Aerobic oxidation of cyclohexane using N-hydroxyphthalimide bearing fluoroalkyl chains

Article abstract of DOI:10.1002/adsc.200800057

The N-hydroxyphthalimide derivatives, F₁₅-and F ₁₇-NHPI, bearing a long fluorinated alkyl chain, were prepared and their catalytic performances were compared with that of the parent compound, N-hydroxyphthalimide (NHPI). The oxidation of cyclohexane under 10 atm of air in the presence of fluorinated F₁₅-or F₁₇-NHPI, cobalt diacetate [Co(OAc)₂], and manganese diacetate [Mn(OAc)₂] without any solvent at 100°C afforded a mixture of cyclohexanol and cyclohexanone (K/A oil) as major products along with a small amount of adipic acid. It was found that F₁₅-and F₁₇-NHPI exhibit higher catalytic activity than NHPI for the oxidation of cyclohexane without a solvent. However, for the oxidation in acetic acid all of these catalysts afforded adipic acid as a major product in good yield and the catalytic activity of NHPI in acetic acid was almost the same as those of F₁₅-and F ₁₇-NHPI. The oxidation by F₁₅-and F₁₇-NHPI catalysts in trifluorotoluene afforded K/A oil in high selectivity with little formation of adipic acid, while NHPI was a poor catalyst under these conditions, forming K/A oil as well as adipic acid in very low yields. The oxidation in trifluorotoluene by F₁₅-and F₁₇-NHPI catalysts was considerably accelerated by the addition of a small amount of zirconium(IV) acetylacetonate [Zr(acac)₄] to the present catalytic system to afford selectively K/A oil, but no such effect was observed in the NHPI-catalyzed oxidation in trifluorotoluene.

Full text of DOI:10.1002/adsc.200800057

FULL PAPERS
DOI: 10.1002/adsc.200800057
Aerobic Oxidation of Cyclohexane using N-Hydroxyphthalimide
BearingFluoroalkyl Chains
Samar Kumar Guha,a Yasushi Obora,a Daisuke Ishihara,b Hiroshi Matsubara,b
Ilhyong Ryu,b and Yasutaka Ishiia,*
a
Department of Chemistry and Material Engineering, Faculty of Chemistry, Materials and Bioengineering & High
Technology Research Center, Kansai University, Suita, Osaka 564-8680, Japan
Fax : (+81)-6-6339-4026; e-mail: ishii@ipcku.kansai-u.ac.jp
Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
b
Received: January 25, 2008; Published online: May 9, 2008
Abstract: The N-hydroxyphthalimide derivatives, ic activity of NHPI in acetic acid was almost the
F15- and F17-NHPI, bearing a long fluorinated alkyl same as those of F15- and F17-NHPI. The oxidation
chain, were prepared and their catalytic performan- by F15- and F17-NHPI catalysts in trifluorotoluene af-
ces were compared with that of the parent com- forded K/A oil in high selectivity with little forma-
pound, N-hydroxyphthalimide (NHPI). The oxida- tion of adipic acid, while NHPI was a poor catalyst
tion of cyclohexane under 10 atm of air in the pres- under these conditions, forming K/A oil as well as
ence of fluorinated F15- or F17-NHPI, cobalt diacetate adipic acid in very low yields. The oxidation in tri-
[Co
without any solvent at 1008Cafforded a mixture of
cyclohexanol and cyclohexanone (K/A oil) as major amount of zirconium(IV) acetylacetonate [Zr
A
ACHTREUNG
AHCTREUNG
products along with a small amount of adipic acid. It to the present catalytic system to afford selectively
was found that F15- and F17-NHPI exhibit higher cat- K/A oil, but no such effect was observed in the
alytic activity than NHPI for the oxidation of cyclo- NHPI-catalyzed oxidation in trifluorotoluene.
