Oxidation of benzylic azides catalysed by iron(III) chloride with hydrogen peroxide as oxidant

Article abstract of DOI:10.3184/174751911X13235135875669

A simple and general method for the oxidation of benzylic azides to aldehydes using the inexpensive and environmentally benign iron (III) chloride as catalyst with 30% aqueous H₂O₂ as oxidant is described. Broad substrate scope and high tolerance against several functional groups make the process synthetically useful.

Full text of DOI:10.3184/174751911X13235135875669

7
20 RESEARCH PAPER
DECEMBER, 720–722
JOURNAL OF CHEMICAL RESEARCH 2011
Oxidation of benzylic azides catalysed by iron(III) chloride with hydrogen
peroxide as oxidant
a
a
b
Hong-Ping Zhang *, You-Zhi Dai and Li-Ming Tao
a
Department of Biology and Chemistry Engineering, Shaoyang University, Shaoyang 422000, P. R. China
bDepartment of Chemistry and Life Science, Xiangnan University, Chenzhou 423000, P. R. China
A simple and general method for the oxidation of benzylic azides to aldehydes using the inexpensive and environ-
mentally benign iron (III) chloride as catalyst with 30% aqueous H O as oxidant is described. Broad substrate scope
2
2
and high tolerance against several functional groups make the process synthetically useful.
Keywords: iron(III) chloride, hydrogen peroxide, benzylic azides, oxidation, benzaldehyde
Azides are reactive molecules and have attracted much
attention, not only as excellent protecting groups, but as key
intermediates for the synthesis of a large number of organic
THF, CH ClCH Cl and toluene was examined. Optimised
2 2
reaction conditions involved benzyl azide (0.5 mmol), FeCl
3
(10 mol%), CH
entry 2).
Cl (5 mL) refluxing in air for 14 h (Table 1,
2
2
1
2
compounds such as nucleosides, carbohydrates and
3
39–43
N-containing heterocycles such as quinolines, quinazolines,
It is known that molecular oxygen
and hydrogen
4
4–47
peroxide
act as good oxidising agents in many organic
benzodiazepines, lactams and cyclic imides. Among their
reactions, the reduction and rearrangement of benzylic azides
to N-arylimine derivatives has been known for quite some
transformations. They would be highly favourable due to high
redox potential which would lead to improved conversion. For
4–7
this purpose, we coupled the FeCl -catalysed oxidation with
time. Although several examples of the conversion of pri-
3
8
–13
these oxidants and the results are summarised in Table 1. It
seemed that the elevated concentration of molecular oxygen
did not appear to be very important, since even 1 atm of air was
enough to achieve the product yield of 75% (vs. 77% with
mary azides into nitriles have been reported, the oxidation
of them to aldehydes is less explored. Recently, Prabhu has
shown that benzyl azide is oxidised to benzaldehyde catalysed
1
4
by molybdenum xanthate. Although this method is available
for aldehydes, the cost of the transition metals, coupled with
concerns about disposal and removal of trace metal residues,
have motivated the search for base metal alternatives. Hence,
the development of selective but less expensive and environ-
mentally more benign catalysts would be very desirable.
Iron catalysts are readily available, inexpensive, and envi-
ronmental friendly with special reactivities. These features
make them valuable and advantageous in synthetic processes.
1
atm of O ) after 14 h reaction time (entry 2). At the same
2
time, a slightly decrease of yield observed implied that the
prolonged reaction time of 18 h may cause further oxidation of
benzaldehyde into benzoic acid (entry 3). To our delight, a
more effective oxidation took place by performing reactions
under similar conditions using 30% aqueous H O as oxidant
2
2
and, in addition, the percent conversion of benzyl azide into
benzaldehyde was independent upon the amount of H O to a
2
2
large extent (entries 4–7). H O tends to decompose in the
1
5–17
24
2
2
Many iron-catalysed reactions such as oxidation,
hydroam-
presence of an iron catalyst. However, oxygen released in the
decomposition scarcely affected the oxidation of benzyl azide,
and the reaction yield remained approximately constant when
carried out only with peroxide in the absence of air (entry 8).
18–21
22,23
ination,
Michael addition,
rearrangement, and other
carbon–carbon bond, carbon–heteroatom bond and hetero-
atom–heteroatom bond forming reactions have been described
25–38
recently.
in the iron-catalysed oxidation of benzylic azides. Recently,
we found that FeCl is an effective catalyst coupled with 30%
On the basis of these results we became interested
Surprisingly, this strategy of FeCl3 coupled with H O2
2
produced only the corresponding aldehyde without any over-
3
oxidation. A 1:2 molar ratio for 1a and H O was found the
2
2
aqueous H O for the oxidation of benzylic azides (Scheme 1).
2
2
optimum ratio with the conversion up to nearly 93%.
Here, we give the first report of our investigations, which result
in a simple method for the oxidation of benzylic azides with a
broad substrate scope.
Table 1 Optimisation of the oxidant used with FeCl a
3
Results and discussion
In our initial attempt to seek a more effective catalyst for the
oxidation of benzyl azide to benzaldehyde, several iron salts
including FeCl , FeCl •6H O, Fe(acac) , FeCl , FeBr , FeF
3
3
2
3
2
3
3,
and iron powder were utilised in air. The results showed that
Entry
Oxidant
(1 atm)
Time/h
Yield/%b
FeCl was the most effective catalyst and giving the product in
3
7
5% yield when using 10 mol% catalyst. Quite similar yields
1
2
3
O
2
14
14
18
12
12
12
12
12
77
75
73
86
93
93
92
92
were obtained when the catalyst loading was slightly increased
or decreased. The addition of various solvents such as DMSO,
Air (1 atm)
(1 atm)
O
2
c
4
H
H
H
H
H
2
O
2
O
2
O
2
O
2
O
2
2
2
2
2
d
5
e
6
f
7
g
8
a
Reaction condition:benzylic azide 1a (0.5 mmol), FeCl
3
(
10 mol%), CH
2
Cl
2
(5 mL) refluxed.
b
Isolated yield.
c
was 1:1; d benzyl azide to
Molar ratios: benzyl azide to H
2
O
2
2
Scheme 1 Iron-catalysed oxidation of benzylic azides.
e
f
H
H
2
O
O
2
was 1:2; g benzyl azide to H
O
2
was 1:3; benzyl azide to
was 1:2 under a nitrogen
2
2
was 1:4; benzyl azide to H
2
O
2
*
Correspondent. E-mail: zhp4901@sina.com
atmosphere.

