Efficient oxidation of cycloalkanols by sodium nitrite with molecular oxygen in trifluoroacetic acid

Article abstract of DOI:10.1016/j.tetlet.2004.09.037

Oxidation of aliphatic cycloalkanols by sodium nitrite in trifluoroacetic acid gave α,ω-dicarboxylic acids in good yields. Adipic acid was obtained in a quantitative yield from cyclohexanol using 1 equiv of sodium nitrite under oxygen atmosphere but the oxidation required more than 3 equiv of sodium nitrite under nitrogen atmosphere. The oxidation method was applicable to the conversion of 1-alkanols to the corresponding carboxylic acids.

Full text of DOI:10.1016/j.tetlet.2004.09.037

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8221–8224
Efficient oxidation of cycloalkanols by sodium nitrite
with molecular oxygen in trifluoroacetic acid
Yoshihiro Matsumura,a,* Yutaka Yamamoto, Noriaki Moriyama, Shigeru Furukubo,
a
a
a
b
Fumiaki Iwasaki and Osamu Onomura
a
a
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
b
Tsukuba Research Lab., Tokuyama Co. Ltd, 40 Wadai, Tsukuba 300-4247, Japan
Received 30 April 2004; revised 2 September 2004; accepted 3 September 2004
Available online 22 September 2004
Abstract—Oxidation of aliphatic cycloalkanols by sodium nitrite in trifluoroacetic acid gave a,x-dicarboxylic acids in good yields.
Adipic acid was obtained in a quantitative yield from cyclohexanol using 1equiv of sodium nitrite under oxygen atmosphere but the
oxidation required more than 3equiv of sodium nitrite under nitrogen atmosphere. The oxidation method was applicable to the
conversion of 1-alkanols to the corresponding carboxylic acids.
Ó 2004 Elsevier Ltd. All rights reserved.
+
Nitrosonium ion (NO ) and nitronium ion (NO ) salts
+
2
Among the oxidation of 1, the oxidation of cyclohexa-
nol (1a) to adipic acid (2a) has been well known to be
have been known to be usable for the oxidation of
1c,2
1
8
alcohols. The reported salts are NOBF , NO BF ,
4
achieved by nitric acid oxidation. The nitric acid oxida-
tion involves an active species such as nitrosonium ion
2
4
3
4
5
NOCl, M(NO ) , and M(NO ) . In spite of their use-
3 2
2
2
+
(NO ) and nitronium ion (NO ), the rates of which form-
+
2
fulness for the conversion of alcohols to carbonyl com-
pounds, there still exists a requirement for more efficient
methods using readily accessible reagents with easy hand-
ation in situ are critical for efficiency of the oxidation.
So, nitric acid oxidation requires careful control of the
reaction temperature, the concentration of the substrate
and nitric acid, and the presence of metal ion (M) addi-
tives such as vanadium(V) or copper(II) catalysts to
ling. Recently, NaNO in acetic anhydride as a solvent
2
has been reported to be effective for the oxidation of pri-
6
mary alcohols to aldehydes. We report herein an effi-
cient oxidation of cycloalkanols 1 to a,x-dicarboxylic
9
smoothly initiate and promote the oxidation, but it
sometimes brings about decrease of the yield as well as
acids 2 using NaNO with molecular oxygen in trifluoro-
2
7
10
acetic acid (Eq. 1). The use of NaNO as an oxidizing
2
formation of overoxidation products. On the other
hand, our method is carried out at room temperature
reagent and trifluoroacetic acid as a solvent is essential
since the use of NOBF or NaNO in place of NaNO
2
1
1
under an atmosphere of molecular oxygen or air.
4
3
in trifluoroacetic acid or NaNO in other solvents (acetic
2
acid, methanesulfonic acid, or acetic anhydride, etc.)
than trifluoroacetic acid did not afford 2.
A typical reaction condition is exemplified by the con-
version of 1a to 2a as follows (Eq. 2). Cyclohexanol
(
(
1a) (1mmol) was dissolved in trifluoroacetic acid
5mL) and then NaNO (2.0mmol) was added to the
2
NaNO2 air
solution at 0°C under an atmosphere of oxygen. After
the resulting solution was stirred at room temperature
for 5h, the solvent was recovered in vacuo (30mmHg)
at room temperature and the residue was added into
an aqueous 5% NaHCO . After the solution was treated
(
CH2)n
OH
(CH2)n CO2H
CO2H
in CF3CO2H
ð1Þ
1
2
12
3
with methylene chloride, the aqueous solution was acidi-
fied with a 10% HCl solution followed by an extraction
with ethyl acetate to give 2a. The yield of 2a was quanti-
tative. Although cyclohexanone (3a) was not observed
in the oxidation, it might be an intermediate in the
Keywords: Cyclohexanol; Oxidation; Nitrosonium ion; Adipic acid;
Trifluoroacetic acid.
*
Corresponding author. Tel.: +81 95 819 2429; fax: +81 95 819 2476;
e-mail: matumura@net.nagasaki-u.ac.jp
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.037

