Chemoselective selenium dioxide oxidation of 1,4-Adducts derived from substituted arylidene acetophenones

Article abstract of DOI:10.1080/00397910802669383

The chemoselective reactions of selenium dioxide with differently substituted adducts generated by 1,4-addition on benzylidene acetophenone are described. This reaction has been shown to be dependent on the nature of the substituent present, leading to di

Full text of DOI:10.1080/00397910802669383

This article was downloaded by: [Moskow State Univ Bibliote]
On: 31 January 2014, At: 04:31
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Chemoselective Selenium
Dioxide Oxidation of 1,4-
Adducts Derived from
Substituted Arylidene
Acetophenones
Sivaperuman Saravanan a , Santhanagopalan
Purushothaman b , Irudayaraj Bernadette Amali b &
Shanmugam Muthusubramanian b
a Department of Chemistry , Ayya Nadar Janaki
Ammal College (Autonomous) , Sivakasi, India
b Department of Organic Chemistry , Madurai
Kamaraj University , Madurai, India
Published online: 14 Jul 2009.
To cite this article: Sivaperuman Saravanan , Santhanagopalan Purushothaman ,
Irudayaraj Bernadette Amali & Shanmugam Muthusubramanian (2009) Chemoselective
Selenium Dioxide Oxidation of 1,4-Adducts Derived from Substituted Arylidene
Acetophenones, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 39:16, 2882-2888, DOI:
10.1080/00397910802669383
To link to this article: http://dx.doi.org/10.1080/00397910802669383
PLEASE SCROLL DOWN FOR ARTICLE

Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communications1, 39: 2882–2888, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802669383
Chemoselective Selenium Dioxide Oxidation
of 1,4-Adducts Derived from Substituted
Arylidene Acetophenones
Sivaperuman Saravanan,1 Santhanagopalan Purushothaman,2
Irudayaraj Bernadette Amali,2 and Shanmugam Muthusubramanian2
1Department of Chemistry, Ayya Nadar Janaki Ammal College
(Autonomous), Sivakasi, India
2Department of Organic Chemistry, Madurai Kamaraj University,
Madurai, India
Abstract: The chemoselective reactions of selenium dioxide with differently
substituted adducts generated by 1,4-addition on benzylidene acetophenone are
described. This reaction has been shown to be dependent on the nature of the
substituent present, leading to different products by a-oxidation=a-oxidation
followed by dehydrogenation=dehydrogenation, enolization, and cyclization.
Keywords: Chemoselectivity, 1,2-diketones, selenium dioxide oxidation
1,2-Diketones are synthetically important because they are well known
as precursors for the synthesis of heterocyclic compounds such as
pyrazine,[1] oxazoline,[2] quinoxaline,[3] imidazoles,[4] and heterocyclic
N-oxides.[5,6] Obviously different methods of generating 1,2-diketones
receive attention, and there are a number of synthetic routes available
for the preparation of 1,2-diketones, the most important being the
selenium dioxide oxidation of active methyl or methylene group a- to
the carbonyl group.[7] 1,2-Diketones can also be prepared by the nitrosa-
tion of enols using sodium nitrite and hydrochloric acid,[8] self-coupling
Received October 19, 2008.
Address correspondence to Shanmugam Muthusubramanian, Department of
Organic Chemistry, Madurai Kamaraj University, Madurai 625 021, India.
E-mail: muthumanian2001@yahoo.com
2882

