Oxidation of benzyl halides and related compounds to carbonyl compounds using hydrogen peroxide catalysed by TEMPO in water

Article abstract of DOI:10.3184/174751912X13545558675784

A green and straightforward method for the oxidation of benzyl halides and some related compounds to the corresponding carbonyl compounds is reported using hydrogen peroxide catalysed by 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) in water. The corresponding carbonyl compounds were obtained with excellent yields in a short time.

Full text of DOI:10.3184/174751912X13545558675784

22 RESEARCH PAPER
JANUARY, 22–24
JOURNAL OF CHEMICAL RESEARCH 2013
Oxidation of benzyl halides and related compounds to carbonyl
compounds using hydrogen peroxide catalysed by TEMPO in water
Ying He, Qifa Liu, Xiaoyun Ma and Ming Lu*
School of Chemical Engineering, Nan Jing University of Science andTechnology Nanjing 210094, P. R. China
A green and straightforward method for the oxidation of benzyl halides and some related compounds to the corre-
sponding carbonyl compounds is reported using hydrogen peroxide catalysed by 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) in water. The corresponding carbonyl compounds were obtained with excellent yields in a short time.
Keywords: oxidation, benzyl halides, carbonyl compounds, hydrogen peroxide, TEMPO
The oxidation of halides to the corresponding carbonyl
compounds plays an important role in organic synthesis.
Many successful methods have been developed for the direct
conversion. The Krohnke reaction,1 the Kornblum reaction2–4
and a number of its variants,5–7 copper(I) chloride/Kieselguhr,8
selenium compounds,9 IBX,10 K2CO3/DMSO,11 MnO2,12
Bi(NO3)3.5H2O/TBAF,13 NaIO4/DMF,14 pyridine N-oxide,15
NaIO4,16 V2O5/Aliquat 336/H2O2,17 bromate exchange resin,18
3,6-bis(triphenylphosphonium)cyclohexene peroxodisulfate,19
and Mg-Al hydrotalcites/DMSO20 have been developed for
this transformation. These oxidation systems are quite useful
for small-scale reactions, but, most of these methods require
hazardous, expensive or toxic reagents or high reaction
temperatures for long reaction times.
Hydrogen peroxide is a desirable oxidant because it is inex-
pensive and environmentally friendly, with water as the
sole by-product. Environmentally benign, new methods for the
oxidation of benzyl halides to benzaldehydes using hydrogen
peroxide have been published recently.21–24 Although great
progress has been made, the development of an efficient
oxidation of various kinds of organic halides with hydrogen
peroxide is still demanded in this field.
we can clearly observe that the yield increased with the increase
in the amount of TEMPO, and it reached a maximum (92%)
when the 0.05 equiv. of the promoter was used (Table 1, entry
4). However, with further addition of TEMPO, under the same
conditions, the yield was not enhanced significantly (Table 1,
entry 5). Based on previous literatures,20–24 we tried adding
1mmol of NaBr to the reaction mixture and this to a remark-
able decrease in reaction time (Table 1, entry 6). Thus, we
switched our attention to a NaBr/H2O2 oxidation system in the
same manner at reflux without TEMPO. The colours of the
reaction mixture varied from colourless to brown and brown
gas was observed in the condenser immediately. The yield
of 2-chlorobenzaldehyde was low due to the volatilisation of
bromine. These experiments revealed that 2 h, 0.05 equiv. of
the TEMPO and 1 mmol of NaBr were necessary to complete
the reaction. The excess amount of hydrogen peroxide required
is a result of its decomposition at the elevated temperature.
In the presence of TEMPO, no 2-chlorobenzoic acid was
observed. The main byproduct was 2-chlorobenzyl alcohol,
which could be fully converted into 2-chlorobenzaldehyde in
92% yield by prolonging the reaction time with excessive
hydrogen peroxide. In addition, the reaction was carried out at
different temperatures and it was found that the rate of the
reaction increased with the increase in the temperature. A
much longer time was required for the hydrolysis of 2-chloro-
benzyl chloride at a lower temperature. The optimal reaction
temperature was at reflux.
In continuation of our research programme to develop new
and efficient methods of oxidation of benzyl halides to their
corresponding aldehydes and ketones,25–28 we report here a
convenient, efficient and simple method for the oxidation
of benzyl halides and some related compounds using H2O2 as
the oxidant catalysed by TEMPO in water in a short time
(Scheme 1).
This observation encouraged us to extend the scope and
generality of this methodology. Thus, a variety of benzyl hal-
ides and some related compounds were oxidised in presence
of TEMPO under the same reaction condition. As can be seen
from Table 2, various benzyl halides could be converted into
the corresponding aldehydes and ketones with good yields
Results and discussion
The initial study was carried out using 2-chlorobenzyl chloride
as the substrate to optimise the reaction conditions, and the
results are summarised in Table 1. In the absence of TEMPO,
the reaction proceeded very slowly and the yield was 7% after
10 h (Table 1, entry 1). When the reaction was performed with
TEMPO, it proceeded well, the yield increasing to 32% in a
shorter time (6 h) when only 0.01 equiv. of TEMPO was used
(Table 1, entry 2). With the use of 0.03 equiv. of the promoter,
the desired reaction was efficiently carried out and the yield
remarkably increased to 54% in 4 h (Table 1, entry 3). Thus,
Table 1 Optimisation of the reaction conditions for oxidising
2-chlorobenzyl chloride to 2-chlorobenzaldehydea
Entry n(TEMPO)/n(2-chlorobenzylchloride) Time/h Yield/%b
1
2
3
4
5
6
–
10
6
7c
32
54
92
92
92d
0.01
0.03
0.05
0.1
4
4
2
0.05
2
a Unless otherwise noted, the reactions were carried out at
reflux with 2-chlorobenzyl chloride (10 mmol) and H2O (20 mL).
30% H2O2 (20 mmol) was added using a syringe slowly in
30–60 min.
b Isolated yields.
c The main byproducts were 2-chlorobenzyl alcohol and 2-
chlorobenzoic acid.
X = Cl, Br
R = H, NO2, Cl, Br, etc.
Scheme 1 Oxidation of benzyl halides and some related
d 1 mmol of NaBr was added.
compounds to carbonyl compounds.
CAUTION: Exercise extreme care when adding hydrogen
peroxide to the hot reaction mixture.
* Correspondent. E-mail: orienthawk@163.com

