Oxidation of secondary alcohols with phenyltrimethylammonium tribromide in the presence of a catalytic amount of antimony(III) bromide or copper(II) bromide

Article abstract of DOI:10.1055/s-2004-832840

The oxidation of alcohols was carried out with phenyltrimethylammonium tribromide in the presence of a catalytic amount of SbBr₃ or CuBr₂. 1,2-Diols, such as hydrobenzoin, were converted into 1,2-diketones or α-ketols without oxidative cleavage of the glycol C-C bond at room temperature. A variety of secondary alcohols were also oxidized to the corresponding carbonyl compounds in a chemoselective manner.

Full text of DOI:10.1055/s-2004-832840

LETTER
2369
Oxidation of Secondary Alcohols with Phenyltrimethylammonium
Tribromide in the Presence of a Catalytic Amount of Antimony(III) Bromide
or Copper(II) Bromide
Oxidation of
S
h
econdar
y
A
l
i
c
ohols
n
with Phenylt
s
rimethyla
m
e
monium
T
i
ribromide Sayama,* Tetsuo Onami
Department of Chemistry, Fukushima Medical University, Hikariga-oka, Fukushima 960-1295, Japan
Fax +81(24)5471369; E-mail: ssayama@fmu.ac.jp
Received 22 July 2004
mo ketones in comparison with those of complex metal
Abstract: The oxidation of alcohols was carried out with phenyl-
trimethylammonium tribromide in the presence of a catalytic
amount of SbBr3 or CuBr2. 1,2-Diols, such as hydrobenzoin, were
converted into 1,2-diketones or a-ketols without oxidative cleavage
hydrides and other metal halides, AlCl3, CuCl2, FeCl3.13,14
Antimony halides are more effective for organic synthesis
and are easier to handle than other metal halides, such as
of the glycol C-C bond at room temperature. A variety of secondary AlCl3 and TiCl4.14–16 There has been interest in the effect
alcohols were also oxidized to the corresponding carbonyl com-
pounds in a chemoselective manner.
of using a catalytic amount of antimony halide in the oxi-
dation of alcohols with PTAB. In this paper, we would
Key words: oxidation, alcohol, phenyltrimethylammonium tribro-
mide, antimony(III) bromide, copper(II) bromide
like to report on the results of our studies concerning the
selective oxidation of a variety of alcohols with PTAB in
the presence of antimony halide or other metal halides.
The oxidation of meso-hydrobenzoin (1), chosen as a rep-
resentative 1,2-diol for this study, with PTAB–SbBr3 in
various stoichiometric ratios was carried out.1,17–23 The re-
sults are summarized in Table 1. A mixture of benzalde-
hyde (2) and benzil (3) was obtained at 1.5 molar
equivalents of PTAB over meso-hydrobenzoin (1) in the
presence of a catalytic amount of SbBr3 (run 2). Benzil (3)
The oxidation of alcohols to the corresponding ketones
plays an important role in organic synthesis. Many effec-
tive oxidation systems have been developed and new
ways to achieve this transformation continue to receive
wide attention in terms of economic benefit, environmen-
tal impact and safety.1–9
Br2 has been used as a reagent in oxidation systems such was mainly obtained at the molar ratio of 1, PTAB, pyri-
as bis(tributyltin)oxide-bromine and Ph3Sb-bromine, dine, and SbBr3 (1:2:2:0.2, run 3). At the ratio of
which have been shown to be efficient reagents for the ox- 1:3:3:0.2, 1 was oxidized to give 3 without oxidative
idation of alcohols to ketones.1,10,11 However, elemental cleavage of the glycol C-C bond in nearly quantitative
bromine is associated with hazards because of its rapid va- yield (run 4). To examine the effects of PTAB, SbBr3 and
porization. Therefore, there has been much interest in a pyridine in this oxidation system, the following experi-
new mild and convenient method for the chemoselective ments were carried out. In the absence of SbBr3, 1 was re-
oxidation of alcohols without using bromine.
covered in over 60% yield accompanied by benzoin (4,
run 7). meso-Hydrobenzoin (1) was also recovered un-
changed without using PTAB (runs 8, 9). Compound 1
was oxidized to give mixtures of 2 and 3 without pyridine
(run 10). Satisfactory yields and selectivity for oxidation
of 1 to 3 or 4 were not observed. PTAB, SbBr3, and pyri-
dine were each confirmed to be essential for the oxidation
of 1 to 3 quantitatively.
Though phenyltrimethylammonium tribromide (PTAB) is
known to be a convenient reagent for brominating the a-
position of carbonyl compounds and for the addition of
bromine to alkenes, other uses of the compound in organic
synthesis have not been studied in detail.12 As PTAB has
been much easier to handle and it maintains the desired
stoichiometry in comparison with bromine, the use of
PTAB was more advantageous and attractive than that of The oxidation of 1 in the presence of a variety of metal ha-
Br2 in organic synthesis. Since selective oxidation of alco- lides was carried out to compare the utility of SbBr3 with
hols with PTAB has not previously been reported, we that of other metal halides. The results are shown in
decided to investigate.
Table 2. First, the oxidation of 1 was examined with
PTAB and bismuth halides (BiBr3, BiCl3) as a homology
of antimony halide. The mixtures of 3 and 4 were obtained
unexpectedly (runs 1, 2). Antimony halides were more se-
lective for the oxidation of 1 to 3 than homologous bis-
muth halides. meso-Hydrobenzoin (1) was not oxidized to
give 3 or 4 in good yields in the presence of other metal
halides, NiCl2, ZnBr2 (runs 6, 7). On the other hand, 1 was
predominantly converted into 4 in the presence of cop-
per(II) halides (runs 3–5).1,24,25 Thus, the addition of a
catalytic amount of SbBr3, CuBr2 or CuCl2 was found to
Further, it has been reported in previous papers that the
combinations of complex metal hydrides (LiAlH4,
NaBH4) and antimony halides (SbBr3, SbCl3) were more
effective for the conjugate reduction of 2-butene-1,4-di-
ones and the reductive debromination of aromatic a-bro-
SYNLETT 2004, No. 13, pp 2369–2373
Advanced online publication: 28.09.2004
DOI: 10.1055/s-2004-832840; Art ID: U20904ST
© Georg Thieme Verlag Stuttgart · New York
0
3
.1
1
.2
0
0
4

