Cation-exchange resin-catalysed acylations and esterifications in fine chemical and perfumery industries

Article abstract of DOI:10.1021/op0255229

Acylation and esterification reactions are typically carried out by using homogeneous acids as catalysts which can be profitably replaced with heterogeneous solid acid catalysts to develop green chemistry. Solid acids that give the desired level of activity but which can be easily removed from the reaction mixture with no residual inorganic contamination of the organic products offer obvious advantages over existing methods. This contribution is concerned with eco-friendly synthesis of some commercially valuable products such as p-methoxyacetophenone, dimethyl phthalate, diethyl phthalate, methyl anthranilate, methyl salicylate, and methyl p-hydroxybenzoate (methyl paraben). The specifications require the esters to be free of halide impurities on ppm level for perfumery use, and thus use of chlorine-containing agents or catalysts must be avoided. The following catalysts were evaluated: Amberlyst-36, Bayer K2441, Amberlyst-15, Dowex 50Wx8, Indion-130, Deloxane ASP, Filtrol-24 clay, K-10 Montmorrilonite clay, and sulphated zirconia. Anisole was acylated with acetic anhydride to get 100% selectivity of p-methoxyacetophenone, and Amberlyst-36 was found to be the most active and reusable catalyst. A kinetic model is also presented. Amberlyst-36 was also the most active catalyst for the esterification reactions.

Full text of DOI:10.1021/op0255229

Organic Process Research & Development 2002, 6, 706−713
Cation-Exchange Resin-Catalysed Acylations and Esterifications in Fine
Chemical and Perfumery Industries
G. D. Yadav* and M. S. M. Mujeebur Rahuman
Department of Chemical Engineering, UniVersity Institute of Chemical Technology (UICT), UniVersity of Mumbai,
Matunga, Mumbai - 400 019, India
Abstract:
homogeneous catalysts leads to several problems such as
corrosion of equipment, hazards of handling the corrosive
acids which are not reused, neutralization of the resulting
reaction mass, and generation of large quantities of dilute
dissolved salts, including loss of conversion, yield, and
selectivity. The biological oxygen demand (BOD), chemical
oxygen demand (COD), and total dissolved solids (TDS)
loads on effluent treatment plants become enormous. Since
the prices of these fine chemicals are very high and volumes
are low, no serious attempts were made until recently to
recover the catalyst or change the processes.
In the case of the Friedel-Crafts acylation, apart from
the fact that the use of homogeneous acids as catalysts is
polluting and hazardous, they have to be employed in at least
two molar excess quantities over the acylating agent. On the
industrial scale, the use of metal halide types of acids, which
are preferred catalysts, create workup and effluent problems.
Indeed, during the workup of acylation mixtures, the destruc-
tion of catalysts produces relatively large amounts of
hydrochloric acid in the off-gas or in the effluent. This
hydrochloric acid, which has to be disposed of, originates
both from the catalyst and also from acyl chloride employed
for the acylation. In addition, the corrosion problem due to
hydrochloric acid must be solved.
Acylation and esterification reactions are typically carried out
by using homogeneous acids as catalysts which can be profitably
replaced with heterogeneous solid acid catalysts to develop green
chemistry. Solid acids that give the desired level of activity but
which can be easily removed from the reaction mixture with
no residual inorganic contamination of the organic products
offer obvious advantages over existing methods. This contribu-
tion is concerned with eco-friendly synthesis of some com-
mercially valuable products such as p-methoxyacetophenone,
dimethyl phthalate, diethyl phthalate, methyl anthranilate,
methyl salicylate, and methyl p-hydroxybenzoate (methyl para-
ben). The specifications require the esters to be free of halide
impurities on ppm level for perfumery use, and thus use of
chlorine-containing agents or catalysts must be avoided. The
following catalysts were evaluated: Amberlyst-36, Bayer K2441,
Amberlyst-15, Dowex 50Wx8, Indion-130, Deloxane ASP, Fil-
trol-24 clay, K-10 Montmorrilonite clay, and sulphated zirconia.
Anisole was acylated with acetic anhydride to get 100%
selectivity of p-methoxyacetophenone, and Amberlyst-36 was
found to be the most active and reusable catalyst. A kinetic
model is also presented. Amberlyst-36 was also the most active
catalyst for the esterification reactions.
