Journal of the Chinese Chemical Society, 2007, 54, 1017-1020 1017

Catalytic Method for Synthesis of Aspirin by a Green, Efficient and

Recyclable Solid Acid Catalyst (Preyssler’s Anion) at Room Temperature

Fatemeh F. Bamoharram,a* Majid M. Heravi,b* Mina Roshani,a Ali Ghariba and Manouchehr Jahangira
a
Department of Chemistry, Islamic Azad University-Mashhad Branch, Mashhad, Iran
b
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran

Synthesis of aspirin at room temperature via O-acetylation of salicylic acid in the presence of Preyssler
type heteropolyacids has been investigated in order to contribute toward clean technology, which is the
most important need of the society. All of the catalysts are recyclable and reusable.

Keywords: Preyssler; Catalyst; Heteropolyacid; Aspirin; Green catalyst.

INTRODUCTION the phosphate groups. The sodium cation is nonlabile on

the NMR time scale and appears to be essential for the an-
It is known that a number of aliphatic and aromatic al- ion synthesis. The presence of the sodium cation reduces
cohols react with a range of acids to give esters in a reaction the overall anion symmetry from D5h to C5v. This anion is
catalyzed by acids.1-6 Generally, in acid-catalyzed reac- even more robust than [P8W48 O184 ] (pH stability range
tions, solid acid catalysts are suitable. Many research groups 0-12). A top and side view of the Preyssler structure is
continue to explore the catalytic properties of strong solid shown schematically in Fig. 1.
acids in an attempt to eliminate environmental concerns Important advantages of this polyanion over the Keggin
caused by the use of liquid acids.7,8 heteropolyacids are: a) more thermal stability, b) more
Heteropolyacids (HPAs) are strong Bronsted acids hydrolytic stability (pH = 0-12), and c) larger number of
composed of heteropolyanions and protons as the counter- protons. These properties are very important in catalytic
cations and are used to replace environmentally harmful processes especially in synthesis of drugs.
liquid acid catalysts.9-11 These bulk compounds catalyze Aspirin is an important drug worldwide and conven-
many reactions much more effectively than the conven- tionally is prepared by an acid-catalyzed process. The most
tional protonic acids, such as sulfuric acid and nitric acid, widely employed catalysts for this reaction are concen-
and they can even be better than BF3 etherate. It has been trated sulfuric and phosphoric acids.15 Both acids are
proposed that such a high catalytic efficiency of these het- strongly corrosive and must be handled with care. Re-
eropolyacids is mainly due to specific properties of the het- cently, an alternative method was reported in which aspirin
eropolyanion with weak basicity and great softness, in ad- could be prepared using acetyl chloride-pyridine as the ac-
dition to the large molecular size of the heteropolyanion. etylating agent via esterification reaction at low tempera-
Among HPAs, Keggins-type HPAs have attracted much
interest since they possess strong acidity. However, only a
few reports have been published on the use of Preyssler’s
anion heteropolyacid.12 In some cases there have been re-
ports of no catalytic activity of Preyssler’s anion.13 For the
first time the exact structure of this polyanion was found in
1985.14 Structure of the anion [NaP5W30O110]14- is a cyclic
assembly of five {PW6O22} groups. The unusual 5-fold sym-
metry of this anion is achieved by fusion of five {PW6O22}
groups. The central sodium ion lies not on the equator of Fig. 1. Structure of Preyssler’s catalyst (left: top view,
the anion but in a plane roughly defined by oxygen atoms of right: side view).

* Corresponding author. E-mail: fbamoharram@mshdiau.ac.ir; mmh1331@yahoo.com

1018 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 Bamoharram et al.

