Oxidative cleavage of 1,3-diaryl/(heteroaryl)benzo[c]furans into 1,2-diaroyl/(heteroaroyl)benzenes using selenium dioxide

Article abstract of DOI:10.1080/00397911.2016.1204461

Reaction of 1,3-disubstituted isobenzofurans (IBFs) with selenium dioxide in tetrahydrofuran (THF) at room temperature led to the formation of 1,2-diaroyl/(heteroaroyl)benzenes in good to excellent yields.

Full text of DOI:10.1080/00397911.2016.1204461

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Oxidative Cleavage of 1,3-Diaryl/
(heteroaryl)benzo[ c]furans into 1,2-Diaroyl/
(Heteroaroyl)benzenes using Selenium Dioxide
Jayachandran Karunakaran, Elumalai Sankar & Arasambattu K
Mohanakrishnan
To cite this article: Jayachandran Karunakaran, Elumalai Sankar & Arasambattu K
Mohanakrishnan (2016): Oxidative Cleavage of 1,3-Diaryl/(heteroaryl)benzo[ c]furans into
1,2-Diaroyl/(Heteroaroyl)benzenes using Selenium Dioxide, Synthetic Communications, DOI:
10.1080/00397911.2016.1204461
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1204461
View supplementary material
Accepted author version posted online: 23
Jun 2016.
Published online: 23 Jun 2016.
Submit your article to this journal
Article views: 14
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [Boston University]
Date: 25 June 2016, At: 04:16

Oxidative Cleavage of 1,3-Diaryl/(heteroaryl)benzo[c]furans into 1,2-
Diaroyl/(heteroaroyl)benzenes using Selenium dioxide
Jayachandran Karunakaran1, Elumalai Sankar1, Arasambattu K Mohanakrishnan1
1Department of Organic Chemistry, School of Chemistry, University of Madras, Chennai,
Tamil Nadu, India
Corresponding author to A. K Mohanakrishnan: E-mail:
mohanakrishnan@unom.ac.in/mohan_67@hotmail.com
Abstract
Reaction of 1,3-disubstituted isobenzofurans (IBFs) with selenium dioxide in THF at
room temperature led to the formation of 1,2-diaroyl/(heteroaroyl)benzenes in good to
excellent yields.
KEYWORDS: Isobenzofuran, Oxidative cleavage, Selenium dioxide, 1,2-
Diaroylbenzenes
INTRODUCTION
Over the years, the 1,3-diarylbenzo[c]furan analogues have been exploited as diene
in the Diels-Alder reaction for the syntheses of π-conjugated carbocycles1 as well as
1

heterocycles2. The benzo[c]furans have also been utilized as an ideal precursor for the
synthesis of 1,3-disusbtituted benzo[c]selenophenes3. The synthesis of stable
benzo[c]furan based cyanovinylenes as near-IR fluorophores have also been explored4.
Nevertheless, the photochemical degradation of 1,3-diarylbenzo[c]furan analogues has
been considered as a potential drawback, severally minimizing their optical applications5.
In further exploitation of their utility, recently, a facile synthetic transformation of
isobenzofurans into the annulated arenes and heteroarenes have also been reported6.
Oxidative transformation of the 1,3-disubstituted benzo[c]furans (IBFs) into their
respective diaroylbenzenes are achieved using lead tetraacetate (LTA)7, singlet oxygen8,
m-CPBA9 and active MnO2.10 Even though, these methods were employed for the
synthetic transformation of 1,3-diarylbenzo[c]furans into 1,2-diaroylbenzenes, each one
of them are having inherent disadvantageous10. The unstable nature of 1,3-
diarylbenzo[c]furans coupled with undesired oxidation of thiophene unit9 prompted us to
explore the oxidative cleavage of these heterocycles with other oxidizing agents. Over the
years, selenium dioxide (SeO2) has been employed for smooth oxidation of allylic as well
as methyl ketone11 functions of organic compounds. An efficient synthesis of
triarylethanones was achieved by Myrboh and coworkers through SeO2-BF3.OEt2
promoted12 bis-arylation of acetophenones at room temperature. Recently, Liu et al.
reported the synthesis of N-arylisatins involving SeO2-mediated oxidative-amidation13 of
2-arylaminoacetophenone. Encouraged by these recent reports and also based on
synthetic utility of 1,2-diaroylbenzenes,6 a systematic study on oxidation of 1,3-
disubstitued benzo[c]furans using SeO2 were initiated.
2

