Simple and efficient synthesis of 3-(N-hydroxylamino)-1,3-diarylpropan-1- one oximes under ultrasound irradiation

Article abstract of DOI:10.1080/00397910801979353

A series of 3-(N-hydroxylamino)-1,3-diarylpropan-1-one oximes have been synthesized through the reaction of chalcones and hydroxylamine hydrochloride in 56-96% yield within 2-3 h in the presence of sodium acetate in EtOH under ultrasound irradiation. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910801979353

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Simple and Efficient Synthesis
of 3-(N-Hydroxylamino)-1,3-
diarylpropan-1-one Oximes
Under Ultrasound Irradiation
Ji-Tai Li a , Xiao-Hui Zhang a & Zhi-Ping Lin a
a College of Chemistry and Environmental Science,
Hebei University , Baoding, China
Published online: 25 Aug 2010.
To cite this article: Ji-Tai Li , Xiao-Hui Zhang & Zhi-Ping Lin (2008) Simple and
Efficient Synthesis of 3-(N-Hydroxylamino)-1,3-diarylpropan-1-one Oximes Under
Ultrasound Irradiation, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 38:16, 2838-2844, DOI:
10.1080/00397910801979353
To link to this article: http://dx.doi.org/10.1080/00397910801979353
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Synthetic Communications1, 38: 2838–2844, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801979353
Simple and Efficient Synthesis of
3-(N-Hydroxylamino)-1,3-diarylpropan-
1-one Oximes Under Ultrasound Irradiation
Ji-Tai Li, Xiao-Hui Zhang, and Zhi-Ping Lin
College of Chemistry and Environmental Science, Hebei University,
Baoding, China
Abstract: A series of 3-(N-hydroxylamino)-1,3-diarylpropan-1-one oximes
have been synthesized through the reaction of chalcones and hydroxylamine
hydrochloride in 56–96% yield within 2–3 h in the presence of sodium acetate
in EtOH under ultrasound irradiation.
Keywords: 3-(N-Hydroxylamino)-1,3-diarylpropan-1-one oximes, sodium acetate,
ultrasound irradiation
INTRODUCTION
In 1998, Powers et al. first studied the reaction of chalcone with hydroxyl-
amine hydrochloride under basic conditions to form the isoxazoline ring
system by heating at 80 ꢀC for 12 h. Chalcones were chosen as the fea-
tured building block because of their chemical flexibility toward further
elaboration and ease of preparation, and by virtue of their already having
incorporated two elements of diversity.[1]
In our previous studies, synthesis of 1,3,5,-triarylpyrazolines via the
reaction of chalcones and phenylhydrazine hydrochloride was carried
out in 83–96% yield within 1.5–2 h in sodium acetate–acetic acid aqueous
solution under ultrasound irradiation.[2]
Oximes are highly crystalline, and the oximation is a very efficient
method for characterization and purification of carbonyl compounds.
Received November 16, 2007
Address correspondence to Ji-Tai Li, College of Chemistry and Environmental
Science, Hebei University, Hezuo Road no. 88, Boading 071002, China. E-mail:
lijitai@mail.hbu.edu.cn
2838

3-(N-hydroxylamino)-1,3-diarylpropan-1-one Oximes
2839
These compounds not only represent a series of carbonyl compounds but
also may be used as intermediates for the preparation of amides.[3]
Usually, the preparation of oximes via condensation of the carbonyl
compounds and hydroxylamine hydrochlorides needs longer reaction
time. Recently, in our experiment, we have found an efficient and con-
venient procedure for the preparation of oximes via the condensation
of aldehydes and ketones with hydroxylamine hydrochloride under ultra-
sound irradiation. Compared with reported procedures, the main advan-
tages of the procedure are milder conditions, higher yields, and shorter
reaction period.[4]
In 1975, Shotter et al. studied the reaction of chalcone with hydroxy-
lamine hydrochloride to form 3-(N-hydroxylamino)-1,3-diphenylpropan-
1-one oxime in the presence of 40%NaOH by refluxing for 4 h and then
refrigerating overnight.[5] However, in spite of its potential utility, the
method suffers from drawbacks, such as longer reaction times and lower
yields. Herein, we report the improved synthesis of 3-(N-hydroxylamino)-
1,3-diarylpropan-1-one oximes with chalcones and hydroxylamine hydro-
chloride in the presence of sodium acetate in EtOH under ultrasound
irradiation (Scheme 1).
RESULTS AND DISCUSSION
The effect of the reaction conditions on the reaction of chalcone and
hydroxylamine hydrochloride under ultrasound irradiation is summar-
ized in Table 1. When the molar ratio of chalcones (1) to hydroxylamine
hydrochloride (2) was 1:1, the yield of 3-(N-hydroxylamino)-1,3-diphe-
nylpropan-1-one oxime was trace (Table 1, Entry a). By increasing the
molar ratio to 1:2 and 1:3, the yields of increased to 36% and 47%
respectively (Table 1, entries b, c). The experimental results showed that
in the presence of sodium acetate, the yields can be increased. It may be
that sodium acetate favors the release of hydroxylamine from hydroxyla-
mine hydrochloride. We also examined the effect of the amount of
CH3COONa on the reaction. When the molar amount of sodium acetate
increased from 1 to 2 and 3, the yield of product increased from 47% to
Scheme 1. Synthesis of 3-(N-hydroxylamino)-1,3-diphenylpropan-1-one oxime.