8222
Y. Matsumura et al. / Tetrahedron Letters 45 (2004) 8221–8224
a
Table 1. Oxidation of cycloalkanols 1 to a,x-dicarboxylic acids 2 by NaNO
2
3 2
in CF CO H
Entry
Cycloalkanols
Reaction time (h)
Dicarboxylic acids
Yield (%)
Ketones
Yield (%)
1
2
3
4
5
6
Cyclohexanol 1a
Cyclopentanol 1b
Cycloheptanol 1c
1c
5
5
HO
HO
HO
2c
2
2
2
C(CH
C(CH
C(CH
2
2
2
)
)
)
4
3
5
CO
CO
CO
2
2
2
H 2a
H 2b
H 2c
100
47
58
73
94
80
Cyclohexanone 3a
Cyclopentanone 3b
Cycloheptanone 3c
3c
0
51
5
30
18
12
5
Cyclooctanol 1d
Cyclododecanol 1e
HO
HO
2
C(CH
C(CH
2
)
)
6
CO
2
H 2d
Cyclooctanone 3d
Cyclododecanone 3e
Trace
10
5
2
2
2
10CO H 2e
t-Bu
b
7
8
4-t-Bu-cyclohexanol 1f
2-Me-cyclohexanol 1g
5
5
92
14
—
HO2CCH2CH(CH2)2CO2H 2f
CO2H 2g
b
—
HO2C
Me
O
2
g'
5
2
HO2C
Me
Me
b
—
9
3-Me-cyclohexanol 1h
5
60
CO2H 2h
HO2C
HO2C
CO2H
2h'
30
Me
a
2 3 2
Reaction condition: alcohol (1mmol), NaNO (2equiv), CF CO H (5mL), 0°C to rt.
Isolation not tried.
b
pathway from 1a to 2a since treatment of 3a with
NaNO in CF CO H also afforded 2a quantitatively.
NaNO2
in CF3CO2H
R
R
OH
2
3
2
OH
O
ð3Þ
OH
O
OCOCF3
5
6
0oC to r.t. 5h
CO2H
CO2H
NaNO2
in CF3CO2H
+
+
Table 3. Oxygen effect on the NaNO
2
oxidation of 1a
1a
2a
3a
4a
Entry
Atmosphere
NaNO (equiv) Yield (%)
2
ð2Þ
Under similar reaction conditions, other cycloalkanols
2
a
3a
4a
1a
1
2
3
4
5
6
7
8
9
N
N
N
N
2
2
2
2
0.5
1
5
34
65
59
33
0
7
18
0
45
0
0
0
0
0
0
0
0
0
0
1
b–h were mainly oxidized to the corresponding a,x-
12
35
62
97
29
69
0
0
dicarboxylic acids 2b–h,h and keto acid 2g , while cyclic
ketones 3 were obtained in some cases depending on the
kind of 1 (Table 1).
2
3
0
N2
4
0
Air
Air
Air
0.5
1
65
25
0
0
Furthermore, aliphatic primary alcohols 5a,b were oxi-
dized to the corresponding carboxylic acids 6a,b (Eq.
3), while aliphatic secondary alcohols 7a,b were mainly
oxidized to ketones 8a,b. The results are shown in Table
0
2
100
53
0
O
2
O
2
O
2
0.5
1
43
0
0
1
1
0
1
99
100
0
2
0
0
2
.
a
Table 2. Oxidation of aliphatic primary alcohols 5a–d and secondary alcohols 7a,b
Entry
Alcohols
Yield (%) of products
1
2
3
1-Dodecanol
1-Octanol
PhCH
5a
5b
5c
5d
7a
CH
CH
3
(CH
(CH
2
)
10CO
2
H
6a (100)
6b (96)
6c (99)
6d (100)
8a (77)
3
2
)
6
CO H
2
2
OH
12OH
PhCO
2
H
b
4
HO(CH
2
)
HO C(CH )10CO H
2 2
2
5
6
2-Octanol
2-Octanone
OH
O
O
CO2H
CO2H
CO2H
7b
8
b (79)
3a (7)
9 (trace) 2a (trace)
a
2 3 2
Reaction condition; alcohol (1mmol), NaNO (2equiv), CF CO H (5mL), 0°C to rt 5h under air.
NaNO (4equiv).
2
b