RESULTS AND DISCUSSION
As a representative case, the reaction of symmetrical 1,3-diarylbenzo[c]furan 1a/1,3-
diheteroaryl 1b with 1.5 eq. of SeO2 in dry THF at room temperature for 5 minutes
afforded the known diketone 2a/2b9 in an excellent yield. While stirring at room
temperature, the sudden change of an orange-yellow fluorescent color of isobenzofuran
1a/1b confirmed its transformation into the respective diketone 2a/2b. Similarly, the aryl
substituted unsymmetrical isobenzofuran 1c/1d also underwent smooth oxidative
cleavage to give the corresponding diketone 2c/2d.
The facile transformation of the isobenzofurans 1a-d into the respective diketones
2a-d using SeO2 encouraged us to do the oxidative cleavage of various types of
unsymmetrical isobenzofuran derivatives 1e-n, Table 1.
The SeO2-mediated oxidative cleavage was found to be successful with
dibenzoheterocycle as well as triphenylamine based isobenzofuran derivatives 1e-g
(entries 1-3). The pyrene, bithiophene and dihexylfluorene tethered benzo[c]furans 1h-j
are also underwent facile oxidative cleavages using SeO2 to afford respective diketones
2h-j (entries 4-6). Next, the oxidative ring opening reaction was also performed with
diphenylmethane as well as dibenzofuran incorporated isobenzofurans 1k and 1l (entries
7, 8). Finally, the biphenyl and benzo[b]thiophene based isobenzofuran 1m, 1n also
3

participated in the SeO2-mediated ring opening reaction to afford the corresponding
diketone 2m and 2n in good yields (entries 9, 10).
Next, the reaction of N-hexylcarbazole tethered bis-benzo[c]furan 3a with 3 eqs. of SeO2
at room temperature led to the formation of the respective tetra ketone 4a in 83% yield.
Under same conditions, the bithiophene-, triphenylamine- and thiophene based bis-
benzo[c]furans 3b-d could be smoothly converted into the respective tetra ketones 4b-d
in good yields.
The triphenylamine based tris-benzo[c]furan 5 also underwent the facile SeO2 mediated
oxidative cleavage to afford tris-diketone 6 in 79% of yield.
4

The classical 2,5-diphenylfuran 7 also underwent SeO2-mediated oxidative cleavage in
toluene at reflux to give the respective cis-diketone 810 in 78% yield.
Finally, an attempted cleavage of 1,3-dithienylbenzo[c]thiophene 9 using 1.5 eq. of SeO2
in THF at room temperature and also at refluxing condition of toluene failed to give the
expected diketone 2b.
A plausible mechanism for the formation of 1,2-diaroylbenzenes from benzo[c]furans
using SeO2 is shown in the Scheme 1. The benzo[c]furans 1a-n upon reaction with SeO2
led to the formation of Diels-Alder type of adducts 10, which upon elimination of
divalent selenoxide furnished the diketones 11. The observed failure to cleave the non-
classical thiophene unit of 1,3-dithienyl benzo[c]thiophene 9 using SeO2 clearly
confirmed the relatively enhanced aromatic character of non-classical thiophene than that
5

of the respective furan. Obviously, the reduced diene character of the non-classical
thiophene unit disfavors the cycloaddition reaction of 9 with SeO2.
EXPERIMENTAL
All melting points were uncorrected. Solvents were dried by standard procedures.
The progression of reaction was monitored by TLC using hexane/ethyl acetate mixture as
an eluent. Column chromatography was carried out on silica gel (230-400 mesh, Merck)
by using increasing polarity. The 1H, 13C and DEPT-135 spectra were recorded in CDCl3
using TMS as an internal standard on a 300 MHz NMR spectrometer at room
temperature. Chemical shift values were quoted in part per million (ppm) and coupling
constants (J) were quoted in hertz (Hz). Selenium dioxide purchased from Sigma-Aldrich
was used as such for oxidation. The required benzo[c]furans/thiophenes 1a-n, 7 and 9
were prepared using the published procedures 3, 6, 9, 10
.
General Procedure For Oxidation Of Benzo[C]Furans Into Diketones Using Seo2:
To a stirred solution of benzo[c]furan (1.0 mmol) in dry THF (20 mL), SeO2 (1.5
mmol) was added and stirred at room temperature until the disappearance of fluorescent
color of benzo[c]furan (~5-10 minutes). After that, the reaction mixture was filtered
through celite bed and washed with ethyl acetate (2 x 10 mL). The combined organic
layer was washed with water (2 x 30 mL) and dried (Na2SO4). Removal of solvent
followed by column chromatographic purification (Silica gel, 20% EA/Hexane) afforded
diketone.
6

