Autocatalytic oxidation of ethers with sodium bromate

Article abstract of DOI:10.1016/S0040-4020(00)00098-3

Sodium and potassium bromate are stable and easily stored oxidants. They can oxidize both open and cyclic ethers in aqueous solution at room temperature yielding esters and lactones. Kinetic studies of the oxidation of tetrahydrofuran to γ-butyrolactone indicate that the major active oxidation species is bromine and not bromate. The bromate is only a supporting agent, responsible for the initiation step and supplying bromine molecules by oxidizing bromide ions during the propagation step. In the oxidation of tetrahydrofuran, high yields of γ-butyrolactone were obtained. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00098-3

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1905–1910
Autocatalytic Oxidation of Ethers with Sodium Bromate
*
Leonid Metsger and Shmuel Bittner
Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
Received 19 November 1999; revised 4 January 2000; accepted 27 January 2000
Abstract—Sodium and potassium bromate are stable and easily stored oxidants. They can oxidize both open and cyclic ethers in aqueous
solution at room temperature yielding esters and lactones. Kinetic studies of the oxidation of tetrahydrofuran to g-butyrolactone indicate that
the major active oxidation species is bromine and not bromate. The bromate is only a supporting agent, responsible for the initiation step and
supplying bromine molecules by oxidizing bromide ions during the propagation step. In the oxidation of tetrahydrofuran, high yields of
g-butyrolactone were obtained. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
formation of esters2,3,5,7,8 and carboxylic acids.4,8,10 Bromate
salts were also shown to oxidize sulfides to sulfoxides,9
hydroquinones and polyaromatics to quinones,9,10 thiols to
disulfides,11 and iodobenzenes to iodoxybenzenes.12 Even
more interesting is the finding that reaction of dialkyl ethers,
or cyclic ethers with sodium bromate in the presence of
catalytic amounts of hydrobromic acid, gave esters or
lactones in fairly good yields.3 In addition it is known
that bromine itself13 and benzyl trimethyl ammonium
tribromide14 all induce the oxidative cleavage of ethers to
carboxylic acids, ketones, esters and alcohols.
Sodium bromate and potassium bromate are commercially
available, very stable solids which can be handled much
more easily than liquid bromine or hypobromous acid
solutions. Oxidation with bromates results in bromide ion
formation, which can be safely treated or recycled. Thus
such oxidations are recognized as friendly to the environ-
ment, compared to the traditional metal containing reagents
such as chromate, permanganate, cerium and ruthenium
salts etc.
According to the literature, bromate itself cannot oxidize
ethers. A ‘counter-reagent’ is needed, which can be of two
types:
In spite of much work, which has been performed on the
oxidation of organic compounds with bromate, organic
synthesis using bromate salts is still scanty. Overoxidation,
bromination and oxidative bromination usually interfere
with clean reactions and a host of products may result.
Reaction conditions, particularly the strength and nature
of the acid used are crucial, and determine in which
direction the reaction proceeds.
(a) A reducing agent, which reacts with the bromate in a
redox type reaction to form bromine. The bromine
formed then oxidizes the ether (Scheme 1). Examples
of counter-reagents of this type are sodium bisulfite15 or
hydrobromic acid.3
Bromate salts can oxidize primary alcohols to alde-
hydes,1–5,7 secondary alcohols to ketones2,3,5,6 and under
different sets of conditions the oxidation can result in
Such a counter-reagent is needed only in catalytic
amounts to initiate the reaction. Beyond this stage the
oxidizing bromine can be supplied by the reaction
Scheme 1.
Keywords: oxidation of ethers; sodium bromate; lactones; esters; bromine.
* Corresponding author. Tel.: ϩ972-7-6461195; fax: ϩ972-7-6472943; e-mail: bittner@bgumail.bgu.ac.il
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00098-3

