Efficient oxidation of alcohols to carbonyl compounds with molecular oxygen catalyzed by N-hydroxyphthalimide combined with a Co species

Article abstract of DOI:10.1021/jo000760s

Highly efficient catalytic oxidation of alcohols with molecular oxygen by N-hydroxyphthalimide (NHPI) combined with a Co species was developed. The oxidation of 2-octanol in the presence of catalytic amounts of NHPI and Co(OAc)₂ under atmospheric dioxygen in AcOEt at 70 °C gave 2-octanone in 93% yield. The oxidation was significantly enhanced by adding a small amount of benzoic acid to proceed smoothly even at room temperature. Primary alcohols were oxidized by NHPI in the absence of any metal catalyst to form the corresponding carboxylic acids in good yields. In the oxidation of terminal vic-diols such as 1,2-butanediol, carbon-carbon bond cleavage was induced to give one carbon less carboxylic acids such as propionic acid, while internal vic-diols were selectively oxidized to 1,2-diketones.

Full text of DOI:10.1021/jo000760s

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6502 J . Org. Chem. 2000, 65, 6502-6507
Efficien t Oxid a tion of Alcoh ols to Ca r bon yl Com p ou n d s w ith
Molecu la r Oxygen Ca ta lyzed by N-Hyd r oxyp h th a lim id e Com bin ed
w ith a Co Sp ecies
Takahiro Iwahama, Yasushi Yoshino, Takashi Keitoku, Satoshi Sakaguchi, and
Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering & High Technology Research Center,
Kansai University, Suita Osaka 564-8680, J apan
ishii@ipcku.kansai-u.ac.jp
Received May 18, 2000
Highly efficient catalytic oxidation of alcohols with molecular oxygen by N-hydroxyphthalimide
(NHPI) combined with a Co species was developed. The oxidation of 2-octanol in the presence of
catalytic amounts of NHPI and Co(OAc)2 under atmospheric dioxygen in AcOEt at 70 °C gave
2-octanone in 93% yield. The oxidation was significantly enhanced by adding a small amount of
benzoic acid to proceed smoothly even at room temperature. Primary alcohols were oxidized by
NHPI in the absence of any metal catalyst to form the corresponding carboxylic acids in good yields.
In the oxidation of terminal vic-diols such as 1,2-butanediol, carbon-carbon bond cleavage was
induced to give one carbon less carboxylic acids such as propionic acid, while internal vic-diols
were selectively oxidized to 1,2-diketones.
In tr od u ction
of aliphatic alcohols catalyzed by copper complexes has
been reported.6
The selective oxidation of alcohols to the corresponding
carbonyl compounds is a frequently used transformation
in organic synthesis, and hence a wide variety of methods
has been developed. Swern oxidation,1 Dess-Martin
oxidation,2 and various metal reagents3 are employed for
this purpose. Unfortunately, these oxidations call for the
use of at least a stoichiometric amount of oxidants and
bring about a large quantity of noxious byproducts. From
an environmental viewpoint, there has been an increas-
ing need for selective oxidation using molecular oxygen
as an oxidant under mild conditions. Although there have
been many catalytic methods for the aerobic oxidation
of alcohols to the corresponding carbonyl compounds,4,5
expensive metal catalysts such as ruthenium and pal-
ladium compounds must be used to complete the oxida-
tion satisfactorily, and some oxidations are carried out
in the presence of reducing agents such as aldehydes
which are eventually converted into carboxylic acids. In
addition, some of these catalysts are only effective for the
oxidation of reactive alcohols such as benzylic and allylic
alcohols. In the practical point of view, the transformation
of alcohols to carbonyl compounds by an inexpensive
catalyst is particularly notable, especially in industrial
chemistry. Quite recently, an efficient aerobic oxidation
In a preceding communication, we described an ef-
ficient catalytic system consisting of N-hydroxyphthal-
imide (NHPI) and a Co ion for the oxidation of alcohols
and diols with molecular oxygen as an oxidant (eq 1).7
(5) Ru: (a) Tang, R.; Diamond, S. E.; Neary, N.; Mares, F. J . Chem.
Soc., Chem. Commun. 1978, 562. (b) Matsumoto, M.; Watanabe, N. J .
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Am. Chem. Soc. 1987, 109, 3786. (d) Backvall, J .-E.; Chowdhury, R.
