Synthesis of 4, 5-Dimethoxy-o-benzoquinone by formal [4+2] cyclization of 2, 3-dimethoxy-1, 3-butadiene with oxalyl chloride

Article abstract of DOI:10.2174/157017809787893055

The cyclization of 2, 3-dimethoxy-1, 3-butadiene with oxalyl chloride provides a new method for the synthesis of 4, 5-dimethoxy-o-benzoquinone. 2009. Bentham Science Publishers Ltd.

Full text of DOI:10.2174/157017809787893055

Letters in Organic Chemistry, 2009, 6, 189-190
189
Synthesis of 4,5-Dimethoxy-o-benzoquinone by Formal [4+2] Cyclization
of 2,3-Dimethoxy-1,3-butadiene with Oxalyl Chloride
Gerson Mroßa and Peter Langer*,a,b
aInstitut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
bLeibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Received June 10, 2008: Revised January 16, 2009: Accepted January 16, 2009
Abstract: The cyclization of 2,3-dimethoxy-1,3-butadiene with oxalyl chloride provides a new method for the synthesis
of 4,5-dimethoxy-o-benzoquinone.
Keywords: Arenes, cyclizations, oxalyl derivatives, enol ethers, quinines.
Ortho-quinones represent versatile synthetic building
blocks [1]. For example, Waldmann and coworkers recently
reported the application of 4,5-dimethoxy-o-benzoquinone
during the synthesis of nakijiquinone natural products [2].
The reaction of 4,5-dimethoxy-o-benzoquinone with
KOH/H2O has been reported to result in the formation of
2,5-dihydroxy-p-benzoquinone in high yield. The reaction of
4,5-dimethoxy-o-benzoquinone with MeOH, in the presence
of catalytic amounts of acid, afforded 2,5-dimethoxy-p-
benzoquinone in quantitative yield [3]. The reaction of 4,5-
dimethoxy-o-benzoquinone with 1,2-diaminobenzene af-
forded fluorindin [3]. 4,5-Dimethoxy-o-benzoquinone and
related compounds have been applied to the synthesis of the
natural product xylerithin and its analogues [4]. Several
other applications have been reported.
Oxalyl chloride, a bulk chemical, represents an important
synthetic building block in one-pot cyclizations with silyl
enol ethers [12]. We have recently reported the synthesis of
ꢀ-alkylidenebutenolides by cyclization of 1,3-bis(trimethyl-
silyloxy)-1,3-butadienes with oxalyl chloride [13]. Recently,
we have studied the synthesis of 4-alkoxycarbonyl-
butenolides by uncatalyzed one-pot cyclization of oxalyl
chloride with 1,3-bis(silyloxy)alk-1-enes [14]. We have also
developed a one-pot synthesis of 3-hydroxymaleic anhy-
drides by cyclization of 1,1-bis(trimethylsilyloxy)ketene
acetals with oxalyl chloride [15].
Herein, we report what is, to the best of our knowledge, a
new synthesis of 4,5-dimethoxy-o-benzoquinone by cycliza-
tion of 2,3-dimethoxy-1,3-butadiene with oxalyl chloride
[16].
4,5-Dimethoxy-o-benzoquinone has been prepared by
several methods and is commercially available (1.0 g,
$79.20) [5]. Recently, 4,5-dimethoxy-o-benzoquinone has
been isolated as a natural product [6]. Its first synthesis was
reported by El’tshov based on a Teuber oxidation of 4-
hydroxy-veratrol [7]. Wanzlick and Jahnke were the first to
report the synthesis of 4,5-dimethoxy-o-benzoquinone by
PbO2-mediated dehydrogenation of 1,2-dihydroxybenzene in
the presence of MeOH/NaOMe [3, 8]. Although this reaction
is nowadays frequently used, a drawback is the employment
of stoichiometric amounts of toxic PbO2. An alternative
method for the synthesis of 4,5-dimethoxy-o-benzoquinone
relies on the oxidation of different substituted phenols by
employment of stoichiometric amounts of Frémy’s salt [9].
However, its high costs prevent this reagent to be used on
large scale. 4,5-Dimethoxy-o-quinone has also been prepared
by copper-mediated oxidation of phenol with oxygen in the
presence of pyridine [10]. Nematollahi and Golabi reported
an efficient electro-organic synthesis of 4,5-dimethoxy-o-
benzoquinone from catechol (95% yield) [11]. In this trans-
formation, methanol was used as the solvent and sodium
acetate as the supporting electrolyte.
Cl
O
O
Cl
O
O
OMe
OMe
i
1
+
MeO
3
OMe
2
HCl
+
Cl
_
O
Cl
O
O
OMe
OMe
_
+
OMe
O
OMe
HCl
Cl
B
A
Scheme 1. Synthesis of 3: i, neat, 0 °C, 6 h.
The reaction of a CH2Cl2 solution (10 mL) of oxalyl
chloride (1) (1.0 mmol) with commercially available 2,3-
dimethoxy-1,3-butadiene (2) (1.0 mmol) at 20 °C afforded
4,5-dimethoxy-o-benzoquinone (3), albeit, in only in 7%
yield. Product 3 was isolated in 18% yield when the reaction
was carried out at -78 °C. After some experimentation we
*Address correspondence to this author at the Leibniz-Institut für Katalyse
an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock,
Germany; E-mail: peter.langer@uni-rostock.de
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

