Oxone/sodium chloride: A simple and efficient catalytic system for the oxidation of alcohols to symmetric esters and ketones

Article abstract of DOI:10.1080/00397910500514030

An efficient method for the oxidation of alcohols is presented. The use of catalytic amounts of sodium chloride in combination with oxone allows the conversion primary aliphatic alcohols to symmetric esters. Secondary alcohols can be easily oxidized to ketones, and benzylic alcohols are converted to the corresponding aldehydes. The method is cost effective and enviromentally benign. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500514030

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Oxone/Sodium Chloride: A Simple and
Efficient Catalytic System for the Oxidation
of Alcohols to Symmetric Esters and Ketones
Agnes Schulze a , Georgia Pagona a & Athanassios Giannis a
a Institut für Organische Chemie, Universität Leipzig, Leipzig, Germany
Version of record first published: 24 Feb 2007
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A Simple and Efficient Catalytic System for the Oxidation of Alcohols to Symmetric Esters and Ketones,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
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Synthetic Communicationsw, 36: 1147–1156, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500514030
Oxone/Sodium Chloride: A Simple
and Efficient Catalytic System
for the Oxidation of Alcohols to Symmetric
Esters and Ketones
Agnes Schulze, Georgia Pagona, and Athanassios Giannis
¨
Institut fu¨r Organische Chemie, Universitat Leipzig, Leipzig, Germany
Abstract: An efficient method for the oxidation of alcohols is presented. The use of
catalytic amounts of sodium chloride in combination with oxone allows the conversion
primary aliphatic alcohols to symmetric esters. Secondary alcohols can be easily
oxidized to ketones, and benzylic alcohols are converted to the corresponding
aldehydes. The method is cost effective and enviromentally benign.
Keywords: Alcohols, aldehydes, catalytic oxidation, esterification, ketones
Oxidation of primary and secondary alcohols to aldehydes or carboxylic acids
and ketones, respectively, is a fundamental process in organic chemistry, and
several reagents have been developed for this purpose.[1] However, many of
the oxidants were subsequently abolished for environmental reasons.
Instead, enzymatic[2] and particularly metal-free[3] oxidations are now of
great interest, and a variety of valuable methods have been developed. To
the last category belong, for example, oxidations mediated by hypervalent
iodine reagents such as IBX[4,5] or TEMPO[1] in combination with
NaClO,[6] Br2,[7] I2,[8] or Cl2.[9] TEMPO has been also used in combination
with oxone and n-Bu4NBr as a phase-transfer catalyst.[10]
Received in Poland July 28, 2005
Address correspondence to Athanassios Giannis, Institut fu¨r Organische Chemie,
¨
Universitat Leipzig, Johannisallee 29, 04103 Leipzig, Germany. Fax: þ49/341 97
36 599; E-mail: giannis@chemie.uni-leipzig.de
1147

1148
A. Schulze, G. Pagona, and A. Giannis
A shortcoming of the TEMPO-mediated oxidations is the fact that one
equivalent sodium chloride is generated per molecule of alcohol oxidized.
Other shortcomings are the use of sodium bromide as a cocatalyst and chlori-
nated solvents. Finally, although TEMPO is used catalytically, it is expensive,
and efficient recycling is an important issue. Several approaches have been
developed[1d] to circumvent these problems.
Because of their importance, several methods for the conversion of
primary alcohols to symmetric esters have been developed.[11] Symmetric
esters are of considerable interest as ingredients for cosmetic, dermatological,
and pharmaceutical preparations. A search in SciFinder revealed more than
300 patents for this class of compounds. They are furthermore utilized for
the production of denture adhesives and stable aqueous surfactant compo-
sitions, in transdermal drug-delivery systems, as lubricants, and as mold-
release agents for polyurethanes. Esters of branched-chain carboxylic acids
with branched-chain alcohols have been described as antibacterial, antimyco-
tic, and antiparasitic substances and are used in skin preparations.[12]
Herein, we present a catalytic method for the oxidation of alcohols with
NaCl/oxone. Using this system, primary aliphatic alcohols are converted to
symmetric esters, and secondary alcohols can be easily oxidized to ketones.
Furthermore, benzylic alcohols are converted to the corresponding aldehydes.
We found that the combination of oxone (1 equiv.) and n-Bu4NBr
(0.1 equiv.) in a biphasic system (EtOAc/H2O) effectively converts
1-octanol (1 equiv.) to the corresponding symmetric ester. Importantly,
employing the same method and KBr (0.1 equiv.) instead of n-Bu4NBr
afforded also octyl octanoate in comparable yield. The later experiment was
a clear indication that 1) tetra-n-butylammonium oxone[13] was not the
actual oxidant and 2) the use of a phase-transfer catalyst was not necessary.
In fact, the use of n-Bu4NHSO4 and oxone or oxone alone did not induce
conversion of 1-octanol to octyl octanoate (or to octanal or octanoic acid) even
after prolonged reaction time.
Encouraged by these results, we next investigated the oxone/NaCl
(0.05–0.1 equiv.) system and were pleased to realize that it was more
effective in terms of yield and reaction time than the combination of oxone
with KBr or with n-Bu4NBr. With this reagent combination, a variety of
aliphatic alcohols could be converted to the corresponding symmetric esters
fast and at room temperature. In several cases formation of the corresponding
carboxylic acid was also observed (see Table 1 and Scheme 1). The use of KI
does not lead to any oxidation products.
In contrast to primary aliphatic alcohols, benzylic alcohols were oxidized
to the corresponding aldehydes (Scheme 2) in moderate yields. In these cases
we observed that the use of 0.5–1 equiv. of NaCl significantly increased the
yield.
Finally, secondary alcohols were oxidized to the corresponding ketones
(Scheme 3) in high yields.
However, our method is not compatible with double and triple bonds.