In the case of esterification reactions, the quantity of
catalyst is not stoichiometric except for aromatics containing
amine groups, but the same problems exist. Many synthetic
routes are available to make esters, but most of them are
not suitable to meet the stringent specifications.3-4 The most
acceptable method of making an ester is to react the
corresponding acid with an alcohol. The reaction is catalysed
by mineral acids and is reversible. Several methods are
available to drive the reaction towards the product. One of
them is to use an excess amount of alcohol, and another is
to remove the ester formed (or the coproduct water)
continuously.3,4
1. Introduction
Acylation and esterification reactions are commercially
important with productions ranging from a few hundred to
thousands of tonnes per year and are used to make ketones
and esters which serve as precursors or additives for a variety
of perfumes and flavours, pharmaceuticals, agrochemicals,
and polymers. The waste generated in these industries ranges
from 50 to 100 kg per kg of the desired product, depending
on the number of stages and the type of functionality
introduced in each stage. These esters and ketones are usually
manufactured in batch reactors, in a multicampaign process
plants, using homogeneous catalysts which include Lewis
acids (AlCl3, BF3, ZnCl2, TiCl4, SnCl4, FeCl3, SbF5, ZrCl4,
SiF4, etc.) and Brønsted acids (HF, H2SO4, HCl, H3PO4,
p-toluenesulphonic acid, dihydroxyfluoroboric acid, etc.),
including finely divided metals such as tin, manganese, silver,
copper, lead, and so forth in conjunction with a proper
reagent where the acid is generated in situ.1-3 The use of
Pressure from legislative and environmental bodies to-
gether with a growing awareness within the chemical industry
has led to a massive search for new eco-friendly processes
to replace unacceptable outdated reactions. Therefore, a
(1) Olah, G. A. Friedel-Crafts and Related Reactions; Wiley-Interscience:
New York, 1963-1964; Vols. I-IV.
(2) Olah, G. A. Friedel-Crafts Chemistry; Wiley-Interscience: New York,
* To whom correspondence should be addressed. Current address: Johansen-
Crosby Visiting Professor of Chemical Engineering, Department of Chemical
Engineering and Material Science, Michigan State University, East Lansing, MI-
48824. Telephone: (517) 355-9291. Fax: (517)-432-1105. E-mail: yadavg@
egr.msu.edu.
1973.
(3) Groggins, P. H. Unit Processes in Organic Synthesis; McGraw-Hill: New
York, 1952.
(4) Ogliaruso, M. A.; Wolfe, J. F. Synthesis of Carboxylic Acids, Esters and
Their DeriVatiVes; John Wiley: New York, 1991.
706
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Vol. 6, No. 5, 2002 / Organic Process Research & Development
10.1021/op0255229 CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/11/2002

Scheme 1. Acylation of anisole by acetic anhydride
Ag3(PO4), CF3COOH, BF3, HClO4, ortho- and polyphos-
phoric acid, ZnCl2, ClCH2COOH, I2, (ClCH2O)2O, (CF3-
CO)2O, and (C3F7CO)2O (see Table 1). The reactions are
typically conducted in a semibatch mode and are highly
exothermic. The reactant is mixed with the catalyst at low
temperature, and on complete addition of the second reagent,
the mass is refluxed over a period of time ranging from 3 to
12 h. The yields vary from 18 to 98%, and all processes are
polluting. On industrial scale, acylation has been carried out
using AlCl3 in chlorobenzene or methylene chloride as a
solvent and acetyl chloride as an acylating agent with 2.2
mol of AlCl3 per mol of acetyl chloride. There are some
recent reports on the reaction between anisole with acetic
anhydride or acid chloride in the presence of reusable
catalysts such as zeolites (H-ZSM5, H-Mordenite, H-â,
H-Y),41-44 clays and modified clays,45 and lanthanide bis-
(trifluoromethylsulphonyl) amides.46
Most esters have a pleasant odour reminiscent of floral
to fruity notes.47 Methyl anthranilate is one such interesting
ester that occurs naturally in several citrus fruits such as
orange and also in some flowers such as neroli and ylang
ylang. It finds more applications in flavouring rather than
perfumery compositions because of its odour, which re-
sembles the musty-fruity-dry floral note imitating concord
grapes and orange blossoms. It blends very well with several
flavours and finds more usage in the flavouring of soft drinks
and alcoholic beverages. The annual production of methyl
anthranilate was 186 t48 in 1964 and is currently estimated
to be over 1000 t. The major commercial routes are based
process that could be environmentally friendly and also
inexpensive, with respect to the disadvantages indicated
above, is the most desirable. Solid acids that give the desired
level of activity, but which can be easily removed from the
reaction mixture with no residual inorganic contamination
of the organic products, offer obvious advantage over existing
methods. Solid acids and superacids contain all their acidity
within the pores, are easy to handle, and can be fine-tuned
to get the desired activity and selectivity. The corrosion
problems are avoided, and the cost of materials of construc-
tion is substantially reduced. There are several choices of
reactor configurations, including modes of heat addition or
removal, and the overall process safety is enhanced. Among
several other researchers all over the world, considerable
progress has been made in achieving these goals through
recent developments in solid acid catalysis for fine chemical
synthesis in our laboratory5-20 including esterification8-14 and
acylation.15-20
This report is concerned with the eco-friendly synthesis
of some commercially valuable products such as p-meth-
oxyacetophenone, dimethyl phthalate, diethyl phthalate,
methyl anthranilate, methyl salicylate, and methyl p-hy-
droxybenzoate (methylparaben). The specifications require
that there be no halide impurities even on the ppm level for
perfumery use; thus, use of chlorine containing agents or
catalysts must be avoided. It is pertinent to review the
pertinent literature related to these products.
