Oxidation of primary alcohols to aldehydes with N-halamine-containing polymers

Article abstract of DOI:10.1055/s-0033-1339840

Polymeric N-halamines have been previously employed for organic reactions such as sulfide oxidation. In the present study, we employed polymeric N-halamines to oxidize primary alcohols selectively to the corresponding aldehydes in excellent yields. After reaction, the polymers can be recycled and then reused for the next reaction process. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1339840

LETTER
▌2451
lOettexr idation of Primary Alcohols to Aldehydes with N-Halamine-Containing
Polymers
Oxidation of Primary Alcohols to Aldehydes
Akin Akdag,* Perihan Öztürk
Department of Chemistry, Middle East Technical University, 06800 Ankara, Turkey
Fax +90(312)2103200; E-mail: aakdag@metu.edu.tr
Received: 18.07.2013; Accepted after revision: 26.08.2013
This work is dedicated to Professor S. D. Worley of Auburn University.
Abstract: Polymeric N-halamines have been previously employed
for organic reactions such as sulfide oxidation. In the present study,
we employed polymeric N-halamines to oxidize primary alcohols
selectively to the corresponding aldehydes in excellent yields. After
reaction, the polymers can be recycled and then reused for the next
reaction process.
Key words: alcohols, aldehydes, oxidation, solid-phase synthesis,
halogens, green chemistry
Oxidation of alcohols to the corresponding carbonyl com-
pounds is one of the key functional group transformations
1
in synthetic organic chemistry. There is a continuing
Akin Akdag received his BS and MS at the Middle East Technical
University, Ankara, Turkey. He then moved to Auburn University
and received his Ph.D. under the supervision of Professor S. W.
search for new methods and reagents tolerating a wide va-
2
riety of conditions for this transformation, particularly
with the aim to develop sustainable and green methodolo- Schneller in 2005. He stayed at the Auburn University for a postdoc
3
gy. When a primary alcohol is oxidized to the corre- with Professor S. D. Worley and then moved to the University of
Colorado at Boulder, where he worked with Professor Josef Michl.
He is currently an Assistant Professor in the Department of Chemistry
at the Middle East Technical University. His current research interests
are green chemistry, molecular recognition, solar energy, polymers,
sponding aldehyde, the aldehyde is sometimes further
oxidized to a carboxylic acid depending upon the oxi-
4
dant. In many situations, the aldehydes are synthetically
more valuable than the carboxylic acids; therefore, termi-
nating oxidation at the aldehyde stage can be crucial.
chiral sulfoxides, and reactive intermediates.
2
,2,6,6-Tetramethylpiperidine N-oxide (TEMPO), a ver- from the reaction medium and regenerated to be reused in
satile organic oxidant, has frequently been used in the ox- further oxidations. These materials have been mainly syn-
5
10
idation of alcohols. TEMPO requires a secondary oxidant thesized for sanitization purposes and one of these poly-
to activate it for the oxidation and to refurbish it after each mers (Scheme 1) was developed by Worley et al. and
completed oxidation and many different co-oxidants have commercialized by HaloSource, Inc., for disinfection of
6
11
been used. Even though such systems have found utility, water. These polymers have also been employed in di-
lengthy purification from unwanted products may limit sulfide formation, detoxification of mustard gas, and oxi-
the use of these oxidants despite the mildness of TEMPO dation of secondary alcohols. However, there have been
oxidation conditions. TEMPO has been incorporated into no reports in which they have been employed to oxidize
polymers, and these polymers have also been employed in primary alcohols to aldehydes.
the oxidation reactions of primary and secondary alcohols
1
2
7
using the co-oxidants mentioned above.
n
n
N-Halamine-containing polymers (containing N–X,
where X is either Cl or Br) were developed and used for
their biocidal properties, although the N–X (X = Cl, Br)
bond can be used as a co-oxidant in TEMPO-mediated ox-
NaOCl
pH 7
8
Cl
H
N
N
idations, in the same way as the related N-chlorosuccin-
O
O
9
O
N
O
N
H
imide (NCS) and trichloroisocyanuric acid (TCA).
Cl
Moreover, polymeric N-halamines offer an advantage
over NCS and TCA because they can be easily separated
Scheme 1 Polystyrene hydantoin and its chlorination with hypochlo-
rous acid
SYNLETT 2013, 24, 2451–2453
Advanced online publication: 13.09.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1339840; Art ID: ST-2013-D0669-L
Georg Thieme Verlag Stuttgart · New York
©

