Syntheses of anthraeenones. 1. Sodium dithionite reduction of peri-substituted anthracenediones

Article abstract of DOI:10.1021/jo9520351

The reaction of peri-substituted anthracenediones with sodium dithionite in dimethylformamide and water has been investigated. The system selectively reduces the carbonyl group flanked by the peri substituents of the anthracenediones to give the corresponding 4,5-disubstituted 9(10H)-anthracenones and thus provides a route to anthracenones which are otherwise difficult to obtain. Many functional groups can be tolerated, the reaction is compatible with the presence of peri alkoxy groups and unsaturated side chains of the starting anthracenediones, and the reduction does not go beyond the anthracenone stage. However, the formation of anthracenones depends on the nature of the peri substituents. No products were obtained from the 1,8-dimethyl-substituted anthracene-dione and the parent compound with no substituents.

Full text of DOI:10.1021/jo9520351

J . Org. Chem. 1996, 61, 2853-2856
2853
Syn th eses of An th r a cen on es. 1. Sod iu m Dith ion ite Red u ction of
per i-Su bstitu ted An th r a cen ed ion es
Helge Prinz, Wolfgang Wiegrebe, and Klaus M u¨ ller*
Institut f u¨ r Pharmazie, Pharmazeutische Chemie I, Universit a¨ t Regensburg,
D-93040 Regensburg, Germany
Received November 16, 1995X
The reaction of peri-substituted anthracenediones with sodium dithionite in dimethylformamide
and water has been investigated. The system selectively reduces the carbonyl group flanked by
the peri substituents of the anthracenediones to give the corresponding 4,5-disubstituted 9(10H)-
anthracenones and thus provides a route to anthracenones which are otherwise difficult to obtain.
Many functional groups can be tolerated, the reaction is compatible with the presence of peri alkoxy
groups and unsaturated side chains of the starting anthracenediones, and the reduction does not
go beyond the anthracenone stage. However, the formation of anthracenones depends on the nature
of the peri substituents. No products were obtained from the 1,8-dimethyl-substituted anthracene-
dione and the parent compound with no substituents.
In tr od u ction
Ta ble 1. P r ep a r a tion of per i-Su bstitu ted An th r a cen on es
a n d th e Isom er s 3 fr om An th r a cen ed ion es 2
1
We have previously shown that 1,8-dihydroxy-9(10H)-
anthracenone (anthralin, 1a , Table 1) provides a useful
template for the design of potent inhibitors of leukotriene
biosynthesis.1 Also, this compound has established itself
,2
3
,4
as an important agent for the treatment of psoriasis.
However, this drug produces side effects such as inflam-
mation and staining of the skin which can be sufficiently
severe as to require treatment to be discontinued. Ac-
cordingly, there is a great need for antipsoriatic agents
which do not have these drawbacks. Several analogs of
1
a have been synthesized for evaluation of antipsoriatic
1
,2,5,6
properties,
but surprisingly it appears that none has
provided a structural change in the position of the keto
function. Therefore, we became interested in efficient
methods for the preparation of the isomeric 4,5-disub-
stituted 9(10H)-anthracenones 3 (Table 1).
