An efficient one-pot synthesis of 2,3-epoxyl-1,3-diaryl-1-propanone directly from acetophenones and aromatic aldehydes under ultrasound irradiation

Article abstract of DOI:10.1016/j.ultsonch.2009.09.007

A convenient and efficient one-pot synthesis of 2,3-epoxyl-1,3-diaryl-1-propanone directly from acetophenones and aromatic aldehydes under ultrasound irradiation at room temperature has been described. In comparison to two-step methods, the present procedure has the advantages of mild conditions, shorter reaction time, without isolation of any intermediate, saves energy and no requirement of toxic solvent.

Full text of DOI:10.1016/j.ultsonch.2009.09.007

Ultrasonics Sonochemistry 17 (2010) 363–366
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Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
An efficient one-pot synthesis of 2,3-epoxyl-1,3-diaryl-1-propanone directly from
acetophenones and aromatic aldehydes under ultrasound irradiation
a,b,c,*
a
a
Ji-Tai Li
, Ying Yin , Ming-Xuan Sun
a
College of Chemistry and Environmental Science, Hebei University, Baoding 071002, PR China
Key Laboratory of Analytical Science and Technology of Hebei Province, Baoding 071002, PR China
Key Laboratory of Medical Chemistry and Molecular Diagnosis, Ministry of Education, Baoding 071002, PR China
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 August 2009
Received in revised form 10 September 2009
Accepted 18 September 2009
Available online 26 September 2009
A convenient and efficient one-pot synthesis of 2,3-epoxyl-1,3-diaryl-1-propanone directly from ace-
tophenones and aromatic aldehydes under ultrasound irradiation at room temperature has been
described. In comparison to two-step methods, the present procedure has the advantages of mild condi-
tions, shorter reaction time, without isolation of any intermediate, saves energy and no requirement of
toxic solvent.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Epoxidation
2
,3-Epoxyl-1,3-diaryl-1-propanone
Synthesis
Ultrasound irradiation
Aromatic aldehyde
1
. Introduction
,3-Epoxyl-1,3-diaryl-1-propanone are very important syn-
large number of organic reactions can be carried out in higher
yield, short reaction time or milder conditions under ultrasonic
2
irradiation [7]. Some two-step reactions have been completed via
one-pot under ultrasound irradiation [8–12]. Herein, we wish to
report an efficient one-pot way to synthesize 2,3-epoxyl-1,3-dia-
ryl-1-propanone directly from acetophenones and aromatic alde-
hydes under ultrasound irradiation (Scheme 1).
thetic intermediates [1] and can serve as versatile precursor in syn-
thesis of many natural product and drug molecules [2], which is
usually prepared via epoxidation of
and usually requires nucleophilic oxidation under basic conditions.
However, various ,b-unsaturated ketones must be obtained from
a,b-unsaturated ketones [3]
a
the aldol reaction of ketones and aldehydes firstly, which then re-
acts with oxidant to form the title compounds. What is more,
2
. Methods
sometimes the preparation of
a,b-unsaturated ketones from ke-
2
.1. Apparatus and analysis
tones and aldehydes is troublesome according to the procedures
reported before [4], and some of the reported methods suffer from
drawbacks such as longer reaction times, lower yields or involving
toxic solvents.
In comparison to two-step methods, the one-pot process has
the advantages of mild conditions, shorter reaction time, without
isolation of any intermediate and saves energy. In 2009, Dai and
Shi reported a convenient and efficient one-pot way to synthesize
Melting points was uncorrected. Sonication was performed in
Shanghai BUG40-06 ultrasonic cleaner (with a frequency of 40 kHz
1
13
and a nominal power 250 W). The H NMR and C NMR spectra
were recorded on Bruker AVANCE 300 (300 MHz) spectrometer
and Bruker AVANCE 600 (600 MHz) spectrometer respectively
using TMS as internal standard and CDCl
3
as solvent.
a
,b-epoxy ketones directly from acetophenones and arylaldehydes,
2
1
.2. Typical procedure for the preparation of 2,3-epoxyl-1,3-diphenyl-
-propanone
but the long reaction times (24 h) were needed [5].