Oxidative Cleavage Of Benzo[C]Furan 1a Using Seo2:
The oxidative cleavage of benzo[c]furan 1a (0.23 g, 0.85 mmol) using SeO2
(0.15 g, 1.35 mmol) adopting the general procedure gave known diketone 2a9 as a
colorless solid (0.21 g, 84%); mp 137-138 oC; 1H-NMR (300 MHz, CDCl3): δ 7.63 (d, J
= 7.2 Hz, 4H, C2-H & C3-H of 1,2-phenylene), 7.54 (s, 4H, C2-H of phenylmethanone),
7.44 (t, J = 7.2 Hz, 2H, C4-H of phenylmethanone) 7.32-7.27 (m, 4H, C3-H of
phenylmethanone) ppm. 13C-NMR (75 MHz, CDCl3): δ 196.6 (C=O), 140.0 (C), 137.2
(C), 133.0 (C-H), 130.4 (C-H), 129.8 (C-H), 129.7 (C-H), 128.3 (C-H) ppm.
1,2-Phenylenebis(Thiophen-2-Ylmethanone) 2b9:
Yield: 0.47 g (81%); colorless solid; mp 152-153 oC ; 1H-NMR (300 MHz,
CDCl3): δ 7.66-7.64 (m, 2H, C3-H of 1,2-phenylene), 7.58-7.56 (m, 4H, C2-H of 1,2-
phenylene & C5-H of thiophene), 7.39-7.38 (m, 2H, C3-H of thiophene), 6.99-6.96 (m,
2H, C4-H of thiophene) ppm. 13C-NMR (75 MHz, CDCl3): δ 188.3 (C=O), 144.0 (C),
139.4 (C), 135.1 (C-H), 135.0 (C-H), 130.6 (C-H), 129.2 (C-H), 128.1 (C-H) ppm.
Procedure For Oxidation Of Furan 7 Into Diketone 810:
To a stirred solution of 2,5-diphenylfuran 7 ( 0.24 g, 1.0 mmol) in dry toluene (10
mL), SeO2 (0.18 g, 1.52 mmol) was added and refluxed for 5 h. After that, the reaction
mixture was filtered through celite bed and washed with ethyl acetate (2 x 10 mL). The
combined organic layer was washed with water (2 x 30 mL) and dried (Na2SO4).
Removal of solvent followed by column chromatographic purification (Silica gel, 15%
EA/Hexane) furnished diketone 8 as a pale yellow solid (0.20 g, 78%); mp 129 oC; 1H-
7

NMR (300 MHz, CDCl3): δ 7.85 (d, J = 7.8 Hz, 4H, C2-H of phenylmethanone), 7.50-
7.46 (m, 2H, C4-H of phenylmethanone), 7.39-7.34 (m, 4H, C3-H of phenylmethanone),
7.07 (s, 2H, vinylic CH) ppm. 13C-NMR (75 MHz, CDCl3): δ 192.5 (C=O), 136.1 (C),
135.6 (C-H), 133.6 (C-H), 128.8 (C-H), 128.6 (C-H) ppm.
CONCLUSION
In summary, we have demonstrated that the mono-, bis- as well as tris-
isobenzofurans can be efficiently transformed into their respective
diaroyl/diheteroaroylbenzenes using SeO2 mediated oxidative cleavage at room
temperature. The methodology was found to be useful for the synthesis of complex
diaroyl/diheteroaroylbenzenes in excellent yields and also the reaction proceeded with
shorter reaction time compared to the existing procedures.
ACKNOWLEDGEMENTS
The authors thank the Department of Science and Technology (DST-FIST) for a
300 MHz NMR facility. J. K and E. S thanks CSIR, New Delhi for CSIR-SRF
fellowship.
REFERENCES
1
(a) Sygula, A.; Sugula, R.; Rabideau, P. W. Org. Lett. 2005, 7, 4999-5001. (b)
Rainboldt, J. E.; Miller, G. P. J. Org. Chem. 2007, 72, 3020-3030. (c) Chun, D.; Cheng,
Y.; Wudl, F. Angew. Chem. Intl. Ed. 2008, 47, 8380-8385. (d) Paraskar, A. S.; Reddy, A.
R.; Patra, A.; Wijsboom, Y. H.; Gidron, O.; Shimon, L. J. W.; Leitus, G.; Bendikov, M.
Chem. Eur. J. 2008, 14, 10639-10647. (e) Mohanty, A. K.; Sen, S. K.; Banerjee, S. J.
8

