Aerobic photo-oxidation of alcohols in the presence of a catalytic inorganic bromo source

Article abstract of DOI:10.1016/j.tet.2006.05.048

Alcohols were found to be oxidized to the corresponding carboxylic acid in the presence of a catalytic inorganic bromo source, for example, lithium bromide, bromine, and hydrobromic acid, under photo-irradiation.

Full text of DOI:10.1016/j.tet.2006.05.048

Tetrahedron 62 (2006) 7887–7891
Aerobic photo-oxidation of alcohols in the presence of a
catalytic inorganic bromo source
*
Shin-ichi Hirashima, Shouei Hashimoto, Yukio Masaki and Akichika Itoh
Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan
Received 27 February 2006; accepted 17 May 2006
Available online 9 June 2006
Abstract—Alcohols were found to be oxidized to the corresponding carboxylic acid in the presence of a catalytic inorganic bromo source, for
example, lithium bromide, bromine, and hydrobromic acid, under photo-irradiation.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Oxidation of alcohols is the foundation of synthetic chemis-
try, and has been the subject of study by many researchers;
however, these reactions essentially involved the use of large
quantities of heavy metals and complex organic compounds,
which generate large amounts of waste, and were not at all
environmentally benign.1 With this background in mind,
we examined a new oxidation method with the catalysis of
alkali metal halides2 and molecular oxygen. Molecular
oxygen has recently received much attention in the field of
synthetic organic chemistry, since it is photosynthesized
by plants and is an effective oxidant of larger atom efficiency
than that of other oxidants.3 In the course of our study of
photo-oxidation, we have found that alcohols were oxidized
directly to the corresponding carboxylic acids in the pres-
ence of catalytic lithium bromide in an oxygen atmosphere
under irradiation by a high-pressure mercury lamp.4 This
new form of oxidation reaction is interesting in keeping
with the notion of Green Chemistry due to non-use of heavy
metals, waste reduction, use of molecular oxygen, and inex-
pensive acquisition of reagents.5,6 We believe that this
oxidation proceeds only if a catalytic amount of a bromo
radical is generated in situ.7 This is the driving force of
our continued studies on this oxidation with a new inorganic
bromo source, which is inexpensive, safe, and easily separa-
ble from the reaction mixture by extraction, and we have
found that bromine, which is more reactive than lithium bro-
mide, and hydrobromic acid, which is less expensive than
lithium bromide, are also suitable for this purpose. Herein,
we report our detailed study on the generality of this
photo-oxidation of alcohols in the presence of a catalytic
inorganic bromo source, such as lithium bromide, bromine,
and hydrobromic acid.
2.1. Aerobic photo-oxidation of alcohols in the presence
of catalytic amount of lithium bromide
Table 1 shows the results of the study of reaction conditions
conducted with 1 (50 mg, 0.269 mmol) as a test substrate
under 6 h external irradiation by a 400-W high-pressure
mercury lamp in an oxygen atmosphere. The temperature
of the final stage of this reaction was about 50 ꢀC. We do
not have any direct evidence; however, we believe an effec-
tive wavelength of the light is 365 nm, which is an emission
line of the strongest and longest wavelength in an ultraviolet
region irradiated from a high-pressure mercury lamp, since
passing through water, a test tube and a cooling jacket, which
are made from Pyrex glass, and air is necessary for the light
to effect this reaction. Among the alkali metal halides and
solvents examined, only lithium bromide and ethyl acetate
were found to afford most efficiently the corresponding
carboxylic acid 2. We were surprised to find, however, re-
duction in the yield of 2 regardless of increase or decrease
in the amount of lithium bromide used, and obtained the
best results from our tests when using 0.3 equiv of lithium
bromide (entries 1–6). That no oxidation proceeded without
either irradiation of UV or the addition of lithium bromide
shows the necessity of both for this reaction. Furthermore,
from the fact that yields of the target substance were reduced
substantially when the reaction was conducted under the
flow of argon, we can assume that the actual oxidant in
this reaction is molecular oxygen.
Table 2 shows the results of the photo-oxidation reaction
using several alcohols in the presence of cat. lithium bro-
mide. Both benzyl and aliphatic alcohols, in general, afford
the corresponding carboxylic acids in good yields, although
there is a difference in reaction times.
