Novel and efficient oxidation of benzyl ethers to benzaldehydes by DMSO/49% aq. HBr

Article abstract of DOI:10.1080/00397910701266042

Dimethylsulfoxide (DMSO) oxidizes benzyl ethers into corresponding benzaldehydes at 110°C; the reaction is accelerated by 49% aq. HBr. The conditions work well for different aryl-substituted benzyl ethers. This protocol is inert toward dialkyl ethers. Copyright Taylor & Francis Group, LLC.

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Novel and Efficient Oxidation of Benzyl
Ethers to Benzaldehydes by DMSO/49% Aq.
HBr
Ramesh Naik a & M. A. Pasha a
a Department of Chemistry , Central College Campus, Bangalore University ,
Bangalore, India
Published online: 22 May 2007.
To cite this article: Ramesh Naik & M. A. Pasha (2007) Novel and Efficient Oxidation of Benzyl Ethers
to Benzaldehydes by DMSO/49% Aq. HBr, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:10, 1723-1726, DOI: 10.1080/00397910701266042
To link to this article: http://dx.doi.org/10.1080/00397910701266042
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Synthetic Communicationsw, 37: 1723–1726, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701266042
Novel and Efficient Oxidation of Benzyl
Ethers to Benzaldehydes by DMSO/49%
Aq. HBr
Ramesh Naik and M. A. Pasha
Department of Chemistry, Central College Campus, Bangalore
University, Bangalore, India
Abstract: Dimethylsulfoxide (DMSO) oxidizes benzyl ethers into corresponding ben-
zaldehydes at 1108C; the reaction is accelerated by 49% aq. HBr. The conditions work
well for different aryl-substituted benzyl ethers. This protocol is inert toward dialkyl
ethers.
Keywords: benzaldehydes, benzyl ethers, DMSO/49% aq. HBr
INTRODUCTION
Investigation from our laboratory has revealed the new paradigms for
dimethylsulfoxide (DMSO) in effecting the oxidation of benzylic substrates.
We successfully employed the oxidation of primary benzyl amines to
benzoic acids by DMSO/aq. HBr/NaNO2.[1] In context of our ongoing
program, we sought to develop DMSO-based synthetic technology over
benzyl ethers to their corresponding benzaldehydes under acidic conditions.
Although a few methods to achieve the oxidation of benzyl ethers are
known, none are both simple and effective. The reported methods involve
use of reagents such as expensive UF6,[2] metallic nitrates,[3] experimentally
.
incontinent reagents in a common laboratory such as HOF CH3CN
complex,[4] and dimethyldioxirane,[5] which requires a specially designed
Received in India October 17, 2006
Address correspondence to M. A. Pasha, Department of Chemistry, Central College
Campus, Bangalore University, Bangalore 560 001, India. E-mail: m_af_pasha@
yahoo.co.in
1723

1724
R. Naik and M. A. Pasha
apparatus and reagents for its preparation. The only method that offers a good
[6]
yield of benzaldehyde is the use of HNO3 at 08C in dichloromethane
(DCM). The disadvantage encountered in this method is the formation of
nitrated product at elevated temperature.
RESULTS AND DISCUSSION
As we noted, the inherent reactivity of DMSO under acidic conditions is suffi-
cient for oxidation of benzyl ethers. To explore the DMSO-based synthetic
paradigm of oxidation, a quick experiment was done with benzyl methyl
ether as our prime substrate. On heating benzyl methyl ether with DMSO
and 49% aq. HBr at 1108C for 4 h, partial conversion of the substrate into ben-
zaldehyde occurred (gas chromatography (GC)). On continuous heating for an
additional 3 h, complete conversion of the substrate to benzaldehyde was
achieved. After workup, the crude product was purified on silica-gel column
1
chromatography and characterized by H NMR, GC-MS, and IR spectral
analysis by comparing with that of authentic benzaldehyde (Scheme 1).
To optimize the reaction conditions, we demonstrated the reaction of
benzyl methyl ether under different acidic conditions such as con. HCl, con.
H2SO4, H3PO4, CH3COOH, CF3COOH, and 49% aq. HBr. Among these,
only 49% aq. HBr gave the pure product with excellent yields at 1108C.
This protocol has been successesfully employed for a variety of substituted
benzyl ethers compiled in Table 1; in all cases, excellent yields of
corresponding benzaldehydes were obtained. A noteworthy feature is that the
electron-releasing groups like -OH, -OCH3, -CH3 accelerate the reaction con-
siderably (Table 1, entries 4–6), and in contrast electron-withdrawing groups
like -NO2 and -Cl retard the rate of the reaction (Table 1, entries 8–10).
Another interesting feature is the presence of an aryl group on the other side
of the benzyl ether (Table 1, entry 3) utilized longer duration to give the title
compound with the formation of phenol. When dibenzyl ether was subjected
to the standard reaction conditions, as expected, the reaction needed a long
duration (15 h) with the formation of 2 equivalents of benzaldehyde.
A similar type of mechanism holds good for this protocol as predicted in
our previous communication for the oxidation of benzyl amines to benzoic
acids[1] (Scheme 2).
In conclusion, we have developed a novel protocol for the oxidation of
benzyl ethers to the corresponding benzaldehydes in excellent yields.
Scheme 1. Oxidation of benzyl ethers.