anthacenedione method Aa method Bb
R1
R2
OH
R3
2
2
2
2d
2e
2
2
2
2
a
b
c
1a
1b
1c
3a
3b
3c
3d
3e
3f
3g
3h
3i
OH
H
H
H
Bn
H
Allyl
H
H
OH
H
H
c
OMe OMe
OMe OH
OMe OH
OMe OAllyl
OMe OH
OBn OBn
Cl
H
H
d
Introduction of side chains onto the anthracenone
nucleus is usually accomplished by a stepwise procedure
via the anthracenedione because of the chemical instabil-
ity of many anthracenones. Therefore, reduction of 9,10-
anthracenediones is required as a final step in the
1d d
e
1e
d
f
f
1f
g
g
h
i
1g
1h
1i
1j
Cl
OH
NH2
Me
H
2
synthesis of C-10-unsubstituted anthracenones. Al-
2j
2
2
3j
e
h
k
l
1k
3k
Me
H
though several excellent methods are available for the
reduction of anthracenediones, many reducing systems
do not lead directly to the anthracenone stage, but result
e
h
1l
3l
H
a
Reagents: SnCl2, HCl, glacial acetic acid, 118 °C. b Reagents:
c
Na2S2O4, DMF, H2O, 90 °C, N2. Compound exists in the tauto-
in the formation of a series of products ranging from
meric anthracenol form, see ref 40. d The reaction was performed
dihydroanthracenediols to dihydroanthracenes.7
-9
The
e
at room temperature, see Experimental Section. Not prepared.
traditionally employed methods that lead preferentially
to the anthracenones include stannous chloride in acetic
f
g
Obtained as a byproduct from the reduction of 2e. Reduction
of 2g gave exclusively 1a . h No reduction occurred.
1
0-14
acid-hydrochloric acid
and zinc in aqueous am-
*
To whom correspondence should be addressed. Phone: +49 941
monia.1
5,16
However, the latter method is often erratic
and may go beyond the anthracenone stage, and acidic
reduction conditions are not compatible with the presence
9
434810. Fax: +49 941 9434809.
X
Abstract published in Advance ACS Abstracts, April 1, 1996.
8
(
1) M u¨ ller, K.; G u¨ rster, D.; Piwek, S.; Wiegrebe, W. J . Med. Chem.
993, 36, 4099.
2) M u¨ ller, K.; Leukel, P.; Ziereis, K.; Gawlik, I. J . Med. Chem. 1994,
7, 1660.
1
3
3
of alkoxy groups.1
3,16,17
There are also other reagents like
(
(
3) Kem e´ ny, L.; Ruzicka, T.; Braun-Falco, O. Skin Pharmacol. 1990,
, 1.
(10) Goodall, F. L.; Perkin, A. G. J . Chem. Soc. 1924, 125, 470.
(11) Cross, E. J .; Perkin, A. G. J . Chem. Soc. 1930, 292.
(12) Auterhoff, H.; Scherff, F. C. Arch. Pharm. (Weinheim) 1960,
(
(
4) Wiegrebe, W.; M u¨ ller, K. Skin Pharmacol. 1995, 8, 1.
5) Van Duuren, B. L.; Segal, A.; Tseng, S.-S.; Rusch, G. M.;
Loewengart, G.; Mat e´ , U.; Roth, D.; Smith, A.; Melchionne, S.;
Seidman, I. J . Med. Chem. 1978, 21, 26.
293, 918.
(13) Cameron, D. W.; Sch u¨ tz, P. E. J . Chem. Soc. C 1967, 2121.
(14) House, H. O.; Koepsell, D. G.; Campbell, W. J . J . Org. Chem.
1972, 37, 1003.
(15) Liebermann, C. Ber. Dtsch. Chem. Ges. 1888, 21, 435.
(16) Attree, G. F.; Perkin, A. G. J . Chem. Soc. 1931, 144.
(
(
(
(
6) d’Ischia, M.; Prota, G. Synthesis 1986, 430.
7) Criswell, T. R.; Klanderman, B. H. J . Org. Chem. 1974, 39, 770.
8) Shyamasundar, N.; Caluwe, P. J . Org. Chem. 1981, 46, 1552.
9) Shyamasundar, N.; Caluwe, P. J . Org. Chem. 1981, 46, 809.
0
022-3263/96/1961-2853$12.00/0 © 1996 American Chemical Society

2
854 J . Org. Chem., Vol. 61, No. 8, 1996
Prinz et al.