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809.
Acylation of anisole with a suitable acylating agent leads
to p-methoxy acetophenone (Scheme 1). p-Methoxyac-
etophenone has a sweet, somewhat harsh, haylike floral
animal note and is extensively used in soap formulations for
it is relatively stable in mild alkaline conditions and is also
used as a flavouring chemical. Acetyl chloride, acetic
anhydride and acetic acid have been used as acylating agents
in the presence of hazardous solvents such as nitromethane,
nitrobenzene, carbon disulphide, methylene chloride and a
variety of homogeneous Lewis acids and Brønsted acids
which include AlCl3, TiCl4, SnCl4, Cu, AgClO4, NaClO4,
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Desmurs, J.-R., Ratton, S., Eds.; Industrial Chemistry Library, Vol. 8;
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707

Table 1. Past work on synthesis of 4-methoxyacetophenone from anisole: use of polluting catalysts or hazardous solventsa
acylating
catalyst to AA AA to anisole
catalyst
agent (AA)
mol ratio
mol ratio
solvent
nitromethane
CS2
nitromethane
yield %
ref
1
2
3
4
5
6
7
8
9
AlCl3
TiCl4
SnCl4
Cu
acetyl chloride
acetyl chloride
acetyl chloride
acetyl chloride
acetyl chloride
acetyl chloride
acetyl chloride
acetyl chloride
acetyl chloride
acetic anhydride
acetic anhydride
acetic anhydride
acetic anhydride
acetic anhydride
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2.2:1
2.2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
1:1
1.5:1
1:1
quant
65
81
30
70
50
59
2
91
94
95
95
80
37
45
84
91
50
90
66
90
78
18
64
98
21, 22
23
24
25
26, 27
28
1:1
CS2
AgClO4
NaClO4
Ag3PO4
H2SO4
1.5:1
1.5:1
1:1
acetic acid + acetic anhydride
acetic acid + acetic anhydride
acetic acid + acetic anhydride
1
1
1:1
CF3COOH
1.5:1
1.5:1
1:1.06
1.1:1
1.5:1
1:1
29
10 AlCl3
11 AlCl3
12 BF3
CS2
30, 31
32, 33
1
30
26
30
34
35
36
37
38
37
39
39
40
36
methylene chloride
Acetic acid
13 TiCl4
14 HClO4
15 orthophosphoric acid acetic anhydride
1:1
16 polyphosphoric acid
17 CF3COOH
18 ZnCl2
19 ClCH2COOH
20 I2
21 (ClCH2O)2O
22 (CF3CO)2O
23 (C3F7CO)2O
24 polyphosphoric acid
22 BF3
acetic anhydride
acetic anhydride
acetic anhydride
acetic anhydride
acetic anhydride
acetic acid
acetic acid
acetic acid
acetic acid
acetic acid
1.5:1
1.5:1
1:1
1.5:1
1:1
1.5:1
1.5:1
1.5:1
1.5:1
1.5:1
a Reaction conditions: All additions slowly over a period of time, allowing the temperature to rise to the reflux and then cooking over 3-8 h. Reagent itself served
as a solvent in some cases.