hexane without a solvent. However, for the oxidation
in acetic acid all of these catalysts afforded adipic Keywords: aerobic oxidation; cyclohexane; fluorinat-
acid as a major product in good yield and the catalyt- ed N-hydroxyphthalimide; K/A oil
Introduction
thalimide (NHPI) combined with Co(II) for the aero-
bic oxidation of saturated hydrocarbons which is gen-
The aerobic oxidation of cyclohexane (1) is a very im- erally referred to as the Ishii oxidation system.[3] By
portant industrial process for the production of pri- the use of our catalytic system, cycloalkanes can be
mary and specialty chemicals like cyclohexanol (2), oxidized in acetic acid even at 1008Cto give oxygen-
cyclohexanone (3), and adipic acid (4).[1] Nowadays, ated products like alcohols, ketones and dicarboxylic
the aerobic oxidation of 1 leading to a mixture of 2 acids in higher conversions.[4] However, the NHPI-cat-
and 3 which is generally referred to as K/A oil is usu- alyzed aerobic oxidation of cycloalkanes like 1 with-
ally carried out under the influence of a small amount out a solvent was difficult to perform in higher con-
of cobalt salts. In the conventional autoxidation of 1 version because of the slight solubility of NHPI bear-
using cobalt catalysts, however, the reaction calls for ing a hydroxyimide (>N-OH) group in hydrophobic
operation at around 1508C.[2] Under these conditions, media like cycloalkane 1. Thus, we prepared lipophilic
the oxidation results in cleaved products like glutaric NHPI derivatives having long alkyl chains which are
acid and maleic acid as well as undesired decarboxy- easily dissolved in hydrocarbons like 1, and the aero-
lated side products. Therefore, the oxidation is usually bic oxidation of 1 without a solvent by these lipophilic
operated in lower conversion (3–5%) of 1 to keep the NHPI catalysts was found to give cyclohexanol 2 and
selectivity to K/A oil. If the aerobic oxidation of 1 is cyclohexanone 3 along with a small amount of adipic
able to run at a lower temperature of around 1008C, acid 4 in higher conversion compared with the oxida-
it is possible to carry out the reaction at higher con- tion by NHPI.[5] In continuation of our study to im-
version of 1. Fortunately, we have recently developed prove the catalytic performance of NHPI for the
a novel catalytic system consisting of N-hydroxyph- aerobic oxidation of 1, we prepared two different
Adv. Synth. Catal. 2008, 350, 1323 – 1330
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Samar Kumar Guha et al.
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types of fluorinated N-hydroxyphthalimide derivatives trimellitic anhydride (5) with O-benzylhydroxylamine
(F-NHPI), F15-NHPI and F17-NHPI, and the catalytic hydrochloride afforded N-benzyloxyphthalimide-4-
performances of these F-NHPI derivatives were com- carboxylic acid (6). Treatment of 6 with SOCl2 fol-
pared with that of the parent NHPI catalyst [Eq.(1)]. lowed by introduction of the fluorinated substituent
led to 8 which, on subsequent hydrogenation over Pd/
C, resulted in F15-NHPI in a total yield of 28%
(Scheme 1). On the other hand, F17-NHPI was pre-
pared from 4-nitrophthalic acid (9) through a 6-step
reaction involving Sandmeyer iodination and a Cu-
catalyzed coupling reaction with fluorinated alkyl
iodide as the key reactions (Scheme 2).
In order to evaluate the catalytic performances of
the fluorinated N-hydroxyphthalimide derivatives (F-
NHPI), the aerobic oxidation of 1 by F15- and F17-
NHPI catalysts was examined and compared with that
Results and Discussion
by the parent NHPI catalyst (Table 1).
The aerobic oxidation of 1 (4 mL, ca. 37 mmol) was
The fluorinated N-hydroxyphthalimide catalysts, F15- carried out under air (10 atm) in the presence of
and F17-NHPI, were prepared according to Scheme 1 NHPI (25 mmol), Co(OAc)2·4H2O (20 mmol), and
(OAc)2·4H2O (10 mmol) without any solvent at
AHCTREUNG
and Scheme 2. The reaction of commercially available Mn
ACHTREUNG
Scheme 1. Preparation of F15-NHPI.
Scheme 2. Preparation of F17-NHPI.
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Aerobic Oxidation of Cyclohexane
FULL PAPERS
Table 1. Solvent-free aerobic oxidation of cyclohexane(1) using N-hydroxyphthalimide derivatives.[a]
Entry
Catalyst
Time [h]
Yield [%][b]
Ratio
TON[c]
2
3
4
2/3
1
2
3
4
5
6
NHPI
NHPI
F15-NHPI
F15-NHPI
F17-NHPI
F17-NHPI
6
14
6
14
6
14
622
468
836
809
2035
1485
2424
trace
5
18
29
21
1.32
1.27
1.48
0.84
0.86
0.87
10.9
19.0
20.3
37.8
27.8
45.6
1060
1200
1712
1278
2108
32
[a]
Compound 1 (37 mmol) was allowed to react under air (10 atm) at 1008Cin the presence of NHPI or F-NHPI (25 mmol),
Co(OAc)2·4H2O (20 mmol), Mn(OAc)2·4H2O (10 mmol).
