Synthesis of new anthracene derivatives

Article abstract of DOI:10.1021/jo051846u

An efficient synthesis is described for hexabromoanthracenes 3 and 4 by direct bromination of 9,10-dibromoanthrecene 2. Whereas base-induced elimination of hexabromide 3 with t-BuOK gave 2,3,9,10-tetrabromoanthracene 5, the reaction of hexabromide 4 with DBU afforded 1,3,9,10-tetrabromoanthracene 6 as the sole product. Tetrabromide 5 was also obtained by aromatization of 1,4-dinitroxy-2,3,9,10-tetrabromo-1,2,3,4-tetrahydroanthracene 17. Efficient and convenient synthetic routes are described for the preparation of dinotroxy 17, dimethoxy 23, and dihydroxides 18 and 19 with silver-induced substitution of hexabromides 3 and 4. The hydroxy compounds 19 and 18 were converted to diepoxide 20 and monoepoxide 21, respectively, with sodium methoxide. Base-promoted aromatization of dimethoxide 23 afforded dibromomonomethoxides 26 and 27. Bromoanthracenes and isomeric arene oxides constitute valuable precursors for the preparation of functionalized substituted anthracene derivatives that are difficult to prepare by other routes.

Full text of DOI:10.1021/jo051846u

Synthesis of New Anthracene Derivatives
Osman Cakmak,*,† Ramazan Erenler,† Ahmet Tutar,‡ and Nuray Celik†
Department of Chemistry, Faculty of Art and Science, Gaziosmanpasa UniVersity, 60240 Tokat, Turkey,
and Department of Chemistry, Faculty of Art and Science, Sakarya UniVersity, Turkey
ocakmak@gop.edu.tr
ReceiVed September 1, 2005
An efficient synthesis is described for hexabromoanthracenes 3 and 4 by direct bromination of 9,10-
dibromoanthrecene 2. Whereas base-induced elimination of hexabromide 3 with t-BuOK gave 2,3,9,10-
tetrabromoanthracene 5, the reaction of hexabromide 4 with DBU afforded 1,3,9,10-tetrabromoanthracene
6 as the sole product. Tetrabromide 5 was also obtained by aromatization of 1,4-dinitroxy-2,3,9,10-
tetrabromo-1,2,3,4-tetrahydroanthracene 17. Efficient and convenient synthetic routes are described for
the preparation of dinotroxy 17, dimethoxy 23, and dihydroxides 18 and 19 with silver-induced substitution
of hexabromides 3 and 4. The hydroxy compounds 19 and 18 were converted to diepoxide 20 and
monoepoxide 21, respectively, with sodium methoxide. Base-promoted aromatization of dimethoxide 23
afforded dibromomonomethoxides 26 and 27. Bromoanthracenes and isomeric arene oxides constitute
valuable precursors for the preparation of functionalized substituted anthracene derivatives that are difficult
to prepare by other routes.
Introduction
tetrahydrodiol and tetrahydro epoxides, little is known about
their chemical reactivity and the mechanisms of their reactions.
Many natural products also contain reduced derivatives of the
anthaquinones (oxanthrones, anthranols, and anthrones). Bro-
moanthracenes have specialty intermediate applications for the
production of amine, ether, nitrile, sulfide, silyl, and organo-
metallic derivatives of anthracene. Studies on the bromination
of anthracene are tedious and unsatisfactory. No reaction details
or spectral data of bromoanthracenes (except for 9,10-dibro-
moanthracene) are available in the earliest research.3
We aimed to employ the exhaustive bromination of 9,10-
dibromoanthracene or anthracene to obtain still higher bromi-
nated anthracenes. We recently described the selective bromi-
nation of 1-bromonaphthalene and efficient preparation methods
for bromonaphthalene derivatives.4 As an extension of this work
we studied the bromination reaction of 9,10-dibromoantracene
in specific reaction conditions. In this paper we describe the
first isolation and identification of two arene oxides from
hexabromoanthracene and other derivatives of anthracene from
Among the polycyclic aromatic hydrocarbons, anthracene and
its derivatives have been extensively investigated; this is
reflected in the tens of thousands of publications dealing with
anthracene since 1970 (see Chemical Abstracts). One of
anthracenes’ specialties is the bimolecular photochemical reac-
tion. The ring is able to act as a light-induced electron donor or
as an acceptor, a property easily tuned by substitution. An-
thracenes also possess photochromic properties that can be used
in the design of optical, electronic, or magnetic switches
incorporated in mesophases, polymers, films, or crystals. These
reversible properties are based on the photodimerization reac-
tion.1
Dihydrodiols and epoxides are implicated as the active forms
of carcinogenic polynuclear aromatic hydrocarbons.2 Despite
the many published studies on the biological activity of
† Gaziosmanpasa University.
‡ Sakarya University.
(1) Bouas-Laurent, H.; Castellan, A.; Desvergne, J.-P.; Lapouyade, R.
Chem. Soc. ReV. 2000, 29, 43-55.
(3) (a) Barry-Barnett, E. D.; Cook, J. W. J. Chem. Soc. 1925, 127, 1490.
(b) Barry-Barnett, E. D.; Cook, J. W. J. Chem. Soc. 1925, 127, 204. (c)
Sampey, J. R.; McCuen, A. K.; Cox, J. M. J. Am. Chem. Soc. 1950, 72,
1854.
(2) (a) Wislocki, P. G.; Lu, A. Y. Polycyclic Aromatic Hydrocarbons
and Carginogenesis: Structure-ActiVity Relationships; Yang, S. K.,
Silverman, B. D., Eds.; CRC Press: Boca Raton, FL, 1988; p 1.
10.1021/jo051846u CCC: $33.50 © 2006 American Chemical Society
Published on Web 02/04/2006
J. Org. Chem. 2006, 71, 1795-1801
1795

Cakmak et al.
SCHEME 1
SCHEME 2
SCHEME 3
hexabromoanthracene. We also aimed to elaborate the conver-
sions and to illustrate the potential utility of isomeric anthracene
oxides for the synthesis of polysubstituted anthracene derivatives
that are difficult to synthesize using other routes.