* Corresponding author. E-mail: itoha@gifu-pu.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.05.048

7888
S.-i. Hirashima et al. / Tetrahedron 62 (2006) 7887–7891
Table 1. Study of reaction conditions of aerobic photo-oxidation in the
presence of cat. LiBr
Table 3. Study of reaction conditions of aerobic photo-oxidation in the
presence of cat. bromine
O
Br2, hv (400 W)
2 - balloon
O
MX , hv (400 W)
O
OH
10
O2 - balloon
OH
10
OH
OH
2
10
10
1 (50 mg)
solvent (5 ml)
solvent (5 ml), 6 h
1 (50 mg)
2
Yield of 2 (%)a
Entry
Br2 (equiv)
Solvent
t (h)
Yield of 2 (%)a
Entry
MX
(Equiv)
Solvent
1
2
3
4
5
6
7
8
0.07
0.07
—
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
EtOAc
CH2Cl2
AcOH
Hexane
THF
4
6
47
46
0
1
2
3
4
5
6
7
8
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiCl
NaBr
KBr
0.1
0.2
0.3
0.4
0.5
1.0
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
Acetone
MeCN
THF
Benzene
H2O
EtOAc
EtOAc
EtOAc
66
76
82
63
10
Trace
0
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
1.4ꢁ10ꢂ4
1.4ꢁ10ꢂ3
0.007
0.07
0
18
65
85
0b
0c
68
33
9
59
13
64
0
0.07
0.07
0.14
0.21
0.35
0.07
0.07
0.07
0
9
9
Trace
12
0
0
0
10
11
12
13
14
15
16
17
18
10
11
12
13
14
0
a
0.07
0.07
0.07
All yields are for pure, isolated products.
0
0
MeOH
a
Table 2. Aerobic photo-oxidation for various alcohol substrates in the
presence of cat. LiBr
All yields are for pure, isolated products.
The reaction was carried out in the dark.
The reaction was carried out in an argon atmosphere.
b
c
LiBr (0.3 equiv.), hv (400W)
O2-balloon
substrate
(50 mg)
product
EtOAc (5 ml)
Table 4. Aerobic photo-oxidation in the presence of cat. bromine
Br2 (0.07 equiv.), hv (400W), O2 - balloon
Entry
1
Substrate
t (h)
Product
Yield (%)a
substrate
(0.3 mmol)
product
MeCN (5 ml), 10 h
O
OH
10
6
82
75
Entry
Substrate
Product
Yield (%)a
OH
10
1
2
O
OH
10
1
2
3
4
5
6
95
80
OH
10
1
2
2
3
4
15
2
O
O
OH
3
9
4
9
O
OH
4
OH
12
4
11
OH
OH
OH 83
t
5
Bu
t
6
Bu
O
61
O
OH
3
9
4
9
5
OH
89
82
7
Cl
8
Cl
OH
O
15b
99
tBu
tBu
14
13
OH
O
10
5
9
O
9
OH
a
OH
All yields are for pure, isolated products.
t
5
Bu
t
6
Bu
2.2. Aerobic photo-oxidation of alcohols in the presence
of catalytic amount of bromine
O
OH
OH
100
7
Cl
8
Cl
Although lithium bromide is undoubtedly an inexpensive
and safe reagent, it is not necessarily easy to handle because
of its hygroscopic property. Table 3 shows our initial study of
the reaction conditions of the aerobic photo-oxidation,
which was carried out using 1 with bromine in various
solvents. Among the solvents and the amounts of bromine
examined, acetonitrile and 0.07 equiv of bromine were
found to be suitable for the reaction. Bromine is a more
O
OH
OH
7
80
MeO
15
MeO
16
a
The reaction was carried out for 20 h.
All yields are for pure, isolated products.
b

S.-i. Hirashima et al. / Tetrahedron 62 (2006) 7887–7891
7889
Table 6. Aerobic photo-oxidation of alcohols in the presence of cat. hydro-
bromic acid
effective catalyst than lithium bromide since the amount of
bromine required for carrying out this oxidation smoothly
is much smaller than that of lithium bromide previously
reported.4 That no oxidation proceeded without either irradi-
ation of UV, or the addition of bromine or molecular oxygen
shows the necessity of all for this reaction (entries 3, 8
and 9).
hv (400W), O2-balloon, HBr aq.
substrate
(0.3 mmol)
product
MeCN (5 ml), 10 h
Entry
1
Substrate
HBr aq
(equiv)
Product
Yield (%)a
O
OH
10
0.14
0.20
0.20
0.20
0.20
0.20
0.20
69
66
Table 4 shows the results for the oxidation of several sub-
strates (0.3 mmol) under the reaction conditions outlined
above. Although in general primary alcohols, including ben-
zyl alcohols, were oxidized to the corresponding carboxylic
acids in high yields, secondary alcohols afforded the product
in modest yield due to recovery of the starting materials.