Chemoselective Selenium Dioxide Oxidation
2883
Scheme 1. Selenium dioxide oxidation of diethyl 2-(3-oxo-1,3-diarylpropyl)
malonate.
reactions of acyl group catalyzed by lanthanide salts such as samarium
diiodide,[9,10] and oxidation of substituted alkenes[11] and alkynes.[12]
Recently, a-diketones have been prepared using cobalt phthalocyanine
tetrasulphonamide[13] and ruthenium complex[14] as catalysts. This article
describes selenium dioxide–mediated oxidation of ketones generated by
1,4-addition on benzylidene acetophenone to give 1,2-diketones.
The starting materials, 1-propanone derivatives (2, 4, and 6), were
prepared by the Michael addition of corresponding nucleophiles to sub-
stituted benzylidene acetophenone 1. Compounds 2 and 4 were prepared
by the addition of diethyl malonate and benzyl cyanide respectively to
substituted chalcones in the presence of sodium ethoxide in diethyl ether
at room temperature.[15]
The selenium dioxide oxidation of compound 2 was effected in
acetic acid in a 1:5 ratio of substrate–selenium dioxide by heating the
reaction mixture on a water bath for 3 h (Scheme 1). The product 3
was isolated as a viscous liquid by silica-gel chromatography in 30%
1
yield. The structure of 3 was analyzed by infrared (IR), mass, and H
and 13C NMR spectroscopy.
It is interesting to note that when 3,5-diaryl-5-oxo-2-phenylpentane-
nitrile (4) has been subjected to selenium dioxide oxidation under the
same conditions, product 5 was obtained in 30–35% yield (Scheme 2).
Scheme 2. Selenium dioxide oxidation of 3,5-diaryl-5-oxo-2-phenylpentanenitrile.

2884
S. Saravanan et al.
Scheme 3. Selenium dioxide oxidation of ethyl 3,5-diaryl-2-cyano-5-oxopentanoate.
1
The structural features of the product, 5, were analyzed by IR and H
and 13C NMR spectroscopy.
The oxidation of ethyl 3,5-diaryl-2-cyano-5-oxopentanoate (6) was
then investigated under identical conditions (Scheme 3). The reaction
led to the formation of two products, 7 and 8, in an overall yield of
40%, with the former one being the major product. Compounds 7a and
8b were separated from the reaction mixture by column chromatography
in pure form, but the other compounds (7b, 8a, 7c, and 8c) could not be
obtained in pure form.
EXPERIMENTAL
Melting points are uncorrected. One- and two-dimensional NMR spectra
were recorded on a Bruker 300-MHz instrument in CDCl3 using tetra-
methylsilane (TMS) as internal standard. Chemical shifts are given in
parts per million (d-scale), and coupling constants are given in hertz.
IR spectra were recorded on a Jasco Fourier transform (FT)–IR instru-
ment (KBr pellet=CHCl3 solution).
General Procedure for the Reaction of Michael Adducts
with Selenium Dioxide
A solution of 2.77 g (0.025 mol) of finely powdered selenium dioxide in
10 mL of glacial acetic acid was added by portions to a warm solution
of 0.005 mol of Michael adduct 2, 4, or 6 in 10 mL of glacial acetic acid,
and the reaction mixture was heated on a water bath for 3 h. The

