An improved method for the esterification of aromatic acids with ethanol and methanol

Article abstract of DOI:10.1081/SCC-100104461

A mixed catalyst Fe₂(SO₄)₃·xH₂O/ concentrated H₂SO₄ has been used to catalyze the esterification of aromatic acids with ethanol and methanol. This catalyst system is found to be effective for the rapid reactions and the esterification yields are excellent.

Full text of DOI:10.1081/SCC-100104461

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AN IMPROVED METHOD FOR THE ESTERIFICATION OF
AROMATIC ACIDS WITH ETHANOL AND METHANOL
Qi-hai Xu a , Wan-yi Liu a , Bao-hua Chen a & Yong-xiang Ma b
a National Laboratory of Applied Organic Chemistry , Lanzhou University , Lanzhou,
730000, P. R. China
b National Laboratory of Applied Organic Chemistry , Lanzhou University , Lanzhou,
730000, P. R. China
Published online: 09 Nov 2006.
To cite this article: Qi-hai Xu , Wan-yi Liu , Bao-hua Chen & Yong-xiang Ma (2001) AN IMPROVED METHOD FOR THE
ESTERIFICATION OF AROMATIC ACIDS WITH ETHANOL AND METHANOL, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 31:14, 2113-2117, DOI: 10.1081/SCC-100104461
To link to this article: http://dx.doi.org/10.1081/SCC-100104461
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SYNTHETIC COMMUNICATIONS, 31(14), 2113–2117 (2001)
AN IMPROVED METHOD FOR THE
ESTERIFICATION OF AROMATIC ACIDS
WITH ETHANOL AND METHANOL
Qi-hai Xu, Wan-yi Liu, Bao-hua Chen,
and Yong-xiang Ma*
National Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou 730000,
P. R. China
ABSTRACT
A mixed catalyst Fe2(SO4)3ÁxH2O/concentrated H2SO4 has
been used to catalyze the esterification of aromatic acids
with ethanol and methanol. This catalyst system is found to
be effective for the rapid reactions and the esterification yields
are excellent.
Aromatic carboxylic esters are important compounds and may be
prepared by various reactions involving the use of acyl halides or anhydrides
and esterification with alcohols.1 A more classical method is esterification of
aromatic acids directly with alcohols in the presence of various catalysts,
such as concentrated sulfuric acid, hydrogen chloride, boron trifluoride,
aluminum chloride, trifluoroacetic anhydride, polyphosphate ester, neody-
mium oxide, dicyclohexylcarbodiimide, graphite bisulfate, etc.2 Other
methods have also been recently suggested.3,4 The disadvantages of using
these catalysts, such as long reaction time, low yield, expensive reagents and
* Corresponding author.
2113
Copyright & 2001 by Marcel Dekker, Inc.
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2114
XU ET AL.
tedious operation are difficult to avoid.2,5 In recent years, esterification using
aqueous sulfate as catalyst has been reported,5,6 and shows some advantages
such as short reaction time, high yields and easy work-up for a variety of
aromatic acids.
In our research, we need various of ethyl and methyl arylcarboxylates
on a large scale. We find that the reported methods do not give satisfactory
results and the yields are relatively low with methanol and ethanol.
However, using a mixed catalyst system, Fe2(SO4)3ÁxH2O/concentrated
H2SO4, instead of Fe2(SO4)3ÁxH2O we observe effective esterification of
aromatic acids with methanol or ethanol, and excellent yields in short reac-
tion times.
First, we used Fe2(SO4)3ÁxH2O to catalyze the esterification of m-nitro-
benzoic acid with ethanol using the procedure reported in the literature.5
Only about 40% of the acid had been transformed (tested by TLC) after
refluxing for 5 hours. When a drop of concentrated sulfuric acid was added
into it, the esterification rapidly continued and, surprisingly, it had under-
gone nearly quantitative transition after successively refluxing for 3 hours.
Next we examined the esterification of 3,5-dinitrobenzoic acid in presence of
concentrated sulfuric acid as catalyst under the same conditions, but only
about 35% of the acid was transformed after 8 hours, while nearly quanti-
tative esterification was observed upon adding some Fe2(SO4)3ÁxH2O after a
further 4 hours.
We thought that this mixed catalyst perhaps was more active, so we
carried out parallel esterification of many aromatic acids with ethanol.7 We
obtained some excellent results as compared with using Fe2(SO4)3ÁxH2O or
H2SO4 alone, as shown in Table 1. It is shown that the esterification reaction
carried out by the mixed catalyst requires shorter times and gives higher yields.
Next we applied this mixed catalyst to the esterification of various
aromatic acids with methanol and ethanol. These esterification processes
all give satisfactory results as shown in Table 2.
Choshi, T. carried out the esterification of o-methoxybenzoic acid
by treating 40mmol o-methoxybenzoic acid with 40–50 ml absolute ethanol
in the presence of 2 ml concentrated sulfuric acid, but only 87% yield was
obtained.9 Hosangadi, B. reported the esterification of acid with alcohol in
the presence of equivalent thionyl chloride. The operation is complicated and
the thionyl chloride is toxic and acrid, although esterification yields obtained
by their method are similar to our result.10
In conclusion, using the available mixed catalyst system, the esterifica-
tion process requires even shorter reaction time and gets much higher yield
than using Fe2(SO4)3ÁxH2O or concentrated H2SO4 alone as catalyst.
The system is especially effective for acids with steric hindrance and for
a,b-unsaturated acids (Entry 5–14, 16–17). In addition, it has other