Results and Discussion
The bromination of anthracene with 2 equiv of molecular
bromine was carried out at 0 °C in the dark in CH2Cl2. A fast
bromination occurred to form 9,10-dibromoanthracene in a yield
of 96%. In the same manner, bromination of 9,10-dibromo-
anthracene in CH2CI2 at -15 °C gave 1,2,3,4,9,10-hexa-
bromotetrahydroanthracene 3 and 4 in a ratio of 60:40. Careful
fractional crystallization in the dark afforded hexabromides 3
and 4 in yields of 45% and 30%, respectively (Scheme 1).
Proton and carbon NMR studies indicate that hexabromide
3 has asymmetry in its structure. There are two possible isomeric
structures, 3 and 8, for unsymmetrical hexabromide. The vicinal
coupling constant value (11.2 Hz) for hexabromide 3 indicates
the trans-configuration of the bromine atoms at C2 and C3
carbon atoms, which is only in agreement with the proposed
structure 3. Similar signal systems and the coupling constants
with those of naphthalene hexabromide 75 confirm the suggested
structure. Analysis of the first-order 1H NMR spectrum indicated
a large coupling constant (11.2 Hz) for the protons bonded to
C2 and C3 atoms, which strongly supports axial-axial alignment
of the protons. In other words, bromine atoms prefer equatorial
1
positions. Abraham et al.6 performed H NMR analysis of all
possible conduritol derivatives and found similar coupling (J
) 11.0 Hz) for conduritol-F. In the case of the cis configuration
(conduritol-C) of hydroxy groups (axial-equatorial), the mea-
sured coupling constant is 2.1 Hz. This comparison indicates
clearly that the isolated hexabromide 3 has the trans,trans,cis
configuration (Scheme 2).
1H NMR spectra exhibited two AA′BB′ for symmetrical
hexabromide 4. Seven lines in the 13C NMR spectra also agreed
with the symmetrical hexabromide. Four symmetrical stereo-
isomers can be formed in the reaction. Attempts to X-ray
hexabromide 4 failed because we could not obtain suitable single
crystal; it readily aromatizes and configuration isomerization
occurs in solvent even in daylight. Although base-induced
aromatization of the hexabromide 4 can lead to three tetra-
bromides, 5, 6, and 16, we obtained only tetrabromide 6. It is
interesting that dehydrobromination of trans,trans,trans-
bromotetralines (9,4a,d Scheme 3) exhibited the same selectivity,
which may be evidence for the suggested trans,trans,trans
configuration.
(4) (a) Cakmak, O. J. Chem. Res. (S) 1999, 366-367. (b) Cakmak, O.;
Kahveci, I.; Demirtas, I.; Hokelek, T.; Smith, K. Collect. Czech. Chem.
Commun. 2000, 65, 1791-1804. (c) Tutar, A.; Cakmak, O.; Balcı, M.
Tetrahedron 2001, 57, 9759-9763. (d) Cakmak, O.; Demirtas, I.; Balaydin,
H. T. Tetrahedron 2002, 58, 5603. (e) Adam, W.; C¸ akmak, O.; Saha-Mo¨ller,
C. R.; Tutar, A. Synlett 2002, 49-52, (f) Tutar, A.; C¸ akmak, O.; Karakas¸,
M.; Onal, A.; Die, S. J. Chem. Res. 2004, 545-549. (g) Erenler, R. C¸ akmak,
O. J. Chem. Res. 2004, 545-549.
(5) Das¸tan, A.; Tahir, M. N.; Ulku, D.; Balci, M. Tetrahedron 1999, 55,
12855-12864.
(6) Abraham, R. J.; Gottschalck, H.; Paulsen, H.; Thomas, W. A. J. Chem.
Soc. 1965, 6268-6275.
1796 J. Org. Chem., Vol. 71, No. 5, 2006

New Anthracene DeriVatiVes
SCHEME 4
zylic positions (i.e. 1,4-positions) in the hexabromides are
expected to be reactive for substitution. Therefore, the silver-
induced nucleophilic substitution of hexabromides 3 or 4 in
benzylic positions followed by base-induced aromatization
would be a prime tool for producing some difficult to obtain
anthracene derivatives.
A solution of hexabromide 3 in dry diethyl ether was
combined with 2 equiv of silver nitrate, followed by stirring
for 3 days at room temperature in dry THF in the dark. After
crystallization and column chromatography, 1,4-dinitrate-
2,3,9,10-tetrabromo-1,2,3,4-tetrahydroanthracene 17 was ob-
tained in a yield of 59%.
SCHEME 5
1
Spectra of H NMR of dinitroxy 17 consist of two AA′BB′
signal systems indicating a symmetry structure. As a result of
the strong inductive effect of the nitroxy group, the resonance
of H1 and H4 shifts to quite a lower field (6.93 ppm) in
comparison to those of the hexabromides. The mass and
elemental analysis results showed a good agreement with the
proposed structure. Surprisingly, base-induced elimination of
dinitroxy 17 with sodium methoxide resulted in the elimination
of HNO3 instead of HBr to give 2,3,9,10-tetrabromoanthracene
5 (Scheme 7). Our findings from the benzylic nitration9 are of
special interest due to the group leaving more easily than bromo
atoms. It is clear from models that the steric interactions of the
bromo atoms have an enormous effect, and presumably smaller
steric requirements can cause the reaction to take place
preferentially from the trans direction.
We also investigated the silver-induced hydrolysis of hexabro-
mides 3 and 4. This procedure in aqueous THF resulted in the
replacement of benzylic bromides to give 1,4-dihydroxy-
anthracenes. After careful chromatography, followed by frac-
tional crystallization, two dihydroxides, 18 and 19, were isolated
in 40% and 35% yields, respectively (Scheme 9).
Further evidence for the stereochemistry of hexabromides 3
and 4 is the fact that bromination of naphthalene (or 1,4-
dibromonaphthalene) in the same conditions gives two hexa-
bromides, 12 and 13, with the same stereochemistry as that of
hexabromides 3 and 4 (Scheme 4). Last, because of the existence
of X-ray analyses of two other symmetrical hexabromides 147
and 15 (Scheme 5; unpublished results), the symmetrical product
must be in the trans configuration of all bromo substituents (i.e.,
hexabromide 4)
After the successful isolation of the hexabromides 3 and 4,
which have the requisite skeletal arrangement and functionality
to permit the easy introduction of two double bonds to form
anthracene derivatives, we submitted both hexabromides 3 and
4 to dehydrobromination. Whereas aromatization of hexa-
bromide 3 with 2 mol of potassium tert-butoxide gave tetra-
bromide 5, dehydrobromination of hexabromide 4 with 2 mol
of DBU afforded 1,3,9,10-tetrabromide 6 in high yields as the
sole products.
