An unusual fragmentation reaction of substituted 2,3-norbornylhydroquinone with CAN: synthesis of 1,4-naphthoquinone

Article abstract of DOI:10.1016/j.tetlet.2008.08.112

When substituted 2,3-norbornylhydroquinone is treated with CAN with or without water, an unusual fragmentation-aromatization reaction occurs which leads to a substituted 1,4-naphthoquinone instead of the desired substituted 2,3-norbornylbenzoquinone.

Full text of DOI:10.1016/j.tetlet.2008.08.112

Tetrahedron Letters 49 (2008) 6466–6467
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An unusual fragmentation reaction of substituted 2,3-norbornylhydroquinone
with CAN: synthesis of 1,4-naphthoquinone
*
V. Sridar , A. Yamuna
Industrial Chemistry Lab, Central Leather Research Institute, Adyar, Chennai 600020, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
When substituted 2,3-norbornylhydroquinone is treated with CAN with or without water, an unusual
fragmentation–aromatization reaction occurs which leads to a substituted 1,4-naphthoquinone instead
of the desired substituted 2,3-norbornylbenzoquinone.
Received 30 July 2008
Revised 26 August 2008
Accepted 29 August 2008
Available online 3 September 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Fragmentation
Aromatization
2
,3-Norbornylhydroquinone
Chlorinated-1,4-naphthoquinone
In the pursuit toward hexa- and heptaprismanes, 5,5-dime-
OMe
Cl
MeO
Cl
1
Cl
Cl
O
thoxy-1,2,3,4-tetrachlorocyclopentadiene 1 is a key precursor.
2
Cl
Cl
Its Diels–Alder adduct 3 from reaction with benzoquinone
2
OMe
OMe
H
O
PhCH3
(
Scheme 1) has been subjected to Luche reduction yielding the
+
3
exo,exo-diol. Dailey and co-workers have converted this diol into
reflux
4
the endo,endo-diol and studied the Diels–Alder reaction with 1.
7
h
Cl
5
Cl
H
It has also been reported by Mehta that the unsubstituted 2,3-nor-
O
73%
O
bornylbenzoquinone undergoes a Diels–Alder reaction with 1 to
furnish endo,anti and endo,syn adducts in the ratio of 77:23 in good
yields. However, the Diels–Alder reaction of the substituted 2,3-
norbornylbenzoquinone 5 with 1 has not been reported in the lit-
erature. If this reaction could be achieved, it would represent a new
1
2
3
Scheme 1.
6
direction in synthetic efforts toward hexa- and heptaprismanes. In
order to secure 5, the known Diels–Alder adduct 3 was subjected to
reaction with silica gel by impregnation to form the hydroquinone
OMe
Cl
MeO
Cl
7
4
in a yield of 42% over two steps from 1 (Scheme 2).
OH
SiO2
We expected a clean oxidation of the hydroquinone with CAN
3
under acetonitrile/water conditions. However, to our surprise, the
product obtained was substituted naphthoquinone 7 and none of
the desired benzoquinone 5 or its hydrolyzed product 6 (Scheme
2
4 h
8%
Cl
Cl
5
HO
3
). Obviously, the hydroquinone part of 4 has been converted into
4
the benzoquinone as desired, but, additionally a fragmentation
8
reaction has occurred followed by aromatization leading to 1,4-
Scheme 2.
naphthoquinone 7 in high yield. The structure of 7 was confirmed
by proton and carbon NMR spectroscopy.9 In the proton NMR, an
AB quartet at d 6.94 and d 7.00 with J = 10.7 Hz corresponded to
the benzoquinone protons and a singlet at d 4.04 was due to the
methyl ester group. The 13C NMR supports the structure of 7 with
two ketone groups at d 181.74 and d 181.44 as expected for an
unsymmetrical benzoquinone.
As is well known, CAN is a one electron oxidant10 and it
oxidizes the oxygen in the methoxy group leading to an oxygen
*
Corresponding author. Tel.: +91 44 24911386; fax: +91 44 24911589.
E-mail address: svenkates@hotmail.com (V. Sridar).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.112

