Oxidative cleavage of 1,3-disubstituted benzo[ c ]furans with activated manganese dioxide: A facile preparation of 1,2-Di(het)aroylbenzenes

Article abstract of DOI:10.1055/s-0034-1378352

Manganese dioxide mediated oxidative cleavage of 1,3-disubstituted benzo[c]furans in dichloromethane at room temperature gave good yields of 1,2-di(het)aroylbenzenes. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0034-1378352

1896▌
LETTER
letter
Oxidative Cleavage of 1,3-Disubstituted Benzo[c]furans with Activated
Manganese Dioxide: A Facile Preparation of 1,2-Di(het)aroylbenzenes
Oxidative Cleavage of 1,3-Disubstituted Benzo[c]furans
Ramakrishnan Sivasakthikumaran, Meganathan Nandakumar, Arasambattu K. Mohanakrishnan*
Department of Organic Chemistry, School of Chemical Sciences, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India
Fax +91(44)22352494; E-mail: mohanakrishnan@unom.ac.in; E-mail: mohan_67@hotmail.com
Received: 05.04.2014; Accepted after revision: 28.05.2014
tivated manganese dioxide (MnO2) has been used for the
Abstract: Manganese dioxide mediated oxidative cleavage of 1,3-
oxidation of a variety of heterocyclic compounds.10
disubstituted benzo[c]furans in dichloromethane at room tempera-
Garofalo and co-workers achieved an efficient synthesis
ture gave good yields of 1,2-di(het)aroylbenzenes.
of pyrroloindolones by a MnO2-promoted intramolecular
Key words: heterocycles, polycycles, diketones, ring opening,
oxidation, manganese dioxide
cyclization.11 Recently, oxidation of arylmethylene
compounds12 with MnO2 and the oxidation of benzylic al-
cohols with a substoichiometric quantity of MnO213 have
been reported. These reports encouraged us to explore the
Since the first report on 1,3-dithienylbenzo[c]thiophenes,1
oxidation of 1,3-disubstitued benzo[c]furans with activat-
the syntheses and characterization of benzo[c]thiophene
ed MnO2.
analogues have been well explored.2 In comparison, the
In a representative case, treatment of 1,3-dithienylben-
zo[c]furan (1a) with four equivalents of MnO2 in dichlo-
romethane at room temperature for four hours gave the
corresponding diketone 2a in 92% yield.14 However, un-
der identical conditions, the corresponding benzo[c]thio-
phene 1a′ failed to give diketone 2a and, even under
reflux conditions, the starting material 1a′ was recovered
unchanged.
chemistry of the corresponding benzo[c]furans is less well
explored because of their unstable nature. Swager and co-
workers reported the first synthesis of benzo[c]furan-
based cyanovinylenes as near-infrared fluorophores.3
Over the years, 1,3-diarylbenzo[c]furans have been used
as dienes in Diels–Alder reactions for the syntheses of a
wide variety of π-conjugated molecules.4 1,3-Disubstitut-
ed benzo[c]furans have also been used as intermediates
for the synthesis of benzo[c]selenophenes.5 We recently
reported the synthesis of annulated arenes and hetarenes
from unsymmetrically substituted benzo[c]furans.6
The ease with which benzo[c]furan 1a underwent MnO2-
mediated oxidative ring opening prompted us to under-
take a comprehensive study with various benzo[c]furan
analogues. We were pleased to find that the MnO2-medi-
ated oxidative cleavage could be successful applied to a
wide variety of 1,3-diaryl- and 1,3-dihetarylbenzo[c]fu-
rans (Table 1). The symmetrical benzo[c]furans 1b–d, on
treatment with four equivalents of MnO2 in dichlorometh-
ane at room temperature, readily underwent oxidative ring
cleavage to give the corresponding diaroylbenzenes 2b–d
in excellent yields (Table 1, entry 1). The nonsymmetrical
1,3-diarylbenzo[c]furans 1e–k similarly underwent cleav-
age with MnO2 in very good yields (entry 2). The MnO2-
