Polymer bromide-DMSO: Novel reagent system for the oxidation of alcohols to carbonyl compounds

Article abstract of DOI:10.1016/j.tetlet.2011.10.086

A novel method for the oxidation of alcohols to aldehydes is described using polymer bromide-DMSO at room temperature. The condition described enables clean and fast conversion to desired carbonyl compounds and a broad range of substrates are tolerated. The resin recovery and recyclability make the protocol more ecofriendly.

Full text of DOI:10.1016/j.tetlet.2011.10.086

Tetrahedron Letters 52 (2011) 6971–6973
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Polymer bromide-DMSO: novel reagent system for the oxidation of alcohols
to carbonyl compounds
⇑
T.S.R. Prasanna, K. Mohanaraju
Synthetic Polymer Laboratory, Department of Polymer Science & Tech, Sri Krisnadevaraya University, Anantapur 515055, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel method for the oxidation of alcohols to aldehydes is described using polymer bromide-DMSO at
room temperature. The condition described enables clean and fast conversion to desired carbonyl com-
pounds and a broad range of substrates are tolerated. The resin recovery and recyclability make the pro-
tocol more ecofriendly.
Received 11 August 2011
Revised 15 October 2011
Accepted 17 October 2011
Available online 21 October 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Polymer bromide
Oxidations
Benzylic alcohols
Carbonyl compounds
The ever-increasing demand for the efficient synthesis of novel
organic compounds and environment conscious chemical pro-
cesses has led to the development of novel techniques in organic
synthesis. Use of polymer bound reagents introduce several advan-
tages in organic synthesis including removing excess reagents and
byproducts by simple filtration and reducing the effort required in
workup and purification of the crude reaction mixture in several
cases. Polymer assisted solution phase synthesis, a widely devel-
oped area in organic synthesis enables the chemist to prepare li-
braries of compounds more quickly and efficiently.1 This line of
chemistry has resulted in the development of a number of useful
polymer-supported reagents which are finding increasing utility
groups are not tolerated, prolonged reaction time, cumbersome
work-up procedures and isolation, and using poisonous and bad
smelling liquids as reagents. Developing suitable reagents which
exclude these limitations in the oxidation of alcohols to carbonyl
compounds in the context of green chemistry appears to be a wel-
come goal.
In continuation of our research interest in developing novel
9
methodologies in organic synthesis using polymer bound reagents
À
3À
we became interested in Amberlyst A 26-Br . It is a source of Br
3
ions, the properties of which are different from those of molecular
bromine. In particular, it is much less electrophilic and less reactive
À
toward aromatic rings. Amberlyst A 26-Br3 is used in various
2
10
in organic synthesis.
transformations including selective para-bromination of phenols,
1
1
Oxidation of alcohols to carbonyl compounds is an important
reaction in organic chemistry and various reagents have been
developed to effect this transformation. These include (a) chro-
a-bromination of ketones, regioselective bromomethoxylation of
1
2
alkenes etc. However to the best of our knowledge we found no
reports employing polymer bromide in the bromination of benzylic
alcohols. If the same can be achieved using polymer bromide in di-
methyl sulfoxide (DMSO) the benzyl bromide formed will be oxi-
dized in situ to a carbonyl compound. This will eventually serve
two purposes, a one pot synthesis of carbonyl compounds with
DMSO as the terminal oxidant and recovery and the recyclability
to ensure that the process will meet the current requirements of
green chemistry.
mium-based reagents, such as Collins reagent (CrO
3
ÁPy
2
), PDC or
PCC (b) activated DMSO,4 resulting from the reaction of DMSO
3
with electrophiles such as oxalyl chloride (Swern oxidation), car-
bodiimide (Pfitzner–Moffatt oxidation) or the complex SO
3
ÁPy
5
(
Parikh–Doering oxidation) (c) hypervalent iodine compounds,
such as Dess–Martin periodinane or 2-iodoxybenzoic acid (d) cat-
6
alytic TRAP in the presence of excess of NMO (Ley-Oxidation) and
7
(
e) catalytic TEMPO in the presence of excess bleach (NaOCl). Sev-
Herein, we wish to report the results of our investigation of
using polymer bromide in the oxidation of benzylic alcohols to
the corresponding carbonyl compounds with DMSO as the termi-
nal oxidant (Scheme 1).
eral other methods employing different reagents and modifications
8
to the above methods have been reported. However many of these
protocols use harsh reagents where acid-sensitive functional
In initial studies we took 4-chlorobenzyl alcohol (1 equiv) and
polymer bromide (1 equiv) in 10 volumes of DMSO and stirred at
room temperature and the course of the reaction was monitored
⇑
Corresponding author. Tel.: +91 08554 255655.