on esterification of anthranilic acid with methanol or isatoic
anhydride with methanol, and these employ homogeneous
acid catalysts, posing problems of disposal. Typically,
sulphuric acid is used as a catalyst with little more than
stoichiometry over anthranilic acid to block the amino group
as hydrogen sulphate and the remaining for catalysis.15,47,48
Methyl salicylate is a valuable ester, having a pungent-
sweet, fruity odor with a burning sensation at high concen-
tration. Methyl salicylate can be obtained from natural
sources by the maceration and subsequent steam distillation
of wintergreen leaves or sweet birch bark. Generally, the
commercial product is synthesised by the esterification of
salicylic acid with methanol. Other than aspirin, methyl
salicylate is by far the most important commercial derivative
of salicylic acid. As a pharmaceutical, it is used in liniments
and ointments for the relief of pain in the lumbar and sciatic
regions and for rheumatic conditions. As a flavor and
fragrance agent, it is used in confectionery, dentifrices,
cosmetics, and perfumes.47 Methyl 4-hydroxybenzoate has
been used as preservative for food, pharmaceuticals, and
cosmetics for many years.47-50 Similarly, phthalate esters
such as dimethyl phthalate (DMP) and diethyl phthalate
(DEP) are also used in the perfumery industry and these can
be prepared by treating methanol and ethanol with phthalic
anhydride.
suitable green process, and to include a kinetic model which
will be useful for reactor design purposes.
2. Experimental Method
2.1. Chemicals and Catalysts. All chemicals and cata-
lysts were procured from firms of repute: anthranilic acid
(LR; Loba Chemie), anisole, salicylic acid, 4-hydroxybenzoic
acid, phthalic anhydride, methanol, acetic anhydride, (AR;
s.d. Fine Chem Ltd, India), ethanol (absolute GR; Merk
KgaA, Germany), Filtrol-24 (Engelhard, U.S.A.), K-10 clay
(Aldrich, U.S.A.), ion-exchange resins (IER) such as Indion-
130 (Ion Exchange Ltd., India), Amberlyst-15, Amberlyst-
36 (Rohm and Hass, U.S.A.), Dowex 50Wx8 (Dow Chemi-
cals, U.S.A.), and Bayer K-2441 (Bayer, Germany), Deloxane
ASP, (Degussa AG, Germany). These catalysts were dried
and used as such.
Sulphated zirconia was prepared according to the method
developed in this laboratory,5,6 by adding aqueous ammonia
solution to zirconium oxychloride solution at a pH of 10.
The precipitate was thoroughly washed with distilled water,
free from ammonium and chloride ions. It was then dried in
an oven at 120 °C for 24 h. The sulphation of the prepared
zirconia was done with 1.0 N sulphuric acid (15 mL/g). It
was dried at 120 °C and calcined at 650 °C for 3 h.
2.2. Catalytic Experiments. 2.2.1. Acylation of Anisole.
Acylation of anisole with acetic anhydride or acetyl chloride
gives p-methoxy acetophenone (Scheme 1).
From the several available catalysts, it was thought
desirable to evaluate a number of solid acids, develop a
The reactor consisted of a flat-bottom glass vessel of 100-
mL capacity, equipped with baffles and a turbine stirrer. The
assembly was kept in an isothermal oil bath at a constant
known temperature and mechanically agitated with an electric
(49) Bedoukian, P. Z. Perfumery and FlaVouring Synthesis, 3rd ed.; Allured
Publishing Corp.: Wheatson, IL, 1986.
(50) Kirk, R. E, Othmer, D. F., Eds. Encyclopaedia of Chemical Technology,
3rd ed.; Wiley-Interscience: New York, 1982; Vol. 20, p 500.
708
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Vol. 6, No. 5, 2002 / Organic Process Research & Development

Scheme 2. Esterification of aromatic carboxylic acids
motor. A typical reaction mixture consisted of 0.05 mol
anisole and 0.15 mol acetic anhydride with a catalyst loading
of 0.095 g/cm3, based on the total volume of the reaction
mixture. The total volume of the reaction mixture was 19.6
mL. The reaction was carried out at 50 °C at a speed of
agitation of 1000 rpm. The conversions were based on the
limiting reactant. The yields of the product were of the
nonisolated product, defined as the amount of product formed
with reference to the amount of limiting reactant reacted.
The selectivity was based on the amount of desired product
formed to the amount of all products formed. A material
balance was done for a few experiments. In a typical
experiment, after arriving at the best parameters, the catalyst
was filtered off, and the reaction mixture was fractionated
under vacuum. The isolated yield of the product was within
3-5% of the nonisolated yield.
A perfumery industry helped in determining the perfume
value of the isolated product. p-Methoxyacetophenone was
found to have a sweet, somewhat harsh, haylike floral, musky
note.
2.2.2. Esterification of Aromatic Carboxylic Acids. The
general reaction for esterification of aromatic carboxylic acid
is as follows (Scheme 2).
