Peroxidation of β-diketones and β-keto esters with tert-butyl hydroperoxide in the presence of Cu(ClO4)2/SiO2

Article abstract of DOI:10.1007/s11172-014-0763-8

Reactions of β-diketones and β-keto esters with tert-butyl hydroperoxide under heterogeneous conditions using SiO₂-supported copper(II) perchlorate as a catalyst give rise to α-peroxidation products in 65 - 82% yields. A possibility to reuse the catalyst was demonstrated.

Full text of DOI:10.1007/s11172-014-0763-8

Russian Chemical Bulletin, International Edition, Vol. 63, No. 11, pp. 2461—2466, November, 2014
2461
Peroxidation of ꢀdiketones and ꢀketo esters
with tertꢀbutyl hydroperoxide in the presence of Cu(ClO4)2/SiO2*
A. O. Terent´ev, V. A. Vil´, O. V. Bityukov, and G. I. Nikishin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Eꢀmail: terentev@ioc.ac.ru
Reactions of -diketones and -keto esters with tertꢀbutyl hydroperoxide under heteroꢀ
geneous conditions using SiO2ꢀsupported copper(II) perchlorate as a catalyst give rise to
ꢀperoxidation products in 65—82% yields. A possibility to reuse the catalyst was demonstrated.
Key words: peroxides, tertꢀbutyl hydroperoxide, -diketones, -keto esters, copper
compounds, silica gel.
For more than half a century, organic peroxides have
been used in industry as initiators of radical polymerizaꢀ
tion and crossꢀlinkage. Their assortment includes dialkyl
peroxides, diacyl peroxides, peroxy esters, peroxy dicarꢀ
bonates, peroxy carbonates, peroxy acetals, cyclic triperꢀ
oxides, and terminal bishydroperoxides.1,2 In the last deꢀ
cades, these compounds were found to possess antimalarꢀ
ial,3 antihelmintic,4 and antitumor activity.5 Peroxides are
of interest as potential explosives.6
The interest to the preparation of efficient inexpensive
initiators of radical polymerization and biologically active
compounds stimulates the development of new methods
for the synthesis of peroxides, mostly from ketones and
their derivatives reacted with hydrogen peroxide and
hydroperoxides.7
In the present work, we continue our studies on the
peroxidation of dicarbonyl compounds.8 Earlier, it was
found that Cu, Fe, Mn, and Co compounds catalyze seꢀ
lective -peroxidation of ꢀdicarbonyl compounds with
tertꢀbutyl hydroperoxide.8a,b
Transition metals such as Cu, Mn, and Co in combiꢀ
nation with hydroperoxides have been used for the first
time by Kharasch for the preparation of peroxides from
alkenes, ketones, and tertiary amines more than 60 years
ago.9 Afterwards, the formation of peroxides was observed
in the reactions of hydroperoxides in the presence of metal
salts (copper,10 cobalt,11 and iron12,13) or their complexes
(nickel complexes,14 palladium acetate,15 and ruthenium
bipyridinate on montmorillonite16). Peroxides were obꢀ
tained in good yields by peroxidation of amines, amides,
and lactams catalyzed by ruthenium salts.17 Formation of
peroxides was observed in the oxidation of cyclic ꢀdiꢀ
ketones with a singlet oxygen,18 the CeCl3/O2 system,19 as
well as in the oxidation of nitrogenꢀcontaining heteroꢀ
cycles upon treatment with manganese salts and oxygen.20
It is important to note that virtually all the studies on
peroxidation were carried out under homogeneous condiꢀ
tions because of the tendency of peroxides to decompose
on a solid surface under heterogeneous conditions.21
The aboveꢀmentioned reactions for the preparation of
peroxides which use salts of metals of variable oxidation
state are rather exceptions from the practice of peroxide
chemistry, since they are applicable only to compounds of
a certain structure, whereas the overwhelming majority of
peroxide transformations in the presence of metal salts
includes the cleavage of the O—O bond.22
In the present work, we accomplished the peroxidaꢀ
tion of ꢀdicarbonyl compounds at ꢀposition with tertꢀ
butyl hydroperoxide under heterogeneous conditions usꢀ
ing copper(II) perchlorate hexahydrate supported on silica
gel as a catalyst.