2452
A. Akdag, P. Öztürk
LETTER
In this communication we report the use of chlorinated Table 1 The Alcohols, Oxidation Products, and the Reaction Dura-
polystyrene hydantoin beads as the co-oxidant for tiona
TEMPO-mediated oxidation reactions of primary alco-
Alcohol
Product
Isolated yield
reaction time)
hols. The polymer was chlorinated on the imide and amide
nitrogens by treating it with household bleach (NaOCl) at
around pH 7. Then, these polymeric beads were used as
the co-oxidant for oxidation of primary alcohols in a wa-
ter/dichloromethane mixture in the presence of TEMPO.
After the reaction was completed (TLC), a simple filtra-
tion separated the partially chlorinated polymer from the
filtrate containing the aldehyde. The polymers could be
reused after they were regenerated with bleach. All of the
experiments reported in this study were performed with
(
OH
O
96% (3 h)
90% (3 h)
MeO
MeO
OH
O
85% (3 h)
OH
O
1
0 grams of polymer repeated at least three times wherein
F
F
we observed no material loss, activity change, or deforma-
tion of the polymer.
OH
O
8
9
8
5% (6 h)
0% (8 h)
5% (6 h)
F
F
We initiated our studies with benzyl alcohol, and water
and dichloromethane mixture (1:1) as the solvent system.
When the reaction was carried out without TEMPO (sim-
ply in the presence of chlorinated polymer); no formation
of the aldehyde was observed after 12 hours. The reaction
was repeated with the addition of TEMPO to the medium,
when we observed only small amounts (<2%) of the oxi-
F3C
F3C
OH
O
N
N
OH
N
N
O
dized products after 12 hours. Next, NaHCO was added
3
85% (6 h)
OH
O
to the reaction medium and complete conversion to the
benzaldehyde was observed within 2 hours. Encouraged
by the results, we repeated the reaction on a range of alco-
hols, most of which were completely oxidized to the cor-
responding aldehydes within 3 hours.13 In fact, the
reactions were usually complete in less than two hours;
the extra hour was spent in order to ascertain whether the
reaction produced any overoxidation product. Gratifying-
ly, we did not observe any carboxylic acids during the
O2N
O2N
9
9
8
0% (8 h)
0% (3 h)
5% (3 h)
OH
OH
O
O
OH
O
1
course of these reactions (Table 1) as monitored by H
OH
O
O
75% (3 h)
NMR and TLC. Substituted benzyl alcohols were oxi-
dized with relative ease. However, when an electron-with-
drawing group was present at the para position of the
benzyl alcohol, additional time was required for complete
conversion to the aldehyde; 4-(trifluoromethyl)benzyl al-
cohol, 4-fluorobenzyl alcohol, and 4-nitrobenzyl alcohol
required more than 3 hours to be completely oxidized.
Meanwhile, the reactions involving benzyl alcohols bear-
ing electron-donating groups proceeded smoothly to com-
pletion within 3 hours. These results are in keeping with
accumulation of positive charge at the benzylic carbon in
the transition state.
7
7
0% (3 h)
5% (3 h)
OH
OH
O
a
A general procedure is given13 and except for the reaction time, all
conditions were identical.
netics are most probably again due to the oxidation
involving positive charge accumulation on the benzylic
carbon.
Aliphatic alcohols were also subjected to the oxidation re-
actions under identical conditions. Although complete
conversion of the alcohol to the corresponding aldehyde
was observed within 3 hours, the isolated yields were not
as high as those of aromatic aldehydes; possibly due to the
low boiling point of these aldehydes. Allylic alcohols and
propargylic alcohols were oxidized efficiently. 3-Pyri-
dinemethanol and 4-pyridinemethanol were also subject-
ed to oxidation to observe the effect of a heteroatom on
these oxidations. Except for a slower conversion than that
for the benzylic alcohols, we did not observe any other ef-
fect of the heteroatom on these oxidations. The slow ki-
After reaction was complete, the mixture was filtered to
remove the solid. This was washed with water and diethyl
ether and the residual polymer was tested for remaining
chlorine by iodometric titration. Since we systematically
used excess of the active polymer, there was always some
chlorine left on the polymer but this did not result in over-
oxidation; whereas overoxidation was noted when hypo-
4
chlorous acid was used in previous studies. In the present
work hypochlorous acid is present only in minute amounts
due to the very low hydrolysis equilibrium constants
1
4
(
Scheme 2). Subsequently, we rechlorinated the poly-
Synlett 2013, 24, 2451–2453
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidation of Primary Alcohols to Aldehydes
2453