OH
10
1
2
O
OH
4
2
3
4
5
6
7
OH
12
4
11
2.3. Aerobic photo-oxidation of alcohols in the presence
of catalytic amount of hydrobromic acid
57
O
OH
3
9
9
4
Although bromine was found to be more effective than lith-
ium bromide, it is difficult to say that bromine is a good
reagent because of its intractable and toxic properties.
Then, hydrobromic acid was examined for this oxidation re-
action. Table 5 shows the results of study of reaction condi-
tions conducted with 1 under the conditions of 10 h external
irradiation by a 400-W high-pressure mercury lamp in an
oxygen atmosphere. Among the solvents examined, aceto-
nitrile was found to afford most efficiently the corresponding
carboxylic acid 2 (entries 9–14). We also found that reduc-
tion in the yield of 2 was observed regardless of increase
or decrease in the amount of hydrobromic acid used, and
obtained the best result among our tests when using
0.14 equiv or 0.20 equiv of hydrobromic acid (entries 2–5
and 8). That no oxidation proceeded without either the addi-
tion of hydrobromic acid or irradiation of UV or molecular
oxygen shows the necessity of all for this reaction (entries
1, 6 and 7).
OH
O
27b
tBu
tBu
14
13
O
OH
OH
99
t
5
Bu
t
6
Bu
O
OH
OH
OH
100
92
7
Cl
8
Cl
O
OH
MeO
15
MeO
16
OH
O
OH
Table 6 shows the generality of this oxidation reaction using
a variety of 0.3 mmol of alcohols in the presence of
8
0.20
0.20
0.20
81
94
18
17
Table 5. Study of conditions for photo-oxidation of 1 in the presence of cat.
hydrobromic acid
O
OH
HBr, hv (400 W)
2 - balloon
O
OH
O
OH
9
10
OH
2
10
solvent (5 ml), 10 h
19
1 (50 mg)
20
Entry
HBr (equiv)
Solvent
Yield of 2 (%)a
O
OH
1
2
3
4
5
6
7
8
—
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
EtOAc
Acetone
Hexane
MeOH
H2O
0
0
OH
10
100
1.4ꢁ10ꢂ3
0.035
0.07
0.14
0.14
0.14
0.20
0.70
0.07
0.07
0.07
0.07
0.07
N
21
N
62
70
81
0b
0c
77
0
56
50
15
0
22
O
OH
OH
11
0.20
83
S
9
23
S
24
10
11
12
13
14
a
All yields are pure, isolated products.
The reaction was carried out for 20 h.
b
0
0.14 equiv or 0.20 equiv of hydrobromic acid. Aliphatic pri-
mary alcohols, in general, afford the corresponding carbox-
ylic acids in moderate yields; however, aliphatic secondary
a
All yields are for pure, isolated products.
The reaction was carried out in the dark.
The reaction was carried out in an argon atmosphere.
b
c

7890
S.-i. Hirashima et al. / Tetrahedron 62 (2006) 7887–7891
, O2
, O2
alcohols were less reactive than primary alcohols (entries
1–4). The corresponding benzoic acids were obtained in
high yield regardless of an electron-donating or electron-
withdrawing group at the aromatic nucleus when using
benzyl alcohols (entries 5–7). Compounds 1- and 2-naph-
thalenemethanols (17 and 19) also afforded the corres-
ponding naphthoic acids (18 and 20) in high yields.
Furthermore, heterocyclic compounds, such as 3-pyridine-
methanol (21) and 3-thiophenemethanol (23), afforded the
corresponding carboxylic acids 22 and 24, respectively, in
high yields.
Li+ Br-
LiOO
HOO
LiBr
+
+
+
Br
H+ Br-
+
(1)
HBr
Br2
Br
2 Br
+
RCHOH HBr
RCH2OH +Br
(2)
(3)
(4)
(5)
26
+
2 HBr 1/2 O2
+
Br2 H2O
+
+
+
Br2
+
+
26
27
28
29
R-CHO HBr Br
27
Br
+
HBr
R-CO
28
2.4. Mechanism
Br2
+
R-COBr Br
29
(6)
(7)
In order to examine the mechanism of this reaction, at first,
aldehyde 25, which is presumed to be an intermediate, was
subjected to similar aerobic photo-oxidation conditions,
and 6 was obtained in 91% yield. Thus, this reaction is
thought to proceed through the aldehyde as an intermediate
(Scheme 1).