Results and Discussion
In our studies, monosubstituted at ꢀposition ꢀdiꢀ
ketones 1a—e and ꢀketo esters 1f—i (Scheme 1) served as
the starting reactants.
Field emission scanning electron microscopy
(FEꢀSEM) studies of the samples of the starting silica gel
and the catalyst prepared on its basis (20% wt.% of
Cu(ClO4)2 on SiO2) showed that the structure of the
sample slightly changes after the treatment. A commercial
sample contains small particles of silica gel on the surface
of larger grains (Fig. 1, a). In the sample of silica gel with
* Dedicated to Academician of the Russian Academy of Sciences
Yu. N. Bubnov on the occasion of his 80th birthday and to the
60th anniversary of the foundation of A. N. Nesmeyanov Instiꢀ
tute of Organoelement Compounds of the Russian Academy of
Sciences.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2461—2466, November, 2014.
1066ꢀ5285/14/6311ꢀ2461 © 2014 Springer Science+Business Media, Inc.

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Terent´ev et al.
Scheme 1
A possibility of the catalyst reuse was shown for the
model synthesis of peroxide 2d in the CHCl3—MeCN
(10 : 1) solvent system, in which the solubility of
Cu(ClO4)2 is insignificant (Table 2).
Good yields of peroxidation product 2d were achieved
in the first three cycles of the catalyst reuse, whereas in
subsequent cycles they were considerably lower. In all the
experiments, the Cu(ClO4)2•6H2O/SiO2 catalyst mass
loss as a result of partial dissolution of copper perchlorate
and losses during regeneration was insignificant, about
3—5% after each cycle.
Other peroxides 2a—c and 2e—i were synthesized under
conditions described in entry 6 (see Table 1). The peroxiꢀ
dation of ꢀketo esters 1f—i required a larger amount of
the catalyst. Using compound 1e as an example, we showed
a possibility of a fiveꢀfold scaling of the synthesis (enꢀ
try 12). The catalyst reuse was also tested in the case of
substrate 1h (entry 15).
Comꢀ
pounds 1, 2
R1
R2
a
b
c
d
e
f
g
h
i
nꢀC6H13
CH2=CHCH2
CH2CH2COOEt
Bn
4ꢀMeC6H4CH2
Me
Me
Me
Me
Me
Me
OEt
OEt
OEt
OEt
Bu
CH2CH2CN
Bn
Conditions: ButOOH, Cu(ClO4)2/SiO2, solvent.
In conclusion, a suggested method for the ꢀperoxidaꢀ
tion of ꢀdiketones and ꢀketo esters can be used for the
structurally different starting compounds. In all the experꢀ
iments, the product yields ranges within 65—82%, that
allows one to extend this procedure to other dicarbonyl
compounds. Despite heterogeneous conditions of the proꢀ
cess, no noticeable decomposition of the peroxide prodꢀ
ucts and tertꢀbutyl hydroperoxide occurs. The catalyst can
be regenerated and efficiently enough used in three conꢀ
secutive cycles.
supported copper(II) perchlorate, the amount of small
particles on the surface of large grains considerably
increases (Fig. 1, b). The Xꢀray microanalysis showed
that the catalyst is uniformly distributed over the surꢀ
face of silica gel. The concentration of copper and
chlorine atoms measured upon scanning along an arꢀ
bitrary chosen lines on the surface of the sample did
not change.
The search for optimal conditions was performed usꢀ
ing ꢀbenzylacetylacetone 1d as a model compound (see
Table 1, entries 4—11).
Experimental
The product 2d was obtained in acceptable yield with
the v/v ratio CHCl3 : MeCN ranging from 4 : 1 to 20 : 1
(Table 1, entries 4—9). Virtually no peroxide 2d was formed
for the ratio CHCl3 : MeCN = 100 : 1 (entry 10). The
formation of 2d was not observed either when pure chloroꢀ
form, 1,2ꢀdichloroethane, or toluene were used (entry 11),
that can be apparently explained by low solubility of
Cu(ClO4)2 in these solvents.
