CuCl catalyzed selective oxidation of primary alcohols to carboxylic acids with tert-butyl hydroperoxide at room temperature

Article abstract of DOI:10.1016/j.tetlet.2008.02.031

Direct oxidation of primary alcohols to the corresponding carboxylic acids is performed highly efficiently at room temperature with anhydrous tert-butyl hydroperoxide in the presence of a catalytic amount of easily available CuCl under ligand free conditions in acetonitrile. Benzylic alcohols are more reactive than aliphatic alcohols, and these benzylic alcohols are selectively oxidized to the corresponding acids in the presence of aliphatic alcohols such as 1-octanol and 1-decanol.

Full text of DOI:10.1016/j.tetlet.2008.02.031

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2457–2460
CuCl catalyzed selective oxidation of primary alcohols to carboxylic
acids with tert-butyl hydroperoxide at room temperature
Sreedevi Mannam, G. Sekar *
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, Tamil Nadu, India
Received 25 June 2007; revised 23 January 2008; accepted 7 February 2008
Available online 10 February 2008
Abstract
Direct oxidation of primary alcohols to the corresponding carboxylic acids is performed highly efficiently at room temperature with
anhydrous tert-butyl hydroperoxide in the presence of a catalytic amount of easily available CuCl under ligand free conditions in
acetonitrile. Benzylic alcohols are more reactive than aliphatic alcohols, and these benzylic alcohols are selectively oxidized to the
corresponding acids in the presence of aliphatic alcohols such as 1-octanol and 1-decanol.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: CuCl; Alcohol oxidation; Selective oxidation; Carboxylic acid; Benzylic alcohols
Oxidation is one of the most fundamental reactions in
synthetic organic chemistry and a variety of reagents have
been developed as oxidants, which is a testimony to the
importance of this reaction.1 However, relatively few gen-
eral methods exist for the direct oxidation of alcohols to
carboxylic acids. Traditionally, this oxidation involves a
two-step process involving oxidation of the alcohol to an
aldehyde followed by further oxidation to the carboxylic
acid. Several reaction conditions have been developed for
the direct oxidation of alcohols to acids such as Jones,2
CrO3/H5IO6,3 RuCl3/H5IO6,4 RuO4,5 RuCl3/K2S2O8,6
Ru–Co bimetallic catalyzed oxidation,7 Cu(MnO4)2 oxida-
tion,8 TEMPO (2,2,6,6-tetramethylpiperidinyl-1-oxy)-cata-
lyzed oxidation with sodium hypochlorite,9 Na2WO4/
Very recently, we developed an efficient method for the
selective oxidation of alcohols to the corresponding alde-
hydes and ketones using a DABCO–Cu complex as a
catalyst.12 As a part of our ongoing research towards
copper catalyzed oxidation chemistry, herein, we report a
CuCl catalyzed direct oxidation of benzylic and allylic
primary alcohols to the corresponding carboxylic acids
using anhydrous tert-butyl hydroperoxide at room temper-
ature under ligand free conditions (Scheme1). This proce-
dure is very simple, mild, clean and works efficiently
without any additives.
In preliminary studies, we used the DABCO–CuCl com-
plex/O2/TEMPO for the oxidation of p-methoxybenzyl
alcohol in nitromethane. The reaction provided only the
corresponding aldehyde with no trace of carboxylic acid
(Table 1, entry 1). When we replaced molecular oxygen
H2O2 and Cu(II)–salen complex/H2O2.11 However, all
10
of these methods have some limitations such as strongly
acidic conditions, a requirement for stoichiometric or super
stoichiometric amounts of costly or hazardous oxidizing
reagents and/or elevated temperatures. Therefore, mild,
catalytic, economic and efficient alternative methods are
still desirable.
t
with 70% BuOOH (in water), the reaction produced a
51% isolated yield of aldehyde and a 23% yield of acid
CuCl (5 mol %)
O
5M tBuOOH (in decane)
R
OH
R
OH
MeCN, rt
*
Corresponding author. Tel.: +91 44 2257 4229; fax: +91 44 2257 4202.
Scheme 1. CuCl catalyzed oxidation of alcohols to acids.
E-mail address: gsekar@iitm.ac.in (G. Sekar).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.031