2840
J.-T. Li, X.-H. Zhang, and Z.-P. Lin
Table 1. Effect of reaction conditions on synthesis of 3-(N-hydroxylamino)-1,
3-diphenylpropan-1-one oximea
Entry Molar ratio of 1=2=NaAc Frequency (kHz) Time (h) Yield (%)
a
b
c
d
e
f
1:1:1
l:2:1
25
25
25
25
25
40
Stirb
2
2
2
2
2
2
6
Trace
36
47
69
89
1:3:1
1:3:2
1:3:3
1:3:3
1:3:3
78
76
g
aReaction temperature: 36–40ꢀC, substrate: PhCOCH ¼ CHPh: 2 mmol;
amount of NaAc: 0.492 g.
bStirred without ultrasound irradiation.
69% and 89%, respectively (Table 1, entries c–e). We also examined the
effect of solvents (H2O, CH3COOH, and EtOH ) on the reaction, and
EtOH was the most effective. The best reaction conditions were a molar
ratio of chalcone–hydroxylamine hydrochloride–sodium acetate of 1:3:3
and EtOH as solvent.
As shown in Table 1, the reaction of chalcone with hydroxylamine
hydrochloride leading to 3-(N-hydroxylamino)-1,3-diphenylpropan-1-
one oxime gives the desired product in higher yield under ultrasound
irradiation than in the classical reflexing strategy. For example, com-
pound 3a was previously prepared in 66% yield in ethanol at reflux tem-
perature for 4 h,[5] whereas under ultrasonication, 3a was obtained in
89% at 35–40ꢀC within 2 h. We also did the experiment in the absence
of ultrasound irradiation; the mixture of 1,3-diphenylpropan-1-one with
hydroxylamine hydrochloride was refluxed in ethanol for 6 h to produce
3a in 76% yield (Table 1, entry g). It was clear that the ultrasound could
accelerate the reaction of chalcone and hydroxylamine hydrochloride.
We also monitored the effect of different irradiation frequencies on
the reaction. When the frequency was 25 kHz, the yield of 3-(N-hydroxyl-
amino)-1,3-diphenylpropan-1-one oxime was 89% (Table 1, entry e)
within 2 h. With 40-kHz frequency, the yield of 3-(N-hydroxylamino)-
1,3-diphenylpropan-1-one oxime was 78% (Table 1, entry f). It seems
that the lower frequency of ultrasound irradiation can improve the yield
of 3-(N-hydroxylamino)-1,3-diphenylpropan-1-one oxime. It is possible
that as the ultrasonic frequency is increased, the production of cavitation
in liquids decreases.[6]
From these results, the optimum reaction conditions were chosen:
chalcone (1, 2 mmol), hydroxylamine hydrochloride (2, 6 mmol), and

3-(N-hydroxylamino)-1,3-diarylpropan-1-one Oximes
2841
sodium acetate (6 mmol). Under this reaction condition, experiments for
the synthesis of 3-(N-hydroxylamino)-1,3-diarylpropan-1-one oximes
were performed under 25-kHz irradiation. The results are summarized
in Table 2.
The following sequence of reaction appears to afford a satisfactory
explanation of the mode of formation of the products (Scheme 2).[7]
CONCLUSION
In summary, we described a practical and convenient procedure for
the synthesis of 3-(N-hydroxylamino)-1,3-diarylpropan-1-one oximes
in the presence of sodium acetate in EtOH at room tempratrue under
ultrasound irradiation.
EXPERIMENTAL
General
Liquid substrates were distilled prior to use. Melting points were uncor-
1
rected. H NMR was measured on a Bruker Avance 400 (400-MHz)
spectrometer using TMS as the internal standard. Elemental analyses
were measured on a Heraeus (CHNO, Rapid) analyzer. Sonication was
performed in a Shanghai Branson-CQX ultrasonic cleaner (with a
frequency of 25 kHz and a nominal power of 250 W) and SK 250 LH ultra-
sonic cleaner (with a frequency of 40 kHz, and a nominal power of 250 W;
Table 2. Synthesis of 3-(N-hydroxylamino)-1,3-diarylpropan-1-one oximes in the
presence of NaAc under ultrasound irradiation
Time Yield
T (ꢀC) (h) (%)
ꢀ
[Lit.]
Entry
Ar1
C6H5
Ar2
Mp ( C)
a
b
c
d
e
f
C6H5
4-CH3OC6H4
3,4-(OCH2O)C6H3 35–40 2.3
35–40
36–41 2.5
2
89 148–150 (146–147)[9]
56 118–120 (116–117)[9]
75 144–146
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-CH3C6H4
2-ClC6H4
3-ClC6H4
35–40
35–40
1
2
94 139–140 (138–139)[9]
92 130–132
88 110–113
36–41 1.5
36–41 1.5
g
h
i
4-ClC6H4
96 160–162 (157–158)[9]
60 122–124
86 134–136
2,4-Cl2C6H3
3,4-Cl2C6H3
4-NO2C6H4
36–41
3
35–40 2.5
35–40 2.5
36–41 1.5
j
95 172–174 (167–168)[9]
89 120–122
k
4-ClC6H4 4-CH3OC6H4

