Efficient and Convenient Oxidation of Organic Halides to Aldehydes ...

28 Journal of the Chinese Chemical Society, 2010, 57, 28-33
Communication
Efficient and Convenient Oxidation of Organic Halides to Aldehydes and
Ketones Catalyzed by H 5 IO 6 /V 2 O 5 in Ionic Liquid [bmpy][PF 6 ]
Yu-Lin Hu ( ), Xiang Liu ( ),
Ming Lu* ( ) and Hui Jiang ( )
Chemical Engineering College, Nanjing University of Science and Technology, Nanjing 210094, P. R. China
A mild, efficient, and eco-friendly procedure for the oxidation of organic halides to aldehydes and ketones
in good to high yields catalyzed by H 5 IO 6 /V 2 O 5 in ionic liquid [bmpy][PF 6 ] with no trace of
overoxidation to carboxylic acids has been developed. The product can be isolated by a simple extraction
with organic solvent, and the catalytic system can be recycled or reused without any significant loss of catalytic
activity.
Keywords: Oxidation; Organic halide; H 5 IO 6 /V 2 O 5 ; Ionic liquid.
INTRODUCTION
Aldehydes and ketones are important classes of chemicals
that have been used extensively as synthetic intermediates
in the preparation of a variety of fine or special
chemicals such as drugs, vitamins, fragnances, etc. 1 Up to
now, many publications in the open literature have been
found in synthesis of these type of compounds, and a well
known method for such a synthesis constitutes the oxidation
of benzyl halides. 2,3 Hass-Bender reaction 4,5 and
Sommelet reaction 6 are two classic methods for such a conversion.
While each has some limitations, the former
method is only satisfied for para-substituted substrates, the
latter unfortunately has limited substrate scope. Various
reagents employed as the oxygen donors have been developed
for this conversion include dimethyl sulfoxide
(DMSO), 7,8 N,N-dimethyl-4-nitrosoaniline, 9 nitronate anion
and Pd(PPh3), 10 pyridine N-oxides, 11 amine oxides, 12,13
N-alkoxypyridinium salts, 14,15 silver nitrate, 16 potassium
chromate, 17 pyrazinyl sulfoxides, 18 NaIO 4 -DMF, 19 selenium
compounds, 20 etc. 21-25 However, some of these procedures
are invariably associated with one or more disadvantages
such as long reaction time, high temperature, low
yields, harmful to the environment, etc. Consequently,
there is a great need to develop new and environment-benign
procedures that address these drawbacks for such a
conversion.
Ionic liquids (ILs) are a class of organic salts with unusually
low melting temperatures that have attracted much
attention from the scientific community in recent years. As
a class of potential greener solvents, ILs exhibit many
unique physicochemical properties, such as negligible volatility
and nonflammability under ambient conditions,
large liquid range, high thermal stability, wide electrochemical
window, and strong ability to dissolve many
chemicals. 26,29 Therefore, ILs have found wide applications
in chemical synthesis, 27-29 biocatalytic transformations,
30,31 electrochemistry, 32 and analytical and separation
science. 33,34
In continuation of our interest in exploring green oxidation
in ionic liquids, we herein report a mild and effective
procedure for the selective oxidation of organic halides to
aldehydes and ketones with H 5 IO 6 /V 2 O 5 using 1-butyl-3-
methylimidazolium hexafluorophosphorate ([bmpy][PF 6 ])
as the solvent (Scheme I). Furthermore, we demonstrate
that the catalytic system can be recycled and reused without
any significant loss of catalytic activity.
Scheme I
* Corresponding author. Tel: +86-025-84315030; Fax: +86-025-84315030; E-mail: luming1963@163.com

Oxidation of Organic Halides by H 5 IO 6 /V 2 O 5 /[bmpy][PF 6 ] J. Chin. Chem. Soc., Vol. 57, No. 1, 2010 29
Table 1. Optimization of the reaction conditions for oxidizing 1-
(chloromethyl)-4-methylbenzene to 4-methylbenzaldehyde
a
Entry Catalyst Ionic liquid Time (h) Yield (%) b
1 V 2 O 5 [bmim]BF 4 7 74
2 V 2 O 5 [bmim]Cl 8 68
3 V 2 O 5 [hmim]OTf 6 76
4 V 2 O 5 [hmim]PF 6 6 83
5 V 2 O 5 [bmpy]PF 6 3 97
6 V 2 O 5 [bpy]PF 6 3 89
7 V 2 O 5 [bmpy]PF 6 3 97 c
8 V 2 O 5 [bmpy]PF 6 3 96 d
9 V 2 O 5 10 53
10 [bmpy]PF 6 6 48
a Reaction conditions: 1-(chloromethyl)-4-methylbenzene (10
mmol), V 2 O 5 (0.3 mmol), H 5 IO 6 (12 mmol), ionic liquid 5 mL, 50
°C. b Isolated yield. c The second run. d The third run.