1
H NMR spectra were recorded on a Bruker AM 300 spectroꢀ
meter (300.13 MHz for H, 75.48 MHz for 13C) in CDCl3. To
1
perform scanning electronic microscopy,23 the samples before
studies were placed on the surface of aluminum stage 25 mm in
diameter and fixed by a conducting glue. A 10 nm conducting
layer of metal (Pt/Pd, 80/20) was applied on the samples using
magnetron sputtering. The microstructures of the samples
were studied by field emission scanning electron microscopy
a
b
10 m
10 m
Fig. 1. Microphotographs of the samples of commercial SiO2 (a) and the catalyst Cu(ClO4)2•6H2O/SiO2 (b).

Peroxidation of ꢀdiketones and ꢀketo esters
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 11, November, 2014 2463
Table 1. Peroxidation of ꢀdicarbonyl compounds 1a—i with tertꢀbutyl hydroperoxidea
Entry
Starting
compound
Method
of stirringb
Solvent
Product
Product yieldc
(%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1d
1d
1d
1d
1d
MS
MS
MS
MS
US
MS
US
MS
US
CHCl3—MeCN (10 : 1)
CHCl3—MeCN (10 : 1)
CHCl3—MeCN (10 : 1)
CHCl3—MeCN (4 : 1)
CHCl3—MeCN (4 : 1)
CHCl3—MeCN (10 : 1)
CHCl3—MeCN (10 : 1)
CHCl3—MeCN (20 : 1)
CHCl3—MeCN (20 : 1)
CHCl3—MeCN (100 : 1)
2a
2b
2c
2d
2d
2d
2d
2d
2d
68
65
72
79
80
73
75
65
59
d
10
11
12
13
14
15
16
1d
1d
1e
1f
1g
1h
1i
MS
MS
MS
MS
MS
MS
MS
2d
2d
2e
2f
2g
2h
2i
—
—
75 (73)f
e
d
CHCl3
CHCl3—MeCN (10 : 1)
CHCl3—MeCN (10 : 1)
CHCl3—MeCN (10 : 1)
CHCl3—MeCN (10 : 1)
CHCl3—MeCN (10 : 1)
75
71
72 (67, 61)g
82
a Conditions: 20 mol.% of [Cu] were used per 1 mol of the starting compound in the case of diketones 1a—e or
40 mol.% of [Cu] in the case of keto esters 1f—i, 6 mmol of ButOOH, 7 mL of the solvent; reflux, 6 h.
b MS stands for mechanical stirring, US stands for sonication.
c Calculated on the isolated product.
d Trace amounts.
e The same result was obtained when 1,2ꢀdichloroethane or toluene were used.
f Fiveꢀfold scaling of loading.
g For two reuses of the catalyst.
Table 2. The efficiency of the catalytic system Cu(ClO4)2•6H2O/
SiO2 in six catalytic cycles of the preparation of peroxide 2d
the Cu(ClO4)2/SiO2 catalyst. Ultrasonic experiments were
performed using a UZVꢀ3/200ꢀTNꢀRELTEK ultrasonic bath
(290 W, 22 kHz).
Dicarbonyl compounds 1a,24 1b,25 1c,26 1d,27 1e,28 1g,29
1h,30 1i31 were synthesized according to the known procedures.
Cycle
Amount of
Loss in weight
of the catalysta
(%)
Yield of 2db
catalyst loaded
in reaction/mg
(%)
1
3ꢀHexylpentaneꢀ2,4ꢀdione (1a).24 An oil. H NMR, : 0.83
(t, 3 H, CH3CH2, J = 6.6 Hz); 1.22—1.26 (m, 8 H); 1.78 (q, 1.5 H,
CHCH2, J = 7.3 Hz); 2.02—2.17 (m, 6.5 H); 3.56 (t, 0.6 H,
CHCH2, J = 7.3 Hz), 16.63 (br.s, 0.4 H, OH).