L.; Karlsson, U. J . Chem. Soc., Chem. Commun. 1991, 473. (e)
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Wang, G. Z.; Andreasson, U.; Backvall, J .-E. J . Chem. Soc., Chem.
Commun. 1994, 1037. (g) Inokuchi, T.; Nakagawa, K.; Torii, S.
Tetrahedron Lett. 1995, 36, 3223. (h) Marko, I. E.; Giles, P. R.;
Tsukazaki, M.; Chelle-Regnaut, M. I.; Urch, C. J .; Brown, S. M. J . Am.
Chem. Soc. 1997, 119, 12661. (i) Lenz, R.; Ley, S. V. J . Chem. Soc.,
Perkin Trans. 1 1997, 3291. (j) Hanyu, A.; Takezawa, E.; Sakaguchi,
S.; Ishii, Y. Tetrahedron Lett. 1998, 39, 5557. (k) Kaneda, K.; Ya-
mashita, T.; Matsushita, T.; Ebitani, K. J . Org. Chem. 1998, 63, 1750.
(l) Marko, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut, M. I.; Urch,
C. J .; Brown, S. M. J . Org. Chem. 1998, 63, 7576. Pd: (m) Blackburn,
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Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. Tetrahedron Lett. 1998,
39, 6011. Co: (q) Yamada, T.; Mukaiyama, T. Chem. Lett. 1989, 519.
(r) Mandal, A. K.; Iqbal, J . Tetrahedron Lett. 1997, 53, 7641. other
metals: (s) Semmelhack, M. F.; Schmid, C. R.; Cortes, D. A.; Chou, C.
S. J . Am. Chem. Soc. 1984, 106, 3374. (t) Coleman, K. S.; Coppe, M.;
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274, 2044.
(1) (a) Mancuso, A. J .; Swern, D. Synthesis 1981, 165. (b) Tidwell,
T. T. Synthesis 1990, 857.
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Dess, D. B.; Martin, J . C. J . Am. Chem. Soc. 1991, 113, 7277.
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Compounds; Mijs, W. J ., J onge, C. R. H. I., Eds.; Plenum Press: New
York, 1986. (b) Piancatelli, G.; Scettri, A.; D’Auria, M. Synthesis 1982,
245. (c) Fetizon, M.; Golfier, M.; Mourgues, P.; Louis, J . M. In Organic
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R. H. I., Eds.; Plenum Press: New York, 1986; pp 503-567.
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p 573. (b) J ames, B. R. In Dioxygen Activation and Homogeneous
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Lett. 1995, 36, 6923.
10.1021/jo000760s CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/07/2000

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Efficient Oxidation of Alcohols to CO Compounds
J . Org. Chem., Vol. 65, No. 20, 2000 6503
Ta ble 1. Oxid a tion of 2-Octa n ol (1) to 2-Octa n on e (2)
w ith Molecu la r Oxygen Ca ta lyzed by NHP I Com bin ed
w ith Co(OAc)2 u n d er Va r iou s Con d ition sa
by the NHPI/Co(OAc)2 system, it was found that benzoic
acids such as m-chlorobenzoic acid (MCBA) also enhance
the oxidation of alcohols to carbonyl compounds. The
effect of benzoic acids on the NHPI/Co(OAc)2-catalyzed
oxidations of alcohols will be discussed later.
Thus, the oxidation of 1 with O2 by the NHPI/Co(OAc)2
system at room temperature was induced by adding a
catalytic amount of MCBA to give 2 in good yield (75%),
while the same oxidation in the absence of MCBA
proceeded slowly to form 2 in low yield (21%) (runs 5 and
6). To our best knowledge, the aerobic oxidation of a
simple alcohol such as 1 at room temperature is only
reported to be catalyzed by Bu4N+RuO4-, although mo-
lecular sieves 4A must be added to the reaction system.5i
When the amount of MCBA was lowered from 5 mol %
to 1 mol %, the yield of 2 slightly decreased (60%) (run
7). The oxidation using 10 mol % of MCBA was almost
the same as that of 5 mol % of MCBA. (run 8). To know
the substituent effect on the benzene ring in benzoic
acids, benzoic acid or p-methoxybenzoic acid was added
in place of MCBA to afford 2 in 70% and 64% yields,
respectively (runs 9 and 10). However, the addition of
p-nitrobenzoic acid resulted in a low yield of 2 (41%)
compared with that of the MCBA (run 11).
