Efficient and convenient oxidation of organic halides to carbonyl compounds by H2O2 in ethanol

Article abstract of DOI:10.1016/j.tetlet.2007.01.084

Various primary and secondary organic bromides were oxidized by hydrogen peroxide in refluxing ethanol to give the corresponding aldehydes/and ketones in high yield up to 94%; organic chlorides were oxidized to the corresponding aldehydes/and ketones by the same oxidant in ethanol in the presence of 10 mol % of KBr as the catalyst.

Full text of DOI:10.1016/j.tetlet.2007.01.084

Tetrahedron Letters 48 (2007) 1919–1921
Efficient and convenient oxidation of organic halides
to carbonyl compounds by H2O2 in ethanol
Jingting Tang, Jinlong Zhu, Zongxuan Shen and Yawen Zhang*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry and Chemical Engineering,
Suzhou University, Suzhou 215123, China
Received 17 November 2006; revised 16 January 2007; accepted 18 January 2007
Available online 23 January 2007
Abstract—Various primary and secondary organic bromides were oxidized by hydrogen peroxide in refluxing ethanol to give the
corresponding aldehydes/and ketones in high yield up to 94%; organic chlorides were oxidized to the corresponding aldehydes/
and ketones by the same oxidant in ethanol in the presence of 10 mol % of KBr as the catalyst.
ꢀ 2007 Elsevier Ltd. All rights reserved.
The oxidation of organic halides to the corresponding
carbonyl compounds is a well known transformation
in organic synthesis. In many cases, it affords more
convenient access to the carbonyl compounds than the
oxidation of the corresponding alcohols.
along with sodium bicarbonate. A high reaction temper-
ature is often required in both methods. Other notable
methods to accomplish this conversion include the use
of various amine N-oxide,7–10 N-alkoxypyridinium
salt,11–14 NaIO4–DMF,15 selenium compounds,16 oxodi-
peroxovanadate,17 and IBX.18 Masaki and co-workers19
have reported the photo-oxidation of aryl bromides with
mesoporous silica FSM-16, which uses oxygen as the
oxidant. Selenium compounds are harmful to the envi-
ronment, and the method of amine N-oxide is not con-
veniently enough. In this Letter, we report an efficient
and convenient method for the oxidation of organic
halides to the carbonyl compounds, wherein H2O2 in
ethanol was used as the oxidant. The reaction proceeded
well for various substituted benzylic halides affording
high yields of aldehydes/or ketones (Table 1).
The oldest method for such a conversion constitutes the
Hass–Bender reaction,1 which involves O-alkylation of
the nitronate anion followed by decomposition of the
resulting intermediate. This method is only satisfied
for para-substituted substrates. Sommelet reaction2 is
another classic method for this transformation. The
reaction of the halides with hexamethylenetetramine
gives the formaldehyde imine of the corresponding pri-
mary amine, which tautomerized into the methyl imine
of the desired carbonyl compound. But benzaldehydes
with electron-deficient or ortho-substituted rings are
not satisfied.
It was found that benzyl bromide could be oxidized to
benzaldehyde by hydrogen peroxide in ethanol at reflux
in 3 h.20 In other solvents such as tetrahydrofuran, chlo-
roform, and methylene chloride, much longer time was
required and the conversion was poorer. The scope of
this transformation was then investigated and the results
are listed in Table 1.
Various reagents have been developed for this transfor-
mation in the ensuing decades. The Kro¨hnke3 reaction
and the Kornblum4–6 reaction are the two most notable
methods. Kro¨hnke reaction involves converting the
halide to the pyridinium salt with p-N,N-dimethyl-
nitroso-aniline to give a nitrone, which is hydrolyzed
in aqueous acid to the carbonyl compounds. The
Kornblum reaction is refluxing organic halide in DMSO
Under the same conditions, various substituted benzylic
bromides including 2-bromomethyl-naphthalene were
readily oxidized to the corresponding aldehydes in high
yields in a few hours (entries 1–7), whilst a strong
electron-withdrawing nitro group at the para-position
resulted in lower conversion, 70% of the starting
material was recovered after 24 h (entry 8). Under the
Keywords: Oxidation; Organic halide; Hydrogen peroxide; Aldehyde;
Ketone.
*
Corresponding author. Tel.: +86 0512 65880339; fax: +86 0512
65880305; e-mail: zhangyw@suda.edu.cn
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.01.084