The reaction was carried out in a Parr autoclave of 100-
mL capacity. In a typical reaction for methyl anthranilate
preparation, 0.05 mol of anthranilic acid, 1.7 mol of
methanol, and 3.0% w/w catalyst were charged to the
autoclave. The reaction mixture was allowed to reach the
desired temperature, and the initial sample was collected.
Agitation was then commenced at a known speed. Samples
were withdrawn periodically for analysis. In most of the
cases, methanol was taken in far molar excess over carboxy-
lic acid to drive the equilibrium away towards the ester
formation. It was interesting to note that the reaction mixture
developed an intense odour of aromatic ester as the reaction
proceeded as in the case of esterification of anthranilic acid
and salicylic acid.
Figure 1. Effect of different catalysts on conversion of anisole.
Catalyst loading: 1.86 g, temperature: 50 °C, speed of agita-
tion: 1000 rpm, particle size: 400-500 µm, Anisole: 5.4 g,
Ac2O: 15.3 g (mole ratio: 1:3), total volume: 19.6 cm3. ([)
K-10. (9) F-24. (2) S-ZrO2 × Indion-130. (f) Amb-15. (b)
Amb-36.
alcohol. The analysis was carried out by high performance
liquid chromatography (Tosoh, UV-8010) at ambient tem-
perature. The Merck 50983 column with a stationary phase
of Lichrospher 100 RP-18, particle size 5 µm, prepacked on
a 250 mm × 4 mm i.d. with Tosoh UV-8010 detector set at
254 nm was used for methyl anthranilate, methyl salicylate,
and methyl 4-hydroxybenzoate and 245 nm was used for
phthalate esters. The eluent used for the analysis for phthalate
esters was HPLC grade methanol with a flow rate of 1.0
mL/min, and for other esters it was an 80:20 methanol-
water mixture with a flow rate of 0.8 mL/min. Pure samples
of the reactants and products and their synthetic mixtures
were used to calibrate the chromatograms.
For isolation of product, the catalyst was filtered off, and
the excess unreacted methanol was removed from the
reaction mixture by using a rotovac. The products were
isolated by standard procedures and characterised by IR and
NMR spectroscopies. In the case of methyl anthranilate, after
removing the excess methanol, the remaining mass was
treated with hexane in which only the ester was extracted,
leaving behind unreacted anthranilic acid. The hexane phase
was treated with charcoal and filtered. The product was
1
purified by distillation. It was confirmed by H NMR (60
2.3. Analysis and Isolation of Product. 2.3.1. Acylation.
Analysis was performed by GC, (Chemito gas chromato-
graph, model 8510) by using a 2 m × 3.2 mm i.d., SS column
packed with 10% OV-17 on Chromosorb WHP, coupled with
a flame ionisation detector. Pure samples of the reactants
and products and their synthetic mixtures were used to
calibrate the chromatograms. For isolation of product, the
catalyst was filtered off, and the excess unreacted acetic
anhydride, anisole, and acetic acid (byproduct) were removed
from the reaction mixture by using a rotovac. The products
were isolated by standard procedures and characterised by
IR and NMR spectroscopies. The product (p-methoxyac-
etophenone) was purified by vacuum distillation. It was
MHz Hitachi, Japan) and FTIR (Bruker IFS-88 single
channel Fourier transform spectrophotometer). Its odour was
also evaluated vis-a`-vis the pure commercial sample. The
final product was a very pale, yellow liquid with a dry odour
resembling that of concord grapes and had a boiling point
of 255 °C matching the reported value.
3. Results and Discussion
3.1. Results and Discussion: Acylation. 3.1.1. Effect of
Various Catalysts. The efficacy of different catalysts under
otherwise similar conditions was tested at 50 °C (Figure 1).
Among the catalysts used cation-exchange resins showed
very high activities followed by sulphated zirconia, Filtrol-
24, and K-10. Catalysts based on zeolite Y did not show
any activity at these reaction conditions. It appears that the
pore sizes of these catalysts pose considerable intraparticle
1
confirmed by H NMR (60 MHz Hitachi, Japan).
2.3.2. Esterification. After filtration of the catalyst the
reaction mixture was analysed without any removal of
Vol. 6, No. 5, 2002 / Organic Process Research & Development
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709

Figure 3. Effect of particle size on conversion of anisole.