NMR spectra indicate symmetry in its structure. Dehydro-
bromination of the hexabromides 3 and 4 can lead to two
symmetrical tetrabromoantracene isomers: 1,4,9,10- (16) and
2,3,9,10-tetrabromoanthracenes. 1H NMR is in accord with only
symmetrical 2,3,9,10-tetrabromoanhtacene structure 5 as a result
of the fact that the shifts downfield (8.8 ppm) of the singlet
resonance of H1 and H4 can only be interpreted for structure 5,
which has a van der Waals interaction between the protons (H1/
H4) and the bromine atoms (Br9/Br10). Simple characteristic 1H
NMR spectra exhibited a singlet for H1 and H4 and AA′BB′
for aryl protons. The obtaining of tetrabromide 5 instead of
tetrabromide 16 may be attributed to the enormous increase in
strain energy (26.10 kJ/mol)8 in the case of structure 16 due to
steric compression of bromo groups in γ-gauche positions
(Scheme 6).
Proton and carbon NMR of tetrabromide 6 is in accord with
the suggested unsymmetrical structure. Resonance of H4 is a
doublet (J ) 1.84 Hz) at 8.89 ppm. A meta coupling doublet
of H2 appears at 8.15. The other protons are multiplets due to
the asymmetry. Fourteen 13C NMR signals of four carbons
bonded, bromine atoms are in accord with the suggested
structure.
The structures were determined by mass analysis and 1H and
13C NMR spectroscopy, including a comparison with literature
values of analogous compounds. Seven lines in the 13C NMR
1
spectra and the H NMR spectrum consisting of two AA′BB′
system, including hydroxyl groups (5.20 ppm), are in good
agreement with the proposed symmetrical structure 19. The
symmetry at dihydroxide 19 can adopt two different configura-
tions, trans,trans,trans or cis,trans,cis. Comparison of this 19
molecule with the Conduritol-E (J12 ) 4.3 Hz) and Conduritol-B
(J12 ) 8.3 Hz) indicate clearly that the isolated symmetry
dihydroxyl 19 has the trans,trans,trans (J12 ) 7.1 Hz) config-
uration (Scheme 9).6 Further confirmation of the stereochemistry
of compound 19 was achieved by cyclization of the trans-
halohydrin 19 to diepoxide 20 (Scheme 9).
1H and 13C NMR spectral studies on the other dihydroxide
18 indicate its asymmetry. It is obvious that there is only one
possible asymmetrical isomeric structure of 18 due to the
configuration retention of bromine-bonded C2 and C3 atoms.
The 1H NMR spectrum of the cis-1,4-diol 18 has a cis coupling
constant (J ) 1.9 Hz) for the H1 and H2 protons and a trans
diaxial coupling constant (J ) 3.2 Hz) for the H3 and H4 protons.
H1 and H4 protons are also coupled with the hydroxyl groups
(J1-OH ) 10.0 Hz; J4-OH ) 4.0 Hz). Resonances of H2 and H4
are a doublet of doublets at δ 4.88 and δ 4.41, respectively. A
doublet of hydroxyl groups appears at 4.38 and 3.59 ppm. The
10 sp2 (six quaternary and four methine carbons) and four sp3
carbons in 13C NMR spectra are consistent with the proposed
structure 18.
On the other hand, the high synthetic potential of benzylic
bromides as precursors of anthracene prompted us to investigate
the silver-induced substitution reaction. The bromides in ben-
(7) Hokelek, T.; Tutar, A.; Cakmak, O. Acta Crystallogr. 2002, E58,
10-12,
(8) ChemOffice 6.0 (ChemBats3D Ultra 6.0, ChemDraw Ultra Version
6.0.) CS ChemBats3D Ultra, 2000; CambridgeSoft.com, 100Cambridge
Park, Dr. Cambridge, MA 02140-2317 U.S.A.
(9) Demirtas, I.; Erenler, R.; Buyukkidan, B.; C¸ akmak, O. Submitted
for publication.
J. Org. Chem, Vol. 71, No. 5, 2006 1797

Cakmak et al.
SCHEME 6
SCHEME 7
SCHEME 8
SCHEME 9
Because the halohydrines 18 and 19 are good precursors for
corresponding arene oxides, we treated them with 2 equiv of
sodium methoxide. Elimination of 2 mol of HBr with dry
sodium methoxide in tetrahydrofuran cyclized the bromohydrins
to the oxiranes in a good yield and high purity, whereas
dihydroxy 19 gave anti-diepoxide 20 as a consequence of trans
alignment of the hydroxyls and bromines. It is expected that
compound 18 afforded monoepoxide 21 due to the existence
of only one trans orientation of hydroxyl and bromine in the
same conditions.
The 1H NMR spectrum of diepoxide 20 exhibits two AA′BB′
splitting patterns of aromatic and aliphatic protons. The A part
of the aliphatic protons resonates at δ 4.46 and the B part of
the system resonates at δ 4.0. Seven lines in the 13C NMR
spectra are also in accord with the proposed symmetrical
diepoxide structure 20. The 1H NMR spectrum of monoepoxide
21 displays a characteristic signal splitting pattern. The H1,
coupled with OH and vicinal proton H2, resonates at 5.41 as a
doublet of doublets (J1-OH ) 11.9 Hz, J12 ) 2.2 Hz). The OH
signal is observed at δ 4.10 as a doublet. H4 and H3 resonate at
δ 5.06 and 4.44, respectively, as a doublet (J43 ) 4.2 Hz). In
the 13C NMR spectrum, 10 lines in the aromatic region and
five lines in the aliphatic region support the proposed structure.
The similarity between the NMR signal system of 21 with that
of tetralin oxide9 22 that we elucidated by X-ray analysis10 is
also consistent with the proposed structure 21 (Scheme 10).