1906
L. Metsger, S. Bittner / Tetrahedron 56 (2000) 1905–1910
with bromates. The oxidations were performed in water at
room temperature using equivalent quantities of sodium
bromate and potassium hydrogen sulfate. An equivalent
amount of dialkyl ether, or cyclic ether was added, which
usually caused an exothermic reaction with coloration of the
system (yellow). After total conversion of the ether (GC),
the esteric or lactonic products were extracted into an
organic solvent and evaluated either by isolation or by gas
chromatography. Acidic products were isolated from the
aqueous solution. All isolated products were characterized
by comparison of their physical and spectral data with those
of known samples.
Scheme 2.
Scheme 3.
The results obtained with several ethers are summarized in
Table 1. Under these conditions, diethyl ether was totally
oxidized to acetic acid (98%) with just traces of ethyl
acetate. Oxidation of the higher homologue, dibutyl ether,
gave mainly butanoic acid (52%), accompanied by appre-
ciable amounts (35%) of butyl butanoate.
bromate–bromide, and the bromide anion becomes the
counter-reagent.
(b) An oxidizing agent, which has the sole responsibility
for the oxidation of the ether. The role of bromate in this
case is to reoxidize the reduced form of the counter-
reagent. Such a counter-reagent can be a cerium(IV)
salt (Scheme 2).16 In this case also only a catalytic amount
of the counter-reagent is needed.
The situation was different with cyclic ethers. Thus oxida-
tion of tetrahydrofuran gave 80% of g-butyrolactone and only
11% of succinic acid. Similarly, tetrahydropyran gave 69%
of d-valerolactone, and only 16% of glutaric acid. 3-Methyl-
tetrahydropyran was oxidized with no selectivity; almost
equal quantities (25 and 28%) of the a- and the g-methyl-
d-valerolactones were obtained. An interesting degradation
reaction took place upon oxidation of 1,4-dioxane. This
cyclic diether was totally oxidized to carbon dioxide. The
mechanism probably starts with oxidation to the bis-lactone,
which is further oxidized to the bis-anhydride (Scheme 4).
Decomposition in water yields 2 equiv. of oxalic acid,
which are finally oxidized to carbon dioxide and water.
Results and Discussion
Oxidation of ethers with bromate salts only, without the
addition of a counter-reagent was performed recently in
our laboratory (Scheme 3), and the results obtained shed
new light on the question of direct or indirect oxidation
Table 1. Oxidation of alkyl ethers by sodium bromate in aqueous solution at room temperature
Ether
Time (h)
Ester
Yield (%)a
Acid
Yield(%)a
Et–O–Et
Bu–O–Bu
72
48
CH3COOEt
CH3(CH2)2COOBu
Traces
35b
CH3COOH
CH3(CH2)2COOH
98
52b
16
20
20
80c
11
69
16
25b
28b
Traces
120
16
87
CO2
Quantitative
a Isolated yield.
1
b The ratio between the products was determined by H NMR.
c GC yield (isolated yield of lactone 73%).

L. Metsger, S. Bittner / Tetrahedron 56 (2000) 1905–1910
1907
Fig. 2 represents the same reaction under different concen-
trations of sodium bromate. The total conversion of the
20 mmoles of THF, under these conditions needed
20 mmoles of bromate and the yield of g-BL was 80%.
Using higher concentrations of bromate lowered the yield
of the lactone.
In a similar set of experiments, we studied the reaction as
function of time (Fig. 3), using the optimal conditions as
found in the two former sets of reactions, namely 20 mmol
of THF, 20 mmol of sodium bromate in 0.7 M KHSO4 solu-
tion. The results indicate maximum conversion after 16 h at
room temperature with an 80% yield of g-butyrolactone.
Scheme 4.
Similar total oxidation with evolution of CO2 was observed
in the bromate oxidation reaction of mono- and disacchar-
ides.
In order to optimize this oxidative process and to learn about
its kinetics, we performed several sets of experiments using
the oxidation of tetrahydrofuran (THF) to g-butyrolactone
(g-BL), as a model reaction.
Upon analyzing the results, two facts deserve mention:
• Under the aforementioned set of conditions the yield of
g-BL is never quantitative, it increases gradually up to
80% and than starts to drop (see for example Fig. 3).
• At any point of the reaction coordinate the total quantities
of THF (starting material) and g-BL (product) are less
than 100%.
First, we studied the reaction as a function of the acidity of
the medium by changing the concentration of KHSO4 (see
Fig. 1).
As can be seen, total conversion was obtained at a concen-
tration of 0.6 M bisulfate, while the maximum yield of g-BL
(80%) was obtained using a 0.7 M concentration of the acid.
Both lower acidities or higher acidities resulted in reduced
yields of the lactone.
These two facts are logical and can be explained if we
recognize that the oxidation of THF by bromate is a multi-
step process which can proceed via several paths. Moreover
the g-BL itself under the reaction conditions can be further
oxidized to succinic acid. The various optional oxidation
Figure 1. Conditions: 20 mmol THF; 20 mmol NaBrO3; 25 mL aqueous solution of KHSO4; room temperature 16 h; quantitative determination by GC analysis
using 1,2-dichlorobenzene as the internal standard. The data in the figure represent an average of two different runs.
Figure 2. Conditions: 20 mmol THF; 25 mL of 0.7 M aqueous solution of KHSO4; room temperature 16 h; quantitative determination as in Fig. 1.