mediated oxidative ring opening of the veratrole-tethered
benzo[c]furans 3a–d similarly gave the corresponding
In general, the oxidative transformation of 1,3-disubstitut-
ed benzo[c]furans into the corresponding diaroylbenzenes
is achieved by using lead tetraacetate (LTA)1b or singlet
oxygen.7 We recently developed a simple oxidative ring
opening of 1,3-disubstituted benzo[c]heterocycles by us-
ing 3-chloroperbenzoic acid (MCPBA).8 Even though this
procedure was successfully applied to a wide variety of
benzo[c]heterocycles, undesired oxidation of the thio-
phene moiety also occurred in some cases. The synthetic
utility of 1,2-diaroylbenzenes6,9 prompted us to undertake
a detailed study of the oxidative cleavage of benzo[c]het-
erocycles with other oxidizing agents. Over the years, ac-
MnO2 (4 equiv), CH2Cl2
S
S
X
r.t., 4 h
92%
S
O
O
S
1a
1a X = O
1a' X = S
2a
MnO2, CH2Cl2
reflux, 10 h
2a
1a'
Scheme 1 Attempted oxidations of furan 1a and thiophene 1a′ with MnO2
SYNLETT 2014, 25, 1896–1900
Advanced online publication: 01.07.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1378352; Art ID: st-2014-d0286-l
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidative Cleavage of 1,3-Disubstituted Benzo[c]furans
1897
diketones 4a–d in 86–91% yield (entry 3). Cleavage of the (entry 6). The benzo[b]thiophene-containing benzo[c]fu-
dibenzothiophene-linked benzo[c]furans 5a and 5b with rans 11a and 11b also readily underwent the oxidative
MnO2 in dichloromethane at room temperature gave the ring-opening reaction to give the corresponding products
corresponding 1,2-diaroylbenzenes 6a and 6b in 82 and 12a and 12b in good yields (entry 7). As expected, the re-
85% yield, respectively (entry 4). Note that the similar ox- actions of the triphenylamine-containing benzo[c]furans
idative cleavage of benzo[c]furans 5a and 5b with 13a and 13b and the N-hexylcarbazole-containing ben-
MCPBA8 gave the 1,2-diaroylbenzenes 6a and 6b in low zo[c]furans 15a and 15b with MnO2 gave the correspond-
yields as a result of oxidation of the dibenzothiophene ing diketones in 81–87% yield (entries 8 and 9). Under
unit. Obviously, the mild oxidizing nature of MnO2 per- identical conditions, various other benzo[c]furans 17, 19,
mits selective oxidation of the benzo[c]furan moiety with- and 21 gave the corresponding diketones 18, 20, and 22 in
out any effect on the dibenzothiophene unit. The MnO2- 83–92% yields (entries 10–12). However, attempts at ox-
mediated oxidative ring-opening reaction was also suc- idative cleavage of the symmetrical 2,5-diarylfurans 23a
cessfully applied to the bithiophene-containing ben- and 23b with MnO2 were unsuccessful and, even under re-
zo[c]furan 7, to give the diketone 8 in 86% yield (entry 5), flux conditions, the starting materials were recovered un-
and to the biphenyl-containing benzo[c]furans 9a and 9b changed (entry 13).
a
Table 1 Oxidations of Benzo[c]furans with MnO2
Entry
Substrate
Product
Yield (%)
94
95
92
Ar1
Ar1
Ar1
O
Ar1
1
O
O
2b Ar1 = Ph
1a
1b
1c
2c Ar1 = 4-Tol
2d Ar1 = 1-naphthyl
Ar1
Ar2
93
90
90
96
90
91
93
Ar1
O
Ar2
O
O
2e Ar1 = 4-MeOC6H4; Ar2 = Ph
1e
1f
1g
1h
1i
2
2f Ar1 = 4-Tol; Ar2 = 1-naphthyl
2g Ar1 = Ph; Ar2 = 2-thienyl
2h Ar1 = 3,4-Me2C6H3 ; Ar2 = 4-MeOC6H4
2i Ar1 = 2-methoxy-1-naphthyl; Ar2 = Ph
2j Ar1 = 2-methoxy-1-naphthyl; Ar2 = 1-naphthyl
2k Ar1 = 2,4-Me2C6H3; Ar2 = 1-naphthyl
1j
1k
R1O
R1O
R1O
Ar1
R1O
Ar1
91
88
89
86
O
O
O
3
4a R1 = Me; Ar1 = 1-naphthyl
4b R1 = Me; Ar1 = 4-Tol
3a
3b
3c
3d
4c R1 = (CH2)5Me; Ar1 = Ph
4d R1 = (CH2)5Me; Ar1 = 2-thienyl
Ar1
Ar1
82
85
O
4
S
O
O
S
6a Ar1 = 2-thienyl
5a
5b
6b Ar1 = 1-naphthyl
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1896–1900

