges to form
an (S)-(acetoxy(phenyl)methyl)(acetyl) oxonium ion. The migra-
tion of proton to PSA results in acylal compounds.
1
2
3
4
5
6
MCM-41-SO3H (10) Neat
3
10
60
1
10
3
95
89
90
95
91
99
22
31
32
33
34
This work
PEG-SO3H (300)
NH2SO3H (200)
ZSM-5-SO3H (20)
SBSSA (4)
Neat
Neat
Neat
Neat
Neat
PSA (2.5 mol %)
a
Reaction conditions: benzaldehyde = 1 mmol and acetic anhydride = 1 mmol.
Scheme 3. Schematic reaction pathways for the PSA-catalyzed protection of aldehydes.

5376
R.M.N. Kalla et al. / Tetrahedron Letters 55 (2014) 5373–5376
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
07.115.
References and notes
1. Shirini, F.; Sadeghzadeh, P.; Abedini, M. Chin. Chem. Lett. 2009, 20, 1457.
2. Perin, G.; Mello, L. G.; Radatz, C. S.; Savegnago, L.; Alves, D.; Jacob, R. G.;
Lenardao, E. J. Tetrahedron Lett. 2010, 51, 4354.
3. Roy, A.; Rahman, M.; Das, S.; Kundu, D.; Kundu, S. K.; Majee, A.; Hajra, A. Synth.
Commun. 2009, 39, 590.
4. Khaligh, N. G.; Shirini, F. J. Mol. Catal. A: Chem. 2011, 348, 20.
5. Madabhushi, S.; Mallu, K. K. R.; Chinthala, N.; Beeram, C. R.; Vangipuram, V. S.
Tetrahedron Lett. 2012, 53, 697.
Figure 3. Effect of recycle of PSA on the yield of acylal 1.
6. Trost, B. M.; Lee, C. B. J. Am. Chem. Soc. 2001, 123, 12191.
7. Sandberg, M.; Sydnes, L. K. Org. Lett. 2000, 2, 687.
8. Held, H.; Rengstle, A.; Mayer, A., 5th ed. In Ullman’s Encyclopedia of Industrial
Chemistry; Gerhartz, W., Ed.; Wiley-VCH: New York, 1985; Vol. 1,.
9. Freeman, F.; Karcherski, E. M. J. Chem. Eng. Data 1977, 22, 355.
10. Frick, J. G., Jr.; Harper, R. J., Jr. J. Appl. Polym. Sci. 1984, 29, 1433.
11. Tomita, M.; Kikuchi, T.; Bessho, K.; Hori, T.; Inubushi, Y. Chem. Pharm. Bull.
1963, 11, 1484.
The reusability of PSA was also examined for the preparation of
acylals 1, formed from the reaction of acetic anhydride with benz-
aldehyde. The catalyst was easily recovered by adding ethanol to
the reaction mixture; the insoluble PSA could then be separated
by simple filtration, washed twice with ethanol (30 mL), and finally
dried under vacuum. The catalyst displayed good reusability after
10 runs (Fig. 3).
The identities of each of the products were confirmed using IR,
1H, and 13C NMR spectroscopy. In the 1H NMR spectra, the (AcO)2-
CHR proton signals appeared as singlets in the region dH 7.96–
7.58 ppm. The signals representing CH3 protons, which appear as
singlets between dH 2.12–2.08, were used to confirm formation
of the products. The remaining proton signals were observed in
the expected regions. In the 13C NMR spectra, the Ar–CH carbon
signals were observed in the region dC 84.3–90.1, confirming the
formation of acylals.20
12. Davey, W.; Gwilt, J. R. J. Chem. Soc. 1957, 1008.
13. Marshall, J. A.; Wuts, P. G. M. J. Org. Chem. 1977, 42, 1794.
14. Ziyaei, A.; Azizi, N.; Saidi, M. R. J. Mol. Catal. A: Chem. 2005, 238, 138.
15. Karimi, B.; Maleki, J. J. Org. Chem. 2003, 68, 4951.
16. Ghosh, R.; Maiti, S.; Chakraborty, A.; Halder, R. J. Mol. Catal. A: Chem. 2004, 215,
49.
17. Khazaei, A.; Manesh, A. A.; Rostami, A. H. A.; Alavi-Nik, Z. T. Asian J. Chem. 2011,
23, 614.