GCyield based on the catalyst used.
A
ACHTREUNG
[b]
[c]
TON=2+3+4 (mmol)/NHPI(or F-NHPI) (mmol).
1008Cfor 6 h or 14 h. The oxidation of 1 by NHPI for catalysts,[7] the effect of Zr species for the aerobic oxi-
6 h led to 2 (622%), 3 (468%) and a trace amount of dation of 1 by the NHPI/Co(OAc)2/Mn(OAc)2 system
4 and the total turnover number (TON) of the NHPI was examined. The results are summarized in Table 2.
was 10.9 (entry 1). The yields and turnover number By the addition of Zr(acac)4 (10 mmol) to the
(TON) were based on the catalyst used. When the re- NHPI/Co(OAc)2/Mn(OAc)2 system, 1 was converted
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
action time was prolonged to 14 h, the yields of 2, 3, to 2 (856%), 3 (794%), and 4 (12%) after 6 h and to 2
and 4 were increased to 1060%, 836% and 5%, re- (1796%), 3 (1962%), and 4 (48%) after 14 h, and the
spectively, and the TON attained was 19 (entry 2). TONs of the NHPI oxidation of 1 were increased
Under these conditions, adipic acid 4 was scarcely from 10.9 at 6 h and 19.0 at 14 h in the absence of Zr-
formed by NHPI (entries 1 and 2). In contrast to the
poor solubility of NHPI in hydrocarbon 1, the F- of Zr
NHPI catalysts were readily dissolved in cyclohexane the TONs of F15-NHPI after adding Zr
ACHTREUNG
AHCTREUNG
AHCTREUNG
1. F15-NHPI catalyst gave 2 (1200%), 3 (809%), and 4 increased from 20.3 to 35.7 at 6 h and from 37.8 to
(18%) in a TON of 20.3 after 6 h (entry 3), and 2 49.2 at 14 h (entries 3 and 4). The formation of adipic
(1712%), 3 (2035%), and 4 (29%) in a TON of 37.8 acid 4 was also increased from 29% to 160% upon
after 14 h (entry 4). Similarly, the oxidation by F17- adding Zr
ACHTREUNG
NHPI catalyst afforded 2 (1278%), 3 (1485%), and 4 considerable accelerating effect of Zr
AHCTREUNG
(21%) in a TON of 27.8 after 6 h (entry 5), and 2 served in the oxidation by F17-NHPI, and the TON
(2108%), 3 (2424%) and 4 (32%) in a TON of 45.6 for F17-NHPI at 14 h was 56.9. In particular, a remark-
after 14 h (entry 6). These results show that fluorinat- able increase of the yield of adipic acid 4 (308%) was
ed catalysts (F-NHPI) were considerably more active observed compared with the yield of 4 (32%) in the
than NHPI for the aerobic oxidation of 1. Among the absence of Zr
three catalysts examined, the F17-NHPI catalyst in-
A
volving a long fluoroalkyl chain was found to be the
Table 2. Effect of Zr
C
most active. The higher activity of F15- and F17-NHPI
compared to NHPI may be attributed to the im-
proved solubility of the F-NHPI catalysts in 1 and the
activation of N-hydroxyphthalimide groups by the in-
troduction of fluorinated substituents having a strong
electron-withdrawing effect. In general, electron-with-
drawing substituents on substituted N-hydroxyphthal-
Entry Catalyst
Time
[h]
1
2
3
4
5
6
NHPI
NHPI
F15-NHPI
F15-NHPI 14
F17-NHPI
F17-NHPI 14
6
14
6
A
drocarbons.[6] Thus, it was found that the catalytic ac-
tivity of NHPI was increased by improving the solu-
bility in 1 and by introducing an electron-withdrawing
substituent like a fluoroalkyl group. We confirmed
that no oxidation reaction took place in the absence
of NHPI.