Oxidation of Benzyl Ethers
1725
Table 1. Oxidation of benzyl ethers into benzaldehydes by
DMSO and aq. HBr.
Entry
1
Ethers
Time (h)
7
Yield (%)a
85
2
3
10
48
80
78
4
5
6
7
4
6
92
86
94
86
5
10
8
9
14
15
12
88
89
84
10
aIsolated yields.
EXPERIMENTAL
1
Melting points were determined on a Buchi melting-point apparatus. IR, H
NMR, and 13C NMR GC-MS spectra were recorded on Nicolet 400 D
FT-IR spectrophotometer, 400-MHz Bruker spectrometer, and Shimadzu
GC-MS QP 5050A respectively. Benzyl ethers were prepared by reported
methods and purified and characterized thoroughly before use.
Scheme 2. Mechanism for the oxidation of benzyl ethers.

1726
R. Naik and M. A. Pasha
General Procedure for Oxidation of Benzyl Ethers by DMSO
Promoted by 49% Aq. HBr
A solution of 4-methoxybenzylmethyl ether (2.0 g, 13.15 mmol), DMSO
(10 mL), and 49% HBr (3.0 mL, 17.80 mmol) was heated to 1108C until
complete conversion was achieved as monitored by thin-layer chromato-
graphy (TLC). Brine (30 mL) was then added, neutralized with saturated
NaHCO3, and extracted with dichloromethane (3 Â 15 mL). The combined
DCM extract was again washed with brine (2 Â 10 mL), dried over anhyd.
Na2SO4, and concentrated. The resulting crude mixture was purified by
silica-gel column chromatography to get 4-methoxybenzaldehyde (1.61 g,
90% yield).
ACKNOWLEDGMENT
Ramesh Naik acknowledges the Bangalore University for financial assistance
and the Deptartment of Organic Chemistry and NMR Research Center, Indian
Institute of Science, Bangalore, for recording NMR spectra.
REFERENCES
1. Pasha, M. A.; Ramesh, N. DMSO/NaNO2/49% HBr: A novel and powerful oxidant
for the direct conversion of primary benzylamines to benzoic acids. Synth. Commun.
2005, 36, 165–168.
2. Olah, G. A.; Welch, J. Synthetic methods and reactions, 46: Oxidation of organic
compounds with uranium hexafluoride in haloalkane solutions. J. Am. Chem. Soc.
1978, 100, 5396–5402.
3. Nishiguchi, T.; Bougauchi, M. Convenient oxidative cleavage of ethers by metallic
nitrates supported on silica gel. J. Org. Chem. 1989, 54, 3001–3002.
4. Rozen, S.; Dayan, S.; Bareket, Y. Oxidative cleavage of methyl ethers using the
.
HOF CH3CN complex. J. Org. Chem. 1995, 60, 8267–8269.
5. Van HeerdenDixon, J. T.; Holzapfel, C. W. Direct transformation of steroidal ethers
into ketones by dimethyldioxirane. Tetrahedron Lett. 1992, 33, 7399–7402.
6. Strazzolini, P.; Runcio, A. Oxidation of benzyl alcohols and ethers to carbonyl
derivatives by nitric acid in dichloromethane. Eur. J. Org. Chem. 2003, 526–536.