Efficient and alternative approach for preparation of O-benzoyloximes using benzoyl peroxide

Article abstract of DOI:10.1080/00397911.2010.545165

Benzoyl peroxide has been used as a mild and efficient reagent for the preparation of benzoyl ester of oxime in moderate to good yields. Copyright Taylor & Francis Group, LLC.

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Efficient and Alternative Approach for
Preparation of O-Benzoyloximes Using
Benzoyl Peroxide
Shrishnu Kumar Kundu a , Matiur Rahman a , Paritosh Dhara b ,
Alakananda Hajra a & Adinath Majee a
a Department of Chemistry , Visva-Bharati University , Santiniketan ,
India
b Syngene International Pvt. Ltd. , Bangalore , Karnataka , India
Accepted author version posted online: 17 Nov 2011.Published
online: 27 Feb 2012.
To cite this article: Shrishnu Kumar Kundu , Matiur Rahman , Paritosh Dhara , Alakananda Hajra &
Adinath Majee (2012) Efficient and Alternative Approach for Preparation of O-Benzoyloximes Using
Benzoyl Peroxide, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 42:12, 1848-1854, DOI: 10.1080/00397911.2010.545165
To link to this article: http://dx.doi.org/10.1080/00397911.2010.545165
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Synthetic Communications1, 42: 1848–1854, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.545165
EFFICIENT AND ALTERNATIVE APPROACH FOR
PREPARATION OF O-BENZOYLOXIMES USING
BENZOYL PEROXIDE
Shrishnu Kumar Kundu,1 Matiur Rahman,1 Paritosh Dhara,2
Alakananda Hajra,1 and Adinath Majee1
1Department of Chemistry, Visva-Bharati University, Santiniketan, India
2Syngene International Pvt. Ltd., Bangalore, Karnataka, India
GRAPHICAL ABSTRACT
Abstract Benzoyl peroxide has been used as a mild and efficient reagent for the preparation
of benzoyl ester of oxime in moderate to good yields.
Keywords Benzoyl peroxide; ester; oxime
INTRODUCTION
There are numerous reports on the use of oxime ester for peptide synthesis.[1]
Because of the lesser reactivity of oxime esters toward an amine component, weak
acids are used to enhance the reaction.[2] Hayashi and Shimizu[3] reported that aro-
matic oxime esters containing hydroxy groups are very effective for peptide synthesis
(Scheme 1).
Another important use of oxime ester is as lipoprotein-associated phospholi-
phase A2 inhibitors.[4] Very recently,[5] it has been observed that oxime ester photo-
initiators such as OXE-1 and OXE-2 (Fig. 1) meet the specific requirements desired
for color filter displays, which usually consist of translucent pixels of three primary
colors (red, green, and blue) surrounded by a black matrix frame in mobile phones,
notebook computers and televisions.
Hence, preparation of oxime ester is of much importance in organic synthesis.
The only available methods in the literature for synthesis of acyl and benzoyl ester of
Received October 21, 2010.
Address correspondence to Alakananda Hajra or Adinath Majee, Department of Chemistry, Visva-
Bharati University, Santiniketan 731235, India. E-mail: alakananda.hajra@visva-bharati.ac.in; adinath.
majee@visva-bharati.ac.in
1848

PREPARATION OF O-BENZOYLOXIMES
1849
Scheme 1. Oxime ester for peptide synthesis.
Scheme 2. Synthesis of benzoyloximes.
Figure 1. Photo-active oximes.
oxime are by treatment with acetic anhydride or acylchloride = benzoyl chloride in
presence of triethylamine or pyridine as base.[6] Reaction of a (E, Z)-mixture or
Z-oxime with benzoyl or acyl chlorides gives only E-isomers of ester as Z-isomer
could be isomerized to the (E)-isomer by triethyl ammonium chloride.[7] Hence, to
avoid this isomerization and use of pyridine in stoichiometric or even excess,[6] devel-
opment of a simple and convenient method that can be applied under milder and
environmentally friendly conditions is highly desirable. Benzoyl peroxide is usually
used as radical initiator. It has been also used as benzoylation reagent of alcohols
to form benzoylesters.[8] As a part of our research project to provide greener meth-
odology,[9] we have observed that the reaction of benzoyl peroxide with oxime gives
benzoyl ester of oxime in moderate to good yields under the present reaction
conditions (Scheme 2).
RESULTS AND DISCUSSION
In a typical experimental procedure, a mixture of oxime (1 mmol) and benzoyl
peroxide (1.5 mmol) in dichloromethane (2 ml) was refluxed in open atmospheric
pressure for a certain period of time as required for the reaction (as monitored by
thin-layer chromatography, TLC). After completion of the reaction, the crude