6
[a]
Compound 1 (37 mmol) was allowed to react under air
(10 atm) at 1008Cin the presence of NHPI or F-NHPI
(25 mmol), Co
A
Since there have been several reports on the accel-
eration effect of Zr species for the aerobic oxidation
of alkylaromatic hydrocarbons like p-xylene over Co
(10 mmol), and Zr
AHCTREUNG
[b]
[c]
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Table 3. Aerobic oxidation of cyclohexane (1) in acetic acid or TFT.[a]
Entry
Catalyst
Solvent
Yield [%][b,c]
Ratio[c]
TON[c,d]
2
3
4
2/3
1
2
3
4
5
6
NHPI
AcOH
AcOH
AcOH
TFT[e]
TFT[e]
TFT[e]
2096 (1824)
2484 (2516)
2596 (2536)
1144 (828)
604 (260)
5000 (4720)
5108 (5280)
5120 (5320)
trace (trace)
120 (12)
3.47 (7.02)
2.38 (6.29)
2.25 (6.22)
1.06 (0.91)
0.62 (1.38)
0.65 (1.18)
77.0 (68.0)
86.4 (82.0)
88.7 (82.6)
22.2 (17.4)
79.2 (25.2)
92.4 (33.1)
F15-NHPI
F17-NHPI
NHPI
F15-NHPI
F17-NHPI
1044 (400)
1152 (408)
1076 (912)
4800 (1052)
5484 (1504)
2996
A
3556 (1772)
196 (36)
[a]
Compound 1 (37 mmol) was allowed to react in the solvent (4 mL) at 1008Cfor 6 h in the presence of NHPI or F-NHPI
(25 mmol), Co(OAc)2·4H2O (20 mmol), Mn(OAc)2·4H2O (10 mmol), and Zr(acac)4 (10 mmol).
GCyield based on the catalyst used.
A
G
ACHTREUNG
[b]
[c]
[d]
[e]
The numbers in parentheses show yields in the reaction without Zr
TON=2+3+4 (mmol)/NHPI(or F-NHPI) (mmol).
TFT=trifluorotoluene.
A
Partenheimer describes that the accelerating effect of (entry 4 in Table 3). However, the TON (22.2) in TFT
Zr species on the Co/Mn/Br-catalyzed aerobic oxida- was very low compared with the TON (77.0) in acetic
tion of p-xylene is a result of the strong Lewis acidity acid. This is believed to be due to the lower solubility
of Zr(IV) species that promotes the decomposition of of NHPI in TFT than that in acetic acid. In contrast,
benzyl hydroperoxide to benzaldehyde and water as the oxidation of 1 by F15- and F17-NHPI catalysts in
well as of the formation of a polynuclear Co/Mn/Zr TFT led to high TONs for F15-NHPI (79.2) and for
coordination compound.[6] In the present work, the F17-NHPI (92.4) (entries 5 and 6). Furthermore, these
effect of Zr species on the aerobic oxidation of 1 by TONs for the F15- and F17-NHPI catalysts in TFT
NHPI and F-NHPI derivatives seems to be similar to were similar to those in acetic acid, probably because
those pointed out by Partenheimer for the aerobic ox- both catalysts can be readily dissolved in TFT solvent.
idation of alkylaromatic hydrocarbons, but it needs Another important feature of the oxidation by F-
more detailed study to reveal the actual effect of the NHPI catalysts in TFT is that the formation of adipic
Zr species on the present oxidation.
acid 4 was markedly suppressed in TFT compared
In order to probe the influence of the polarity of with acetic acid (entries 2, 3, 5, and 6). These results
solvents, we next examined the oxidation of 1 by suggest that the solvent used is a crucial factor to de-
NHPI and F-NHPI catalysts in acetic acid (Table 3). termine the product selectivity and the catalyst per-
As expected, NHPI is readily dissolved in acetic acid formance for the oxidation of 1. It is interesting to
and 1 was smoothly oxidized to give 2 (1824%), 3 note that there is no considerable addition effect of
(260%), and 4 (4720%) in higher yields as compared Zr
with the oxidation of 1 without solvent. The TON of tion of 1 in TFT (entry 4), while a remarkable acceler-
the NHPI oxidation was considerably increased from ation effect of Zr(acac)4 was observed in the oxida-
10.9 without solvent (entry 1 in Table 1) to 68 in tion by F-NHPI in TFT (entries 5 and 6).