E-mail address: kmohanaraju@gmail.com (K. Mohanaraju).
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.086

6
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T. S. R. Prasanna, K. Mohanaraju / Tetrahedron Letters 52 (2011) 6971–6973
Polymer bromide-DMSO
Room Temperature
CHO
OH
R
R
1
2 a-l
8
8-93 %
R = H,CN, NO , Cl etc
2
Scheme 1. Oxidation of alcohols to carbonyl compounds using polymer bromide-DMSO at room temperature.
by thin layer chromatography. Interestingly a nonpolar spot
formed after 6 h and the starting material disappeared and the
TLC plate that was dipped in 2,4-DNP solution developed a brown
color. Analysis of the reaction mixture in GCMS showed the corre-
sponding aldehyde mass. It is interesting to note that the reaction
was clean and no purification was required after an aqueous work-
up. Encouraged by the result the reaction was performed using
benzyl alcohol and different alcohols containing various functional
groups. Representative examples are shown in Table 1 (entries 1,
Table 1
Conversion of alcohols to aldehydes using polymer bromide-DMSO
Entry Alcohol
Product Product timea (h) Yieldb (%)
CH OH
2
c
1
2a
2b
4
6
92
CH OH
2
2
95c
Cl
CH OH
2
3
–5) and the corresponding aldehydes were obtained in excellent
3
2c
2d
2e
4
5
6
91c
yields. It is noteworthy to mention that there was no ring bromin-
ation with any of the substrate alcohols. The generality of the
methodology was further confirmed by applying the same to
heterocyclic alcohols (Table 1, entries 7, 11) and cinnamyl alcohol
NC
CH OH
2
92c
4
Br
(Table 1, entry 12). In all the cases the reactions went into comple-
CH OH
2
tion within the time reported. When the reaction was performed
on 4-methoxy benzyl alcohol we observed 25% of the demethylat-
ed product and to circumvent the problem we tried to reduce the
amount of catalyst and it was observed that the reaction did not
go to completion after prolonged stirring. When we were thinking
of neutralizing agents which can absorb the liberated HBr we came
across a procedure which employs phenyl trimethyl ammonium
93c
5
O N
2
CH OH
2
90d
6
2f
5
6
MeO
CH OH
2
94c
7
2g
tribromide for the
a
-bromination of arylalkyl ketones with anhy-
Cl
N
OH
drous tetrahydrofuran (THF) as the buffer which reacts with liber-
1
3
ated HBr. An equal ratio of DMSO and anhydrous THF did the job
in the case of acid-sensitive methoxy group containing benzyl
alcohols and the demethylation could be reduced to less than 5%.
Then we turned our attention toward benzylic secondary alco-
hols (Table 1, entries 8, 10). By employing the nonTHF condition
used for 4-chlorobenzyl alcohol both benzylic and heterocyclic sec-
ondary alcohols could be converted to the corresponding ketones
in good yield. With the same method we wanted to see whether
the carbonyl compounds can be obtained when aliphatic alcohols
are employed. However the reaction did not yield the correspond-
ing aldehydes when aliphatic primary and secondary alcohols were
used (Table 1, entries 13–15). This may be presumably because
polymer bromide is efficient only in converting highly reactive
alcohols like benzylic and allylic to the corresponding bromides
under the reaction conditions which are oxidized by DMSO to
the corresponding carbonyl compounds and in the case of aliphatic
alcohols where such reactivity is not present, the corresponding
bromides are not formed. Based on the above observations the
optimized condition for alcohols not containing acid-sensitive
groups employs 1 equiv of polymer bromide in DMSO. For the alco-
hols containing acid-sensitive groups, 1 equiv of polymer bromide
in equal ratio of DMSO/THF serves the purpose.
90c
8
2h
5
O
O
CH OH
2
9
1
2i
2j
5
6
89d
88c
OH
0
O
N
1
1
1
2
2k
2l
4
5
91c
90c
CH OH
2
CH OH
2
1
1
3
4
OH
2m
2n
5
5
No reactionc
OH
OH
No reactionc
1
5
2o
5
No reactionc
a
b
c
Reactions were monitored by GC–MS.
Yields refer to pure products.
Ref. 14i.