RESULTS AND DISCUSSION
The initial study was carried out using 1-(chloromethyl)-4-methylbenzene
as the substrate to optimize the
reaction conditions, and the results are summarized in Table
1. At first, six type of ionic liquids, 1-butyl-3-methylimidazolium
tetrafluoroborate ([bmim]BF 4 ), 1-butyl-3-
methylimidazolium chloride ([bmim]Cl), 1-hexyl-3-methylimidazolium
trifluoromethansulfonate ([hmim]OTf),
1-hexyl-3-methylimidazolium hexafluorophosphate
([hmim]PF 6 ), 1-butyl-4-methylpyridinium hexafluorophosphate
([bmpy]PF 6 ), and butylpyridinium hexafluorophosphorate
([bpy]PF 6 ), were tested with V 2 O 5 as the catalyst
precursor in the reaction (Table 1, entries 1-6), it was observed
that [bmpy]PF 6 demonstrated the best performance,
providing a 97% high yield (Table 1, entry 5). The different
effects of ILs in the reaction may be attributed to their different
abilities of stabilizing and dissolving the oxidant
H 5 IO 6 and the catalyst V 2 O 5 . Under the same conditions,
the IL who stabilizes and dissolves them more easily will
leads to a larger increase in the effective reactant concentration,
which increases the encounter probabilities between
the substrate and reactive species, and so the higher
rate and yield of the reaction is observed. In addition, the
catalytic system could be typically recovered and reused
with no appreciable decrease in yields and reaction rates
(Table 1, entries 7 and 8). Furthermore, the catalyst V 2 O 5
and the solvent [bmpy]PF 6 are crucial for this oxidation,
and the lack of any component leads to a lower yield (Table
1, entries 9 and 10). In addition, no over-oxidized product
(4-methylbenzoic acid) was detected by 1 H NMR analysis
of the crude reaction mixtures in all the cases.
With these results in hand, the catalytic system was
then applied to various organic halides as summarized in
Table 2. It is clear that various types of benzylic and allylic
halides, both primary and secondary, have been successfully
oxidized to the corresponding aldehydes and ketones
in good to high yields (Table 2, entries 1-19), whereas the
aliphatic halides were less reactive, and the reactions proceeded
more slowly, and even under more drastic reaction
conditions, the reactions were still incomplete (Table 2, entries
20 and 21). Surprisingly, the oxidation of primary
halides to the corresponding carbonyl compounds is faster
and more efficient than secondary halides (Table 2, entries
13-15 and 17). This is not in agreement with reactions performed
in classical organic solvents, 19,22,23 which are excellent
results for a V 2 O 5 -catalyzed halide oxidation performed
in an ionic liquid. Further, the reaction is faster with
benzyl chlorides than with benzyl bromides (Table 2, entries
2 and 3). In addition, the electron deficiency and nature
of the substituents on the aromatic ring have influence
on the oxidation rate, benzylic halides having electronwithdrawing
groups on the aromatic ring (Table 2, entries
9, 13 and 16) react more slowly than those having electron-donating
groups (Table 2, entries 2-8 and 10).
A possible mechanism for the oxidation of organic
halides, similar to that of alcohols catalyzed by H 2 O 2 /V 2 O 5 ,
proposed by Butler and co-workers, 35 isshowninScheme
II. In acidic solution, V 2 O 5 can exist as VO 2 + and VO 3 at
first. Addition of H 5 IO 6 to VO 2 + can give the red oxoperoxo
Scheme II Possible mechanism for the oxidation of organic
halides

30 J. Chin. Chem. Soc., Vol. 57, No. 1, 2010 Hu et al.

Oxidation of Organic Halides by H 5 IO 6 /V 2 O 5 /[bmpy][PF 6 ] J. Chin. Chem. Soc., Vol. 57, No. 1, 2010 31
VO(O 2 ) + (I) and the yellow oxodiperoxo VO(O 2 ) 2 species
(II), which reacts with organic halide to form transition
state (III) andthen,III eliminated the oxoperoxo (I) and
H + to yield the desired product. The low activities of the
secondary halides might be attributed to steric effects of the
complex II, and which suggests that II is a bulky nucleophile
and is sensitive to steric hindrance. The reason why
benzyl chlorides reacted faster than that of benzyl bromides
possibly lies that II is such a good leaving group that
it is more easily substituted by the better nucleophile, bromide
ion, than by the chloride ion. It looks like that the formation
of III between II and organic halide is the rate-determining
step.
