Room-Temperature oxidation of secondary alcohols by bromate-bromide coupling in acidic water

Article abstract of DOI:10.1080/00397911.2010.526283

The use of environmentally benign reactions is currently an important topic in the field of synthetic chemistry. Here we report a high-yielding method to oxidize aliphatic or aromatic secondary alcohols into corresponding ketones using nonhazardous and inexpensive BrOH reagent at room temperature in water. BrOH reagent was derived from NaBr and NaBrO₃ in aqueous acid. Based on the presented results, a mechanism was proposed for this oxidation. The reported method offers a facile, efficient procedure to produce various ketones with a low amount of side products. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.526283

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Room-Temperature Oxidation of
Secondary Alcohols by Bromate–Bromide
Coupling in Acidic Water
Sanna Pääkkönen a , Jouni Pursiainen a & Marja Lajunen a
a Department of Chemistry , University of Oulu , Oulu , Finland
Accepted author version posted online: 04 Aug 2011.Published
online: 17 Oct 2011.
To cite this article: Sanna Pääkkönen , Jouni Pursiainen & Marja Lajunen (2012) Room-Temperature
Oxidation of Secondary Alcohols by Bromate–Bromide Coupling in Acidic Water, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
42:4, 534-540, DOI: 10.1080/00397911.2010.526283
To link to this article: http://dx.doi.org/10.1080/00397911.2010.526283
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Synthetic Communications1, 42: 534–540, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.526283
ROOM-TEMPERATURE OXIDATION OF SECONDARY
ALCOHOLS BY BROMATE–BROMIDE COUPLING IN
ACIDIC WATER
¨ ¨
Sanna Paakkonen, Jouni Pursiainen, and Marja Lajunen
Department of Chemistry, University of Oulu, Oulu, Finland
¨
GRAPHICAL ABSTRACT
Abstract The use of environmentally benign reactions is currently an important topic in the
field of synthetic chemistry. Here we report a high-yielding method to oxidize aliphatic or
aromatic secondary alcohols into corresponding ketones using nonhazardous and inexpen-
sive BrOH reagent at room temperature in water. BrOH reagent was derived from NaBr
and NaBrO3 in aqueous acid. Based on the presented results, a mechanism was proposed
for this oxidation. The reported method offers a facile, efficient procedure to produce
various ketones with a low amount of side products.
Keywords Alcohol oxidation; hypobromous acid; ketone; water
INTRODUCTION
Oxidation of primary or secondary alcohols to corresponding aldehydes or
ketones is an important transformation reported in several reviews.[1] Various
reagents have been successfully used for that purpose.[2]
These days it is important to plan synthetic strategies from an ecological point
of view. The possibility of recycling reagents is also an important aspect. The opti-
mum solution to minimize solvent wastes would be a solventless reaction.[3] The use
of environmentally friendly solvents, such as water, is preferable, as well.[4] Addition-
ally, catalytic reactions contain interesting possibilities for oxidation.[5]
Recently, iodine-based reagents have been introduced as oxidizing agents with
low toxicity, easy availability or handling, and high stability.[6] Bromine compounds
have been used in brominations as ecofriendly and safe reagents.[7] Bromate has
been reported to oxidize secondary alcohols in acidic solution[8] and with metal
catalysts.[9]
Molecular bromine is a strong oxidant. A drawback of bromine oxidations of
secondary alcohols in acidic solution is the formation of brominated by-products.
Received August 24, 2010.
Address correspondence to Marja Lajunen, Department of Chemistry, University of Oulu,
P.O. Box 3000, Oulu, FI-90014, Finland. E-mail: Marja.Lajunen@oulu.fi
534