A tentative mechanism for the oxidation of alcohols to carbonyl
compounds based on the above facts is represented below.
d
Ref. 14ii.
(Scheme 2)
Recovery and reusability of the catalyst
the addition of bromine.10 Reuse of the same using the optimized
conditions (Ref. 14), with 4-chlorobenzyl alcohol as the model sub-
strate gave the corresponding 4-chlorobenzaldehyde with yields
almost comparable. The resin could be recovered without much
loss in quantity and its reuse checked up to four cycles and the cor-
responding yields obtained in each cycle are tabulated in Table 2.
With the objective of reducing the cost, especially when intend-
ing to carry out large scale reaction, the catalyst reusability is also
checked by recovering the resin. After the reaction is over the
decolorized resin was filtered and converted into tribromide by

T. S. R. Prasanna, K. Mohanaraju / Tetrahedron Letters 52 (2011) 6971–6973
6973
OH
Br
Step 1
NMe Br
NMe3 Br2
3
3
CH3
S
H
CH3
S
O
CH3
CHO
Br
S
Step 2
O
CH3
H C
CH3
3
Scheme 2. Proposed mechanism for the oxidation of alcohols to carbonyl compounds using polymer bromide-DMSO.
4
.
.
(a) Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651; (b) Pfitzner, K. E.; Moffatt,
J. G. J. Am. Chem. Soc. 1963, 85, 3027; (c) Parikh, J. R.; Doering, W. E. J. Am. Chem.
Soc. 1967, 89, 5505.
Table 2
Recovery and reusability of polymer bromide in the conversion of 4-chlorobenzyl
alcohol to 4-chlorobenzaldehyde
5
Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
Yield of producta,b (%)
6.
Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P. Synthesis 1994, 639.
(a) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem. 1987, 52, 2559; (b)
Rozantsev, E. G.; Sholle, V. D. Synthesis 1971, 190; (c) Leanna, M. R.; Sowin, T. J.;
Morton, H. E. Tetrahedron Lett. 1992, 33, 5029.
(a) Uyanik, M.; Akakura, M.; Ishihara, K. J. Am. Chem. Soc. 2009, 131, 251; (b)
Surendra, K.; Srilakshmi, K. N.; Arjun Reddy, M.; Nageswar, Y. V. D.; Rama Rao,
K. J. Org. Chem. 2003, 68, 2058; (c) Bolm, C.; Magnus, A. S.; Hildebrand, J. P. Org.
Lett. 2000, 2, 1173; (d) Park, H. J.; Lee, J. C. Synlett 2009, 79; (e) Gheorghe, A.;
Chinnusamy, T.; Cuevas-Yañez, E.; Hilgers, P.; Reiser, O. Org. Lett. 2008, 10,
Entry
Cycles
Recovery of resin (wt %)
7.
1
2
3
4
I
II
III
IV
96
95
94
94
93
91
90
90
8.
a
Isolated yields.
Ref. 14i.
b
4171; (f) Vatèle, J. M. Synlett 2006, 2055; (g) Jiang, N.; Ragauskas, A. J. J. Org.
Chem. 2007, 72, 7030; (h) Kim, S. S.; Jung, H. C. Synthesis 2003, 2135; (i) Yang,
G.; Wang, W.; Zhu, W.; An, C.; Gao, X.; Song, M. Synlett 2010, 437.
9
.
An improved procedure for 2-amino-5-nitro-4,6-diarylcyclohex-1-ene-1,3,3-
tricarbonitriles; Carbonate on polymer support (Amberlyst A-26 NaCO3 ) as
mild and reusable catalyst. Prasanna. T.S.R.; Mohanraju. K. Paper accepted in
Journal of Korean Chemical Society 2011 (K-11-OC-034-A).
This makes the resin reusability possible eliminating the drawback
of the cost factor.
À
In summary we have developed and demonstrated a novel use
À
10. Smith, K.; James, M.; Matthews, I.; Bye, M. R. J. Chem. Soc., Perkin Trans. 1 1992,
877.
of polymer tribromide, amberlyst A 26-Br3 for the oxidation of
1
benzylic alcohols to the corresponding carbonyl compounds.
When compared to the previously reported procedures our meth-
od offers several advantages. The reaction is done at room tem-
perature, a broad range of substituents are tolerated, and the
recovery and reusability of the resin makes the entire protocol
economical and environment friendly. Although the protocol is
similar to Corey–Kim oxidation, the amount of bad smelling, vol-
atile and poisonous dimethyl sulfide released into the environ-
ment is only stoichiometric which is far less than the amount
required by Corey–Kim oxidation where the amount of dimethyl
sulfide employed varies from 2.5 to 5 equiv. Taken together, the
use of polymer tribromide for the oxidation of benzylic alcohols
to carbonyl compounds represents an approach suitable for prac-
ticing green chemistry and thus should find wide application in
organic synthesis.
