16
Y. Ma et al. / Catalysis Communications 48 (2014) 15–18
3
. Results and discussion
100
A
Con:Glu
Con:Ben
Yield
8
6
0
0
3
.1. Esterification of glutamic acid by benzyl alcohol promoted by different
catalysts
Sel
In the present study, we used metal chloride, homogeneous organic
40
acid and solid acids as catalyst to catalyze the synthesis of benzyl ester of
L-glutamic acid. Results were shown in Fig. 1. When homogeneous
20
CH
6.88%, but the yield and selectivity of γ-benzyl ester of L-glutamic
acid only reached 44.44% and 57.81%. It is well known that CH SO H is
capable of achieving selective and efficient esterification of L-glutamic
acid in γ position, but the performance of CH SO H in this transforma-
tion is out of our expectation, which was attributed to the much less
CH SO H usage. In CH SO H catalytic process, the necessary amount
3 3
SO H was used as catalyst, L-glutamic acid conversion can achieve
0
7
30
40
50
60
70
80
90
o
Reaction temperature ( C)
3
3
Con:Glu
Con:Ben
Yield
3
3
1
20
Sel
B
3
3
3
3
100
of alkanesulfonic acid to be added is at least 1 mol per mole of glutamic
acid because the amine functional group needs to be neutralized [9],
8
6
4
2
0
0
0
0
3 3
however, the amount of CH SO H used in this catalytic tests was only
1
0 mol% of glutamic acid amount. Importantly, benzyl alcohol un-
dergoes benzaldehyde easily in the presence of strong organic acid,
and α-benzyl ester of glutamic acid and diester diester dibenzyl 2-
aminopentanedioate appeared simultaneously. In addition, racemiza-
tion also occurs to give L or D derivatives at the same time [9].
The solid acids, such as phosphomolybdic acid, phosphotungstic acid
0
THF
DMF
N-hexane
DMSO
Water
Fig. 2. A: Esterification of benzyl alcohol with L-glutamic acid at different temperatures over
CuCl catalyst (6.8 mmol L-glutamic acid, L-glutamic acid/benzyl alcohol molar ratio = 1:1.5,
h, 0.68 mmol CuCl , racemization was not detected). B: Esterification of benzyl alcohol and
L-glutamic acid with different solvents over CuCl at 60 °C (conditions: L-glutamic acid
.8 mmol, 2 h, CuCl 0.68 mmol, solvent 10 ml).
and H
2 4 2 3
SO /Al O , were used as catalysts, and the selectivity of γ-benzyl
2
ester of L-glutamic acid came up to 100%, but low glutamic acid conver-
sion was obtained. Among FeCl
2
2
3 2 2
, ZnCl , CoCl , CuCl
2
, CrCl
3
, BiCl
3
and
was
2
6
2
SnCl , CuCl shows the best performance despite much less CuCl
4
2
2
used, and the selectivity and yield of γ-benzyl ester of L-glutamic acid
achieved 100% and 95.31%. The esterification activity of metal
Usually, the solvents, which do not dissolve the γ-benzyl ester of
L-glutamic acid, are very suitable, such as benzene, toluene, xylene
and chlorobenzene. Herein, THF, DMF, n-hexane, DMSO and H O were
loaded into the reaction system to allow better stirring of the medium
see Fig. 2B). When THF and n-hexane were used, γ-benzyl ester of
chloride catalysts is in the following order: CuCl
CoCl N BiCl N SnCl N CrCl . When CuCl and FeCl
lysts, benzyl alcohol does not undergo any side reactions.
2
N FeCl
3 2
N ZnCl N
were used as cata-
2
2
3
4
3
2
3
(
L-glutamic acid yields achieved 80.00% and 77.91% under condition
with distillation of the solvent/water azeotrope. If the reactions
3
.2. Effect of temperature and solvent on esterification
were carried out in DMF, DMSO and H
the removal of by-producing H O, γ-benzyl ester of L-glutamic acid
yields still reach 70.39%, 73.64% and 78.99%, respectively, which in-
dicated that H O has no effect on esterification of glutamic acid by
benzyl alcohol in the presence of CuCl
2
O under condition without
Temperature plays a key role on esterification (see Fig. 2A). A better
yield of γ-benzyl ester of glutamic acid achieved 77.58% even at 37 °C.
This result is markedly improved if the choice is made to maintain the
temperature at 60 °C which are not excessively high and low. High tem-
perature deteriorates the yield and selectivity of γ-benzyl ester of
glutamic acid.
2
2
2
.
3.3. Effect of mole ratio of L-glutamic acid/benzyl alcohol on esterification
Con:Glu
Con:Ben
Yield
As the amount of benzyl alcohol increase, L-glutamic acid conversion
and γ-benzyl ester of L-glutamic acid yield increased (see Fig. 3). When
1
1
20
00
Sel
Con:Glu
1
1
20
00
Con:Ben
Yield
Sel
8
6
4
2
0
0
0
0
0
8
6
0
0
40
20
0
H
S
l2
/Al2 ZnC CrCl FeC C
3
l3
2
Cu
2
nk
Bla
3
O3 O3
Cl
Cl4
BiCl3
Sn
oCl
SO SPP
1
2W 4
Ph
CH3SO3H
O4 12MoO3
SO
H2
1:0.9
1:1.3
1:1.5
1:1.7
1:2.1
H3P H3PO4
L-glutamic acid/ benzyl alcohol molar ratio
Fig. 1. Results of the esterification of benzyl alcohol and L-glutamic acid over different cat-
alysts at 60 °C. (6.8 mmol L-glutamic acid, L-glutamic acid/benzyl alcohol molar ratio =
Fig. 3. Esterification of benzyl alcohol and L-glutamic acid at different L-glutamic acid/benzyl
alcohol molar ratios (conditions: L-glutamic acid 6.8 mmol, 60 °C, 2 h, CuCl 0.68 mmol).
1:1.5, 2 h, solid catalyst 0.1 g, others 0.68 mmol, racemization was not detected).
2