1352 Shi et al.
Asian J. Chem.
The aim of this study was to establish an efficient strategy
RESULTS AND DISCUSSION
for synthesis of alkyl gallates (Scheme-I) through optimization
of catalyst, reaction time, reaction temperature and the ratio
of gallic acid to alcohol under the microwave irradiation.
In present research, ethanol (2b) was selected as a represen-
tative alcohol to optimize the reaction condition. For the reactant
and solvent of this esterification were all the ethanol, which
was a kind of polar solvent, it could absorb the microwave much
more efficiently. Firstly, we tried this esterification without
any catalyst where the gallic acid (1) reacted with the ethanol
(2b) directly under the microwave irradiation at 200W (Table-1,
Runs 1-2). Unfortunately, the result was that there was no indi-
cation of the product even the reaction time had proceeded 20
min. To make this reaction much easier to proceed, we added
the catalyst of conc. sulfuric acid into the reaction mixture.
This time the esterification was found to be finished after 10
min at 88 ºC, in the presence of 10 mol % H2SO4 in ethanol,
giving the corresponding ethyl gallate (3b) in 96 % (Table-1,
Run 7). When the amount of H2SO4 was increased to 12 mol %,
the yield of the product was reduced to 88 % (Table-1, Runs
8), this could be that the ethyl gallate was hydrolyzed in the
presence of excessive H2SO4. However, when the amount of
H2SO4 was decreased (2, 4, 6, 8 mol %), the reaction proceeded
more slowly, and the yields of ethyl gallate (3b) were reduced
into 58, 72, 88 and 92 %, respectively, even after the reaction
mixture had proceeded 10 min at 88 ºC (Table-1, Runs 3-6).
Subsequently, we selected p-toluenesulfonic acid as the catalyst
to investigate this esterification, and it was found that this
catalyst could make the esterification of gallic acid much more
easily. From the report, it is observed that this esterification
was finished after 10 min in 88 ºC, in the presence of 4 mol %
p-toluenesulfonic acid in ethanol, giving the corresponding
ethyl gallate (3b) in 96 % yield (Table-1, Run 10). Compared
to the H2SO4, the demand of p-toluenesulfonic acid was much
less to make this esterification proceed completely, so we chose
p-toluenesulfonic acid as the catalyst in this microwave assisted
esterification.
HO
HO
HO
HO
Catalyst
HO
COOH
+
ROH
COOR
Microwave irradiation
HO
2
1
3
Scheme-I: Esterification of gallic acid under microwave irradiation
EXPERIMENTAL
All the reagents are commercially available and used
directly. The 1H NMR spectra were recorded on a Bruker AV
300 spectrometer using DMSO-d6 as the solvent and TMS as
the internal standard. Chemical shifts are reported in parts per
million (ppm). The ESI-MS were obtained onAgilent 1946A-
MSD.
General procedures for the esterification of gallic acid
through microwave irradiation: To a stirring mixture of gallic
acid (170 mg, 1 mmol) in alcohol (6 mmol) was added the
p-toluenesulfonic acid (6.88 mg, 0.04 mmol), and the reaction
mixture was heated in a sealed reaction vessel of discover
(CEM, USA) under microwave irradiation, where the power
was set at 200 W, the temperature was set at some centigrade
which was 10 ºC above the boiling point of the alcohol, and
the PSI was set at 180. All of the alkyl gallate are known
compounds and were identified on the basis of 1H NMR and
ESI-MS spectral data.
1
Compound 3a11: White solid, H NMR (300 MHz,
DMSO-d6) δ 3.75 (s, 3H), 6.94 (s, 2H), 8.94 (s, 1H), 9.26 (s,
2H); ESI-MS m/z: 185 [M + H]+ (100).
1
Compound 3b11: White solid, H NMR (300 MHz,
DMSO-d6) δ 1.27 (t, 3H), 4.19 (q, 2H), 6.94 (s, 2H), 8.91 (s,
TABLE-1
1H), 9.24 (s, 2H); ESI-MS m/z:199 [M + H]+ (100).
OPTIMIZATION OF THE CATALYST FOR THE
SYNTHESIS OF ETHYL GALLATE (3b)a
1
Compound 3c11: White solid, H NMR (300 MHz,
Run
1
2
3
4
5
6
7
8
Catalyst (mol %)
Time (min)d
Yield (%)e
DMSO-d6) δ 0.95 (t, 3H), 1.65 (m, 2H), 4.11 (t, 2H), 6.95 (s,
2H), 8.92 (s, 1H), 9.25 (s, 2H); ESI-MS m/z: 213 [M + H]+ (100).
0
0
10
20
10
10
10
10
10
10
10
10
10
10
10
10
0
0
1
Compound 3d19: White solid, H NMR (300 MHz,
2b
58
72
88
92
96
88
88
96
94
87
74
67
DMSO-d6) δ 1.25 (d, J = 6.3 Hz, 6H), 5.03 (m, 1H), 6.93 (s,
4b
2H), 8.89 (s, 1H), 9.23 (s, 2H); ESI-MS m/z: 213 [M + H]+ (100).
6b
1
Compound 3e11: White solid, H NMR (300 MHz,
8b
10b
12b
2c
DMSO-d6) δ 0.93 (t, 3H), 1.44 (m, 2H), 1.64 (m, 2H), 4.16 (t,
2H), 6.94 (s, 2H), 8.92 (s, 1H), 9.25 (s, 2H); ESI-MS m/z: 227
[M + H]+ (100).
9
10
11
12
13
14
4c
1
Compound 3f23: White solid, H NMR (300 MHz,
6c
DMSO-d6) δ 0.97 (d, J = 6.6 Hz, 6H), 1.97 (m, 1H), 4.03 (d, J
= 7.1 Hz, 2H), 6.96 (s, 2H), 9.16 (s, 3H); ESI-MS m/z: 227 [M
+ H]+ (100).
8c
10c
12c
1
Compound 3g11: White solid, H NMR (300 MHz,
aReaction conditions: Gallic acid (1) (1 mmol), ethanol (2b) (5 mL),
temperature 88 °C; Conc. sulfuric acid as the catalyst; p-Toluene-
sulfonic acid as the catalyst; dMonitored by TLC; eIsolated yield, purity
confirmed by MS and 1H NMR
b
c
DMSO-d6) δ 0.83 (t, 3H), 1.36 (m, 4H), 1.64 (m, 2H), 4.12 (t,
2H), 6.92 (s, 2H), 9.08 (s, 1H); ESI-MS m/z: 241 [M + H]+ (100).
1
Compound 3h19: White solid, H NMR (300 MHz,
DMSO-d6) δ 0.89 (d, J = 6.6 Hz, 6H), 1.56 (m, 2H), 1.70 (m,
1H), 4.16 (t, 2H), 6.94 (s, 2H), 9.08 (s, 3H); ESI-MS m/z: 241
[M + H]+ (100).
Reaction temperature played a crucial role in this micro-
wave-assisted esterification. It was reported that the yields
of ethyl gallate might sometimes be dramatically affected by