2370
S. Sayama, T. Onami
LETTER
Table 1 Oxidation of meso-Hydrobenzoin (1) with PTAB in MeOHa
O
O
OH
Ph
PTAB/SbBr3/Pyridine
MeOH
Ph
Ph
Ph
PhCHO
Ph
Ph
O
OH
OH
2
1
3
4
Run
Molar ratio of 1
Time (h)
Yield (%)b
PTAB
SbBr3
Pyridine
2
3
4
1
1
2
2.0
1.5
2.0
3.0
4.0
4.0
4.0
–
–
–
16
16
17
16
14
24
17
15
22
15
22
2
6
50
–
38
6
0.2
0.2
0.2
0.2
0.2
–
–
54
–
31
78
96
90
96
–
3
2.0
3.0
2.0
4.0
4.0
4.0
–
–
18
–
4
–
–
5
2
–
4
6
–
–
–
7
–
32
–
66
93
96
6
8
0.2
2.0
2.0
–
3
–
9
–
–
–
–
10
11
4.0
4.0
–
45
5
45
2
–
–
47
30
a Compound 1: 0.5 mmol, MeOH (15 mL), r.t.
b Isolated yield.
Table 2 Oxidation of meso-Hydrobenzoin (1) with PTAB–Metal Halides–Pyridine in MeOHa
Run
MXn
Time (h)
Yield (%)b
2
2
2
–
–
–
2
3
3
4
1c
1
2
3
4
5
6
7
BiBr3
BiCl3
CuBr2
CuBr2
CuCl2
NiCl2
ZnBr2
70
70
67
7d
8
62
53
78
81
77
56
61
23
22
18
8
19
2
5
70
72
72
2
18
25
24
12
7
a Compound 1: 0.25 mmol, PTAB (1.0 mmol), pyridine (1.0 mmol) MXn (0.05 mmol), MeOH (8 mL), r.t.
b Isolated yield.
c Recovered yield of 1.
d Temp: 65 °C.
be more effective for obtaining benzil or benzoin than oth- vage of the glycol C-C bonds (runs 1–3). The oxidation of
er metal halides in the oxidation of 1 with PTAB–pyri- a-ketols, benzoin (4), anisoin (10), and 11 also afforded
dine.
the corresponding 1,2-diketones in high yields (runs 4–6).
On the other hand, the oxidation of 5 and 8 with PTAB–
CuBr2–pyridine took place to give corresponding a-ketols
4, 11 predominantly (runs 7, 8).26 To examine this selec-
tivity for the oxidation of 1,2-diols to a-ketols with
PTAB–CuBr2–pyridine, the oxidation of a-ketols 4, 10
was carried out under the same reaction conditions. Com-
pounds 4 and 10 were not oxidized to give the correspond-
ing 1,2-diketones or other ketones in high yields. Benzoin
The oxidation of a variety of 1,2-diols and a-ketols was
carried out to elucidate the oxidizing power of the PTAB–
SbBr3–pyridine and PTAB–CuBr2–pyridine systems. The
results are shown in Table 3. dl-Hydrobenzoin (5), hy-
droanisoin (6), and 1,2-dicyclohexyl-1,2-ethanediol (8)
with PTAB–SbBr3–pyridine, were selectively oxidized to
the corresponding 1,2-diketones without oxidative clea-
Synlett 2004, No. 13, 2369–2373 © Thieme Stuttgart · New York