3ꢀAllylpentaneꢀ2,4ꢀdione (1b).25 An oil. 1H NMR, : 2.06
(s, 3 H, CH3); 2.13 (s, 3 H, CH3); 2.57 (m, 1 H, CHCH2CH); 2.95
(d, 1 H, CHCH2C, J = 5.1 Hz); 3.69 (t, 0.5 H, CHCO,
J = 7.3 Hz); 4.93—5.86 (m, 3 H, CH2CHCH2); 16.67 (br.s,
0.5 H, OH).
1
2
3
4
5
6
687
667
646
627
596
572
—
3
3
3
5
73
71
68
55
43
33
4
a Based on the initial amount of the catalyst taken in the cycle.
b Yield of the isolated product.
Ethyl 4ꢀacetylꢀ5ꢀoxohexanoate (1c).26 An oil. 1H NMR,
: 1.22 (t, 3 H, CH3CH2, J = 6.9 Hz); 2.04—2.58 (m, 10 H,
CH3CO, 2 CH2); 3.70 (t, 0.6 H, CH, J = 6.9 Hz); 4.06—4.13
(m, 2 H, CH2O); 16.82 (br.s, 0.4 H, OH).
1
(FEꢀSEM) on a Hitachi SU8000 electron microscope. The imꢀ
ages were obtained in the mode of registration of secondary elecꢀ
trons at accelerating voltage of 10 kV and operating distance of
8—10 mm. The morphology of the samples was studied with the
correction on the surface effects of the conducting layer sputtering.
Thinꢀlayer chromatography was carried out on Silufol UVꢀ254
plates with Silpearl sorbent in petroleum—ethyl acetate solvent
systems. Commercially available reactants were purchased from
Acros. Domestically produced solvents were distilled before use.
Silica gel (0.060—0.200 mm, 60 Å, CAS 7631ꢀ86ꢀ9, Acros) was
used for column chromatography and for the preparation of
3ꢀBenzylpentaneꢀ2,4ꢀdione (1d).27 An oil. H NMR, : 2.07
(s, 3 H, CH3); 2.12 (s, 3 H, CH3); 3.15 (d, 1 H, CH2CH, J = 7.3 Hz);
3.65 (s, 1 H, CH2); 4.00 (t, 0.7 H, CH, J = 7.3 Hz); 7.13—7.30
(m, 5 H, CHAr); 16.82 (br.s, 0.3 H, OH).
3ꢀ(4ꢀMethylbenzyl)pentaneꢀ2,4ꢀdione (1e).28 An oil. 1H NMR,
: 2.06 (s, 3 H, CH3); 2.11 (s, 6 H, CH3); 2.30 (s, 1.5 H, CH3CAr);
2.32 (s, 1.5 H, CH3CAr); 3.10 (d, 1 H, CH2CH, J = 7.3 Hz); 3.61
(s, 1 H, CH2); 3.99 (t, 0.5 H, CH, J = 7.3 Hz); 6.97—7.15 (m, 4 H,
CHAr); 16.81—16.83 (br.s, 0.5 H, OH).
Ethyl 2ꢀacetylhexanoate (1g).29 A colorless oil. 1H NMR,
: 0.84 (t, 3 H, CH3CH2CH2, J = 6.6 Hz); 1.16—1.35 (m, 7 H,

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Terent´ev et al.
CH3CH2O, CH2CH2); 1.72—1.87 (m, 2 H, CH2CH); 2.17 (s, 3 H,
CH3CO); 3.33 (t, 1 H, CH, J = 7.3 Hz); 4.14 (q, 2 H, CH2O,
J = 7.3 Hz).
alyst was regenerated by evaporation of the residual solvents at
room temperature in vacuo of a waterꢀjet pump for 30 min. The
yields of product 2d are given in Table 2.
Ethyl 2ꢀ(2ꢀcyanoethyl)ꢀ3ꢀoxobutanoate (1h).30 A colorless
oil. 1H NMR, : 1.25 (t, 3 H, CH3CH2O, J = 6.9 Hz); 2.05—2.16
(m, 2 H, CH2CH); 2.25 (s, 3 H, CH3COCH); 2.40 (t, 2 H,
CH2CN, J = 7.0 Hz); 3.60 (t, 1 H, CH, J = 6.9 Hz); 4.19 (q, 2 H,
CH2O, J = 7.0 Hz).