JOURNAL OF CHEMICAL RESEARCH 2011 721
Under the optimised reaction conditions, a wide range
of benzylic azides were oxidised similarly to afford the
corresponding aldehydes in moderate to high yields. The
results are summarised in Table 2. Findings showed that
the iron-catalysed oxidation reaction tolerated a variety of
functional groups, and the yields and rates varied with the
substrates. For the oxidation of benzylic azides with electron-
donating groups 1b–e and 1i, the corresponding aldehydes
(1k). In the presence of 1:2 molar ratio for 1k and H O , treat-
ment of 1k gave the corresponding aldehyde 2k in 63% yield.
(entry 10)
2
2
Here we have developed a simple and general method
for the oxidation of benzylic azides to aldehydes using the
inexpensive and enviromentally benign iron (III) chloride as
catalyst with 30% aqueous H O as oxidant. The method offers
2
2
several advantages including high yields and a simple experi-
mental workup procedure, which makes it a useful process for
the synthesis of aldehydes. Interestingly, over-oxidation to the
acid was not observed.
2
b–e and 2i were obtained in 95, 93, 94, 90 and 90% yields,
respectively, in the presence of 10 mol% FeCl with 30%
3
aqueous H O2 as oxidant (entries 1–4 and 8). Similarly,
2
1
9
-(azidomethyl)-3-bromobenzene provided a good yield (entry
). However, we found that less effective reactions occurred
Experimental
with substrates 1f–h bearing electron-withdrawing groups
NMR spectroscopy was performed on a Varian Mercury 300 spec-
(
entries 5–8). We were pleased to discover that the standard
1
13
trometer operating at 300 MHz ( H NMR) and 75 MHz ( C NMR).
conditionswerealsocompatiblewith2-(azidomethyl)thiophene
TMS was used as an internal standard and CD Cl as the solvent. Mass
3
spectrometric analysis was performed on a GC-MS instrument
(Shimadzu GCMS-QP2010 plus). Melting points were recorded on an
Electrothermal type 9100 melting point apparatus. All melting points
are uncorrected. Benzyl azides were prepared according to the pub-
lished method. Other reagents, which were commercially available,
were obtained from the Alfa Aesar and TCI companies.
Table 2 Catalytic oxidation of benzylic azides to aldehydes a
48
CAUTION: Many low-molecular-weight azides are known to be
explosive. In this laboratory, no problems have been encountered,
but great caution should be exercised when heating compounds of
this type, especially when used neat. The reactions described here
were run on only a few grams; an increase in the scale of these reac-
tions will decrease the efficiency of heat dissipation and explosions
may result.
Entry
Substrate
Productb
Time Yield
c,d
(
h)
(%)
1
2
14
14
95
Oxidation of benzylic azides catalysed by iron chloride(III) with 30%
93
94
aqueous H O ; general procedure
2 2
Benzyl azide 1 (0.5 mmol), FeCl (10 mol%), H O (30% aqueous
3
2
2
solution, 1 to H O molar ratio was 1:2) and CH Cl (5 mL) were
2
2
2
2
added in turn to a Schlenk tube. Then, the mixture was stirred and
refluxed in air for the indicated time until complete consumption
of starting material as monitored by TLC and GC-MS analysis
3
4
5
6
13
14
16
16
(
ca 12–18 h). After completion of the reaction, the mixture was poured
into H O (3 mL), and extracted with EtOAc (3 × 5 mL). The combined
2
90
78
75
organic layers were dried with Na SO and evaporated under reduced
2 4
pressure. The residue was purified by flash column chromatography
on silica gel (hexane–EtOAc) to afford the desired product.
The authors thank the youth in the institutions of higher educa-
tion of Hunan Province (No. 10B097) for financial support.
Electronic Supplementary Information
General information, General procedures, Analytical data for
1
13
2
a–k, Scanned H NMR and C NMR spectra of compounds
have been deposited in the ESI available through stl.publisher.
ingentaconnect.com/content/stl/jcr/supp-data.
7
18
70
Received 6 September 2011; accepted 30 November 2011
Paper 1100879 doi: 10.3184/174751911X13235135875669
Published online: 27 December 2011
8
9
12
18
14
90
86
63
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