(acac)4 on the NHPI catalyst system in the oxida-
AHCTREUNG
acetic acid (entry 1). It is noteworthy that adipic acid
The features of the oxidation of 1 by NHPI and F-
4 was obtained as a major product in preference to 2 NHPI in acetic acid and TFT may be illustrated as
and 3 (entry 1). A similar tendency was also observed shown below (Scheme 3).
in the oxidations by F15- and F17-NHPI catalysts in
In the case of the aerobic oxidation using acetic
acetic acid (entries 2 and 3). The TON for the oxida- acid as a solvent, NHPI and F-NHPI as well as sub-
tion of 1 by F17-NHPI in acetic acid was 82.6 strate 1 are easily dissolved in acetic acid, and the oxi-
(entry 3). The fact that the ratio of 2 to 3 in acetic dation of 1 is thought to proceed smoothly to give cy-
acid was approximately 6 to7 indicates that cyclohexa- clohexanol 2 and cyclohexanone 3 (1st stage). Since
none 3 was oxidized in preference to 2 to give adipic the resulting 2 and 3, which are also easily dissolved
acid 4.
in the solvent, are more reactive than cycloalkane 1,
It is very attractive to compare the aerobic oxida- they are further oxidized with ease to give adipic acid
tion of 1 by NHPI with that by the F-NHPI catalysts 4 as a main product (2nd stage). In the oxidation in
in several solvents under the same reaction conditions acetic acid, all of the compounds involving NHPI and
(Table 3). The oxidation of 1 by NHPI in trifluoro- F-NHPI catalysts used are readily dissolved in acetic
A
extent compared with that in the absence of solvent, and 3 would be smoothly oxidized by both catalysts
and the TON of the reaction was increased from 16.6 to give adipic acid 4 in a similar extent. Therefore,
without solvent (entry 1 in Table 2) to 22.2 in TFT there seems to be no considerable difference in the
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Aerobic Oxidation of Cyclohexane
FULL PAPERS
Scheme 3. Illustration of the selectivity for the aerobic oxidation of 1 in AcOH and TFT.
Figure 1. Time-conversion curves of the aerobic oxidation of 1 with NHPI, F15-NHPI, and F17-NHPI catalyst system. Reac-
tion conditions were the same as entry 2 (for NHPI), entry 4 (for F15-NHPI), and entry 6 (for F17-NHPI) in Table 2.
Adv. Synth. Catal. 2008, 350, 1323 – 1330
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Samar Kumar Guha et al.
FULL PAPERS
spectra were obtained at an ionization energy of 70 eV. The
yields of products were estimated from the peak areas on
the basis of the internal standard technique by the use of
GC.
catalytic performance of the NHPI and F-NHPI for
the oxidation of 1. On the other hand, in the oxida-
tion of 1 by F-NHPI in TFT, since both F-NHPI and
1 can be readily dissolved in TFT, 1 would be oxi-
dized to 2 and 3 (1st stage). However, it is thought
that the generated 2 and 3 may be excluded to the
outer sphere of TFT, because they, in particular 2, are
difficult to be dissolved in TFT. In fact, a mixture of 2
and TFT gave a cloudy solution. As a result, the oxi-
dation of the 2nd stage by F-NHPI in TFT may be
negligibly small. Therefore, the oxidation of 1 by F-
NHPI in TFT is thought to lead to 2 and 3 in high se-
lectivity with little formation of 4.
The highest TON (92.4) was obtained in the oxida-
tion by F17-NHPI in TFT rather than acetic acid
(entry 6). Therefore, the oxidation of 1 by fluorinated
NHPI catalysts in TFT would provide to an attractive
selective route to the K/A oil, in particular to 3.
These results show that fluorinated groups, possessing
strong electron-withdrawing character and lipophilici-
ty play dual functions, i.e., the activation of the N-hy-
droxyphthalimide group and increasing of the solubil-
ity in 1 and TFT of the catalyst.
General Procedure for the Oxidation of Cyclohexane
(1) under Air
Cyclohexane (4 mL, ca. 37 mmol), NHPI derivatives (25
mmol), Co
N
N
Teflon-coated autoclave, and 10 atm of air was charged.
After stirring at 1008Cfor 6 h, the mixture was cooled to
room temperature, diluted with ethanol, and GCanalysis
was performed to determine the amount of cyclohexanol,
cyclohexanone, and the unreacted cyclohexane. After re-
moval of the solvent under reduced pressure, a catalytic
amount of concentrated sulfuric acid and ethanol (10 mL)
were added to the resulting mixture, and the solution was
stirred at 1008Cfor 15 h. The resulting solution was cooled
to room temperature, and GCanalysis was performed to de-
termine the yield of adipic acid.
Preparation of (2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-Pentadeca-
fluoro)-octyl N-Benzyloxyphthalimide-4-carboxylate
(8)
Figure 1 shows the time-conversion curves of the
aerobic oxidation of 1 by the three catalytic systems.