On the basis of these results, various alcohols were
allowed to react at room temperature using the NHPI/
Co(OAc)2/MCBA system under an oxygen atmosphere
(Table 2).
Like 2-octanol 1, 1-phenylethanol (3) was smoothly
oxidized at room temperature to give acetophenone (4)
in almost quantitative yield (run 2). Cyclic alcohols such
as cyclohexanol (5) and cyclooctanol (7) were also oxidized
under these conditions to the corresponding ketones, 6
and 8, in good yields (runs 3 and 4), but l-menthol (9)
was difficult to be effectively oxidized at room tempera-
ture (run 5).
A primary alcohol, 1-octanol (13), was oxidized to
octanoic acid (14) in good yield (78%), although mCPBA
was added instead of MCBA (runs 7 and 8). It is
noteworthy that carboxylic acids were obtained from
primary alcohols in high yields by the present oxidation,
because the aerobic oxidation by metal complexes of Ru,
Cu, or Pd often produces a mixture of aldehydes and
carboxylic acids.10 In our oxidation which proceeds via a
free radical process as discussed later, the formed alde-
hydes are rapidly oxidized to carboxylic acids, since the
hydrogen atom abstraction from aldehydes to acyl radi-
cals takes place more easily than that from alcohols to
R-hydroxy alkyl radicals.11 The application of this pro-
cedure to the oxidation of lauryl alcohol (17) led to lauric
acid (18) in 66% yield which can be used as a surfactant
source (run 10).
On the other hand, allylic alcohol such as 1-octen-3-ol
(19) was oxidized to R,â-unsaturated ketone (20) in
moderate selectivity, probably because of the attacking
of radical species to their double bonds (run 11). Needless
to say, in the oxidation of a tertiary alcohol such as
1-methyl-1-cyclohexanol (21), no oxidation occurred and
the starting 21 was recovered unchanged (run 12).
2. Oxid a t ion of Va r iou s Diols w it h Molecu la r
Oxygen . The oxidation of diols has been widely inves-
a
1 (3 mmol) was allowed to react with molecular oxygen (1 atm)
in the presence of NHPI (10 mol %), Co(OAc)2 (0.5 mol %), and
b
additive (5 mol %) in solvent (5 mL). MCBA ) m-chlorobenzoic
acid, BA ) benzoic acid, PMBA ) p-methoxybenzoic acid, PNBA
) p-nitrobenzoic acid. c GC yield. Without Co(OAc)2. e MCBA (1
d
mol %) used. f MCBA (10 mol %) was used.
The NHPI used as the catalyst is a commercially avail-
able compound and can be easily prepared from phthalic
anhydride, which is manufactured in large scale as a bulk
chemical, and hydroxylamine.
We now find that primary and secondary alcohols can
be oxidized with molecular oxygen at room temperature
by the use of the NHPI combined with a Co(II) ion as
the catalyst, which is very important from the viewpoint
of energy-saving. In this paper, we wish to report the
NHPI-catalyzed aerobic oxidation of alcohols and diols
in detail.
Resu lts
1. Oxid a tion of Alcoh ols w ith Molecu la r Oxygen .
Table 1 shows representative results for the oxidation of
2-octanol (1) to 2-octanone (2) with molecular oxygen (1
atm) under various conditions. The oxidation of 1 in the
presence of catalytic amounts of NHPI (10 mol %) and
Co(OAc)2 (0.5 mol %) in CH3CN at 70 °C for 20 h gave 2
in high yield (93%) (run 2). From a survey of solvents,
AcOEt was found to be the most efficient (run 3). In a
previous paper, we showed that toluenes can be oxidized
to benzoic acids by the NHPI/Co(OAc)2 system under
normal pressure and temperature of O2.8 In this oxida-
tion, we found that an oxygenated product, benzoic acid,
exerts efficient rate enhancement of the oxidation of
toluenes.9 Furthermore, even in the oxidation of alcohols
(8) Yoshino, Y.; Hayashi, Y.; Iwahama, T.; Sakaguchi, S.; Ishii, Y.
J . Org. Chem. 1997, 62, 6810.