Sch em e 1
rearranged 4,5-disubstituted anthracenone 3f were iso-
lated. The 4,5-disubstitution pattern received support
from the spectroscopic properties of 3f. The nonchelated
-1
carbonyl IR band occurred at 1642 cm , which contrasts
with those expected for the alternate chelated 9-carbonyl
groups of 1-hydroxyanthracenones which absorb near
-
1 26,27
1
615 cm
.
This is also confirmed by an upfield
shifted singlet at δ 9.05, indicating a non-hydrogen-
1
bonded phenolic proton in the H NMR spectrum, com-
pared to those of hydrogen-bonded 1-hydroxyanthra-
cenones at δ 12.1-12.3.1
,2,27
Conducting the reaction of sodium dithionite in DMF-
water (1 + 1) with the anthracenedione 2b at 90 °C gave
good yields of 3b. The reaction was complete after 24 h.
The formation of 3b as the sole reduction product is
surprising, because steric effects were expected to favor
reduction of the more accessible 10-keto group of the
the mixture of hydrogen iodide and acetic acid or red
phosphorus1
Furthermore, the situation with the 1,8-disubstituted
,10-anthracenediones 2 is confused by the fact that
8-20
which are not generally applicable.
1
anthracenedione 2b. Examination of its H NMR spec-
trum revealed a doublet of doublets (δ 7.97) assigned to
9
8,28
the protons peri to the carbonyl group.
This outcome
reduction may occur at the keto group remote from the
substituents or that adjacent to them to give 1,8-
disubstituted 9(10H)-anthracenones 1 or the isomeric
is significantly different from the one found with stan-
nous chloride in acetic acid-hydrochloric acid. Reduction
of 2b using this reagent gave exclusively the 1,8-
substituted isomer 1a in which both peri methyl ethers
had been cleaved. In order to illustrate the utility of the
sodium dithionite method, we examined a number of peri-
substituted anthracenediones.
4
,5-disubstituted 9(10H)-anthracenones 3, respectively.7,8
Thus, development of an alternative approach appeared
to be desirable. This paper describes an efficient proce-
dure for the reduction of anthracenediones using sodium
dithionite in the presence of DMF in neutral solution.
The present system selectively reduces the carbonyl
group flanked by the peri substituents of the anthracene-
dione to the corresponding 4,5-disubstituted 9(10H)-
anthracenones 3.
Thus, reduction of 1,8-dihydroxy- (2a ), 1-hydroxy-8-
methoxy- (2c), 1-hydroxy-2-benzyl-8-methoxy- (2d ), and
1
,8-bis(benzyloxy)-9,10-anthracenedione (2g) with sodium
dithionite in DMF-water (1 + 1) gave the corresponding
,5-disubstituted anthracenones 3a ,c,d ,g, respectively.
4
The formation of the latter requires 4 days to go to
completion. By contrast, 3h is formed with remarkable
ease from 1,8-dichloroanthracenedione (2h ) under the
same conditions after just 1 h.
Furthermore, the reduction of 2j to 4-aminoanthra-
cenone (3j) was successful, which is otherwise difficult
to synthesize,29 whereas 4,5-dimethylanthracenone (3k )
and the unsubstituted anthracenone (3l) could not be
prepared by the sodium dithionite-DMF method. Table
1 summarizes the substitution patterns of anthracenones
Resu lts a n d Discu ssion
1
-Hydroxy-9,10-anthracenediones are reduced in situ
to the anthrahydroquinones under the conditions of the
Marschalk reaction, involving treatment with sodium
dithionite in basic solution.2
1-23
Similar conditions can
also be applied to the reductive Claisen rearrange-
ment.2
4,25
The reactions are performed with the ap-
propriate anthracenediones and sodium dithionite (1-2
2
4
mol equiv) in DMF-water (1 + 1) with gentle heating.
When preparing the 2-allylanthracenedione (2f)25 from
3. The structures of the compounds were definitely
confirmed by comparison with their peri-substituted
isomers 1, most of which were prepared by reduction of
the anthracenediones 2 using stannous chloride in acetic
acid-hydrochloric acid (see Experimental Section).