1920
J. Tang et al. / Tetrahedron Letters 48 (2007) 1919–1921
Table 1. Oxidation of primary and secondary organic bromides by H2O2 in ethanola
O
Br
H2O2, EtOH
reflux
R1
R2
R1
R2
Entry
Substrate
Product
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
PhCH2Br
PhCHO
3
3.5
3.5
3
6
10
3
24
1
0.5
2
2.5
24
89
90
93
76
85
80
83
20c
91
94
85
86
nd
4-Cl–C6H4CH2Br
2-Cl–C6H4CH2Br
4-CH3–C6H4CH2Br
3,5-(CH3)2–C6H4CH2Br
3-Cl–C6H4CH2Br
2-Naph–CH2Br
4-NO2–C6H4CH2Br
PhCHBrCH3
4-Cl–C6H4CHO
2-Cl–C6H4CHO
4-CH3–C6H4CHO
3,5-(CH3)2–C6H4CHO
3-Cl–C6H4CHO
2-Naph–CHO
4-NO2–C6H4CHO
PhCOCH3
Ph2CHBr
Ph2CO
4-F–C6H4CHBrCH3
4-Br–C6H4CHBrPh
CH3(CH2)3CH2Br
4-F–C6H4COCH3
4-Br–C6H4COPh
—
a General reaction conditions: bromide (2 mmol), H2O2 (30%, 2 mL), ethanol (15 mL), reflux.
b Isolated yield.
c 70% of starting material was recovered.
Table 2. KBr catalyzed oxidation of organic chlorides by H2O2 in
reaction conditions (refluxing in ethanol), further oxida-
tion of benzaldehyde to benzoic acid was not observed.
However, on exposure to air, oxidation of benzaldehyde
to benzoic acid occurred.
ethanola
O
Cl
H2O2, KBr (10 mol%)
EtOH, reflux
R1
R2
Time Yieldb
R1
R2
Secondary bromides such as (1-bromoethyl)benzene
(entry 9), benzhydryl bromide (entry 10), 1-(1-bromo-
ethyl)-4-fluorobenzene (entry 11), and 1-bromo-4-(bromo-
(phenyl)-methyl)benzene (entry 12) were readily
oxidized to the corresponding ketones in high yields.
The reaction rate of secondary bromide was obviously
faster than that of primary bromide.
Entry Substrate
Product
(h)
(%)
1
2
3
4
5
6
7
PhCH2Cl
PhCHO
3.5 82
4-Br–C6H4–CH2Cl
4-Cl–C6H4–CH2Cl
Ph2CHCl
PhCHClCH3
4-F–C6H4–CHClCH3 4-F–C6H4–COCH3
4-Br–C6H4–CHClPh 4-Br–C6H4–COPh
4-Br–C6H4–CHO
4-Cl–C6H4–CHO
Ph2CO
24
4
1
70
90
90
PhCOCH3
1.5 82
2.5 83
2.5 88
Alkyl bromide such as n-pentyl bromide (entry 13) was
found inert to this reaction, no product was detected.
a General reaction conditions: chloride (2 mmol), KBr (0.2 mmol),
H2O2 (30%, 2 mL), ethanol (15 mL), reflux.
b Isolated yield.
When these reaction conditions were applied to benzyl
chloride, no desired product was obtained. Since the
conversion of benzylic or allylic chloride to the corre-
sponding bromide by KBr occurs readily, addition of
catalytic amount of KBr may be helpful to this reaction.
Indeed, in the presence of 10 mol % of KBr, benzyl chlo-
ride could be oxidized to benzaldehyde by H2O2 in
refluxing ethanol. Similarly, conversion of a series of
benzylic chlorides to the corresponding aldehydes/
ketones was achieved using KBr as the catalyst21 (Table
2).
Secondary halides hydrolyzed faster than primary ones,
so that they were oxidized faster.
In conclusion, we have discovered an efficient and
convenient method for the transformation of organic
halides to carbonyl compounds, though it is not satisfied
for aliphatic bromides. It provides an easy way to
A plausible mechanistic pathway for the oxidation of
bromides, similar to that of alcohol, proposed by Sain
and co-workers,22 is shown in Scheme 1. Hydrolysis of
starting material 1 yielded the corresponding alcohol
2, which was then oxidized to hypobromite 3 by the
hypobromous acid, formed in situ by the reaction of
hydrobromic acid with hydrogen peroxide. This hypo-
bromite species, on abstraction of hydrogen, provided
the final product, with regeneration of HBr. In the oxi-
dation of organic chlorides, addition of catalytic amount
of KBr was desired, to produce the actual oxidizing
agent, hypobromous acid. It looks likely that the hydro-
lysis of the organic halide is the rate-determining step.
R1 C R2
O
4
H2O2
H
H2O
HOBr
H2O HBr
H2O
H
H
R1
C R2
R1 C R2
R1 C R2
OH
2
Br
1
OBr
3
Scheme 1. A plausible mechanistic pathway for the oxidation of
organic bromide.

J. Tang et al. / Tetrahedron Letters 48 (2007) 1919–1921
1921
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Acknowledgement
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