Facile aerobic photooxidation of alcohols in the presence of catalytic N-bromosuccinimide

Article abstract of DOI:10.1055/s-2006-942374

Alcohols were found to be oxidized to the corresponding carboxylic acid in the presence of catalytic N-bromosuccinimide in an oxygen atmosphere. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-942374

PAPER
1949
Facile Aerobic Photooxidation of Alcohols in the Presence of Catalytic
N-Bromosuccinimide
A
K
erobic Photooxid
i
ationo
y
f
A
lcohols oto Kuwabara, Akichika Itoh*
Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan
E-mail: itoha@gifu-pu.ac.jp
Received 18 January 2006; revised 17 February 2006
6
ing carboxylic acid 2 (entries 1–4). We also found the
yields of 2 were almost the same when the reactions were
carried out in the presence of more than 0.1 equivalent of
NBS. That yields of 2 were reduced substantially when
conducting the reaction in the dark or in an argon atmo-
sphere shows the necessity of both photoirradiation, not
heating, and molecular oxygen for this reaction (entries
1–13). Furthermore, N-chlorosuccinimide (NCS) and
N-iodosuccinimide (NIS) were examined as another addi-
Abstract: Alcohols were found to be oxidized to the corresponding
carboxylic acid in the presence of catalytic N-bromosuccinimide in
an oxygen atmosphere.
Key words: aerobic, alcohols, N-bromosuccinimide, carboxylic
acid, photooxidation
1
N-Bromosuccinimide (NBS) is a convenient and widely
used reagent not only for bromination but also for oxida-
1
tion of a variety of organic compounds. Although oxida-
Table 1 Conditions Studied for the Photooxidation of 4-tert-Butyl-
benzyl Alcohol (1)
tion of alcohols to aldehydes or ketones with NBS has
2
been reported by several research groups, to our knowl-
edge, direct oxidation of alcohols to carboxylic acids has
not been studied previously. On the other hand, with the
additive
2
CO H
OH hν, O -balloon
2
solvent (5 mL)
tBu
notion of Green Chemistry in mind, we searched for direc-
tions for the use of molecular oxygen, which is considered
to be an infinite resource because it is photosynthesized
by plants and is an effective oxidant of larger atom effi-
ciency than that of other oxidants. In the course of our
study of photooxidation, we have found that 4-tert-butyl-
toluene was oxidized directly to 4-tert-butylbenzoic acid
in the presence of catalytic N-bromosuccinimide in an ox-
ygen atmosphere under irradiation by a high-pressure
tBu
1
(0.27 mmol)
2
Yield (%)a
Entry
1
Solvent
EtOAc
acetone
CH Cl
Additive (equiv) Time (h)
NBS (1.0)
NBS (1.0)
NBS (1.0)
NBS (1.0)
NBS (0.5)
NBS (0.2)
NBS (0.1)
NBS (0.1)
NBS (0.1)
NBS (0.05)
NBS (0.1)
NBS (0.1)
NBS (0.1)
NCS (0.1)
NIS (0.1)
–
10
10
10
10
10
10
4
95
2
81
3
80
2
2
4
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
95
3
mercury lamp. We further observed through experiments
to expand applications of this reaction that an oxidation
reaction also proceeds using the aliphatic alcohol 4-tert-
5
95
6
97
butylbenzyl alcohol (1) as the test substrate, affording
4
4
-tert-butylbenzoic acid (2) (Scheme 1). In this paper, we
7
80
report in detail our investigation of the generality of this
reaction.
8
2
98
9
1
99
O2-balloon
CO2H
cat. NBS, hν
OH
10
11
12
10
1
84
tBu
tBu
traceb
tracec
traced
29
1
2
Scheme 1 Aerobic photooxidation of 4-tert-butylbenzyl alcohol
1
1
1
1
1
3
4
5
6
1
Table 1 shows the results of a study of reaction conditions
conducted with 1 as test substrate under the conditions of
external irradiation by a 400 W high-pressure mercury
1
1
6
5
lamp in an oxygen atmosphere at ambient temperature.
1
trace
Among the solvents examined, ethyl acetate and acetoni-
trile were found to most efficiently afford the correspond-
a
b
c
d
All yields are for pure, isolated products.
The reaction was carried out in the dark.
The reaction was carried out under argon.
SYNTHESIS 2006, No. 12, pp 1949–1952
x
x.
x
x
.
2
0
0
6
The reaction was carried out at 60 °C in the dark.
Advanced online publication: 05.05.2006
DOI: 10.1055/s-2006-942374; Art ID: F01106SS
Georg Thieme Verlag Stuttgart · New York
©