Ultrasound irradiation has been considered as a clean and use-
ful protocol in organic synthesis in the last three decades [6]. A
A 50 mL round-bottomed flask was charged with benzaldehyde
(1a, 2.5 mmol) and acetophenone (2a, 2.5 mmol), ethanol (5 mL)
and 10 mol/L aqueous potassium hydroxide (0.75 equiv). The
reaction flask was located in the cleaner bath, where the surface
of reactants is slightly lower than the level of the water. Observa-
*
Corresponding author. Address: College of Chemistry and Environmental
Science, Hebei University, Baoding 071002, PR China. Fax: +86 312 5079628.
E-mail addresses: lijitai@hbu.cn, lijitai@mail.hbu.edu.cn (J.-T. Li).
1
350-4177/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2009.09.007

3
64
J.-T. Li et al. / Ultrasonics Sonochemistry 17 (2010) 363–366
O
O
3
(CDCl ): 192.2, 148.7, 137.9, 135.3, 134.3, 131.8, 130.0, 129.0,
CHO
1
. EtOH/KOH, r.t., u.s.
128.4, 123.9, 120.8, 60.7, 58.0 ppm.
R1
R2
R1
R2
+
O
2
. H , u.s., 18-20
2
O
2
o
C
1
2
3
2.2.7. Compound 3g
2
,3-Epoxyl-3-(2-nitrophenyl)-1-phenyl-1-propanone, gray so-
1
Scheme 1. One-pot synthesis of 2,3-epoxyl-1,3-diaryl-1-propanone.
lid, H NMR (300 MHz, CDCl
d, 1H, J = 1.8 Hz, CH), 7.50–8.27 (m, 9H, Ph-H); C NMR (CDCl ):
3
): d
H
: 4.25 (d, 1H, J = 1.8 Hz, CH), 4.67
1
3
(
3
1
1
92.5, 147.6, 135.4, 134.6, 134.0, 132.6, 129.4, 128.9, 128.5, 127.4,
24.9, 59.6, 57.6 ppm.
tion of the surface of the reaction solution during vertical adjust-
ment of vessel depth will show the optimum position by the point
at which maximum surface disturbance occurs. Sonication was
continued until acetophenone (or benzaldehyde) had disappeared
as indicated by TLC (petroleum ether:ethyl acetate, 5:1). Then,
2.2.8. Compound 3h
2
,3-Epoxyl-3-(4-methylphenyl)-1-phenyl-1-propanone, white
1
solid, H NMR (300 MHz, CDCl
1
Ph-H); C NMR (CDCl
3 H 3
): d : 2.41 (s, 3H, CH ), 4.07 (d,
1
.5 equiv of 30% hydrogen peroxide was added to the mixture
H, J = 1.8 Hz, CH), 4.32 (d, 1H, J = 1.8 Hz, CH), 7.23–8.05 (m, 9H,
and continued to irradiate for a period of time at 18–20 °C. The
reaction temperature was controlled by addition or removal of cir-
culated water from ultrasonic bath. After the completion of the
reaction, the resulting suspension was neutralized by hydrochloric
acid, and then extracted with ethyl acetate (3 Â 10 mL). The com-
bined organic layers were dried over anhydrous magnesium sul-
fate, filtered, and evaporated the solvent in reduced pressure to
give the crude products, which was purified by column chromatog-
raphy on silica gel (200–300 mesh) eluted with a mixture of petro-
leum ether and ethyl acetate to afford the product 3. The
13
3
): 193.2, 139.1, 135.6, 133.9, 132.5, 129.5,
1
28.9, 128.4, 125.8, 61.1, 59.5, 21.3 ppm.