Table 1. Catalytic oxidation of primary and secondary alcohols with NaCl/oxone
Reaction
time (h)
Ratio
E:Aa
Total yield
(%)b
Entry
Substrate
Product
1
2
3
5
6:1
4:1
98
95
79
5.5
4.5
3.2:1
4
4.5
1:0
85
90
5
6
3.5
5
1:0
2.2:1
93
(continued)

Table 1. Continued
Reaction
time (h)
Ratio
E:Aa
Total yield
(%)b
Entry
Substrate
Product
7
8
5
5
1.1:1
—
68
60c
9
7
2
—
—
30c
10
85c

11
12
3.5
4
—
—
85
80
13
14
1.5
1
—
—
90c
94
15
4
—
80c
aE: ester, A: acid.
bYield of isolated product.
cThe yield was determined by GC/MS.

1152
A. Schulze, G. Pagona, and A. Giannis
Scheme 1. Oxidation of primary aliphatic alcohols.
Oxone has been applied in the past for several oxidations. For example, at
elevated temperature and in combination with concentrated sulfuric acid or
with acetic acid/ethanol, it has been used for the conversion of alkenes to
diols, phenols to quinones, pyridine to pyridin-1-oxide, sulfides to sulfoxides,
and ketones to esters or to lactones.[14] Recently, oxone has also been utilized
for the oxidation of aromatic and aliphatic aldehydes to the corresponding car-
boxylic acids or esters.[15] Furthermore, oxone is the reagent of choice for the
synthesis of dimethyldioxirane[16] and IBX.[4a]
It is known that treatment of NaCl or NaBr with oxone generates chlorine
and bromine respectively.[17] This system has been used for chlorinations and
brominations of a,b-unsaturated carbonyl compounds or for the conversion of
oximes to gem-chloro-nitro derivatives.[18] The combination of NaBr/oxone
was also reported to oxidize benzylic alcohols to aldehydes, secondary
alcohols to ketones, and butanol to the symmetric ester. An important short-
coming of this method is the bromination of the aromatic system and the
need for an excess of NaBr.[19]
The oxidation of primary alcohols to symmetric esters is described in
Scheme 4: First, the aldehyde is formed, which is then attacked by the
parent alcohol to form the corresponding hemiacetal. Oxidation of the latter
affords the symmetric ester. The isolation of aromatic aldehydes (see
Table 1, entries 8–10) supports this suggestion. They do not form
symmetric esters probably because their carbonyl group is not sufficiently
electrophilic[20] to allow a nucleophilic attack by a second molecule of the
aromatic alcohol present in the reaction mixture. Attempts to convert
primary alcohols to tert. butylesters by performing the oxidations in the
presence of tert. butanol have been unsuccessful.
In conclusion we presented a new, efficient, and fast method for the con-
version of primary aliphatic alcohols to symmetric esters as well for the
oxidation of secondary alcohols to ketones. Our method is cost-effective
and enviromentally benign. In fact, only catalytic amounts of sodium
chloride are used, whereas oxone is inexpensive, stable, easy to transport,
and nontoxic. The resulting inorganic by-products are also nonpolluting.
Scheme 2. Oxidation of benzylic alcohols.

