Improved synthesis of 1,8-diiodoanthracene and its application to the synthesis of multiple phenylethynyl-substituted anthracenes

Article abstract of DOI:10.1055/s-2005-869999

1,8-Diiodoanthracene was synthesized from 1,8-dichloroanthraquinone in three steps by improved procedures in 41% overall yield. Some anthracene derivatives carrying multiple phenylethynyl groups were synthesized from 1,8-diiodoanthracene and 4,5-diiodo-9-

Full text of DOI:10.1055/s-2005-869999

2116
SHORT PAPER
Improved Synthesis of 1,8-Diiodoanthracene and Its Application to the
Synthesis of Multiple Phenylethynyl-Substituted Anthracenes
S
ynthesis andCouplin
ic
h
i
a
cene o Goichi, Kazushi Segawa, Shinya Suzuki, Shinji Toyota*
Department of Chemistry, Faculty of Science, Okayama University of Science, 1-1 Ridaicho, Okayama 700-0005, Japan
E-mail: stoyo@chem.ous.ac.jp
Received 28 February 2005; revised 22 March 2005
logue 5 as well as their applications to the synthesis of
Abstract: 1,8-Diiodoanthracene was synthesized from 1,8-dichlo-
roanthraquinone in three steps by improved procedures in 41%
overall yield. Some anthracene derivatives carrying multiple phe-
nylethynyl groups were synthesized from 1,8-diiodoanthracene and
4,5-diiodo-9-anthrone.
anthracene derivatives with multiple phenylethynyl
groups as novel fluorophors.8
Compound 2 was prepared from 1,8-dichloroanthraqui-
none in three steps as shown in Scheme 1, in which the
improved yields are indicated together with those reported
in the literature.6
Key words: halogenation, reduction, cross-coupling, ethynylation,
anthracenes
Cl
Cl
I
I
O
O
1) NaBH4, MeOH
2) HClaq
NaI, Cu
nitrobenzene
A 1,8-anthrylene unit 1 has been utilized as a spacer con-
necting two functional groups at an appropriate interval of
ca. 5.0 Å (Figure 1).1,2 In some cases, the fluorescent
property of anthracene chromophores is intelligently ap-
plied for the design of molecular sensors.3 One of the most
practical precursors of these compounds is 1,8-dichloro-
anthracene, which can be coupled with organometallic re-
agents or amines by metal-catalyzed reactions to give the
corresponding alkyl, alkynyl, aryl, and amino deriva-
tives.1,4 Occasionally, 1,8-dibromoanthracene is also used
in the Sonogashira and other related coupling reactions.5
Although these precursors are sufficient for a range of re-
actions, the more reactive derivative, 1,8-diiodoan-
thracene (2), is expected to widen the scope of
applications of this spacer. The literature survey revealed
that compound 2 has been unknown until Lovell and Joule
reported the first synthesis in 1997.6 Although 2 and its
10-OCH3 analogue were used for reactants of the Suzuki
and Sonogashira couplings since then, further applica-
tions of these precursors were rather limited because of
the synthetic inaccessibility. Recently, we reported the
synthesis and properties of 1,8-anthrylene-ethynylene oli-
gomers, where 1,8-diiodoanthracene was a key building
unit.7 Therefore, we needed to facilitate the supply of the
starting material to promote the series of studies. We here-
in report an improved synthesis of 2 and its anthrone ana-
56%
(33%)
82%
(36%)
O
O
3
4
I
I
I
I
1) NaBH4, n-PrOH
2) HClaq
89%
(39%)
O
2
5
Scheme 1 Synthesis of 1,8-diiodoanthracene (2). The yields from
the original procedure6 are indicated in parentheses.
In the first step of iodination, the reaction time was ex-
tended from 16 to 43 hours to give the diiodide 4 in 56%
yield. It is important to purify this product sufficiently by
recrystallization from chlorobenzene for the next reaction.
The anthraquinone 4 was reduced with NaBH4 in metha-
nol followed by acid-catalyzed dehydration to give the an-
throne 5. After several attempts, we found that the use of
finely powdered 4 and the slow addition of NaBH4 afford-
ed a satisfactory result. When NaBH4 was added in small
portions to a suspension of 4 in methanol over three hours
(cf. 15 min in the original procedure), 5 was obtained in
82% yield after chromatographic purification together
with small amounts of 2 and its 10-OCH3 derivative. No
1,8-diiodo-9-anthrone was found in the reaction mixture.