tures.16 However the obnoxious and irritating odors of Table 1. Yields of aspirin in O-acetylation of salicylic acid with
these reagents make them unsuitable for industrial scale various heteropolyacid catalysts at room temperature
operations. Keggin-type heteropolyacids and other deriva- Entry Time (min) Catalyst %Yield
tives have also been reported to be efficient catalysts for the 1 10 H14[NaP5W30O110] 78
esterification reactions.17,18 It appears from the open litera- 2 10 H14[NaP5W29MoO110] 69
ture that attention has been focused on obtaining maximum 3 15 H4[SiMo12O40] 57
4 15 H4[SiW12O40] 61
yield rather than maximum selectivity and greenness.
5 15 H3[PW12O40] 59
In continuation of our research on the synthesis and 6 15 H3[PMo12O40] 47
application of heteropolyanions in organic syntheses,19-22 7 10 H14[NaP5W30O110]/SiO2(%10) 20
we now report the application of a novel and recyclable 8 10 H14[NaP5W30O110]/SiO2(%20) 35
solid acid catalyst, Preyssler catalyst, with exclusive prop- 9 10 H14[NaP5W30O110]/SiO2(%30) 62
10 10 H14[NaP5W30O110]/SiO2(%40) 68
erties surpassing the Keggin heteropolyacids, for highly 11 10 H14[NaP5W30O110]/SiO2(%50) 73
selective and rapid liquid-phase O-acetylation of salicylic
acid in order to synthesize aspirin at room temperature.
Recently we have been exploring the application of the heteropolyacid with tungsten atom shows higher acidity
Preyssler catalyst,19,20 and the major aim described in this than a molybdenum analogue.18 When tungsten is replaced
work is also the design and extension of the applications of by molybdenum, the negative charge on the oxygen atoms
the Preyssler catalyst. increases which leads to a decrease in acidity.18,23
In homogeneous conditions higher activity of Preyssler
is attributed to the higher number of acidic protons. The re-
RESULTS AND DISCUSSIONS sults point out that the catalytic effectiveness may be en-
hanced as the number of tungsten atoms (or the number of
Highly selective acetylation of salicylic acid with protons) is increased. Both possibilities are logical. The
acetic anhydride at room temperature has been carried out large anion with the larger number of tungsten atoms also
for the first time by an inexpensive, recyclable, and easily provides many “sites” on the oval-shaped molecule that are
prepared Preyssler’s anion. The performance of this poly- likely to render the catalyst effective.
anion in different forms was compared with Keggin types: It is also interesting to consider that, like the Keggin
H4[SiMo12O40], H4[SiW12O40], H3[PW12O40] and H3[PMo12O40] types, by replacing one of the tungsten atoms of H14 -P5
and H2SO4. with molybdenum in H14-P5Mo, the yield of aspirin de-
In all cases, the heteropolyacids with Preyssler struc- creases. By replacing tungsten with molybdenum, symme-
tures show higher activity in esterification reactions com- try is also decreased, and this distortion may affect the na-
pared with Keggin type heteropolyacids and H2SO4. The ture of polyacid and acidity of a heteropolyacid. However,
yields of O-acetylation of salicylic acid into aspirin with the results show that among all of the heteropolyacid cata-
various heteropolyacids are given in Table 1. In the pres- lysts, H14–P5 shows the highest yield.
ence of H14-P5, salicylic acid was converted to aspirin with Compared with mineral acids, such as H2SO4, H14-P5
acetic anhydride in 78% yield with 100% selectivity at is more active and shows a higher selectivity and a mini-
room temperature in 10 minutes (entry 1). H14P5-Mo has mizing of side reactions. Fig. 2 gives the yield of aspirin in
lower activity than H14 -P5. It leads to 69% aspirin with esterification obtained under the same conditions and over
100% selectivity after 10 minutes (entry 2). H2SO4 and H14-P5. It can be seen from the Figure that the
Catalytic activity of Keggin heteropolyacids such as activity of H14–P5 is higher than that of sulfuric acid. In or-
H4[SiMo12O40], H4[SiW12O40], H3[PW12O40] and H3[PMo12O40], der to achieve heterogeneous catalysis, the esterification
was less than Preyssler’s anion. They lead to 57, 61, 59 and was carried out by H14P5/SiO2 with different loadings. Cat-
47%, respectively, with 90-95% selectivity (entries 3-6). alyst loading was varied from 10% to 50%. As illustrated in
The yield of aspirin in the presence of silica-supported Table 1, the yield of aspirin increased with an increase in
Preyssler increased from 19% to 73% with an increase in catalyst loading from 10% to 50%. It is attributed to the in-
catalyst loading from 10% to 50% (entries 7-11). It is clear crease in the total number of available active catalytic sites
that esterification yield depends on the nature of the acid. A for the reaction. For heterogeneous catalyzed reactions, it
Catalytic Method for Synthesis of Aspirin J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1019

