Solvent-free aerobic chemoselective oxidation of β-ionone catalyzed by N-hydroxyphthalimide/Co(acac)2

Article abstract of DOI:10.1080/00397910701857568

β-Ionone was oxidized with O2 under solvent-free conditions catalyzed by an N-hydroxyphthalimide/Co(acac)2 system in mild conditions with high conversion and excellent selectivity to oxo-β-ionone or 5,6-epoxy-β-ionone in different reaction conditions, respectively. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701857568

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Solvent‐Free Aerobic Chemoselective
Oxidation of β‐Ionone catalyzed by
N‐Hydroxyphthalimide/Co(acac)
Nian‐hua Gong , Rui‐Ren Tang , Ya‐ping Zhou & Hai‐feng Xu
2
a
a
a
a
a
School of Chemistry and Chemical Engineering, Central South University ,
Changsha, China
Published online: 12 Mar 2008.
To cite this article: Nian‐hua Gong , Rui‐Ren Tang , Ya‐ping Zhou & Hai‐feng Xu (2008) Solvent‐Free
Aerobic Chemoselective Oxidation of β‐Ionone catalyzed by N‐Hydroxyphthalimide/Co(acac) , Synthetic
2
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:7,
1020-1027, DOI: 10.1080/00397910701857568
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Synthetic Communications , 38: 1020–1027, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701857568
Solvent-Free Aerobic Chemoselective
Oxidation of b-Ionone catalyzed by
N-Hydroxyphthalimide/Co(acac)2
Nian-hua Gong, Rui-Ren Tang, Ya-ping Zhou,
and Hai-feng Xu
School of Chemistry and Chemical Engineering, Central South
University, Changsha, China
Abstract: b-Ionone was oxidized with O under solvent-free conditions catalyzed by
2
2
an N-hydroxyphthalimide/Co(acac) system in mild conditions with high conversion
and excellent selectivity to oxo-b-ionone or 5,6-epoxy-b-ionone in different reaction
conditions, respectively.
Keywords: Aerobic oxidation, 5,6-epoxy-b-ionone, N-hydroxyphthalimide, oxo-b-
ionone, solvent free
Oxidation of olefins in particular is a key reaction in the synthesis of complex
[1]
organic molecules and fine chemicals. Selective catalytic oxygenation of
hydrocarbons with dioxygen as the terminal oxidant is a fundamental indus-
trial technology; its economical and environmentally benign nature attracts
[
2]
much attention. In recent years, the novel catalytic aerobic oxidation
system using N-hydroxyphthalimide (NHPI) and its analogs as the key
catalyst combined with some cocatalysts, including transition metals Co,
Mn, and Cu, and some free radical initiators, benzoyl peroxide (BPO) and
Received in Japan May 12, 2007
Address correspondence to Rui-Ren Tang, School of Chemistry and Chemical
Engineering, Central South University, Changsha 410083, China. E-mail: trr@mail.
csu.edu.cn
1
020