Compound 4 was poorly soluble in methanol, but the solid
dissolved in the solvent as the reaction proceeded. When
NaBH4 was added rapidly, not only the formation of the
by-products but also the recovery of the insoluble starting
material became significant. We consider that the above
condition meets the balance between the solubility of the
substrate and the concentration of NaBH4 for the smooth
conversion into the anthrone. In the next reduction step,
the poor solubility of 5 in methanol was a problem in the
original procedure. When the reaction was carried out in
propan-1-ol instead of methanol, the reduction occurred
I
I
1
2
Figure 1 1,8-Anthrylene unit 1 as spacer and 1,8-diiodoanthracene
(2)
SYNTHESIS 2005, No. 13, pp 2116–2118
x
x.
x
x
.
2
0
0
5
Advanced online publication: 13.07.2005
DOI: 10.1055/s-2005-869999; Art ID: F04405SS
© Georg Thieme Verlag Stuttgart · New York

SHORT PAPER
Synthesis and Coupling Reactions of 1,8-Diiodoanthracene
2117
(110 mL) was heated under reflux for 43 h. The solvent was re-
moved by steam distillation, and H2O was removed by decantation
followed by evaporation. The solid was dissolved in a minimum
amount of boiling chlorobenzene (ca. 1.0 L), and the insoluble ma-
terials were removed by filtration while hot. The filtrate was al-
lowed to stand for 3 d, and the formed brown crystals were collected
by filtration. The filtrate was concentrated by evaporation to give an
extra amount of pure 1. The total yield was 23.5 g (56%); mp 269–
270 °C (Lit.6,9 mp 278–280 °C).
1H NMR (CDCl3): d = 7.35 (t, J = 7.7 Hz, 2 H), 8.28 (dd, J = 1.4,
7.7 Hz, 2 H), 8.40 (dd, J = 1.4, 7.7 Hz, 2 H).
13C NMR (CDCl3): d = 93.19, 127.51, 133.39, 134.60, 134.69,
smoothly at room temperature. The reduced product was
treated with concentrated HCl to give the anthracene 2 in
89% yield. So far, the overall yield of the three-step con-
version was considerably improved from 4.6% to 41% by
the optimization of the reaction conditions.
We applied compounds 2 and 5 to the synthesis of phenyl-
ethynyl substituted anthracene derivatives, which were at-
tractive as highly fluorescent compounds (Scheme 2).
The Sonogashira reaction of 2 with phenylacetylene
worked smoothly at room temperature to form the 1,8-di-
substituted derivative 6 in moderate yield. The treatment
of anthrone 5 with lithium phenylacetylide, which was
prepared from phenylacetylene and butyllithium, fol-
lowed by P2O5 afforded the 10-substituted derivative 7.
The coupling of this compound with phenylacetylene af-
forded the 1,8,10-trisubstituted derivative 8. Compounds
6 and 8 showed strong emission bands at 423 and 464 nm,
respectively, upon excitation at 393 nm in cyclohexane.
The fluorescence quantum yields were 0.80 and 0.67 for 6
and 8, respectively, these values being a little smaller than
that of 9,10-bis(phenylethynyl)anthracene (Ff 0.96).8
148.23, 180.82.
4,5-Diiodo-9-anthrone (5)
To a stirred suspension of 4 (2.76 g, 6.00 mmol), which was ground
to a fine powder with a motor prior to use, in MeOH (120 mL) was
added NaBH4 (1.13 g, 30.0 mmol) in small portions over 3 h (ca. 0.3
g every 1 h). The mixture was further stirred for 1 h at r.t. to give a
clear brown solution. After addition of conc. HCl (15 mL), the mix-
ture was refluxed for 1 h. The formed solid was collected by filtra-
tion, washed with H2O (300 mL), and air-dried. The solid was
separated by chromatography on silica gel (hexane–CH2Cl2, 10:1 to
1:1). The desired compound was separated as the most polar frac-
tion (2.19 g, 82%, Rf 0.32, hexane–CH2Cl2, 1:1) from two by-prod-
ucts, 1,8-diiodoanthracene (26 mg, 1%, Rf 0.35, hexane) and 1,8-
diiodo-10-methoxyanthracene (243 mg, 9%, Rf 0.11, hexane). Re-
crystallization from toluene afforded 5 as yellow crystals; mp 211–
212 °C (Lit.6 mp 210–212 °C).
Ph
Ph
PhC≡CH,
Pd(PPh3)4, CuI,
Et3N, THF
2
64%
1H NMR (CD2Cl2): d = 4.06 (s, 2 H), 7.26 (t, J = 7.8 Hz, 2 H), 8.20
(d, J = 7.8 Hz, 2 H), 8.33 (d, J = 7.8 Hz, 2 H).
6
Ph
Ph
13C NMR (CDCl3): d = 46.87, 101.23, 128.05, 129.16, 132.87,
I
I
PhC≡CH,
1) PhC≡CLi, Et2O
142.65, 144.10, 183.25.