Oxone/Sodium Chloride
1153
Scheme 3. Oxidation of secondary alcohols.
EXPERIMENTAL
Reagents and solvents were commercially available and were used without
1
further purification. H and 13C NMR spectra were recorded on a Varian
1
Gemini 200 (200 MHz for H NMR; 50 MHz for 13C NMR) and Varian
1
Gemini 2000 (200 MHz for H NMR; 50 MHz for 13C NMR). Chemical
shifts were reported in the scale relative to the solvent used as an internal
reference. HR MS was obtained on a Bruker Daltonics APEX II (for ESI).
The reaction progress was monitored with a Varian Saturn 2200 GC/MS.
Flash column chromatography was performed on Merck silica gel 60
(0.040–0.063 mm).
Typical Experimental Procedure
Oxone (1 mmol), NaCl (0.1 mmol), and finally H2O (0.5 ml) were added to a
solution of the alcohol (1 mmol) in EtOAc (2 ml). The reaction mixture was
stirred at room temperature for 1–7 h depending on the alcohol (see
Table 1). After completion of the reaction, the mixture was diluted with
H2O (5 ml) and EtOAc (3 ml), and the layers were separated. The aqueous
layer was extracted with EtOAc (3 ꢀ 5 ml), and the combined organic
layers were dried over Na2SO4. The solvent was removed under reduced
pressure to give the desired product. Analytical pure products were obtained
by column chromatography.
1
6-Chlorohexyl 6-chlorohexanoate (3): oil; H NMR (CDCl3, 200 MHz):
d ¼ 1.41–1.82 (m, 14H), 2.28–2.37 (m, 2H), 3.54 (t, 4H, J ¼ 6.6 Hz), 4.07
(t, J ¼ 6.6 Hz, 2H); 13C NMR (CDCl3, 50 MHz): d ¼ 24.4, 25.4, 26.5, 26.6,
28.6, 32.4, 32.6, 34.2, 44.8, 44.9, 64.4, 173.7; HR ESI-MS: calcd. for
(M þ Na)þ: 291.08891; found: 291.08935.
2-Ethylbutyl 2-ethylbutanoate (4): oil; 1H NMR (CDCl3, 200 MHz):
d ¼ 0.89 (t, 12H, J ¼ 7.4 Hz), 1.29–1.66 (m, 9H), 2.13–2.28 (m, 1H), 4.01
(d, 2H, J ¼ 5.5 Hz); analytical data were consistent with those reported in
the literature.[21]
Scheme 4. Oxidation of primary alcohols to symmetric esters by NaCl/oxone.

1154
A. Schulze, G. Pagona, and A. Giannis
2-Ethylhexyl 2-ethylhexanoate (5): oil; 1H NMR (CDCl3, 200 MHz):
d ¼ 0.85–0.93 (m, 12H), 1.19–1.66 (m, 17H), 2.19–2.32 (m, 1H), 4.07
(d, 2H, J ¼ 5.6 Hz); analytical data were consistent with those reported in
the literature.[11c]
1
Compound (6): oil; H NMR (CDCl3, 200 MHz): d ¼ 0.88–1.00 (m, 18H),
1.11–1.72 (m, 17H), 2.08–2.41 (m, 3H), 4.11–4.16 (m, 2H); analytical
data were consistent with those reported in the literature.[22]
Cyclohexylmethyl cyclohexylcarboxylate (7): oil; 1H NMR (CDCl3,
200 MHz): d ¼ 0.98–1.93 (m, 21H), 2.21–2.40 (m, 1H), 3.87 (d, 2H,
J ¼ 6.4 Hz); analytical data were consistent with those reported in the
literature.[23]
Compounds 1, 2, 3, 8, 9, 10, 11, 12, 13, 14, and 15 are commercially
available.
ACKNOWLEDGMENTS
A. Schulze is grateful for grants from the Graduiertenkolleg Mechanistische
und Anwendungsaspekte nicht-konventioneller Oxidationsreaktionen.
G. Pagona is grateful for a grant from European Union under the auspices
of the Socrates Exchange Program.
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