Aerobic Chemoselective Oxidation of b-Ionone
1021
0
2
variety of hydrocarbons.
,2 -azobisisobutyronitrile (ABIN), catalyze molecular oxygen and oxidize a
[
3–10]
b-Ionone (1) was oxidized to 4-oxo-b-ionone (2) and 5,6-epoxy-b-ionone
3), which are valuable flavors and chemical intermediates, extensively used
(
in food, makeup, fragrances and medication.
[11,12]
Many methods have been
developed for conversion of b-ionone to the corresponding 4-oxo-b-ionone
or 5,6-epoxy-b-ionone. They can be prepared through oxidizing b-ionone
[
13]
[14]
by NaIO /NaI.
Au/ZSM-5 zeolite can catalyze molecular oxygen
and copper halide or active copper powder can catalyze tert-butyl alcohol
3
[
15]
peroxide,
but most oxidation reactions in organic chemistry are contradic-
tory to the principles of green chemistry and sustainable developments
because of their low yields, lack of selectivity, and use of toxic and volatile
organic solvents. Therefore, there is great interest in developing a new
efficient and environmentally benign catalytic procedure for oxidation of
b-ionone using inexpensive and nonpolluting O2.
It is the first report of chemoselective aerobic oxidation of b-ionone 1 by
NHPI/Co(acac) at ambient conditions under solvent-free conditions to obtain
a high conversion (almost 100%) and excellent selectivity of 4-oxo-b-ionone
2
2
or 5,6-epoxy-b-ionone 3, respectively by changing the reaction conditions
Scheme 1).
The reaction process can be interpreted as Scheme 2. The substrate 1 by
oxidizing first creates hydroxypeoxide 4, which has two transformation forms.
(
[
16,17]
Hydropeoxide 4 can be utilized as oxidant,
substrate 1 to obtain epoxide 3; at the same time, hydropeoxide 4 can be
oxidizing double-band of
[18]
decomposed to get the ketone 2 and alcohol 5,
translated rapidly to ketone 2 with NHPI as catalyst with Co(acac) . If the
and the alcohol 5 can be
2
decomposition rate of hydropeoxide 4 is more rapid than the catalyzing
oxidation rate, the main product will be oxo-b-ionone; otherwise, the main
product will be the epoxy-b-ionone.
First, we study the influences of the amount of the catalyst NHPI with
Co(acac)2 on the catalytic oxidation of b-ionone with dioxygen under
solvent-free conditions.
Table 1 shows the influences of NHPI. The reaction of 1 by Co(acac)2
alone at 858C takes place to give 2 (28.9% selectivity) and 3 (71.1% selectiv-
ity), and the selectivity of 2 rises slowly as the amount of NHPI increasing
from 5 mol% to 10 mol%. When NHPI added is increased to 20 mol%, the
Scheme 1.

1
022
N.-h. Gong et al.
Scheme 2.
selectivity of 2 enhances remarkably and reaches 71.6%. A larger amount
NHPI (30 mol%) results in no improvement of the final selectivity of 2
(72.3%). Along with increasing the NHPI amount, the reaction time is
prolonged.
Table 1. Effect of quantity of NHPI on aerobic oxidation
Select (%)
NHPI
(mol%)
Time
(h)
Run
2
3
1
2
3
4
5
0
10
6
28.9
35.7
40.1
71.6
72.3
71.1
64.3
59.9
28.4
27.7
5
10
20
30
6.5
7.7
8
Note. Conditions: 1 (10 g, 0.52 mol), Co(acac) (0.15 g,
2
1
2
mol%), O (1 atm), and no solvent at 858C.

Aerobic Chemoselective Oxidation of b-Ionone
1023
Table 2. Effect of quantity of Co(acac)
dation of 1
2
on aerobic oxi-
Select (%)
Co(acac)2
(mol%)
Time
(h)
Run
2
3
1
2
3
4
5
6
0
0.2
0.5
1
12.8
11.5
10.5
7.7
7.5
7
43.6
61.4
63.4
71.6
69.7
50.3
56.4
38.6
36.6
28.4
30.3
49.7
2
4
Note. Conditions: 1 (10 g, 0.52 mol), NHPI (1.72 g,
0 mol%), O (1 atm), and no solvent at 858C.
2
2
The influence of quantity of Co(acac) on aerobic oxidation of 1 is
2
presented in Table 2. In the absence of Co(acac) , 1 is directly oxygenated,
2
giving only 43.6% of 2 but 56.4% of 3 by NHPI (20 mol%) catalyzing at
8
is clearly much less than that of NHPI, because with the oxidation of 1 in the
58C. However, the effect of the concentration of Co(acac) as the cocatalyst
2
presence of NHPI (20 mol%) with Co(acac) (1 mol%) the result is almost the
2
same as with 2 mol%, but the reaction time is shortened gradually.
To carry out the reaction at optimum conditions, the effect of the tempera-
ture on aerobic oxidation of 1 is also investigated, and the results are shown in
Table 3.
At 708C, 14 h are necessary to get 48.6% selectivity of 2 and 51.4% selec-
tivity of 3. At 858C, 71.6% selectivity of 2 is obtained after 7.7 h. At 1008C,
the selectivity of 2 is 50.5% in less than 6.5 h. These results clearly indicate
Table 3. Effect of temperature on aerobic oxidation of 1
by NHPI/Co(acac)
2
Select (%)
Temp
(8C)
Time
(h)
Run
2
3
1
2
3
4
5
6
70
80
12.5
10
48.6
54.5
71.6
69.8
65.4
50.5
51.4
45.5
28.4
30.2
34.6
49.5
85
90
7.7
7.2
7
95
100
6.5
Note. Conditions: 1 (10 g, 0.52 mol), NHPI (1.72 g,
0 mol%), Co(acac) (0.15 g, 1 mol%), O (1 atm), and no
2
solvent.
2
2