Pd(PPh3)4, CuI,
Et3N, THF
2) P2O5, CCl4
5
1,8-Diiodoanthracene (2)
71%
98%
To a stirred suspension of 5 (2.00 g, 4.48 mmol) in n-PrOH (90 mL)
was added NaBH4 (0.847 g, 22.4 mmol) with small portions over 30
min (ca. 0.1 g every 5 min). The mixture was further stirred for 1 h
at r.t. to give a clear orange solution. After addition of conc. HCl (12
mL), the mixture was refluxed for 1 h. The formed solid was col-
lected by filtration, washed with H2O (100 mL), and air-dried. The
solid was separated by chromatography on silica gel (hexane–
CH2Cl2, 5:1) to give the desired compound as a yellow solid (1.72
g, 89%, Rf 0.35, hexane) with the recovery of the starting material
(123 mg, 6%). Recrystallization from EtOH afforded 2 as yellow
crystals; mp 190–191 °C (Lit.6,9 mp 201–202 °C).
Ph
Ph
7
8
Scheme 2 Synthesis of anthracene derivatives with multiple phe-
nylethynyl groups.
These examples reveal that 2 and 5 are versatile precur-
sors toward multiply substituted anthracenes. Iodo groups
in these compounds can be converted to various function-
al groups by metal-catalyzed coupling reactions more
readily than the corresponding bromides and chlorides.
1H NMR (CDCl3): d = 7.21 (dd, J = 6.9, 8.2 Hz, 2 H), 8.02 (d,
J = 8.5 Hz, 2 H), 8.16 (d, J = 6.9 Hz, 2 H), 8.33 (s, 1 H), 8.96 (s, 1
H).
13C NMR (CDCl3): d = 99.94, 126.75, 128.12, 128.81, 132.12,
133.24, 136.80, 137.70.
Melting points are uncorrected. Elemental analyses were performed
1
by a Perkin-Elmer 2400 series analyzer. H and 13C NMR spectra
were measured on a JEOL GSX 400 (1H: 400 MHz and 13C: 100
MHz) or a Varian Gemini-300 (1H: 300 MHz and 13C: 75 MHz)
spectrometer with TMS as an internal reference. High-resolution
FAB mass spectra were measured on a JEOL MStation-700 spec-
trometer. UV and fluorescence spectra were measured on a Hitachi
U-3000 spectrometer and a JASCO FP-6500 spectrofluorometer,
respectively, with a 10 mm cell in spectroscopic grade solvents.
Column chromatography and TLC were carried out with Merck Sil-
ica Gel 60 and Silica Gel 60 F254, respectively. Product yields are
values after chromatographic separation except for 4.
1,8-Bis(phenylethynyl)anthracene (6)
A solution of 1,8-diiodoanthracene (2; 172 mg, 400 mmol) in a mix-
ture of THF (10 mL) and Et3N (10 mL) was degassed by bubbling
argon for 20 min. To the solution were added phenylacetylene (176
mL, 1.60 mmol), Pd(PPh3)4 (69 mg, 60 mmol), and CuI (11 mg, 60
mmol). The mixture was refluxed for 24 h under argon. The solvent
was removed by evaporation. The crude product was purified by
chromatography on silica gel (hexane–CHCl3, 8:1) to give the de-
sired product as a yellow solid (96 mg, 64%). Recrystallization
from hexane afforded 6 as yellow crystals; mp 152–153 °C (Lit.10
mp 153–154 °C).
1,8-Diiodoanthraquinone (4)
A mixture of 1,8-dichloroanthraquinone (3; 25.0 g, 90.2 mmol), Cu
powder (2.01 g, 31.5 mmol), and NaI (50.0 g, 334 mmol) in PhNO2
Synthesis 2005, No. 13, 2116–2118 © Thieme Stuttgart · New York

2118
M. Goichi et al.
SHORT PAPER
1H NMR (CDCl3): d = 7.22 (m, 4 H), 7.33 (m, 2 H), 7.48 (dd,
J = 6.8, 8.8 Hz, 2 H), 7.59 (m, 4 H), 7.81 (dd, J = 1.0, 6.8 Hz, 2 H),
8.02 (d, J = 8.8 Hz, 2 H), 8.47 (s, 1 H), 9.64 (s, 1 H).
13C NMR (CDCl3): d = 86.03, 87.49, 101.49, 104.42, 118.67,
122.03, 123.15, 123.34, 125.23, 126.29, 127.54, 128.34, 128.39,
128.54, 128.68, 130.86, 130.98, 131.65, 131.79, 132.41.
13C NMR (CDCl3): d = 87.67, 94.96, 121.56, 123.35, 124.15,
125.16, 127.47, 128.25, 128.38, 128.91, 130.52, 131.48, 131.56,
131.80.