In the oxidation by the NHPI/Mn(II)/Co(II)/
To
a solution of O-benzylhydroxylamine hydrochloride
(1.60 g, 10 mmol) in pyridine (32 mL) was added trimellitic
Zr(IV), the yields of 2 and 3 were linearly increased anhydride (5) (1.92 g, 10 mmol) slowly at room temperature.
When all the trimellitic anhydride had dissolved in the solu-
tion, the reaction mixture was refluxed for 14 h. Then it was
cooled to room temperature, and acidified with 4M HCl so-
lution. The organic substances were extracted with EtOAc
(60 mLꢁ3), followed by washing with 1M HCl solution, and
dried over Na2SO4. After evaporating the solvent at reduced
pressure, the crude N-benzyloxythalimide-4-carboxylic acid
(6) was obtained; yield: 2.7 g (9.09 mmol).
with time and the ratio of 2 to 3 was close to unity
during the oxidation. On the other hand, in the oxida-
tion by the F15- and F17-NHPI/Mn(II)/Co(II)/Zr(IV)
systems, 2 and 3 were rapidly formed up to 6 h, but
the rate of formation rate of these products became
slower as time proceeded, which is probably due to
degradation of the catalyst.
Then compound 6 was dissolved in toluene (50 mL), and
thionyl chloride (3.98 mL, 54.54 mmol) and a catalytic
amount of DMF (0.1 mL) were added to the mixture at
room temperature. The reaction mixture was stirred at 808C
for 3 h. Then it was cooled to room temperature, and the
excess thionyl chloride and toluene was evaporated by distil-
lation under reduced pressure. The resulting residue was
washed with hexane (10 mLꢁ3), and dried under vacuum to
afford 7.
Conclusions
We have prepared N-hydroxyphthalimide derivatives
(F15- and F17-NHPI) bearing a long fluorinated alkyl
chain. The F15- and F17-NHPI catalysts efficiently pro-
moted the aerobic oxidation of cyclohexane 1. The
oxidation by F15- and F17-NHPI catalysts in TFT pro-
vides a useful synthetic method for K/A oil from cy-
clohexane 1 under mild conditions.
Then, to a suspension of NaH (0.33 g, 8.25 mmol, ca.
60%) in THF (20 mL) was added
a
solution of
2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluoro-1-octanol (3.3 g,
8.25 mmol) in THF (10 mL) at room temperature under
argon atmosphere. After stirring 15 min at 408C, the solu-
tion of 7 (2.6 g, 8.25 mmol) in THF (30 mL) was added to
the reaction mixture. After stirring for 1.5 h at 408Cand at
reflux for 5 h, the mixture was cooled to room temperature,
acidified with 1M HCl solution, and Et2O (80 mL) was
added. The organic layer was separated and dried over
Na2SO4. After evaporating the solvent at reduced pressure,
the crude product was purified by silica gel column chroma-
tography (n-hexane/EtOAc=5/1) to afford 8 in a pure form;
yield: 2.31 g (34% over 3 steps). 1H NMR (270 MHz,
CDCl3): d=4.89 (t, J=13.2 Hz, 2H), 5.22 (s, 2H), 7.33–7.45
(m, 3H), 7.47–7.57 (m, 2H), 7.93 (dd, J=7.3, 1.4 Hz, 1H),
Experimental Section
General Methods
The starting materials are commercially available and used
without further purification. GCanalysis was performed
with a flame ionization detector using a 0.2 mmꢁ30 mm ca-
pillary column (OV-17). H NMR, 13CNMR and 19F NMR
1
spectra were measured in CDCl3, C DOD, or acetone-d6
3
with Me4Si or CFCl3 (for 19F) as the internal standard. Infra-
red (IR) spectra were measured using KBr pellets. Mass
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Aerobic Oxidation of Cyclohexane
FULL PAPERS
8.44 (dd, J=7.3, 1.4 Hz, 2H); 13C NMR (67.5 MHz, CDCl3):
d=60.7, 80.0, 110.6, 114.4, 123.7, 124.7, 128.5, 129.2, 129.4,
129.9, 133.0, 133.2, 133.9, 136.0, 162.0, 162.1, 162.8; MS:
m/z=679 [M+], 660, 649, 573, 554, 530, 280, 174, 91.