V. Sridar, A. Yamuna / Tetrahedron Letters 49 (2008) 6466–6467
6467
X
In order to determine that aromatization is the driving force for
the above reaction, we subjected Diels–Alder adduct 3 with CAN,
wherein aromatization is not possible. In fact, there was no reac-
tion and the substrate was returned in almost quantitative yield.
The acetal was not affected by CAN and it is known in the literature
that this type of acetal is robust, even under reflux over 48 h in 10%
HCl it is not hydrolyzed. Therefore, one of the oxygens in the di-
methyl acetal is oxidized and then cleaved only under aromatiza-
tion conditions.
In conclusion, we have described a CAN-induced serendipitous
reaction leading to a tri-chlorinated 1,4-naphthoquinone in excel-
lent yield which is otherwise difficult to prepare. Work is in pro-
gress in our laboratory to form polychlorinated anthraquinone12
from this product via the above iterative process of Diels–Alder
reaction, hydroquinone formation, and CAN oxidation.
OMe
O
O
Cl
Cl
O
CAN
CAN
Cl
Cl
4
Cl
Cl
1d
O
Cl
O
5
6
X=(OMe)2
X=O
7
Scheme 3.
+
OMe
.
O
O
OMe
Cl
Acknowledgments
Cl
O
Cl
Cl
O
-e-
CAN
The authors thank Dr. A. B. Mandal, Director, for providing
infrastructural facilities and Dr. B. S. R. Reddy for his support. V.S.
thanks the reviewer of this manuscript for useful suggestions.
Thanks are due to Mr. K. Madhavan and Mr. S. Nagarajan for pro-
viding NMR and MS data, respectively.
4
Cl
Cl
Cl
Cl
O
O
-
CH +
3
References and notes
OMe
O
O
O
MeOOC Cl
Cl
1.
(a) Mehta, G.; Padma, S. Tetrahedron 1991, 47, 7783; (b) Mehta, G.; Reddy, S. H.
K.; Padma, S. Tetrahedron 1991, 47, 7821. For other unnatural products, see: (c)
Khan, F. A.; Dash, J. J. Am. Chem. Soc. 2002, 124, 2424; (d) Khan, F. A.; Dwivedi,
V.; Rout, B. Tetrahedron Lett. 2007, 48, 207.
Cl
Cl
.
Cl
-
2
.
Marchand, A. P.; Chou, T.-C. J. Chem. Soc., Perkin Trans. 1 1973, 1948.
.
3. Marchand, A. P.; LaRoe, W. D.; Sharma, G. V. M.; Suri, S. C.; Reddy, D. S. J. Org.
Chem. 1986, 51, 1622.
4. Forman, M. A.; Dailey, W. P. J. Org. Chem. 1993, 58, 1501.
Cl
Cl
O
Cl
O
5
.
Mehta, G.; Padma, S.; Karra, S. R.; Gopidas, K. R.; Cyr, D. R.; Das, P. K.; George, M.
V. J. Org. Chem. 1989, 54, 1342.
7
6
.
Golobish, T. D.; Dailey, W. P. Tetrahedron Lett. 1996, 37, 3239.
Scheme 4.
7. Synthesis of hydroquinone 4: To a powdered dione 3 (781 mg, 2.1 mmol), silica
gel (60–120 mesh, 2 g) was added and thoroughly mixed. This mixture was
then loaded onto a column of silica gel (60–120 mesh) in 25% EtOAc/pet. ether
and left for 24 h. The column was then eluted using the same solvent mixture
to collect the hydroquinone 4 (452 mg, 58%) as a white solid. R
f
: 0.21 (25%
Table 1
Oxidation of hydroquinone 4 with CAN
EtOAc/pet. ether); Mp 156 °C; IR (KBr): 3347, 2981, 1677, 1603, 1488, 1454,
À1
1
1
360 cm
;
H NMR (DMSO-d