190 Letters in Organic Chemistry, 2009, Vol. 6, No. 3
Mroß and Langer
[6]
[7]
[8]
Yang, J.; Lou, F.; Niu, Y. Zhongguo Zhongyao Zazhi, 2007,
32(14), 1416.
El’tshov, A. V. J. Gen. Chem. USSR, 1963, 33, 1952; Chem. Abstr.
1963, 59, 11463.
For applications of this method, see for example: Cole, E. R.;
Crank, G.; Minh, H. T. H. Aust. J. Chem., 1980, 33, 527; see also
ref. 2.
(a) Deya, P. M.; Dopico, M.; Raso, A. G.; Morey, J.; Saa, J. M.
Tetrahedron, 1987, 43, 3523. (b) Saa, J. M.; Capo, M.; Marti, C.;
Garcia-Raso, A. J. Org. Chem., 1990, 55, 288.
Prati, L.; Rossi, M. Gazz. Chim. Ital., 1995, 125, 83.
Nematollahi, D.; Golabi, S. M. J. Electroanal. Chem., 1996, 405(1-
2), 133.
For a review, see: Langer, P. Synlett, 2006, 3369-3381.
Langer, P.; Stoll, M.; Schneider, T. Chem. Eur. J., 2000, 6, 3204.
Dede, R.; Michaelis, L.; Fuentes, D.; Yawer, M. A.; Hussain, I.;
Fischer, C.; Langer, P. Tetrahedron, 2007, 63, 12547.
Rotzoll, S.; Ullah, E.; Görls, H. Langer, P. Tetrahedron, 2007, 63,
2647.
have found that the reaction of 1 (1.0 mmol) with 2 (2.5
mmol) at 0 °C (neat) resulted in the formation of 3 in up to
51% yield (Scheme 1) [17] It is worth to be noted that the
reaction can be successfully carried out on a 20 mmol scale.
The presence of tertiary amine bases resulted in a decrease of
the yield, due to the difficult separation of the ammonium
salts.
[9]
The formation of 3 can be explained by attack of enol
ether 2 onto 1 to give intermediate A, extrusion of HCl and
subsequent cyclization (intermediate B) and extrusion of a
second molecule of HCl.
[10]
[11]
[12]
[13]
[14]
In conclusion, we have reported a new and convenient
synthesis of 4,5-dimethoxy-o-benzoquinone by formal [4+2]
cyclization of 2,3-dimethoxy-1,3-butadiene with oxalyl chlo-
ride. This strategy complements known methods for the syn-
thesis of the synthetically important title compound.
[15]
[16]
[17]
Effenberger, F.; Maier, R.; Schoenwaelder, K.-H.; Ziegler, T.
Chem. Ber., 1982, 115, 2766.
Procedure for the synthesis of 3: A mixture of 2,3- dimethoxy-1,3-
butadiene (1.0 mmol) and of oxalyl chloride (2.5 mmol) was stirred
at 0 °C for 6 h. The mixture was dissolved in CH2Cl2 (1 mL). The
solution was poured into water (10 mL). The mixture was extracted
with CH2Cl2 (3 x 5 mL). The combined organic layers were dried
(Na2SO4), filtered and concentrated in vacuo. A saturated CH2Cl2
solution of the residue was poured into n-heptane (150 mL) to give
a precipitate. The latter was filtered off to give 3 as a colourless
solid (137 mg, 51%). The reactions can be successfully carried out
on larger scale following the procedure given above. 1H-NMR (300
ACKNOWLEDGEMENTS
Financial support by the State of Mecklenburg-
Vorpommern is gratefully acknowledged.
REFERENCES AND NOTES
MHz, CDCl3): ꢀ = 3.90 (s, 6H, OCH3), 5.77 (s, 2H, CH). 13C-NMR
(300 MHz, CDCl3): ꢀ = 57.0 (OCH3), 102.9 (C), 163.6 (CH), 178.8
[1]
Reviews: (a) Wanzlick, H. W.; Lehmann-Horchler, M.; Mohrmann,
S.; Gritzky, R.; Heidepriem, H.; Pankow, B. Angew. Chem. Int. Ed.
Engl., 1964, 3, 401. (b) Nair, V.; Radhakrishnan, K. V. Product
class 2: benzo-1,2-quinones in Sci. Synth., 2006, 28, 181-215.
Stahl, P.; Kissau, L.; Mazitschek, R.; Huwe, A.; Furet, P.; Giannis,
A.; Waldmann, H. J. Am. Chem. Soc., 2001, 123, 11586.
Wanzlick, H.-W.; Jahnke, U. Chem. Ber., 1968, 101, 3744.
Wanzlick, H.-W.; Jahnke, U. Chem. Ber., 1968, 101, 3753.
Pfaltz & Bauer, Inc., 172 E. Aurora Street, Waterbury, CT, 06708,
USA. Aug 13th 2008.
1
(C=O). IR (KBr, cmꢁ ): 3436 (br, w), 1650 (s), 1580 (s), 1250 (s),
980 (m), 824 (m). MS (EI, 70 eV): m/z (%) = 168 [M+] (3), 153
(10), 140 (100), 125 (26), 82 (10), 86 (95). Anal.: calcd. for
C8H8O4: C 57.14, H 4.80. Found: C 57.07, H 4.83.
[2]
[3]
[4]
[5]