A green procedure for the oxidation of benzyl halides to aromatic aldehydes or ketones in aqueous media

Article abstract of DOI:10.1080/00397910903531623

Green oxidation of benzyl halides to the corresponding aldehydes or ketones was achieved in aqueous media using trimethylamine N-oxide generated in situ from trimethylamine and H₂O₂. The yield of the reaction was excellent and the workup was simple. Copyright

Full text of DOI:10.1080/00397910903531623

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A Green Procedure for the Oxidation of
Benzyl Halides to Aromatic Aldehydes or
Ketones in Aqueous Media
Pengwu Zheng a , Li Yan a , Xiujie Ji b & Xuemin Duan a
a School of Pharmacy, Jiangxi Science and Technology Normal
University, Nanchang, P. R. China
b School of Material Science and Engineering, Tianjin Polytechnic
University, Tianjin, P. R. China
Version of record first published: 14 Dec 2010.
To cite this article: Pengwu Zheng, Li Yan, Xiujie Ji & Xuemin Duan (2010): A Green Procedure
for the Oxidation of Benzyl Halides to Aromatic Aldehydes or Ketones in Aqueous Media, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:1, 16-19
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Synthetic Communications1, 41: 16–19, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903531623
A GREEN PROCEDURE FOR THE OXIDATION OF
BENZYL HALIDES TO AROMATIC ALDEHYDES
OR KETONES IN AQUEOUS MEDIA
Pengwu Zheng,1 Li Yan,1 Xiujie Ji,2 and
Xuemin Duan1
1School of Pharmacy, Jiangxi Science and Technology Normal University,
Nanchang, P. R. China
2School of Material Science and Engineering, Tianjin Polytechnic University,
Tianjin, P. R. China
Green oxidation of benzyl halides to the corresponding aldehydes or ketones was achieved
in aqueous media using trimethylamine N-oxide generated in situ from trimethylamine
and H2O2. The yield of the reaction was excellent and the workup was simple.
Keywords: Aldehydes; benzyl halides; green oxidation; ketones; trimethylamine N-oxide
INTRODUCTION
The oxidation of benzyl halides to carbonyl compounds is a significant reac-
tion because aromatic aldehydes and ketones are used widely and benzyl halides
are easily available. Several oxidations of organic halides to carbonyl compounds
are known. These include the Hass-Bender reaction,[1] the Sommelet reaction,[2]
the Krohnke reaction,[3] the Kornblum reaction,[4] the Masaki photooxidation,[5]
and oxidations using NaOCl,[6] MnO2,[7] KNO3,[8] DMSO,[9] Pyridine N-Oxide in
the presence of Ag2O,[10] and transition metal complexes.[11] Our group[12] discov-
ered the first green oxidation of benzyl halides with V2O5-H2O2 in aqueous
media.
Trimethylamine N-oxide (TMANO) has been used as an oxidant in the
oxidation of benzyl halides to carbonyl compounds.[13] The solvents used include
DMF, DMSO, CHCl3, CH3CN. There has been no oxidation performed in H2O,
that is an environmentally benign solvent. Replacement of organic solvents with
water would help to reduce the environment problems associated with the oxidation.
For this purpose, we carried out the following investigations. First, we heated benzyl
chloride and 1.5 eq. of TMANO in H2O to reflux. The reaction completed quickly
and the conversion of benzyl chloride to benzaldehyde was quantitative. This proved
Received April 23, 2009.
Address correspondence to Professor Pengwu Zheng, School of Pharmacy, Jiangxi Science and
Technology Normal University, Nanchang 330013, China. E-mail: zhengpw@126.com
16