1850
S. K. KUNDU ET AL.
Table 1. Preparation of benzoyl ester of oxime
Entry
R1
R2
Time (h)
Yield (%)a
Ref.
1
2
C6H5
4-CH3-C6H4
C6H5
H
7
7
5
8
6
6
4
3
3
6
4
3
84
86
80
70
87
85
85
78
90
88
90
90
[10]
—
H
3
CH3
C2H5
H
[10]
—
4
C6H5
5
4-OCH3-C6H4
4-OAllyl-C6H4
C6H5
—
—
6
CH3
C6H5
CH3
C2H5
7
[10]
—
8
(CH3)2CHCH2
C2H5
9
—
—
10
11
12
a-Tetralone
Cyclohexanone
Cyclopentanone
—
—
aPure isolated product.
mixture was washed with sodium bicarbonate solution and finally with brine
solution. Evaporation of the organic solvent under reduced pressure afforded the
product. A wide range of structurally diverse oxime was subjected to this procedure
to get the corresponding ester as summarized in Table 1.
It has been observed that the aromatic ring containing electron-donating group
such as –O-allyl, OMe, and Me is unaffected under the present reaction conditions
and gives ester as the sole product. No amide or other product has been isolated
in this reaction condition. Aldoxime with electron-withdrawing group such as
-NO2 and Cl in the benzene ring is inert under the present reaction conditions.
The yields of some products were verified by repeating some experiments two or
three times. The reaction conditions are same for all the reactions.
CONCLUSION
In conclusion, we have developed a highly efficient methodology for the
synthesis of O-benzoyloxime derivatives with moderate to good yields under mild
conditions without use of a base such as triethyl amine or pyridine. Operational
simplicity and the compatibility with various functional groups are the advantages
of the present procedure. We believe that this will present a very simple and more
practical alternative to the existing methodologies for the synthesis of oxime ester.
EXPERIMENTAL
Melting points were determined on a glass disk with an electrical bath and were
1
uncorrected. H NMR (400-MHz) and 13C NMR (100-MHz) spectra were run in

PREPARATION OF O-BENZOYLOXIMES
1851
CDCl3 solutions. Infrared (IR) spectra were taken as KBr pellets in a Shimazdu
8400S FTIR. Elemental analyses were done on a Perkin-Elmer autoanalyzer.
Synthesis of Oxime Ester (Entry 3)
A mixture containing acetophenoneoxime (120 mg, 1 mmol) and benzoyl per-
oxide (363 mg, 1.5 mmol) in dichloromethane (2 ml) was refluxed in an open atmos-
pheric pressure for a certain period of time as required for the reaction (TLC). After
completion of the reaction, the crude mixture was washed with sodium bicarbonate
solution (3 ꢀ 10 ml) and finally with brine solution (2 ꢀ 5 ml). Evaporation of the
organic solvent under reduced pressure afforded the product. The crude product
was purified (192 mg, 80%) by column chromatography (ethyl acetate and petroleum
ether 60–80 ꢁC). Solid; mp 96 ꢁC (lit. 98–99 ꢁC)[10]; IR (KBr, cmꢂ1): 3021, 2921, 1740,
1596, 1490, 1448. 1H NMR (CDCl3): d 2.85 (s, 3H), 7.39–7.52 (m, 6H), 7.57–7.62 (m,
1H), 7.80–7.83 (m, 1H), 8.05–8.14 (m, 2H). 13C NMR (CDCl3): d 15.12, 127.56 (2C),
128.82, 129.02 (2C), 129.29, 130.06, 130.19 (2C), 131.10, 133.78, 134.74, 164.09,
164.24.
All products were characterized by their spectral and analytical data.
Benzaldehyde Oxime Benzoyl Ester (1)
Yellow solid; mp 98 ꢁC (lit. 99–100 ꢁC)[10]; IR (KBr): 1764, 1741, 1596, 1450,
1
1226 cmꢂ1; H NMR (CDCl3): d 7.44–7.62 (m, 5H), 7.79–7.83 (m, 2H), 8.07–8.15
(m, 3H), 8.5 (s, 1H, -NH). 13C NMR (CDCl3): d 128.43, 128.53, 128.54, 128.83,
128.91, 129.75, 129.81, 130.21, 131.76, 133.38, 133.67, 134.21, 156.68, 171.79.
p-Methyl Benzaldehyde Oxime Benzoyl Ester (2)
Solid; mp 97 ꢁC; IR (KBr): 1737, 1606, 1449 cmꢂ1; 1H NMR (CDCl3): d 2.41 (s,
3H), 7.26 (d, 2H, J ¼ 8 Hz), 7.49 (t, 2H, J ¼ 8 Hz), 7.60 (t, 1H, J ¼ 8 Hz), 7.71 (d, 2H,
J ¼ 8 Hz), 8.13 (d, 2H, J ¼ 3 Hz), 8.53 (s, 1H, NH). 13C NMR (CDCl3): d 21.65,
127.30, 128.50, 128.55, 128.73, 129.67, 129.71, 133.36, 142.40, 156.78, 164.07. Anal.
calcd. for C15H13NO2: C, 75.30; H, 5.48; N, 5.85. Found: C, 75.25; H, 5.41; N, 5.69.
Propeophenoneoxime Benzoyl Ester (4)
Solid; mp 98 ꢁC; IR (KBr): 1747, 1604, 1452 cmꢂ1; 1H NMR (CDCl3): d 1.29 (t,
3H, J ¼ 7.5 Hz), 2.96 (t, 3H, J ¼ 7.5 Hz), 7.25–7.36 (m, 6H), 7.93 (d, 2H, J ¼ 8.7 Hz),
8.10 (d, 2H, J ¼ 7.8 Hz). 13C NMR (CDCl3): d 11.14, 21.81, 127 (2C), 128.11, 128.22,
128.34, 128.46, 128.79, 129.21, 130.11, 133.08, 133.48, 163.58, 168.14. Anal. calcd.
for C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C, 75.69; H, 5.91; N, 5.48.
4-Methoxybenzaldehyde Oxime Benzoyl Ester (5)
IR (KBr): 1746, 1607, 1461 cmꢂ1; 1H NMR (CDCl3): d 1.19 (s, 3H), 3.84 (s, 3H),
6.94 (m, 2H), 7.23–7.26 (d, 1H, J ¼ 9 Hz), 7.28–7.33 (t, 1H, J ¼ 7.5 Hz), 7.43–7.49 (t,
2H, J ¼ 9 Hz), 7.57–7.63 (m, 2H), 7.92–7.93 (d, 1H, J ¼ 1.5 Hz), 7.96–8.12 (m, 1H).