1
024
Table 4. Effect of additives on oxidation of 1 by NHPI combined Co(acac)
Select (%)
N.-h. Gong et al.
2
Time
(h)
Run
Additive
Mol%
2
3
1
2
3
4
BPO
BPO
Pyridine
1
2
10
8
68.7
49.7
59.2
55.6
15.6
49.0
31.3
50.3
40.8
44.4
84.4
51.0
2
10.5
11
p-Toluene sulfonic acid
NHSI
LiCl
2
a
5
10
1
12.7
4.5
6
Note. Conditions: 1 (10 g, 0.52 mol), NHPI (1.72 g, 20 mol%), Co(acac)
mol%), O (1 atm), and no solvent at 858C.
NHSI in place of NHPI.
2
(0.15 g,
1
2
a
that catalysis by NHPI/Co(acac) is more rapid at a higher temperature, but
2
the excellent selectivity of 2 is obtained at moderate temperature (858C).
[
19]
Figiel et al.
catalyst, resulting in higher conversion and selectivity. To obtain further
reported that LiCl might increase the activity of the
insight into the present reaction, the oxidation is followed by NHPI/
Co(acac) combined with some additives at 858C. The results are displayed
in Table 4.
2
On the basis of these results, it can be concluded that a neutral circum-
stance is better for this chemoselective oxidation reaction. Under acid or
basic conditions or a small amount of BPO, the results are similar and have
poor selectivity. However, it is notable and interesting that when N-hydroxy-
succinimide (NHSI) is employed instead of NHPI, compound 3 (84.4%) is
formed as the principal product along with compound 2 (15.6%), showing
an excellent selectivity to 3. The oxidation of 1 by NHPI/Co(acac) is only
2
remarkably accelerated by the addition of a small amount of LiCl in less
than 4.5 h.
Table 5. Effect of the pressure on oxidation of 1 by NHPI
combined Co(acac)
2
Select (%)
Pressure
(MPa)
Temp.
(8C)
Time
(h)
Run
2
3
1
2
3
3
2
1
85
85
85
2.7
3.5
4.5
82.1
75.2
72.2
17.9
25.8
27.8
Note. Condition: 1 (10 g, 0.52 mol), NHPI (1.72 g,
0 mol%), Co(acac) (0.15 g, 1 mol%), and no solvent at
2
8
2
58C.