LETTER
Oxidation of Secondary Alcohols with Phenyltrimethylammonium Tribromide
2371
(4) and anisoin (10) were recovered in over 76% yields also afforded a small amount of dimethylacetal (8%) be-
(runs 9, 10). The system PTAB–CuBr2–pyridine was sup- sides ketone 21 (Table 4, run 6). The oxidation reaction of
posed to be applicable for the oxidation of 1,2-diol to a- 18, 22 took place rapidly at 65 °C but ketones 19, 21 were
ketols consequently. 1,1,2-Triphenyl-1,2-ethanediol (12) successively converted to dimethylacetal derivatives.
was oxidized to a-ketol 13 without rearrangement of the Room temperature turned out to be the optimum tempera-
phenyl group by PTAB–SbBr3–pyridine (run 11). The ture for obtaining ketones in good yields. Furthermore,
PTAB–SbBr3–pyridine and PTAB–CuBr2–pyridine sys- aliphatic primary alcohol, 1-dodecanol (23) was not
tems were ascertained to be more selective for the oxida- affected under the same oxidation conditions (Table 4,
tion of 1,2-diols to 1,2-diketones or a-ketols than PTAB– run 7; Table 5, run 5). To clarify this chemoselectivity, the
other metal halide systems.
oxidation of 2-ethyl-1,3-hexanediol (24) containing both
secondary and primary hydroxyl groups, was examined
with PTAB–SbBr3–pyridine, PTAB–CuBr2–pyridine, re-
spectively. Only the secondary 3-hydroxyl group of 24
was selectively oxidized to give hydroxyketone 25 in 79–
93% yields (Table 4, run 8; Table 5, run 6). In contrast,
mandelic acid methylester, ethyl 3-hydroxybutyrate and
1,4-dichloro-2-butanol were not oxidized to the respective
ketones under the same reaction conditions. These results
suggested that the steric hindrance between alkyl sub-
stituents and functional groups probably exerted a great
influence on the decrease in reactivity of polyfunctional
In addition, the oxidation of a variety of alcohols with
PTAB–SbBr3–pyridine or PTAB–CuBr2–pyridine, was
carried out to clarify the chemoselectivity for alco-
hols.1,27–35 The results are shown in Table 4 and Table 5.
Secondary alcohols, cycloheptanol (14), 4-decanol (16),
1-phenylethanol (18), benzhydrol (20) were oxidized to
the corresponding ketones 15, 17, 19, 21 in good yields at
room temperature (Table 4 and Table 5, runs 1–4). On the
other hand, compound 18 was converted to a-bromo-
dimethylacetal (22) in high yield at 65 °C for 5 hours
(Table 4, run 5). The oxidation of 20, at 65 °C for 5 hours,
Table 3 Oxidation of 1,2-Diols and a-Ketols with PTAB–MXn–Pyridine in MeOHa
Run Substrates
S
MXnb
A
Time (h)
19
Product
Yield (%)c
91
1
5 dl
3
Ph
OH
O
Ph
HO
Ph
Ph
O
2
3
Hydroanisoin
6
8
A
A
14
10
7
9
91
95
O
C
MeO
)
2
OH
OH
O
)
2
4
4
A
15
3
98
O
Ph
O
OH
Ph
Ph
Ph
O
5
6
Anisoin
10
11
A
A
15
19
7
9
91
92
O
C
MeO
)
2
O
OH
)
2
O
7
8
5 dl
B
B
72
60
4
54
77
OH
Ph
Ph
OH
Ph
Ph
O
HO
8
4
11
OH
OH
O
OH
9
B
66
Recovered
Recovered
4
82
OH
Ph
Ph
O
10
11
Anisoin
10
12
B
A
10
48
10
13
92
92
Ph
OH
Ph
Ph
Ph
OH
Ph
Ph
HO
Ph
O
12
12
B
48
Recovered
12
88
OH
Ph
Ph
HO
a Substrate S (0.25mmol), PTAB (1.0 mmol), pyridine (1.0 mmol), MeOH (8 mL), r.t.
b MXn: A = SbBr3, B = CuBr2.
c Isolated yield.
Synlett 2004, No. 13, 2369–2373 © Thieme Stuttgart · New York