1852
S. K. KUNDU ET AL.
13C NMR (CDCl3): d 19.95, 55.33, 113.52 (2C), 125.10, 127.99, 128.28, 128.52,
128.56, 129.40, 130.02, 161.56, 172.37. Anal. calcd. for C15H13NO3: C, 70.58; H,
5.13; N, 5.49. Found: C, 70.45; H, 5.09; N, 5.46.
4-O-Allylacetophenone Oxime Benzoyl Ester (6)
1
IR (KBr): 1743, 1602, 1452 cmꢂ1; H NMR (CDCl3): d 2.51 (s, 3 H), 4.56 (d,
2H, J ¼ 5.2 Hz), 5.30 (d, 1H, J ¼ 10.5 Hz), 5.41 (d, 1H, J ¼ 17.1 Hz), 5.99–6.09 (m,
1H), 6.94 (d, 2H, J ¼ 8.0 Hz), 7.48 (t, 2H, J ¼ 7.5 Hz), 7.76 (d, 1H, J ¼ 7.5 Hz),
7.78 (d, 2H, J ¼ 8 Hz), 8.12 (d, 2H, J ¼ 7.5 Hz). 13C NMR (CDCl3): d 14.26, 68.78,
114.33, 114.65, 118.00, 127.17, 128.47, 128.58, 129.29, 129.51, 129.97, 130.38,
130.46, 132.73, 133.13, 160.60, 162.92, 163.78. Anal. calcd. for C18H17NO3: C,
73.20; H, 5.80; N, 4.74. Found: C, 73.15; H, 5.76; N, 4.71.
Benzophenone Oxime Benzoyl Ester (7)
1
Solid; mp 99 ꢁC (lit. 98–99 ꢁC)[10]; IR (KBr): 1758, 1596, 1450, 1317 cmꢂ1; H
NMR (CDCl3): d 7.25–7.70 (m, 11H), 7.77 (t, 1H, J ¼ 3 Hz), 7.81 (t, 1H, J ¼ 3 Hz),
8.05 (t, 1H, J ¼ 3 Hz), 8.09 (t, 1H, J ¼ 3 Hz). 13CNMR (CDCl3): d 125.58, 128.14
(2C), 128.32, 128.73 (2C), 129.00, 129.52, 129.66 (2C), 129.92 (2C), 130.89, 132.25
(2C), 134.11 (2C), 137.49, 162.79, 165.26.
Isobutyl Methyl Ketone Oxime Benzoyl Ester (8)
IR (KBr): 1746, 1600, 1453 cmꢂ1; 1H NMR (CDCl3): d 1.07 (d, 6H, J ¼ 7.4 Hz),
1.98–2.05 (m, 1H), 2.10 (s, 3H), 2.32 (d, 2H, J ¼ 7.4 Hz), 7.60 (t, 2H, J ¼ 6.4 Hz), 7.66
(t, 1H, J ¼ 6.4 Hz), 8.07 (d, 2H, J ¼ 6.4 Hz). 13C NMR (CDCl3): d 15.60, 22.36, 22.78,
25.93, 44.46, 125.25, 128.49, 128.87, 129.55, 129.78, 134.38, 163.07, 167.05. Anal.
calcd. for C13H17NO2: C, 71.21; H, 7.81; N, 6.39. Found: C, 71.11; H, 7.75; N, 6.35.
Diethylketone Oxime Benzoyl Ester (9)
1
IR (KBr): 1743, 1633, 1456 cmꢂ1; H NMR (CDCl3): d 1.18–1.24 (m, 6 H),
2.42–2.69 (m, 4H), 7.46 (t, 2H, J ¼ 7.2 Hz), 7.55 (d, 1H, J ¼ 7.2 Hz), 8.06–8.12 (d,
2H, J ¼ 7.2 Hz). 13C NMR (CDCl3): d 10.29, 10.57, 22.44, 27.12, 128.03, 128.23,
129.03, 129.15, 129.70, 132.87, 163.74, 172.47. Anal. calcd. for C12H15NO2: C,
70.22; H, 7.37; N, 6.82. Found: C, 70.17; H, 7.31; N, 6.79.
a-Tetraloneoxime Benzoyl Ester (10)
IR (KBr): 1735, 1596, 1452 cmꢂ1; 1H NMR (CDCl3): d 1.92–1.99 (m, 2H), 2.83
(t, 2H, J ¼ 6.4 Hz), 3.04 (t, 2H, J ¼ 6.4 Hz), 7.2 (d, 1H, J ¼ 7.6 Hz), 7.27 (t, 1H,
J ¼ 7.6 Hz), 7.38 (t, 1H, J ¼ 7.6 Hz), 7.50 (t, 1H, J ¼ 7.6 Hz), 7.61 (t, 2H, J ¼ 7.6 Hz),
7.66 (d, 1H, J ¼ 7.6 Hz), 8.19 (d, 2H, J ¼ 7.6 Hz), 8.31 (d, 1H, J ¼ 7.6 Hz). 13C NMR
(CDCl3): d 21.37, 25.85, 29.56, 125.91, 126.65, 128.57 (2C), 128.68, 128.95, 129.33
(2C), 130.85, 133.27, 140.94, 162.47, 163.85. Anal. calcd. for C17H15NO2: C,
76.96; H, 5.70; N, 5.28. Found: C, 76.79; H, 5.62; N, 5.20.