1898
R. Sivasakthikumaran et al.
LETTER
a
Table 1 Oxidations of Benzo[c]furans with MnO2 (continued)
Entry
Substrate
Product
Yield (%)
S
O
5
86
S
O
O
S
S
8
7
Ar1
88
87
6
7
O
Ar1
O
O
10a Ar1 = Ph
9a
9b
10b Ar1 = 3-hexyl-2-thienyl
Ar1
Ar1
87
89
S
O
O
O
S
R1
R1
12a R1 = H; Ar1 = 4-Tol
11a
11b
12b R1 = Me; Ar1 = 2-thienyl
N
Ar1
N
84
87
O
O
8
O
Ar1
13a
13b
14a Ar1 = 2-thienyl
14b Ar1 = 4-MeOC6H4
Ar1
81
85
N
Ar1
O
9
N
H13C6
O
O
H13C6
16a Ar1 = 4-Tol
15a
15b
16b Ar1 = 4-MeOC6H4
C6H13
C6H13
H13C6
H13C6
10
11
83
92
O
O
O
18
17
O
O
O
20
19
Synlett 2014, 25, 1896–1900
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidative Cleavage of 1,3-Disubstituted Benzo[c]furans
1899
a
Table 1 Oxidations of Benzo[c]furans with MnO2 (continued)
Entry
12
Substrate
Product
Yield (%)
S
S
C6H13
C6H13
91
O
O
O
O
O
22
21
Ar1
Ar1
Ar1
Ar1
O
0
0
O
O
13
24a Ar1 = 2-thienyl
24b Ar1 = Ph
23a
23b
a Reaction conditions: substrate (1 equiv), MnO2 (4 equiv), anhyd CH2Cl2, r.t., ~4 h.
To understand the efficacy of MnO2-mediated oxidative A plausible mechanism for the formation of 1,2-diaroyl-
cleavage in more detail we needed to compare the MnO2- benzenes 2 from benzo[c]furans 1 by MnO2-mediated ox-
mediated ring-opening reactions of benzo[c]furans with idation is shown in Scheme 2.
those mediated by other oxidizing agents. Accordingly,
we examined the reactions of representative benzo[c]fu-
rans with LTA, MCPBA, and MnO2, and the yields ob-
tained are shown in Table 2.
Ar1
O
Ar1
Ar1
+
Ar1
••
O
•
O
O
Mn
Table 2 Comparative Study on the Oxidation of Benzo[c]furans
with LTA, MCPBA, and MnO2
Mn
–O
O
25
1
Entry
Substrate Product
Yielda (%)
MCPBAc MnO2
b
d
Pb(OAc)4
Ar1
1
2
3
4
5
6
1a
1c
2a
2c
83
84
80
83
24
25
89
92
41
44
83
82
92
94
82
85
84
81
O
Ar1
Ar1
Ar1
O
Mn
– Mn
O
O
O
O
2
26
5a
6a
Scheme 2 Proposed mechanism for the oxidative cleavage of 1,3-di-
substituted benzo[c]furans by MnO2
5b
6b
13a
15a
14a
16a
Nucleophilic attack by MnO2 on benzo[c]furan 1, fol-
lowed by intramolecular cyclization, gives intermediate
26, which undergoes elimination of MnO to give the diar-
oylbenzene 2.
a Isolated yield
b Reactions were carried out by using LTA (2 equiv) in THF.
c Reactions were carried out by using MCPBA (1.5 equiv) in CH2Cl2.
d Reactions were carried out by using MnO2 (4 equiv) in CH2Cl2.
In summary, we have developed a mild MnO2-mediated
oxidative ring opening of symmetrical or unsymmetrical
1,3-diarylbenzo[c]furans at room temperature. The reac-
tion generally proceeds in excellent yields. In most cases,
yields of the 1,2-di(het)aroylbenzenes obtained by the
MnO2-mediated oxidative cleavage are comparable to or
better than those produced by existing methods.