1908
L. Metsger, S. Bittner / Tetrahedron 56 (2000) 1905–1910
Figure 3. Conditions: 20 mmol THF; 20 mmol NaBrO3; 25 mL of 0.7 M aqueous solution of KHSO4; room temperature; quantitative determination as in
Fig. 1.
paths are shown in Scheme 5. a-Hydroxylation of the ether
(1) and formation of the hemiacetal (2) is the first step. The
hemiacetal can now be directly oxidized to g-BL (5), or be
hydrolyzed to the open chain 4-hydroxybutanal (3). The
hydroxy aldehyde is easily oxidized to the 4-hydroxybuta-
noic acid (4) which undergoes spontaneous cyclization to
yield g-BL (5). The g-BL itself can undergo further oxi-
dation to form lactone hemiacetal (6), succinic anhydride
(7), and the final product, succinic acid (8).
reaction acceleration posed a question as to the nature of
the active oxidant in this reaction. It is very well established
that bromine can oxidize alicyclic and cyclic ethers and thus
can convert THF to g-BL.13 At least two oxidizing species
are present in our reaction mixture, the bromate and the
bromine. Is it possible that two parallel mechanisms are
active in this process? Or maybe the bromate is not oxi-
dizing the ethers at all, and bromine, formed during the
initial stage of the process, is the principal active agent?
This course of events explains why the yield of g-BL is
never quantitative (further oxidation of 5), and it also
explains why at any time during the reaction, the sum of
THF and g-BL do not reach 100% (presence of stable and
semi-stable intermediates e.g. 2, 3 and 4).
We ran an extra few crucial experiments, in which we
oxidized THF with bromate under the aforementioned opti-
mized conditions, but with the addition of 1 equiv. of an
alkene (e.g. cyclohexene). We reasoned that the alkene
would act as a scavenger adding spontaneously any bromine
formed. Indeed the yield of g-BL, which without cyclohex-
ene was ϳ80%, dropped dramatically to less than 5%, and
most of the starting ether was recovered.
Two other observations need explanation:
• All the oxidative reactions are characterized by an initial
slow phase, followed by a second phase, in which the
reaction rate accelerates. The mass oxidation takes
place in this second phase.
• During the oxidative reaction free bromine appears in the
mixture. The appearance of the bromine coincides with
the start of acceleration.
These three facts: (a) acceleration of the rate of reaction; (b)
formation of Br2; and (c) dramatic drop in oxidation, when
Br2 scavengers are present, suggest that two different
mechanisms might be responsible for the oxidation of
THF: (1) Oxidation by bromate itself, which seems to be
a slow process; (2) Oxidation by bromine, which is a fast
process.
These two observations, namely bromine formation and
Scheme 5. Oxidation paths of THF.
Scheme 6. Mechanism of THF oxidation by bromate.