18. Hajipour, A. R.; Zarei, A.; Ruoho, A. E. Tetrahedron Lett. 2007, 48, 2881.
19. Mirjalili, B. F.; Zolfigol, M. A.; Bamoniri, A.; Amrollahi, M. A.; Sheikhan, N. Russ.
J. Org. Chem. 2007, 43, 852.
20. Romanelli, G.; Dimitroff, P.; Vazquez, P.; Autino, J. C. Eur. J. Chem. 2007, 4, 83.
21. Wu, H.; Shen, Y.; Fan, L.; Wan, Y.; Shai, D. Tetrahedron 2006, 62, 7995.
22. Tourani, H.; Naimi-Jamal, M. R.; Dekamin, M. G.; Amirnejad, M. C. R. Chimie
2012, 1072, 15.
23. Xie, W.; Wang, H.; Li, Hui Ind. Eng. Chem. Res. 2012, 51, 225.
24. Kiasat, A. R.; Mouradzadegun, A.; Saghanezhad, S. J. J. Serb. Chem. Soc. 2013, 78,
469.
Conclusion
25. Kiasat A. R.; Hemat-Alian, L. Res Chem. Intermed. doi: 10.1007/s11164-013-
1239-4.
A cost effective, mild, efficient, and reusable solid acid catalyst
has been developed for the synthesis of acylals from aldehydes
and acetic anhydride in the absence of solvent at room tempera-
ture. We show that a wide variety of aldehydes can be converted
to acetals in quantitative yields, and that the reaction is complete
within minutes. We also show that the catalyst can be reused up
to 10 times, and that it is superior to other reported heterogeneous
acid catalysts. Furthermore, we report the first characterizations of
PSA by IR, XRD, and SEM-EDX.
26. Kalla, R. M. N.; Byeon, S. J.; Heo, M. S.; Kim, Il Tetrahedron 2013, 69, 10544.
27. Kalla, R. M. N.; Choi, J. S.; Yoo, J. W.; Byeon, S. J.; Heo, M. S.; Kim, Il Eur. J. Med.
Chem. 2014, 76, 61.
28. Naidu, K. R. M.; Dadapeer, E.; Reddy, C. B.; Rao, A. J.; Reddy, C. S.; Raju, C. N.
Synth. Commun. 2011, 41, 3462.
29. Naidu, K. R. M.; Khalivulla, S. I.; Kumar, P. C. R.; Lasekan, O. Org. Commun. 2012,
5, 150.
30. To a mixture of aldehyde (1 mmol) and acetic anhydride (1 mmol) in a 25-mL
reaction flask equipped with
a magnetic stirring bar was added PSA
(2.5 mol %); the resulting reaction mixture was stirred at rt. After completion
of the reaction (monitored by TLC), the product was extracted with 20 mL of
ethanol. The solvent was evaporated under reduced pressure, and the obtained
solid was washed with hexane to afford the acylals. The insoluble PSA was
separated by simple filtration, washed twice with ethanol, and then dried
under vacuum before reuse. All previously known products afforded spectral
and physical data consistent with those reported in the literature for samples
prepared using previously reported methods. The new product was
characterized by their melting points, IR, 1H NMR, and 13C NMR spectra. A
detailed description of spectral data for all compounds 1–16 is given in
Supporting information (S.I).
Acknowledgments
This work was supported by the Basic Science Research Pro-
gram through the National Research Foundation of Korea funded
by the Ministry of Education (2012R1A1A2041315), and by the
Fusion Research Program for Green Technologies through the
National Research Foundation of Korea funded by the Ministry of
Science, ICT and Future Planning (2012M3C1A1054502). The
authors would also like to thank the BK21 PLUS Program for partial
financial support.
31. Zong, Y. X.; Wang, J. K.; Niu, Y. Y.; Li, Z. L.; Song, Z. E.; Quan, Z. J.; Wang, X. C.;
Yue, G. R.; Pan, Y. Chin. Chem. Lett. 2013, 24, 140.
32. Jin, T. S.; Sun, G.; Li, Y. W.; Li, T. S. Green Chem. 2002, 4, 255.
33. Massah, A. R.; Kalbasi, R. J.; Shafiei, A. Monatsh Chem. 2012, 143, 643.
34. Niknam, K.; Saberi, D.; Sefat, M. N. Tetrahedron Lett. 2009, 50, 4058.