HRMS: m/z calcd for C38H22 [M+]: 478.1722; found: 478.1687.
UV (C6H12): lmax (e) = 270 (138400), 309 (12400), 330 (6800), 426
(30300), 452 nm (31600).
UV (cyclohexane): lmax (e) = 264 (126000), 283 (41600), 354
(7400), 373 (12300), 393 (19500), 416 nm (18400).
FL (C6H12): lmax = 464 nm (lex = 393 nm).
FL (cyclohexane): lmax = 423 nm (lex = 393 nm).
Acknowledgment
1,8-Diiodo-10-(phenylethynyl)anthracene (7)
This work was partly supported by ‘High-Tech Research Center’
Project for Private Universities: matching fund subsidy from
MEXT (Ministry of Education, Culture, Sports, Science and Tech-
nology, Japan), 2000–2005. We thank Dr. Shinichi Saito, Tokyo
University of Science, for useful discussion.
To a solution of phenylacetylene (330 mL, 3.00 mmol) in anhyd
Et2O (10 mL) was added a 1.56 mol/L hexane solution of BuLi
(1.47 mL, 2.70 mmol) with a syringe over 5 min at –78 °C under ar-
gon. The mixture was allowed to warm up to r.t., and stirred for 1.5
h. After addition of 5 (233 mg, 0.500 mmol), the mixture was stirred
for 48 h at r.t. and then quenched with aq NH4Cl (5 mL). The organ-
ic layer was separated, and the aqueous layer was extracted with
Et2O (10 mL). The combined organic layers were dried (MgSO4),
and evaporated. The residue was dissolved in CCl4 (5 mL), and the
solution was heated with P2O5 (500 mg) under reflux for 20 min.
The solid was washed with CHCl3 (3 × 50 mL), and the combined
solution was evaporated. The crude product was purified by chro-
matography on silica gel (hexane–CH2Cl2, 5:1) to give the desired
compound as a yellow solid (188 mg, 71%, Rf 0.60, hexane–
CH2Cl2, 2:1). Recrystallization from hexane afforded 7 as yellow
crystals; mp 239–241 °C.
1H NMR (CDCl3): d = 7.31 (dd, J = 7.3, 8.8 Hz, 2 H), 7.42–7.49 (m,
3 H), 7.75–7.77 (m, 2 H), 8.20 (d, J = 6.8 Hz, 2 H), 8.67 (d, J = 8.3
Hz, 2 H), 9.01 (s, 1 H).
13C NMR (CDCl3): d = 85.38, 100.56, 101.70, 119.54, 123.07,
127.69, 127.73, 128.54, 128.84, 131.64, 132.63, 133.06, 137.93,
138.09.
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(19000), 432 nm (18400).
Anal. Calcd for C22H12I2: C, 49.84; H, 2.28. Found: C, 50.05; H,
2.30.
1,8,10-Tris(phenylethynyl)anthracene (8)
A solution of 7 (106 mg, 200 mmol) in a mixture of THF (10 mL)
and Et3N (10 mL) was degassed by bubbling argon for 20 min. To
the solution were added phenylacetylene (88 mL, 0.80 mmol),
Pd(PPh3)4 (35 mg, 30 mmol), and CuI (5.7 mg, 30 mmol). The mix-
ture was refluxed for 14 h under argon. The solvent was removed by
evaporation. The crude product was purified by chromatography on
silica gel (hexane–CH2Cl2, 3:1) to give the desired product as a yel-
low solid (94 mg, 98%). Recrystallization from hexane–CHCl3 af-
forded 8 as yellow crystals; mp 207–208 °C. The elemental analysis
of this compound was difficult because of the incomplete combus-
tion, and the compound was characterized by HRMS and its purity
was confirmed by 1H and 13C NMR spectra.
(9) Although we carefully checked the purity of a sample of the
compound for the melting point measurement, the observed
temperature was lower than the literature value.
(10) Moroz, A. A.; Piskunov, A. V.; Shvartsberg, M. S. Izv. Akad.
Nauk SSSR, Ser. Khim. 1981, 386; Chem. Abstr. 1981, 95,
24621r.
1H NMR (CDCl3): d = 7.20 (t, J = 7.3 Hz, 4 H), 7.33 (t, J = 7.3 Hz,
2 H), 7.43–7.48 (m, 3 H), 7.57–7.61 (m, 6 H), 7.77 (d, J = 6.8 Hz, 2
H), 7.84 (d, J = 6.8 Hz, 2 H), 8.66 (d, J = 8.8 Hz, 2 H), 9.65 (s, 1 H).
Synthesis 2005, No. 13, 2116–2118 © Thieme Stuttgart · New York