Silver-induced methanolysis followed by aromatization can
lead to methoxy derivatives of anthracene. For this reason, a
solution of hexabromides 3 and 4 in dry methanol was combined
with 2 equiv of silver sulfate at room temperature. After
crystallization and column chromatography of the solvolysis
mixture, 1,4-dimethoxy-2,3,9,10-tetrabromo-1,2,3,4-tetrahy-
droanthracene 23 was selectively obtained in a yield of 75%
(Scheme 11).
Proton and carbon NMR studies indicate that dimethoxide
23 has asymmetry in its structure. The vicinal coupling constant
(10) Celik, I.; Demirtas, I.; Akkurt, M.; Erenler, R.; Guven, K.; Cakmak,
O. Cryst. Res. Technol. 2003, 38, 193-196.
1798 J. Org. Chem., Vol. 71, No. 5, 2006

New Anthracene DeriVatiVes
SCHEME 10
observed AB system (8.27 and 7.60 ppm; J43 ) 9.5 Hz) is in
good agreement with the proposed structure 27. 13C NMR
spectra of the compounds’ eight quaternary and six methine
carbons and one sp3 carbon atom (methoxyl group) are in accord
with both compounds 26 and 27.
Conclusion
A convenient and effective procedure for the synthesis of
hexabromoanthracenes 3 and 4 has been developed, whose base-
mediated elimination affords the synthetically valuable 2,3,9,10-
tetrabromoanthracene 5 and 1,3,9,10-tetrabromoanthracene 6 as
the sole products in high yield. The synthesis employs readily
available anthracene as a starting material and is applicable to
the large-scale preparation of compounds that constitute excel-
lent precursors for substituted anthracenes.
SCHEME 11
Silver-induced substitution of a mixture of hexabromides 3
and 4 with various nucleophiles, followed by aromatization,
opened up a new route to various anthracene derivatives
important in terms of the synthesis of pharmaceutical chemi-
cals,11 natural products,12 and donor properties.13 For example,
tribromo methoxides 26 and 27 are very useful precursors for
the synthesis of many other substituted anthracenes as a result
of the easy substitution of the bromo groups. The chemistry of
anti-9,10-dibromo-1,2;3,4-anthracene dioxide 20 and mono-
epoxide 21 is not important for the polyfunctionalization of
anthracene nor is the chemistry of non K-region arene oxide.
Experimental Section
Preparation of 9,10-Dibromoanthracene (2). A magnetically
stirred solution of anthracene (1.78 g, 10 mmol) in CH2Cl2 (110
mL) was cooled to 0 °C. The device for absorbing the evolved
hydrogen bromide was attached to the reaction flask. [CARE!! The
reaction evolves HBr and is best connected to a HBr gas trap
(bubbler containing 1 M NaOH solution) preferably in a fumehood.]
To the solution which is protected from light was added dropwise
Br2 (3.45 g, 22 mmol) in CH2Cl2 (10 mL) over 5 min and the
mixture was stirred for 1 h. Reaction progress was checked by 1H
NMR and TLC. After removing the solvent, the precipitated
material was filtered and purified in a short Al2O3 column (10 g).
The residue was dissolved in hot chloroform (120 mL) and allowed
to stand at room temperature for 1 day, 9,10-Dibromoanthracene
(1) was collected as pure yellow needles (3.22 g, 96%), mp 218-
220 °C (lit.14 220-222 °C). 1H NMR (400 MHz, CDCl3): δ 8.60
(AA′ part of AA′BB′ system, 4H, H1, H4, H5, H8), 7.66 (BB′ part
of AA′BB′ system, 4H, H2, H3, H6, H7). Anal. Calcd for C14H8Br2
(336.0): C 50.04, H 2.40. Found: C 50.10, H 2.35.
value for the H1 and H2 protons (J12 ) 2.3 Hz) indicates that
the methoxy and the bromine groups have a cis orientation (see
Scheme 2). The downfield shift of the resonance of H5 and H8
protons (8.44 ppm, m) is attributable to a van der Waals
interaction (steric compression) between the related protons and
bromines. The reaction can afford three stereisomeric dimeth-
oxides (23, 24, and 25); only structure 23 is unsymmetrical and
its strain energy (SE)8 is the lowest (SE ) 27.84 kJ/mol total
strain energy, Scheme 11) among the possible stereoisomers,
which may explain why compound 23 is selectively formed.
After the successful isolation of the methoxide 23, which has
the requisite skeletal arrangement and functionality to permit
the easy introduction of two double bonds to form anthracene
derivatives, compound 23 was subjected to base-induced
elimination with sodium methoxide in dry THF at room
temperature. The reaction afforded 1-methoxy-3-bromide 26 and
1-methoxy-2-bromide 27, which were easily separated by
column chromatography in high yields due to convenient Rf
values and ready crystallizable materials (Scheme 11). It is
noteworthy that MeOH elimination occurs as well as 2 mol HBr
elimination dehydrohalogenation; otherwise, in the case of
forming compound 28, strain energy increases enormously
(26.57 kJ/mol) due to the bulky groups in γ-gauche positions
(Scheme 11).
Bromination of 9,10-Dibromoanthrecene (2). The solution of
9,10-dibromoanthracene (2) (3.76 g, 11.22 mmol) in CH2Cl2 (150
mL) was cooled to -15 °C. To the solution which is protected
from light was added Br2 (5.27 g, 1.7 mL, 33 mmol) in one portion.
The mixture was allowed to stand in a frezeer at -15 °C. Reaction
1
1
progress was monitored by TLC and H NMR. H NMR control
of reaction mixture after 1 week showed that conversion is 50%.
After completing the reaction in 20 day, excess bromine and the
(11) Sajewicz, W.; Dlugosz, A. J. Appl. Toxicol. 2000, 20 (4), 305-
312. (b) Hangartner, P. J.; Munch, R.; Meier, J.; Ammann, R.; Buhler, H.
Endoscopy 1989, 21 (6), 272-275. (c) de Witte P.; Dreessen, M.; Lemli,
J. Pharm. Acta HelV. 1991, 3, 70-73. (e) de Witte, P.; Cuveele, J.; Lemli,
J. Planta Med. 1991, 57, 440-443.
(12) Marques, W. B.; Santos, H. S.; Pessoa, O. D. L.; Filho, R.; Lemos,
T. L. G. Phytochemistry 2000, 55, 793-797. (b) Chang, L. C.; Chavez,
D.; Gills, J. J.; Fong, H. H. S.; Pezzuto, J. M.; Kinghorn, A. D. D.