1
950
K. Kuwabara, A. Itoh
PAPER
tive; however, the target product was obtained only in low tained only in 15% yield. Aliphatic primary and
yield (entries 14 and 15).
secondary alcohols, in general, afforded the correspond-
ing carboxylic acids in moderate yields (entries 9–11).
Table 2 shows the generality of this oxidation reaction us-
ing a variety of alcohols (1 mmol) in the presence of NBS We present in Scheme 2 what we believe is a path of this
0.1 equiv). The corresponding benzoic acid was obtained oxidation, postulated by considering both the necessity of
(
in good yield regardless of an electron-donating or elec- a catalytic amount of NBS and of molecular oxygen in this
tron-withdrawing group at the aromatic nucleus when reaction. We believe that the radical species 23 is generat-
using benzyl alcohols (entries 1–4). 1- and 2-Naphtha- ed by abstraction of a hydrogen radical with a bromo rad-
lenemethanol (9 and 11) also afforded the corresponding ical, formed under irradiation from NBS. The radical
naphthoic acids 10 and 12 in high yield (entries 5 and 6). species traps molecular oxygen to afford peroxy radical
Among the heterocyclic substrates examined, 3-py- species 24, which subsequently transforms to a carboxylic
ridinemethanol (13) was found to afford 14 in high yield; acid via hydroperoxide 25. Although we do not have any
however, 3-thiophenemethanol (15) gave a complex mix- evidence, 23 is assumed to be quenched through dimeriza-
ture and the corresponding carboxylic acid 16 was ob- tion or with a bromo radical to afford 26 or 27, which are
Table 2 Aerobic Photooxidation of Various Alcohol Substrates
substrate
1 mmol)
hν (400 W-Hg), NBS (0.1 equiv)
product
(
MeCN (8 mL)
Entry
1
Substrate
Time (h)
3
Product
Yield (%)a
74
CO2H
OH
tBu
tBu
1
2
2
3
10
10
CO H
78
56
2
OH
O2N
Cl
3
O N
4
2
CO H
2
OH
5
Cl
6
4
5
6
CO H
77
97
2
OH
MeO
7
8
MeO
OH
10
CO H
2
1
0
9
6
7
8
9
10
10
10
CO H
97
90
15
2
OH
1
1
1
2
CO H
2
OH
13
N
S
N
14
CO H
2
OH
15
S
16
10
6
CO H
64
57
2
OH
0
1
1
0
17
18
1
1
0
1
CO H
2
OH
6
6
2
0
1
9
3
53
OH
O
9
9
21
22
a
All yields are for pure, isolated products.
Synthesis 2006, No. 12, 1949–1952 © Thieme Stuttgart · New York