+
R-CO2H HBr
+
H2O
Scheme 3. Plausible path of aerobic photo-oxidation of alcohols.
3. Conclusion
CHO
CO2H
(400W), O2-balloon
LiBr (0.3 equiv.)
As mentioned above, photo-oxidation with molecular oxy-
gen of alcohols in the presence of a catalytic amount of an
inorganic reagent, lithium bromide, bromine, and hydrogen
bromide, was studied, and the corresponding carboxylic acid
was obtained in good yield. Especially, among the reagents
examined, hydrobromic acid is inexpensive, safe, and easy
to handle due to its non-hygroscopic property, and thus,
this oxidation is a facile and convenient method in the
view point of synthetic organic chemistry.
tBu
tBu
EtOAc (5 ml), 5 h
25 (50 mg)
6 (91%)
Scheme 1. Aerobic photo-oxidation of aldehyde.
Also, lowering of the yield (68%) under the condition
whereby 1 was reacted under irradiation for 3 h with
a 400-W high-pressure mercury lamp and then reacted in
the dark for 7 h, shows the necessity of continuous irradia-
tion to complete this oxidation, and this reaction does not
involve an auto-oxidation path (Scheme 2).
4. Experimental
4.1. General
O
HBr (0.14 equiv.)
O2-balloon
in the
dark
(400W)
3 h
OH
OH
10
10
Methylene chloride was freshly distilled from CaH2 under
nitrogen. THF was freshly distilled from Na metal/benzo-
phenone ketyl. All other dry solvents were obtained from
Kanto Kagaku Co., Ltd. Other chemicals used were of
reagent grade and were obtained from Aldrich Chemical
Co., Tokyo Kasei Kogyo Co., Ltd and Wako Pure Chemical
Industries, Ltd. All reactions were carried out in a Pyrex test
tube equipped with an O2-balloon, which was set up from the
center of 400-W high-pressure mercury lamp to the distance
MeCN
7 h
1 (50 mg)
2 (68%)
10 h
Scheme 2. Study of auto-oxidation path.
Furthermore, ethyl acetate or acetonitrile is thought to be
suitable for liberating the ‘naked’ bromo anion due to its
solvation effect to the corresponding counter cation by the
oxygen or nitrogen atom. We present in Scheme 3 what
we assume is a plausible path of this oxidation, which is pos-
tulated by considering all of the results mentioned above,
and the necessity of a catalytic amount of an inorganic
bromo source and of molecular oxygen in this reaction.6
The radical species 26 is thought to be generated by abstrac-
tion of a hydrogen radical with a bromo radical, formed by
continuous aerobic photo-oxidation of the bromo anion
from the inorganic bromo source (Eqs. 1 and 2). Bromine,
then, was formed by aerobic photo-oxidation of hydrogen
bromide, which is generated in Eq. 2 (Eq. 3). Aldehyde 27
was afforded by abstraction of a hydrogen radical with bro-
mine (Eq. 4), and the re-generated bromo radical abstracted
a hydrogen radical from 27 to give radical species 28, which
was transformed to acyl bromide 29 (Eqs. 5 and 6). The car-
boxylic acid was formed by reaction with water (Eq. 7).
1
of 37.5 mm. All of the products are known compounds. H
NMR spectra were recorded on JEOL 400-MHz spectrome-
ter (EX-400 and AL-400) using TMS as an internal standard
or solvent peak as a standard. 13C NMR spectrum was
recorded on JEOL EX-400 (100 MHz) spectrometer using
TMS as an internal standard. Mass spectrometric data
were collected on a JEOL JMS-SX 102A mass spectrometer.
4.1.1. Oxidation of primary alcohols in the presence of
cat. LiBr, bromine, or hydrobromic acid. A typical proce-
dure is as follows: in a Pyrex test tube with an O2-balloon,
a solution (5 mL) of the substrate and catalytic bromo source
in dry solvent was stirred and irradiated at room temperature
with a 400-W high-pressure mercury lamp, which was
equipped with a cooling jacket, externally for the indicated
time. The reaction mixture was concentrated under reduced

S.-i. Hirashima et al. / Tetrahedron 62 (2006) 7887–7891
7891
pressure, and 10% NaOH aqueous solution was added. The
aqueous solution was washed with diethyl ether, and then
acidified with 2 N HCl aqueous solution, which was ex-
tracted with diethyl ether. The organic layer was washed
with brine and dried over Na2SO4, and concentrated under
reduced pressure. The product was pure without further
purification.