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ESTERIFICATION OF AROMATIC ACIDS
2115
Table 1. The Esterifying Results of Aromatic Acid with Ethanol by
Different Catalysts
Reaction time
(h)
Yield
(%)
ArCOOH
Catalyst7
3,5-Dinitrobenzoic acid
A
B
C
8
8
2
34a
32a
95b
m-Nitrobenzoic acid
p-Methylbenzoic acid
o-Methoxybenzoic acid
A
B
C
5
5
3
41a
38a
90b
60a
90a
98b
89a
10a
93b
A
B
C
2.5
2.5
2.5
A
B
C
7
3
3
b
aDetermined by MS–GS; Isolated yields.
advantages such as mild conditions and easy work-up. While we have
increased the quantity of acids substrate to 200–300 times (Entry 5, 9, 11, 13)
and the amount of ethanol used is only 50–70 ml, the reactions do not
require a water-separator and the yields are excellent. We believe that
the present work may provide a more efficient catalytic system for the
preparation of aromatic esters from the corresponding acids and alcohols
on any scale.
EXPERIMENTAL
All reagents are commercially available and used directly. All melting
and boiling points are uncorrected.
General Procedure for the Esterification
1 mmol acid, 5 ml methanol or anhydrous ethanol, 2% of
Fe2(SO4)3ÁxH2O (based on the acid weight) and 0.001 ml concentrated
H2SO4 (1.87 mg) are mixed and placed in a flask with a condenser, and
heated in an oil bath at reflux. After the required time as showed in the
table, the free alcohol is removed by distillation, the reaction mixture is

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XU ET AL.
Table 2. The Esterification of Aromatic Acid with Ethanol and Methanol
Mp (ꢀC) or Bp (ꢀC/mmHg)
Reaction Yield
Entry ArCOOH
Ra
Time (h)
(%)
Found
Lit.8
1
2
3
Benzoic acid
Benzoic acid
p-Methyl
Et
Me
Et
4
2
2.5
97b
90c
98b
88/11
201/760
99/11
213/760
199.6/760
110/12
benzoic acid
p-Methyl
4
5
6
7
8
9
Me
Et
2
96.5c
93b
211/760217/760
134/11
benzoic acid
o-Methoxy
benzoic acid
o-Methoxy
benzoic acid
m-Methyl
benzoic acid
m-Methyl
benzoic acid
3,5-Dinitro
benzoic acid
3
135/12
Me
Et
3
>99c
215/760228/760
106/11
5
90b
89.3c
95b
95c
90b
84c
65c
60c
95c
105/10
215/760
93
Me
Et
3
207/760
91–93
2
103,5-Dinitro
benzoic acid
Me
Et
2
108
112
11
12
13
14
15
m-Nitro
benzoic acid
m-Nitro
benzoic acid
o-Nitro
benzoic acid
o-Nitro
benzoic acid
p-Nitro
benzoic acid
3
40–41
41–47
78
Me
Et
3
77–79
5
173/18
173/18
169/19
57
Me
Et
5
160/18
1.5
56
16
17
Cinnamic acid Me
Cinnamic acid Et
2
1.5
99c
97c
36
117/18
36
159/24
aR in alcohol ROH; bIsolated yields (the isolated compounds have identical spectral
c
characteristic with the corresponding authentic samples); Determined by MS-GS.
cooled to room temperature, 10ml water added and the mixture extracted
with ether (10ml  3). The extract is washed with sodium carbonate solution
(1%), then with water until the ester is neutral to litmus. The ether layer is
dried over sodium sulfate overnight, then filtered and distilled the residue is
recrystallized or distilled under reduced pressure.

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REFERENCES
2117
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are A: Fe2(SO4)3ÁxH2O (2% of the acid weight), B: 0.001 ml concen-
trated H2SO4 and C: the mixed catalyst respectively.
8. Dictionary of Organic Compounds, Chapman and Hall: London, 6th
ed., 1996.
9. Choshi, T.; Horimoto, S. and Wany, C.Y. Chem. Pharm. Bull. 1992,
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11. This work has been also supported by the Youth Foundation of the
Institute of Chemistry and Technology, Lanzhou University.

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