L. Metsger, S. Bittner / Tetrahedron 56 (2000) 1905–1910
1909
Scheme 7. Mechanism of THF oxidation by bromine.
Scheme 9. General process of THF oxidation by bromate.
We suggest that under the aforementioned reaction
conditions, the first mechanism is meaningful only in the
initiation phase of the reaction, otherwise most of the
oxidation proceeds via the second mechanism, namely,
oxidation by bromine.
according to Scheme 7 to yield five bromide ions, these
ions will then react with one molecule of bromate to
produce three molecules of bromine. Thus, in this cyclic
process in which we start with 2.5 and produce three
molecules, which can now further oxidize the ether, we
gain half a molecule of Br2. In each oxidative cycle we
produce an extra half a molecule of bromine and the result
is acceleration of the oxidation reaction. This is a typical
autocatalytic process.
The oxidation of THF by bromate can be formulated as in
Scheme 6.
The protonated ether (1) undergoes substitution with
bromate at the activated a-carbon to yield a bromate ester
(2). Elimination of bromite (4) yields the a-hydroxy
aldehyde (3) which undergoes further oxidation to the
g-hydroxy acid, concurrently with formation of bromine.
The g-hydroxy acid cyclizes to the g-BL (5).
We suggest the following general scheme (Scheme 9) to
describe the oxidation process of ethers with bromate
salts: a slow initiation process, in which Br2 is formed
followed by an accelerated propagation process.
In conclusion, our data on direct oxidation of ethers with
bromate point towards bromine as the main active oxidant.
Bromate itself is responsible only for the initiation step and
than plays the role of a co-oxidizer or bromine supplier.
This is a slow mechanism representing only the initiation
step of the oxidation process. Its importance is in the for-
mation of bromine, which is a faster oxidizer of ethers.
Beyond this initiating step the bromate becomes only a
reservoir supplying molecular bromine.
Experimental
The mechanism of THF oxidation by bromine can be formu-
lated as in Scheme 7.
All starting materials were commercially available. GC
analysis was performed on a Perkin–Elmer 8310 chromato-
graph with a flame ionization detector (FID) fitted with a
2×1000 mm column, packed with 10% Carbowax in
Chromosorb. The yields of products were determinated by
isolation using distillation techniques and from the peak
area based on internal standart GC technique. The internal
Charge transfer complexation of bromine with THF (1)13
facilitates elimination of HBr to yield the intermediary
oxonium salt (2). Addition of a molecule of water and elimi-
nation of a second molecule of HBr gives the hemiacetal (4).
The hemiacetal is in equilibrium with the open-chain g-hy-
droxy aldehyde (5), which can undergo a second oxidation
followed by cyclization to the g-BL (6). The possibility of
direct oxidation of the hemiacetal (4) to g-BL (6) is not
excluded.
1
standart used was 1,2-dichlorobenzene. H NMR spectra
were recorded on a Bruker DPX-200 spectrometer.
General procedures for oxidation of ethers with sodium
bromate
The fact that the rate of oxidation accelerates during the
process, strengthens our assumption that oxidation with
bromine is the main operating mechanism. When bromine
oxidizes THF, bromide is formed. Bromate can react with
the bromide in the acidic medium to yield bromine (Scheme
8).
To a stirred mixture of ether and water (0.1 mol ether and
100 mL of water) were added 15.1 g (0.1 mol) of sodium
bromate and 13.6 g (0.1 mol) of potassium hydrogen sul-
fate. Both cooling of the reaction mixture and an efficient
reflux condenser were used in order to minimize evapo-
ration of the ether and keeping the reaction temperature in
the range 25–30ЊC. Stirring was continued at room tempera-
ture for 16–20 h. To quench any excess of bromine formed,
acidic sodium sulfite solution was used. Thus, 10% aqueous
solution of sodium sulfite (about 140–150 mL) and 13.6 g
(0.1 mol) of potassium hydrogen sulfate were added. The
mixture was cooled and extracted with CH2Cl2 (5×30 mL in
the case of lactone formation, or 3×30 mL in the case of
If we assume that 2.5 molecules of Br2 react with THF
Scheme 8.

1910
L. Metsger, S. Bittner / Tetrahedron 56 (2000) 1905–1910
linear esters). The combined organic layer was dried over
magnesium sulfate, the solvent removed in vacuum and
the residue purified by distillation. g-Butyrolactone was
distilled at 204–205ЊC/760 mm. Yield: 6.3 g (73%). d-Valero-
lactone was distilled under reduced pressure at 97–98ЊC/
10 mm. Yield: 6.9 g (69%). The mixture of a-methyl-d-
valerolactone and g-methyl-d-valerolactone was distilled
under reduced pressure at 97–101ЊC/10 mm. Yield: 6.4 g
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We thank Ethel Solomon for skillful technical help.