Our results indicate that the reduction with sodium
dithionite in DMF-water (1 + 1) fails if there are no peri
substituents. This conclusion is based upon the results
obtained with the parent anthracenedione (2l) which was
not reduced. Furthermore, the mere presence of peri
substituents is not sufficient for a successful reduction
of anthracenediones. In addition, the electronic effects
of the peri substituents play a critical role, since 1,8-
dimethyl substituents (2k ) did not enable anthracenone
formation. Methoxy (3b-f) and benzyloxy (3g) substit-
uents remain intact, and aryl halides (3h ) are not
reduced. Moreover, the successful preparations of 3d and
3f demonstrate that this reduction method will tolerate
2
e according to this method, we noted the formation of a
byproduct which was identified as anthracenone 3e
(Scheme 1). However, no reference to anthracenone
2
4,25
formation is found in previous reports.
We subse-
quently attempted to extend this method to the selective
reduction of anthracenediones to the corresponding an-
thracenones having the substituents remote from the
keto group. To this end, we increased the molar ratio of
sodium dithionite to anthracenedione (10:1) and raised
the reaction temperature to 90 °C. Upon an extended
period of time (48 h), anthracenone 3e was obtained as
the main product. In addition, small amounts of the
(
(
(
(
(
17) Cook, J . W.; Pauson, P. L. J . Chem. Soc. 1949, 2726.
18) Hesse, O. Liebigs Ann. Chem. 1895, 284, 191.
19) Oesterle, O. A. Arch. Pharm. (Weinheim) 1911, 249, 445.
20) Konieczny, M.; Harvey, R. G. J . Org. Chem. 1979, 44, 4813.
21) Marschalk, C.; Koenig, F.; Ouroussoff, N. Bull. Soc. Chim. Fr.
1
1
936, 3, 1545.
22) Suzuki, F.; Trenbeath, S.; Gleim, R. D.; Sih, C. J . J . Org. Chem.
978, 43, 4159.
(
(26) Alexander, J .; Bhatia, A. V.; Clark, G. W.; Leutzow, A.;
Mitscher, L. A.; Omoto, S.; Suzuki, T. J . Org. Chem. 1980, 45, 24.
(27) Avdovich, H. W.; Neville, G. A. Can. J . Spectrosc. 1980, 25, 110.
(28) Meek, J . S.; Koh, L. L. J . Org. Chem. 1968, 33, 2942.
(29) Bayer, O. In Methoden der Organischen Chemie (Houben-Weyl);
M u¨ ller, E., Bayer, O., Eds.; Thieme: Stuttgart, 1979; Vol. VII/3c, pp
39-44.
(
23) Krohn, K. Tetrahedron 1990, 46, 291.
(24) Boddy, I. K.; Boniface, P. J .; Cambie, R. C.; Craw, P. A.; Larsen,
D. S.; McDonald, H.; Rutledge, P. S.; Woodgate, P. D. Tetrahedron Lett.
982, 23, 4407.
25) Zembower, D. E.; Kam, C.-M.; Powers, J . C.; Zalkow, L. H. J .
Med. Chem. 1992, 35, 1597.
1
(

Syntheses of Anthracenones. 1
Sch em e 2
J . Org. Chem., Vol. 61, No. 8, 1996 2855
tendency of 9,10-dihydro-9,10-dihydroxyanthracenes to-
ward elimination of water is well known.36 However, we
are at present in no position to comment upon the
mechanism of anthracenone formation and the role
played therein by the peri substituents, since we were
not able to isolate any intermediates. The situation with
dihydroanthracenes such as 4 is further complicated by
the fact that 4 can be considered a dibenzo-1,4-cyclo-
hexadiene and as such exists in the boat conformation
(with unknown stereochemistry of the hydroxyl group),
wherein interactions between equatorial positions and
neigboring peri groups are very pronounced.36
In conclusion, this work represents an improved and
efficient method for the preparation of 4,5-disubstituted
9
(10H)-anthracenones from their corresponding anthra-
cenediones. The reduction of anthracenediones with
sodium dithionite in DMF-water (1 + 1) provides a
potential route to many anthracenones which are other-
wise difficult to obtain. The procedure is superior to
those reported in that it can be performed in neutral
solution, the reduction does not go beyond the anthra-
cenone stage, and the reaction is compatible with the
presence of peri alkoxy groups and unsaturated side
chains of the starting anthracenediones. Studies are in
progress aimed at evaluating these compounds for an-
tipsoriatic activity.