mer [NaOCl solution (HOCl) at pH ca. 7] for reuse. The
polymers were recycled for at least ten reactions and
could still be reused after this. Acetonitrile was also exam-
ined as a substitute for dichloromethane. However, even
though complete oxidation was observed (TLC and GC–MS),
the isolated yields were less than 20%. This observation is
still under investigation.
VCH: Weinheim, 2005. (b) Adam, W.; Saha-Möller, C. R.;
Ganeshpure, P. A. Chem. Rev. 2001, 101, 3499.
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B. Tetrahedron Lett. 1999, 40, 1201. (b) Kajjout, M.;
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(
4738. (c) Bekish, A. V. Tetrahedron Lett. 2012, 53, 3082.
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I. W. C. E.; Brink, G.-J. T.; Dijksman, A. Acc. Chem. Res.
(
n
n
2
002, 35, 774.
(
(
(
7) (a) Dijksman, A.; Arends, I. W. C. E.; Sheldon, R. A. Chem.
Commun. 2000, 271. (b) Tanyeli, C.; Gumus, A.
Tetrahedron Lett 2003, 44, 1639. (c) Wan, C.; Chung, Y.;
Toy, P. H. J. Comb. Chem. 2007, 9, 115. (d) Ferreira, P.;
Hayes, W.; Phillips, E.; Rippon, D.; Tsang, S. C. Green
Chem. 2004, 6, 310.
8) (a) Kenawy, E.-R.; Worley, S. D.; Broughton, R.
Biomacromolecules 2007, 8, 1359. (b) Sun, G.; Wheatley,
W. B.; Worley, S. D. Ind. Eng. Chem. Res. 1994, 33, 168.
+ HOCl
k < 10–4
+
H2O
Cl
Cl
N
N
O
O
O
N
H
O
N
Cl
n
n
(
c) Chen, Y.; Worley, S. D.; Kim, J.; Wei, C.-I.; Chen, T.-Y.;
Santiago, J. I.; Williams, J. F.; Sun, G. Ind. Eng. Chem. Res.
003, 42, 280.
+ HOCl
k < 10–9
H2O
+
H
2
Cl
N
9) (a) Einhorn, J.; Einhorn, C.; Ratajczak, F.; Pierre, J.-L.
J. Org. Chem. 1996, 61, 7452. (b) Angelin, M.; Hermansson,
M.; Dong, H.; Ramström, O. Eur. J. Org. Chem. 2006, 4323.
N
O
O
N
O
O
N
H
H
(
10) (a) Sun, G.; Chen, T. Y.; Worley, S. D. Polymer 1996, 37,
753. (b) Kou, L.; Liang, J.; Ren, X.; Kocer, H. B.; Worley,
S. D.; Tzou, T.-M.; Huang, T. S. Ind. Eng. Chem. Res. 2009,
3
Scheme 2 Dissociation constants for the chlorinated polymer
4
8
2
8, 6521. (c) Sun, Y.; Sun, G. Macromolecules 2002, 35,
909. (d) Cao, Z.; Sun, Y. ACS Appl. Mater. Interfaces
009, 1, 494.
In conclusion, we have utilized a polymeric N-halamine
as co-oxidant for TEMPO oxidation of a wide variety of
primary alcohols chemoselectively to aldehydes and it has
been shown that the reaction conditions are tolerant of dif-
ferent functional groups. The ease of performing the reac-
tion and workup provides the synthetic community with
an efficient method for chemoselective oxidation of pri-
mary alcohols to aldehydes.
(
11) Chen, Y.; Worley, S. D.; Kim, J.; Wei, C.-I.; Chen, T.-Y.;
Suess, J.; Kawai, H.; Williams, J. F. Ind. Eng. Chem. Res.
2003, 42, 5715.
(12) (a) Akdag, A.; Webb, T.; Worley, S. D. Tetrahedron Lett.
006, 47, 3509. (b) Akdag, A.; Liang, J.; Worley, S. D.
Phosphorus, Sulfur Silicon Relat. Elem. 2007, 182, 1525.
c) Sun, G.; Worley, S. D. Chem. Oxid. 1997, 134.
2
(
(
13) The procedure for the oxidation of benzyl alcohol is as
follows: A mixture of H O (5 mL) and CH Cl (5 mL) was
2
2
2
added to the chlorinated polymeric beads (2 g). (The
unchlorinated beads were obtained from HaloSource, Inc.
The unchlorinated beads were chlorinated by soaking the
beads in bleach solution, with pH adjusted to 7 by addition
of AcOH, for an hour. Then, the chlorinated beads were
filtered and dried in air.) After addition of TEMPO (10 mg,
Acknowledgment
We would like to thank HaloSource, Inc., for providing the unchlo-
rinated polystyrene hydantoin beads. We also would like to thank
the Middle East Technical University (METU) Department of Che-
mistry and METU research funds (BAP-08-11-2012-120) for provi-
ding financial support.
0.064 mmol) and benzyl alcohol (0.2 g, 1.8 mmol), NaHCO
0.5 g) was added to the mixture. The mixture was stirred at
3
(
r.t. for 3 h and filtered. The residue on the filter paper was
washed with H O (20 mL) and CH Cl (10 mL), and the
References and Notes
2
2
2
organic phase of the filtrate was separated, dried over
(
(
1) De Souza, M. V. N. Mini-Rev. Org. Chem. 2006, 3, 155.
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Chemical Society: Washington D.C., 1990.
MgSO , and filtered. The solvent was removed under
4
vacuum to obtain benzaldehyde.
(
14) Akdag, A.; Okur, S.; Mckee, M. L.; Worley, S. D. J. Chem.
(
3) (a) Arends, I. W. C. E.; Sheldon, R. A. Modern Oxidation of
Alcohols Using Environmentally Benign Oxidants, In
Modern Oxidation Methods; Bäckvall, J.-E., Ed.; Wiley-
Theory Comput. 2006, 2, 879.
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2451–2453

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