CONCLUSIONS
In conclusion, we have demonstrated an efficient and
selective oxidation of organic halides to aldehydes and ketones
by using H 5 IO 6 /V 2 O 5 catalyst system in the ionic liquid
[bmpy]PF 6 . Most importantly, the catalysts are very
easy to handle and can be recycled and reused without any
significant loss of catalytic activity. The scope, the defination
of the mechanism, and synthetic applications of the oxidation
are currently under investigation.
EXPERIMENTAL
Apparatus and reagents
All the used chemicals were from commercial sources
without any pretreatment. All reagents were of analytical
grade. The ionic liquids were synthesized according to the
literature procedures. 28,32,36 The reduced pressure distillation
were performed on a micro-distillation apparatus
(Model MRS 255). Melting points were recorded on a
Buchi R-535 apparatus and are uncorrected. 1 HNMRspectra
were recorded on a Bruker 400-MHz spectrometer using
CDCl 3 as the solvent with tetramethylsilane (TMS) as
an internal standard. Elemental analysis were performed on
a Vario EL III instrument (Elmentar Anlalysensy Teme
GmbH, Germany).
General procedure for the oxidation of organic
halides
To a stirred solution of organic halide (10 mmol) in
ionic liquid [bmpy]PF 6 (5 mL) was added H 5 IO 6 (12 mmol)
and V 2 O 5 (0.3 mmol) at room temperature and stirring was
continued at 50 °C for the appropriate time (Table 2). After
completion of the reaction, as indicated by TLC, the product
was extracted with dichloromethane (3 × 10 mL). The
combined organic layer was washed to neutral with 5%
NaHCO 3 solution (3 × 10 mL ) and water (3 × 10 mL), and
then dried over anhydrous Na 2 SO 4 . The solvent was removed
and the residue was distilled under vacuum to give
the desired pure product. The rest of the ionic liquid and the
catalyst were recovered by decantation of aqueous hydrogen
halide produced in the reaction and concentration under
vacuum. Fresh subtrates were then recharged to the recovered
catalyst system and then recycled under identical
reaction conditions. The target substrates were characterized
by Elemental analysis, 1 H NMR or compared with
their authentic samples. Spectroscopic data for selected
products is as follows.
4-Methylbenzaldehyde (2)
Colourless oil. 1 H NMR (400 MHz, CDCl 3 ): 2.24
(s, CH 3 ,3H),7.32(d,J = 7.6 Hz, Ar-H, 2H), 7.68 (d, J =7.6
Hz, Ar-H, 2H), 9.96 (s, CHO, 1H). Anal. Calcd for C 8 H 8 O:
C, 79.94; H, 6.72; O, 13.33. Found: C, 79.97; H, 6.71; O,
13.32.
2-Isopropylbenzaldehyde (4)
Colourless oil. 1 H NMR (400 MHz, CDCl 3 ): 1.28
(d, J =7.8Hz,CH 3 , 6H), 2.98 (m, CH, 1H), 7.49-7.99 (m,
Ar-H, 4H), 9.86 (s, CHO, 1H). Anal. Calcd. for C 10 H 12 O:
C, 80.97; H, 8.15; O, 10.82. Found: C, 81.04; H, 8.16; O,
10.80.
4-Tert-butylbenzaldehyde (5)
Colourless oil. 1 H NMR (400 MHz, CDCl 3 ): 1.31
(s, CH 3 , 9H), 7.53-7.79 (m, Ar-H, 4H), 9.96 (s, CHO, 1H).
Anal. Calcd. for C 11 H 14 O: C, 81.38; H, 8.71; O, 9.85.
Found: C, 81.44; H, 8.70; O, 9.86.
2,4,6-Trimethylbenzaldehyde (6)
Colourless oil. 1 H NMR (400 MHz, CDCl 3 ): 2.17
(s, CH 3 ,3H),2.43(s,CH 3 , 6H), 7.24 (s, Ar-H, 2H), 9.91 (s,
CHO, 1H). Anal. Calcd. for C 10 H 12 O: C, 81.03; H, 8.17; O,
10.77. Found: C, 81.04; H, 8.16; O, 10.80.
3,4-(Methylenedioxy)-benzaldehyde (7)
White solid, mp: 36-38 °C. 1 H NMR (400 MHz,
CDCl 3 ): 6.04 (s, CH 2 , 2H), 6.86-7.53 (m, Ar-H, 3H), 9.86
(s, CHO, 1H). Anal. Calcd for C 8 H 6 O 3 : C, 63.99; H, 4.01;
O, 31.98. Found: C, 64.00; H, 4.03; O, 31.97.