Tetrahedron Lett. 2000, 41, 7157-7162.
(13) El-Kemary, M. Can. J. Appl. Spectrosc. 1996, 41, 109-112. (b)
Ihmels, H.; Meiswinkel, A.; Mohrschladt, C. J. Org. Lett. 2000, 2 (18),
2865-2867.
(14) Jones, S.; Christian Atherton, J. C. Synth. Commun. 2001, 31, 1799-
1802.
The 1H NMR spectra of 26 and 27 consist of three
characteristic signals, indicating one methoxy group in each
compound and showing the position of the bromine group. The
observed meta coupling in the 1H NMR spectrum of 26 (J24
)
1.7 Hz) is consistent with the 1-methoxy and 3-bromo constitu-
tion. While H4 (δ 8.30) resonates at quite an upper field due to
the steric compression of Br10, H2 (δ 6.83) appears at a lower
field due to the electron donor OMe group bonded to C1. The
J. Org. Chem, Vol. 71, No. 5, 2006 1799

Cakmak et al.
1
solvent were removed. H NMR investigation of the rest showed
organic layers were washed with water (2 × 50 mL) and dried
over CaCl2. After evaporation of the solvent (20 °C, 10 Torr), the
residue was placed on a short silica gel (15 g) column and eluted
with hexane. Recrystallization from hot benzene afforded 2.69 g
(85%) of pure tetrabromoanthracene 5 as yellow needles from
formation of two hexabromide 3 and 4 in a ratio of 60:40,
respectively. It was seen that hexabromide 4 is quite sensitive to
daylight and aromatizes, with configuration isomerization occuring
in ca. 0.5 h. Chromatographic separation failed due to nearly same
Rf values (Rf ) 0.4, hexane) of compound 3 and 4. Moreover, during
column chromatography, aromatization of compound 4 and con-
figuration isomerizations of both hexabromides occurred. Crude
product (7.08 g) was applied to fractionally crystallize (THF) in
benzene (170 mL) in the dark at room temperature (or refrigerator).
The crystallized materials were taken as several fractions. Unsepa-
rated fractions were combined, and further recrystallization was
applied. Hexabromide 4 (2.2 g 30%) and hexabromide 3 (3.3 g,
45%) were separated in pure form, and the products were saved in
dark in freezer.
trans,trans,cis-1,2,3,4,9,10-Hexabromo-1,2,3,4-tetrahydroan-
thracene (3). Crystallized from benzene, mp 160-170 °C (dec).
1H NMR (200 MHz, CDCl3) δ 8.41 (m, 2H, H5, H8), 7.69 (m, 2H,
H6 and H7), 6.31 (d, J12 3.8, 1H, H1), 6.02 (d, J43 ) 2.8, 1H, H4),
5.36 (dd, J21 ) 3.8, J23 ) 11.2, 1H, H2), 4.33 (dd, J32 ) 11.2, J34
2.8, 1H, H3); 13C NMR (50 MHz, CDCl3) δ 135.6, 135.3, 134.6,
133.8, 131.9, 131.8, 130.7, 129.8, 126.9, 113.9, 59.6, 59.4, 56.7,
54.9; MS (CI) m/z 652/654/656/658/660 (M+) 571/573/575/577/
579/581/582 (M+, -Br), 490/492/494/496/498/500 (M+-2Br); 410/
412/414/416/418(M+-3Br); 333/334/336/338/339 (M+, -4Br); 254/
256/257/259 (M+, -5Br); 174/176/177. (M+ -6Br), 149/150, 98/
99, 87/88, 74, 62, 39; IR (KBr) νmax 2990, 1480, 1220, 1220, 1120,
1020, 910, 830, 820. Anal. Calcd for C14H8Br6 (655.6): C, 25.65;
H, 1.23. Found: C, 25.55; H, 1.27. Anal. Calcd for C14H8Br6
(655.6): C, 25.65; H, 1.23. Found: C, 25.52; H, 1.26.
cis,trans,cis-1,2,3,4,9,10-Hexabromo-1,2,3,4-tetrahydroan-
thracene (4). Crystallized from benzene, mp 146-150 °C (dec).
1H NMR (400 MHz, CDCl3) δ 8.45 (m, AA′ part of AA′BB′
system, 2H, H5, H8), 7.73 (m, BB′ part of AA′BB′ system, 2H,
H6,H7), 6.52 (AA′ part of AA′BB′ system, 2H, H1, H4), 5.55 (BB′
part of AA′BB′ system, 2H, H2, H3); 13C NMR (100 MHz, CDCl3)
δ 138.6, 133.2, 126.4, 125.8, 122.5, 54.0, 44.3; IR (KBr) νmax 2996,
1398, 1330, 1251, 1160, 1135 1037, 914, 759. Anal. Calcd for
C14H8Br6 (655.6): C, 25.65; H, 1.23. Found: C, 25.57; H, 1.28.
Synthesis of 1,3,9,10-Tetrabromoanthracene (6). To a stirred
solution of hexabromide 4 (1.0 g, 1.52 mmol) in dry and freshly
distilled THF (60 mL) was added dropwise 1,5-diazabicyclo[5.4.0]-
undec-5-ene (DBU, 0.532 g, 3.5 mmol) in THF (20 mL) over 30
min. The reaction mixture was protected from light and stirred at
room temperature for 4 h. After the reaction was complete (TLC
control), the precipitated material was filtered and the reaction
material was diluted with methylene chloride (100 mL). The organic
layer was washed with H2O (3 × 25 mL) and dilute KOH and
dried over K2CO3. After removal of the solvent, the precipitated
material was recrystallized from chloroform. 1,3,9,10-Tetrabro-
moanthracene was obtained in a yield of 85% (0.65 g) as yellow
needles, mp 161-162 °C (from hexane, Rf 0.59). 1H NMR spectra
of the rest after crystallization showed a product mixture; chroma-
tography gave no pure products because of their similar Rf values.