benzyl groups and unsaturated side chains on the an-
thracenone nucleus. Also, the reaction time depends on
the nature of the peri substituents of the anthracenedione
being reduced, increasing in the following order: Cl <
OH, MeO < NH
2
2
< OCH Ph.
Although the reducing properties of sodium dithionite
toward several functional groups are well documented,30
reduction of anthracenediones by this reagent has re-
sulted in conflicting reports: In contrast to the reduction
of the parent anthracenedione in alcoholic solution or
hydroxy- and methoxy-substituted anthracenediones in
5
0% aqueous acetonitrile, which give the anthrahydro-
3
1,32
quinones,
it has been reported that in alkaline solu-
Exp er im en ta l Section
tion the reduction of substituted anthracenediones could
proceed further, anthracenones being formed.33 On the
other hand, anthracenediones are known to be reduced
to anthrahydroquinones under the basic conditions of the
Marschalk reaction.23 However, according to our method
the presence of peri substituents in anthracenediones
promotes reduction to the anthracenone stage rather
than anthrahydroquinones, and basic conditions are not
necessary for an effective reduction. This is of great
advantage because hydroxyanthracenones are unstable
in basic solution and give rise to the dimeric dianthrones
and polymeric dark structures (so-called anthralin-
Gen er a l. For analytical instruments and methods, see ref
. Thin layer chromatography (TLC) was conducted on Merck
Kieselgel 60 F254 precoated silica gel plates. Column chroma-
tography was performed on Merck silica gel (70-230 mesh)
2 2
with CH Cl as eluant, unless otherwise stated. Elemental
analyses were determined by the Microanalytical Laboratories
at the University of Regensburg.
1
The 9,10-anthracenediones 2 were commercial products
(Aldrich) or prepared as indicated.
1,8-Bis(ben zyloxy)-9,10-a n th r a cen ed ion e (2g). To a
suspension of 2a (10.0 g, 41.60 mmol) and K CO (30.0 g, 21.75
2 3
mmol) in dry acetone (300 mL) was added dropwise benzyl
chloride (45.5 g, 359 mmol). The mixture was refluxed for 3
days, cooled, and then filtered by suction. The residue was
washed with petroleum ether (40-60) and dried. Then it was
brown).3
4,35
The mechanism or even the active species of the
reducing system sodium dithionite in DMF-water (1 +
1
) is still not clear. De Vries et al. suggested that
suspended in water and thoroughly extracted with CH
combined organic phase was dried over Na SO and evaporated
to afford orange-yellow crystals: 85% yield; mp 221-222 °C;