3,4,5-Trimethoxybenzaldehyde (8)
White solid, mp: 74-76 °C. 1 H NMR (400 MHz,
CDCl 3 ): 3.77 (s, CH 3 O, 3H), 3.92 (s, CH 3 O, 6H), 7.12-
7.16 (s, Ar-H, 2H), 9.86 (s, CHO, 1H). Anal. Calcd for
C 10 H 12 O 4 : C, 61.18; H, 6.17; O, 32.64. Found: C, 61.22; H,
6.16; O, 32.62.

32 J. Chin. Chem. Soc., Vol. 57, No. 1, 2010 Hu et al.
4-Methoxybenzaldehyde (10)
Colourless oil. 1 H NMR (400 MHz, CDCl 3 ): 3.96
(s, CH 3 O, 3H), 7.37 (d, J = 7.9 Hz, Ar-H, 2H), 7.72 (d, J =
7.9 Hz, Ar-H, 2H), 9.97 (s, CHO, 1H). Anal. Calcd for
C 8 H 8 O 2 : C, 70.54; H, 5.92; O, 23.51. Found: C, 70.57; H,
5.92; O, 23.50.
3,7-Dimethyl-2,6-octadienal (12)
Colorless liquid. 1 H NMR (400 MHz, CDCl 3 ): 1.57
(s, CH 3 ,3H),1.91(s,CH 3 ,3H),2.23(s,CH 3 ,3H),2.61(m,
CH 2 CH 2 ,4H),5.10(s,CH,1H),5.85(d,J = 7.0 Hz, CH,
1H), 9.80 (d, J = 7.0 Hz, CHO, 1H). Anal. Calcd for
C 10 H 16 O: C, 78.87; H, 10.59; O, 10.52. Found: C, 78.90; H,
10.59; O, 10.51.
1-(4-Fluorophenyl)ethanone (13)
Colourless oil. 1 H NMR (400 MHz, CDCl 3 ): 2.53
(s, CH 3 ,3H), 7.27-7.31 (m, Ar-H, 2H), 7.96-8.03 (m, Ar-H,
2H). Anal. Calcd. for C 8 H 7 FO: C, 69.51; H, 5.07; F, 13.74;
O, 11.59. Found: C, 69.56; H, 5.11; F, 13.75; O, 11.58.
Propiophenone (14)
Colourless oil. 1 H NMR (400 MHz, CDCl 3 ): 1.23 (t,
J =7.2Hz,CH 3 ,3H),3.48(q,J =7.8Hz,CH 2 ,2H),
7.37-7.54 (m, Ar-H, 3H), 7.88-7.94 (m, Ar-H, 2H). Anal.
Calcd for C 9 H 10 O: C, 80.51; H, 7.53; O, 11.92. Found: C,
80.56; H, 7.51; O, 11.92.
Benzophenone (15)
White solid, mp: 47-48 °C. 1 H NMR (400 MHz,
CDCl 3 ): 7.31-7.56 (m, Ar-H, 6H), 7.93-8.02 (m, Ar-H,
4H). Anal. Calcd for C 13 H 10 O: C, 85.65; H, 5.53; O, 8.79.
Found: C, 85.69; H, 5.53; O, 8.78.
4-Nitro-benzaldehyde (16)
Light yellow solid, mp: 104-106 °C. 1 H NMR (400
MHz, CDCl 3 ): 8.11-8.34 (m, Ar-H, 4H), 10.22 (s, CHO,
1H). Anal. Calcd for C 7 H 5 NO 3 : C, 55.61; H, 3.34; N, 9.26;
O, 31.77. Found: C, 55.63; H, 3.33; N, 9.27; O, 31.76.
trans-Cinnamaldehyde (18)
Colourless oil. 1 H NMR (400 MHz, CDCl 3 ): 6.65
(d, J = 16.7 Hz, CH, 1H), 6.69 (dd, J = 6.5, 16.7 Hz, CH,
1H), 7.36-7.51 (m, Ar-H, 5H), 9.65 (d, J = 6.5 Hz, CHO,
1H). Anal. Calcd for C 9 H 8 O: C, 81.79; H, 6.10; O, 12.11.
Found: C, 81.79; H, 6.10; O, 12.11.
2-Octanone (20)
Colourless oil. 1 H NMR (400 MHz, CDCl 3 ): 0.90 (t,
J =7.0Hz,CH 3 ,3H),1.30(m,CH 2 ,6H),1.56(m,CH 2 ,
2H), 2.16 (s, CH 3 ,3H),2.44(m,CH 2 ,2H).Anal.Calcdfor
C 8 H 16 O: C, 74.91; H, 12.57; O, 12.49. Found: C, 74.94; H,
12.58; O, 12.48.
ACKNOWLEDGEMENTS
We thank the National Basic Research Program (973)
of China (No. 613740101) and Natural Science Foundation
of Jiangsu Province for supporting this research.
Received November 8, 2009.
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