6
, 400 MHz): d 8.5 (s, 2H, OH), 6.44 (s, 2H, CH),
13
Entry
Conditions
Oxidant (equiv)
Yield (7, %)
3.50 (s, 3H, OCH
3 3 3
), 3.35 (s, 3H, OCH ); C NMR (CDCl , 100 MHz): d 145.68,
1
35.98, 122.92, 122.55, 119.51, 78.3, 53.18, 52.92; MS (ESI): m/z (%): 392
1
2
3
4
CAN, CH
CAN, CH
CAN, CH
3
3
3
CN/H
CN/H
2
O, 1 h
O, 1 h
5.3
2.0
2.0
78
82
76
47
37 35 37 35
(
2 2
[M+H O], [ Cl, Cl], 30), 391 ([M+H O+1], [ Cl, Cl], 100).
2
8
9
.
.
Nair, V.; Sheeba, V. J. Org. Chem. 1999, 64, 6898.
CN, 1 h
SO , toluene, 3 h
Synthesis of trichlorinated 1,4-naphthoquinone 7: To
a
solution of diol
4
Ag
2
O, Na
2
4
12.7
(90 mg, 0.24 mmol) in CH
3
CN (2.7 mL), CAN (710 mg, 1.3 mmol) in
H
2
O
(
1 mL) was added dropwise with stirring at rt, and the reaction was
continued for 1 h. Then, the reaction mixture was treated with H O (5 mL)
and extracted with EtOAc (3 Â 10 mL). The combined organic layer was dried
over Na SO and evaporated in vacuo to provide crude naphthoquinone
81.6 mg) which upon column chromatography with 30% EtOAc/pet. ether
provided as dark red solid (60.3 mg, 78%). 0.39 (25% EtOAc/pet.
2
cation-radical. This cation-radical undergoes a fragmentation reac-
tion followed by aromatization with the leaving group being a
chlorine radical (Scheme 4). It is also known in the literature that
an acetal is converted into a ketone using CAN.11 Here, instead of
forming a ketone, a fragmentation reaction occurs leading to a
2
4
(
7
a
f
R :
ether); Mp 148 °C; IR (KBr): 3188, 2937, 1734, 1668, 1620, 1443 cmÀ1
1
; H
NMR (CDCl
COOMe);
3
, 400 MHz): d 7.00, 6.94 (AB q, 2H, J = 10.7 Hz, CH), 4.04 (s, 3H,
C NMR (CDCl , 100 MHz): d 181.74, 181.44, 165.44, 141.22,
3
1
3
1
40.20, 136.95, 136.42, 135.48, 133.38, 129.03, 127.56, 53.48; HRMS calcd
for C12 Cl (M+Na): 340.9151. Found: 340.9144.
10. Nair, V.; Deepthi, A. Chem. Rev. 2007, 107, 1862.
11. (a) Nair, V.; Nair, L. G.; Balagopal, L.; Rajan, R. Indian J. Chem. 1999, 38B,
234; (b) Ates, A.; Gautier, A.; Leroy, B.; Plancher, J. M.; Quesnel, Y.;
9
substituted 1,4-naphthoquinone in high yield under various con-
H
5
3 4
O
ditions (Table 1), including non-aqueous conditions. Since it is also
known that silver oxide5 can oxidize hydroquinone to benzoqui-
1
none, we studied these conditions. Here again, we observed the
same fragmentation reaction in addition to oxidation of hydroqui-
none. Using silver oxide, the yield was moderate; however, we did
not observe any color change during the reaction as previously
Vanherk, J. C.; Marko, I. E. Tetrahedron 2003, 59, 8989; (c) Marko, I. E.; Ates,
A.; Augustyns, B.; Gautier, A.; Quesnel, Y.; Turet, L.; Wiaux, M. Tetrahedron
Lett. 1999, 40, 5613.
1
2. For
a recent synthesis of substituted anthraquinones, see: Barluenga, J.;
Martinez, S.; Suarez-Sobrino, A. L.; Tomas, M. Org. Lett. 2008, 10, 677.
5
reported.