2842
J.-T. Li, X.-H. Zhang, and Z.-P. Lin
Scheme 2. Formation of 3-(N-hydroxylamino)-1,3-diphenylpropan-1-one oxime.
Shanghai Kudos Ultrasonic Instrument Co., Ltd.). The reaction flask
was located in the cleaner, where the surface of reactants is slightly lower
than the level of the water. The reaction temperature was controlled by
addition or removal of water from the ultrasonic bath.
Syntheses
The chalcones were prepared as described in Ref.[8]
Chalcones (1, 2 mmol), hydroxylamine hydrochloride (2, 6 mmol),
and sodium acetate (6 mmol) were dissolved in 95% EtOH solution
(6 mL) in a 50-mL conical flask. The mixture was irradiated in the water
bath of an ultrasonic cleaner for the period as indicated in Table 2. The
reaction mixture was then poured into crushed ice. The precipitate was
separated by filtration, washed with water, and crystallized from ethanol
to obtain the 3-(N-hydroxylamino)-1,3-diarylpropan-1-one oximes. The
authenticity of 3a, 3b, 3c, 3d, 3g, and 3j was established by comparing
their melting points with literature data.[9] The other structures were
1
established by their H NMR and elemental analysis data.
Data
Compound 3c. 1H NMR (CDCl3): d3.04 (dd, J ¼ 8, 12 Hz, 1H), 3.55 (dd,
J ¼ 8, 12 Hz, 1H), 4.28(dd, J ¼ 8, 8 Hz, 1H), 5.94 (s, 2H, CH2), 6.74–7.55

3-(N-hydroxylamino)-1,3-diarylpropan-1-one Oximes
2843
(m, 8H) ppm. Anal. calcd for C22H20N2: C, 84.62: H, 6.41:N, 8.97; found:
C, 84.60: H, 6.44; N, 8.99.
Compound 3e. 1H NMR (CDCl3): d3.08 (dd, J ¼ 4, 16 Hz, 1H), 3.69
(dd, J ¼ 8, 12 Hz, 1H), 4.86 (dd, J ¼ 4, 12 Hz, 1H), 7.19–7.63 (m, 9H)
ppm. Anal. calcd for C22H20N2: C, 84.62; H, 6.41; N, 8.97; found: C,
84.60; H, 6.44; N, 8.99.
Compound 3f. 1H NMR (CDCl3): d3.06 (dd, J ¼ 4, 12 Hz, 1H), 3.56
(dd, J ¼ 8, 12 Hz, 1H), 4.34 (dd, J ¼ 8, 8 Hz, 1H), 7.26–7.54 (m, 9H)
ppm. Anal. calcd for C22H20N2: C, 84.62; H, 6.41; N, 8.97; found: C,
84.60; H, 6.44; N, 8.99.
Compound 3h 1H NMR (CDCl3): d3.06 (dd, J ¼ 4, 12 Hz, 1H), 3.61
(dd, J ¼ 8, 16 Hz, 1H), 4.81 (dd, J ¼ 4, 8 Hz, 1H), 7.19–7.57 (m, 8H)
ppm. Anal. calcd for C22H20N2: C, 84.62; H, 6.41; N, 8.97; found: C,
84.60; H, 6.44; N, 8.99.
Compound 3i. 1H NMR (CDCl3): d3.04 (dd, J ¼ 4, 12 Hz, 1H), 3.61
(dd, J ¼ 8, 16 Hz, 1H), 4.31 (dd, J ¼ 4, 8 Hz, 1H), 7.18–7.52 (m, 8H)
ppm. Anal. calcd for C22H20N2: C, 84.62;, H, 6.41; N, 8.97; found: C,
84.60; H, 6.44; N, 8.99.
Compound 3k 1H NMR (CDCl3): d3.03 (dd, J ¼ 4, 12 Hz, 1H), 3.56
(dd, J ¼ 8, 12 Hz, 1H), 3.80 (s, 3H, OCH3), 4.28 (dd, J ¼ 4, 8 Hz, 1H)
6.834–7.44 (m, 8H) ppm. Anal. calcd for C22H20N2: C, 84.62; H, 6.41;
N, 8.97; found: C, 84.60; H, 6.44; N, 8.99.
ACKNOWLEDGMENTS
We thank the Natural Science Foundation of Hebei Province
(B2006000969), China, for financial support.
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2844
J.-T. Li, X.-H. Zhang, and Z.-P. Lin
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