Catalyst: Amberlyst-36: 1.86 g (0.095 g/cm3), temperature: 50
°C, speed of agitation: 1000 rpm, Anisole: 5.4 g, Ac2O: 15.3
g (mole ratio: 1:3), total volume: 19.6 cm3. ([) 250-350µm.
(9) 400-500µm. (2) 550-650µm.
Figure 2. Effect of speed of agitation on conversion of anisole.
Catalyst: Amberlyst-36: 1.86 g, temperature: 50 °C, particle
size: 400-500 µm, Anisole: 5.4 g, Ac2O: 15.3 g (mole ratio:
1:3), total volume: 19.6 cm3. ([) 800 rpm. (9) 1000 rpm (2)
1200 rpm.
resistance for the reactant anisole to access the catalytic sites.
Further experiments were conducted with cation-exchange
resin Amberlyst-36, which was the most efficient heteroge-
neous catalyst. The meq/g exchange capacity on dry basis
for Amberlyst-36, Indion-130, and Amberlyst-15 are >5.45,
4.8, and 4.9, respectively. The value of meq/g for Amberlyst-
36 is maximum, and also the final conversion by using this
catalyst was observed to be the maximum. It is obvious that
the Brønsted acidity is mainly responsible for the activity
with acetic anhydride as acylating agent, and therefore other
catalysts were ineffective. Amberlyst-36 was used as the
catalyst for all further experiments.
3.1.2. Effect of Speed of Agitation. The effect of the speed
of agitation on the reaction rate and conversion was studied
at 800, 1000, and 1200 rpm (Figure 2). There was no
significant change in conversion patterns. This implies that
there was no resistance to mass transfer of acetic anhydride
to the external surface of the catalyst. All subsequent
reactions were conducted at 1000 rpm.
3.1.3. Effect of Particle Size. The effect of intraparticle
diffusion resistance was studied by varying the average
catalyst particle size in the range of 250-650 µm at the same
loading, and the results are shown in the Figure 3. It was
observed that as the particle size was reduced from the range
550-650 µm to 450-500 µm there was an increase in
conversion. However, further decrease in size to 250-350
µm did not increase the conversion appreciably. This suggests
the internal diffusion resistance was absent. A theoretical
analysis based on the Wiesz-Prater criterion was also
performed to confirm the experimental observation.15 De-
termining the activation energy as will be discussed later
provided a further proof of the absence of intraparticle
diffusion resistance.
Figure 4. Effect of catalyst loading on conversion of anisole.
Catalyst: Amberlyst-36, temperature: 50 °C, speed of agita-
tion: 1000 rpm, particle size: 400-500 µm, Anisole: 5.4 g,
Ac2O: 15.3 g (mole ratio: 1:3), total volume: 19.6 cm3: ([)
0.0317 g/cm3. (9) 0.0633 g/cm3. (2) 0.095 g/cm3 × 0.127 g/cm3.
3.1.5. Effect of Mole Ratio. The effect of mole ratio was
studied at an anisole-to-acetic anhydride ratio of 1:1 to 1:5
without adding any solvent. The catalyst loading for all four
reactions was maintained at 0.095 g/cm3. The conversion
was found to increase with the amount of acetic anhydride
concentration (Figure 5). However, the selectivity towards
the monoacylated product was found to decrease with an
increase in acetic anhydride concentration. Between the mole
ratio of 1:1 to 1:3 no significant change in the selectivity
was observed. Therefore, all the reactions were conducted
at a mole ratio of 1:3 without any solvent.
3.1.6. Effect of Temperature. The effect of temperature
for the reaction of anisole with acetic anhydride was studied
from 30 to 90 °C (Figure 6). The conversion was found to
increase substantially with increasing temperatures. Although
an increase in temperature gave a substantial increase in the
conversion of anisole, the selectivity towards the monoacy-
lated product PMAP was found to decrease. The selectivity
of p-methoxy acetophenone was 98.3, 97.8, 94.2, and 84.4%
at 30, 50, 70, and 90 °C respectively, after 5 h. There was
a diacylated product formed with an increase in temperature.
Therefore, a temperature 50 °C was selected as the most
suitable condition for further experiments.
3.1.4. Effect of Catalyst Loading. The reaction was
conducted at four different loadings of Amberlyst-36 in the
range of 0.0316-0.127 g/cm3 of the total volume of the
reaction mixture (Figure 4). The conversion had increased
with an increase in catalyst loadings, which was due to the
proportional increase in the number of acidic sites and surface
area with catalyst loadings.