3ꢀ(tertꢀButylperoxy)ꢀ3ꢀhexylpentaneꢀ2,4ꢀdione (2a). Rf 0.60
(light petroleum—ethyl acetate, 20 : 1). An oil. 1H NMR, : 0.83
(t, 3 H, CH3CH2, J = 6.9 Hz); 1.22—1.26 (m, 17 H, 3 CH3C,
(CH2)4); 1.96—2.03 (m, 2 H, CCH2); 2.18 (s, 6 H, CH3CO).
13C NMR, : 13.9 (CH3CH2), 22.5, 22.8, 26.5 (CH3C), 26.9,
29.4, 31.2, 31.4, 80.7 (CH3C), 97.3 (CH2C), 203.5 (CO).
3ꢀAllylꢀ3ꢀ(tertꢀbutylperoxy)pentaneꢀ2,4ꢀdione (2b). Rf 0.65
(light petroleum—ethyl acetate, 20 : 1). An oil. 1H NMR, : 1.29
(s, 9 H, CH3C); 2.16 (s, 6 H, CH3CO); 2.79 (d, 2 H, CH2C,
J = 7.3 Hz); 5.04—5.10 (m, 2 H, CH2CH); 5.65—5.79 (m, 1 H,
CH). 13C NMR, : 26.5 (CH3C), 26.9 (CH3CO), 35.6 (CH2C),
80.9 (CH3C), 97.0 (CH2C), 119.1 (CH2CH), 131.5 (CH),
202.7 (CO).
Ethyl 4ꢀacetylꢀ4ꢀ(tertꢀbutylperoxy)ꢀ5ꢀoxohexanoate (2c).
Rf 0.68 (light petroleum—ethyl acetate, 10 : 1). An oil. 1H NMR,
: 1.20 (t, 3 H, CH3CH2, J = 7.3 Hz); 1.27 (s, 9 H, CH3C); 2.18
(s, 6 H, CH3CO); 2.24—2.38 (m, 4 H, CH2CH2); 4.07 (q, 2 H,
CH2O, J = 7.3 Hz). 13C NMR, : 14.1 (CH3CH2), 26.3 (CH2C),
26.4 (CH3C), 26.7 (CH3CO), 28.2 (CH2C), 60.5 (CH2O), 81.0
(CH3C), 96.2 (C), 172.6 (COO), 202.6 (COCH3).
Ethyl 2ꢀbenzylꢀ3ꢀoxobutanoate (1i).31 A colorless oil. 1H NMR,
: 1.18 (t, 3 H, CH3CH2, J = 7.3 Hz); 2.16 (s, 3 H, CH3CO);
3.14 (d, 2 H, CH2CH, J = 8.1 Hz); 3.76 (t, 1 H, CH, J = 7.3 Hz);
4.13 (q, 2 H, CH2O, J = 7.3 Hz); 7.14—7.27 (m, 5 H, CHAr).
A catalyst Cu(ClO4)2•6H2O/SiO2. The salt Cu(ClO4)2•
6H2O (195 mg) was added to MeOH (5 mL) with stirring, after
its complete dissolution SiO2 (495 mg, 80 wt.% calculated on
Cu(ClO4)2) was added. The mixture was treated with ultrasound
for 10 min. The solvent was evaporated in vacuo of a waterꢀjet
pump at 60 C for 20 min to obtain Cu(ClO4)2•6H2O/SiO2
(687 mg) with the mass content of Cu(ClO4)2 about 20%. The
catalyst with the content of Cu(ClO4)2 about 40% was obtained
similarly, using SiO2 (150 mg, 60 wt.% of SiO2 calculated on
Cu(ClO4)2.).