OXIDATION OF ALCOHOLS BY BROMATE–BROMIDE
535
Primary alcohols instead produce esters without side products.[10] It has been pro-
posed that in acidic bromate–bromide oxidation, hypobromous acid and bromine
are in equilibrium and that hypobromous acid acts as the oxidizing species.[11]
Bromate–bromide oxidation has been used to oxidize ethers to esters[12] and in
aqueous organic solvents secondary alcohols to ketones.[11a,13a] Very recently, bro-
mate has been successfully used to produce a-bromoketones from olefins.[13b] The
reaction was performed in a dioxane–water mixture and it contained bromohydrin
as an intermediate, which further reacted with another BrOH equivalent.
In this article, we report a mild and simple method to oxidize various second-
ary alcohols to ketones at room temperature in plain water by using BrOH as the
oxidizing agent. Hypobromous acid was generated from harmless NaBr with
NaBrO3 [Eq. (1)] in aqueous acid.[13]
BrOꢀ3 þ 2Brꢀ þ 3Hþ ! 3BrOH
ð1Þ
RESULTS AND DISCUSSION
In connection with our oxidation studies of 2-butanol by using bromide–
bromate reagent in dioxane–water or tetrahydrofuran (THF)–water (1:4) mixture,
it was noticed that the oxidation could be successfully performed in plain water.
The oxidation produced, in addition to 2-butanone, brominated compounds
3-bromo-2-butanone and 1-bromo-2-butanone. To support the formation of 2-buta-
none, and simultaneously avoid the formation of undesired bromo compounds, the
effect of the amount of BrOH, the addition rate of acid and the total reaction time on
the product distribution was studied.
During the experiments it was noticed that the increased concentration of
BrOH accelerated the oxidation of 2-butanol, but simultaneously increased the
amount of bromo compounds. The addition rate of the acid affected the product dis-
tribution. A slow addition kept the oxidation rate low and decreased the formation
of bromo compounds. The dilution of the concentration of BrOH reagent did not
significantly affect the reaction rate and the additional advantage was that only trace
amounts of brominated products formed.
It was concluded that optimum reaction conditions in water required 1.05
equiv. (0.21 mol=L) of active BrOH as prepared from bromide–bromate solution
(2:1, respectively) with 10% H2SO4. The acid should be added slowly over the course
of at least 2 h. These reaction parameters were applied to oxidations of various
secondary alcohols, and their results are presented in Table 1.
The reaction time of the oxidations mainly varied between 2 h 15 min and 6 h.
Electron-donating groups in the vicinity of the hydroxyl group shortened the oxi-
dation time (Table 1, entries 3–5 vs. entry 1). Benzylic alcohols oxidized concurrently
with the addition of the acid (Table 1, entries 7–10). An electron-withdrawing group
next to the hydroxyl group (Table 1, entry 11) decreased the reaction rate remark-
ably, and the diol (Table 1, entry 12) did not react at all. Experiments with primary
alcohols showed that they oxidized to esters as reported in the literature.[11]
Results in Table 1 show that an electronic effect affects these oxidations. They
indicate that the slow step of the reaction includes the generation of the positive

¨ ¨
S. PAAKKONEN, J. PURSIAINEN, AND M. LAJUNEN
¨
536
Table 1. Oxidation of secondary alcohols (0.2 mol=L) in water at room temperature using 1.05 equiv. of
BrOH reagent
Reaction products (%)
Yielda Purity
Entry Time (h)
Alcohol (%)
Product
Side products
(%)
(%)
1b
2b
3b
6
49
96
2.25
90
71
96
92
4
4b
3
65
97
5b
3.5
4
52
—
92
—
6c
7
8
2.25
2.25
100
100
>99
>99
9
2.25
95
95
(Continued )

OXIDATION OF ALCOHOLS BY BROMATE–BROMIDE
537
Table 1. Continued
Reaction products (%)
Yielda Purity
Entry Time (h)
Alcohol (%)
Product
Side products
(%)
(%)
10
2.25
87
100
11b
12
48
Several minor products
—
—
24
No reaction
aYield of isolated, properly characterized (1H NMR, 13C NMR, MS) product.
bYield of the pure ketone was determined from the 1H NMR spectrum of a mixture that contained
CH2Cl2 based on the ratio of the integral of CH2Cl2 singlet (d: 5.284 ppm) and COCH3 singlet or COCH2
quartet of the ketone.
cOnly GC-MS analysis of the product mixture.
charge. Patil et al. has proposed that a reaction of alkene to a-bromoketone by using
BrOH reagent happens via a bromohydrin intermediate.[13b] Kajigaeshi et al. believe
that the oxidizing species in their ketone- and ester-producing oxidations was mol-
ecular bromine or BrOH.[11a] Farcas et al. has reported that in the oxidation of pri-
mary alcohols with bromine the formation of hypobromite ester (R-OBr) is the slow
step.[10a] However, Ogata et al. has pointed out that in the reaction mixture hypo-
bromite ester and alcohol are in equilibrium.[11b]
Based on these studies and our results in Table 1, we concluded that the oxidizing
species Brþ ion can be generated either from BrOH or Br2 by the release of H2O or HBr.
It is believed, that Hꢀ attacked Brþ, resulting in a release of HBr in a slow step leading
to the development of a partial positive charge on the carbonyl carbon (Scheme 1).
In Scheme 1, according to mechanism 1, the release of HBr in the slow step
would generate the partial positive charge on carbonyl carbon although the adjacent
Scheme 1. Two alternative mechanisms zfor the oxidation of secondary alcohol by using BrOH reagent.
The supposed slow step is marked with
.