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Figure 7. Kinetic plot in integrated from of eq 3 for acylation
of anisole. Catalyst: Amberlyst-36, temperature: 50 °C, speed
of agitation: 1000 rpm, particle size: 400-500 µm. Anisole:
5.4 g; Ac2O: 15.3 g (mole ratio: 1:3), total volume: 19.6 cm3.
Figure 5. Effect of mole ratio on conversion of anisole.
Catalyst: Amberlyst-36 (0.095 g/cm3), temperature: 50 °C,
speed of agitation: 1000 rpm, particle size: 400-500 µm: ([)
1:1. (9) 1:2. (2) 1:3 × 1:5.
Figure 8. Plot of initial rate vs catalyst loading (w) for acylation
of anisole. Catalyst: Amberlyst-36, temperature: 50 °C, speed
of agitation: 1000 rpm, particle size: 400-500 µm. Anisole:
5.4 g; Ac2O: 15.3 g (mole ratio: 1:3), total volume: 19.6 cm3.
Figure 6. Effect of temperature on conversion of anisole.
Catalyst: Amberlyst-36: 1.86 g (0.095 g/cm3), speed of
agitation: 1000 rpm, particle size: 400-500 µm. Anisole: 5.4
g; Ac2O: 15.3 g (mole ratio: 1:3), total volume: 19.6 cm3; ([)
30 °C. (9) 50 °C. (2) 70 °C × 90 °C.
in most cases), and t is the time. A plot of left-hand side
terms (LHS) versus t for a known Ka will be a straight line
passing through the origin. Otherwise, Ka can be assumed
and the equation fitted to get results.
For M ) 1, the final integrated form of the said equation
is:
3.1.7. Kinetics of Reaction. The kinetics of the acylation
reaction has already been developed by Yadav and co-
workers17,20 for 2-methoxynaphthalene and acetic anhydride.
According to this model, acetic anhydride is adsorbed on a
site to generate carbocation (AS) and acetic acid (C). This
model was found to hold for the current case. The final
integrated form of the said equation is eq 2 given below:
XB
ln(1 - XB) + KaXB +
) ksrKawt
(3)
(
)
1 - XB
A plot of LHS versus time of eq 3 will be a straight line
passing through the origin (Figure 7) with a slope of ksrKaw.
The adsorption constant ka was very small, and hence the
term contribution kaXB was negligible.
The initial rate of the reaction is proportional to w. A
plot was made of initial rate versus w as shown in the Figure
8 to confirm the same.
3.1.8. Reusability of the Catalyst. Ion-exchange resin
catalysts are generally reusable, and therefore the catalyst
was filtered and reused thrice. There was a drop of 5-8%
in the final conversion from the previous run. This may be
due to the loss of catalyst during filtration. Thus, it can be
assumed to be reasonable because the quantity used is quite
small in laboratory experiments.
M - XB
M
ln
-
(
M - 1) (
)
M
1
K + K M +
ln(1 - X ) + X ) k K wt (2)
B B sr a
(
)
a
a
M - 1
This is the complete solution for all ratios of M other than
1. Where M is the molar ratio of acetic anhydride to anisole,
Ka is the adsorption equilibrium constant for chemisorption
of acetic anhydride, ksr is the surface reaction rate constant,
w is the catalyst loading (mass per unit liquid volume), XB
is the fractional conversion of the limiting reactant (anisole
3.2. Esterification. The esterification of phthalic anhy-
dride with alcohols involves two steps. The first reaction
giving the monoester is very fast and is completed in a short
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Table 2. Esterification of anthranilic acid and phthalic
anhydride with methanol in the presence of solid acid
catalysts
Table 3. Esterification reactions of different subtracts using
Amberlyst-36 as catalyst
H+ Capacity conversion conversion
entry
catalyst
(meq/g)
(%)b
(%)c
1.
2.
3.
4.
5.
6.
7.
8.
Indion -130
Dowex 50w x 8
Amberlyst -36
Amberlyst -15
Deloxane ASP
Bayer K2441
Filtrol-24
4.8
a
5.45
4.9
0.7-1.1
a
0.3
0.35
57.0
57.1
68.7
61.0
37.0
55.0
5.2
73.1
73.3
80.4
75.1
51.0
76.9
30.7
6.3
K-10 clay
<1.0
a Not available in catalogue (should be around 5). b Conversion of anthranilic
acid. c Conversion of phthalic acid monoester.
time without any catalyst; thus, the kinetics of the overall
reaction is normally studied by considering the diester
formation in the second stage for the reaction between the
monoester and alcohol, wherein the catalyst can have a real
influence.