2.2.9. Compound 3i
2
,3-Epoxy-1-(4-methoxyphenyl)-3-phenyl-1-propanone, white
1
solid, H NMR (300 MHz, CDCl
3 H 3
): d : 3.91 (s, 3H, OCH ), 4.10 (d, 1H,
J = 1.5 Hz, CH), 4.27 (d, 1H, J = 1.5 Hz, CH), 6.97–8.06 (m, 9H, Ph-H);
13
3
C NMR (CDCl ): 191.3, 164.3, 135.7, 130.8, 129.0, 128.8, 128.6,
125.8, 114.1, 60.9, 59.1, 55.6 ppm.
1
13
authenticity of the product 3 was established by its H NMR,
C
2.2.10. Compound 3j
NMR and melting points compared with that reported in
literatures [13–21].
2
,3-Epoxyl-1,3-di(4-methoxyphenyl)-1-propanone, white so-
1
lid, H NMR (300 MHz, CDCl
3 H 3
): d : 3.86 (s, 3H, OCH ), 3.90 (s, 3H,
OCH ), 4.04 (d, 1H, J = 1.8 Hz, CH), 4.27 (d, 1H, J = 1.8 Hz, CH),
3
2
.2.1. Compound 3a
,3-Epoxyl-1,3-diphenyl-1-propanone, white solid, 1H NMR
300 MHz, CDCl ): d : 4.08 (d, 1H, J = 1.8 Hz, CH), 4.30 (d, 1H,
J = 1.8 Hz, CH), 7.37–8.01 (m, 10H, Ph-H); C NMR (CDCl
35.5, 134.0, 129.1, 128.9, 128.8, 128.4, 125.8, 61.1, 59.4 ppm.
13
6
.94–8.05 (m, 8H, Ph-H); C NMR (CDCl
3
): 191.6, 164.2, 160.3,
2
1
30.7, 128.7, 127.6, 127.2, 114.2, 114.1, 60.9, 59.1, 55.6, 55.4 ppm.
(
3
H
3
3
): 193.1,
2.2.11. Compound 3k
1
2
,3-Epoxyl-1-(4-methoxyphenyl)-3-(4-nitrophenyl)-1-propa-
1
none, yellow solid, H NMR (300 MHz, CDCl
OCH ), 4.23 (d, 2H, J = 1.8 Hz, CH), 6.99–8.31 (m, 8H, Ph-H);
NMR (CDCl ): 190.3, 164.5, 148.3, 143.1, 130.9, 128.3, 126.6,
24.0, 114.3, 60.7, 57.8, 55.6 ppm.
3 H
): d : 3.92 (s, 3H,
2
.2.2. Compound 3b
13
3
C
3
-(4-Chlorophenyl)-2,3-epoxyl-1-phenyl-1-propanone, white
3
1
solid, H NMR (300 MHz, CDCl
.28 (d, 1H, J = 1.2 Hz, CH), 7.29–8.04 (m, 9H, Ph-H); C NMR
CDCl ): 192.7, 135.4, 135.0, 134.1, 129.1, 128.9, 128.4, 127.1,
1.0, 58.7 ppm.
3 H
): d : 4.09 (d, 1H, J = 1.2 Hz, CH),
1
13
4
(
6
3
3
. Results and discussion
The effect of reaction conditions on epoxidation under ultra-
2.2.3. Compound 3c
sound irradiation by one-pot process from benzaldehyde and ace-
tophenone is summarized in Table 1. As shown in Table 1, we
compared the catalytic effect of KOH and NaOH, and found KOH
is better than NaOH. For example, under the same conditions,
when we use NaOH as catalyst, the yield was 76% (Entry 1), while
we use KOH as catalyst, the yield was 83% (Entry 3). With the
increasing of the molar ratio of benzaldehyde (or acetophenone)
and potassium hydroxide from 1:0.5–1:0.75, the higher yield
(83%) was achieved within 45 min (Entry 3). When increasing
the molar ratio to 1:1, not only the reaction time was prolonged,
but also the yield was reduced to 52% (Entry 4). The results
showed that changing the molar ratio of 1a (or 2a) with potassium
hydroxide had a significant effect on the yield of 3a, and the opti-
3
-(3-Chlorophenyl)-2,3-epoxyl-1-phenyl-1-propanone, white
1
solid, H NMR (300 MHz, CDCl
.28 (d, 1H, J = 1.8 Hz, CH), 7.29–8.05 (m, 9H, Ph-H); C NMR
CDCl ): 192.6, 137.7, 135.4, 135.0, 134.1, 130.1, 129.2, 129.0,
28.4, 125.8, 124.1, 60.8, 58.5 ppm.