A mixture of 12 (5.01 g), Cu (2.81 g), 2,2-bipyridine
(0.48 g) and DMSO (20 mL) was stirred at 1108Cfor 32 h
under argon. After being cooled down the reaction, it was
filtered using celite and the organic substances were extract-
ed with Et2O, followed by washing with brine and dried
over Na2SO4. The crude product was purified by silica gel
column chromatography using CHCl3 as the eluent to afford
13 as a yellow solid; yield: 7.62 g (83%).
A mixture of 13 (0.50 g), 30% KOH solution (15 mL),
and EtOH (10 mL) was stirred at 908Cfor 24 h. Then the
reaction mixture was concentrated until the volume was re-
duced to ca. 10 mL and acidified by concentrated HCl. The
resulting mixture was then filtered, washed with CHCl3, and
evaporated the solvent to afford 14 as a white solid; yield:
0.455 g (99.5%).
Preparation of (2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-Pentadeca-
fluoro)-octyl N-Hydroxyphthalimide-4-carboxylate
(F15-NHPI)
To a solution of 8 (554 mg, 0.82 mmol) in EtOAc (12 mL)
was added palladium on activated carbon (10%, 30 mg)
under argon. The flask was charged with hydrogen gas, and
the solution was stirred under an atmosphere of hydrogen at
458Cfor 4 h. Then the mixture was cooled to room temper-
ature and filtered. The filtrate was evaporated under re-
duced pressure, and the resulting product was purified by
silica gel column chromatography (n-hexane/EtOAc=2/1 to
1/1) and F15-NHPI was obtained in the pure form; yield:
A mixture of 14 (2.51 g) and Ac2O (4 mL) was stirred for
15 min at 1508C. After cooling to room temperature, the re-
action mixture was concentrated. Pyridine (8 mL) and
NH2OH·HCl (0.341 g) were added to the resulting solid and
stirred for 14 h at 958C. After cooling the reaction mixture,
it was concentrated and was acidified by concentrated HCl.
The resulting mixture was then filtered and washed with
CHCl3. A dark-brown solid was obtained, which on recrys-
tallization from EtOH afforded pure F17-NHPI as a pale
1
0.393 g (82%). H NMR (270 MHz, CD3OD): d=5.08 (t, J=
13.5 Hz, 2H), 7.99 (dd, J=7.6, 0.5 Hz, 1H), 8.34–8.40 (m,
1H), 8.46 (dd, J=7.6, 1.6 Hz, 1H); 13CNMR (67.5 MHz,
CD3OD): d=61.5, 116.4, 124.6, 124.7, 130.6, 131.2, 131.7,
132.4, 134.9, 135.2, 137.0, 164.4, 164.6; IR (KBr): n=3547,
2361, 1788, 1721, 1204, 1145, 710 cmÀ1; anal. calcd. for
C17H6F15NO5: C34.65, H 1.03, N 2.38; found: C34.38, H
1.12, N 2.55.
1
yellow solid; yield: 1.22 g (49%). H NMR (500 MHz, ace-
tone-d6): d=8.15 (s, 1H), 8.17 (d, J=7.8 Hz, 1H,), 8.27 (d,
J=7.8 Hz,1H); 13CNMR (125 MHz, acetone- d6): d = 121.2,
123.8, 130.5, 133.3, 162.6, 162.7; 19F NMR (471 MHz, ace-
tone-d6): d=À126.6, À123.2, À122.3, À122.2, À121.8,
Preparation of 4-(1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-Hep-
tadecafluoro)octyl-N-hydroxyphthalimide (F17-NHPI)
À121.5, À110.8, À81.6; IR (KBr): n=3275, 1786, 1734 cmÀ1
anal. calcd. for C16H4F17NO3: C33.07, H 0.69, N 2.41; found:
C33.05, H 0.77, N 2.64.
;
To a solution of 4-nitrophthalic acid (9) (25.0 g) in EtOH
(200 mL) was added concentrated H2SO4 (10 mL) dropwise
and the reaction mixture was stirred at 1008Cfor 24 h.
After cooling the reaction mixture to room temperature, the
organic substances were extracted three times with Et2O,
followed by washing with saturated NaHCO3 solution, and
dried over Na2SO4. The solvent was evaporated and 4-nitro-
phthalic acid diethyl ester 10 was obtained as a dark-brown
oil; yield: 31.13 g (98%).
To a solution of 10 (31.13 g) in EtOH (400 mL) was
added Pd/C(1.02 g) under argon. Then the flask was
charged with hydrogen gas and the reaction mixture was
stirred for 23 h at room temperature under a hydrogen at-
mosphere. The reaction mixture was then filtered by using
celite, and the filtrate was evaporated under vacuum. The
compound 4-aminophthalic acid diethyl ester 11 was ob-
tained as a yellow solid; yield: 25.16 g (91%).