Appl. Poly. Sci. 2011, 122, 3038-3047. (f) Kuninnobu, Y.; Seiki, T.; Kanamaru, S.;
Nishina, Y.; Takai, K. Org. Lett. 2010, 12, 5287-5289. (g) Parkhurst, R. R.; Swager, T.
M. J. Am. Chem. Soc. 2012, 134, 15351-15356.
2
Nandakumar, M.; Karunakaran, J.; Mohanakrishnan, A. K. Org. Lett. 2014, 16,
3068-3071.
3
(a) Mohanakrishnan, A. K.; Amaladass, P. Tetrahedron Lett. 2005, 46, 7201-
7204. (b) Mohanakrishnan, A. K.; Amaladass, P.; Senthil Kumar, N. Tetrahedron Lett.
2008, 49, 4792-4795. (c) Amaladass, P.; Senthil Kumar, N.; Mohanakrishnan, A. K.
Tetrahedron, 2008, 64, 7992-7998. (d) Senthil Kumar, N.; Mohanakrishnan, A. K.
Tetrahedron, 2010, 66, 5660-5670.
4
5
Meek, S. T.; Nesterov, E. E.; Swager, T. M. Org. Lett. 2008, 10, 2991-2994.
Tan, S.; Bhowmik, A. K.; Thakur, M.; Lakshmikantham, M. V.; Cava, M. P. J.
Chem. Phys. 2000, 112, 383-385.
(a) Sivasakthikumaran, R.; Nandakumar, M.; Mohanakrishnan, A. K. J. Org.
6
Chem. 2012, 77, 9053-9071. (b) Sivasakthikumaran, R.; Rafiq, M. S.; Sankar, E.; Arul
Clement, J.; Mohanakrishnan, A. K. Eur. J. Org. Chem. 2015, 7816-7835.
7
Bauerle, P.; Gotz, G.; Emerle, P.; Port, H. Adv. Mater. (Weinheim, Ger.) 1992, 4,
564-568.
8
(a) Pierlot, C.; Nardello, V.; Schrive, J.; Matrille, C.; Barbillat, J.; Sambret, B.;
Aubry, J. M. J. Org. Chem. 2002, 67, 2418-2413. (b) Catir, M.; Kilic, H. Synlett 2003, 8,
1180-1182. (c) Matsumoto, M.; Yamada, M.; Watanabe, N. Chem. Commun. 2005, 483-
485. (d) Sels, B. F.; De Vos, D. E.; Jacobs, P. A. J. Am. Chem. Soc. 2007, 129, 6916-
6926. (e) Hsu, D. T.; Lin, C. H. J. Org. Chem. 2009, 74, 9180-9187. (f) Hang, J.; Ghorai,
9

P.; Finkenstaedt-Quinn, S. A.; Findik, I.; Sliz, E.; Kuwata, K. T.; Dussault, P. H. J. Org.
Chem. 2012, 77, 1233-1243.
9
Nandakumar, M.; Sivasakthikumaran, R.; Mohanakrishnan, A. K. Eur. J. Org.
Chem. 2012, 3647-3657.
10
Sivasakthikumaran, R.; Nandakumar, M.; Mohanakrishnan, A. K. Synlett 2014,
25, 1896-1900.
11
(a) Hach, C. C.; Banks, C. V.; Diehl, H. Org. Synth. 1963, 4, 229-231. (b) Coxon,
J. M.; Dansted, E.; Hartshorn, M. P. Org. Synth. 1988, 6, 946-947.
12
Laloo, B. M.; Mecadon, H.; Rumum Rohman, Md.; Kharbangar, I.; Kharkongor,
I.; Rajbangshi, M.; Nongkhlaw, R.; Myrboh, B. J. Org. Chem. 2012, 77, 707-712.
13
Liu, Y.; Chen, H.; Hu, X.; Zhou, W.; Deng, G. Eur. J. Org. Chem. 2013, 4229-
4232.
10

Table 1. Oxidative ring opening of isobenzofurans 1e-n using SeO2
Time
(min.)
entry
1
Substrate
Product
Yield (%)
82
10
6
2
3
4
80
83
88
8
4
5
6
7
5
5
6
88
78
83
8
5
85
11

9
5
6
82
81
10
aIsolated yield by column chromatography.
12

Scheme 1. Mechanism for oxidative cleavage of 1,3-disubstituted benzo[c]furans using
SeO2
13