2 2
Cl . The
R-hydroxy sulfinates are probable intermediates in the
reduction of ketones by this reagent, followed by reduc-
2
4
-
1
1
tive decomposition with loss of SO
2
to give the corre-
FTIR 1667 cm ; H NMR (90 MHz, CDCl ) δ 7.95-7.30 (m,
3
3
0
sponding alcohols. Also, they suggested that the radical
16 H), 5.35 (s, 4 H). Anal. Calcd for C28
4.79. Found: C, 79.80; H, 4.79.
20 4
H O : C, 80.00; H,
•
-
anion SO
2
was the putative reductant in the formation
1,8-Dim eth yl-9,10-a n th r a cen ed ion e (2k ).37
of R-hydroxy sulfinates. However, the observation that
dimers of anthracenones were not formed during our
reactions strongly suggests that radical species are not
involved in the course of the reduction of anthracenedi-
Meth od A: Gen er a l P r oced u r e for th e Red u ction of
An t h r a cen ed ion es t o p er i-Su b st it u t ed An t h r a cen on es
(
1). To a solution of the anthracenedione (2, 0.70 mmol) in
glacial acetic acid (20 mL) heated to reflux was added,
dropwise over 3 h, a solution of SnCl (2.5 g, 13.19 mmol) in
7% HCl (5.2 mL). The solution was then cooled, and the
ones to the anthracenones. On the basis of the work of
de Vries et al.,30 the reduction of anthracenediones 2 by
2
3
sodium dithionite would lead to the 9,10-dihydro-9,10-
dihydroxyanthracene 4, which upon dehydration would
give the hydroxyanthracene 5, followed by tautomeriza-
tion to the corresponding anthracenone 3 (Scheme 2). The
resulting crystals were collected by filtration. Purification by
column chromatography provided the anthracenone 1. 1,8-
12
Dihydroxy-9(10H)-anthracenone (1a ), 1,8-dichloro-9(10H)-
anthracenone (1h ),38 1,2-dihydroxy-9(10H)-anthracenone (1i),
11
3
9
and 1-amino-9(10H)-anthracenone (1j) were prepared ac-
(30) de Vries, J . G.; Kellogg, R. M. J . Org. Chem. 1980, 45, 4126.
(31) Grandmougin, E. Ber. Dtsch. Chem. Ges. 1906, 39, 3561.
(32) Blankespoor, R. L.; Kosters, E. L.; Post, A. J .; VanMeurs, D. P.
cording to this method.
J . Org. Chem. 1991, 56, 1609.
(36) Cristol, S. J . Acc. Chem. Res. 1971, 4, 393.
(37) Cristol, S. J .; Caspar, M. L. J . Org. Chem. 1968, 33, 2020.
(38) House, H. O.; Ghali, N. I.; Haack, J . L.; VanDerveer, D. J . Org.
Chem. 1980, 45, 1807.
(33) Battegay, M.; Hueber. Bull. Soc. Chim. Fr. 1923, 33, 1094.
(34) Cavey, D.; Caron, J .-C.; Shroot, B. J . Pharm. Sci. 1982, 71, 980.
(35) M u¨ ller, K.; Mayer, K. K.; Wiegrebe, W. Arch. Pharm. (Wein-
heim) 1986, 319, 1009.
(39) Bradley, W.; Maisey, R. F. J . Chem. Soc. 1954, 274.

2
856 J . Org. Chem., Vol. 61, No. 8, 1996
Prinz et al.
1
1
,8-Dim eth oxy-9(10H)-a n th r a cen on e (1b).40
4-Hyd r oxy-5-m eth oxy-9(10H)-a n th r a cen on e (3c) was
obtained from 2c.41 Column chromatography using CH
Cl
-
-Hyd r oxy-8-m eth oxy-9(10H)-a n th r a cen on e (1c). An-
2
2
4
1
thracenedione 2c (1.50 g, 5.90 mmol) was suspended in
glacial acetic acid (50 mL). A solution of SnCl (7.57 g, 33.54
methanol (99 + 1) gave colorless needles: 48% yield; mp 230
-
1 1
2
6
°C (dec); FTIR 3253, 1652 cm ; H NMR (90 MHz, DMSO-d )
mmol) in 37% HCl (15 mL) was added in one portion, and the
mixture was stirred at room temperature until the reaction
was complete (TLC control). It was then poured into water
δ 10.20 (s, 1 H), 7.88-7.13 (m, 6 H), 3.97 (s, 5 H). Attempts
to obtain a satisfactory elemental analysis of 3c were unsuc-
cessful. However, acetylation of 3c gave pure 1,10-di-
1
(
500 mL), stirred for 10 min, and extracted with CH
0 mL). The combined organic phase was washed with water
3 × 100 mL) and then with a saturated solution of NaHCO
100 mL), dried over Na SO , and evaporated. Purification by
2
Cl
2
(3 ×
acetoxy-8-methoxyanthracene: H NMR (90 MHz, CDCl
3
) δ
5
8.87 (s, 1 H), 7.92-6.68 (m, 6 H), 4.03 (s, 3 H), 2.57 (s, 3 H),
2.52 (s, 3 H). Anal. Calcd for C19
Found: C, 70.25; H, 5.01.