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search on Priority Areas “Advanced Molecular Transforma-
tion of Carbon Resources” from the Ministry of Education,
Culture, Sports, Science and Technology, Japan, “High-Tech
Research Center” Project for Private Universities: matching
fund subsidy from the Ministry of Education, Culture, Sports,
Science and Technology, 2005–2009, and Research Associa-
tion forIshii Oxidation Technology.
Dilute HCl (200 mL) was added slowly to the flask con-
taining 11 (24.99 g). The reaction mixture was stirred at References
room temperature for 1 h, and cooled down to À108C. Then
a solution of NaNO2 (11.18 g) in H2O (70 mL) was added
slowly to the reaction mixture at 58Cand stirred for 30 min
at À108C. The resulting mixture was added slowly to anoth-
er flask containing a solution of KI (35.96 g) in H2O
(300 mL). After finishing the addition, the mixture was
stirred for 30 min. Then the organic layer was extracted for
3 times by Et2O, followed by washing with saturated
Na2S2O3 solution, and dried over Na2SO4. After filtration
and evaporation of the solvent, the resulting crude product
was purified by silica gel column chromatography with
CHCl3 as an eluent and 4-iodophthalic acid diethyl ester 12
was obtained as a brown oil; yield: 29.3 g (80%).
[1] a) C. Park, J. R. Sheehan, in: Kirk-Othmer Encyclopedia
of Chemical Technology, 4th edn., Vol. 18, (Eds.: J. I.
Kroschwite, M. Howe-Grant), John Wiley and Sons,
New York, 1996, pp 991–1043; b) J. R. Sheehan, in: Ull-
mannꢀs Encycropedia Industrial Organic Chemicals, Vol.
8, Wiley-VCH, Weinhelm, 1999, pp. 4575–4591; c) A. K.
Suresh, M. M. Sharma, T. Sridhar, Ind. Eng. Chem. Res.
2000, 39, 3958.
[2] a) G. W. Parshall, S. D. Ittel, Homogeneous Catalysis,
2nd edn., Wiley, New York 1992; b) K. Weissermel, H.-
J. Arpe, Industrial Organic Chemistry, 4th edn., Wiley-
VCH, Weinheim, 2003, pp 239–246.
Adv. Synth. Catal. 2008, 350, 1323 – 1330
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1329

Samar Kumar Guha et al.
FULL PAPERS
[3] a) A. E. Shilov, G. B. Shul’pin, Activation and Catalytic
Reactions of Saturated Hydrocarbons in the Presence of
Metal Complexes, Kluwer Academic Publishers, Dor-
drecht, The Netherlands 2000, p 55 and 388; b) F. Recu-
pero, C. Punta, Chem. Rev. 2007, 107, 3800; c) Y. Ishii, S.
Sakaguchi, Catal. Today 2006, 117, 105.
[4] a) Y. Ishii, K. Nakayama, M. Takeno, S. Sakaguchi, T.
Iwahama, Y. Nishiyama, J.Org. Chem. 1995, 60, 3934;
b) Y. Ishii, T. Iwahama, S. Sakaguchi, K. Nakayama, Y.
Nishiyama, J. Org. Chem. 1996, 61, 4520; c) Y. Ishii, S.
Sakaguchi, T. Iwahama, Adv. Synth. Catal. 2001, 343,
393.
[5] N. Sawatari, T. Yokota, S. Sakaguchi, Y. Ishii, J. Org.
Chem. 2001, 66, 7889.
[6] B. B. Wentzel, M. P. J. Donners, P. L. Alsters, M. C. Feit-
ers, R. J. M. Norte, Tetrahedron 2000, 56, 7797.
[7] a) A. W. Chester, E. J. Y. Scott, P. S. Landis, J. Catal.
1977, 46, 308; W. Partenheimer, J. Mol. Cat. A: Chemical
2003, 206, 105 and 131; b) B. Saha, J. H. Espenson, J.
Mol. Cat. A: Chemical 2007, 271, 1; c) N. Hirai, Y. Tatsu-
kawa, M. Kameda, S. Sakaguchi, Y. Ishii, Tetrahedron
2006, 62, 6695.
[8] W. Partenheimer, Catal. Today 1995, 23, 69.
1330
asc.wiley-vch.de
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 1323 – 1330