JOURNAL OF CHEMICAL RESEARCH 2013 23
Table 2 Oxidation of various benzyl halides and some related
4-Bromobenzaldehyde (Table 2, entry 3): White solid; m.p. (found/
lit.): 66–67/66–68 °C 25; 1H NMR (500 MHz, CDC13): δ = 7.67–7.75
(m, 4H), 9.97 (s, 1H). 13C NMR (100 MHz, CDC13): δ = 129.6, 130.8,
132.3, 135.0, 190.8.32
compounds to the corresponding carbonyl compoundsa
Entry
Substrate
Productb
Time/h Yield/%c
1
4-Chlorobenzaldehyde (Table 2, entry 4): H NMR (300 MHz,
1
2
PhCH2Cl
PhCH2Br
4-BrC6H4CH2Br
4-ClC6H4CH2Cl
2,4-Cl2C6H3CH2Cl 2,4-Cl2C6H3CHO
2-ClC6H4CH2Cl
2-ClC6H4CH2Br
4-NO2C6H4CH2Cl 4-NO2C6H4CHO
4-CH3OC6H4CH2Cl 4-CH3OC6H4CHO
PhCHClPh
4-OHC6H4CH2Br 4-OHC6H4CHO
PhCHClCH3 PhCOCH3
PhCHO
PhCHO
4-BrC6H4CHO
4-ClC6H4CHO
3
91
92
92
93
91
92
91
85e
72f
93
86
94
2d
2
CDC13): δ = 7.51 (d, 2H, J = 8 Hz), 7.82 (d, 2H, J = 8.5 Hz), 9.98;
(s, 1H). 13C NMR (100 MHz, CDC13): δ = 129.4, 130.8, 190.7.33
2, 4-Dichlorobenzaldehyde (Table 2, entry 5): White solid; m.p.
(found/lit.): 74–75/73–74 °C 34; 1H NMR (500 MHz, CDC13): δ = 7.37
(d, 1H, J = 10 Hz), 7.47 (s, 1H), 7.86 (d, 1H, J = 8 Hz), 10.41 (s, 1H).
13C NMR (100 MHz, CDC13): δ = 127.8, 130.2, 130.3, 130.8, 138.4,
140.9, 188.2.33
3
4
3
5
3
6
2-ClC6H4CHO
2-ClC6H4CHO
2
7
2
8
2d
5
9
1
2-Chlorobenzaldehyde (Table 2, entry 6): H NMR (300 MHz,
10
11
12
PhCOPh
1
CDC13): δ = 7.35–7.52 (m, 3H), 7.91 (d, 1H, J = 8 Hz), 10.48 (s, 1H).
13C NMR (100 MHz, CDC13): δ = 127.2, 129.3, 130.5, 135.0,
189.7.33
3
1
a Unless otherwise noted, the reactions were carried out with
halide (10 mmol), TEMPO (0.05 mmol) and H2O (20 mL), 30%
H2O2 (20 mmol) was added using syringe at low speed in 30–
60 min at reflux. In the case of a chloride, NaBr (1 mmol) was
added.
4-Nitrobenzaldehyde (Table 2, entry 8): Yellow solid; m.p. (found/
35
lit.): 106–107/106–108 °C 1H NMR (500 MHz, CDC13): δ = 8.09
(d, 2H, J = 8.5 Hz), 8.40 (d, 2H, J = 9 Hz), 10.17 (s, 1H). 13C NMR
(100 MHz, CDC13): δ = 124.2, 130.4, 140.0, 190.2.33
1
b All the products are known compounds which were compared
with authentic samples by 1H and 13C NMR spectroscopy.
c Isolated yields.
4-Methoxybenzaldehyde (Table 2, entry 9): H NMR (300 MHz,
CDC13): δ = 3.86 (s, 3H), 6.99 (d, 2H, J = 8 Hz), 7.82 (d, 2H, J =
8.5Hz), 9.86 (s, 1H). 13C NMR (100 MHz, CDC13): δ = 55.3, 114.1,
131.7, 164.4, 190.5.33
d The reaction time was shortened greatly compared with the
previous literature.23
1
Acetophenone (Table 2, entry 10): H NMR (300 MHz, CDC13):
e The yields were higher than that of TEMPO/KNO2/O2 and H2O2/