The results of the screening experiments carried out on
anthranilic acid and methanol at a mole ratio of 1:34 at 120
°C and an agitation speed of 800 rpm with 3.0% w/w loading
of different cation-exchange resins and clays are presented
in Table 2.
The values of the exchange capacity, meq/g-dry resin, for
Amberlyst-36, Indion-130, and Amberlyst-15 are >5.45, 4.8,
and 4.9, respectively. The value of meq/g dry for Amberlyst-
36 is maximum, and also the final conversion by using this
catalyst was observed to be maximum.
resins are commercially available and reusable, the major
problems of effluent treatment and the cost associated with
it are overcome. There is no halide present in the products
for their use in perfumery industry, and this fetches a higher
price. The current bulk prices of these important esters are
in the range of $1.70-8.20 (U.S.) per kg: p-methoxyac-
etophenone, $3.50; dimethyl phthalate, $1.72; diethyl ph-
thalate, $2.20; methyl anthranilate, $8.14; methyl paraben,
$7.7; and methyl salicylate, $5.53. The product separation
using solid acids is very easy, and thereby the overall yields
are also increased. The scale-up of these reactions for a
mechanically agitated contactor is straightforward, wherein
the same tip speed would be a criterion. In the case of
p-methoxyacetophenone for the process based on AlCl3 as
a catalyst, the cost of catalyst is more than the raw materials
on a kilogram basis since 2 mol are used per mole of anisole,
apart from the effluent treatment cost. The catalyst cost on
the basis of laboratory experiments with a minimum of 10
recycle times turns out to be less than 5% of the product
cost in most of the cases, which is economical. In the case
of esterifications, the homogeneous catalysts are cheaper. We
can compare this with a typical sulphuric acid-based process
for which the cost is 1% including the cost of neutralisation
of the liquid acid. However, the corrosion and treatment of
salt generated after neutralisation of the liquid acid would
be much greater.
The conventional inorganic catalysts such as H-ZSM-5,
acid-treated clays Filtrol-24 and K10, as well as heteropoly-
acid (dodecatungstophosphoric acid, as homogeneous cata-
lyst) did not show much activity for this reaction. These
catalysts are well-known for their sensitivity towards aqueous
conditions, and that might have caused the deactivation of
these catalysts. The reaction requires catalysts of a hydro-
phobic nature such as IERs because the catalysts with the
hydrophilic surface deactivate rapidly in the presence of
water formed during the reaction. It was found that Am-
berlyst-36 showed higher conversions vis-a`-vis other cata-
lysts. Hence, further experiments were conducted with
Amberlyst-36 as the catalyst. The effect of different sub-
strates by using Amberlyst-36 as the catalyst is presented in
Table 3.
3.2.1. Reusability of Catalyst. The catalyst was employed
as such without any posttreatment/washings for three runs.
It was found that the activity had decreased with each use,
but the subsequent reduction in activity was marginal. Thus,
after the third use, the catalyst was washed with methanol
to see that the same activity was maintained at the end of
fourth use.
5. Conclusions
4. Economic Evaluation
This contribution has addressed an important problem
related to green chemistry, wherein the polluting homoge-
neous acids can be replaced by cation-exchange resins in
acylation and esterification reactions. Anisole was efficiently
The successful application of heterogeneous catalysts for
the preparation of these products demonstrates that the
product can be economically produced. Since ion-exchange
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acylated in liquid phase with cation-exchange resins as the
catalyst under mild conditions, without undergoing dem-
ethylation, giving rise only to the para isomer. The coproduct
acidic acid can be easily recovered. Amberlyst-36 was found
to be the best catalyst. Esterification reactions of phthalic
anhydride with methanol and ethanol, and those of anthranilic
acid, salicylic acid, and 4-hydroxybenzoic acid with methanol
were studied by using a variety of catalysts: The order of
catalytic activity was found to be as follows: Amberlyst-36
> Bayer K2441 > Amberlyst-15 > Dowex 50Wx8 >
Indion-130 > Deloxane ASP > Filtrol-24 > K-10 Mont-
morrilonite.
Acknowledgment
Thanks are due to the following for their support in
carrying out research described: University Grants Com-
mission, for Senior Research Fellowship to M.S.M.M.R.,
AICTE and Darbari Seth Endowments to G.D.Y. Thanks are
also due to the Michigan State University for hosting G.D.Y.
as the Johansen-Crosby Visiting Professor of Chemical
Engineering during 2001-2002 which provided excellent
atmosphere for creative pursuits.
Received for review February 16, 2002.
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