Peroxides 2a—e (general procedure). A catalyst Cu(ClO4)2•
6H2O/SiO2 (642—935 mg, 0.2 mol of [Cu] per 1 mol of the
substrate) was added to a solution of diketone 1a—e (500 mg,
2.45—3.57 mmol) in a proper solvent (7 mL), the mixture was
brought to reflux and 70% aqueous ButOOH (1.89—2.76 g,
14.7—21.4 mmol, 6 mol of ButOOH per 1 mol of the substrate)
was added in six portions (0.32—0.46 g each) every 1 h. After
addition of the last portion, the mixture was refluxed for 1 h. The
mixture was subjected to ultrasound or vigorous mechanical stirꢀ
ring using an upperꢀdrive stirrer. Then, the reaction mixture was
cooled to room temperature, diluted with CH2Cl2 (15 mL), the
solvent (13 mL) was decanted from the precipitate, repeating
this procedure five times. The combined organic phases were
washed with 1% aqueous HCl (10 mL) and water (2×15 mL) and
dried with Na2SO4. The solvent was evaporated in vacuo of
a waterꢀjet pump. The residue was subjected to chromatography
using gradient 530% ethyl acetate in light petroleum. The yields
of the products are given in Table 1.
3ꢀBenzylꢀ3ꢀ(tertꢀbutylperoxy)pentaneꢀ2,4ꢀdione (2d). Rf 0.56
(light petroleum—ethyl acetate, 20 : 1). An oil. 1H NMR, : 1.33
(s, 9 H, CH3C); 1.97 (s, 6 H, CH3CO); 3.35 (s, 2 H, CH2);
7.15—7.23 (m, 5 H, CHAr). 13C NMR, : 26.6 (CH3C), 27.2
(CH3CO), 37.0 (CH2), 81.3 (CH3C), 97.0 (CH2C), 126.7, 128.0,
130.5, 135.0 (CAr), 203.3 (CO).
3ꢀ(tertꢀButylperoxy)ꢀ3ꢀ(4ꢀmethylbenzyl)pentaneꢀ2,4ꢀdione (2e).
Rf 0.47 (light petroleum—ethyl acetate, 20 : 1). An oil. 1H NMR,
: 1.33 (s, 9 H, CH3C); 1.98 (s, 6 H, CH3CO); 2.29 (s, 3 H); 3.31
(s, 2 H, CH2); 7.05 (m, 4 H, CHAr). 13C NMR, : 21.0, 26.7
(CH3C), 27.3 (CH3CO), 36.7 (CH2), 81.3 (CH3C), 97.0 (CH2C),
128.8, 130.4, 131.8, 136.3 (CAr), 203.6 (CO).
Ethyl 2ꢀ(tertꢀbutylperoxy)ꢀ2ꢀmethylꢀ3ꢀoxobutanoate (2f).
Rf 0.77 (light petroleum—ethyl acetate, 10 : 1). An oil. 1H NMR,
: 1.20—1.25 (m, 12 H, 3 CH3C, CH3CH2); 1.54 (s, 3 H, CH3);
2.24 (s, 3 H, CH3); 4.17 (q, 2 H, CH3CH2, J = 7.3 Hz).
13C NMR, : 13.9 (CH3), 18.2 (CH3), 25.5 (CH3), 26.3 (CH3C),
61.6 (OCH2), 80.6 (CH3C), 89.6 (C), 167.9 (COO), 203.6 (CO).
Ethyl 2ꢀacetylꢀ2ꢀ(tertꢀbutylperoxy)hexanoate (2g). Rf 0.79
(light petroleum—ethyl acetate, 20 : 1). An oil. 1H NMR, : 0.86
(t, 3 H, CH3CH2CH2, J = 7.3 Hz); 1.18—1.33 (m, 16 H, CH3C,
CH3CH2O, CH3CH2CH2); 1.99—2.14 (m, 2 H, CH2C); 2.22
(s, 3 H, CH3CO); 4.17 (q, 2 H, CH2O, J = 7.3 Hz). 13C NMR,
: 13.8, 14.0 (CH3), 22.2 (CH3CH2CH2), 24.9 (CH3CO), 26.4
(CH3C), 30.8 (CH2C), 61.4 (CH2O), 80.5 (CH3C), 92.1 (C),
167.6 (COO), 203.5 (CO).
Ethyl 2ꢀ(tertꢀbutylperoxy)ꢀ2ꢀ(2ꢀcyanoethyl)ꢀ3ꢀoxobutanoate
(2h). Rf 0.48 (light petroleum—ethyl acetate, 10 : 1). An oil.