In the case of the symmetrical 1,3-diarylbenzo[c]furans
1a and 1c, similar yields of diketones 2a and 2c were ob-
tained with all three oxidizing agents (Table 2, entries 1
and 2). In the case of the dibenzothiophene-linked ben-
zo[c]furans 5a and 5b, better yields of the diketones were
obtained by using LTA or MnO2 than with MCPBA
(entries 3 and 4). Oxidative ring-opening reactions of the
triphenylamine- and N-hexylcarbazole-capped ben-
zo[c]furans 13a and 15a with MnO2 and with MnO2 gave
comparable yields, whereas the corresponding reactions
with LTA gave low yields of the corresponding diketones
14a and 16a (entries 5 and 6).
Acknowledgment
We thank the Department of Science and Technology (DST), New
Delhi, for financial support. R.S. and M.N. thank the University
Grants Commission (UGC) and the Council of Scientific and Indu-
strial Research (CSIR), New Delhi, for fellowships. The authors
thank the Department of Science and Technology Funds for the Im-
provement of Science and Technology (DST-FIST) for NMR faci-
lities.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1896–1900

1900
R. Sivasakthikumaran et al.
LETTER
C.-H. J. Org. Chem. 2009, 74, 9180. (f) Hang, J.; Ghorai, P.;
Finkenstaedt-Quinn, S. A.; Findik, I.; Sliz, E.; Kuwata, K.
T.; Dussault, P. H. J. Org. Chem. 2012, 77, 1233.
(8) Nandakumar, M.; Sivasakthikumaran, R.; Mohanakrishnan,
A. K. Eur. J. Org. Chem. 2012, 3647.
(9) (a) Letizia, J. A.; Cronin, S.; Ponce Ortiz, R.; Facchetti, A.;
Ratner, M. A.; Marks, T. J. Chem. Eur. J. 2010, 16, 1911.
(b) Steinberger, S.; Mishra, A.; Reinold, E.; Müller, C. M.;
Uhrich, C.; Pfeiffer, M.; Bäuerle, P. Org. Lett. 2011, 13, 90.
(c) Mei, Q.; Wang, L.; Tian, B.; Tong, B.; Weng, J.; Zhang,
B.; Jiang, Y.; Huang, W. Dyes Pigm. 2013, 97, 43. (d) Liu,
Y.; Zhang, F.; He, C.; Wu, D.; Zhuang, X.; Xue, M.; Liu, Y.;
Feng, X. Chem. Commun. 2012, 48, 4166. (e) Harikrishna,
K.; Mukkamala, R.; Hinkelmann, B.; Sasse, F.; Aidhen, I. S.
Eur. J. Org. Chem. 2014, 1066.
Supporting Information for this article is available online
at http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000083.SunpfgIpi
o
o
nr
i
References and Notes
(1) (a) Lorcy, D.; Cava, M. P. Adv. Mater. (Weinheim, Ger.)
1992, 4, 562. (b) Bäuerle, P.; Götz, G.; Emerle, P.; Port, H.
Adv. Mater. (Weinheim, Ger.) 1992, 4, 564. (c) Musinanni,
S.; Ferraris, J. P. J. Chem. Soc., Chem. Commun. 1993, 172.
(2) (a) Kiebooms, R. H. L.; Adriaensens, P. J. A.; Vanderzande,
D. J. N.; Gelan, J. M. J. V. J. Org. Chem. 1997, 62, 1473.
(b) Mohanakrishnan, A. K.; Lakshmikantham, M. V.;
McDougal, C. D.; Cava, M. P.; Baldwin, J. W.; Metzger, R.
M. J. Org. Chem. 1998, 63, 3105. (c) Amaladass, P.; Arul
Clement, J.; Mohanakrishnan, A. K. Eur. J. Org. Chem.
2008, 3798.
(10) Soldatenkov, A. T.; Polyanskii, K. B.; Kolyadina, N. M.;
Soldatova, S. A. Chem. Heterocycl. Compd. (N. Y., NY U. S.)
2009, 45, 633.