(9) For example, the oxidation of p-methoxytoluene in the presence
of NHPI (10 mol %), Co(OAc)2 (0.5 mol %), and MCBA (5 mol %) in
CH3CN at room temperature under atmospheric dioxygen for 3 h gave
p-methoxybenzoic acid in 73% yield, although the same oxidation
without MCBA produced low yield (13%) of p-methoxybenzoic acid.
(10) Ru and Cu complex-catalyzed aerobic oxidations of primary
alcohols proceed through the formation of metal-alkoxide intermedi-
ates; see ref 5 and references therein.
(11) Sheldon, R. A.; Kochi, J . K. In Metal-Catalyzed Oxidations of
Organic Compounds; Academic Press: New York, 1981.

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6504 J . Org. Chem., Vol. 65, No. 20, 2000
Iwahama et al.
Ta ble 2. Oxid a tion of Va r iou s Alcoh ols w ith Molecu la r
Oxygen Ca ta lyzed by NHP I Com bin ed w ith Co(OAc)2 a t
Room Tem p er a tu r ea
Ta ble 3. Oxid a tion of 1,2-Octa n ed iol (22) w ith Molecu la r
Oxygen a
a
22 (3 mmol) was allowed to react with molecular oxygen (1
atm) in the presence of NHPI (10 mol %), Co(OAc)2 (0.5 mol %),
b
and additive (5 mol %) in AcOEt (5 mL). GC yield. For runs 2 to
4, heptanal was confirmed as a side product. c Co(acac)3 (1 mol
d
%) was used instead of Co(OAc)2 in CH3CN. Co(OAc)2 (1 mol %)
was used without MCBA.
mechanistic and synthetic aspects. Thus, we examined
the aerobic oxidation of various diols by the NHPI
catalyst.
The oxidation of 1,2-octanediol (22) was carried out
under several reaction conditions (Table 3). Although
secondary alcohols were successfully oxidized even at
room temperature by the use of the NHPI/Co(OAc)2/
MCBA system, the oxidation of 22 under the same
conditions formed a trace amount of 1-hydroxy-2-octa-
none (23) after 12 h (run 1). Interestingly, when Co(acac)3
was used instead of Co(OAc)2, the oxidation proceeded
smoothly to give a one carbon less oxidized product,
heptanoic acid (24), in good selectivity (run 3). Until now,
there is no report on the selective cleavage of 1,2-diols
to carboxylic acids with molecular oxygen. In this oxida-
tion, the main product was found to be 1-hydroxy-2-
octanone (23) at the early stage of the reaction (run 4).
This indicates that a precursor to carboxylic acid 24 is
R-ketol 23. Indeed, the oxidation of 23 under these
conditions led to 24 in good yield (eq 2).
a
Alcohol (3 mmol) was allowed to react with molecular oxygen
(1 atm) in the presence of NHPI (10 mol %), Co(OAc)2 (0.5 mol %),
b
and MCBA (5 mol %) in AcOEt (5 mL) at room temperature. GC
yield. c mCPBA (1 mol %) was used instead of MCBA.
tigated in oxidation chemistry, since the selective oxida-
tion of vic-diols to R-ketols, diketones, or cleaved products
(aldehydes or carboxylic acids) is an important transfor-
mation in organic synthesis.12 Recently, hydrogen per-
oxide has been shown to be a useful oxidant for these
transformations.13 However, there is only a limited
number of reports on the oxidation of diols by molecular
oxygen as the oxidant.14 In particular, the radical type
of oxidation of diols with O2 is rarely reported.15 There-
fore, investigating the oxidation of diols via a radical
process seems to be an interesting subject from both
On the other hand, it was found that internal vic-diols
such as 2,3-octanediol (25) are selectively oxidized to
diketones such as 2,3-octanedione (26) rather than
cleaved carboxylic acids. After the optimization of the
reaction conditions, diketone 26 was obtained in 73%
yield (eq 3). This is the first successful transformation of
(12) Hudlicky, M. In Oxidation in Organic Chemistry, ACS Mono-
graph 186; American Chemical Society: Washington, DC, 1986 and
references therein.
(13) (a) Venturello, C.; Ricci, M. J . Org. Chem. 1986, 51, 1599. (b)
Sakata, Y.; Ishii, Y. J . Org. Chem. 1991, 56, 6233. (c) Sakata, Y.;
Katayama, Y.; Ishii, Y. Chem. Lett. 1992, 671 and references therein.