2458
S. Mannam, G. Sekar / Tetrahedron Letters 49 (2008) 2457–2460
Table 1
Optimizing the conditions for direct oxidation of p-methoxybenzyl alcohol to p-methoxybenzoic acid
5 mol % Cu salt
Oxidant ( 5 equiv.)
+
MeO
CH2OH
MeO
CHO
MeO
COOH
solvent, rt
Entry
Catalyst
Additive
Oxidant
Solvent
Time (h)
Isolated yield (%)
Aldehyde Acid
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
DABCO–CuCl
DABCO–CuCl
DABCO–CuCl
DABCO–CuCl
DABCO–CuCl
DABCO–CuCl
DABCO–CuCl
CuCl
CuCl
—
CuCl
CuCl
CuCl
CuCl
CuBr
CuI
CuNO2Á3H2O
CuCl2Á2H2O
Cu(OAc)2ÁH2O
Cu(OTf)2
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
—
TEMPO
—
—
—
—
—
—
—
—
—
O2
CH3NO2
CH3NO2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
5
12
6
24
24
1
1
1
1
95
51
35
0
0
23
59
0
20
92
91
92
93
0
32
24
89
45
90
48
71
80
25
49
t
70% BuOOH
70% BuOOH
KIO4
30% H2O2
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
t
51
t
Trace
Trace
Trace
—
t
t
t
t
24
24
24
6
24
6
12
12
8
14
12
20
42
20
5
37
2
33
27
t
t
DCM
EtOAc
t
t
Benzene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
t
t
t
t
—
—
—
5 M BuOOH (in decane)
5 M BuOOH (in decane)
5 M BuOOH (in decane)
14
47
45
t
t
but the reaction took 12 h (entry 2). Changing the solvent
from nitromethane to acetonitrile led to the acid as the
major product (entry 3). Replacement of aq 70% BuOOH
a 90% yield of furan-2-carboxylic acid at room temperature
(entry 7). However, pyridin-2-ylmethanol needed refluxing
conditions and 7 equiv of tBuOOH for the direct oxidation
(entry 8). Benzylic diols yielded the corresponding dicarb-
oxylic acids at room temperature with good yields when
t
by H2O2 reduced the yield of acid and the reaction took
one day to complete (entry 5).
t
t
Surprisingly, when 70% BuOOH was replaced with
14 equiv of BuOOH was used (entries 9 and 10). Benzylic
t
anhydrous BuOOH (5 M in decane) all the starting mate-
secondary alcohols were quantitatively oxidized to the
corresponding ketones at room temperature (entries 16–19).
Aliphatic primary alcohols such as n-octanol and n-decanol
were not oxidized even at elevated temperature. To our
surprise, 3-phenylpropan-1-ol and cyclohexylmethanol
were oxidized to the corresponding acids at room temper-
ature in 91% and 87% isolated yields, respectively (entries
11 and 12). Similarly, cyclohexanol (aliphatic secondary
alcohol) was converted to the corresponding ketone in
76% yield. Importantly, we were able to selectively oxidize
benzylic, allylic primary and secondary alcohols in the
presence of aliphatic primary alcohols such as n-octanol
and n-decanol.13 When the substrate is a diol, having both
primary and secondary benzylic alcohol groups, under the
optimized conditions both alcoholic groups oxidized to
give the corresponding keto acid as the major product
(entry 20).
rial was consumed in 1 h at room temperature and the reac-
tion afforded a 92% yield of acid and a trace amount of
aldehyde (entry 8). To our surprise, the real catalyst in this
reaction is ligand free CuCl. CuCl without DABCO or
TEMPO or without both gave similar results (entries 6–9).
However, without CuCl, the reaction produced only 20%
of aldehyde after 24 h and not even a trace amount of acid
was present in the reaction mixture (entry 10). Next, the
reaction was screened with several other solvents and
acetonitrile proved to be the best. Other solvents led to
longer reaction times and gave a mixture of aldehyde and
acid with poor conversion. Similarly, CuCl was the Cu salt
of choice in view of the selectivity, yield and reaction rate.
To determine the scope of this new catalytic system, a
wide range of alcohols were oxidized under the optimized
conditions (5 mol % ligand free CuCl, 5 equiv of anhydrous
tert-butyl hydroperoxide in acetonitrile at room tempera-
ture) and the results are summarized in Table 2. All the
benzylic, allylic and propargylic primary alcohols were oxi-
dized directly to the corresponding acids at room tempera-
ture in a very short time (1–6 h) with almost quantitative
conversion and excellent isolated yields. Heteroatom-con-
taining primary alcohols such as furan-2-ylmethanol gave
In view of the mechanism of this direct oxidation, we
assume that the primary alcohol is oxidized to the aldehyde
and the resulting aldehyde is further oxidized to the acid.
We assume that initially copper(I) will be oxidized to
t
copper(II) by BuOOH and hydroperoxide homolysis is
catalyzed by the copper salt. However, detailed mechanistic
studies of this reaction and increasing the catalytic activity