Chemoselective Selenium Dioxide Oxidation
2885
deposited selenium metal was filtered off, and the filtrate was poured
onto crushed ice and extracted with chloroform. The product was
purified by column chromatography using silica gel (60–120 mesh) with
petroleum ether–ethyl acetate (98:2).
Data
Diethyl 2-(2,3-dioxo-1,3-diphenylpropyl)malonate (3a)
Viscous liquid (30%): IR (CHCl3) cmꢀ1: nmax 2983, 2939, 2906, 2873,
1
1730, 1676, 1597, 1371, 1306. H NMR (300 MHz, CDCl3): d 0.95 (t,
J ¼ 7.2 Hz, 3H), 1.25 (t, J ¼ 7.2 Hz, 3H), 3.95 (q, J ¼ 7.2 Hz, 2H), 4.22
(q, J ¼ 7.2 Hz, 2H), 4.41 (d, J ¼ 12.0 Hz, 1H), 5.34 (d, J ¼ 12.0 Hz, 1H),
7.22–7.36 (m, 5H), 7.40 (m, 2H), 7.54 (t, J ¼ 7.5 Hz, 1H), 7.87 (d, J ¼
8.1 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3): d 14.1, 14.4, 52.6, 55.0,
61.9, 62.6, 128.9, 129.0, 129.5, 129.9, 130.7, 132.4, 132.8, 134.7, 167.6,
168.3, 190.2, 197.0 ppm.
Diethyl 2-[1-(4-methylphenyl)-2,3-dioxo-3-phenylpropyl]malonate (3b)
Viscous liquid (28%): IR (CHCl3) cmꢀ1: nmax 2983, 2939, 2906, 2873,
1730, 1676, 1597, 1371, 1306 cmꢀ1 1H NMR (300 MHz, CDCl3): d
.
1.00 (t, J ¼ 7.2 Hz, 3H), 1.26 (t, J ¼ 7.2 Hz, 3H), 2.26 (s, 3H), 3.97 (q, J ¼
7.2 Hz, 2H), 4.22 (q, J ¼ 7.2 Hz, 2H), 4.36 (d, J ¼ 11.7 Hz, 1H), 5.30 (d,
J ¼ 11.7 Hz, 1H), 7.09 (d, J ¼ 8.1 Hz, 2H), 7.20 (d, J ¼ 8.1 Hz, 2H), 7.40
(t, J ¼ 7.5 Hz, 2H), 7.55 (tt, J ¼ 7.5, 1.8 Hz, 1H), 7.87 (dd, J ¼ 7.5,
1.8 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3): d 13.8, 14.0, 21.1, 51.9,
54.6, 61.5, 62.2, 128.5, 128.7, 129.3, 129.8, 130.3, 132.5, 134.2, 138.3,
167.2, 168.0, 189.9, 196.7 ppm.
Diethyl 2-[3-(4-chlorophenyl)-1-(4-methylphenyl)-2,3-
dioxopropyl]malonate (3c)
Viscous liquid (27%): IR (CHCl3) cmꢀ1: nmax 2983, 2939, 2906, 2873,
1730, 1680, 1589, 1371, 1307 cmꢀ1 1H NMR (300 MHz, CDCl3): d
.
1.00 (t, J ¼ 7.2 Hz, 3H), 1.26 (t, J ¼ 7.2 Hz, 3H), 2.27 (s, 3H), 4.00 (q, J ¼
7.2 Hz, 2H), 4.22 (q, J ¼ 7.2 Hz, 2H), 4.36 (d, J ¼ 12.0 Hz, 1H), 5.27 (d,
J ¼ 12.0 Hz, 1H), 7.09 (d, J ¼ 8.1 Hz, 2H), 7.20 (d, J ¼ 8.1 Hz, 2H), 7.39
(d, J ¼ 8.4 Hz, 2H), 7.84 (d, J ¼ 8.4 Hz, 2H) ppm. 13C NMR (75 MHz,
CDCl3): d 13.8, 14.0, 21.1, 51.7, 54.6, 61.5, 62.2, 128.6, 128.9, 129.2,
129.9, 130.8, 131.7, 138.4, 140.9, 167.1, 168.0, 188.5, 196.3 ppm.