1H NMR (400 MHz, CDCl3) δ 8.89 (d, J42 ) 1.84, H4), 8.77 (m,
H8), 8.56 (m, H5), 8.15 (d, J24 ) 1.84, H2), 7. 69 (m, H6 and H7);
13C NMR (50 MHz, CDCl3 + DMSO) δ 140.6, 139.2, 134.5, 133.5,
131.5, 130.9, 130.6, 129.9, 129.1, 128.9, 123.8, 122.9, 121.9, 121.4;
IR (KBr) νmax 3079, 3027, 2923, 1585, 1506, 1284,1250, 1178,
1238, 1178, 954,750. Anal. Calcd for C14H6Br4 (493.8): C, 34.05;
H, 1.22. Found: C, 34.17; H, 1.19.
1
benzene, mp 273-274 °C from benzene. H NMR spectra of the
rest after crystallization showed a product mixture. Chromatography
gave no pure products because of similar Rf values (the rest consist
of possible other bromoisomers along with 9,10-dibromo-
anthracene). It was not possible to measure 13C NMR for tetrabro-
mide 5 due to unsolubility of the tetrabromide 5 (ca. 35 mg of
tetrabromide 5 is solved in 10 mL of benzene. Solubility of
tetrabromide 5 is lower in other solvents such as acetone, THF,
1
DMF, and CHCl3). H NMR (200 MHz, DMSO-d6) δ 8.8 (s, 2H,
H1/H4), 8.5 (AA′ part of AA′BB′ sys. 2H, H5/H8), 7.9 (BB′ part of
AA′BB′ sys. H6/H7); MS (CI) (m/z) 489.63/491.63/493.63/495.63/
497.63 (M+), 411.75/413.75/415.75/417.75 (M+, -Br), 331.87/
333.87/335.87), 251.99/253.99/255.99, 173.07/174.07/176.07, 149.06,
135, 122.07, 97, 81, 69. Anal. Calcd for C14H6Br4 (493.8): C, 34.05;
H,1.22. Found: C, 34.15; H, 1.25.
Preparation of 2,4-Dinitroxy-2,3,9,10-tetrabromo-1,2,3,4-hy-
droanthracene (17). To a solution of a mixture of hexabromides
3 and 4 (3.0 g, 4.57 mmol) (obtained from bromination of 9,10-
dibromoanthracene) in dry diethyl ether (150 mL) was added silver
nitrate (2.33 g, 13.7 mmol.). The reaction mixture was magnetically
stirred under nitrogen gas atmosphere in the dark for 3 days.
Reaction progress was monitored TLC. After the reaction was
complete, precipitated solid material was filtered and the solvent
was removed by vacuo. The residue was passed through a short
silica gel (10 g) column by elution with a dichloromethane-hexane
mixture. After separation of the crystallizing material (dinitroxy
17, 150 mg), the mother liquor (2.85 g) was applied to a silica gel
column (190 g) eluting with hexanes-ethyl asetate (9:1). Dinitroxy
17 was recrystallized from dichloromethane-hexane; isolated yield
1.56 g (total yield 59%). Other fractions from the column
chromatography, which was unable to isolate purely, were mixtures
consisting of probable other dinitoxy stereoisomers, mp 176-177
1
°C (dec). H NMR (400 MHz, CDCI3) δ 8.46 (m, 2H, H5, H8),
7.82(m, 2H, H6, H7), 6.93 (brs, 2H, H1,H4), 5.25 (brs,2H, H2, H3);
13C NMR (400 MHz, CDCI3) δ 133.7, 130.6, 130.2, 128.5, 124.5,
80.0, 77.9; MS (CI) m/z 620 (M+), 575, 528, 512, 495, 368, 336,
176, 125, 98, 74, 63; IR (KBr) Vmax 3564, 3269, 2999, 2978, 2902,
2538, 2337, 1973, 1946, 1846, 1817, 1718, 1651, 1566, 1483, 1414,
1375, 1356, 1275, 1184, 1155, 1120, 1039, 1018, 952. Anal. Calcd
for C14H8Br4N2O6 (619,84): C, 27,13; H, 1,30. Found: C, 26.95;
H, 1.25.
Preparation of 2,3,9,10-Tetrabromoanthracene 5 from Di-
nitroxy 17. 1,4-Dinitrate-2,3,9,10-tetrabromo-1,2,3,4-tetrahydro-
anthracene 17 (1.24 g, 2 mmol) in dry THF (30 mL) was treated
with sodium methoxide (0.27 g, 2.5 equiv) in dry THF (10 mL).
The mixture was stirred at room temperature overnight. After being
worked up (3 × 20 mL diethyl ether), dried (Na2SO4), and
evaporated, the residue was filtered by using a short silica gel (10
g) column eluting with hexane-chloroform. The precipitated
product was recrystallized from hot benzene, and 2,3,9,10-tetra-
bromide 5 was isolated in a yield of 691 mg (70%). Other fractions
from the column chromatography could not be isolated purely.
Hydrolysis of Hexabromides 3 and 4. To a stirred solution of
a mixture of hexabromides 3 and 4 (obtained from bromination of
9,10-dibromoanthracene) (3.0 g, 4.57 mmol) in acetone (50 mL)
was added a solution of AgCIO4‚H2O (3.1 g, 13.7 mmol) in aqueous
acetone (7 mL acetone-3 mL H2O) in the dark. The resulting
mixture was stirred at room temperature for 2 days in dark. The
precipitated AgBr was removed by filtration. After removal of the
solvent, the residue was chromatographed on silica gel (200 g),
eluted with ethyl acetate-hexane (4:1) to give 1,4-dihidroxy-
2,3,9,10-tetrabromoanthracenes 18 and 19.
Synthesis of 2,3,9,10-Tetrabromoanthracene (5). To a solution
of hexabromide 3 (4.2. g, 6.4 mmol) in dry and freshly distilled
THF (150 mL) was added 1.44 g (12.8 mmol) of potassium tert-
butoxide solution in dry and freshly THF (40 mL). The resulting
reaction mixture was magnetically stirred for 12 h at 20 °C in dark.