GREEN OXIDATION OF BENZYL HALIDES IN AQUEOUS MEDIA
17
Table 1. Green oxidation of benzyl halides to aldehydes or ketones by TMA=H2O2 in aqueous media
Entry
Substrates
C6H5CH2Cl
Product
C6H5CHO
Time
Yield (%)a
1
2
30 min
1 h
1 h
82
85
93
92
93
92
88
94
87
85
86
80
78
p-ClC6H4CH2Cl
o-ClC6H4CH2Cl
p-CH3C6H4CH2Cl
o-HOC6H4CH2Cl
o-nBuOC6H4CH2Cl
o-iBuOC6H4CH2Cl
2,6-Cl2C6H3CH2Cl
C6H5CHClC6H5
p-ClC6H4CHClC4H9
p-NO2C6H4CH2Cl
C6H5CH2Br
p-ClC6H4CHO
o-ClC6H4CHO
p-CH3C6H4CHO
o-HOC6H4CHO
o-nBuOC6H4CHO
o-iBuOC6H4CHO
2,6-Cl2C6H3CHO
C6H5COC6H5
3
4
20 min
20 min
20 min
1 h
5
6
7
8
2 h
4 h
9
10
11
12
13
p-ClC6H4COC4H9
p-NO2C6H4CHO
C6H5CHO
6 h
4 h
15 min
12 h
1,4-(BrCH2)2C6H4
1,4-(CHO)2C6H4
aIsolated yield after column chromatography on SiO2.
that the oxidation can equally be performed in aqueous media. Then, we theorized
that TMANO, commercially prepared through oxidation of trimethylamine (TMA)
with H2O2, could be generated in situ from TMA and H2O2 and function as an oxi-
dant for benzyl chloride. We refluxed a mixture of benzyl chloride, TMA (1.5 eq.),
H2O2 (1.5 eq.) in H2O for 30 min. This led to the formation of benzaldehyde as
the only product in 82% yield. When the reaction was conducted at large scales,
the product was separated from water layer after cooling to room temperature.
We have successfully replaced the TMANO with TMA and H2O2 in the oxidation.
Altogether 13 halides were similarly oxidized to the corresponding benzaldehydes
and aromatic ketones in high yields. As shown in Table 1, electron donating groups
such as –OH or –OR on aromatic ring lead to higher reaction rates (entries 4, 5, 6).
Electron withdrawing groups such as –NO2 or –X reduce the reaction rates substan-
tially (entries 2, 3, 11). Bulky groups and ortho substituents reduced the reaction
rates (entry 7 vs 6, entry 8 vs 3). Generally, primary halides are oxidized faster than
secondary halides (entries 1, 2 vs 9, 10). The reaction is faster with benzyl bromide
than with benzyl chloride (entry 12 vs 1). All the oxidations produced a single
product as determined by TLC and GC. All the products are known compounds
1
and were fully identified by IR and H NMR.
Based on these facts, we put forward the following mechanism (Scheme 1).
Under refluxing conditions, TMA and H2O2 reacted to form TMANO quickly.
Scheme 1. The mechanism of the oxidation of benzyl halides to aromatic aldehydes or ketones.

18
P. ZHENG ET AL.
The oxygen atom on TMANO is partially negatively charged and can react as a
nucleophilic oxidant toward halides that are converted into aldehydes or ketones.
In conclusion, we successfully improved the literature methods from two
aspects. One is that the organic solvents was replaced by water. The other is
that TMANO could be generated in situ from TMA and H2O2 during the
oxidation. Compared with the known procedure, the new green method we
have developed has the following advantages: (1) Environmental friendly water
was used as reaction media. Because no organic solvents were used in the whole
process, green oxidation of benzyl halides was achieved. (2) TMA and H2O2
were used to generate TMANO in situ and this avoided the use of TMANO,
which simplified the workup procedure. (3) No side products were formed in
the oxidation. The reaction rate was high and the yield of the reaction was close
to quantitative. The product was easily separated from water and the workup
was much simplified.
Typical procedure: A mixture of H2O (30 mL), benzyl chloride (3.03 g), TMA
(33%, 1.5 eq.), H2O2 (30%, 1.5 eq.) was refluxed for 30 min. TLC was used to moni-
tor the completion of the reaction. After cooling to room temperature, the oil layer
was separated and subsequent isolation by column chromatography on SiO2 pro-
duced 2.08 g of benzaldehyde in 82% yield.
ACKNOWLEDGMENTS
This work was supported by the Science Funds of the Education Office of
Jiangxi, China (granted No. [2006] 246 and [2007] 414) and by the Science Funds
of Jiangxi Provincial Department of Science and Technology, China (granted
No.[2005] 224).
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