is not very good to use more than 50% (w/w) catalyst load- neously catalyzed processes, is a well-known difficulty in
ing, and hence it can be concluded that the optimal catalyst catalyst recovery and recycling. The recycling of HPA cat-
loading based on the current findings was 50% (w/w). In all alysts is the key issue to their application. In both homoge-
cases, the supported polyacid is less active than that of the neous and heterogeneous conditions Preyssler catalyst can
non-supported. be easily recovered and recycled. IR spectrum of the recov-
Oxide supports such as SiO2 have a large surface area ered solid catalyst indicated that the catalyst can be recov-
and a peculiar pore structure. In the process of adsorption, ered without structural degradation. The recovered solids
surface hydroxyl groups play a very important role in ad- were reused as catalyst for new reactions. The recovery had
sorbing different ions from solution. On the other hand, al- only slightly decreased its catalytic activity and yield (2-
though SiO2-supported HPAs are more stable, the interac- 5%), pointing to the stability and retention capability of this
tion of HPA and the OH surface groups can bring about the useful polyanion.
decrease of acidity and redox property of HPAs.22 On the
basis of the obtained results, we can suggest that there is a
direct interaction between Preyssler and the surface of sup- EXPERIMENTAL SECTION
port. So it is reasonable to assume that the adsorption of
Preyssler on support could be ascribed to an acid-base reac- Materials
tion. Acetic anhydride, salicylic acid, sodium tungstate
It is well known that heteropolyacid is an acid with dihydrate, molybdotungstate dihydrate, orthophosphoric
higher acid strength. In view of the difference in softness or acid, sulfuric acid, ethyl acetate, potassium chloride and
hardness of hydroxyl of various supports and HPAs, the re- silica gel were commercially available.
action between heteropolyanion and hydroxyl on the sup-
port may proceed according to a two-step ligand exchange Instruments
1
mechanism (hard-hard reaction) or coordination of pro- H-NMR spectra were recorded on an FT-NMR Bruker
tonated surface hydroxyl with heteropolyanion in solution 100 MHz Aspect 3000 spectrometer. IR spectra were ob-
to form an outer sphere surface complex instead of ex- tained with a Buck 500 scientific spectrometer (KBr pel-
change reaction (hard-soft reaction). lets).

Catalyst Preparation
REUSABILITY OF PREYSSLER CATALYST Keggin type heteropolyacids were acquired from
commercial sources. Potassium salt of Preyssler’s anion
The major problem, limiting the utility of homoge- was prepared according to the procedure developed in our
laboratory.20 The free acid was prepared by passage of a
solution of the potassium salt in water through a column
of Dowex 50wx8 in the H+ form and evaporation of the
elute to dryness under vacuum.20 Molybdenum substituted
Preyssler heteropolyanion, H14-P5Mo, was prepared as fol-
lows: 2.8 g (0.169 mol) Na2WO4 .2H2O and 2 g (0.008 mol)
Na2MoO4.2H2O were dissolved in 35 mL of water and
mixed at 60 °C for 30 min. Then this solution was cooled to
room temperature, and 25 mL of concentrated phosphoric
acid was added. The resulting yellow solution was refluxed
for 18 h. The solution was brought to room temperature, di-
luted with water and then during stirring, 10 g of KCl was
added. The mixture was stirred and then heated up to dry-
ness. The product was dissolved in warm water and upon
Fig. 2. Yield of aspirin as a function of time in the pres- cooling to room temperature yellow crystals formed. The
ence of H14[NaP5W30O110] and H2SO4. acidic form of molybdenum substituted heteropolyacid
1020 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 Bamoharram et al.

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M.; Gharib, A. Appl. Catal. 2006, 302, 42. (b) Alizadeh,
Preyssler catalyst is an effective solid acid catalyst for M.-H.; Razavi, H.; Farrash Bamoharram, F.; Hassanzadeh,
preparation of aspirin. Among various forms of Preyssler M.-H. Kinet. Catal. 2003, 44, 524.
20. Bamoharram, F.-F.; Roshani, M.; Alizadeh, M.-H.; Razavi,
catalyst used, the H14 -P5 shows higher activity than the
H.; Moghayadi, M. J. Brazilian Chem. Soc. 2006, 17, 505.
other forms of Preyssler, as well as Keggin types and sulfu-
21. Alizadeh, M.-H.; Razavi, H.; Bamoharram, F.-F.; Daneshvar,
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Preyssler’s anion for some reactions that require a solid cat- 22. (a) Bamoharram, F.-F.; Heravi, M.-M.; Roshani, M.; Gharib,
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