Y. Matsumura et al. / Tetrahedron Letters 45 (2004) 8221–8224
8223
+
-
NaNO2
+
2CF CO H
NO CF CO
+
CF CO Na
2
+ H O
3
2
3
2
3
2
O2-. + H+
O2
NO+
HNO
OH
OH
O
NO+
- H+
-
H+
1
a
3
a
3a'
H
O
N
O
N
OH
O
O
O
HO
HO
N
H2O
C
A
B
O2-. + H+
O2
NO+
O
HNO
O
HO
O
HO
H2O
OH
CHO
- H+
-
NH2OH
2
a
D
Scheme 1. Plausible mechanism for oxidation of cyclohexanol (1a) by NANO
2
in CF
3
CO
2
H.
In order to clarify the reaction mechanism, oxidation of
1
The method presented herein is very promising from a
practical viewpoint for oxidation of alcohols since the
reaction conditions are mild, yields are high, sodium
nitrite is a very cheap oxidizing reagent, and most of tri-
fluoroacetic acid can be recovered. Further application
of this method to other organic compounds than alco-
hols is now under investigation.
a to 2a was carried out under an atmosphere of oxygen,
air, and nitrogen, respectively. The results are shown in
Table 3.
Under an atmosphere of nitrogen, 4equiv of NaNO2
were necessary to complete the conversion of 1a to 2a
(
a mixture of 2a and 3a (entries 3 and 4), and the use
of less than 1equiv of NaNO resulted in formation of
2
entry 5), while the use of 2 or 3equiv of NaNO gave
2
References and notes
cyclohexyl trifluoroacetate (4a) and/or recovery of some
amount of 2a (entries 1 and 2). Aerobic atmosphere con-
dition improved the efficiency of NaNO as an oxidant
1
2
. (a) Smith, J. R. L.; Loeppky, R. N. J. Am. Chem. Soc.
1967, 89, 1147–1157; (b) Olah, G. A.; Ho, T.-L. Synthesis
1976, 609–610; (c) Olah, G. A.; Ho, T.-L. Synthesis 1976,
610–611.
2
(
than 1equiv of NaNO completed the conversion of 1a
entries 6–8), and under an oxygen atmosphere more
2
. (a) Ho, T.-L.; Olah, G. A. J. Org. Chem. 1977, 42, 3097–
098; (b) Olah, G. A.; Shih, J. G.; Singh, B. P. J. Org.
Chem. 1983, 48, 3356–3358.
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NO by oxidation of HNO with the oxygen atom, while
3
+
a mixture of 2a and 3a was formed by a half equivalent
of NaNO under an oxygen atmosphere (entry 9).
3. (a) Rogi c´ , M.; Vitrone, J.; Swerdloff, M. D. J. Am. Chem.
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1171.
2
On the basis of these results and the reported mecha-
nism for the nitric acid oxidation of 1a, we pro-
pose a plausible mechanism for the oxidation of 1a to 2a
8a,10b,d,e
4
. (a) Tovrog, B. S.; Diamond, S. E.; Mares, F.; Szalkiewicz,
A. J. Am. Chem. Soc. 1981, 103, 3522–3526; (b) Nyarady,
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2
2
3
1
1
intermediates A–D may be involved. The fact that
more than 1equiv of NaNO was necessary for the com-
3727; (c) Nishiguchi, T.; Asano, F. J. Org. Chem. 1989, 54,
1531–1535.
2
pletion of the oxidation of 1a to 2a suggests a consump-
tion of 1equiv of NaNO as hydroxylamine, though
hydroxylamine was not detected.
5
. Cornelis, A.; Laszlo, P. Synthesis 1985, 909–918.
2
6. Bandgar, B. P.; Sadavarte, V. S.; Uppalla, L. S. J. Chem.
Soc., Perkin Trans. 1 2000, 3559–3560.

8224
Y. Matsumura et al. / Tetrahedron Letters 45 (2004) 8221–8224
7
. There has been a report on the oxidation of benzyl and
secondary alcohols with NaNO in an aqueous trifluoro-
10. (a) Ellis, B. Org. Syn., Coll. 1932, 1, 18–20; (b) Smith, J. R.
2
L.; Richards, D. I.; Thomas, C. B.; Whittaker, M. J.
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acetic acid afforded the corresponding carbonyl com-
pounds but it has pointed out that the oxidation products
carbonyl compounds are not further oxidized by the use of
excess sodium nitrite: Rodkin, M. A.; Shpern, M. M.;
Cheprakov, A. V.; MakhonÕkov, D. I.; Mardaleishvili, R.
E.; Beletskaya, I. P. Zh. Org. Khim. 1988, 24, 488–495.
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8
9
1991, 9, 255–283; From cyclohexane: (b) Ishii, Y.;
Iwahama, T.; Sakaguchi, S.; Nakayama, K.; Nishiyama,
Y. J. Org. Chem. 1996, 61, 4520–4526; From cyclohexene:
(
c) Sato, K.; Aoki, M.; Noyori, R. Science 1998, 281,
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be excluded as intermediates instead of B–D.
12. The used trifluoroacetic acid was recovered by the
reported procedure: Spitzer, U. A.; Stewart, R. J. Org.
Chem. 1974, 39, 3936–3937.
1646–1647; (d) Usui, Y.; Sato, K. Green Chem. 2003, 5,
373–375.
. Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis;
John Wiley and Sons: New York, 1967; p 733.