Reaction progress was monitored by TLC (Rf ) 0.64 eluted with
petroleum ether). The reaction mixture was diluted with water (100
mL) and extracted with ether (2 × 100 mL), and the combined
[2R(S),3R(S]-9,10-Tetrabromo-1,2,3,4-tetrahydroanthracene-
[1S(R),4S(R)]-diol (18). The compound was recrystallized from
1800 J. Org. Chem., Vol. 71, No. 5, 2006

New Anthracene DeriVatiVes
dichloromethane-hexane as colorless needles, yield 0.97 g (40%),
mp 160-161 °C, Rf ) 0.58 (hexanes-EtOAc, 7:3). 1H NMR (400
MHz, d-DMSO) δ 8.42-7.72 (4H, m, aryl H), 5.92 (1H, dd, J1-OH
) 10.0, J12 1.9, H1), 5.77 (1H, dd, J4-OH ) 4.0, J43 ) 3.2, H4),
4.88 (1H, dd, J23 ) 7.4, H2), 4.41 (1H, dd, H3), 4.38 (1H, d, J1-OH
) 10.0, C1-OH), 3.59 (1H, d, J4-OH ) 4.0, C4-OH); 13C NMR
(100 MHz, d-DMSO) δ 135.4, 133.8, 132.8, 132.3, 128.7, 128.2,
125.6, 123.8, 119.5, 118.9, 76.5, 73.1, 57.9, 56.7; IR (KBr) νmax
3192, 2997, 1707, 1583, 1551, 1481, 1390, 1348, 1325, 1296, 1244,
1189, 1160, 1122, 1095, 1053, 1022, 970. Anal. Calcd for C14H10-
Br4O2 (529.84): C, 31.74; H, 1.90. Found: C, 31.45; H, 1.95.
[2R(S),3R(S)]-9,10-Tetrabromo-1,2,3,4-tetrahydroanthracene-
[1S(R),4S(R)]-diol (19). The compound was recyrstallized from
acetone-hexane as colorless needles, yield 0.85 g (35%), mp 208-
Synthesis of (2R(S),3R(S))-9,10-Tetrabromo-(1R(S),4S(R))-
dimethoxy-1,2,3,4-tetrahydroanthracene (23). To a solution of
a mixture of hexabromides 3 and 4 (obtained from bromination of
9,10-dibromoanthracene) (3.0 g, 4.59 mmol) in dry methanol (40
mL) was added Ag2SO4 (2.85 g, 9.15 mmol) under a nitrogen
atmosphere in the dark. The resulting reaction mixture was stirred
magnetically at room temperature for 3 days. Reaction progress
was monitored by TLC for consumption of the starting material.
After removal of the residual by filtration and then removal of the
solvent, the crude product was passed through a short column
packed with silica gel (10 g). Recrytallization from chloroform-
hexane in the refrigerator gave the clear yellow crystals of
methoxide 23, yield 0.91 g, (75%), mp 144-145 °C (from
chloroform-hexane), Rf ) 0.59 (hexanes-EtOAc, 6:1). 1H NMR
(400 MHz, CDCI3) δ 8.42 (m, 1H, H5/H8), 8.47 (m, 1H, H5/H8),
7.70 (2H, m, H6, H7), 5.62 (1H, d, J43 ) 2.3, H4), 5.52 (1H, d, J12
)1.8, H1), 4.97 (1H, dd, J32 ) 10.7, H3), 4.26 (1H, dd, J32 ) 10.7,
1
209 °C, Rf ) 0.52 (hexanes-EtOAc, 3:1). H NMR (400 MHz,
d-DMSO) δ 8.48 (2H, AA′ part of AA′BB′ system, H5, H8), 7.90
(2H, BB′ part of AA′BB′ system, H6, H7), 6.32 (2H, d, J12 J34 7.15,
H1, H4), 5.48 (2H, d, H2, H3), 5.20 (2H, brs, 2-OH); 13C NMR
(100 MHz, d-DMSO) δ 136.08 (C11-C12), 133.7 (C13-C14), 130.20
(C6-C7), 127.1 (C9-C10), 123.2 (C5-C8), 72.9 (C1-C4), 57.3 (C2-
C3); IR (KBr) νmax 3855, 3839, 3677, 3529, 2916, 1701, 1655, 1560,
1477, 1439, 1373, 1331, 1288, 1245, 1159, 1072, 956, 901, 862.
Anal. Calcd for C14H10Br4O2 (529.84): C, 31.74; H, 1.90. Found:
C, 31.37; H, 1.95.
J12 )1.8, H2), 3.72 (3H, s, C1-OMe), 3.53 (3H, s, C4-OMe); 13
C
NMR (100 MHz, CDCl3) δ 133.7, 133.4, 132.7, 132.6, 129.3, 129.1,
129.0, 128.8, 128.6, 125.3, 86.5, 80.9, 58.2, 58.2, 57.2, 54.9; MS
(CI) m/z 576 (M++18), 558 (M+ +1), 544, 527, 510, 496, 479,
464, 445; IR (KBr) νmax 2994, 2929, 2825, 2023, 1832, 1801, 1706,
1612, 1572, 1481, 1458, 1400, 1371, 1325, 1288, 1250, 1205, 1184,
1163, 1082, 1043, 997. Anal. Calcd for C16H14Br4O2 (557.9): C,
34.45; H, 2.53. Found: C, 34.42; H, 2.17.
Aromatization of dimethoxide 23. To a solution of dimethoxide
23 (1.72 g, 3.08 mmol) in freshly distilled THF (50 mL) was added
a solution of sodium methoxide (0.5 g, 9.2 mmol) in dried THF
(20 mL). The mixture was stirred at ambient temperature for 8 h.
Reaction progress was monitored by TLC for consumption of the
starting material. Diethyl ether (60 mL) and H2O (50 mL) were
added to the reaction mixture and the resulting precipitate was
removed by filtration. The organic layer was separated, washed
with H2O (3 × 35 mL), and dried over CaCl2. The filtrate was
concentrated in vacuo to give crude product, which was chromato-
graphed using a SiO2 (140 g) column eluted with hexane (3.5 L)
to give the two methoxides 26 and 27.