3 H
): d : 4.09 (d, 1H, J = 1.8 Hz, CH),
13
4
(
1
3
2
.2.4. Compound 3d
3
solid, H NMR (300 MHz, CDCl
.44 (d, 1H, J = 1.5 Hz, CH), 7.16–8.10 (m, 9H, Ph-H); C NMR
CDCl ): 192.8, 135.4, 134.1, 133.8, 132.8, 129.8, 129.4, 128.8,
28.5, 128.2, 126.6, 60.1, 57.1 ppm.
-(2-Chlorophenyl)-2,3-epoxyl-1-phenyl-1-propanone, white
1
3 H
): d : 4.19 (d, 1H, J = 1.5 Hz, CH),
13
4
(
1
3
2.2.5. Compound 3e
2
,3-Epoxyl-3-(4-nitrophenyl)-1-phenyl-1-propanone, yellow
1
Table 1
solid, H NMR (300 MHz, CDCl
.30 (d, 1H, J = 1.5 Hz, CH), 7.48–8.31 (m, 9H, Ph-H); C NMR
CDCl ): 192.1, 148.4, 142.8, 135.2, 134.3, 129.0, 128.4, 126.7,
24.1, 60.9, 58.0 ppm.
3 H
): d : 4.23 (d, 1H, J = 1.5 Hz, CH),
13
The effect of the amount of potassium hydroxide on the yield of phenyl(3-
phenyloxiran-2-yl)methanone under ultrasound irradiation .
4
(
1
*
3
Entry
Catalyst
Substrate/catalyst, molar ratio
Time (min)
Yield (%)
1
2
3
4
NaOH
KOH
KOH
KOH
0.75
0.5
0.75
1.0
45
66
45
50
76
70
83
52
2
.2.6. Compound 3f
2
,3-Epoxyl-3-(3-nitrophenyl)-1-phenyl-1-propanone, yellow
1
solid, H NMR (300 MHz, CDCl
4
3 H
): d : 4.24 (d, 1H, J = 1.2 Hz, CH),
*
13
2
Benzaldehyde, 1 mmol; acetophenone, 1 mmol; H O2 (30% aq.), 1.5 equiv.
.33 (d, 1H, J = 1.2 Hz, CH), 7.52–8.28 (m, 9H, Ph-H); C NMR

J.-T. Li et al. / Ultrasonics Sonochemistry 17 (2010) 363–366
365
Table 2
Synthesis of 2,3-epoxyl-1,3-diaryl-1-propanone catalyzed by KOH from aromatic aldehydes and acetophenones under ultrasound irradiation.
Entry
R1
R2
Product
Time (min)
Yield (%) (stir.a)
Melting point °C [lit.]
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
45
60
100
120
120
60
35
63
164
35
180
83(56)
62
57
71
85(66)
82
73
78(28)
51
17
75
85–87 (84–85) [14]
77–78 (80–81) [15]
52–54 (56–58) [13]
71–73 (70–71) [16]
150–151 (150–152) [17]
116–118 (115–116) [13]
113–115 (110–111) [13]
75–76 (76) [18]
4-Cl
3-Cl
2-Cl
4-NO
3-NO
2-NO
4-CH
H
4-OCH
4-NO
2
2
2
3
4-OCH
4-OCH
4-OCH
3
3
3
80–81 (79–80) [19]
120–122 (118–119) [20]
142–144 (145–145.5) [21]
1
1
0
1
3
3j
3k
2
a
Stirring without ultrasound irradiation; the molar ratio of 1(or 2) and KOH, 1:0.75.
mum molar ratio of 1a (or 2a) with potassium hydroxide was
:0.75.