Aerobic Chemoselective Oxidation of b-Ionone
1025
The optimum amount of 1 and NHPI/Co(acac) are further employed
2
to catalyze oxygenation of 1 under the same conditions except for pressure
in order to get better selectivity of 2, and the results are presented in Table 5.
The high pressure exhibits excellent selectivity of 2. When the pressure
reaches to 3 MPa, the reaction obtains 82.1% selectivity for 2 and the
reaction time also shortens to about 3 h, but if the pressure too high, as the
experimental equipment is limited in our laboratory, it will be unsafe.
In conclusion, we have succeeded in the oxidation of b-ionone under
mild conditions in the absence of any solvent by NHPI combined with
Co(acac) and got high conversion and selectivity: with higher pressure
2
(3 MPa), the more NHPI (20 mol%), and the moderate temperature (858C)
with Co(acac) (1 mol%), we can obtain 82.1% selectivity of 4-oxo-b-ionon
2
2
under an atmosphere of O (1 atm) we mainly get 5,6-epoxy-b-ionone 3
; but using NHSI (10 mol%) instead of NHPI with Co(acac) (1 mol%)
2
2
(84.4%). This method would provide an interesting approach to oxidize
the unsaturated ketones or epoxides in industrial chemistry, although
further improvement of the catalyst is needed to run the reaction on a
practical scale.
EXPERIMENTAL
b-Ionone and catalysts were purchased from a commercial source and used
without further treatment. Gas Chromatography (GC) was performed with a
flame ionization detector using a 0.2-mm ꢀ 30-m capillary column (OV-
1
7). H NMR spectra were measured using Me Si as the internal standard.
1
4
Infrared (IR) spectra were measure using KBr pellets. Gas chromatography-
mass spectra united (GC-MS) spectra were obtained at an ionization energy
of 70 eV. The selectivity of products was estimated from the peak areas
based on the internal standard technique using GC. Oxo-b-ionone and 5,6-
epoxide-b-ionone are known compounds and were identified by comparison
spectra and physical data with those of Refs. (11, 20, 21).
General Procedure for Oxidation of b-Ionone with O by NHPI/
2
Co(acac) without Solvent
2
A definite amount of b-ionone, NHPI, and Co(acac) were placed in a three-
2
necked flask under an atmosphere of O (1 atm) or an autoclave under high
2
pressure. The mixture was stirred at the temperatures for the reported times.
The progress of the reaction was monitored by thin-layer chromatography
(TLC). After the substrate completely converted into products, the sample
was taken to GC-MS. The reaction mixture was added to appropriate CCl4
and stirred at 408C for 1 h, and the precipitate was filtered off after cooling
the reaction mixture to room temperature to recover partial NHPI. The

1
026
N.-h. Gong et al.
filtrate was evaporated on a rotary evaporator, and the oily residue was
separated by flash chromatography on silica to yield pure product 2 and 3.
ACKNOWLEDGMENTS
Financial support from the National Natural Science Foundation of China (No.
50573019) is gratefully acknowledged.
REFERENCES
1
2
3
. Shing, T. K. M.; Yeung, Y. Y.; Su, P. L. Mild manganese (III) acetate catalyzed
allylic oxidation: Application to simple and complex alkenes. Org. Lett. 2006,
8
(14), 3149.
. Yang, G. Y.; Zhang, Q. H.; Miao, H.; Tong, X. L.; Xu, J. Selective organocatalytic
oxygenation of hydrocarbons by dioxygen using anthraquinones and N-hydroxy-
phalimide. Org. Lett. 2005, 7 (2), 263.
. Minisci, F.; Recupero, F.; Pedulli, G. F.; Lucarini, M. Transition metal salts
catalysis in the aerobic oxidation of organic compounds: Thermochemical and
kinetic aspects and new synthetic developments in the presence of N-hydroxy-
derivative catalysts. J. Mol. Catal. A: Chem. 2003, 204–205, 63.
. Sheldon, R. A.; Arends, I. W. C. E. Organocatalytic oxidations mediated by
nitroxyl radicals. Adv. Synth. Catal. 2004, 346, 1051.
. Ishii, Y.; Sakaguchi, S. Recent progress in aerobic oxidation of hydrocarbons by N-
hydroxyimides. Catal. Today 2006, 117, 105.
. Baucherel, X.; Arends, I. W. C. E.; Ellwood, S.; Sheldon, R. A. A new catalytic
system for the selective aerobic oxidation of large ring cycloalkanes to ketones.
Org. Prog. Res. Devel. 2003, 7, 426.
4
5
6
7
. Hara, T.; Iwahama, T.; Sakaguchi, S.; Ishii, Y. Catalytic oxyalkylation of alkenes
with alkanes and molecular oxygen via a radical process using N-hydroxyphthali-
mide. J. Org. Chem. 2001, 66, 6425.
8
. Nechab, M.; Einhorn, C.; Einhorn, J. New aerobic oxidation of benzylic
compounds: Efficient catalysis by N-hydroxy-3,4,5,6-tetraphenylphthalimide
(NHTPPI)/CuCl under mild conditions and low catalyst loading. Chem.
Commun. 2004, 4 (13), 1500.
9
. Yokota, T.; Sakaguchi, S.; Ishii, Y. Synthesis of aromatic aldehydes by aerobic
oxidation of hydroaromatic compounds and diarylalkanes using N-hydroxyphtha-
limide (NHPI) as a key catalyst. Tetrahedron 2006, 62, 2497.
1
1
0. Sawatari, N.; Yokota, T.; Sakaguchi, S.; Ishii, Y. Alkane oxidation with air
catalyzed by lipophilic N-hydroxyphthalimide without any solvent. J. Org.
Chem. 2001, 66, 7889.
1. Aleu, J.; Brenna, E.; Fuganti, C.; Serra, S. Lipase-mediated synthesis of the enan-
tiomeric forms of 4,5-epoxy-4,5-dihydro-a-ionone and 5,6-epoxy-5,6-dihydro-b-
Ionone. A new direct access to enantiopure(R)- and (S)-a-ionone. J. Chem. Soc.,
Perkin Trans. 1. 1999, 999 (3), 271.
1
2. Babler. C-15 phosphonate reagent compositions for the manufacture of
compounds such as canthaxanthin and methods of synthesizing the same. US
Patent 5952519, 1999.