(14) (a) Felthouse, T. R. J . Am. Chem. Soc. 1987, 109, 7566. (b)
Okamoto, T.; Sakai, K.; Oka, S. J . Am. Chem. Soc. 1988, 110, 1187.
(c) Takezawa, E.; Sakaguchi, S.; Ishii, Y. Org. Lett. 1999, 1, 713. (d)
Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. J . Org. Chem. 1999,
64, 6750.
vic-diols to diketones with O2. The conversion of vic-diols
to diketones is usually carried out by the use of metal
(15) Vries, G. D.; Schors, S. Tetrahedron Lett. 1968, 9, 5689.

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Efficient Oxidation of Alcohols to CO Compounds
J . Org. Chem., Vol. 65, No. 20, 2000 6505
Ta ble 4. Oxid a tion of Va r iou s vic-Diols w ith Molecu la r Oxygen a
a
Diols (3 mmol) were allowed to react with molecular oxygen (1 atm) in the presence of NHPI (10 mol %) and Co(acac)3 (1 mol %) in
b
CH3CN (5 mL). GC yield.
Ta ble 5. Oxid a tion of Va r iou s Diols w ith Molecu la r
Oxygen a
16
oxidants such as AgCO3 and permanganate17 or by the
TEMPO-NaOCl system under electrochemical condi-
tions18 as well as by the heteropolyoxometalate-catalyzed
H2O2 oxidation.19
On the basis of these results, several vic-diols were
allowed to react using the NHPI/Co(acac)3 system with
molecular oxygen (1 atm) under selected reaction condi-
tions (Table 4).
Terminal 1,2-diols such as 1,2-butanediol (27), 3,3-
dimethyl-1,2-butanediol (29), and 1,2-phenylethanediol
(31) were oxidized to the corresponding carboxylic acids,
28, 30, and 32, respectively, in good yields. From 1,2-
diphenylethanediol (33), benzyl (34) was obtained in 84%
yield with a small amount of benzoin (35) (12%). How-
ever, cyclic vis-diols such as 1,2-cyclohexanediol (36) and
1,2-cyclooctanediol (39) were difficult to be selectively
oxidized to the corresponding 1,2-diketones because of
over-oxidation to dicarboxylic acids.
Table 5 shows the aerobic oxidation of several diols by
the NHPI/Co(acac)3 system. In contrast to the oxidation
of 1,2-diols to diketones, 1,3- and 1,4-diols were oxidized
to the corresponding hydroxy ketones rather than dike-
tones in good selectivity. 1,3- and 1,4-cyclohexanediols,
42 and 44, were converted into 3- and 4-hydroxycyclo-
hexanones, 43 and 45, respectively, rather than dike-
tones, in good yields. 2-Methyl-2,4-pentanediol (47) and
1,3-butanediol (49) were oxidized to 4-hydroxy-4-methyl-
2-pentanone (48) and 4-hydroxy-2-butanone (50), respec-
tively. On the other hand, an R,ω-diol such as 1,5-
pentanediol (51) gave a dicarboxylic acid in 66% yield.
Since diols such as 51 are difficult to be oxidized to
dicarboxylic acids by Ru and Pd complexes,14d,20 the
a
Diols (3 mmol) were allowed to react with molecular oxygen
(1 atm) in the presence of NHPI (10 mol %) and Co(acac)3 (1 mol
b
%) in CH3CN (5 mL). GC yield.
present reaction provides an alternative method for the
synthesis of dicarboxylic acids from diols with molecular
oxygen.
Discu ssion
(16) Fetizon, M.; Golfier, M.; Louis, J . M. J . Chem. Soc., Chem.
Commun. 1969, 1102.
(17) Baskaran, S.; Das, J .; Chandrasekaran, S. J . Org. Chem. 1989,
54, 5182.
(18) Inokuchi, T.; Matsumoto, S.; Nishiyama, T.; Torii, S. Synlett
1990, 57.
A plausible reaction path for the aerobic oxidation of
1 by the present catalytic system is illustrated in Scheme
1. In previous papers on the aerobic oxidation of alkanes
(19) Iwahama, T.; Skaguchi, S.; Nishiyama, Y.; Ishii, Y. Tetrahedron
Lett. 1995, 36, 1523.
(20) Naota, T.; Takaya, H.; Murahashi, S.-I. Chem. Rev. 1998, 98,
2599 and references therein.