(
(
3
16 5
H O : C, 70.36; H, 4.97.
2
4
column chromatography afforded yellow platelets: 71% yield;
4-Hydr oxy-5-m eth oxy-3-(ph en ylm eth yl)-9(10H)-an th r a-
1
6
25
mp 154 °C (lit. mp 183-185 °C). Although a disparity of
the mp between the literature and the reported value was
observed, a satisfactory elemental analysis was obtained.
cen on e (3d ) was obtained from 2d as pale yellow crystals:
-
1
1
66% yield; mp 223 °C; FTIR 3383, 1642 cm ; H NMR (90
MHz, CDCl
3
) δ 9.83 (s, 1 H), 8.03-6.78 (m, 10 H), 4.20 (s, 2
Anal. Calcd for C15
H, 5.08.
H
12
O
3
: C, 74.99; H, 5.03. Found: C, 74.71;
18 3
H), 4.12-4.02 (m, 5 H). Anal. Calcd for C22H O : C, 79.98;
H, 5.49. Found: C, 79.69; H, 5.50.
1
-Hydr oxy-8-m eth oxy-2-(ph en ylm eth yl)-9(10H)-an th r a-
4-Allyloxy-5-m eth oxy-9(10H)-a n th r a cen on e (3e) was
2
5
25
cen on e (1d ) was prepared from 2d as described for 1c to
obtained from 2e as colorless needles: 48% yield; mp 151
-
1 1
afford yellow crystals: 71% yield; mp 162 °C; FTIR 3425, 1629
3
°C; FTIR 1663 cm ; H NMR (400 MHz, CDCl ) δ 7.98-7.07
-
1
1
cm ; H NMR (90 MHz, CDCl
m, 10 H), 4.23 (s, 2 H), 4.00 (s, 2 H), 3.97 (s, 3 H). Anal. Calcd
for C22 : C, 79.98; H, 5.49. Found: C, 79.98; H, 5.63.
-Allyl-1-h yd r oxy-8-m eth oxy-9(10H)-a n th r a cen on e (1f)
3
) δ 13.48 (s, 1 H), 7.58-6.62
(m, 6 H), 6.19-6.09 (m, 1 H), 5.51-5.32 (m, 2 H), 4.70-4.68
+
(
(m, 2 H), 4.06 (s, 2 H), 3.95 (s, 3 H); MS m/ z ) 280 (68, M ).
H
18
O
3
Anal. Calcd for C18
H, 5.71.
16 3
H O : C, 77.12; H, 5.75. Found: C, 76.94;
2
2
5
was prepared from 2f as described for 1c to afford pale yellow
3-Allyl-4-h yd r oxy-5-m eth oxy-9(10H)-a n th r a cen on e (3f)
-
1
1
25
platelets: 34% yield; mp 223 °C; FTIR 1627 cm ; H NMR
250 MHz, CDCl
was obtained from 2e, along with 3e, as pale yellow
-
1
(
5
3
3
) δ 13.39 (s, 1 H), 7.55-6.78 (m, 5 H), 6.12-
.96 (m, 1 H), 5.26-5.05 (m, 2 H), 4.31 (s, 2 H), 4.01 (s, 3 H),
.45 (d, J ) 6.56 Hz, 2 H). Anal. Calcd for C18 : C, 77.12;
needles: 21% yield; mp 187 °C; FTIR 3425, 2842, 1642 cm ;
1
3
H NMR (90 MHz, CDCl ) δ 9.05 (s, 1 H), 8.02-6.73 (m, 5 H),
H
16
O
3
6.30-5.78 (m, 1 H), 5.23-4.95 (m, 2 H), 4.03 (s, 2 H), 3.95 (s,
+
H, 5.75. Found: C, 76.94; H, 5.86.