¨ ¨
S. PAAKKONEN, J. PURSIAINEN, AND M. LAJUNEN
¨
538
oxygen atom carries a positive charge. The slow step of mechanism 2 (Scheme 1)
induces a rational charge distribution consistent with the results of Table 1. We
believe that the reaction follows this mechanism. As a small species, Brþ ion does
not suffer any steric hindrance in this oxidation.
CONCLUSIONS
This study demonstrates that NaBr-NaBrO3 salt mixture in acidic conditions
can be used as a readily available, nontoxic, and low-cost oxidation system at room
temperature in plain water. It provides an efficient, mild, and convenient method for
the oxidation of aliphatic or benzylic secondary alcohols without any organic solvent.
The optimum oxidation conditions required 1.05 equiv. of active BrOH as
dilute aqueous solution prepared from bromide–bromate mixture (2:1, respectively)
with 10% H2SO4. It was essential for the clean room-temperature oxidation that the
acid was slowly added over the course of at least 2 h. This, with the dilute reaction
mixture, kept the amount of the oxidizing species low and thus reduced the
possibility of side reactions.
With benzylic alcohols the isolated yields of corresponding ketones were good
(87–100%) and with aliphatic alcohols were moderate to good (49–90%). Poor yields
were obtained with highly evaporative ketones. Commonly, the purity of the
products was good without further purification.
In summary, this study offers improvements in terms of simplicity, benign pro-
cedure, mild reaction conditions, commercially available reagents, and good yield of
an isolated product with a small amount of side products. The method avoids the use
of hazardous organic solvents and toxic metal catalysts and thus provides a clean
and practical alternative to existing procedures.
EXPERIMENTAL
Materials and Product Analysis
All commercially available reagents (Aldrich, TCI, RdH) were used as pur-
chased. Bromohydrin (entry 11, Table 1) was prepared from octene.[14] 1H and
13C NMR spectra were recorded on a Bruker DPX 200 spectrometer and are
reported in parts per million (ppm) from tetramethylsilane (TMS) or solvent residue
(CDCl3, dH ¼ 7.26 ppm, dC ¼ 77.16 ppm) as an internal standard. Gas chromato-
grams were recorded on a Perkin-Elmer Auto System XL by using an OV-1 column
equipped with a FI detector. Electron-impact (EI) mass spectra (GC-MS) were
recorded at 70 eV ionization energies using a HP 5973 mass spectrometer and a
HP 6890 series GC system with a DB-624 column. High-resolution mass spectra
(ESI-MS) were recorded in positive mode on a Micromass LCT-TOF mass spec-
1
trometer. The purity of the products was determined by H NMR and GC.
General Procedure for Oxidation of Secondary Alcohols
Alcohol (10 mmol), distilled water (40 mL), and aqueous solution (5 mL) con-
taining a 2:1 molar ratio of NaBr (0.72 g, 7 mmol) and NaBrO3 (0.528 g, 3.5 mmol)

OXIDATION OF ALCOHOLS BY BROMATE–BROMIDE
539
reagent were placed in a round-bottomed flask. The reaction mixture was stirred at
room temperature, and 10% H2SO4 (5 mL, 5.25 mmol) was added within 135 min.
The reaction was followed by GC-MS and was stopped by adding ca. 10 drops of
saturated aqueous Na2S2O3 solution. The aqueous solution was extracted with
3 ꢁ 50 mL CH2Cl2. The combined organic layers were washed with brine and dried
with MgSO4.
Spectral Data
1
All oxidation products are known compounds, and their recorded H and 13C
NMR as well HRMS [with <100 g=mol compounds MS(EI)] data were in good
agreement with the values reported in the literature.
ACKNOWLEDGMENTS
This work was financially supported by the Inorganic Materials Chemistry
Graduate Program and Magnus Ehrnrooth Foundation. The authors thank Pa¨ivi
Joensuu and Petri Reponen for their assistance with the MS measurements, Anu
Kantola for her assistance with the quantitative NMR measurements, and Matti
Vaismaa for his advice.
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