S. Mannam, G. Sekar / Tetrahedron Letters 49 (2008) 2457–2460
2459
Table 2
CuCl catalyzed alcohol oxidation with tert-butyl hydroperoxide in acetonitrile at room temperaturea
Entry
1
Alcohol
Product
Time (h)
6
Isolated yield (%)
92
Ph–CH2OH
Ph–COOH
CH2OH
NO2
COOH
NO2
2
3
2
5
88b
89c
COOH
CH2OH
O2N
O2N
4
5
1
4
93
MeO
Cl
MeO
Cl
CH2OH
CH2OH
COOH
COOH
90c
COOH
CH2OH
6
7
8
5
5
6
91
Cl
Cl
90
CH2OH
O
COOH
O
82d
CH2OH
N
N
COOH
9
6
6
83e
85e
CH2OH
HOH2C
HOOC
COOH
CH2OH
CH2OH
COOH
COOH
10
86f
91
87
COOH
11
12
13
5
3
6
Ph
Ph
OH
OH
Ph
Ph
COOH
COOH
CH2OH
OH
14
15
4
5
75
93
COOH
CH2OH
COOH
OH
O
O
16
17
3
2
93
96
Ph
Ph
Ph
Ph
OH
Ph
Ph
OH
O
MeO
MeO
MeO
MeO
18
2.5
91
OMe
OMe
(continued on next page)