1
1
1
1. (a) Cacchi, S.; Caglioti, L. Synthesis 1979, 64; (b) Ploypradith, P.; Kagan, R. K.;
Ruchirwat, S. J. Org. Chem. 2005, 70, 5119.
2. Gopalakrishnan, G.; Kasinath, V.; Pradeep Singh, N. D.; Santhana Krishnan, V.
P.; Anand Soloman, K.; Rajan, S. S. Molecules 2002, 7, 412.
3. Jacques, J.; Marquet, J. Organic Synthesis 1988, 6, 175.
14. General Procedure for the oxidation of alcohols to carbonyl compounds.
i) Procedure for alcohols not containing acid-sensitive groups.
(
To a mixture of alcohol in dry DMSO (10 volume) was added 1 equiv of
polymer bromide and the reaction mixture was stirred at room temperature
for a given period of time (Table 1). After the completion of the reaction, the
reaction mixture was filtered and the polymer bed washed with DMSO.
Combined DMSO layers were quenched with ice–water mixture and extracted
with ether. The ether layer was given water wash, brine wash, dried over
anhydrous sodium sulphate, and concentrated to get the pure carbonyl
compounds. All the products were characterized by NMR and MS analysis.
(
ii) Procedure for alcohols containing acid-sensitive groups.
To a mixture of alcohol in dry DMSO/THF (10 volume, 50:50 mixture) was
added 1 equiv of polymer bromide and the reaction mixture was stirred at
room temperature for a given period of time (Table 1). After completion of the
reaction, the reaction mixture was filtered and the polymer bed was washed
with THF. Combined DMSO/THF layers were quenched with ice–water mixture
and extracted with ether. The ether layer was given water wash, brine wash,
dried over anhydrous sodium sulphate, and concentrated to get the pure
carbonyl compounds.
References and notes
1
.
.
(a) Shuttleworth, S. J.; Allin, S. M.; Wilson, R. D.; Nasturica, D. Synthesis 2000,
035; (b) Bhalay, G.; Dunstan, A.; Glen, A. Synlett 2000, 1846.
For a review of polymer-supported reagents, see: (a) Ley, S. V.; Baxendale, I. R.;
Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.;
Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815 (special review
issue); (b) Petchmanee, T.; Ploypradith, P.; Ruchirawat, S. J. Org. Chem. 2006, 71,
1
Selected spectral data
2
4-bromobenzaldehyde (3b)
Mp: 59–60 °C, H NMR (CDCl , 400 MHz): d (ppm) 7.6 (m, 4H), 9.9 (s, 1H). 13C
1
3
NMR (CDCl3 400 MHz); d 129.5, 131.8, 132.3, 135.0 and 190.8. Analysis:
C H BrO requires C: 45.44, H: 2.72, Br: 43.18; found C: 45.44, H: 2.70, Br:
7
5
7
(
6
82; (c) Flowers, R. A.; Xu, X.; Timmoons, C.; Li, G. Eur. J. Org. Chem. 2004, 2988;
d) Pennington, T. E.; Kardiman, C.; Hutton, C. A. Tetrahedron Lett. 2004, 45,
657; (e) Chiang, G. C. H.; Olsson, T. Org. Lett. 2004, 6, 3079; (f) Tashino, Y.;
43.18.
4-nitrobenzaldehyde (4b)
1
Mp: 105–106 °C, H NMR (CDCl , 400 MHz): d (ppm) 7.6 (d, 2H, J = 9 Hz), 8.37
3
(d, 2H, J = 9 Hz). 13C NMR (CDCl , 400 MHz); d 123.5, 130.8, 139.3, 150.0 and
Togo, H. Synlett 2004, 2010; (g) Jaunzems, J.; Kashin, D.; Schonberger, A.;
Kirschning, A. Eur. J. Org., Chem. 2004, 3435.
3
190.8. Analysis: C H NO requires C: 55.63, H: 3.34, N: 9.26 found; C: 55.62, H:
7
5
3
3
.
Collins, J. C.; Hess, W. W.; Frank, F. J. Tetrahedron Lett. 1968, 9, 3363.
3.33, Br: 9.26.