PREPARATION OF O-BENZOYLOXIMES
1853
Cyclohexanoneoxime Benzoyl Ester (11)
IR (KBr): 1741, 1637, 1448 cmꢂ1; 1H NMR (CDCl3): d 1.58–1.76 (m, 6 H), 2.41
(t, 2H, J ¼ 6.3 Hz), 2.62 (t, 2H, J ¼ 6.3 Hz), 7.43 (t, 2H, J ¼ 6.9 Hz), 7.55 (t, 1H,
J ¼ 6.9 Hz), 8.01 (d, 2H, J ¼ 6.9 Hz). 13C NMR (CDCl3): d 25.49, 25.66, 26.57,
26.92, 31.98, 128.11 (2C), 128.27, 129.14 (2C), 129.32, 129.79, 132.94, 164.09,
164.41. Anal. calcd. for C13H15NO2: C, 71.87; H, 6.96; N, 6.45. Found: C, 71.80;
H, 6.90; N, 6.41.
Cyclopentanone Oxime Benzoyl Ester (12)
1
IR (KBr): 1742, 1658, 1450, 1255 cmꢂ1; H NMR (CDCl3): d 1.81 (bs, 4H),
2.60 (t, 2H, J ¼ 6.8 Hz), 2.66 (t, 2H, J ¼ 6.8 Hz), 7.44 (t, 2H, J ¼ 7.3 Hz), 7.56 (t,
1H, J ¼ 7.3 Hz), 8.05 (d, 2H, J ¼ 7.3 Hz). 13C NMR (CDCl3): d 24.09, 24.69,
28.92, 31.06, 128.08 (2C), 128.69, 129.08 (2C), 132.79, 163.59, 175.88. Anal. calcd.
for C12H13NO2: C, 70.92; H, 6.45; N, 6.89. Found: C, 70.81; H, 6.41; N, 6.79.
ACKNOWLEDGMENTS
A. M. is pleased to acknowledge the financial support from the Council of
Scientific and Industrial Research (Grant No. 01(2251)=08=EMR-II. A. H. is pleased
to acknowledge the financial support from the Department of Science and Tech-
nology, DST (Grant No. SR=FTP=CS-107=2006). We are thankful to DST–Funding
for Infrastructure in Science and Technology and SAP–University Grants
Commission.
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