2886
S. Saravanan et al.
5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4,5-dioxo-2-phenyl-2-
pentenenitrile (5a)
Colorless solid (30%), mp 150ꢁC. Anal. calcd. for C24H16ClNO3: C,
71.73; H, 4.01; N, 3.49. Found: C, 71.79; H, 4.10; N, 3.51. IR (KBr): nmax
1604, 1670, 2208 cmꢀ1. 1H NMR (300 MHz, CDCl3): d 3.87 (s, 3H), 7.00
(d, J ¼ 7.5 Hz, 2H), 7.15–7.45 (m, 7H), 7.54 (d, J ¼ 8.7 Hz, 2H), 7.75 (d,
J ¼ 8.7 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3): d 55.4, 114.5, 117.6,
117.8, 126.7, 128.7, 129.4, 129.7, 129.9, 130.5, 130.6, 130.9, 131.3,
141.1, 152.6, 161.5, 187.7, 193.4 ppm.
3-(4-Methoxyphenyl)-5-(4-methylphenyl)-4,5-dioxo-2-phenyl-2-
pentenenitrile (5b)
Colorless solid (34%), mp 156ꢁC. Anal. calcd. for C25H19NO3: C, 78.72;
H, 5.02; N, 3.67. Found: C, 78.75; H, 5.09; N, 3.71. IR (KBr): nmax 1602,
1658, 1677, 2212 cmꢀ1. 1H NMR (300 MHz, CDCl3): d 2.41 (s, 3H), 3.92
(s, 3H), 6.97 (d, J ¼ 9.0 Hz, 2H), 7.38 (d, J ¼ 8.4 Hz, 2H), 7.43 (m, 5H),
7.52 (d, J ¼ 9.0 Hz, 2H), 7.70 (d, J ¼ 8.4 Hz, 2H) ppm. 13C NMR
(75 MHz, CDCl3): d 21.9, 55.4, 114.5, 117.6, 117.8, 126.8, 128.8, 129.1,
129.2, 129.5, 130.2, 130.3, 130.9, 132.9, 145.8, 153.0, 161.3, 188.5,
193.5 ppm.
3,5-Bis(4-methylphenyl)-4,5-dioxo-2-phenyl-2-pentenenitrile (5c)
Colorless solid (31%), mp 117ꢁC. Anal. calcd. for C25H19NO2: C, 82.17;
H, 5.24; N, 3.83. Found: C, 82.20; H, 5.27; N, 3.86. IR (KBr): nmax 1656,
1
1691, 2206 cmꢀ1. H NMR (300 MHz, CDCl3): d 2.39 (s, 3H), 2.41 (s,
3H), 7.12–7.52 (m, 11H), 7.72 (d, J ¼ 8.4 Hz, 2H) ppm. 13C NMR
(75 MHz, CDCl3): d 21.5, 21.9, 117.6, 118.7, 129.0, 129.1, 129.1, 129.2,
129.5, 129.8, 130.3, 130.4, 131.6, 132.8, 141.0, 149.9, 153.5, 188.6,
193.6 ppm.
Ethyl 6-(4-chlorophenyl)-4-(methoxyphenyl)-2-oxo-2H-pyran-3-carboxylate (7a)
Colorless solid (32%), mp 119ꢁC. Anal. calcd. for C21H17ClO5: C, 65.55;
H, 4.45. Found: C, 65.59; H, 4.52. IR (KBr): nmax 1604, 1625, 1708 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d 1.13 (t, J ¼ 7.2 Hz, 3H), 3.84 (s, 3H), 4.20
(q, J ¼ 7.2 Hz, 2H), 6.71 (s, 1H), 6.96 (d, J ¼ 8.7 Hz, 2H), 7.41 (d,
J ¼ 8.7 Hz, 2H), 7.42 (d, J ¼ 9.0 Hz, 2H), 7.79 (d, J ¼ 9.0 Hz, 2H) ppm.
13C NMR (75 MHz, CDCl3): d 13.8, 55.4, 61.8, 103.6, 114.3, 115.9,

Chemoselective Selenium Dioxide Oxidation
2887
127.1, 128.0, 128.9, 129.2, 129.3, 137.6, 154.5, 158.9, 159.3, 161.3,
165.1 ppm.
4-(4-Methoxyphenyl)-6-(4-methylphenyl)-2-oxo-2H-pyran-3-
carbonitrile (8b)
Colorless solid (37%), mp 199ꢁC. Anal. calcd. for C20H15NO3: C, 75.70; H,
4.76; N, 4.41. Found: C, 75.68; H, 4.77; N, 4.43. IR (KBr): nmax 1602, 1617,
1743, 2217 cmꢀ1. 1H NMR (300 MHz, CDCl3): d 2.44 (s, 3H), 3.90 (s, 3H),
6.89 (s, 1H), 7.07 (d, J ¼ 8.7 Hz, 2H), 7.32 (d, J ¼ 8.4 Hz, 2H), 7.76 (d,
J ¼ 8.7 Hz, 2H), 7.82 (d, J ¼ 8.4 Hz, 2H) ppm. 13C NMR (75 MHz,
CDCl3): d 21.6, 55.4, 102.2, 114.6, 115.2, 126.3, 126.4, 127.2, 129.9 (two
carbons merged here), 130.0, 143.6, 157.6, 162.7, 162.9, 163 ppm.
ACKNOWLEDGMENTS
The authors thank the Department of Science and Technology, New
Delhi, for use of the NMR spectrometer facility. Financial support from
the Council of Scientific and Industrial Research, New Delhi, for one of
the authors (S. S.) is gratefully acknowledged.
REFERENCES
1. (a) Gallagher, J. J.; Newbold, G. T.; Spring, F. S.; Woods, J. C. Pyrazine
derivatives, part IX: The conversion of DL-phenylglycine anhydride into
3-hydroxy-2:5-diphenylpyrazine. J. Chem. Soc. 1949, 910–912; (b) Schubert,
H.; Eissfeldt, I.; Lange, R.; Trefflich, F. n-Alkyl- und n-alkoxyderivate des
3-hydroxy-2,5-diphenyl-pyrazins. J. Prakt. Chem. 1966, 33, 265–276.
2. Rizzi, G. P. The formation of tetramethylpyrazine and 2-isopropyl-4,
5-dimethyl-3-oxazoline in the Strecker degradation of DL-valine with
2,3-butanedione. J. Org. Chem. 1969, 34, 2002–2004.
3. Bhosale, R. S.; Sarda, S. R.; Ardhapure, S. S.; Jadhav, W. N.; Bhusare, S. R.;
Pawar, R. P. An efficient protocol for the synthesis of quinoxaline derivatives
at room temperature using molecular iodine as the catalyst. Tetrahedron Lett.
2005, 46, 7183–7186.
4. Usyatinsky, A. Y.; Khmelnitsky, Y. L. Microwave-assisted synthesis of
substituted imidazoles on a solid support under solvent-free conditions.
Tetrahedron Lett. 2000, 41, 5031–5034.
5. Pedersen, C. L. Preparation of disubstituted 1,2,5-selenadiazole N-oxides from
1,2-diketone dioximes and diselenium dichloride: Thermolysis and photolysis
of 2,1,3-benzoselenadiazole N-oxide. J. Chem. Soc., Chem. Commun. 1974,
17, 704–705.