From the results above, a typical experimental procedure was
chosen: benzaldehyde (1a, 2.5 mmol) and acetophenone (2a,
.5 mmol), ethanol (5 mL), hydrogen peroxide (1.5 equiv) and
It is noteworthy that some of inter-product (chalcone) has not
been oxidized completely and led to the lower yield (Table 2, Entry
10).
1
1
From H NMR data we can confirm that the stereochemistry of
1
2
product is anti-structure. For example, in H NMR of 2,3-epoxyl-
aqueous potassium hydroxide (0.75 equiv). Using this system, we
did a series of experiments to prepare 2,3-epoxyl-1,3-diaryl-1-
propanone under ultrasound irradiation. The results were summa-
rized in Table 2.
1,3-diphenyl-1-propanone, the protons signals of the 2 and 3-posi-
tion hydrogen appeared at 4.30 ppm as doublet peaks (J = 1.8 Hz)
and 4.08 ppm doublet peaks (J = 1.8 Hz), respectively, which is
basically consistent with the data reported in the literature [22].
As shown in Table 2, the reactions were carried out in good
yields catalyzed by potassium hydroxide under ultrasound irradia-
tion. In order to verify the effect of ultrasound irradiation, we have
performed some reactions of aromatic aldehydes (Table 2, Entries
4
. Conclusion
In conclusion, we have found an efficient and practical proce-
1
, 5 and 8) and acetophenone catalyzed by potassium hydroxide by
stirring alone, the yields of 2,3-epoxyl-1,3-diaryl-1-propanone, 3a,
e and 3h were obtained in 56%, 66% and 28%, respectively; while
under ultrasound these reactions can be completed in 83%, 85% and
8%, respectively (Table 2, Entries 1, 5 and 8). It showed that ultra-
dure for the synthesis of some 2,3-epoxyl-1,3-diaryl-1-propanone
directly from benzaldehydes and acetophenones in the presence
of aqueous potassium hydroxide under ultrasound irradiation.
Especially, the reaction time is much shorter than classical meth-
ods with stirring.
3
7
sound irradiation improved the result.
Compared with the reported method [5], the dramatic improve-
ment observed is with regard to reaction time. In reported methods,
the reaction time was about 24 h and needed toxic organic solvent
Acknowledgement
The project was supported by Natural Science Foundation of
Hebei Province (B2006000969), China.
(
3
CH OH); whereas in the present procedure, the reactions only
needed 0.5–3 h to get a good result, and did not require toxic organ-
ic solvent. For example, 2,3-epoxyl-1,3-diphenyl-1-propanone (3a)
was previously prepared in 56% yield catalyzed by sodium hydrox-
ide in methanol with stirring at room temperature for about 24 h,
whereas present procedure offered 3a in 83% yield at room temper-
ature within 45 min (Table 2, Entry 1). It is apparently that one-pot
reaction could be completed in short time under ultrasound
irradiation.
In the present procedure, aromatic aldehydes carrying electron-
withdrawing or infirm electron-donating substituents in the ben-
zene ring reacted with acetophenone to afford products in higher
yields. For example, 4-nitrobenzaldehyde gave 3e in 85% yield (Ta-
ble 2, Entry 5). However, aromatic aldehydes carrying strong elec-
tron-donating substituents in the benzene ring gave products in
lower yields. Such as, 4-methoxybenzaldehyde gave the corre-
sponding 2,3-epoxyl-3-(4-methoxyphenyl)-1-phenyl-1-propanone
in very lower yield, and 4-(dimethylamino) benzaldehyde only
gave (E)-3-(4-(dimethylamino)phenyl)-1-phenylprop-2-en-1-one
rather than 2,3-epoxyl-3-(4-(dimethylamino)phenyl)-1-phenyl-1-
propanone. It indicates that the method has some limitations with
respect to some aldehydes.
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