2460
S. Mannam, G. Sekar / Tetrahedron Letters 49 (2008) 2457–2460
Table 2 (continued)
Entry
Alcohol
Product
Time (h)
Isolated yield (%)
76
19
4
OH
O
HO
OH
O
HOOC
20
1.5
82
a
t
All reactions were carried out with 5 mol % of CuCl and 5 equiv of BuOOH (5 M in decane) in MeCN at rt unless otherwise mentioned. All the
products gave satisfactory spectral data.14
b
5% Aldehyde isolated.
c
2% Aldehyde isolated.
d
e
f
t
Refluxing conditions and 7 equiv of BuOOH (5 M in decane) were required.
14 equiv of BuOOH (5 M in decane) was used. The reaction provided a 10% yield of the mono acid as well.
t
The reaction produced a 5% yield of benzoic acid.
7. (a) Murahashi, S. I.; Naota, T.; Hirai, N. J. Org. Chem. 1993, 58,
7318; (b) Hongbing, J.; Mizugaki, T.; Ebitani, K.; Kaneda, K.
Tetrahedron Lett. 2002, 43, 7179.
towards the oxidation of aliphatic alcohols such as n-octa-
nol and n-decanol are under study.
In conclusion, we have developed a new procedure for
the direct oxidation of primary alcohols to acids using a
8. Noureldin, N. A.; Donald, G. L. J. Org. Chem. 1982, 47, 2790.
9. (a) Nooy, A. E. J. de.; Besemer, A. C.; Bekkum, H. V. Synthesis 1996,
1153; (b) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem.
1987, 52, 2559; (c) Tashino, Y.; Togo, H. Synlett 2004, 2010; (d)
Miyazawa, T.; Endo, T.; Shiihashi, S.; Okawara, M. J. Org. Chem.
1985, 50, 1332; (e) Rychnovsky, S. D.; Vaidyanathan, R. J. Org.
Chem. 1999, 64, 310; (f) Zhao, M.; Li, J.; Song, Z.; Desmond, R.;
Tschaen, D. M.; Grabowski, E. J. J.; Reider, P. J. J. Org. Chem. 1999,
64, 2564; (g) Zhao, M.; Li, J.; Song, Z.; Tschaen, D. M.; Mano, E.
Org. Synth. 2005, 81, 195.
t
catalytic amount of CuCl and anhydrous BuOOH (5 M
in decane) in acetonitrile under very mild conditions.
Secondary benzylic alcohols were also oxidized to the
corresponding ketones efficiently using CuCl at room
temperature. Benzylic alcohols are more reactive than ali-
phatic alcohols and these benzylic alcohols can be oxidized
to the corresponding acids in the presence of aliphatic alco-
hols such as n-octanol and n-decanol. This procedure is
very simple and works efficiently without any additives.
10. (a) Sato, K.; Aoki, M.; Tagaki, J.; Noyori, R. J. Am. Chem. Soc. 1997,
119, 12386; (b) Sato, K.; Tagaki, J.; Aoki, M.; Noyori, R. Tetrahedron
Lett. 1998, 39, 7549.
11. Salen–Cu(II) complex (synthesized by three steps) was used as catalyst
with H2O2 at 80 °C. Velusamy, S.; Punniyamurthy, T. Eur J. Org.
Chem. 2003, 3913.
Acknowledgements
12. Sekar, G.; Sreedevi, M.; Alamsetti, S. K. Adv. Synth. Catal. 2007, 349,
2253.
We thank DST, New Delhi (SERC Fast Track Research
Project No.: SR/FTP/CS-19/2004) for the financial sup-
port. S.M. thanks CSIR for a Junior Research Fellowship.
13. When a mixture of p-methoxybenzyl alcohol and n-octanol (1 mmol
each) was reacted with 5 mol % CuCl and 5 mmol of 5 M tBuOOH in
CH3CN for 1 h, p-methoxybenzyl alcohol was fully consumed and
produced a 92% isolated yield of the corresponding carboxylic acid
and n-octanol was left intact. Similarly, allylic and propargylic
alcohols were selectively oxidized over aliphatic alcohols.
14. Typical experimental procedure: To a solution of CuCl (4.95 mg,
0.05 mmol) in 2 mL of CH3CN and p-methoxybenzyl alcohol
References and notes
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t
(138.16 mg, 1 mmol) was slowly added BuOOH (1.23 mL, 5 mmol,
5 M solution in decane). The resulting mixture was stirred at room
temperature until the disappearance of starting material (observed by
TLC). After completion of the reaction, the solvent was evaporated
and to the resulting crude reaction mixture water (5 mL) was added.
The pH of the reaction mixture was adjusted to 8.0–8.5 with saturated
NaHCO3 and was then extracted with ethyl acetate. The aqueous
layer was acidified to pH 2.0 using 2 N HCl and extracted with ethyl
acetate. The organic layer was concentrated and purified using silica
gel column chromatography to give p-methoxybenzoic acid
(141.6 mg, 93% yield).
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