2372
S. Sayama, T. Onami
LETTER
Table 4 Oxidation of Alcohols with PTAB–SbBr3–Pyridine in MeOHa
Run
1
Substrates
S
Time (h)
15
Product
Yield (%)b
14
15
88
O
OH
2
3
16
18
47
65
17
19
83
86
OH
O
Ph
O
Ph
CH3
Ph
OH
CH3
4
5
20
18
68c
5e
21
22
70d
84f
Ph
O
Ph
OH
OH
Ph
Ph
Ph
OMe
OMe
CH3
Br
6
20
5c,e
21
63g
Ph
Ph
Ph
OH
O
Ph
7
8
CH3(CH2)11OH
23
24
48
6
Recovered
23
25
85
93
OH
OH
O
OH
a Substrate S (0.25 mmol), PTAB (1.0 mmol), pyridine (1.0 mmol), SbBr3 (0.05 mmol), MeOH (15 mL), r.t.
b Isolated yield.
c PTAB (0.75 mmol), pyridine (0.75 mmol).
d Recovered 20: 25%.
e Temp: 65 °C.
f Recovered 18: 11%.
g Dimethyl acetal was obtained in 8% yield. Recovered 20: 24%.
secondary alcohols such as a- and b-hydroxyesters, a- also examined. 2-Chloro-, 4-bromo-, 2-bromo-, 4-methyl
haloalcohol.36 As aromatic primary alcohols behaved and 2-methyl benzyl alcohols were recovered unchanged
quite differently from aliphatic ones and were oxidized in over 50–80% yields under the same reaction condi-
easily by many oxidation systems, the oxidation of benzyl tions. These results sufficiently accounted for the mild
alcohol was carried out to test the limitation of this and chemoselective oxidation of secondary alcohols by
chemoselectivity with PTAB–SbBr3–pyridine and PTAB–SbBr3–pyridine and PTAB–CuBr2–pyridine.38
PTAB–CuBr2–pyridine. Benzyl alcohol was not oxidized
In conclusion, the combination of PTAB and a catalytic
to benzaldehyde and benzoic acid easily.37 The oxidation
amount of SbBr3 or CuBr2 provided an alternative and
of a variety of mono-substituted benzylic alcohols was
convenient chemoselective procedure for the oxidation of
secondary alcohols and substituted 1,2-diols to the corre-
Table 5 Oxidation of Alcohols with PTAB–CuBr2–Pyridine in
sponding ketones, 1,2-diketones and a-ketols. Further
application to the oxidation of alcohols with ammonium
tribromides is now in progress.
MeOHa
Run
1
Substrates S Time (h)
Product
Yield (%)b
90
14
16
18
20
23
24
20
34
42
42
17
60
15
References
2
3
4
5
6
17
19
21
23
25
88
84
80
93
79c
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CuBr2 (0.05 mmol), MeOH (15 mL), r.t.
b Isolated yield.
c Recovered 24: 13%.
(7) Martin, S. E.; Suares, D. F. Tetrahedron Lett. 2002, 43,
4475.
Synlett 2004, No. 13, 2369–2373 © Thieme Stuttgart · New York

LETTER
Oxidation of Secondary Alcohols with Phenyltrimethylammonium Tribromide
2373
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32% yields for 48–72 h.
(38) A typical procedure is described for the oxidation of meso-
hydrobenzoin 1. To a solution of SbBr3 (18 mg, 0.05 mmol)
in MeOH (8 mL) were added pyridine (60 mL) and PTAB
(281 mg, 0.75 mmol) at r.t. After stirring for 5 min meso-
hydrobenzoin 1 (53 mg, 0.25 mmol) was added. The reaction
mixture was treated with 0.5 M aq Na2S2O3 after stirring for
16 h at r.t. and extracted with EtOAc. The organic layer was
washed by 0.5 M aq Na2S2O3 and successively sat. aq NaCl
and dried by MgSO4. After removal of the solvent in vacuo,
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silica gel (Wakogel C-200) with CCl4 and CHCl3 (3:1 v/v).
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example, compound 8 was converted to 11 in 42% yield for
14 h. 1,2-Dicyclohexyl-1,2-ethanediol (8) was recovered
Synlett 2004, No. 13, 2369–2373 © Thieme Stuttgart · New York