A Waste-Free and Highly Effective Catalytic System for the Oxidation of Cysteine to Cystine
293
reaction, the cystine sinks to the bottom of the reactor as
soon as it is produced. Thus, not only is the product easily
separated but also the over-oxidation of the cystine is
limited, and the higher selectivity for cystine can be
obtained. At the end of reaction, the homogeneous system
turns into three-layer heterogeneous system at ambient
temperature. The top layer is the aqueous solution con-
taining residue cysteine, the bottom layer is the product
cystine, and the middle layer is the ionic liquid solution of
the metal phthalocyanine complex (Fig. 2c).
approached to the invariant (entries 1, 4–5). The results in
entries 1, 6–7 in Table 1 illustrated that the yield of cystine
evidently increased with the increase of oxygen pressure
below 2.0 MPa and its change was unobvious when oxygen
pressure was further increased above 2.0 MPa. The yield of
cystine increased by only 0.2% when the oxygen pressure
increased from 2.0 to 2.5 MPa. This may be because the
dissolved amount of the oxygen in the reaction medium
almost reached the maximum under 2.0 MPa and the extra
increase in the pressure of oxygen had less effect on the
concentration of oxygen. As shown in entries 1, 8–10, the
ionic liquid played an important role in the highly effective
oxidation reaction of cysteine and the best result was
obtained by using [hmim][BF4] as an ionic liquid phase. It
may be ascribed to that [hmim][Tf2N] and [dmim][BF4]
were water-immiscible and [hmim][BF4] was water-mis-
cible at/above 80 °C. The possibility of recycling of the
aqueous-ionic liquid catalyst system was also examined.
After the product was separated from the reaction system at
the end of each reaction, the used catalytic system was
recharged with cysteine into the reactor and the reaction
was conducted once again. The isolated yield of 96.4% was
maintained after the aqueous-ionic liquid catalyst system
was repeatedly used for 6 times (entry 11).
To characterize behaviors of the catalytic system, the
catalytic activities of the phthalocyanine complexes with
central Fe3?, Fe2? and Cu2? cations were investigated in a
water-ionic liquid [hmim][BF4] system, and the results
were summarized in Table 1. The high yields of cystine
were gotten in all the cases. However, the catalytic system
containing FeIIPc possessed the highest activity among
them (entries 1–3 in Table 1). The previous investigations
indicate that the active oxo-bridged intermediate of l-oxo
FeIIIPc was produced in the oxidation system containing
the FeIIPc as catalyst and molecular oxygen as oxidant.
However, in the same system, the active intermediate of
O = FeIVPc was produced when the FeIIIPc was used as
catalyst [21, 22]. The different catalytic efficiency among
the phthalocyanine complexes in the reaction system
reported herein may be ascribed to the different interme-
diates. This result indicated that the oxidation states and
kinds of the central metal ions in the phthalocyanine
complexes had some impact on the catalytic performance.
The experimental results for influence of the amounts of
catalyst on the reaction testified that the reaction yield
increased as increasing the amount of catalyst and finally
4 Conclusion
A novel method was established in this work to obtain
cystine by the oxidation of cysteine in the water-ionic
liquid catalytic system containing the metal phthalocyanine
complexes. The method possesses several advantages as
follows: (1) It is a very clean process without production of
the wastes; (2) The procedure is simple and easy for the
separation of the catalytic system and the product by
simple filtration; (3) The catalytic system is highly effec-
tive and to be easily recycled. So this is an organic syn-
thesis process conforming to the fundamental principles of
green chemistry and can provide a novel way to prepare
cystine in chemical industry.
Table 1 The oxidation of cysteine to cystine
Entry Ionic liquid (g)
Catalyst (mg) P(O2)(MPa) Isolated
yield (%)
1
[hmim][BF4](1.0)
FeIIPc(10.0)
2.0
98.0
88.7
82.3
98.1
70.1
98.2
83.5
22.7
32.4
13.5
96.4
2
[hmim][BF4] (1.0) FeIIIPc(10.0) 2.0
[hmim][BF4] (1.0) CuIIPc(10.0) 2.0
3
Acknowledgments We thank the key project of shanghai science
and technology committee (Nos. 05JC14070, 06DZ05025,
08JC1408600) and the Natural Sciences Foundation of China (No.
20971044) for financial support.
4
[hmim][BF4] (1.0) FeIIPc(15.0)
[hmim][BF4] (1.0) FeIIPc (5.0)
[hmim][BF4] (1.0) FeIIPc(10.0)
[hmim][BF4] (1.0) FeIIPc(10.0)
[hmim][Tf2N] (1.0) FeIIPc(10.0)
[dmim][BF4] (1.0) FeIIPc(10.0)
2.0
2.0
2.5
1.5
2.0
2.0
2.0
2.0
5
6
7
8
References
9
10
11a
No ionic liquid
[hmim][BF4] (1.0) FeIIPc(10.0)
FeIIPc(10.0)
1. Sheldon RA, Kochi JK (1981) Metal-catalyzed oxidations of
organic compounds. Academic Press, New York
2. Jacob C, Giles GI, Giles NM, Sies H (2003) Angew Chem Int Ed
42:4742–4758
3. Hand CE, Honek JF (2005) J Nat Prod 68:293–308
4. Wang X, Stanbury DM (2008) Inorg Chem 47:1224–1236
The reactions were carried out with 0.242 g cysteine (2.0 mmol)
(dissolved in 4 mL water) at 80 °C for 12 h
a
Reused at the 6th time
123