1H NMR, : 1.20—1.24 (m, 12 H, CH3C, CH3CH2O); 2.24 (s, 3 H,
CH3CO); 2.30—2.35 (m, 2 H, CH2CH2); 2.48 (t, 2 H, CH2CH2,
J = 7.33 Hz); 4.18 (q, 2 H, CH2O, J = 7.3 Hz). 13C NMR,
: 11.3 (NCCH2), 13.7 (CH3CH2), 25.9, 26.2, 26.5 (CH2C, CH3C,
CH3CO), 62.2 (CH2O), 81.3 (CH3C), 90.4 (CH2C), 118.9 (CN),
165.8 (COO), 201.0 (CO).
Peroxides 2f—i were obtained similarly using 0.594—1.148 g
(0.4 mol of [Cu] per 1 mol of the substrate) of the catalyst. The
yields of the products are given in Table 1.
Synthesis of peroxides using a regenerated catalyst. The cataꢀ
lyst Cu(ClO4)2•6H2O/SiO2 (687 mg, 0.2 mol of Cu(ClO4)2 per
1 mol of diketone 1d) was added to a solution of diketone 1d
(500 mg, 2.63 mmol) in the CHCl3—MeCN solvent system (7 mL,
10 : 1 v/v) (in the 2—6 cycles, a catalyst regenerated from the
preceding cycle was used), the mixture was brought to reflux and
70% aqueous ButOOH (2.04 g, 15.8 mmol, 6 mol of ButOOH
per 1 mol of 1d) was added in six portions (0.34 g each) every 1 h.
After addition of the last portion, the mixture was refluxed for
1 h. The mixture was subjected to vigorous mechanical stirring
using an upperꢀdrive stirrer. Then, the reaction mixture was
cooled to room temperature, diluted with CH2Cl2 (15 mL), the
solvent (13 mL) was decanted from the precipitate, repeating
this procedure five times. The combined organic phases were
washed with 1% aqueous HCl (10 mL) and water (215 mL) and
dried with Na2SO4. The solvent was evaporated in vacuo of
a waterꢀjet pump. The residue was subjected to chromatography
using gradient 530% ethyl acetate in light petroleum. The catꢀ
Ethyl 2ꢀbenzylꢀ2ꢀ(tertꢀbutylperoxy)ꢀ3ꢀoxobutanoate (2i).
Rf 0.60 (light petroleum—ethyl acetate, 10 : 1). An oil. 1H NMR,
: 1.22 (t, 3 H, CH3CH2, J = 7.3 Hz); 1.30 (s, 9 H, CH3C); 1.89
(s, 3 H, CH3CO); 3.33 (d, 1 H, CH2C, J = 13.9 Hz); 3.56 (d, 1 H,

Peroxidation of ꢀdiketones and ꢀketo esters
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 11, November, 2014 2465
CH2C, J = 13.9 Hz); 4.11—4.24 (m, 2 H, CH2O); 7.16—7.26
(m, 5 H, CHAr). 13C NMR, : 13.9 (CH3CH2), 26.6 (CH3C),
27.1 (CH3CO), 37.1 (CArCH2), 61.6 (CH3CH2), 81.1 (CH3C),
92.6 (CH2C), 126.7, 127.9, 130.6, 134.9 (CAr), 167.6 (COO),
203.5 (CO).
V. Veneziano, L. Rinaldi, L. Mezzino, U. Duthaler, G. Crinꢀ
goli, Res. Vet. Sci., 2010, 88, 107—110; (c) K. Ingram, I. A.
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. i ak, Z. Juranic´, D. Opsenica,
The authors are grateful to the Division of Structural
Studies of the N. D. Zelinsky Institute of Organic Chemꢀ
istry of the Russian Academy of Sciences for the studies of
the samples by electronic microscopy.
B. A. Šolaja, Invest. New Drugs, 2009, 27, 432—439; (c) N.
Terzic´, D. Opsenica, D. Milic´, B. Tinant, K. S. Smith, W.
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This work was financially supported by the Russian
Scientific Foundation (Grant 14ꢀ23ꢀ00150).
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Received October 6, 2014;
in revised form October 27, 2014