TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9125–9126
Methylation of 1,8-dihydroxy-9,10-anthraquinone with and
without use of solvent-free techniqueꢀ
Grigoriy A. Sereda* and David G. Akhvlediani
University of South Dakota, Department of Chemistry, 414 E. Clark Street, Vermillion, SD 57069, USA
Received 23 July 2003; accepted 8 October 2003
Abstract—A convenient and environmentally friendly solvent-free procedure has been developed for dimethylation of 1,8-dihy-
droxy-9,10-anthraquinone with excellent yield. A highly selective monomethylation of 1,8-dihydroxy-9,10-anthraquinone in
refluxing tetraglyme makes monomethylated peri-dihydroxy-9,10-anthraquinones easily available. Alternatively, irradiation in a
domestic microwave oven has been employed for the solvent-free monomethylation of 1,8-dihydroxy-9,10-anthraquinone.
© 2003 Elsevier Ltd. All rights reserved.
In the course of our current research we encountered a
necessity to synthesize 1,8-dimethoxy-9,10-anthraquin-
one (2) in large quantities. The known procedure of
dimethylation1 of 1,8-dihydroxy-9,10-anthraquinone (1)
employs carcinogenic dimethylsulfate, dangerous
sodium hydride, flammable tetrahydrofuran, takes 2–4
days for completion and provides a moderate yield of
57%.
The methylation system used (methyl tosylate with
sodium carbonate) is known and was applied before to
the methylation of 1,4-dihydroxy-9,10-anthraquinone
and required continuous refluxing (20 h) in toxic 1,2-
dichlorobenzene followed by concentration in vacuum
and chromatographic separation.3
Refluxing of the same reactants taken at the same ratio,
in tetraglyme for 2 h led to highly selective monomethy-
lation of the starting 1 (Scheme 1) and produced 1-
hydroxy-8-methoxy-9,10-anthraquinone (3)4 in excellent
yield (93%). The use of a high boiling solvent is essen-
tial for the reaction. Our attempt to methylate 1 by
refluxing with methyl tosylate and sodium carbonate in
acetone failed and only the starting material 1 was
isolated.
The suggested procedure is a fast, convenient and envi-
ronmentally friendly method for the complete methyla-
tion of 1 by heating of a ground mixture of 1, methyl
tosylate and sodium carbonate taken in a molar ratio of
1:2.8:1.6 at 320°C in a 6¦ test tube open to air for 5 min
(Scheme 1). This procedure represents solvent-free reac-
tions that have received a great deal of attention due to
their simplicity and usefulness in novel green chemistry
technologies2
Use of a microwave-assisted solvent-free technique for
monomethylation of 1 also proved to be quite selective.
Although the solvent-free procedure provided a lesser
yield of monomethylation (61% versus 93%), it required
less time (20 min versus 2 h) and did not require any
solvents.
The procedure does not require chromatographic sepa-
ration and provided a nearly quantitative yield (95%) of
2.
Although both 1,8-dimethoxy-9,10-anthraquinone 2
and 1-hydroxy-8-methoxy-9,10-anthraquinone 3 are
known,1,4 we obtained an additional proof of the struc-
ture of 2 by the single crystal X-ray analysis and a
proof for the structure of 3 by a separate experiment of
its methylation to 2.
Scheme 1.
ꢀ Supplementary data associated with this article can be found at
doi:10.1016/j.tetlet.2003.10.057
* Corresponding author.
Interestingly, monomethylation of 1 in tetraglyme
proved to be very selective. The methylating system
taken in a two-fold excess produced exclusively the
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.057