(11) Aiello, F.; Garofolo, A.; Grande, F. Tetrahedron 2010, 66,
274.
(3) Meek, S. T.; Nesterov, E. E.; Swager, T. M. Org. Lett. 2008,
10, 2991.
(4) (a) Sygula, A.; Sugula, R.; Rabideau, P. W. Org. Lett. 2005,
7, 4999. (b) Rainboldt, J. E.; Miller, G. P. J. Org. Chem.
2007, 72, 3020. (c) Chun, D.; Cheng, Y.; Wudl, F. Angew.
Chem. Int. Ed. 2008, 47, 8380. (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.
(e) Mohanty, A. K.; Sen, S. K.; Banerjee, S. J. Appl. Polym.
Sci. 2011, 122, 3038. (f) Kuninobu, Y.; Seiki, T.; Kanamaru,
S.; Nishina, Y.; Takai, K. Org. Lett. 2010, 12, 5287.
(g) Parkhurst, R. R.; Swager, T. M. J. Am. Chem. Soc. 2012,
134, 15351.
(5) (a) Mohanakrishnan, A. K.; Amaladass, P. Tetrahedron Lett.
2005, 46, 7201. (b) Mohanakrishnan, A. K.; Amaladass, P.;
Senthil Kumar, N. Tetrahedron Lett. 2008, 49, 4792.
(c) Amaladass, P.; Senthil Kumar, N.; Mohanakrishnan, A.
K. Tetrahedron 2008, 64, 7992. (d) Senthil Kumar, N.;
Mohanakrishnan, A. K. Tetrahedron 2010, 66, 5660.
(6) Sivasakthikumaran, R.; Nandakumar, M.; Mohanakrishnan,
A. K. J. Org. Chem. 2012, 77, 9053.
(12) Kamimura, A.; Komatsu, H.; Moriyama, T.; Nozaki, Y.
Tetrahedron 2013, 69, 5968.
(13) Nammalvar, B.; Fortenberry, C.; Bunce, R. A.; Lageshetty,
S. K.; Ausman, K. D. Tetrahedron Lett. 2013, 54, 2010.
(14) 1,2-Phenylenebis(2-thienylmethanone) (2a); Typical
Procedure
MnO2 (0.57 g, 7.09 mmol) was added to a stirred solution of
benzo[c]furan 1a (0.5 g, 1.77 mmol) in CH2Cl2 (20 mL), and
the mixture was stirred at r.t until the benzo[c]furan was
consumed (~4 h). The mixture was then filtered through
Celite and the residue was washed with CH2Cl2 (2 × 10 mL).
The combined filtrate was concentrated under reduced
pressure and the residue was purified by column
chromatography (silica gel; 5% EtOAc–hexane) to give a
brown solid; yield: 0.48 g (92%); mp 150–152 °C (Lit. see
ref. 1b 149–150 °C); IR (KBr): 1623, 1582, 1568, 1514,
1416 cm–1; 1H NMR (300 MHz, CDCl3): δ = 7.66–7.64 (m,
2 H, ArH), 7.58–7.56 (m, 4 H, ArH), 7.39–7.38 (m, 2 H,
ArH), 6.99–6.96 (m, 2 H, ArH); 13C NMR (75 MHz, CDCl3):
δ = 188.3, 144.0, 139.4, 135.1, 135.0, 130.6, 129.2, 128.1;
DEPT-135 (75 MHz, CDCl3): δ = 135.2, 135.0, 130.6, 129.2,
128.1; HRMS (EI): m/z [M+] calcd for C16H10O2S2:
298.0122; found: 298.0121.
(7) (a) Pierlot, C.; Nardello, V.; Schrive, J.; Matrille, C.;
Barbillat, J.; Sambret, B.; Aubry, J. M. J. Org. Chem. 2002,
67, 2418. (b) Catir, M.; Kilic, H. Synlett 2003, 1180.
(c) Matsumoto, M.; Yamada, M.; Watanabe, N. Chem.
Commun. 2005, 483. (d) Sels, B. F.; De Vos, D. E.; Jacobs,
P. A. J. Am. Chem. Soc. 2007, 129, 6916. (e) Hsu, D.-T.; Lin,
Synlett 2014, 25, 1896–1900
© Georg Thieme Verlag Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.