PAPER
Aerobic Photooxidation of Alcohols
4-Chlorobenzoic Acid (6)
1951
O
1
H NMR (400 MHz, acetone-d ): d = 8.03 (d, J = 8.7 Hz, 2 H, H-2,
6
N
Br
H-6), 7.55 (d, J = 8.7 Hz, 2 H, H-3, H-5).
RCHOH
RCHOH
MS: m/z = 139.
RCH2OH
O
hν
4-Anisic Acid (8)
2
6
hν
Br
1
H NMR (400 MHz, CD OD): d = 7.98 (d, J = 8.7 Hz, 2 H, H-2, H-
3
Br
6
), 7.01 (d, J = 8.7 Hz, 2 H, H-3, H-5), 3.87 (s, 3 H, OCH3).
Br
RCHOH
RCHOH
hν
23
27
MS: m/z = 152.
1
-Naphthoic Acid (10)
O2
1
H NMR (400 MHz, CDCl ): d = 9.07 (d, J = 8.0 Hz, 1 H, H-8),
8
7
1
3
HBr
.40 (dd, J = 7.3, 1.5 Hz, 1 H, H-2), 8.08 (d, J = 8.0 Hz, 1 H, H-4),
.91 (dd, J = 8.0, 0.7 Hz, 1 H, H-5), 7.65 (ddd, J = 8.5, 7.0, 1.5 Hz,
H, H-7), 7.58 (m, 2 H, H-3, H-6).
O
O
RCHOH
MS: m/z = 172.
24
2
-Naphthoic Acid (12)
1
O
OH
H NMR (400 MHz, CDCl ): d = 8.70 (s, 1 H, H-1), 8.10 (dd,
3
RCO2H
J = 8.7, 1.5 Hz, 1 H, CH), 7.98 (d, J = 7.8 Hz, 1 H, CH), 7.90 (m, 2
H, CH), 7.62 (dd, J = 7.0, 1.3 Hz, 1 H, H-5), 7.58 (dd, J = 7.7, 1.3
Hz, 1 H, H-6), 7.55 (dd, J = 6.8, 1.2 Hz, 1 H, H-7).
RCHOH
2
5
Scheme 2 Possible paths for the aerobic photooxidation of alcohols
MS: m/z = 172.
Nicotinic Acid (14)
H NMR (400 MHz, CD OD): d = 9.12 (s, 1 H, H-2), 8.73 (dd,
J = 5.0, 1.5 Hz, 1 H, H-6), 8.42 (ddd, J = 6.0, 1.9, 1.9 Hz, 1 H, H-
4), 7.57 (ddd, J = 7.2, 5.0, 0.7 Hz, 1 H, H-5).
cleaved again to 23 under photoirradiation since the con-
tinuous photoirradiation is necessary for the progress of
this reaction.
1
3
We have only studied the system for this reaction in small MS: m/z = 123.
scale; however, this new form of oxidation reaction is in-
3
-Thiophenecarboxylic Acid (16)
teresting in keeping with the notion of Green chemistry
due to non-use of heavy metals, waste reduction, use of
molecular oxygen, inexpensive acquisition of reagents,
and possible solvent recovery.
1
H NMR (400 MHz, CDCl ): d = 8.17 (dd, J = 2.9, 1.5 Hz, 1 H, H-
2
H, H-5).
3
), 7.50 (dd, J = 5.3, 1.5 Hz, 1 H, H-4), 7.27 (dd, J = 5.3, 2.9 Hz, 1
MS: m/z = 128.
All reactions were carried out under O . All of the products are
known compounds. H NMR spectra were recorded on JEOL 400
MHz instruments (EX-400 and AL-400) using solvent peak as a
standard. Mass spectrometric data were collected on a JEOL JMS-
SX 102A mass spectrometer.
Dodecanoic Acid (18)
H NMR (400 MHz, CDCl
2
1
1
): d = 2.32 (t, J = 7.4 Hz, 2 H,
CH CO H), 1.23 (m, 16 H, 8 CH ),
3
CH
CO
H), 1.60 (m, 2 H, CH
2
2
2
2
2
2
0.86 (t, J = 6.8 Hz, 3 H, CH
).
3
MS: m/z = 200.
Oxidation of Primary Alcohols; 4-tert-Butylbenzoic Acid (2);
Typical Procedure
A solution of 4-tert-butylbenzyl alcohol (1; 164 mg, 1 mmol) and
Octanoic Acid (20)
1
H NMR (400 MHz, CDCl ): d = 2.32 (t, J = 7.6 Hz, 2 H,
3
CH CO H), 1.60 (q, J = 7.4 Hz, 2 H, CH CH CO H), 1.40–1.25 (m,
2
2
2
2
2
N-bromosuccinimide (17.8 mg, 0.1 mmol) in anhyd MeCN (8 mL)
8
H, 4 CH ), 0.85 (t, J = 7.1 Hz, 3 H, CH ).
2
3
was stirred in a test tube fitted with an O -balloon (1 atm) and irra-
2
MS: m/z = 144.
diated externally with a 400 W high-pressure mercury lamp for 3 h
at r.t.. The mixture was concentrated under reduced pressure, and aq
Dodecan-2-one (22)
A solution of dodecan-2-ol (21; 186 mg, 1 mmol) and N-bromosuc-
cinimide (17.8 mg, 0.1 mmol) in anhyd MeCN (8 mL) was stirred
in a test tube fitted with an O -balloon (1 atm) and irradiated exter-
nally with a 400 W high-pressure mercury lamp at r.t. for 3 h. The
mixture was concentrated under reduced pressure, and aq 10%
NaOH solution was added. The aqueous solution was extracted with
1
0% NaOH solution was added. The aqueous solution was washed
with Et O, and then acidified with aq 2 N HCl, which was extracted
2
with Et O. The organic layer was washed with brine, dried
2
2
(
MgSO ), and concentrated under reduced pressure. The product
4
was obtained pure and needed no further purification; yield: 132 mg
(
74%) (Table 2).
1
H NMR (400 MHz, acetone-d ): d = 7.96 (d, J = 8.7 Hz, 2 H, H-2,
6
Et O, the organic layer concentrated, and the residue was purified
2
H-6), 7.54 (d, J = 8.7 Hz, 2 H, H-3, H-5), 1.34 (s, 9 H, t-C H ).
4
9
by preparative TLC (eluent: hexane–EtOAc, 5:1); yield: 97.4 mg
(53%) (Table 2).
MS: m/z = 163.
1
H NMR (400 MHz, CDCl ): d = 2.35 (t, J = 7.4 Hz, 2 H, CH CO),
3
2
4
-Nitrobenzoic Acid (4)
2
.07 (s, 3 H, CH CO), 1.50 (m, 2 H, CH CH CO), 1.20 (m, 14 H, 7
3
2
2
1
H NMR (400 MHz, acetone-d ): d = 8.36 (d, J = 9.2 Hz, 2 H, H-3,
H-5), 8.28 (d, J = 9.2 Hz, 2 H, H-2, H-6).
6
CH ), 0.82 (t, J = 6.8 Hz, 3 H, CH ).
2
3
MS: m/z = 184.
MS: m/z = 167.
Synthesis 2006, No. 12, 1949–1952 © Thieme Stuttgart · New York

1
952
K. Kuwabara, A. Itoh
PAPER
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2
003, 2289.
(
(
1) Larock, R. C. Comprehensive Organic Transformations: A
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York, 1999.
(
4) Aerobic radical oxidation of alcohols to carboxylic acids has
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Sakaguchi, S.; Iwahana, T.; Nishiyama, Y. J. Org. Chem.
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995, 60, 3934.
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(
(
5) We believe the effective wavelength of the light for this
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6) Since purification of 2 was difficult due to the residue of the
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exclusively used for subsequent studies.
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Synthesis 2006, No. 12, 1949–1952 © Thieme Stuttgart · New York