Aerobic Chemoselective Oxidation of b-Ionone
1027
1
1
3. Liu, C. H.; Luo, Y. M.; Tang, R. R.; Yang, H. W. Study on oxidation of b-ionone
by sodium chlorate. Chem. React. Engin. Technol. 2005, 21 (5), 437.
4. Peng, Z. G.; L u¨ , G. X. Synthesis of nanometer Au/ZSM-5 catalyst and its catalytic
performance for oxidation of b-ionone with molecular oxygen. Chin. J. Catal.
2007, 28 (3), 240.
1
1
1
1
5. Peng, Q. R.; Yang, M.; Xie, R. G.; Song, Z. X.; Wang, D. S.; Cai, Y. Q. Synthesis
of ketone-substituted alpha-ionone, ketone-substituted beta-ionone, ether and ester
derivative by one-step method. CN Patent 1817842, 2006.
6. Iwahama, T.; Hatta, G.; Sakaguchi, S.; Ishii, Y. Epoxidation of alkenes using alkyl
hydroperoxides generated in situ by catalytic autoxidation of hydrocarbons with
dioxygen. Chem. Commun. 2000, 2, 163.
7. Iwahama, T.; Sakaguchi, S.; Ishii, Y. Epoxidation of alkenes using dioxygen in the
presence of an alcohol catalyzed by N-hydroxyphthalimide and hexafluoroacetone
without any metal catalyst. Chem. Commun. 1999, 999 (8), 727.
8. Iwahama, T.; Yoshino, Y.; Keitoku, T.; Sakaguchi, S.; Ishii, Y. Efficient oxidation
of alcohols to carbonyl compounds with molecular oxygen catalyzed by
N-hydroxyphthalimide combined with a Co specials. J. Org. Chem. 2000,
65 (20), 6502.
1
2
2
9. Figiel, P. J.; Sobczak, J. M.; Zi o´ lkowski, J. J. New efficient aerobic oxidation of
some alcohols with dioxygen catalysed by N-hydrophthalimide with vanadium
co-catalysts. Chem. Commun. 2004, 4 (2), 244.
0. Davis, L. D.; Stevens, L. K.; Jurd, L. Chemistry of tobacco constituents. oxidation
of a-ionone and the acid-catalyzed rearrangement of 5-keto-a-ionone. J. Agric.
Food Chem. 1976, 24 (1), l87.
1. Becher, E.; Albrecht, R.; Bernhard, K.; Leuenberger, H. G. W.; Mayer, H.;
Mueller, R. K.; Schuep, W.; Wagner, H. P. Synthesis of astaxanthin from
b-ionone, l: Enantiomeric CI5-witting salts by chemical and microbial resolution
of (+)-3-acetoxy 4-oxo-ionone. Helv. Chim. Acta. 1981, 64 (7), 2419.