G Model
CCLET-3378; No. of Pages 4
2
C. Fang et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
OH
OH
CuCl/TEMPO/Bipy
O2, 50 oC
VOPO4·2H2O
Air, 150 oC
O
O
O
O
O
O
(d)
(e)
O
(a)
(b)
(c)
Riisager 2013
Carlini 2005
O
OH
O
OH
O
Vanadyl-pyridine
Air, 130 oC
K-OMS-2
O2, 110 oC
O
O
Fu 2012
Corma 2009
2,5-DFF
OH
O
OH
O
Fe(NO3)3·9H2O
TEMPO
Cu(NO3)3/VOSO4
O2, r.t.
O
Air, r.t.
This work
Xu 2011
Scheme 1. The processes for the oxidation of 5-HMF to 2,5-DFF.
chemical shift (
constant (Hz). Data for 13C NMR are reported in chemical shifts
ppm). Gas chromatographic (GC) analyses were performed on a
Shimadzu GC-2014 series GC system equipped with a flame-
ionization detector using biphenyl as an internal standard. The
temperature was 150 8C. Organic solutions were concentrated
under reduced pressure on a Buchi rotary evaporator. Flash column
chromatographic purification of products was accomplished using
forced-flow chromatography on Silica Gel (200–300 mesh).
d
ppm), multiplicity, integration, and coupling
entries 4–6). NaF is the only exception, which slightly decreased
the yield of 2 to 54% (Table 1, entry 7). Halide anions have been
shown to act as ligands for transition metals [19]. The ClÀ from
NaCl may act as a special electron-donating ligand to provide
electrons to the d orbitals of Fe3+ to accelerate the semi-oxidative
addition-type coupling with TEMPO (A proposed mechanism was
shown in the Supporting information) [18]. Other metal catalysts
such as Cu(NO3)2Á3H2O, AgNO3, Pd(NO3)2 and FeCl3 could also
initiate the reaction, albeit giving lower yields of 2 (Table 1, entries
8–11). In general, the reaction yield can be further improved by
using other organic solvents (Table 1, entries 12–17). However,
when the reaction was conducted in water, only a trace amount
of 2 could be obtained (Table 1, entry 18). The use of 1,2-
dichloroethane (DCE) as the solvent gave the best result (GC yield,
92%; isolated yield, 88%) (Table 1, entry 16).
(
d
2.2. The typical process for aerobic oxidation of 5-HMF to 2,5-DFF
5-HMF
(63 mg,
0.5 mmol),
Fe(NO3)3Á9H2O
(10.1 mg,
0.025 mmol, 5 mol%), TEMPO (7.8 mg, 0.025 mmol, 5 mol%), NaCl
(1.5 mg, 0.025 mol, 5 mol%) were charged into a tube, and then
2 mL of DCE was added. The reaction mixture was stirred at room
temperature for 4 h in open air. Then, the reaction was monitored
by GC analysis using 5-methyl-2-furaldehyde as an internal
standard.
Table 1
Fe/TEMPO catalyzed oxidation of 5-HMF to 2,5-DFF in air at room temperaturea.
5 mol% Catalyst
5 mol% TEMPO
OH
O
Separation of 2,5-DFF from reaction solution: after the
epinephelos solution was filtered and washed with ethyl acetate
for three times, the organic solvents were evaporated and the
crude product was purified by flash column chromatography
(PE:EA = 3:1) to give the desired product in 88% yield (detected by
O
O
O
O
5 mol% Additive
Solvent, Air, r.t.
1
2
1H NMR). 1H NMR (400 MHz, CDCl3):
d C
9.84 (s, 2H), 7.33 (s, 2H). 13
Entry
Additive
Catalyst
Solvent
Yield (%)b
NMR (100 MHz, CDCl3): 179.34, 154.30, 119.43.
d
1c
2d
3e
4
–
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
/
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
EtOAc
THF
59
2.3. The synthesis of 2,5-FDCA
–
Trace
Trace
68
–
NaBr
KCl
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
Cu(NO3)2Á3H2O
AgNO3
2,5-DFF (62 mg, 0.5 mmol) were charged into a tube, and 0.5 mL
of tert-butyl hydroperoxide (TBHP, 70% in water) (7 equiv.) was
added. The tube was stirred at 110 8C for 6 h. The liquid was
evaporated under reduced pressure, and then washed by ethyl
acetate for 3 times, the remaining solid was dried in high vacuum
to afford 90% yield of 2,5-FDCA (detected by 1H NMR). 1H NMR
5
78
6
NaCl
NaF
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
NaCl
80
7
54
8
20
9
17
10
11
12
13
14
15
16f
17
18
Pd(NO3)2
37
FeCl3
32
(DMSO-d6, 400 MHz):
(DMSO-d6, 100 MHz):
d
d
7.29 (s, 2H), 13.67 (br. s, 2H) .13C NMR
118.84, 147.52, 159.40.
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
Fe(NO3)3Á9H2O
86
80
CH3CN
Dioxane
DCE
70
85
3. Results and discussion
92 (88)g
84
Toluene
H2O
Our results indicate that Fe(NO3)3Á9H2O/TEMPO can catalyze
the oxidation of 1–2 in air at room temperature. The initial test
was performed in dichloromethane (DCM), giving a 59% yield and
a 99% selectivity (Table 1, entry 1). Control experiments revealed
that the reaction shut down completely without the addition
of Fe(NO3)3Á9H2O or TEMPO (Table 1, entries 2 and 3). Next, we
examined a number of halide salts for the oxidation process. It was
found that the use of NaBr, KCl and NaCl can improve significantly
the yield of 2 from 59% to 68%, 78% and 80%, respectively (Table 1,
trace
a
Reaction conditions: 5-HMF (0.5 mmol), additive (0.025 mmol, 5 mol%), TEMPO
(0.025 mmol, 5 mol%), catalyst (0.025 mmol, 5 mol%), in solvent (2 mL), open to air
at room temperature for 4 h.
b
GC yields were determined using 5-methyl furfural as an internal standard.
c
DCM =dichloromethane.
d
Without TEMPO.
e
Without Fe(NO3)3Á9H2O.
f
DCE = 1,2-dichloroethane.
g
Isolated yield in the parenthesis.
Please cite this article in press as: C. Fang, et al., Iron-catalyzed selective oxidation of 5-hydroxylmethylfurfural in air: A facile synthesis