J¼7.3, 1.5 Hz, 1H, C2-H), 8.08 (d, J¼8.0 Hz, 1H, C4-H),
7.91 (dd, J¼8.0, 0.7 Hz, 1H, C5-H), 7.65 (ddd, J¼8.5, 7.0,
1.5 Hz, 1H, C7-H), 7.58 (m, 2H, C3 and C6-H). MS:
m/z¼172.
4.1.12. 2-Naphthoic acid (20). 1H NMR (400 MHz,
CDCl3): d¼8.70 (s, 1H, C1-H), 8.10 (dd, J¼8.7, 1.5 Hz,
1H, C-H), 7.98 (d, J¼7.8 Hz, 1H, C-H), 7.90 (m, 2H,
C-H), 7.62 (dd, J¼7.0, 1.3 Hz, 1H, C5-H), 7.58 (dd,
J¼7.7, 1.3 Hz, 1H, C6-H), 7.55 (dd, J¼6.8, 1.2 Hz, 1H,
C7-H). MS: m/z¼172.
4.1.2. Oxidation of secondary alcohols in the presence of
cat. LiBr, bromine, or hydrobromic acid. A typical proce-
dure is as follows: in a Pyrex test tube with an O2-balloon,
a solution (5 mL) of the substrate and catalytic bromo source
in dry solvent were stirred and irradiated at room tempera-
ture with a 400-W high-pressure mercury lamp, which was
equipped with a cooling jacket, externally for the indicated
time. The reaction mixture was concentrated under reduced
pressure, and 10% NaOH aqueous solution was added. The
aqueous solution was washed with diethyl ether and the
organic layer was concentrated, and the residue was purified
by preparative tlc.
1
4.1.13. Nicotinic acid (22). H NMR (400 MHz, CD3OD):
d¼9.12 (s, 1H, C2-H), 8.73 (dd, J¼5.0, 1.5 Hz, 1H, C6-
H), 8.42 (ddd, J¼6.0, 1.9, 1.9 Hz, 1H, C4-H), 7.57 (ddd,
J¼7.2, 5.0, 0.7 Hz, 1H, C5-H). MS: m/z¼123.
4.1.14. 3-Thiophene carboxylic acid (24). 1H NMR
(400 MHz, CDCl3): d¼8.17 (dd, J¼2.9, 1.5 Hz, 1H, C2-
H), 7.50 (dd, J¼5.3, 1.5 Hz, 1H, C4-H), 7.27 (dd, J¼5.3,
2.9 Hz, 1H, C5-H). MS: m/z¼128.
1
4.1.3. Dodecanoic acid (2). H NMR (400 MHz, CDCl3):
d¼2.32 (t, J¼7.4 Hz, 2H, –CH2–COOH), 1.60 (m, 2H,
–CH2–CH2–COOH), 1.23 (m, 16H), 0.86 (t, J¼6.8 Hz,
3H, –CH3). MS: m/z¼200.
References and notes
4.1.4. 2-Dodecanone (4). 1H NMR (400 MHz, CDCl3):
d¼2.35 (t, J¼7.4 Hz, 2H, –CH2–CO–), 2.07 (s, 3H, CH3–
CO–), 1.50 (m, 2H, –CH2–CH2–CO–), 1.20 (m, 14H), 0.82
(t, J¼6.8 Hz, 3H, –CH3). MS: m/z¼184.
1. Comprehensive Organic Transformations:
A
Guide to
Functional Group Preparations; Larock, R. C., Ed.; Wiley-
VCH: New York, NY, 1999.
2. Regarding photo-oxidation with alkali metal halides, the conver-
sion of CO to CO2 and H2 to H2O in the presence of hydrogen
exposed to over 200 nm of ultraviolet light has been previously
reported, see: Ryabchuk, V. Catal. Today 2000, 58, 89.
3. Sheldon, R. A. CHEMTECH 1994, 24, 38.
1
4.1.5. 4-tert-Butylbenzoic acid (6). H NMR (400 MHz,
acetone-d6): d¼7.96 (d, J¼8.7 Hz, 2H, C2 and C6-H),
7.54 (d, J¼8.7 Hz, 2H, C3 and C5-H), 1.34 (s, 9H, t-Bu).
MS: m/z¼163.