3 H), 3.63-3.42 (m, 2 H); MS m/ z ) 280 (100, M ). Anal.
Calcd for C18
.84.
,5-Bis(ben zyloxy)-9(10H)-a n th r a cen on e (3g) was ob-
tained from 2g as colorless needles: 68% yield; mp 163 °C;
16 3
H O : C, 77.12; H, 5.75. Found: C, 76.94; H,
Meth od B: Gen er a l P r oced u r e for th e Red u ction of
An t h r a cen ed ion es t o An t h r a cen on es (3) w it h Sod iu m
Dith ion ite in DMF -Wa ter . To a suspension of the an-
thracenedione (2, 2.0 g, 4.76-8.96 mmol) in DMF (100 mL)
and water (100 mL) was added Na
and the solution was slowly heated to 90 °C within 30 min
under N . Then the mixture was stirred until the reaction
was complete (TLC control). The mixture was cooled to room
temperature and then poured into water (1 L) and extracted
2 2
with CH Cl
5
4
-
1
1
2 2 4
S O (14.0 g, 80.41 mmol),
FTIR 1659 cm ; H NMR (90 MHz, CDCl ) δ 8.10-6.93 (m,
3
16 H), 5.20 (s, 4 H), 4.20 (s, 2 H). Anal. Calcd for C28
C, 82.74; H, 5.46. Found: C, 82.44; H, 5.38.
22 3
H O :
2
4,5-Dich lor o-9(10H)-a n th r a cen on e (3h ) was obtained
mp 198-199 °C).
from 2h : 79% yield; mp 194 °C (lit.38
,4-Dih yd r oxy-9(10H)-a n th r a cen on e (a n th r a r obin , 3i)
(4 × 100 mL). The combined organic phase was
3
4
4
washed with water (4 × 200 mL), dried over Na
2
SO , evapo-
4
was obtained from 2i (alizarin): 51% yield; mp 208 °C (lit.
rated, and purified by column chromatography to provide the
mp 208 °C).
anthracenone 3.
4
from 2a as colorless needles: 28% yield; mp 260 °C dec (lit.
mp 293-295 °C, 260 °C).
4
from 2b as colorless needles: 72% yield; mp 237 °C (lit.
mp 244-245 °C, 234-236 °C).
4-Am in o-9(10H)-a n th r a cen on e (3j) was obtained from
2
j: 71% yield; mp 171 °C (lit.29 mp 172-173 °C).
,5-Dih yd r oxy-9(10H)-a n th r a cen on e (3a ) was obtained
1
1,40
J O9520351
,5-Dim eth oxy-9(10H)-a n th r a cen on e (3b) was obtained
(41) Krohn, K.; M u¨ ller, U.; Priyono, W.; Sarstedt, B.; Stoffregen, A.
Liebigs Ann. Chem. 1984, 306.
4
2
8,43
(42) Brockmann, H.; Neef, R.; M u¨ hlmann, E. Chem. Ber. 1950, 83,
4
67.
(
43) Zahn, K.; Koch, H. Ber. Dtsch. Chem. Ges. 1938, 71, 172.
(40) Prinz, H.; Burgemeister, T.; Wiegrebe, W.; M u¨ ller, K. J . Org.
(44) The Merck Index, 11th Ed.; Budavari, S., Ed.; Merck & Co.:
Chem. 1996, 61, 2857.
Rahway, NJ , 1989.