2888
S. Saravanan et al.
6. (a) Dunn, G.; Elvidge, J. A.; Newbold, G. T.; Ramsay, D. W. C.; Spring, R.
S.; Sweeny, W. Synthesis of pyrazine cyclic hydroxamic acids related to asper-
gillic acid. Nature 1949, 164, 181–181; (b) Dunn, G.; Elvidge, J. A.; Newbold,
G. T.; Ramsay, D. W. C.; Spring, R. S.; Sweeny, W. Pyrazine derivatives,
part XI: Synthesis of cyclic hydroxamic acids related to aspergillic acid. J.
Chem. Soc. 1949, 2707–2712.
7. Corey, E. J.; Schaefer, J. P. Studies on the mechanism of oxidation of ketones
by selenium dioxide (part I). J. Am. Chem. Soc. 1960, 82, 918–929.
8. Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic Chemistry; Oxford
University Press: New York, 2001; p. 539.
9. Wang, X.; Zhang, Y. Samarium diiodide promoted formation of 1,2-
diketones and 1-acylamido-2-substituted benzimidazoles from N-acylbenzo-
triazoles. Tetrahedron 2003, 59, 4201–4207.
10. Saikia, P.; Laskar, D. D.; Prajapati, D.; Sandhu, J. S. A new ytterbium
iodide mediated coupling of acyl cyanides and synthesis of 1,2-diketones.
Tetrahedron Lett. 2002, 43, 7525–7526.
11. Boyer, J.; Bernardes-Genisson, V.; Nepveu, F. Access to unsymmetrical
1,2-diketone intermediates via benzeneseleninic anhydride-promoted
oxidation: Application to indolone-N-oxide synthesis. J. Chem. Res. Synop.
2003, 8, 507–508.
12. Wan, Z.; Jones, C. D.; Mitchell, D.; Pu, J. Y.; Zhang, T. Y. Practical method
for transforming alkynes into diketones. J. Org. Chem. 2006, 71, 826–828.
13. Jain, S. L.; Sain, B. Cobalt phthalocyaninetetrasulphonamide catalyzed
aerobic oxidation of a-hydroxyketones: An efficient and simple synthesis of
a-diketones. J. Mol. Catal. A: Chem. 2001, 176, 101–104.
14. Chang, C.-L.; Kumar, M. P.; Liu, R.-S. A highly efficient ruthenium-
catalyzed rearrangement of epoxyketones to 1,2-diketones. J. Org. Chem.
2004, 69, 2793–2796.
15. (a) Saravanan, S.; Muthusubramanian, S. Synthesis and spectral chara-
cterization of diethyl 2-[aryl(4-aryl-1,2,3-selenadiazol-5-yl)methyl]malonate.
Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 2411–2421; (b) Saravanan,
S.; Sridharan, V.; Muthusubramanian, S. Chemoselective addition of
hydrazine to d-keto esters and dimethylformamide mediated deesterification.
Synth. Commun. 2006, 36, 849–858.