Synthesis of anti-1,2:3,4-Dioxide-9,10-dibromo-1,2,3,4-tet-
rahydroanthracene (20). To a solution of dihydroxide 19 (1.2 g,
2.28 mmol) in freshly distilled THF (40 mL) was added a solution
of sodium methoxide (0.384 g, 5.68 mmol) in THF (30 mL). The
mixture was stirred at ambient temperature under a nitrogen gas
atmosphere for 8 h. After consumption of the starting material
(monitoring TLC), to the reaction mixture were added diethyl ether
(70 mL) and H2O (50 mL), and precipitated material was removed
by filtration. The organic layer was washed with H2O (3 × 40 mL)
and dried over CaCl2. After removing the solvent at reduced
pressure, crude product was chromatographed using an aluminum
oxide (30 g, neutral) column, eluted with hexane. The product which
was recrytallised from chloroform/hexane as colorless needles, yield
0.58 g (70%), mp 214-220 °C (dec), Rf ) 0.59 (hexane/chloroform,
1-methoxy-3,9,10-tribromoanthracene (26). The product was
recrystallized from chloroform-hexane, yield 0.42 g (31%), mp
1
4:1). H NMR (400 MHz, CDCI3 δ 8.32 (AA′ part of AA′BB′
1
159-160 °C, Rf ) 0.41 (hexane). H NMR (400 MHz, CDCI3) δ
system, 2H, H5/H8), 7.63 (BB′ part of AA′BB′ system, 2H, H6/
H7), 4.46 (AA′ part of AA′BB′ system, 2H, H1/H4), 4.00 (B part
of AA′BB′ system, 2H, H2/H3); 13C NMR (100 MHz, CDCl3) δ
138.1, 134.7, 134.3, 133,8, 133.4, 59.6, 57.54; IR (KBr) νmax 2923,
1629, 1484, 1253, 1174, 927, 860, 756, 507. Anal. Calcd for C14H8-
Br2O2 (368.02): C, 45.69; H, 2.19. Found: C, 45.80; H, 2.10.
Synthesis of 1-Hydroxy-2-bromo-3,4-oxide-1,2,3,4-tetrahy-
droanthracene (21). To a solution of dihydroxide 18 (1.5 g, 2.85
mmol) in freshly distilled THF (40 mL) was added a solution of
sodium methoxide (0.45 g, 8.4 mmol) in dried THF (30 mL). The
mixture was stirred at ambient temperature under a nitrogen gas
atmosphere for 6 h in the dark. Reaction progress was monitored
by TLC for consumption of the starting material. Diethyl ether (60
mL) and H2O (50 mL) were added to the reaction mixture and the
resulting precipitate was removed by filtration. The organic layer
was washed with H2O (3 × 25 mL), dried over CaCl2, and
concentrated at reduced pressure. After the crude product was
purified by column chromatography (Al2O3, 100 g), monoepoxide
21 was recrystallized from hexane-chloroform, yield 0.95 g (75%),
8.66 (1H, m, H5), 8.39 (1H, m, H8), 8.30 (1H, d, J42 1.7, H4), 7.50
(2H, m, H6, H7), 6.83 (1H, d, J24 1.7, H2), 3.93 (3H, s, OMe); 13
C
NMR (100 MHz, CDCl3) δ 156.9 (C1), 109.9 (C2), 122.8 (C3),
123.3(C4), 129.8 (C5), 127.9(C6), 128.5 (C7), 128.7 (C8), 119.7 (C9),
121.9 (C10), 131.9 (C11), 123.4 (C12), 132.5 (C13), 133.4 (C14), 56.2
(OMe); MS (EI+): m/z 442(M+), 427, 403, 399, 394, 368, 366,
351, 349, 325, 323, 321, 319, 287; IR (KBr) νmax 2956, 2925, 2831,
1618, 1597, 1541, 1524, 1458, 1439, 1427, 1402, 1373, 1350, 1304,
1248, 1230, 1155, 1115, 1095, 984. Anal. Calcd for C15H9Br3O
(444.94): C, 40.49; H, 2.04. Found: C, 40.34; H, 2.10.
1-Methoxy-2,9,10-tribromoanthracene (27). The product was
recrystallized from chloroform-hexane, yield 0.60 g (44%), mp
164-165 °C (chloroform-hexane); Rf ) 0.24 (hexane). 1H NMR
(400 MHz, CDCI3) δ 8.76 (1H, m, H5), 8.46 (1H, m, H8), 8.27
(1H, d, J43 ) 9.5, H4), 7.60 (1H, d, J34 ) 9.5, H3), 7.57 (2H, m,
H1, H7), 3.84 (3H, s, OMe). 13C NMR (100 MHz, CDCl3) δ 153.2,
117.1, 131.7, 126.4, 129.4, 128.5, 128.6, 128.8, 117.7, 125.1, 127.1,
132.2, 131.6, 133.1, 62.2; MS (CI) m/z 442 (M+), 427, 403, 387,
386, 384, 382, 370, 369, 367, 366, 365, 364, 363, 351; IR (KBr)
1
mp 182-184 °C (dec), Rf ) 1.67 (hexane-chloroform, 4:1). H
νmax 2935, 1618, 1591, 1537, 1512, 1446, 1427, 1379, 1333, 1290,
NMR (400 MHz, CDCI3) δ 8.34 (2H, m, H5/H8), 7.63 (2H, m,
H6/H7), 5.41 (1H, dd, J1-OH ) 11.9, J12 ) 2.2, H1), 5.06 (1H, d,
J43 ) 4.2, H4), 4.44 (1H, d, J34 ) 4.2, H3), 4.10 (1H, d, J21 ) 2.2
H2), 3.12 (d, OH); 13C NMR (100 MHz, CDCl3) δ 134.6, 133.8,
133.3, 129.7, 129.6, 129.3, 128.7, 128.6, 127.7, 127.4, 71.8, 60.6,
58.7, 48.7; IR (KBr) νmax 3500, 2932, 1568, 1483, 1306, 1254,
1163, 1043, 962, 889, 804, 760, 669, 648, 607, 573, 544, 459. Anal.
Calcd for C14H9Br3O2 (448.93): C, 37.46; H, 2.0. Found: C, 37.10;
H, 2.07.
1250, 1209, 1155, 1059, 1033, 964. Anal. Calcd for C15H9Br3O
(444.94): C, 40.49; H, 2.04. Found: C, 40.37; H, 2.06.
Acknowledgment. The authors thank the Gaziosmanpasa
University Research Foundation (Grants 2003/43 and 2000/26)
and The Scientific and Technical Research Council of Turkey
(TUBITAK, Grant TBAG-1322) for financial support.
JO051846U
J. Org. Chem, Vol. 71, No. 5, 2006 1801