4.1.6. 4-Chlorobenzoic acid (8). 1H NMR (400 MHz, ace-
tone-d6): d¼8.03 (d, J¼8.7 Hz, 2H, C2 and C6-H), 7.55
(d, J¼8.7 Hz, 2H, C3 and C5-H). MS: m/z¼139.
4. Itoh, A.; Hashimoto, S.; Masaki, Y. Synlett 2005, 2639.
5. For recent examples of oxidation of alcohols to the carboxylic
acids with molecular oxygen, see: (a) Figiel, P. J.; Sobczak,
J. M.; Ziolkowski, J. J. Chem. Commun. 2004, 244; (b)
Ebitani, K.; Ji, H.-B.; Mizugaki, T.; Kaneda, K. J. Mol. Catal.
A: Chem. 2004, 212, 161; (c) Baucherel, X.; Gonsalvi, L.;
Arends, I. W. C. E.; Ellwood, S.; Sheldon, R. A. Adv. Synth.
Catal. 2004, 346, 286; (d) Matsumura, Y.; Yamamoto, Y.;
Moriyama, N.; Furukubo, S.; Iwasaki, F.; Onomura, O.
Tetrahedron Lett. 2004, 45, 8221; (e) Uozumi, Y.; Nakao, R.
Angew.Chem., Int. Ed. 2003, 42, 194; (f) Ji, H.; Mizugaki, T.;
Ebitani, K.; Kaneda, K. Tetrahedron Lett. 2002, 43, 7179; (g)
Bjorsvik, H.-R.; Liguori, L.; Merinero, J. A. V. J. Org. Chem.
2002, 67, 7493; (h) Cicco, S. R.; Latronico, M.; Mastrorilli, P.;
Suranna, G. P.; Nobile, C. F. J. Mol. Catal. A: Chem. 2001,
165, 135; (i) Jenzer, G.; Schneider, M. S.; Wandeler, R.;
Mallat, T.; Baiker, A. J. Catal. 2001, 199, 141; (j) Iwahama,
T.; Yoshino, Y.; Keitoku, T.; Sakaguchi, S.; Ishii, Y. J. Org.
Chem. 2000, 65, 6502; (k) Vocanson, F.; Guo, Y. P.; Namy,
J. L.; Kagan, H. B. Synth. Commun. 1998, 28, 2577.
1
4.1.7. Acetophenone (10). H NMR (400 MHz, CDCl3):
d¼7.94 (d, J¼7.2 Hz, 2H, C2 and C6-H), 7.54 (t,
J¼7.2 Hz, 1H, C4-H), 7.44 (t, J¼7.2 Hz, 2H, C3 and C5-
H), 2.59 (s, 3H). MS: m/z¼120.
1
4.1.8. Hexanoic acid (12). H NMR (400 MHz, CDCl3):
d¼2.35 (t, J¼7.6 Hz, 2H, –CH2–CO2H), 1.64 (quin,
J¼7.4 Hz, 2H, –CH2–CH2–CO2H), 1.36–1.29 (m, 4H),
0.90 (t, J¼7.1 Hz, 3H, –CH3); 13C NMR (100 MHz,
CDCl3): d¼180.2, 34.0, 31.2, 24.3, 22.3, 13.9.
4.1.9. 4-tert-Butylcyclohexanone (14). 1H NMR (400 MHz,
CDCl3): d¼2.42–2.26 (m, 4H), 2.17–2.05 (m, 2H), 1.53–
1.39 (m, 3H), 0.92 (s, 9H, t-Bu). MS: m/z¼154.
6. For recent examples of oxidation of alcohols with molecular
oxygen in the presence of catalytic bromine, see: Minisci, F.;
Porta, O.; Recupero, F.; Punta, C.; Gambarotti, C.; Pierini, M.;
Galimberti, L. Synlett 2004, 2203.
7. Aerobic radical oxidation of alcohols to carboxylic acids has
been reported, see: Ishii, Y.; Nakayama, K.; Takeno, M.;
Sakaguchi, S.; Iwahama, T.; Nishiyama, Y. J. Org. Chem.
1995, 60, 3934.
1
4.1.10. 4-Anisic acid (16). H NMR (400 MHz, CD3OD):
d¼7.98 (d, J¼8.7 Hz, 2H, C2 and C6-H), 7.01 (d,
J¼8.7 Hz, 2H, C3 and C5-H), 3.87 (s, 3H, –OCH3). MS:
m/z¼152.
4.1.11. 1-Naphthoic acid (18). 1H NMR (400 MHz,
CDCl3): d¼9.07 (d, J¼8.0 Hz, 1H, C8-H), 8.40 (dd,