EtOH system.19,23
δ = 2.58 (s, 3H), 7.41–7.54 (m, 3H), 7.94 (d, 2H, J = 8.5 Hz). 13C
NMR (100 MHz, CDC13): δ = 26.2, 128.1, 128.4, 132.9, 136.9,
197.9.33
f The reaction was carried out with p-methoxybenzyl chloride
(10 mmol), TEMPO (1 mmol), 30% H2O2 (40 mmol), H2O (30 mL),
reflux. If NaBr was added, demethylation could occur. In this
oxidation system, the yields were higher than that of TEMPO/
KNO2/O2 system.23
4-Hydroxybenzaldehyde (Table 2, entry 11): White solid; m.p.
36
(found/lit.): 114–116/114–117 °C 1H NMR (500 MHz, CDC13):
δ = 6.34 (s, 1H), 6.98 (d, 2H, J = 8.5 Hz), 7.82 (d, 2H, J = 8 Hz), 9.86
(s, 1H). 13C NMR (100 MHz, DMSO): δ = 115.8, 128.4, 132.0, 163.2,
190.9.33
Conclusion
in short times. Benzyl bromides were more reactive than the
corresponding chlorides and the reaction rates of secondary
halides were clearly larger than those of primary ones. Benzyl
halides with electron-withdrawing groups could be more easily
oxidised to the corresponding aldehydes than those containing
electron-donating ones. Thus, many halides with electron-
donating groups need a longer reaction time and a large excess
of hydrogen peroxide to obtain higher yields.
In summary, we have found a useful method for the oxidation
of benzylic halides and some realted compounds directly to the
corresponding aldehydes and ketones respectively using H2O2
with catalytic amounts of TEMPO. The method offers several
advantages such as good yields, shorter reaction times, cleaner
reaction profiles and simple experimental procedures.
We thank the National Basic Research Programme (973) of
China and the Natural Science Foundation of Jiangsu Province
for support of this research.
A likely mechanism for the benzylhalides may be the for-
mation of benzyl peroxide by nucleophilic displacement of
halide by hydrogen peroxide, followed by benzyl hydrogen
atom abstraction by TEMPO and cleavage of the peroxide
bond.21–23,29–32
Received 1 June 2012; accepted 5 November 2012
Paper 1201347 doi: 10.3184/174751912X13545558675784
Published online: 15 January 2013
Experimental
All the chemicals were of analytical grade, purchased from commer-
cial sources and used without further purification. Melting points were
recorded on a Buchi R-535 apparatus and were uncorrected. 1H NMR
spectra were recorded on a Bruker spectrometer using CDCl3 as the
solvent with tetramethylsilane (TMS) as an internal standard.
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